Selected Abstracts from the National Congress of the Italian Society of Hypertension (SIIA 2009): 2009 October 1–4, Rome, Italy

Atherosclerosis and Inflammation

1.1 Effects of the Duration of the Disease and of Antiretroviral Treatment on Carotid Wall Structure in HIV Patients

M. Failla,¹ F. Citterio,¹ D. Dozio,¹ M. Rigoldi,¹ M. Pozzi,¹ M. Bettel,¹ A. Salvioni,¹ A. Dolara,² A. Gori,² R. Facchetti,¹ C. Giannattasio¹ and G. Mancia¹

1 Clinica Medica, Univ-Milan Bicocca e Ospedale San Gerardo di Monza, Monza, Italy; 2 Malattie Infettive, Univ-Milan Bicocca e Ospedale San Gerardo di Monza, Monza, Italy

Introduction: Several studies have shown an increased intima-media thickness of the common carotid artery in HIV patients suggesting that this condition may favour atherosclerosis. It is unknown, however, whether this is typical of HIV per se or it is due to the adverse metabolic effects of antiretroviral treatment and specifically of protease inhibitors, possibly through alterations of metabolic variables.

Aim: To measure common carotid intima-media thickness by a standard echocolorDoppler in HIV patients with and without protease inhibitors treatment, and characterize carotid wall composition by a dedicated software (HP technologies) based on the integrated backscatter analysis (IBS) of the native signals from the wall tissues, marker of fibrosis.

Methods: We studied 44 HIV patients (38 males) with a mean age 45.9 ± 8.4 years (mean ± SD) and a mean duration of the disease of 47.7 ± 33.2 months.

Results: All patients were normotensive and had no history or evidence of cardiovascular disease or diabetes. Their total cholesterol was 161.3 ± 46.3 mg/dL and serum triglycerides value was 165.7 ± 117.0 mg/dL. The average IMT was 0.64 ± 0.22 mm (RCCA) and 0.68 ± 0.26 mm (LCCA) which was similar to the value of age, sex and blood pressure matched controls. There was no significant difference between the IMT value in HIV patients treated (n = 29) or not treated (n = 15) with protease inhibitors. In HIV patients there was a significant correlation between the duration of the disease and the IMT value (r = 0.36, p < 0.01). Also carotid artery wall composition evaluated by IBS significantly correlated with the duration of the disease (r = 0.29, p < 0.05).

Conclusions: Our study shows in patients with HIV a relationship between carotid artery IMT and IBS and the duration of the disease, even in the absence of a pathological increase of the IMT. This correlation suggests an association between the disease and wall structural abnormalities, in term of fibrosis, independently from the type of the antiretroviral therapy. Thus, the increased cardiovascular mortality in HIV patients may be explained by arterial structural changes favouring atherosclerosis.

1.2 Resistance Artery Mechanics and Composition in Angiotensin II-Infused Mice: Effects of Cyclo-Oxygenase-1 Inhibition

A. Virdis, E. Daghini, E. Duranti, I. Rugani, R. Colucci, M. Fornai, S. Andreoni, F. Basolo, A. Salvetti, M. Del Tacca, C. Blandizzi and S. Taddei

Università di Pisa, Pisa, Italy

Introduction: An increased intravascular expression/activity of cyclo-oxygenase (COX)-1 participates in angiotensin (Ang) II-induced endothelial dysfunction.

Methods: We investigated the contribution of COX-1 to vascular alterations in structure, mechanics and collagen deposition in mesenteric arteries from Ang II-treated mice. Male mice received vehicle or Ang II (400 ng/kg/min, s.c.) ±SC-560 (COX-1 inhibitor, 10 mg/Kg/day i.p.) or celecoxib (cele, COX-2 inhibitor, 400 mg/Kg/day, food) (2 weeks, n = 7 each). Mesenteric vessels, studied on pressurized myograph, were exposed to intraluminal pressures (3–140 mmHg). Media thickness and lumen diameter were measured to determine mechanical properties. Collagen type I was evaluated by immunohistochemistry.

Results: Systolic blood pressure (SBP), increased by Ang II, was unmodified by COX-1 or COX-2 treatment (table). Media/lumen ratio (M/L) and media cross-sectional area (CSA), increased by Ang II, were partially reduced by COX-1 and not modified by COX-2 inhibition (table). Ang II-treated group showed stiffer vessels, with leftward shift of the stress-strain relationship and a raised slope of the incremental elastic modulus-stress relationship as compared to controls (p < 0.01). This was attenuated (p < 0.05) by COX-1 inhibitor and unchanged by COX-2 blockade. The enhanced collagen deposition induced by Ang II was prevented by COX-1 and only slightly reduced by COX-2 inhibitor (table).

Conclusions: Ang II-induced vascular alterations in structure, mechanics and composition were partially prevented by SC-560 treatment, providing some evidence that some actions of Ang II on resistance arteries are mediated by COX-1 isoenzyme.

1.3 A Functional LDL Receptor-Related Protein 6 (LRP6) Gene Variant is Associated with Different LRP6 Expression Levels in Atherosclerotic Plaques of Hypertensive Patients

R. Sarzani,¹ M. Bordicchia,¹ F. Salvi,¹ F. Guerra,¹ L. Carbonari,² G. Pagliariccio,² R. Catalini,¹ O. Zingaretti,¹ L. Giantomassi,¹ P. Dessì-Fulgheri¹ and A. Rappelli¹

1 Clinica di Medicina Interna, Univ. Politec. Marche, Ancona, Italy; 2 Clinica di Chirurgia Vascolare, Univ. Politec. Marche, Ancona, Italy

Introduction: LRP6 is a co-receptor in the canonical Wnt/beta-catenin signaling pathway and has recently been involved in vascular development and remodeling. LRP6 is expressed in vascular smooth muscle cells and in rat carotid arteries but it is unknown whether it is expressed in human carotid atherosclerotic plaques and if a common 1062V LRP6 variant with reduced function can be related to carotid artery atherosclerosis (CAA) in hypertensive patients.

Aim: This study verified the LRP6 gene expression in human carotid atherosclerotic plaques analyzing also the relationship between LRP6 variants and CAA in hypertensive patients.

Methods: Human carotid plaque samples were obtained from 24 hypertensive patients undergoing carotid endarterectomy for carotid artery stenosis ≥70% of the lumen. Expression was evaluated by Real Time PCR. Electronic records of 334 hypertensive patients (<65 years-old) who underwent carotid artery ultrasonography were retrospectively reviewed: presence of hypertension, type 2 diabetes, dyslipidemia, glomerular filtration rate, and smoking habit was evaluated. CAA was defined by the presence of atherosclerotic plaques (focal intima-media thickness ≥1.3 mm). Logistic regression models were used to estimate the independent effect of 1062V allele.

Results: LRP6 transcripts were present in carotid artery plaques. Significantly lower LRP6 expression levels (p < 0.0001) were present in 1062V carriers compared with I1062I homozygous subjects. In the association study, no difference was observed between genotypes in clinic variables except for a slightly higher fasting glucose in 1062V carriers. The 1062V LRP6 variant was an independent risk factor for CAA in both unadjusted (OR 2.08, 95%CI 1.27, 3.41, p = 0.003) and adjusted models (OR 1.92, 95%CI 1.09, 3.39, p = 0.02).

Conclusions: LRP6 1062V variant is strongly linked to carotid artery atherosclerosis in hypertensive patients beyond the role of established risk factors for atherosclerosis. Different LRP6 expression levels in human atherosclerotic plaques in vivo suggest that LRP6 may have a key functional role in the plaque-development process.

1.4 Association of a Prothrombotic State with Carotid Intima-Media Thickness in Hypertensive Patients

C. Catena, Gl. Colussi, E. Nadalini, W. Bragagnini, A. Di Fabio, M. Valeri, L. Marzano and L.A. Sechi

Clinica Medica, Univarsità di Udine, Udine, Italy

Introduction: Elevated plasma levels of fibrinogen and a prothrombotic state are associated with the presence and severity of target organ damage in hypertensive patients (Hypertension, 2000). The carotid intima-media thickness (IMT) is an early marker of vascular damage that anticipates the development of atheroma.

Aim: To investigate the relationships between IMT and markers of prothrombotic and proinflammatory state in primary hypertension.

Methods: Two-hundred-and-three consecutive patients (age 56 ± 12 years; M, 111; F, 92) were evaluated with carotid scan and blood was collected to measure plasma fibrinogen, fibrin D-dimer, prothrombin fragment 1 + 2, and homocysteine levels, serum lipoprotein(a), CRP, HOMA index, and the glucose and insulin response to an oral glucose load.

Results: Patients with a IMT above the median for the distribution (700 ìm) were older (61 ± 9 vs. 51 ± 11 y; p < 0.001), had greater BMI (28.7 ± 4.5 vs. 27.5 ± 4.1 Kg/2 p = 0.040), greater systolic and differential blood pressure (respectively 149 ± 20 vs 142 ± 15 mmHg; p = 0.005 and 61 ± 14 vs. 52 ± 9 mmHg; p<0.001), longer duration of hypertension (13 ± 11 vs. 10 ± 8 y; p = 0.011), and greater prevalence of coronary artery (13% vs. 1%; p = 0.002) and cerebrovascular disease (5% vs 0%; p = 0.042) than patients with a IMT below the median. Regression analysis showed a direct relationship of IMT with age (r = 0.543; p < 0.001), waist circumference (r = 0.166; p = 0.013), systolic and differential blood pressure (respectively, r = 0.187; p = 0.008 and r = 0.358; p < 0.001), duration of hypertension (r = 0.284; p = 0.004), fibrinogen (r = 0.289; p = 0.002), D-dimer (r = 0.403; p < 0.001), CRP (r = 0.143; p = 0.041), and the glycemic response to the oral glucose load (r = 0.255; p = 0.001). At multivariate analysis, only age and D-dimer were independently related with IMT.

Conclusions: These data show that an elevated plasma D-dimer is associated with the presence of an increased IMT and may contribute to development of carotid artery disease.

1.5 Interferon Inducible Protein-10 Expression in a Free Living Population: Potential Correlation with Cardiovascular Risk

M. Rosticci,¹ F. Santi,¹ S. Cristino,² E. Baldi,² A. Dormi¹ and C. Borghi¹

1 Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Università di Bologna, Bologna, Italy; 2 Dipartimento di Medicina e Sanità Pubblica, Bologna, Italy

Introduction: Atherosclerosis is associated with vascular inflammatory responses but molecular and cellular mechanisms are still unclear. Inflammatory cell infiltration and oxidative stress in vascular walls contribute to the pathogenesis of high blood pressure levels in experimental animals, thus, controlling chemokines production is important to regulate inflammatory reactions in hypertensive arterial walls.

Aim: To evaluate IP-10, inflammatory chemokine, serum concentration in a free living human population with different levels of cardiovascular diseases (CVD) risk.

Methods: We randomly selected 193 subjects, divided into 4 groups from Brisighella Heart Study Population: women aged less then 50 years (group A, n = 44), men under 50 (group B, n = 21), postmenopausal women (more than 10 years) aged 50 or more (group C, n = 48), and men aged 50 or more (group D, n = 80).

Results: Main findings of our study are shown in the table. The prevalence of CVD increased from group A (0%) to group B (4.78%), group C (8.33%) and group D (17.5%). We examined IP-10 release by multiplex proteomics in human serum using BioPlex platform and IP-10 serum concentration was compared by Kruskall Wallis test and a statistically significant differences was found in all groups (p < 0.001). In particular, we observed differences between group A and C (p < 0.0001) and between group B and C (p < 0.02). Group C was higher than Group A (p < 0.05) and higher than group D (p < 0.05).A similar trend was observed in all groups for serum TC, LDL and HDL. IP-10 values seem to be linked with hypertension and, especially, with lipidemic profile.

Conclusions: We observed a peak of IP-10 concentration and lipidemic parameters in group C. We supposed that a highest IP-10 increase was associated with osteoporosis in menopausal women. Further experiments will be performed to amplify the chemokines panel to evaluate the role of inflammatory pathway in high blood pressure levels.

1.6 Atorvastatin Reduces Macrophage Accumulation in the Atherosclerotic Plaque: A Comparison versus Non-Statin Based Regimen in Patients Undergoing Carotid Endarterectomy

M. Puato,¹ E. Faggin,¹ M. Zanardo,¹ M. Rattazzi,¹ F. Cipollone,² A. Zambon,³ A. Mezzetti² and P. Pauletto¹

1 Dipartimento di Medicina Clinica e Sperimentale, Padova, Italy; 2 Società Italyna per lo Studio dell’Aterosclerosi, Sezione Abruzzo, Chieti, Italy; 3 Dipartimento di Scienze Mediche e Chirurgiche, Padova, Italy

Introduction: Several studies suggested that statins may exert anti-atherosclerotic effects beyond cholesterol lowering. No definite data on humans are available confirming this hypothesis.

Aim: To compare the effect of high dose vs low dose of atorvastatin vs non-statin based treatment (cholestyearsamine plus sistosterol) on carotid plaque composition.

Methods: We studied 60 hypercholesterolemic patients (total cholesterol, TC, 225–295 mg/dL) eligible for carotid endarterectomy. Three months prior surgery patients were randomized into 3 groups (n = 20) receiving atorvastatin 10 mg/day (AT-10), or atorvastatin 80 mg/day (AT-80), or cholestyearsamine 8 g/day plus sitosterol 2.5 g/day (C-S). Blood samples were collected to assess lipid profile and inflammatory markers levels. Analysis of carotid plaque cell composition and lipid content was performed on endarterectomy specimens.

Results: The AT-80 group showed the highest reduction in TC and LDL cholesterol (LDL-C) levels. A similar level in TC and LDL-C was achieved in the AT-10 and C-S groups. The three regimens did not significantly influence the levels of inflammatory markers (including hs-PCR). A lower content in macrophages was observed in the AT-10 group plaques compared to the C-S group (AT-10: 11.0% vs C-S: 20.9% of plaque area). The macrophage content was further on reduced in the AT-80 group plaques (5.9% of plaque area). No difference in lymphocyte number was observed among treatments while the content of smooth muscle cells was higher in the AT-80 group. The plaque lipid content was similar in the 3 groups.

Conclusions: Despite a comparable reduction in cholesterol levels, atorvastatin treatment was superior to a non statin-based regimen in blunting macrophage accumulation inside carotid atherosclerotic plaque.

1.7 Pattern of Expression of Inflammatory Markers in Adipose Tissue of Untreated Patients with Essential Hypertension

A. Solini,¹ S. Madec,¹ M. Chiarugi,² E. Santini,¹ C. Rossi¹ and E. Ferrannini¹

1 Dipartimento di Medicina Interna Università di Pisa, Pisa, Italy; 2 Sezione di Chirurgia d’Urgenza Università di Pisa, Pisa, Italy

Introduction: Subcutaneous (SAT) and visceral adipose tissue (VAT) may contribute to the pathogenesis of hypertension by promoting endothelial dysfunction and inducing insulin resistance. In hypertensive patients, the inflammatory network and the MMP/TIMP system modulate vascular structure and function.

Methods: We measured TNFα, TGFβ, IL6, PAI1, MMP2, MMP9, TIMP1, TIMP2 expression (exp) by realtime PCR, reporting results as targeted/reference ratio, MMP2 and MMP9 activity (act) by zymography and TIMP1 and TIMP2 protein expression by Western blot in mature adipocytes (ADP) isolated from paired samples of VAT and SAT of 30 non-diabetic, lean, never-treated hypertensive patients (HT) and 20 normotensive controls (C). Plasma IL6, TGFβ and PAI1 levels (pl-lev) were also determined.

Results: MMP9 expression was similar in HT and C (0.4 ± 0.04 vs 0.5 ± 0.03 in VAT and 0.9 ± 0.05 vs 1.0 ± 0.05 in SAT), while MMP2 exp was reduced in HT SAT(2.4 ± 0.2 vs 0.9 ± 0.03, p < 0.0001), but not in VAT (0.9 ± 0.05 vs 0.8 ± 0.04).VATTIMP1 expression was similar in C and HT (1.0 ± 0.03 vs 1.0 ± 0.06), while it was reduced in HT SAT (0.5 ± 0.03 vs 0.4 ± 0.03; p = 0.0005). TIMP2 expression was reduced in HT SAT and VAT (2.0 ± 0.06 vs 1.0 ± 0.03 in VAT, and 3.1 ± 0.1 vs 1.2 ± 0.04 in SAT, both p < 0.0001). These results were confirmed at the protein level. MMP2 activity was reduced in HT VAT and SAT (4674 ± 209 vs 3889 ± 87 and 5329 ± 113 vs 3965 ± 64 AU, p = 0.0008 and p < 0.0001). Despite similar expression in C and HT, MMP9 activity was strongly reduced in HT (13408 ± 552 vs 1021 ± 32 in VAT and 3398 ± 98 vs 633 ± 11 AU in SAT; both p < 0.0001). IL6 expression was higher in HT (15.3 ± 2.4 vs 186.8 ± 21.5 in VAT and 9.8 ± 0.8 vs 38.4 ± 3.2 in SAT, both p < 0.0001). TNFα expression, similar in C VAT and SAT (1.2 ± 0.04 vs 1.1 ± 0.05) was increased in HT VAT (3.9 ± 0.3 vs 1.4 ± 0.2, p < 0.0001). VAT and SAT TGFβ expression were reduced in HT (1.7 ± 0.04 vs 1.2 ± 0.05 and 1.4 ± 0.05 vs 1.2 ± 0.09, both p < 0.0001). Lastly, VAT PAI1 expression was 2.4 ± 0.02 in C vs 35.0 ± 4.3 in HT (p < 0.0001), and SAT PAI1 expression was 2.3 ± 0.03 in C vs 19.0 ± 2.4 in HT (p < 0.0001). IL6 pl-lev was 2.5 ± 0.2 in C vs 5.4 ± 0.5 pg/mL in HT, p < 0.0001, while TGFβ plasma levels did not differ (19.0 ± 1.3 vs 20.7 ± 1.4 ng/mL). PAI1 plasma levels was 49.0 ± 1.4 in HT vs 27.7 ± 1.8 ng/mL in C, p < 0.0001. In the whole dataset, VAT IL6 expression was directly related with systolic and diastolic blood pressure values, and pressure levels were inversely related to VAT and SAT MMP2 and MMP9 act.

Conclusions: Untreated HT show a peculiar expression pattern of MMP/TIMP and inflammatory molecules in ADP: MMP2, TIMP1, TIMP2 and TGFβ expression and act are markedly reduced, while PAI1 and IL6 expression are increased, as reflected by plasma levels. These results support an important role for SAT and VAT in sustaining a pro-inflammatory and pro-thrombotic state in lean HT patients.

1.8 Assessment of Vascular Changes in Patients with Apolipoprotein A-I Amyloidosis (LEU75PRO)

M.L. Muiesan,¹ M. Salvetti,¹ A. Paini,¹ E. Belotti,¹ C. Agabiti Rosei,¹ C. Aggiusti,¹ C. Monteduro,¹ A. Negrinelli,² L. Calabresi,³ G. Franceschini,³ L. Obici,⁴ G. Gregorini,² G. Cancarini² and E. Agabiti Rosei¹

1 Clinica Medica, Università di Brescia, Brescia, Italy; 2 Nefrologia, Università di Brescia, Brescia, Italy; 3 Centro Grossi Paoletti, Università di Milan, Milan, Italy; 4 Centro per l’amiloidosi, Laboratori di Biotecnologia, Pavia, Italy

Introduction: Hereditary amyloidosis are late-onset autosomal dominant disorders characterized by amyloid deposition in various tissues. Among them, Apolipoprotein A-I amyloidosis (Leu75Pro) is a rare, autosomal dominant condition in which renal, hepatic, and testicular involvement has been demonstrated. No data are available on carotid artery structural changes in this condition, although other mutations of APO-AI lipoprotein have different (protective or favouring) effect on atherosclerosis.

Aim: To evaluate carotid artery structural alterations, as assessed by ultrasound, in patients with Apolipoprotein A-I amyloidosis (APO A-I amyloidosis).

Methods: In 104 patients with Apolipoprotein A-I amyloidosis (Leu75Pro) [mean age 52 ± 16 years, 56 F, 57% hypertensive patients] and in 104 subjects matched for age, sex, body mass index (BMI) and clinic blood pressure (BP), carotid artery intima media thickness (IMT) was measured by B-Mode ultrasound.

Results: By definition no differences were observed for age, sex, BMI, BP and heart rate. Mean common (CC), bifurcation (Bif) and internal carotid artery (ICA) IMT were comparable in the two groups (0.87 ± 0.21 vs 0.88 ± 0.17; 1.23 ± 0.41 vs 1.25 ± 0.38 and 0.95 ± 0.33 vs 0.95 ± 0.28 respectively for APO A-I amyloidosis vs controls, p = ns). Similar results were obtained for MeanMax IMT and T Max (1.02 ± 0.29 vs 1.03 ± 0.26 and 1.60 ± 0.69 vs 1.56 ± 0.58 p = ns).

Conclusions: Our data demonstrate that in patients with Apolipoprotein A-I amyloidosis (Leu75Pro) carotid artery intima media thickness is comparable to that of matched control subjects. These results, obtained in a wide sample of patients, may add significant information to the clinic features of this rare genetic disorder, possibly suggesting a protective effect on carotid atherosclerosis.

1.9 Does Low Salt Intake Influence Inflammation in Essential Hypertension?

D. Leonardis, S. Cutrupi, G. Tripepi, R. Tripepi, C. Zoccali and F. Mallamaci

CNR-IBIM & UO di Nefrologia, Reggio Calabria, Italy

Introduction: Salt is one of the main environmental ‘toxin’ involved in atherogenesis and in the high cardiovascular (CV) risk in atherogenesis-related diseases. Atherosclerosis is an inflammatory process and population based studies suggest that blood pressure is associated to inflammatory cytokines. The relationship between salt and inflammation is still controversial. In fact, observational studies showed a direct relationship between inflammation biomarkers and salt intake while interventional, not randomised studies did not show such an association.

Aim: Therefore, we analysed the relationship between salt intake and cytokines (pro-inflammatory cytokines TNF-alfa and IL-6 and the two main cytokines produced in the adipose tissue, Leptin and Adiponectin) in 32 patients with mild to moderate essential hypertension (mean age: 48 ± 8 years).

Methods: All patients underwent a high (200 mMol/d) or low (20 mMol/L) sodium diet in a randomized cross over design. Each diet lasted 1 week.

Results: Systolic (135 ± 9 mmHg vs 128 ± 9 mmHg) and diastolic pressure (86 ± 7 mmHg vs 84 ± 7 mmHg) decreased during the low salt diet (p < 0.005). As expected, there was an activation of the renin-angiotensin-aldosterone system during the low salt diet (PRA, median: 2.5 ng/mL/h vs 0.9 ng/mL/h; aldosterone, median: 119 pg/mL vs 49 pg/mL). Plasma ADPN significantly reduced (−16%) in low-sodium diet (48 ± 24 mg/mL) as compared to high sodium diet (57 ± 29 mg/mL) (p < 0.001). Changes in salt intake significantly reduced plasma TNFα (p = 0.003) but the reduction in circulating levels of this cytokine was clinically meaningless (low sodium: 2.5 ± 1.0 pg/mL vs high sodium: 2.3 ± 1.0 pg/mL). Changes in salt intake had no influence both on IL-6 (low sodium: 2.6 ± 2.2 pg/mL vs high sodium: 2.6 ± 1.9 pg/mL) and Leptin levels (7.7 ± 5.1 ng/mL vs 7.4 ± 5.2 ng/mL). Multiple regression analysis (data adjusted for age and sex) showed that ADPN changes were largely independent of concomitant blood pressure variations.

Conclusions: In the mid term, independently from blood pressure variations, low sodium diet decreases plasma adiponectin levels, a cytokine with important anti-inflammatory properties, and seems to have very little effect on pro-inflammatory cytokines. These findings indicate that in essential hypertensive patients the beneficial effect of low sodium diet on CV risk does not seem to be dependent on the attenuation of systemic inflammation and would suggest that reduced levels of adiponectin observed at low salt intake, could decrease the beneficial effect of this not pharmacological treatment.

1.10 Cigarette Smoking and Inflammation: Gene-Environment Interaction in the Development of Vascular Damage

M. Castellano, M.L. Muiesan, L. Mori, A. Orsini, M. Salvetti, M. Giacché, A. Panarotto, R. Tosini and E. Agabiti Rosei

Clinica Medica-Università di Brescia, Brescia, Italy

Introduction: Cigarette smoking is an independent cardiovascular risk factor and although its pathogenic mechanisms are not well understood, inflammatory pathway seems to play a pivotal role. In this context, it is possible that genetic variability of genes involved in leukotrienes synthesis may modulate the effects of smoking on the development of subclinic atherosclerotic damage.

Methods: We have examined about 600 individuals (Vobarno Study population), who have been characterized for traditional cardiovascular risk factors, including cigarette smoking. Vascular damage has been assessed as intima-media thickness (CB_max = mean maximum IMT of the 4 far walls in the distal common carotids and carotid bifurcations, bilaterally) and as the number of sites carrying atheromatic plaques, according to Mannheim criteria (AP-score). We have analyzed a 5-lipoxygenase promoter (5-ALOX) tandem-repeat polymorphism and 7 SNPs (SG13S25, S377, S114, S89, S32, S41 and S35) of the 5- lipoxygenase-activating protein (5-ALOX-AP); the 5-ALOX-AP haplotypes have been reconstructed by a Bayesian algorithm (software Phase 2.1). The association between atherosclerosis indexes and predictive variables, including genetic polymorphisms, has been assessed by univariate and multivariate analysis (SPSS 13.0).

Results: Among traditional risk factors, cigarette smoking is an important predictor of CBmax, particularly in men, but it is not significantly associated to AP-score, whose main predictor is age. At the univariate analysis, only 5-ALOX-AP S35 polymorphism revealed a statistically significant association with Cbmax (GG = 0.99 ± 0.01,GA = 0.92 ± 0.02,AA = 0.65 ± 0.08; p = 0.005) but it was not associated with AP (GG = 0.47 ± 0.04, GA = 0.46 ± 0.09, AA = 0.25 ± 0.25; NS). At the multivariate analysis S35 remained significantly associated with CB_max, and the pro-atherometous effect of the G allele was more evident in smokers than in non smokers (p = 0.05); after data correction for possible confounding factors, also haplotype A (G, T, G e A in S25, S114, S89 and S32 respectively) showed a statistically significant association with CBmax in smokers (p = 0.05). At multivariate analysis, homozygotes for the 5-repeat allele of the 5-ALOX promoter showed significantly lower CBmax values, both in smokers and in non smokers.

Conclusions: This study suggests that the pro-inflammatory action of cigarette smoke on vascular walls may be mediated, at least in part, by interaction with genetic variability in the leukotrienes synthesis pathway.

Blood Pressure Monitoring

2.1 Support to the General Practitioners Using an Integrated Platform of Telemedicine® for the Analysis of Ambulatory Blood Pressure Records

J.A. Octavio,¹ J. Contreras,¹ A. Cárdenas,¹ H. Matiz,² F. Cura,³ E. Escobar⁴ and F. Fernández⁴

1 ITMS Telemedicina de Venezuela, Caracas-Venezuela; 2 ITMS Telemedicina de Colombia, Bogotá-Columbia; 3 ITMS Telemedicina de Argentina, Buenos Aires, Argentina; 4 ITMS Telemedicina de Chile, Santiago, Chile

Introduction: Ambulatory Blood Pressure monitoring (ABPM) is a widespread tool for the study and control of arterial hypertension. However, its use is time consuming and requires trained personnel for a proper interpretation of results. It is also known that the care of the majority of hypertensive patients is assigned to general practitioners (GPs), working generally in ambulatories located far from the specialized centers. The alternative of transmission of records by phone or internet is gaining interest in many countries.

Methods: A web-based integrated platform of telemedicine (PIT®) has been developed and used by our group for 2 years, initially for the transmission of ECGs. In the last year, it was introduced in the PIT® a software for analysis of ABPM, which allows to return in the next hours the interpreted ABPM to the ambulatory centers. As the ABPM records arrive to a web page, the specialists can analyze the results from wherever they can have access to internet. For this practice, we have employed standards ABPM devices (Mobil-O-Graph®) connected to internet by means of a devote software, from where the trained GPs sends the study and all relevant information of the patients (Name, age, sex weight, height) and the blood pressure record (time of awaking and sleep, quality of sleep). The GPs can also inform about drugs taking by patients, pathological data etc.).

Results: Until now, we have used this approach in 20 public and private centers in the countries convolved in this project. In this period, we have received more than 15.000 ABPM records. The studies are interpreted and returned to the GPs the same day or at least the next day. Exceptionally (less than 0.5% of cases) the studies had been rejected by the specialized center because of poor quality of records and had been repeated. Since the software of interpretation calculates all the values relevant to the ABPM study, and allows electronically chose the different diagnostic possibilities, the interpretation by the specialist take only 2 or 3 minutes. The GPs receive the report with all the relevant tables, graphics and conclusions, signed by the specialist.

Conclusions: The use of PIT® allows the rapid interpretation of ABPMs in order to support the General Practitioner practice. Moreover, since with the same approach the GPs also obtain ECGs and recently in our centers, spirometric studies, the PIT® is providing an important database of the population and of individual patients included in this novel integrated platform.

2.2 Relationship of Morning Blood Pressure Surge with Cardiovascular Events and Total Mortality in a General Population

M. Bombelli,¹ H. Polo Friz,² L. Primitz,² E. Toso,¹ F. Ganz,¹ G. Pirovano,² F. Cicolari,² S. Buzzi,¹ D. Ferlicca,² D. Fodri,¹ V. Galbiati,² R. Facchetti,¹ G. Grassi,¹ R. Sega² and G. Mancia¹

1 Clinica Medica Università Studi Milan Bicocca, Monza, Italy; 2 Medicina Interna, Ospedale di Vimercate, Vimercate, Italy

Introduction: Cardiovascular (CV) events have their greatest prevalence in the morning period and are believed to be associated with and depending on morning surge in blood pressure (BP). However, direct evidence is limited.

Methods: In 2011 subjects of the PAMELA (Pressioni Arteriose Monitorate e Loro Associazioni) study randomly selected to be representative of the general population of Monza (MI, Italy) for gender and age decades (25–74 ys), we performed 24 hour ambulatory blood pressure (24 h BP) by a validated oscillometric device, set to obtain automatic measurements every 20 minutes. The morning BP surge (MBPS) was calculated as the average of the systolic (S) BP readings of the 2 hours after awake minus the average of the lowest SBP readings, the SBP reading immediately preceding and the one immediately following, during the night time. Spectral analysis of BP profile was performed to identify the main cyclic components of SBP variability (1° and 2° cyclic components of variability, respectively day night and post prandial variability), and residual, non-cyclic variability. Subjects were followed for an average of 148 months, during which CV events (fatal and non fatal) and all-cause deaths were recorded.

Results: MBPS was significantly correlated (p < 0.0001) with several other 24 h BP variables, i.e. 24 h mean SBP, day-night SBP difference and other cyclic and non-cyclic components of SBP variability, the correlation coefficients ranging from 0.24 to 0.47 (r values). During the follow up there were 231 all cause deaths and 178 CV events. MBPS showed a significant predictive relationship with the incidence of all cause death (p < 0.001), and with the incidence of CV events (p < 0.01). The significant relationship with all cause death and CV events, however, disappeared after adjustment for potential confounders such as age and other 24 h BP variables. Similar findings were obtained when another method to calculate the morning BP surge, such as the post and preawake BP difference, was used.

Conclusions: In the PAMELA population, MBPS reflects overall BP variability phenomena and does not appear to be an independent predictor of CV or all cause death risk.

2.3 Evaluation of the Blood Pressure and of the Cardiovascular Risk with Ambulatory Monitoring: Criteria Proposal

G. Malgieri,¹ M. Santoro,² R. Battista,² M. Ciaburri² and C. Santoro²

1 Centro per l’ipertensione-ASL BN1, CERRETO SANNITA, Italy; 2 U.O.C. Cardiologia-P.O. Maria Delle Grazie, Cerreto Sannita, Italy

Aim: To find a criteria and formula incorporating the entire range of information supplied by ambulatory blood pressure monitoring (ABPM) to avoid subjective interpretation and eliminate the incidence of the symphatic tone connected to physical activity and/or daily emotions and stratify the cardiovascular risk.

Methods: The results of 1708 ABPM tests were divided into 4 different groups: A-BP <130/80 mmHg; B-BP >130/80 mmHg; C-SBP >140 mmHg; D-SBP >150 mmHg. The mean, the standard deviation (SD), the confidence interval (CI) of the following were measured: the 24-hour mean arterial pressure (MAP), which also provides information about pulse pressure; the 24-hour mean Heart Rate (mHR), which is a recognized tool for measuring the cardiac autonomic activity; MAP/mHR, named normalization quotient (NQ); SD MAP/SD mHR, named Relationship of Variability (RV). A Pressure Index (PI) was obtained: NQ + (RV × 0.5), which, applied to group A has given the following Risk Equation (RE): 0.54 × NQ + (0.27 × RV) = 1.

Results: The main findings of our study are shown in the table. There is a significant difference in the data of the various groups except for HRm and age and a significant correlation between NQ, RV, PI means and the MAP means (r = 0.89, 0.85, and 0.87, respectively). A patient with MAP > 90 and NQ > 1.27 is hypertensive and with major risk if the result of RE is higher than 1, with moderate, severe risk, and values up to 1.14, 1.23 or higher, respectively. NQ < 1.26 identifies 537 patients in hypertensive groups that are not hypertensive, younger and with higher mHR (group E).

Conclusions: The PI incorporates the different information by the ABPM and avoids any interference from the sympathic tone. The RE formula also assesses cardiovascular risk.

2.4 Blood Pressure and Pulse Wave Velocity Values in the Institutionalized Elderly Aged 80 and Over: Baseline of the PARTAGE Study

P. Salvi,¹ F. Marino,² S. Buatois,¹ S. Capelli,³ F. Valbusa,⁴ F. Vaienti,³ S. Gautier,¹ D. Agnoletti,³ D. Dubail,⁵ O. Toulza,⁶ O. Hanon,⁵ A. Kearney-Schwartz,¹ C. Labat,¹ P. Manckoundia⁷ and A. Benetos¹

1 Dipartimento di Medicina Interna e Geriatria, Università di Nancy, INSERM U961, Nancy, France; 2 Dipartimento di Geriatria, Università di Verona, Verona, Italy; 3 Medicina Interna, Ospedale Bufalini, Cesena, Italy; 4 Ospedale s.Pellegrino, Castiglione delle Stiviere, Italy; 5 Ospedale geriatrico Broca, Paris, France; 6 CHU di Toulouse, Toulouse, France; 7 Dipartimento di Geriatria, Dijon, France

Introduction: In the report herein, we present the baseline data values of the PARTAGE study (Predictive values of blood pressure and arterial stiffness in institutionalized very aged population). The aim this longitudinal study was to determine the predictive value of blood pressure (BP) and arterial stiffness for overall mortality, major cardiovascular events and cognitive decline in a large population of institutionalized subjects aged 80 and over.

Methods: A total of 1130 subjects were recruited (878 women), living in French and Italian nursing homes. Clinic and 3-day self-measurements of BP were conducted. Central BP, as well as aortic and upper limb pulse wave velocity were obtained using a PulsePen tonometer.

Results: Of this population, 76% of women and 60% of men had a known hypertension and over 91% of the subjects were under antihypertensive treatment; 51% of the treated hypertensive patients were well controlled (systolic BP < 140 mmHg). No significant differences were found between clinic and self-measured BP. With age, there was an increase in peripheral (p < 0.001) as well as central (p = 0.005) pulse pressure due to a decrease in diastolic BP (p < 0.001), without any increase in systolic BP. Aortic but not peripheral pulse wave velocity significantly increased with age (p < 0.005).

Conclusions: Baseline values obtained herein demonstrate that elderly subjects living in nursing homes present hemodynamic characteristics which are different to those described in community-living elderly populations, and indicate the interest of assessing, in longitudinal studies, the role of BP and arterial stiffness in morbidity and mortality in this population.

2.5 The Normalization Quotient for Hypertension Diagnosis with Ambulatory Blood Pressure Monitoring

G. Malgieri,¹ M. Santoro,² R. Battista,² M. Ciaburri² and C. Santoro²

1 Centro per l’ipertensione-ASL BN1, Cerreto Sannita, Italy; 2 U.O.C. Cardiologia-P.O. Maria Delle Grazie, Cerreto Sannita, Italy

Introduction: The whole psychophysical stress which occurs during the ambulatory blood pressure monitoring (ABPM), leads to an increase of the symphatic tonus and to an increase of the recorded blood pressure (BP) as a consequence, and thus, to a wrong arterial hypertension diagnosis. It also entails an increase of the heart rate, that is recognized as a measure of the neuro-vegetative system.

Aim: To find an index in order to identify those patients who come out with a high arterial pressure after the ABPM, because of an increased symphatic tonus, but who aren’t hypertensive.

Methods: The reports of 1708 ABPM tests have been analyzed. Patients have been split into two groups: A. Normotensive patients with 24 hours average pressure values lower than or equal to 130/80 mmHg; B. Hypertensive patients with 24 hours average pressure values higher than 130/80 mmHg. The following measures have been calculated: the mean, the standard deviation, the confidence interval to 99%(CI) of the following data: 24-hour mean arterial pressure (MAP), 24-hour mean hearth rate (mHR), the relationship between MAP and mHR, which has been called Normalization Quotient (NQ), the relationship between the systolic blood pressure and the diastolic blood pressure (SBP/DBP).

Results: The main findings of our study are shown in the table. In Group B 312 patients have been identified with an NQ equal to or lower than the average of the one belonging to Group A (NQ = 1.26). Those patient formed Group E with significantly different features (p < 0001) from the other two groups. As matter of fact, they have a lower SBP/DBP and age, but a higher mHR.

Conclusions: The NQ represents the MAP (which provides information on the systolic, diastolic and pulse pressure) indexed for the mHR, that is to say for each heartbeat, removing in this way the influence of the symphatic tonus. By increasing the symphatic tonus and the mHR, the NQ decreases. Patients of Group E, with a low NQ relationship, have to be considered as normotensive.

2.6 Validation of the Automatic Device for Wrist Self-Measurement of Blood Pressure — The PIC Travel Check — According to the European Society of Hypertension Protocol

A. Caparra,¹ L. Valente,¹ L. Sperduti,¹ E. Mandylakis,¹ V. Pecchioli,¹ R. Asmar² and G. Germanò¹

1 Dipartimento di Geriatria, Università “Sapienza”, Rome, Italy; 2 Centro di Medicina Cardiovascolare, Parigi, France

Introduction: Current guidelines recommend that only validated devices for self-measurement of blood pressure (BP) should be used. This study presents the validation results of the PIC Travel Check (Artsana, Italy) monitor for self-measurement of BP, according to the European Society of Hypertension International Protocol (ESH). This device measures BP (range of 30–260 mmHg) using the oscillometric method at the wrist level.

Methods: The International validation Protocol is divided into 2 phases: the phase one (15 subjects and 45 pairs of BP measurements) and the phase 2 (18 supplementary subjects and 54 pairs of BP measurements) making a total number of 33 subjects (99 pairs of BP measurements) on which the final validation is performed. For each subject, 4 BP measurements were performed simultaneously by 2 trained observers using mercury sphygmomanometers alternately with 3 measurements by the tested device. The difference between the BP value given by the device and that obtained by the 2 observers (mean of the 2 observers) was calculated for each measure. The 99 pairs BP differences were classified into 3 categories (≤5, ≤10, ≤15 mmHg). The number of differences in each category was compared to the number required by the International Protocol.

Results: The 33 included subjects were (17M, 16F) aged of 54 ± 14 years (range: 30–79), wrist circumference 18 ± 2 cm (15–22 cm), mean BP = 146 ± 24/91 ± 14 mmHg. The average differences between the 2 observers were 0.5 ± 1.6 and 0.3 ± 1.8 mmHg for Systolic and diastolic BP. The average difference between the PIC Travel Check device and mercury sphygmomanometer readings were for systolic BP and diastolic BP respectively: −0.1 ± 2.0 and 0.6 ± 1.7 mmHg. Readings differing by less than 5, 10 and 15 mmHg for SBP and DBP values fulfil the recommendation criteria of the ESH Protocol. The tested device passed the first and the second phase of the validation protocol.

Conclusions: The wrist device for self-measurement of BP, the PIC Travel check, fulfilled the validation criteria of the ESH validation protocol.

2.7 Validation of the PIC Indolor Professional Check Device for Office Blood Pressure Measurement According to the European Society of Hypertension Protocol

A. Caparra,¹ L. Valente,¹ L. Sperduti,¹ E. Mandylakis,¹ V. Pecchioli,¹ R. Asmar² and G. Germanò¹

1 Dipartimento di Geriatria, Università “Sapienza”, Rome, Italy; 2 Centro di Medicina Cardiovascolare, Parigi, France

Introduction: Current guidelines recommend that only validated and mercury-free devices for office blood pressure (BP) measurement should be used. This study presents the validation results of the PIC-indolor Professional Check (Artsana, Italy) device for office BP measurement, according to the European Society of Hypertension (ESH) International Protocol. This device consists of a mercury-free pressure gauge with bar LCD, inflatable cuff and inflation bulb for auscultatory BP measurement.

Methods: The International validation Protocol is divided into 2 phases: the phase one (15 subjects and 45 pairs of BP measurements) and the phase 2 (18 supplementary subjects and 54 pairs of BP measurements) making a total number of 33 subjects (99 pairs of BP measurements) on which the final validation is performed. For each subject, 4 BP measurements were performed simultaneously by 2 trained observers using mercury sphygmomanometers alternately with 3 measurements by the tested device. The difference between the BP value given by the device and that obtained by the 2 observers (mean of the 2 observers) was calculated for each measure. The 99 pairs BP differences were classified into 3 categories (≤5, ≤10, ≤15 mmHg). The number of differences in each category was compared to the number required by the International Protocol

Results: The 33 included subjects were (16M, 17F) aged of 56 ± 14 years (range: 31–75), with mean arm circumference 29 ± 4 cm (range 24–37 cm) and mean BP 147 ± 22/92 ± 15 mmHg. The average differences between the 2 observers were 0.6 ± 1.8 and 0.5 ± 1.8 mmHg for Systolic and diastolic BP. The average difference between the PIC Professional Check device and mercury sphygmomanometer readings were for systolic BP and diastolic BP respectively: −0.6 ± 1.7 and −0.4 ± 1.5 mmHg. Readings differing by less than 5, 10 and 15 mmHg for SBP and DBP values fulfil the recommendation criteria of the ESH Protocol. The tested device passed the first and the second phase of the validation protocol.

Conclusions: The Professional ‘hybrid’ mercury-free device for office BP measurements, the PIC Professional check, fulfilled the validation criteria of the ESH validation protocol.

2.8 Validation of Three Automatic Devices Self-Measurement of Brachial Blood Pressure According to the European Society of Hypertension Protocol: The PIC-Indolor Personal Check, the PIC-Indolor Comfort Check and the PIC-Indolor My Check

L. Valente,¹ A. Caparra,¹ A.I. La Ruina,¹ E. Mandylakis,¹ V. Pecchioli,¹ R. Asmar² and G. Germanò¹

1 Dipartimento di Geriatria, Università “Sapienza”, Rome, Italy; 2 Centro di Medicina Cardiovascolare, Parigi, France

Introduction: Three electronic devices for self-measurement of blood pressure (BP) at the brachial level — the PIC-indolor Personal check, the PIC-indolor Comfort check and the PIC-indolor My check (Artsana, Italy) — were evaluated in 3 separate studies according to the International Protocol of the European Society of Hypertension (ESH). All devices record BP using the oscillometric method with a BP range of 30–260 mmHg and heart rate range of 40–199 beats/min. Among the three devices, the PIC-indolor Comfort check uses a pre-formed cuff designed to improve the compliance of the patient, it is easier to be wrapped around the arm because of a special preformed shape.

Methods: The International validation Protocol is divided into 2 phases: the phase one (15 subjects and 45 pairs of BP measurements) and the phase 2 (18 supplementary subjects and 54 pairs of BP measurements) making a total number of 33 subjects (99 pairs of BP measurements) on which the final validation is performed. The same methodology was applied for the 3 studies. In each study and for each subject, 4 BP measurements were performed simultaneously by 2 trained observers using mercury sphygmomanometers alternately with 3 measurements by the tested device. The difference between the BP value given by the device and that obtained by the 2 observers (mean of the 2 observers) was calculated for each measure. The 99 pairs BP differences were classified into 3 categories (≤5, ≤10, ≤15 mmHg). The number of differences in each category was compared to the number required by the ESH Protocol.

Results: The 3 tested devices passed the first and the second phase of the validation protocol. The average differences between the device and mercury sphygmomanometer readings were for Systolic BP and Diastolic BP respectively: 0.1 ± 2.9 and −0.1 ± 3.8 mmHg for the PIC-indolor Personal check, −1.0 ± 3.7 and 0.2 ± 3.2 mmHg for the PIC-indolor Comfort check; −0.6 ± 4.5 and −1.5 ± 4.3 mmHg for the PIC-indolor My check. For the 3 devices, readings differing by less than 5, 10 and 15 mmHg for SBP and DBP values fulfil the recommendation criteria of the ESH Protocol.

Conclusions: The PIC-indolor Personal check, the PIC-indolor Comfort check and the PIC-indolor My check (Artsana, Italy) devices for self-measurement of brachial BP fulfilled the validation protocol of the ESH.

2.9 Effect of Lactotri-Peptides Extracted from Lactobacillus helveticum on Ambulatory and 24-Hour Blood Pressure in Subjects with Normal or Normal-High Blood Pressure: a Cross-Over, Double-Blind, Randomized, Clinic Trial

A.F.G. Cicero, M. Rosticci, E. Grandi, M. Giovannini, S. Bacchelli, E. Strocchi, M. Veronesi and C. Borghi

Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Università di Bologna, Bologna, Italy

Introduction: In small Finnish and Japanese clinic trials, Lactotripeptides extracted from Lactobacillus helveticum (Ile-Pro-Pro/Val-Pro-Pro) have shown to have a mild antihypertensive effect, maybe related to an ACE-inhibitor activity and/or to induction of NO synthesis by the endothelium.

Aim: the aim of our study was to evaluate the effect of the dietary supplementation of that lactotripeptides on Mediterranean subjects with normal or normal-high blood pressure.

Methods: We have planned a cross-over, double-blind, randomized clinic trial. The 50 volunteers had to drink 1 fruit juice added with the lactotripeptides or with a placebo powder (250 ml b.i.d.), beginning with the active product or the inactive one, in two consecutive periods separated by a 28 day wash-out. Ambulatory blood pressure was evaluated by a standard sphygmomanometer, while the 24 hour one by an automatic ABPM measure; moreover, the plasma renin activity, plasma lipids, fasting plasma glucose and renal and liver markers have been dosed.

Results: The preliminary results of the study (evaluated on the 75% of patients who concluded the study) show how in the active treatment phases it can be observed a significant or nearly significant change in the following parameters:

• percentage of 24 hour diastolic blood pressure records over the normal: Reduction from 29 ± 24% to 23 ± 20% (p = 0.03);

• daytime systolic blood pressure: Reduction from 128 ± 12 to 125 ± 12 mmHg (p = 0.05);

• daytime diastolic blood pressure: Reduction from 80 ± 9 to 78 ± 9 mmHg (p = 0.06);

• daytime mean blood pressure: Reduction from 97 ± 10 to 94 ± 10 mmHg (p = 0.04);

• percentage of day diastolic blood pressure records over the normal: Reduction from 35 ± 28% to 28 ± 24% (p = 0.04).

No significant change in plasma renin activity has been observed, so probably the antihypertensive effect of lactotritpeptide is no related to the ACE-inhibition activity. No significant change in glycaemia, plasma lipids, nor liver and kidney parameters has been observed. The treatment has been generally well tolerated (1 dyspepsia, 1 gastroesophageal reflux), but compliance was imitated (70%) and this could have partly reduced the entity of the observed results.

Conclusions: The daily use of fruit juices added in lactotripeptides extracted from L. helveticum seem to positively modulate day blood pressure in healthy subjects or patients with normal-high blood pressure.

2.10 Effects of Angiotensin Receptor Antagonism by Telmisartan on Ambulatory Blood Pressure Response to High Altitude Exposure — the HIGHCARE2008 Project

G. Bilo,¹ B. Bilo,² G. Caldara,² A. Faini,¹ A. Giuliano,¹ F. Gregorini,¹ C. Lombardi,¹ M. Revera,¹ K. Styczkiewicz,³ G. Mancia¹ and G. Parati¹ on behalf of ricercatori HIGHCARE (HIGH altitude CArdiovascular REsearch)

1 Univ. Milano-Bicocca, Istituto Auxologico Italiano IRCCS, Milan, Italy; 2 Istituto Auxologico Italiano, Milan, Italy; 3 I Department of Cardiology and Hypertension, Jagiellonian University, Cracovia, Poland

Introduction: Exposure to hypobaric hypoxia at high altitude is responsible for cardiovascular and metabolic changes that may simulate the effects of chronic pathological conditions such as obesity related hypertension. These include increase in blood pressure (BP) associated with an increase in sympathetic activity, while contradictory data were reported on the role of renin-angiotensin-aldosterone system (RAAS) activation in determining such BP changes. Aim of this study was to assess changes in ambulatory BP under acute and prolonged high altitude exposure in subjects receiving the angiotensin II blocker telmisartan or placebo.

Methods: Forty-seven healthy normotensive volunteers were randomized in double blind fashion to receive telmisartan 80 mg once daily (TE) or placebo (PL). Out of them 38 subjects (age 39.0 ± 10.4, 25 M, 13 F, BMI 22.5 ± 2.8 kg/m2), in whom complete and good quality ambulatory BP monitoring (ABPM) data were available, were included in the present analysis. ABPM was performed with Spacelabs 90207 and 90217 devices:

1. at sea level off treatment (SLoff);

2. at SL after 6 weeks of treatment (SLtx);

3. during acute (1–3 days) exposure to altitude of 3500 m a.s.l. (Ac);

4. 1–3 days after ascent to Everest Base Camp at 5400 m a.s.l. (BC1);

5. after 7–9 days’ permanence at Base Camp (BC2);

6. within 5 days after return to SL (SLret) still on treatment.

Results: 24-hour average systolic (S) and diastolic (D) BP values ±SE for each condition are shown in the table. Similar patterns were found also for daytime and night-time BP. Renin and angiotensin II plasma levels for each condition are currently under assessment.

2.11 Effects of High Altitude Exposure on 24-Hour Ambulatory Blood Pressure — the HIGHCARE2008 Project

G. Bilo,¹ B. Bilo,² G. Caldara,² A. Faini,¹ A. Giuliano,¹ F. Gregorini,¹ C. Lombardi,¹ M. Revera,¹ K. Styczkiewicz,³ G. Mancia¹ and G. Parati¹

1 Univ. Milano-Bicocca, Istituto Auxologico It IRCCS, Milan, Italy; 2 Istituto Auxologico Italiano, Milan, Italy; 3 I Department of Cardiology and Hypertension, Jagiellonian University, Cracovia, Poland

Introduction: Exposure to hypobaric hypoxia at high altitude is responsible for cardiovascular and metabolic changes that may simulate the effects of chronic pathological conditions such as obesity related hypertension. These include increase in blood pressure (BP), as previously reported on the basis of spot conventional measurements mostly obtained under acute altitude exposure, while the possible occurrence of acute changes in 24 h BP profile and their time course under prolonged permanence at high altitude are still largely unknown.

Aim: To assess changes in 24-hour ambulatory BP in response to acute and prolonged high altitude exposure in the Himalaya region.

Methods: In 21 healthy, normotensive volunteers (age 37.6 ± 9.5, 14 M, 7 F, BMI 21.7 ± 2.4 kg/m²) participating in HIGHCARE project and not receiving any active treatment, 24-hour ambulatory BP monitoring (ABPM) was performed with Spacelabs 90207 and 90217 devices:

1. at sea level (SLbas);

2. during acute (1–3 days) exposure to altitude of 3500 m a.s.l. (Ac);

3. 1–3 days after ascent to Everest Base Camp at 5400 m a.s.l. (BC1);

4. after 7–9 days’ permanence at Base Camp (BC2);

5. within 5 days after return to sea level (SLret).

Results: Average systolic (S) and diastolic (D) BP values as well as heart rate (HR) for 24 hours day and night are shown in the table [p (ANOVA) always <0.001 between SL and altitude conditions].

Conclusions: Ambulatory BP shows a sustained increase over 24 h under high altitude hypoxia, roughly proportional to the altitude reached, with no significant attenuation under prolonged permanence at very high altitude. At very high altitude BP rise was particularly pronounced at night leading to a more flat 24-hour BP profile. BP values returned to baseline immediately after return to sea level. These data may have implications for the management of subjects exposed to high altitude hypoxia because of either work or leisure. They may also be relevant to the management of BP changes in patients with diseases combined with chronic hypoxemia.

2.12 Accuracy of Different Types of Blood Pressure Measuring Devices at High and Very High Altitude — Evidence from the HIGHCARE2008 Project

G. Parati,¹ G. Bilo,¹ G. Caldara,² A. Faini,¹ A. Giuliano,² F. Gregorini,¹ C. Lombardi,¹ M. Revera,¹ K. Styczkiewicz³ and G. Mancia¹ on behalf of ricercatori HIGHCARE (HIGH altitude CArdiovascular REsearch)

1 Univ. Milano-Bicocca, Istituto Auxologico It IRCCS, Milan, Italy; 2 Istituto Auxologico Italiano, Milan, Italy; 3 I Department of Cardiology and Hypertension, Jagiellonian University, Cracovia, Poland

Introduction: Blood pressure (BP) appears to increase at high altitude, probably due to hypoxia induced sympathetic activation. Proper assessment of this phenomenon may however be prevented by the fact that, at high altitude-induced low barometric pressure, some BP measuring devices may become inaccurate.

Aim: To cross-check the values provided by three different types of BP measuring devices at high and very high altitude, taking the mercury manometer as the standard reference.

Methods: In 43 healthy, normotensive volunteers (age 39.9 ± 10, 29 M, 14 F) participating in the HIGHCARE2008 project, duplicate BP measurements were obtained in random order with mercury (MER), aneroid (ANE) and the validated oscillometric Microlife BP A100 Plus device (OSC) at Namche Bazaar (NB, 3400 m a.s.l.) and at Mt. Everest Base Camp (BC, 5400 m a.s.l.), after demonstration that, at sea level, no significant BP difference could be observed between MER and either ANE or OSC.

Results: At NB mean BP measured by MER, ANE and OSC device was, respectively: 124.1 ± 13.4, 121.1 ± 11.5 and 124.4 ± 16.2 mmHg for systolic and 82.6 ± 10.7, 80.7 ± 9.3 and 80.8 ± 12.6 mmHg for diastolic BP (all differences NS). At BC it was 128.1 ± 11.6, 123.2 ± 12.6 and 128.5 ± 11.4 mmHg for systolic (p < 0.001 for ANE vs. both MER and OSC) and 85.7 ± 9.3, 81.7 ± 10.8 and 84.4 ± 9.6 mmHg for diastolic BP (p < 0.001 for ANE vs MER). Correlation coefficients (r) between BP measured by MER device and the other two devices as well as percentages of ANE and OSC BP values falling within ±5 mmHg of BP measured with mercury device are shown in the table.

Conclusions: When BP measurement with a mercury sphygmomanometer is taken as a reference, both calibrated aneroid and oscillometric devices have acceptable precision at high altitude. The accuracy of aneroid devices is reduced at very high altitudes due to an underestimation of both systolic and diastolic BP, while the oscillometric device used in this study remained reasonably accurate. These data have practical implications for accurate BP measurements also in people leaving at high altitude.

2.13 The Expert Nurse in Chronic Care Model Arterial Hypertension: a Step into Management Assistance

S. Lenti,¹ P. Corradini,² P. Monaco,³ V. Cincinelli³ and C. Frigerio¹

1 Ospedale San Donato USL 8 Arezzo, Arezzo, Italy; 2 Medicina Interna USL9, Casteldelpiano, Italy; 3 Corso di Laurea Infermieristica, Arezzo, Italy

Introduction: The Nurse plays a key role in the Chronic Care Model of arterial hypertension, as it integrates into care model as the best expert in counselling for a better empowerment in reducing cardiovascular risk.

Methods: On the Base of these premises it was formed a Nurse to evaluate the pressure load, the management of clinic measurement of Blood Pressure BP) and of self-measurement, through training and monitoring of therapeutic compliance of the patient and, through focus group, has explored and delineated the risk factors and appropriate lifestyle.

Results: In one month there were enrolled 120 patients with arterial hypertension, 51% Men and 49% Women, with an average age of 62 years: it was collected all the data concerning on the habits of life, and the associated risk factors, it was measured the clinic BP and administered questionnaires about quality of life and self-measurement methods. Then, in random they were divided into 2 groups of 60 patients: control (53% women and 47% men, 60-year average) and experimental (46% women and 54% men, 63-year average). Only the experimental group was given training, once a month, with focus groups made of workshop lesson. After 3 months all the 120 patients were subjected to a post-test. The control group has not changed its life style, 42% has gone to the doctor because of pressure increases, has measured the BP once a month and has obtained 40% of therapeutic change, although 60% consider hypertension a serious illness. While the experimental group has correctly measured the BP once a week, with 3 measurements in each session, has not produced pharmacological shifts, 40% had stopped smoking, 39% performed regular physical activity, 48% takes more vegetables and less sugar, 26% had decreased by 7 kg his body weight and has not even once gone to his doctor because of pressure increases. Finally all patients proved to be willing to continue this type of educational strategy.

Conclusions: Our pilot study aimed at demonstrating how the model of 3 actors integrated assistance necessarily takes to better empowerment of health education, besides the figure of the Doctor, it’s the Nurse who mainly manages the training and education of the patient, who, in turn, becomes ‘expert’ in managing on his own his health, obtaining a proper certification. All this could lead to an improvement in the system efficiency including economic and health side for an appropriate use of medications and operations.

2.14 Field Testing Results for a New Blood Pressure Measuring Device Satisfying WHO Criteria for Use in Low Resource Settings

G. Parati,¹ M. Ochan Kilama,² A. Faini,¹ E. Facelli,³ S. Mendis⁴ and E. O’Brien⁵

1 Univ. Milano-Bicocca, Istituto Auxologico It IRCCS, Milan, Italy; 2 Medical Department, Benedict Medical Center, Kampala, Uganda; 3 Mtendere Hospital, Chirundu, Zambia; 4 Cardiovascular Diseases Dept, WHO, Geneva, Switzerland; 5 University College Dublin, Belfield, Dublin, Ireland

Introduction: High blood pressure (BP) prevalence is increasing in low resource settings (LRS) like Africa, while BP monitoring and treatment remain poor. A major problem in LRS is unavailability of reliable, durable and affordable BP measuring devices, in particular facing withdrawal of mercury sphygmomanometers (M). A WHO expert committee defined the features of BP measuring devices suitable to LRS. One device (OMRON M1 Plus, OM1) fulfilling these criteria (including low cost) was recently validated using the ESH Protocol.

Aim: To assess the usability, acceptability and accuracy of OM1 under field conditions in LRS.

Methods: The study was conducted in three centers in two African countries (Uganda: Benedict Medical Center in Kampala and Lacor Hospital; and Zambia: Mtendere Hospital, Chirundu). A total of 716 subjects (aged 15–75 years), consecutively attending these centres for various medical problems, were recruited after obtaining informed consent. In each subject BP measurements were performed 4 times within 8 min: twice with OM1 and twice with M, according to ESH guidelines in a randomized sequential order. At each centre two trained physicians or nurses performed device evaluation, BP measurement, clinic and demographic data collection.

Results: 700 subjects with no violations in data collection protocol were included in this study (35 ± 14 years old, 58% female, 97% being of African race, BMI 24.6 ± 5 kg/m2). Average waist circumference and heart rate were 86.7 ± 12.6 cm and 74.6 ± 11.6 b/min, respectively. As compared to M, OM1 was rated as ‘good’ in 82% and as ‘preferred’ in 95.1% of cases, mainly because of its easy use and the availability of automated measures (84.6%) and solar power (79.1%). OM1 was also found more comfortable to use (69.3%), while M was subjectively felt as more durable in 29.6% of cases. Concerning OM1 performance, the display was found clearly legible in 98%, the cuff appropriately inflating and deflating in 96.7% and the on/off switch correctly working in 98.3% of cases. Average systolic (S)/diastolic(D) BP were 120.5 ± 21.6/74.6 ± 13.8 and 122.3 ± 21.8/71.2 ± 14.0 mmHg with M and OM1, respectively (NS). 20% of subjects were classified as hypertensive with M and 18.9% with OM1, the between-device agreement in defining subjects’ BP status being 93.7%, as confirmed by Bland-Altman plots, mainly for SBP.

Conclusions: The results of our field testing confirm in a LRS the accuracy of OM1, previously shown in laboratory conditions. The field test demonstrates, moreover, that OM1 was well accepted by health care givers and patients and was found easy and practical to use. Considering its low cost, the new OM1 is likely to prove a suitable and reliable device to improve the diagnosis and management of hypertension in LRS.

2.15 Sleep Efficacy, but not Supposed Sleep Duration, is Associated to Microvascular Damage in Mild Hypertensive Patients

P. Nazzaro,¹ G. Schirosi,¹ G. Grandolfo,¹ V. Lucivero,¹ M. Petruzzellis,¹ V. Vulpis² and F. Federico¹

1 DipartimentoScienze Neurologiche e Psichiatriche, Stroke Unit, Univerità di Bari, Bari, Italy; 2 Medicina Generale, Policlinico Consorziale, Bari, Italy

Introduction: The impact of sleep on blood pressure circadian rhythm, although difficult to identify, has been largely demonstrated by the association between vascular damage and reduced blood pressure nocturnal fall (BPNF).

Aim: To recognize the impact of duration and efficacy of the ‘real sleep’ on the microcirculatory vascular damage.

Methods: By means of medical visit (off), ambulatory blood pressure monitoring and simultaneous actigraphy we identify duration (min) of nocturnal sleep as ‘real sleep’, recognizable by the severe reduction of energy expenditure in recumbent position (SLEEP), its efficacy (SLEEP%), recognizable for a further fall in muscular tone during SLEEP and the individualized BPNF (PER = ‘awake-real sleep’) were calculated in 70 treated males hypertensive patients (133 ± 3/81 ± 2 mmHg) distinguished in order of higher (H-) or lower (L-) SLEEP%. Then, they underwent videocapillaroscopy of periungueal, phalangeal and forearm skin of the non-dominant arm to determine basal capillarity (CAP) and, by venous congestion, maximized (CVC) and recruited secondary capillarity (GAIN), as indices of structural and functional microvascular damage.

Results: History of hypertension, metabolic and anthropometric assessment were similar but significant differences (m ± s.e: *p < 0.05, **p < 0.01, ***p < 0.001 vs H-SLEEP%) in capillarity occurred, as shown in the table. Pearson analysis, adjusted for smoke, age, metabolic and anthropometric assessment, showed that SLEEP% is associated to CAP (0.383*),CVC(0.547***) e GAIN (0.418**). The microcirculatory indices were not related to SLEEP.

Conclusions: The findings show that the reduced nocturnal sleep efficacy, more than its duration, may increase the structural microcirculatory damage even those hypertensive patients apparently controlled by the therapy.

2.16 The ‘See and Treat’ Model for the Clinical Management of Asymptomatic Blood Pressure Increase

S. Lenti,¹ P. Corradini,² S. Pietrelli,¹ G. Pinna,³ C. Pascale,³ A. Donati,⁴ S. Fatucchi⁴ and G. Iannelli¹

1 Medicina d’Urgenza Ospedale San Donato USL8, Arezzo, Italy; 2 Medicina Interna USL9, Casteldelpiano, Italy; 3 Medicina Interna Ospedale Cottolengo, Torino, Italy; 4 Università degli Studi, Firenze, Italy

Introduction: The Tuscan Region approved, in 2008, an experimental model of ‘See and Treat’ in First Aid in the field of health emergency which creates the basis for the reorganization of low priority codes care and which introduces nursing figures trained and experienced in the treatment of a number of diseases in order to reduce waiting times. The asymptomatic blood pressure increases, representing approximately 10% of access to emergency room have been included in the regional act as appropriate to the minor emergency treatment area See and Treat.

Aim: To evaluate the applicability of this model on the treatment, from See and Treat area the doctor and the nurse figures, of asymptomatic pressure increases in a population of citizens who arrived at the emergency room.

Methods: In 3 months, 284 patients have been (153 M and 131 M, with an average age of 64.5 years) who had 160/120 mmHg Blood Pressure (BP), and who have been divided in random into 2 groups: the group control treated by the doctor and the experimental group treated by the nurses in the same area of See and Treat. After a period of 10 minutes of relaxation, in all patients it was measured the clinic BP in a sitting position (3 measurements at a distance of 2 minutes), and it was personal and pharmacological case; no patient reported associated symptoms.

Results: In the control group we obtained a reduction in average blood pressure to 148/90 mmHg in 62% of patients, while in the remaining 38% (54 patients) the values of PA were >160/120 mmHg. In the experimental group, instead 88% of patients had a reduction in average blood pressure to 144/84 mmHg, while only 12% (17 patients) did not present significant reduction. Therefore among 284 patients, only 25% (71 patients) needed further doctor study.

Conclusions: Our pilot study aimed at confirming the well-known almost complete absence of the white coat effect in the case of measurements from the nurse figure, but mainly wanted to point our how the use of the See and Treat from a properly trained nurse was able to reduce waiting times in low priority codes, identifying the See and Treat as an effective assistance response regarding asymptomatic pressure increases, in order to improve the perceived quality and granting a prompt medical/nursing response by the immediate take-over of the patient. The See and Treat model obviously requires an accurate and complete scientific professional and medico-legal definition.

2.17 The Microvascular Damage is Associated to the Blood Pressure during the Recognized Wakeful Resting Phases in Grade 1 Hypertensive Patients

P. Nazzaro,¹ G. Schirosi,¹ G. Grandolfo,¹ V. Vulpis,² V. Lucivero,¹ D. Mezzapesa,¹ M. Catalano¹ and F. Federico¹

1 DipartimentoScienze Neurologiche e Psichiatriche -Stroke Unit- Univerità di Bari, Bari, Italy; 2 Medicina Generale-Policlinico Consorziale, Bari, Italy

Introduction: Capillary rarefaction was recognized since early phases of hypertension. This is also associate to blood pressure variability during wakeful hours, in particular.

Aim: To identify the blood pressure level reached during different activities and their influence on microvascular damage.

Methods: Seventy treated hypertensive patients (143 ± 2/88 ± 3 mmHg), with similar metabolic and anthropometric assessment, underwent medical visit (off) and videocapillaroscopy of periungueal, phalangeal and forearm skin of the non-dominant arm to determine basal capillarity (CAP) and, by venous congestion, maximized (CVC) and recruited secondary capillarity (GAIN), as indices of structural and functional microvascular damage. Then, they were divided in subjects with lower (L-) and higher (H-) microvascular damage (MSD). The carotid intima-media thickness (IMT) served as index of pre-clinic macrovascular damage. By ABPM, activity diary and simultaneous actigraphy, measuring muscular tone and energy expenditure (METs), waking (AWA) and sleeping (SLE) phase, working (WRK) and extra-working (EWRK) time, time at home (HOM) and during relax (RLX), as resting wakeful time with scarce muscular activity (<3 METs), were identified.

Results: The main findings of our study are shown in the table (data are expressed as mean ± SE. *p < 0.05, **p < 0.01, ***p < 0.001 vs L-MSD) Pearson analysis, adjusted for age, smoke anthropometric and metabolic assessment, showed inverse association between CVC and SBP-EWRK (−0.254**) and SBP-RLX (−0.259***).

Conclusions: The results show that the structural and functional microvascular damage may be increased, before the onset of the preclinic macrovascular damage, by the scarce ability to reduce blood pressure during the low energy expenditure in wakeful hours even in hypertensive patients satisfactorily controlled for blood pressure.

2.18 Short-Term Blood Pressure Variability is an Independent Predictor of Large-Artery Stiffness

G. Schillaci, G. Pucci, M. Pirro, M.R. Mannarino, R. Hijazi, S. Innocente and E. Mannarino

Università di Perugia, Perugia, Italy

Introduction: Aortic stiffness, a prognostically adverse early noninvasive marker of arteriosclerosis, is strongly affected by blood pressure (BP). Increasing evidence suggests a link between short-term BP variability and cardiovascular complications in hypertension, but the effects of BP variability on large-artery stiffness are understudied.

Methods: 540 consecutive untreated patients with uncomplicated essential hypertension (59% men, BP 151/94 ± 16/10 mmHg) underwent determination of carotid-to-femoral pulse wave velocity (cfPWV), an accurate and reproducible index of aortic stiffness, by high-fidelity applanation tonometry (SphygmoCor), and 24-hour ambulatory BP monitoring with a validated oscillometric device (SpaceLabs 90207, 1 reading every 15 min for 24 hours). The standard deviation of daytime and night time systolic BP (SBP) was taken as a measure of short-term BP variability.

Results: The standard deviation of daytime and night-time SBP (r = 0.18/0.18; both p < 0.001), but not of diastolic BP, showed a significant correlation with cfPWV. Since the standard deviation of daytime SBP showed a direct association with average daytime SBP (r = 0.26), subjects were ranked into sex-specific quartiles of the distribution of daytime SBP. For each quartile, the subjects with standard deviation of daytime (and night-time) SBP below or above the median were classified at low or high BP variability. cfPWV was 9.3 ± 2 and 9.8 ± 2 m/s in the subjects at low and high daytime SBP variability (p = 0.02), and 9.3 ± 2 and 9.9 ± 2 m/s in the subjects at low and high night-time SBP variability (p = 0.07). In a multivariate linear regression model, the standard deviation of daytime SBP was cfPWV was an independent predictor of cfPWV together with age, sex, average daytime SBP, and cigarette smoking.

Conclusions: After taking into account the confounding effect of average BP, age and several other risk factors, BP variability assessed with noninvasive monitoring is independently related to aortic stiffness in hypertension.

2.19 Blood Pressure Control and Variability: Differences between Diabetic and Non-Diabetic Patients Undergoing Ambulatory Blood Pressure Monitoring

G. Ferraro, G. Palmieri, F. Colombo and A.M. Agrati

Ospedale Niguarda Cà Granda, Milan, Italy

Introduction: Diabetes mellitus increases cardiovascular risk connected with hypertension; for this reason guidelines recommend tight blood pressure control in diabetic patients. We analyzed diabetic patients undergoing ambulatory blood pressure monitoring (ABPM) in order to evaluate their 24 hr BP control and variability in comparison with a non diabetic population.

Methods: In our database of 6543 subjects undergoing ABPM (January 1998 to November 2008) we identified 1209 type 2 diabetic subjects according to the fact that they were treated with glucose lowering drugs (whether oral or insulin) and/or the answer to the question “are you diabetic?” 136 patients receiving only insulin were not taken into account because the exact type of diabetes could not be correctly detailed. We evaluated the percentages of patients with a 24 hr BP <125/80 in relation to the number of antihypertensive drugs (from 0 to 5 or more); results were compared with a non diabetic population undergoing ABPM in the same period of time. We also considered the prevalence of the morning surge phenomenon (mean systolic blood pressure in the hour after awakening — minimum systolic pressure in the night), 24 hours blood pressure variability and the dipper/non-dipper percentages.

Results: The table reports data from our study population.

Conclusions: Our data support the fact that the percentage of good 24 hr BP control is lower in the diabetic population in spite of a higher number of drugs used in these subjects. A higher BP variability can be identified in this population and this can partially explain their overall higher cardiovascular risk.

2.20 Human Immunodeficiency Virus (HIV) Infection and Attenuated Day-Night Blood Pressure Rhythm

G. Schillaci,¹ G. Pucci,¹ R. Hijazi,¹ C. Martinelli,² T. Quirino,³ P. Bonfanti⁴ and G.V. De Socio¹

1 Università di Perugia, Perugia, Italy; 2 Ospedale Careggi, Firenze, Italy; 3 Ospedale di Busto Arsizio, Busto Arsizio, Italy; 4 Ospedale “L. Sacco”,Milan, Italy

Introduction: An attenuated day-night blood pressure (BP) reduction is an important predictor of cardiovascular events and death. HIV infection has been linked with atherosclerotic cardiovascular complications, irrespective of antiretroviral therapy. It is unclear whether patients with HIV infection have an attenuated nocturnal BP reduction.

Methods: Fifty-two consecutive patients with untreated HIV infection (85% men, age 39 ± 11 years, 50% smokers, BP 125/78 ± 11/10 mmHg) were individually matched with 104 healthy control in a case-control study (cases : controls ratio 1 : 2). Matching criteria were age ( ± 10 years), sex (same sex), smoking habits (smoker or non-smoker) and office systolic BP ( ± 10 mmHg). All participants underwent 24-hour BP monitoring with a validated oscillometric device (SpaceLabs 90207, 1 reading/15 min). Hypertension (BP ≥140/90 mmHg or antihypertensive treatment), diabetes, cardiovascular disease, obesity, treatment with cardiovascular drugs and concomitant important disease were exclusion criteria. Day and night were defined on the basis of wide fixed clock intervals (06–22 and 22–06, respectively). Subjects with a nocturnal reduction of systolic and diastolic BP <10% were defined ‘non-dippers’.

Results: As expected on the basis of selection criteria, age, office BP and proportion of smokers were identical in the 2 groups. Average daytime BP did not differ in HIV and control subjects (124/80 ± 11/9 vs 124/80 ± 9/7 mmHg, p = n.s.). Night time BP was higher in HIV-infected subjects (113/69 ± 11/9 vs 109/67 ± 8/6 mmHg, p = 0.02/0.09). Nocturnal systolic/diastolic BP reduction was 8.8/11.7% in cases and 11.7/15.8% in controls (p = 0.003/0.043). The proportion of ‘non-dippers’ was 33% in cases and 16% in controls (p = 0.018). In a multiple linear regression, nocturnal BP fall was predicted by cigarette smoking (b = 0.22, p = 0.028) and HIV infection (b = −0.24, p = 0.003).

Conclusions: HIV infection is accompanied by a significantly reduced day-night BP change. These findings, obtained in subjects without major cardiovascular risk factors and not receiving antiretroviral treatment, suggest that day-night BP changes may play a role in HIV-related increase in cardiovascular risk.

Epidemiology

3.1 The BP-Care Study: Blood Pressure Control and Cardiovascular Risk Profile of Hypertensive Patients in Central and East European Countries

G. Grassi,¹ F. Quarti-Trevano,¹ G. Brambilla,¹ S. Laurent,² K. Narkiewicz,³ J. Redon,⁴ M. Viigimaa,⁵ S. Erdine,⁶ R. Cifkova⁷ and G. Mancia¹

1 Clinica Medica, Università Milan Bicocca, Monza, Italy; 2 Department Pharmacology and INSERM U970, Paris, France; 3 Department Hypertension and Diabetology, Univ Gdansk, Gdansk, Poland; 4 Hypertension Clinic, Univ Valencia, Valencia, Spain; 5 Centre of Cardiology, North Estonia Medical Centre, Tallin, Estonia, Tallin, Estonia; 6 Department Cardiology, Univ Istanbul, Istambul, Turkey; 7 Inst Clinic and Exper Medicine, Prague, Czech Republic

Introduction: Limited information is available on the association between hypertension and other cardiovascular (CV) risk factors as well as on blood pressure (BP) control in Central and East European countries, i.e. in a geographic area characterized by a high prevalence of CV disease.

Methods: In 2007, a survey in 7923 hypertensive patients followed by general practitioners or specialists was carried out in Albania (n = 463), Belarus (n = 3219), Bosnia (n = 812), Czech Republic (n = 539), Latvia (n = 437), Romania (n = 491), Serbia (n = 502), Slovakia (n = 1360) and Ukraine (n = 100). CV risk assessment was based on clinic history, sitting BP and target organ damage (TOD) assessment.

Results: Patients had a mean (±SEM) age of 59.2 ± 0.1 years and the majority of them (83.5%) were followed by specialists mainly working in the hospital (67.6%). Average clinic BP was 149.3 ± 1.5/88.8 ± 1.0 mmHg. The most common concomitant CV risk factors were hypercholesterolemia (>200mg/dL, 59.3%), history of coronary heart disease (50.7%), metabolic syndrome (40.4%), obesity (39.5%), diabetes (23.7%), smoking (15.1%), previous stroke (11.5%) and renal failure (creat clear <60mL/min, 2.5%). About 70% of patients displayed a very high risk profile. EKG was performed in 99% of patients, echocardiography in 65%, carotid ultrasonography in 24%, fundoscopy in 68% and microalbuminuria in 10%. ABPM was performed in about all patients. Despite the presence of antihypertensive drug treatment in almost all patients (87.0% was on combination treatment), BP control (<140/90mmHg) was achieved in only 27.1%. BP control was:

1. variable among countries;

2. worse for systolic than for diastolic BP;

3. better in patients followed by specialists than by general practitioners;

4. unrelated to patients age and;

5. more unsatisfactory in high risk, diabetic, CHD and renal failure patients.

The most frequently used drugs (monotherapy or combination) were ACE Inhibitors (70.0%), beta-blockers (57.0%), calcium antagonists (51.2%), diuretics (45.8%) and ARBs (13.0%). Drug treatment included lipid-lowering (54.4%) and antiplatelet (66.6%) agents.

Conclusions: In Central and East European countries:

1. the BP control is low, particularly for patients at very high CV risk, and does not differ from that seen in Western Europe;

2. TOD assessment is quite common, except for microalbuminuria; and

3. combination drug treatment is frequently used.

Acknowledgement. This study was supported by an Educational Grant from Menarini, Italy.

3.2 Prevalence and Patterns of Hypertension in Obese Bariatric Patients

Alessio Montereggi,¹ Alessandra Leone,¹ Roberto Pieraccioli,¹ Lucia Bracci,¹ Katia Baldini,¹ Katalin Viràg,¹ Gabriele Castelli,¹ Carmelo Guido² and Marcello Lucchese³

1 Cardiologia S.Luca AOU Careggi, Firenze, Italy; 2 Anestesia e Rianimazione 2 AOU Careggi, Firenze, Italy; 3 Chirurgia Generale 1 AOU Careggi, Firenze, Italy

Introduction: Extreme obesity, with body mass index (BMI) over 40, is a disease increasingly more frequent and bariatric surgery is proving to be one of the solutions to this problem.

Aim: To evaluate the prevalence of known and unknown arterial hypertension in a group of 177 patients (41 M, 136 F, mean age 42.2, mean BMI 44.2) before bariatric surgical intervention (gastric bending, gastric bypass or biliopancreatic diversion).

Methods: Patients were divided as follows: patients with known hypertension or in hypotensive therapy: 78 (44%); patients with no history of hypertension and without therapy: 99 (56%). This last group was submitted to clinic blood pressure measurement (clinic BP) and to 24 hour ambulatory blood pressure monitoring (ABPM); a value over 140 and/or 90 mmHg was considered pathological at clinic BP and over 130 and/or 80 on the ABPM.

Results: Ambulatory hypertensive patients (clinic BP >140/90 mmHg) were 45/99 (46%). Integrating the results of the clinic BP and the ABPM, patients were further subdivided into 4 groups: true hypertensive patients (clinic BP >140/90 mmHg and ABPM >130/80 mmHg): 22%; isolated clinic hypertensive patients or white coat hypertensive patients (clinic BP >140/90 mmHg and ABPM<130/80 mmHg): 24%; masked hypertensive patients (clinic BP <140/90 mmHg and ABPM >130/80 mmHg): 13%; true normotensives (clinic BP <140/90 mmHg and ABPM <130/80 mmHg): 41%. Prevalence of hypertension in a population of the extremely obese, even if relatively young, individuals is quite high (known + true + masked hypertensive patients): 63.8%.

Conclusions: We maintain that ABPM is an extremely useful tool and must be always recommended in these patients in order to correctly identify the degree of hypertension. It proved helpful to evaluate a correct hypotensive therapy in order to reduce surgical and cardiovascular risk.

3.3 ‘Heart and Climbing’: a Public Training Test for Cardiovascular Prevention

S. Carugo,¹ F. Brasca,² A. Esposito,¹ B. Caimi,¹ D. Solari,³ A. Pernigotti,⁴ G. Rossetti¹ and F. Magrini²

1 Dipart. toraco-polmonare e cardiocircolatorio, Università di Milan; IMMes e PAT, I UOC Cardiologia, Milan, Italy; 2 Dipartimento toraco-polmonare e cardiocircolatorio-Università degli Studi di Milan, Milan, Italy; 3 IMMeS e PAT, I UOC Cardiologia, Milan, Italy; 4 Università degli Studi, Milan, Italy

Introduction: The most recent guidelines lay emphasis on the importance of maintaining adequate life style and regularly physical activity is one of the most important factors of cardiovascular prevention. However, the percentage of obese and sedentary subjects is increasing among general population in last years. We therefore assessed the attitude to perform physical activity in a period of 6 years in a group of residents/tourists in Milan.

Methods: From 2002 to 2008, once a year, we had evaluated the physical attitude, the degree of training, heart rate and life style of a group of 1995 people (mean age 50 ± 40 ys; 57% males and 43% females; BMI 23.1 ± 4.2) attempting to climb the stairs (about 250 steps) toward the top of the Cathedral of Milan (average time 16’30” ± 4’47”). The subjects were assessed in baseline and after the climb by monitoring heart rate and oxygen saturation. We also collected data about lifestyle, risk factors and cardiovascular disease.

Results: During the 6 years we found a reduction in the percentage of smoking people (18.8% vs 14.1%, ns) with a significant prevalence in women and an increase in people practicing regularly exercise (2 hours a week 56.8% vs 60.9%, ns).

Conclusions: These studies may provide a useful model for public education and to assess the evolution of lifestyle in the general population in particular as regards the attitude to perform physical activity.

3.4 Drug Resistant Arterial Hypertension in Public Specialist Outpatient Department

M. D’avino, A. Ilardi, U. Valentino, V. Piedimonte, G. Caruso and D. Caruso

AORN Cardarelli, Napoli, Italy

Introduction: The research is aimed to survey the number of outpatients affected by IAR who have applied to outpatient department in a year, how long they have been affected and try to find a short and low-cost therapy.

Methods: 341 hypertensive patients (190 M and 151 F), average age 61.8 being affected on average for 7.8 years IA have been examined for the first time in 2008 at our department. The anamnesis and the medical examination show that 56 P (30 M) average age 52.8, average PAS 165 and average PAD 98, seem to be affected by IAR. They have been treated and had a follow up after one month. Patients who have not shown any remarkable PA decrease have been doing a renal and suprarenal echo, renal arteries IR evaluation and when required, renal TC, polisomnography, hormonal dosage and renal arteries arteriography according to ESH 2007 Guidelines and the GOIP (internal protocol).

Results: 18 patients out of 56 (32.1% 8 M) are affected by IAR; 21 (37.5% 16 M) are affected by OSAS and treated with C-PAP; 5 (8.9% 1 M) are affected by suprarenal disease and were treated by endoscopic surgery; 7 (12.5% 4 M) were affected by nephrovascular IA and treated with revascularization; 5 (8.9% 3 M) were affected by nephrovascular. Removing the cause was effective for 16 patients out of 21 who suffered from OSAS, 3 out of 5 who were affected by suprarenal disease, 7 out of 7 with nephrovascular IA, 1 out of 5 with nephroparenchymal disease.

Conclusions: The IAR spread is high and an early diagnosis can cut drugs expenditure, first aid and family doctor referrals and, most of all, severe organ damage. An extended debate is necessary to find out a quick and inexpensive diagnostic process.

3.5 Role of Body Weight Class in Determining Casual Hypertension, Pre-Hypertension and Hypertension in a Paediatric Population

S. Genovesi,¹ M. Giussani,² P. Brambilla,² V. Tono,¹ V. Barbieri,¹ V. Sala,¹ F. Pieruzzi,¹ L. Antolini¹ and A. Stella¹

1 Università degli Studi di Milan Bicocca, Monza, Italy; 2 FIMP, Milan, Italy

Aim: To evaluate the prevalence of casual hypertension, pre-hypertension and hypertension in a paediatric population in relation to body weight.

Methods: Body weight, height and blood pressure (BP) were measured in 5131 children (8.2 ± 1.5 years, 51.8% males). Underweight (UW), normal weight (NW), overweight (OW), and obese (OB) children were defined according to the International Obesity Task Force. In children with systolic (SBP) and/or diastolic (DBP) blood pressure values obtained from a first measurement >90th percentile (according to the National High Blood Pressure Education Program) 3 consecutive blood pressure measurements were performed in a different occasion. The mean of the 3 blood pressure measurements defined blood pressure categories as follows: casual hypertensive patients (CH): SBP and DBP <90th; pre-hypertensive patients (PH): SBP and/or DBP >90th and <95th; hypertensive patients (HY): SBP and/or DBP >95th. Children with SBP and/or DBP <90th at the first measurement were considered normotensives (NT).

Results: UW children were 409 (8.0%), NW 3371 (65.6%), OW 1025 (20.0%) and OB 326 (6.4%). The distribution of BP categories according to body weight classes is shown in the table. The percentage of subjects with casual hypertension, pre-hypertension and hypertension progressively increased with the increase in body weight class. The multivariate analysis showed that body weight class was significantly associated to elevated BP categories adjusted for gender, height and age. The mean SBP and DBP z-scores of the 3 BP measurements of the children with SBP and/or DBP >90th at the first measurement (casual hypertensive patients) were significantly greater than those obtained in normotensive children.

Conclusions: In the studied population the prevalence of hypertension and pre-hypertension was high, about 6% of the total. Body weight excess was significantly associated not only with sustained high blood pressure categories but also to casual hypertension. In addition, absolute SBP and DBP values of the children with casual hypertension were still higher as compared to normotensive subjects, even when within the normal range. These data suggest that body weight and life style normalization is a goal that should be pursued not only in hypertensive and pre-hypertensive children but also in those with casual hypertension.

3.6 Cardiovascular Risk Factors Distribution and Organ Damage Prevalence in a Hypertensive Population of Val Trompia

M. Crippa,¹ F. Lazzari,¹ S. Camanini,² F. Del Magro,² R. Costa,¹ F. Zani,¹ S. Ettori³ and R. Fariello³

1 Divisione di Medicina Interna, P.O. Gardone Val Trompia, Spedali Civili di Brescia, Gardone Val Trompia, Italy; 2 Università degli Studi di Brescia, Brescia, Italy; 3 Azienda Ospedaliera Mellino Mellini, Chiari, Italy

Introduction: In the recent years we observed in P.O Gardone Val Trompia an increasing number of hospital admissions for ACS and cerebrovascular pathologies in patients having positive case history only for Hypertension.

Methods: In order to identify the prevalence of CV risk factors and their associations, as well as the prevalence of organ damage, we evaluated 213 patients (121 M; 92 W; mean age 54.1 ± 11.6) suffering from essential hypertension not in treatment, or with office BP not normalized by the current therapy (mean BP: 149.1 ± 17.8/94.5±10.1 mmHg). Patients underwent to outpatient medical examination (case history, office BP, waist circumference), laboratory tests (glycaemia, lipid profile, renal function, 24 hour albuminuria and creatinine by Cockroft and Gault) and instrumental investigations (ECG, echocardiogram, fundus oculi).

Results: As the only risk factor Hypertension was present in 5% of cases; in 27% cases it was associated with 1 RF; in 44% with 2 RF; in 21% with 3 RF; in 3% with 4 RF (figure). The most prevalent risk factor (47%), alone and in combination resulted LDL-c >115mg/dL. The prevalence of organ damage was as follows arranged: LVH eco 10%, while 1% with ECG (p < 0.001); microalbuminuria 17%; creatinine cl. <60mL/min 10%. Fundus oculi didn’t reveal any retinopathy >II grade.

Conclusions: The frequent association of more CV risk factors and the high prevalence of Metabolic Syndrome (30%) in hypertensive patients of Val Trompia, could justify the risen incidence of hospitalization in our P.O. for major cardiovascular events. Echocardiogram confirms itself as more sensible and specific compared with ECG in LVH detection. Fundus oculi doesn’t provide additional information for the correct stratification of cardiovascular risk in our hypertensive patients.

3.7 “Dieci Anni Di Vita In Più” (A Life Ten Years Longer) for Hypertensive Patients: State of the Art

M. D’avino, D. Scala, G. Caruso, S. Cozzolino, A. Mancini, B. Andria, R. Muschera’ and D. Caruso

AORN Cardarelli, Napoli, Italy

Introduction: The Hypertension Working Group of Cardarelli Hospital in Naples, Italy developed a therapeutic education project “10 anni di vita in più” (a life ten years longer) to reduce blood pressure (BP) in patients with hypertension through a change of their lifestyle.

Methods: 336 patients were randomly assigned to Control group (163) and to Intervention group (173). Ten multiple choice questionnaire was developed to evaluate the effect of the intervention on lifestyle modification. Patients were given the questionnaire and the Short Form Health Survey (SF-36) questionnaire, had BP measured, laboratory data collected, and drug therapy registered before educational intervention and 12 months later. Group I patients (mean age 56.7 ± 10.2, 46.2%, male) participated to 3 interactive educational sessions respectively 2, 4 and 9 months after the recruitment. Sessions were set in a way that patients could easily talk about what they were learning, write reflectively about it, relate it to past experiences, and apply it to their daily lives. What they learnt became a part of themselves. Group C patients (mean age 56.4 ± 10.7, 47.9%, male) received oral information and were followed-up at 2, 4 and 9 months after the recruitment to make both groups comparable. Analysis was performed using SPSS version 15.0.

Results: After 12 months there was a significant reduction of BP for both groups (group I t = 0: SBP = 136.9 ± 18.3 DBP = 85.1 ± 9.1, t = 12 months SBP = 127.4 ± 15.4 DBP = 81.9 ± 8.9; group C t = 0: SBP = 138.7 ± 12.0 DBP = 86.6 ± 5.9, t = 12 months SBP = 133.2 ± 9.7 DBP = 83.8 ± 6.1) (p < 0.001). In group I, 26.8% of patients reduced and 7.1% increased drug therapy while for 66.1% drug therapy remained unchanged. For group C 16.7% reduced and 33.3% increased drug therapy, while for 50% drug therapy remained unchanged. The reduction of BP values in group I was due to an increased adherence to recommendations given by physicians while in group C was especially due to an increase of drug therapy. As a consequence group I patients saved 3.15 euros per capita per month and groupC patients spent 1.8 euros more per capita per month. We found a significant improvement of lifestyle modification after 12 months of follow-up concerning some aspects in both groups, while SF-36 showed better results for the majority of the items in group I.

Conclusions: Our findings show that this approach is a powerful tool for reaching better blood pressure control and underline the essential role of patients involvement in the management of their care.

3.8 “Dieci Anni Di Vita In Più” (A Life Ten Years Longer), a Therapeutic Patient Education Project for Hypertensive Patients: from the Hospital to the Community

D. Scala, M. D’avino, G. Caruso, S. Cozzolino, A. Mancini, B. Andria, R. Muschera’ and D. Caruso

AORN Cardarelli, Napoli, Italy

Introduction: The Hypertension Working Group of Cardarelli Hospital, transferred from hospital to the community the therapeutic patient project “10 anni di vita in più” (a life ten years longer) whose objective was to reduce blood pressure (BP) through better adherence to the recommendations given by physicians. This transfer was possible thank to the collaboration of the Benevento’s Order of Physicians, the Benevento’s General Practitioners (GP) [Samnium Medica Cooperative, Ippocrate Cooperative, Medical 2000 Cooperative] and the Department of Metabolic Diseases of Rummo Hospital of Benevento.

Methods: 11 GPs participated to the project. The educational intervention consisted of 3 interactive sessions with patients. Patients were given ten multiple choice questionnaire, developed to evaluate the effect of the intervention on lifestyle modification, together with the Short Form Health Survey (SF-36) questionnaire before educational intervention and 12 months later. Patients participated to the interactive sessions respectively 2, 4 and 9 months after the recruitment. Analysis was performed using SPSS version 15.0.

Results: Two hundred eighty-nine patients were recruited; mean age was 62.8 ± 3.1, 54.5% of the sample was male. At the time of recruitment SBP was 137.6 ± 12.8 and DBP was 81.4 ± 7.7. After 12 months there was a significant reduction of BPr (SBP = 134.4 ± 11.9 and DBP = 80.9 ± 6.9; p < 0.001). This reduction is associated with better adherence to recommendations given by the physicians. 20.7% of patients reduced drug therapy, 12.9% % increased drug therapy while for 66.4% drug therapy remained unchanged. We registered a total reduction on drugs expenditure of 2.3 euros per capita per month. The lifestyle questionnaire showed a positive trend towards a change of lifestyle. The SF-36 values showed slightly improved after 1 year. Data of control group are in progress.

Conclusions: A better relationship between GPs and patients can make significantly contribute to the prevention of diseases, especially those with high social impact, to the modification of behaviour, to the improved use of drugs and health services and to reduce health costs.

3.9 Risk of Arterial Hypertension Development in Patients Treated with Sorafenib for Hepatocellular Carcinoma: a Single Center Experience

A. Venturi, B. Stagni, C. Caprara, S. Flori, S. Leoni, P. Pini, G. Imbriaco and L. Bolondi

Policlinico S.Orsola-Malpighi, Bologna, Italy

Introduction: Sorafenib, an antiangiogenetic and antiproliferative drug used to treat patients with advanced renal cell carcinoma, was recently been approved for hepatocellular carcinoma treatment also. Major side-effects of this drug are fatigue, diarrhoea, anorexia, hand and foot skin reactions and arterial hypertension development, that might be related to its inhibitory effect on Vascular Endothelial Growth Factor receptor.

Aim: To establish the incidence of arterial hypertension in 45 patients receiving Sorafenib for hepatocellular carcinoma and to evaluate the best clinic management of treated subjects.

Methods: We retrospectively reviewed 45 subjects with hepatocellular carcinoma arisen on hepatic cirrhosis treated with Sorafenib 800 mg/day (37 males, 8 females, mean age 69.8 years, range 48–88). According to guidelines, the diagnosis of arterial hypertension was defined as the threefold presence of arterial blood pressure >140/90 mmHg.

Results: Nine of 45 patients (20%) developed arterial hypertension during Sorafenib treatment. Eight of them were hypertensive well controlled with antihypertensive drugs before Sorafenib therapy. In all patients hypertension occurred early in the course of treatment (two weeks). In 8 patients the dose of antihypertensive medication was increased and in 6 new antihypertensive drugs were added. In the remaining subject antihypertensive treatment was started. In 3/9 patients (33%) Sorafenib treatment was interrupted, considering also others side effects presentation.

Conclusions: Arterial hypertension development is a frequent side-effect during Sorafenib treatment. Patients given Sorafenib need to be closely monitored, especially when they start therapy, to an early hypertension detection and an effective treatment, allowing prevention of cardiovascular complications. In case of persistent hypertension, additionally to antihypertensive treatment, temporary or permanent Sorafenib discontinuation should be considered.

3.10 Obesity is a Risk Factor for Gastroesophageal Disease and Influences the Choice of Antihypertensive Therapy

A. Pucci,¹ G. Salvetti,¹ N. De Bortoli,² M. Parlanti,² S. Martinelli,¹ F. Fierabracci,¹ S. Marchi,² A. Pinchera,¹ A. Salvetti² and F. Santini¹

1 Dipartimento di Endocrinologia e Rene-Azienda Ospedaliero-Universitaria Pisa, Pisa, Italy; 2 Dipartimento di Medicina Interna-Azienda Ospedaliero-Universitaria Pisa, Pisa, Italy

Introduction: The presence of gastroesophageal reflux disease (GERD) can influence the choice of antihypertensive therapy. An association between high body mass index (BMI) and GERD has been proposed but is still unclear the relationship between the severity of obesity and the prevalence or gravity of esophagitis.

Aim: To evaluate the prevalence of erosive GERD in female obese subjects as compared with normal weight women with or without GERD symptoms.

Methods: 145 obese women (Group A) scheduled for bariatric surgery, 146 women with GERD symptoms (Group B) and 146 women with various gastrointestinal presentations but no GERD symptoms were submitted to esophago-gastric endoscopy. Erosive reflux disease was diagnosed according to the Los Angeles Classification of esophagitis. There were among the three groups no differences in coffee, alcohol consumption and smoke habits. All data were analysed by logistical regression.

Results: In the Group A (age 41.3 ± 11.6 years) mean BMI was 43.8 ± 6.8, in Group B (age 54.4 ± 14.8 years) mean BMI was 24.9 ± 2.7, in Group C (age 46.4 ± 17 years) mean BMI was 23.4 ± 3.5. The prevalence of esophagitis was significantly higher in Group A (43%) as compared with Group B (23.3%) and Group C (16.4%).

Conclusions: Obese women with severe obesity, without obvious symptoms of GERD, showed a higher risk for erosive reflux disease than normal weight women GERD related symptoms and normal weight women without superior gastrointestinal tract symptoms. These findings indicate that the choice of antihypertensive therapy in obese women should take into account the high prevalence of GERD.

3.11 Cardiometabolic Risk Profile in a Cardiovascular Screening Survey: Results of the Cardiolab Project

R. Dell’Oro,¹ F. Arenare,¹ C. Mineo,¹ M. Volpe,¹ L. Magni,¹ M. Smith,² P. Montanari,³ G. Grassi¹ and G. Mancia¹

1 Clinica Medica, Università Milano-Bicocca, Monza, Italy; 2 Statistico CardioLab, Milan, Italy; 3 Bayer, Milan, Italy

Introduction: Limited information is available on the awareness and on the therapeutic control of hypertension, diabetes mellitus and dyslipidemia, when these pathological conditions are present simultaneously in the same patient.

Methods: An epidemiological survey was performed (2004–2008) in subjects aged 18–70 years both men and women from 140 Italian towns, aimed at:

1. collecting clinic history,

2. measuring clinic blood pressure (BP), anthropometric {body mass index (BMI) and abdominal circumference (AC)} and metabolic (serum glucose and total cholesterol) variables and

3. assessing cardiovascular (CV) risk profile.

Results: 38503 subjects 60 ± 13.8 (mean ± SD) years old were recruited. 11.2% had history of cardiac or cerebrovascular event, while 21.2% were current smokers. Obese and overweight patients were 43.6% and 21% respectively. 33.1% of the population was affected by hypertension, of which 1/3 showed a satisfactory blood pressure profile at the time of the visit, while 2/3 did not. 27.5% of patients without history of hypertension showed blood pressure values >140/90 mmHg, due either to alarm reaction or to new onset hypertension. Of these, 53.3% had mild, 31.8% moderate and 9.9% severe hypertension. 8.5% had a history of diabetes, of which 1/3 had normal and 2/3 uncontrolled glycaemic values (cut-off 100 mg/dL). Patients without a history of diabetes with serum glucose >100 mg/dL were 28.8%, of which 81.9% was classified as pre-diabetes and 18.1% as new onset diabetes. 24.9% had history of hypercholesterolaemia, of which 1/3 was controlled by treatment. 39.5% of subjects with no history of dyslipidemia showed total cholesterol values >180 mg/dL and were classified as new onset dyslipidemia. Total cardiovascular risk profile (SCORE) resulted high in 12.6%, moderate in 64.5% and low in 22.9% of the population.

Conclusions: In a population characterized by a high-moderate CV risk profile, the awareness of the conditions of diabetes or hypercholesterolaemia is superior than the awareness of hypertension. In patients under treatment, however, cardiometabolic control results were not adequate.

Acknowledgment: This study was supported by an Educational Grant from Bayer, Italy.

3.12 Quantification of Habitual Physical Activity in a Sample of Hypertensive Patients of the City of Bologna

E. Strocchi,¹ M. Rosticci,¹ G. Ermini,² S. Quadrelli,² A. Verri,² M. Giovannini¹ and C. Borghi¹

1 Dipartimento di Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Università di Bologna, Bologna, Italy; 2 Medici di Medicina Generale, Bologna, Italy

Introduction: Inactivity and a reduced physical activity are causes of well known cardiovascular risks. The principal guidelines for prevention from cardiovascular diseases advise a moderate physical activity, equal to walks of 30–60 minutes at fast pace, for most days; these recommendations derive for studies which have demonstrated how advantages in terms of risks reduction are already evident also with low levels of physical activity. Other studies have documented how, in order to have positive effects, it is not necessary for the physical activity to be structured nor continuative. Less known are the levels of basic physical activity of patients to whom we recommend this type of activity in terms of prevention.

Aim: To determine the physical activity of patients suffering from hypertension, of middle age, resident in a city, through the use of a pedometer (for a week), together with data collected through questionnaires aimed at establish the occasional physical activity in various months of the year and that in the past.

Methods: 50 patients with hypertension were examined (16 females and 34 males) not selected: with an average age of 51 years old (ranging from 45 to 55 years).

Results: 80% of the patients resulted already under treatment for hypertension at the time of visit and the medical PA at the time of visit was 132/82 mmHg. Approximately 30% of the patients presented signs for the metabolic syndrome. The 90% of patients declared a precedent physical activity and only in one quarter of the cases physical activity at professional level. As far as hours dedicated to physical activities in the last 12 months were concerned, 75% of the patients declared to dedicate less than 2 hours weekly. On the basis of data provided from the pedometer, approximately 10% of the patients could be classified as sedentary (less than 5000 steps/day); 30% presented a low level of activity (between 5000 and 7500 steps/day); 45% showed signs of a discreet physical activity (from 7500 to 10000 steps/day) while only 15% resulted active or very active (more than 10000 steps/day).

Conclusions: Since this latter limit is indicated in some guidelines as the minimal level of physical activity which protects from risks, our research confirms that the basic physical activity of a urban population is significantly low and the consequential benefit of an increase of the physical activity, in most cases.

3.13 Prevalence of Hypertensive Crisis in Emergency Room: Observational Multicenter Six-Months Follow-Up

G. Pinna,¹ P. Fornengo,² C. Pascale,¹ S. Arras,³ V. Semeraro,⁴ M. Pesenti,⁵ R. Fiorini,⁶ G. Santoro,⁷ D. Bergandi,⁸ R. Musso,⁹ S. Panzone,¹⁰ B. Traverso,¹¹ S. Lenti,¹² C. Bracco¹⁰ and B. Zampaglione⁸

1 Ospedale Cottolengo, Torino, Italy; 2 AOU San Giovanni Battista, Torino, Italy; 3 Ospedale Civile, Alghero, Italy; 4 Ospedale Cardinal Massaia, Asti, Italy; 5 Ospedale Regionale, Aosta, Italy; 6 Ospedale civile, Fidenza, Italy; 7 Ospedale Civile, Rovigo, Italy; 8 Ospedale Martini, Torino, Italy; 9 Ospedale Santa Croce, Moncalieri, Italy; 10 Ospedale S. Croce e Chiarle, Cuneo, Italy; 11 Osapedale Civile, Tortona, Italy; 12 Osapedale Civile, Arezzo, Italy

Introduction: Cardiovascular diseases are an important health problem. In particular, arterial hypertension stand out with an estimated prevalence around 20–30% of the population over 18 years. A serious complication of arterial hypertension are hypertensive crises, characterized by a rapid, inappropriate, strong and often symptomatic elevation in blood pressure levels, with or without the risk of rapid deterioration of target organs, (TOD), which may represent an immediate or potential life threat. A hypertensive crisis may be manifested as a hypertensive emergency or urgency. The real epidemiologic extent of the hypertensive emergency and urgency has been not clearly assessed.

Aim: To evaluate the prevalence of hypertensive crisis (emergency, urgency), of their clinic presentation and of the type of organ damage.

Methods: We collected the case files of all the patients admitted to the Emergency Department of the 9 centers involved in the Study between the first of January and 31 December 2008. Hypertensive crisis was defined as systolic blood pressure >220 and diastolic >120 mmHg. Hypertensive urgency was defined as symptomatic increase of blood pressure in absence of TOD; hypertensive emergency was defined as symptomatic increase of blood pressure in presence of acute or progressive TOD.

Results: A total of 192294 clinic files, of the first six months, were screened. Prevalence of hypertensive crisis was 0.43% (804 cases). The hypertensive emergencies were 37.6% and urgencies were 62.4%. 12% of the patients was unaware of their hypertension. Patients with hypertensive emergencies were more frequently male (66.3%; p < 0.002), older (60.1 ± 14.2 years, p < 0.001) and with higher diastolic blood pressure (128.1 ± 12 vs 125.6 ± 14 mmHg, p < 0.05) compared with patients with hypertensive urgencies. The emergencies clinic presentation was more frequently ischemic stroke and pulmonary oedema.

Conclusions: Hypertensive crisis represent the 0.43% of all the Emergency Department admission in this wide population. Hypertensive urgencies were more frequent than emergencies. Pulmonary oedema and ischemic stroke were the more frequent TOD clinic presentation of the hypertensive emergencies.

3.14 Association between Hypertension and Anthropometric Indices in Brisighella Heart Study

F. Imola, L. Laghi, V. Grasso, M. Pombeni, E. Rizzoli, S. D’Addato, A. Dormi and C. Borghi

Università degli Studi di Bologna, Bologna, Italy

Introduction: Obesity is a very common condition closely connected with various cardiovascular risk factors, and there is growing evidence about the role of fat distribution in this association.

Aim: To evaluate the association between anthropometric indices and hypertension.

Methods: Between May 2008-March 2009 we analysed 1638 adult subjects (789 male, 849 female; 19–97 years), randomly selected, from the cohort of the population-based longitudinal Brisighella Heart Study (BHS; 1972–2008). We measured blood pressure (BP), weight (W), height (H), waist and hip circumference (WC, HC); then, we calculated waist to hip ratio (WHR), body mass index (BMI), BMI to WHR ratio (BMI/WHR), waist to height ratio (WHtR) and a new index waist circumference for weight to height ratio (WCW/H). Anthropometric indices were grouped into quintiles and we calculated, with the chi-quadrate test, the association with hypertension, with the cut-off at 25 for BMI and at the third quintile for the other parameters. Hypertension was defined by a blood pressure measurement ≥140/90 mmHg or the use of blood pressure lowering drugs. All data were adjusted for age, cholesterolaemia and diabetes.

Results: All anthropometric parameters (BMI,BMI/WHR,WHtR,WCW/H) have a predict power to develop hypertension in all the subjects of 30–64 years and in the female >64 years; for male >64 years there is a significant correlation only between BMI/WHR and hypertension (table).

Conclusions: Among various anthropometric measurements that showed a significant association with hypertension,WHtR was more predictive, and its valuation could be useful in the clinic practice.

3.15 Salt Intake, Stroke and Cardiovascular Disease: a Meta-Analysis of Prospective Studies

P. Strazzullo,¹ N.B. Kandala,² L. D’Elia¹ and FP. Cappuccio²

1 Università di Napoli Federico II, Napoli, Italy; 2 Warwick Medical School, Coventry, UK

Introduction: The association of sodium intake and adverse cardiovascular outcomes have long been recognised, with reduction in salt intake now considered a major public health intervention. The population benefits of salt reduction have been extrapolated by those expected through its blood pressure lowering effect.

Aim: To assess whether the population longitudinal evidence supports the presence of a relationship between levels of salt intake and both stroke and cardiovascular outcomes, and to obtain an estimate of the risk.

Methods: We performed a systematic search of publications using MEDLINE (1966–2008), EMBASE (from 1980), AMED, CINHAL, PsycINFO, the Cochrane Library and manual searches without language restrictions and, when necessary, authors were contacted. Criteria for inclusion were: population studies with assessment of salt intake as baseline exposure and either stroke or total CVD determined prospectively as outcome. For each study several characteristics were recorded, relative risks and 95% C.I. were extracted and pooled using a random effect model, weighting for the inverse of the variance. Sensitivity analysis was performed, heterogeneity and publication bias were also assessed.

Results: Overall, 11 studies were identified providing 16 cohort samples. They included 156 697 male and female participants (follow-up range 3.5–19 years), 5 183 stroke and 4 129 CVD events. Salt intake was assed by 24-hour dietary recall (n = 3), FFQ (n = 3), urine excretion (n = 4) and questionnaire (n = 1). In the pooled analysis, higher salt intake was associated with greater risk of stroke (RR: 1.26; 95% CI 1.07, 1.48; p = 0.004) and CVD (1.20; 0.95, 1.50; p = 0.12), with no evidence of publication bias but significant heterogeneity between studies (p < 0.001 for both endpoints). For stroke the pooled estimate did not vary substantially with the exclusion of individual studies. However, for CVD the exclusion of a single outlier led to a pooled estimate of 1.28 (1.03–1.58); p < 0.01.

Conclusions: High salt intake is associated with significantly greater risk of both stroke and total CVD. These results support worldwide recommendations for a population reduction in salt intake to prevent cardio and cerebrovascular disease.

3.16 Excess Body Weight and Incidence of Stroke: a Meta-Analysis of 21 Prospective Studies with One Million Participants

P. Strazzullo,¹ L. D’Elia,¹ G. Cairella,² F. Garbagnati² and L. Scalfi¹

1 Università di Napoli Federico II, Napoli, Italy; 2 CeSAR-IRCCS Fondazione Santa Lucia, Rome, Italy

Introduction: Obesity was shown to be associated with increased risk of stroke in most but not all epidemiological studies, and the extent of the association with the various types of stroke remains uncertain.

Aim: To determine whether a graded association occurs between excess body weight and the incidence of stroke and its subtypes by performing a meta-analysis of the cohort studies available.

Methods: We searched MEDLINE, EMBASE, the Cochrane Library, and bibliographies of retrieved articles. Studies were included if their follow-up observation was at least 5 years and if they reported the number of individuals exposed and the corresponding number of events in each weight category. We used a random effect model and a funnel plot and Egger’s test with trim-and-fill procedure, when necessary.

Results: Overall 21 studies (1 035 399 individuals and 17 530 stroke events) met the inclusion criteria and between 7 and 19 of them were available for direct comparisons depending on the stroke subtype and the body weight categories analysed. Compared with normal weight individuals, the pooled RR (95% CI) for total stroke were 1.07 (0.94–1.22) for overweight and 1.47 (1.24–1.75) for obese individuals. Separate analysis for ischemic stroke indicated RR = 1.29 (1.12–1.50) for overweight and RR = 1.86 (1.54–2.25) for obese individuals; separate analysis for hemorrhagic stroke provided RR = 0.99 (0.89–1.12) and 1.31 (1.16–1.47), respectively. Further analyses taking into account the most relevant potential confounders of the association between excess body weight and ischemic stroke showed that the association was independent of age, blood pressure, diabetes, physical activity and alcohol intake; this was not the case for hemorrhagic stroke.

Conclusions: Overweight and obesity were associated with progressively increasing risk of ischemic stroke, independently of the main potential confounders, including blood pressure.

3.17 Association between Not HDL Cholesterol Levels and Hypertension in the Brisighella Heart Study

S. D’Addato, L. Laghi, A. Dormi, F. Imola, V. Grasso, A.F.G. Cicero, M. Giovannini, M. Pombeni and C. Borghi

Dipartimento Medicina Interna, dell’Invecchiamento e Malattie Nefrologiche, Ospedale S. Orsola-Malpighi, Università di Bologna, Italy

Introduction: Hypercholesterolemia and hypertension are two important cardiovascular risk factors strictly related but it’s not clear if there is a particular subclass of cholesterol most linked to the development of hypertension.

Aim: To evaluate if there is an association between not HDL cholesterol (n-HDL-c) and the development of hypertension in a rural Italian population.

Methods: The Brisighella Heart Study (BHS; 1972–2009) is a prospective, longitudinal epidemiological study with four years follow up. For this study, we take the level of 160 mg/dL such as cut-off for n-HDL-c and we selected 1099 adult subjects representative of the Brisighella population, consecutively visited during the BHS surveys 1988–1992, with no important modification of their lipid profile.

Results: Among the 1099 subjects that didn’t change their lipid profile during the follow up, 43% had n-hdl-c levels <160 mg/dL (41% males, 45.1% women) and 57% had n-HDL-c levels >160 mg/dL (59% males, 54.9% females). In subgroup that developed hypertension during the follow up there is an higher prevalence of subjects high levels of n-HDL-C (16.5% of subjects with n-HDL-C >160 mg/dL vs 6.2% of subjects with n-HDL <160 mg/dL, p < 0.001). After adjusting for BMI, glycaemia, triglycerides and HDL-C plasma levels we divided our population in subgroups for sex and age and we found an higher prevalence of new cases of hypertension in subjects <65 years old (males: 11.5% for subjects with n-HDL-C level >160 mg/dL vs. 1% subjects with n-HDL-C level <160 mg/dL, p = 0.006; females: 12.5% for subjects with n-HDL-C level >160 mg/dL vs 2.2% n-HDL-C level <160 mg/dL, p = 0.007).

Conclusions: These data are not confirmed in subgroup with subjects older than 65. We have also evaluated the association between hypertension and others subclasses of serum lipids such as LDL-C but we didn’t found a stronger correlation. In conclusion we can say that n-HDL-C levels could be a useful parameter to predict the development of hypertension among people <65 years but not in subjects> 65 years, where the age probably plays a dominant role.

3.18 Effect of Gender on the Relation between Blood Pressure and Body Composition in Overweight-Obese Subjects

F. Cipollini,¹ E. Arcangeli,¹ E. Greco,¹ A. Berti,¹ G. Seghieri¹ and F. Franconi²

1 Spedali Riuniti, Pistoia, Italy; 2 Istituto di Farmacologia Università, Sassari, Italy

Introduction: In obese-overweight people blood pressure (BP) and arterial hypertension are, as known, both related to body weight. The influence of gender as well as of body composition in this relationship has nevertheless not yet been well clarified.

Aim: To evaluate whether gender affects BP by a different relationship with fat or fat-free mass in overweight-obese patients.

Methods: We studied 431 overweight-obese (BMI ≥25 kg/m²) non diabetic people, of whom 118 males and 313 females who consecutively approached the Diabetic Outpatient Clinic of our Hospital to obtain diabetic advice. In all patients we measured BMI and body composition (FM and FFM) through bioelectrical impedance. Blood pressure was measured by standardised methods and hypertension was defined as a systolic blood pressure ≥140 mmHg and/or a diastolic blood pressure ≥90 mmHg and/or current use of anti-hypertensive drugs.

Results: Fat mass was similar in both sexes (32.2 ± 9.5 kg in M and 32.3 ± 10.4 kg in F; p = ns) while FFM was higher in males than in females (68 ± 10 kg vs. 49 ± 6 kg; p = 0.0001). Mean BP was related to FM in females (r = 0.27; p = 0.0001) but not in males (r = 0.06; p = ns); while, on the contrary, FFM was significantly related to BP in males (r = 0.27; p = 0.004), and only weakly in females (r = 0.12; p = 0.03). These results were moreover confirmed after adjusting for age. Finally the relative risk of arterial hypertension significantly increased by 6% for each 1 kg increase of FFM in males (OR = 1.06 [95% CI: 1.011, 1.17]) and respectively by about 4% for each 1 kg increase of FM in women (OR = 1.039 [1.010–1.039]), after adjusting for possible confounders. These same results were obtained after substituting FM with waist circumference, with good reason considered as a proxy of FM.

Conclusions: These preliminary data suggest that gender affects the relationship between BP and body composition in obese people, indicating that BP is in some ways more FM-dependent in women and more FFM-dependent in males. In conclusion these findings can, altogether, hypothetically suggest that any decrease of body weight in obese people could lead to different BP reduction between sexes.

3.19 Blood Pressure Control and Variability in Diabetic Patients Undergoing Ambulatory Blood Pressure

A.M. Agrati, G. Palmieri, F. Colombo and G. Ferraro

Ospedale Niguarda Cà Granda, Milan, Italy

Introduction: Diabetic patients show an increased cardiovascular risk even at blood pressure (BP) values considered normal in non diabetics. Ambulatory blood pressure monitoring (ABPM), apart from accurate BP measurements, can give useful information on some parameters considered important in the evaluation of the total cardiovascular risk. Differences in the prevalence of these parameters could be an important factor in this increased cardiovascular risk.

Aim: We analyzed diabetic subjects type 2 undergoing ambulatory blood pressure monitoring (ABPM) in order to evaluate their 24-hour BP profile and BP variability.

Methods: Data regarding 1209 diabetic (type 2) subjects undergoing ABPM (from January 1998 to November 2008) at our institution were analyzed. Normotension was defined as a mean 24 BP <125/80 while hypertension as a mean 24 BP >125/80. We considered as non-dippers subjects with mean night systolic pressure values above 90% of day values. Systolic blood pressure variability was expressed as the standard deviation of the 24 hr systolic pressure. Morning surge phenomenon (MS) was also calculated considering the mean systolic blood pressure in the two hours after awakening — minimum systolic pressure in the night. The table reports data from the study diabetic population.

Results: The main findings of our study are shown in the table.

Conclusions: Spontaneously normotensive diabetics show less alterations in BP variability in comparison with the whole diabetic population examined. Diabetics with normalized BP profile do not show a significant reduction in BP variability in comparison with hypertensive diabetics. Part of the higher cardiovascular risk of diabetic subjects could be related to this phenomenon.

3.20 Global Cardiovascular Risk Management in Different Italian Macro-Areas: an Analysis of the Results of the Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation (EFFECTUS) Study

G. Tocci,¹ A. Avogaro,² M. Comaschi,³ A. Corsini,⁴ C. Cortese,⁵ C.B. Giorda,⁶ P. Guida,⁷ G. Madeda,⁸ G.F. Mureddu,⁹ G. Titta,¹⁰ G. Ventriglia,⁸ G.B. Zito,¹¹ E. Manzato,¹² A. Ferrucci¹ and M. Volpe¹

1 Università Sapienza, II Facoltà Medicina Chirurgia, Rome, Italy; 2 Dipartimento di Medicina Clinica e Sperimentale, Cattedra di Malattie Metaboliche, Università Padova, Padova, Italy; 3 Dipartimento di Emergenza, Università di Genova, Ospedale San Martino, Genova, Italy; 4 Dipartimento di Scienze Farmacologiche, Università di Milan, Milan, Italy; 5 Dipartimento di Medicina Interna, Università “Tor Vergata”, Rome, Italy; 6 Unità di Diabete e Malattie del Metabolismo, ASL Torino 5, Chiari, Italy; 7 Divisione di Cardiologia, Dipartimento di Emergenza e Trapianto d’Organi, Università di Bari, Bari, Italy; 8 Società Italyna di Medicina Generale, Rome, Italy; 9 Dipartimento di Malattie Cardiovascolari, Azienda Ospedaliera San Giovanni-Addolorata, Rome, Italy; 10 Federazione Italyna di Medicina Generale, Torino, Italy; 11 Unità di Cardiologa, ASL Napoli 5, Pompei, Napoli, Italy; 12 Dipartimento di Scienze Mediche e Chirurgiche, Università di Padova, Padova, Italy

Introduction: Recent surveys have shown that the implementation of guidelines’ recommendations for cardiovascular (CV) disease management is often difficult to apply in the daily clinic practice. This may be related to several factors, including national health care systems’ rules, physicians’ behaviours and attitudes and patients’ preferences among European Countries, including Italy. In this view, the Evaluation of Final Feasible Effect of Control Training and Ultra Sensitisation (EFFECTUS) study, an observational, multicenter, educational program, has recently evaluated the global CV risk management in different clinic settings in Italy.

Aim: To evaluate similarities and differences in the global CV risk management in patients included in the EFFECTUS study, stratified in different macro-areas (north, middle and south) throughout the Italian territory.

Methods: The EFFECTUS study involved physicians who agreed to participate in an educational project, aimed at implementing the knowledge and management of global CV risk. Physicians were asked to report in a dedicated case report form data already available in their medical records from 10 consecutive adult outpatients, during the month of May 2006. Data collection included patients’ medical history, drug treatment, physical examination, laboratory results or diagnostic tests. Data were then centrally analyzed for the assessment of global CV risk in the overall population.

Results: The EFFECTUS study involved a total of 1078 physicians (27% female, mean age 50.3 ± 7.6 years), who collected data from 9904 outpatients (46.5% females, mean age 67 ± 9 years), of which 3219 (32.5%) residents in the north, 3652 (36.9%) in the center and 3003 (30.3%) in the south areas of our country. Overall, a high prevalence of major CV risk factors was recorded. In particular, “southern patients” have shown a higher prevalence of family history of CV disease, smoking, hypertension, dyslipidemia, diabetes and coronary artery disease. With the exception of triglycerides, the absolute values of blood pressure, cholesterolaemia (total and LDL), blood glucose and creatinine were significantly higher in the middle as compared to those recorded in the north and south Italy. Significant differences were also recorded in relation to requested diagnostic tests and therapeutic strategies used to manage global CV risk across the Italian territory.

Conclusions: This analysis of the EFFECTUS study confirms the high prevalence of CV risk factors in Italy, particularly in southern Italian regions, and some differences in the clinic management of global CV risk, which may have relevance for planning future preventive strategies aimed at reducing the global burden of CV disease in our Country.

3.21 Cognitive Impairment and Comorbidity in Elderly Patients with Hypertension

Alessandro Grippa and Ferdinando D’Amico

UOC Geriatria PO Patti-AUSL n. 5 Messina, Patti-Messina, Italy

Introduction: Epidemiological studies showed that elderly people with cognitive impairment have a higher risk of death. Cognitive impairment can come up in different ways. The most common cognitive impairment can be mnesic, or can affect just one non-mnesic area, or it can involve more than one area. Each aspect can have different causes. A demential syndrome with mnesic impairment can be the result of a neurodegenerative process, an ischaemic damage, a trauma or a metabolic disorder. According to this theory other causes can be responsible such as psychiatric disorders (burn out, depression), organ damage like cardiovascular diseases.

Aim: This study evaluated the prevalence of cognitive impairment and the incidence of comorbidity in elderly people affected by hypertension.

Methods: 157 elderly hypertensive patients (74 Males, 83 Females, mean age 78 + 9 years) were included. We recorded:

1. blood tests;

2. measurement of blood pressure (BP);

3. measurement of blood pressure in the 24 hours (ABPM);

4. Mini Mental State Examination (MMSE);

5. Cumulative Illness Rating Scale (CIRS) BP control was for values <140/90 mmHg and BP < 130/80 mmHg in patients with diabetes mellitus.

Cognitive impairment was assessed through the MMSE adapted to the grade of education and age. Patients were divided in four groups:

1. severe cognitive impairment (MMSE score between 0 and 10);

2. moderate cognitive impairment (MMSE score between 11 and 20);

3. mild cognitive impairment (MMSE score between 21 and 23);

4. normal cognitive function (MMSE score >24.

Results: We detected the following BP values: SBP 147 + 18 mmHg and DBP 86.8 + 9 mmHg. 39.6% had controlled BP. 46.85% had Left ventricular hypertrophy and 59.8% had carotid plaques. 25.2% had hypertension associated to diabetes mellitus and 42.7% had hypertension associated to dyslipidemia. 28.7% patients with cognitive impairment had a MMSE mean score of 22.3 + 5.3. MMSE score were inversely related to the Pulse pressure [PP] (p < 0.001) and to the history of hypertension (p < 0.001). Cognitive impairment was strongly related to age >80. Through CIRS we detected a stronger severity in associating cognitive decline to: stroke, Parkinson disease, cardiovascular disease and depression. In detail we detected depression in 32.4% elderly hypertensive subjects, prevalently in women (p < 0.05). In male elderly hypertensive and depressed patients we detected a higher prevalence of cardiovascular risk compared to the non-depressed ones (12.40% vs 7.3%, p < 0.05). In female elderly depressed subjects there was a slighter difference.

Conclusions: Prevalence of cognitive impairment was 28.7% in elderly hypertensive patients. If we consider that just 39.6% had controlled BP we assessed that an appropriate BP control was related to a higher MMSE score. Cognitive impairment was strongly related to older age and geriatric diseases.

3.22 Metabolic and Cardiovascular Characteristics of Diabetes in Adolescents and Young Adults: the Strong Heart Study

M. De Marco,¹ G. de Simone,¹ M.J. Romen,² M. Russell,³ M. Chinali,¹ E.T. Lee,⁴ B.V. Howard⁵ and R.B. Devereux²

1 Università Federico II, Napoli, Italy; 2 Weill Cornell Medical College, New York, NY, USA; 3 MedStar Research Phoenix, Phoenix, AZ, USA; 4 University of Oklahoma, Oklahoma City, OK, USA; 5 Medstar Research Institute, Washington, DC, USA

Introduction: The epidemic of overweight is increasing prevalence of diabetes (DM) in adolescents and young adults.

Aim: To evaluate in a population-based study the early metabolic and cardiovascular impact of DM in young adults.

Methods: We analyzed anthropometric, metabolic and hemodynamic characteristics, left ventricular (LV) geometry and function (by Doppler-echocardiography) in 1644, 14-to-39 year old participants (57% female, mean age 26 ± 8 years) to the 4th Strong Heart Study (SHS) examination, 173 (11%) of whom had DM. Comparison between groups was obtained by ANCOVA, adjusting for blood pressure (BP), age, gender and BMI.

Results: Participants with DM were more often obese (80% vs 51%), older (age 32 ± 6 vs 26 ± 8 years), and hypertensive (44% vs 14%) and had more dyslipidemia (84% vs 54%) and proteinuria (41% vs 8%; all p < 0.0001) than non diabetic participants (ND). After adjustment for major covariates, participants with DM had higher LV relative wall thickness (0.31 vs 0.30, p = 0.007), higher cardiac output (5.7 vs 5.2 L/min p < 0.0001), lower stress-corrected midwall shortening (99 vs 101%, p = 0.01); higher LV elastance (mean arterial BP/LV end-systolic volume: 2.00 vs 1.89 mmHg/mL, p = 0.01), arterial elastance (mean BP/stroke volume: 1.19 vs 1.14 mmHg/mL/beat, p = 0.03) central pulse pressure (39.4 vs 37.8 mmHg, p < 0.0001), with lower total peripheral resistance (1311 vs 1412 dynes/sec/cm⁵, p < 0.0001). Participants with DM also exhibited diastolic dysfunction with higher transmitral A velocity, longer isovolumic relaxation time and lower transmitral E/A ratio than ND participants (all <0.001), without significant differences for other echocardiographic variables.

Conclusions: Among adolescent and young adult of the SHS, with high prevalence of obesity and arterial hypertension, DM is associated with early metabolic and cardiovascular abnormalities, characterized by alterations of vascular-ventricular coupling and unfavorable LV geometric modifications.

3.23 Prevalence of Cardiovascular Diseases in Hypertensive Elderly Patients

Ferdinando D’Amico

UOC Geriatria PO Patti-Università Studi Messina, Patti-Messina, Italy

Introduction: To determine the prevalence of cardiovascular diseases in elderly subjects with a clinic history of hypertension (H), diabetes mellitus and microalbuminuria. This study is one of the objectives of the PATTI-for Stroke model (Profili di Assistenza e Terapia Territorio Integrato).

Methods: 133 hypertensive subjects were examined (61 males, 72 females, mean age 79 + 9). The design of the study included:

1. clinic measurement of blood pressure (PA);

2. Blood tests;

3. microalbuminuria (MA) on a 24-hour basis;

4. electrocardiogram;

5. echocardiogram.

Blood pressure control was considered for BP values <140/90 mmHg and <130/80 mmHg in patients affected by diabetes mellitus. Hypertensive subjects were split in two groups:

1. 61 subjects (M 28,F 33, mean age 77 + 8) with hypertension (H) and diabetes mellitus (DM) type 2;

2. 72 subjects (M 33, F 39, mean age 76 + 9) with hypertension.

The follow-up lasted 12 months with 4 control visits. In all subjects we evaluated the prevalence of cardiovascular diseases:myocardial infarct, angina, silent myocardial ischemia, sudden cardiac death.

Results: In the whole group we detected the following systolic blood pressure values: 148 ± 18 mmHg while the diastolic values were: 93 + 12 mmHg. 39.3% of the subjects had MAU. We split the subjects in two groups: (1) patients affected by H, DM and MA; (2) subjects affected by H and MA. The first group had a higher cardiovascular risk and a higher prevalence of ischemic cardiopathy (27.3% vs 16.7%, p < 0.001). 47.3% had controlled BP. In the first group we detected a larger group of patients with a less controlled BP (58.7%, p > 0.05) despite a combined therapy. In the same group we also detected: obesity BMI >30 kg/m² (33.3% vs 27.5%, p = 0.06), dyslipidemia (38.4% vs 31.3%, p < 0.005), TIA and stroke (9.3% vs 4.5%, p < 0.001), peripheral artery disease (14.7% vs 7.5%, p < 0.001).

Conclusions: This study shows the importance of risk stratification for elderly people affected by hypertension and diabetes mellitus type 2. The prevalence of microalbuminuria is higher in elderly subjects with hypertension and diabetes mellitus mostly when there is a lesser control of blood pressure. In the same patients the prevalence of cardiovascular risk, ischemic cardiopathy and comorbidity is higher.

Genetics and Pharmacogenomics

4.1 Relationship between Alpha-1a-Adrenoreceptor Gene Polymorphism and Sympathetic Activation in Patients with the Metabolic Syndrome

G.L. Seravalle,¹ G. Grassi,² S. Padmanabhan,³ M. Bombelli,² C. Delles,³ W.K. Lee,³ A. Dominiczack,³ F. Arenare² and G. Mancia²

1 Ospedale San Luca, Milan, Italy; 2 Clinica Medica, Università Milan, Bicocca, Monza, Italy; 3 BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK

Introduction: We have previously shown that in large population sample belonging to the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) cohort alpha-1A-adrenoreceptor (ADRA1A) was the candidate gene showing the strongest association with metabolic syndrome. Whether and to what extent the reported association has a functional counterpart as far as adrenergic function is concerned is unknown.

Methods: In 78 patients with metabolic syndrome (MS, NCEP ATPIII criteria) aged 57.4 ± 1.2 years (mean ± SEM, 64 males, 14 females), we measured, along with routine metabolic and anthropometric parameters useful for MS diagnosis), beat-to-beat blood pressure (Finapres), heart rate (HR, EKG), plasma norepinephrine (NE, venous sample, HPLC assay) and efferent post-ganglionic muscle sympathetic nerve traffic (MSNA, microneurography, peroneal nerve) during a 30 min resting period. Measurements also included genotype rs17055869ADRA1A (Illumina BeadChip platform) allele frequency analysis.

Results: According to the behaviour of the adrenergic function, MS patients were subdivided in 2 groups, one with normal values of the adrenergic function (n = 8, HR:72.3 ± 1.9 beats/min, NE: 204.2 ± 16 pg/mL and MSNA:41.2 ± 2.9 bursts/100 heart beats) and the other one with a marked cardiovascular adrenergic overdrive (n = 70, HR: 78.1 ± 1.6 beats/min, NE: 407.5 ± 22 pg/mL and MSNA: 60.8 ± 2.0 bursts/100 heart beats, p < 0.01 vs MS with normal adrenergic function). All MS patients with normal adrenergic function displayed a C/C genotype, with no presence of C/T or T/T. In contrast MS patients with sympathetic overactivity displayed a C/C, C/T or T/T genotype frequency in 55, 14 and 1 respectively. The homozygotic and heterozygotic status of the T allele was more represented in people with a sustained sympathetic activation, i.e. with all 3 the above mentioned adrenergic markers increased. MS patients with C/T or T/T genotype did not differ from the C/C genotype group for age, gender, body mass index, waist circumference, waist/hip ratio, blood pressure, HOMA index or leptin values.

Conclusions: These findings provide evidence that in MS sympathetic activation shows a trend towards the presence of CT or T allele of rs17055869ADRA1A. These preliminary data, which require to be confirmed in a larger MS population sample given the low frequency of T allele in the population, may suggest that in MS ADRA1A gene may be linked, both qualitatively and quantitatively, to a functional status of marked sympathetic overdrive.

4.2 Homozygosity for the EPHX2 K55R Polymorphism Increases the Long Term Risk of Ischemic Stroke in Men: a Study in Swedes

C. Fava,¹ M. Montagnana,¹ P. Almgren,² G. Berglund,² A. Lechi,¹ P. Minuz¹ and O. Melander²

1 Università di Verona, Verona, Italy; 2 Università di Lund, Lund, Sweden

Introduction: 5,6- 8,9- 11,12- and 14,15- epoxyeicosatrienoic acids (EETs) are lipid mediator with vasodilator properties and in some vascular act as endothelium derived hyperpolarizing factor (EDHF). Moreover, these compounds have diuretic and anti-inflammatory properties. The soluble Epoxide Hydrolase (gene name EPHX2) is responsible for metabolism of EETs to their correspondent inactive diols. Two functional polymorphisms of the EPHX2 gene, K55R and R287Q, showed respectively augmented and diminished metabolic activity in vitro and were associated with coronary heart disease and ischemic stroke in previous studies.

Aim: To evaluate the effect of these polymorphisms on blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events in more than 6000 middle-aged Swedes.

Methods: The polymorphisms were genotyped in the cardiovascular cohort of the Malmö Diet and Cancer Study. The incidence of cardiovascular events (coronary events, n = 274; ischemic stroke, n = 197) was monitored over 10 years of follow-up. The analysis of BP levels was performed twice: either excluding or including subjects under antihypertensive treatment.

Results: In the whole population, both polymorphisms had no effect on the studied parameters but a positive interaction between male and K55R was evident: male, but not female, EPHX2 gene R55R homozygotes had significantly higher crude and adjusted systolic BP and higher hypertension prevalence with respect to K-carriers. Kaplan-Meier curves showed higher incidence of ischemic strokes in male R55R homozygotes with respect to K-carriers (p = 0.015 by log rank test). After adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke in male R55R homozygotes remained significantly higher (hazard ratio: 4.8; 95% CI: 1.2, 19.9) even when baseline BP levels and hypertension prevalence were included in the Cox proportional hazard model. These polymorphisms were not associated with other metabolic syndrome related phenotypes.

Conclusions: A common K55R polymorphism of the EPHX2 gene confers a higher risk of hypertension prevalence and increases the risk of incident ischemic stroke in male homozygotes. Additional studies are needed to confirm these data and to elucidate the interaction between gender and the EPHX2 K55R polymorphism.

4.3 The Common Functional Polymorphism −50G>T of the CYP2J2 Gene is Not Associated with Coronary and Cerebrovascular Events in an Urban-Based Sample of Swedes

C. Fava,¹ M. Montagana,¹ P. Almgren,² G. Berglund,² A. Lechi,¹ P. Minuz¹ and O. Melander²

1 Università di Verona, Verona, Italy; 2 Università di Lund, Lund, Sweden

Introduction: CYP2J2 is responsible for the production of 5,6- 8,9- 11,12- and 14,15- epoxy-eicosatrienoic acids, vasodilator and anti-inflammatory substances. It is abundantly expressed in human heart and also present in kidney and vasculature. Carriers of a common polymorphism, the CYP2J2 −50G>T, within the promoter region, have reduced expression of CYP2J2 mRNA level in the heart putatively through the interference with a binding site for a transcription factor with consequently reduced circulating levels of CYP2J2 epoxygenase metabolites in vivo.

Aim: To evaluate the effect of this polymorphism on blood pressure (BP) levels, hypertension prevalence, and risk of incident cardiovascular events in middle-aged Swedes.

Methods: The polymorphisms were genotyped in nearly 6000 subjects recruited in the cardiovascular cohort of the ‘Malmö Diet and Cancer’ Study. The incidence of cardiovascular events (coronary events, n = 261; ischemic stroke, n = 185) was monitored over 10 years of follow-up. The analysis of BP levels was performed twice: either excluding or including subjects under antihypertensive treatment.

Results: In the whole population the polymorphism had no effect on BP and hypertension prevalence and no interaction was found between the polymorphism and gender, age or body mass index. Before and after adjustment for major cardiovascular risk factors, the hazard ratio for incident ischemic stroke and coronary events was not significantly different in carriers of different genotypes.

Conclusions: Our data do not support a major role for the CYP2J2 −50G>T variant in determining BP level and incident ischemic events in middle aged Caucasians. Other studies are needed to elucidate if other polymorphisms in the same gene could have a role in BP homeostasis or incidence of cardiovascular events.

4.4 Neuropeptide Y Receptor Y2 (NPY2R) Gene Polymorphism is a Modifier for the Effect of NPY on Left Ventricular Mass Index (LVMI) in End-Stage Renal Disease (ESRD) Patients

A. Testa,¹ F. Mallamaci,¹ F.A. Benedetto,² R. Macrì,¹ A. Piano,¹ R.M. Parlongo,¹ B. Spoto,¹ G. Tripepi¹ and C. Zoccali¹

1 CNR-Az. Osp., Reggio Calabria, Italy; 2 Servizio di Cardiologia Osp., Reggio Calabria, Italy

Introduction: Neuropeptide Y (NPY) is a sympathetic neurotransmitter that acts on multiple receptors (Y1–Y6) which regulate vascular remodelling and angiogenesis. Plasma levels of NPY are increased in patients with end stage renal disease (ESRD) and are independently related to left ventricular hypertrophy (LVH) and incident CV events in these patients.

Methods: Since Mendelian randomization studies are better than purely associative studies for assessing causality, we investigated the relationship between a polymorphism of NPY2R gene (T585C) and the severity of LVH at echocardiography in 239 ESRD patients (age: 60 ± 15 years; M: 135; F: 104). Furthermore, we analysed the association between NPY2R polymorphism and atherosclerosis in a representative subgroup of 133 ESRD patients who underwent the Eco-Colour Doppler study of the carotid arteries.

Results: The distribution of NPY2R polymorphism (TT genotype: 23%; TC genotype: 46%; CC genotype: 31%) did not deviate from Hardy Weinberg equilibrium. Overall, LVMI was directly related to plasma NPY concentration (r = 0.29, p < 0.001). In a fully adjusted analysis, the presence of the C allele (CC and CG genotypes) was a clear-cut modifier for the effect of NPY on LVMI (highly significant interaction term in the multiple regression analysis, p = 0.008). Furthermore, the total number of atherosclerotic plaques was significantly higher (p = 0.008) in patients with the C allele (median: 4 plaques, inter-quartile range: 1–6 plaques) than in those without this allele (median: 1 plaque, inter-quartile 0–3 plaques) and this relationship remained statistically significant (α = 0.21, p = 0.01) in multiple linear regression analysis. No interaction was found between the presence of C allele and plasma levels of NPY for predicting the total number of atherosclerotic plaques.

Conclusions: The C allele of the NPY2R polymorphism is a modifier for the relationship between circulating levels of NPY and the severity of LVH in ESRD patients and it is independently related to the severity of carotid atherosclerosis in these patients. These results offer a genetic basis to the hypothesis that NPY is causally implicated in the high CV risk in ESRD patients.

Heart

5.1 Pre-Clinic Cardiac Damage in Uncomplicated Sclerodermic Patients

A.C.M. Capra,¹ M.R. Pozzi,² E. Allevi,² E. Banfi,³ E. Montemerlo,³ P. Campadello,³ M. Papalettera,⁴ M. Betelli,³ M. Pozzi,³ C. Giannattasio¹ and G. Mancia⁵

1 Clinica Medica, ospedale San gerardo e Università Milan Bicocca, Monza, Italy; 2 Clinicamedica, ospedale san Gerardo, Monza, Italy; 3 Università degli studi Milan Bicocca, Monza, Italy; 4 Centro Trasfusionale, Ospedale san Gerardo Monza, Monza, Italy; 5 Centro Auxologico Italiano, Milan, Italy

Introduction: Structural cardiac alterations may occur in patients affected by systemic sclerosis, due at least in part, to substitution of myocardial tissue with collagen. However it is not known at which stage of the disease cardiac fibrosis is detectable by ultrasonography.

Aim: To investigate by ultrasonography if cardiac fibrosis is already detectable at an early stage in sclerodermic patients, without clinic cardiopathy and no respiratory or muscle involvement.

Methods: We studied 27 patients (22 females, 5 males, age 60.7 ± 1.7 years, means ± SE) affected by systemic sclerosis without clinically relevant cardiac, pulmonary and skeletal muscle impairment (carbon dioxide lung diffusibility DLCO, 6 min walking test, echocardiography). In each patient the presence of cardiac fibrosis was assessed by integrated backscatter (IBS) analysis. 13 healthy age and sex matched subjects served as controls (age 51 ± 2.4 years).

Results: Left ventricular (LV) end diastolic diameter (EDD) LV mass indexed by BSA, LV ejection fraction (EF) and diastolic function (transmitral PW E/A, DEC time, and Mitral annulus TDI) were similar in the 2 groups and in the range of normality, although E/A’m and especially Sm are higher in the control group in compared to sclerodermic patients (Sm 10 ± 0.1 vs 6.5 ± 0.4 msec, p < 0.05). Average IBS was significantly increased in the sclerodermic patients compared to controls (average value of IBS 26.4 ± 1.3 dB vs 22.1 ± 1.5, plus 20%, p < 0.04).

Conclusions: In systemic sclerosis patients the average value of IBS is higher compared to controls, suggesting early cardiac fibrosis, in absence of any other structural or functional echographically detectable cardiac impairment, and such data may be related to initial reduction of tissue contractility showed by TDI analysis. Thus IBS evaluation may provide additional information on the presence of early cardiac fibrosis, even in asymptomatic patients.

5.2 Diastolic Function Evaluated by Tissue Doppler Analysis and Arterial Stiffness after Cardiac Revascularization

A.C.M. Capra,¹ A. Cafro,² E. Scanziani,² P. Canova,² M. Pozzi,² M. Betelli,² F. Cesana,² I. Calchera,³ V. Colombo,³ F. Formica,⁴ G. Paolini,⁴ C. Giannattasio¹ and G. Mancia⁵

1 Clinica Medica, ospedale San gerardo e Università Milan Bicocca, Monza, Italy; 2 Università degli studi Milan Bicocca, Monza, Italy; 3 Cardiologia, Ospedale san Gerardo, Monza, Italy; 4 Clinica Cardiochirurgica, ospedale san gerardo e Università Milan Bicocca, Monza, Italy; 5 Centro Auxologico Italiano, Milan, Italy

Introduction: Ischemic cardiopathy can be associated with diastolic dysfunction and with an increase in arterial stiffness. It has not established, however, if these alterations can be modified by myocardial revascularization.

Methods: We investigated 39 patients (age 59 ± 3.2 years, SBP/DBP 127/72 ± 3/7 mmHg HR 66 ± 3.3, means ± SE) admitted to hospital to undergo coronary angiography because of stable ischemic cardiopathy. In 21 patients coronary angiography led to a diagnosis of significant coronary stenosis which implied a treatment by PTCA and stenting or by-pass surgery (group A). The remaining 18 patients were not treated because of the absence of significant coronary stenosis (group B). All patients were on antihypertensive, lipid lowering and antiplatelet drugs. In each patient we performed a standard echocardiogram to evaluate LV diameters, systolic and diastolic function (EF and E/A respectively) plus tissue doppler (TDI) analysis (lateral and septal mitral annulus E/Am). Moreover we assessed vascular function by means of pulse wave velocity (as index of arterial distensibility) and flow mediated dilatation (as index of endothelial function). Measurements were obtained at baseline (B) and six months later.

Results: At B, there was no difference in the two group as far as BP, standard systolic and diastolic function, c-f PWV (12.3 ± 0.7 vs 12.1 ± 0.7 m/s), and percentage of radial FMD increase (+11 vs 10%) were concerned, LVMI was increased and E/Am decreased in the group with severe coronary stenosis (LVMI 130.3 ± 5.3 vs 100.4 ± 7.2 gr/mq, p < 0.002), (E/Am 0.6 ± 0.01 vs 0.8 ± 0.01, p < 0.05). After six months the two groups A and B showed no significant change in the measured variables, except for LVMI which showed a reduction (from 130.3 ± 5.3 to 115.6 ± 8.7 gr/mq, NS.) and diastolic function evaluated by TDI which was significantly increased (septal E/Am 0.9 ± 0.01 vs 0.6 ± 0.09, p < 0.03) in the group who underwent cardiac revascularization. C-f PWV and FMD remained unchanged after revascularization.

Conclusions: Cardiac revascularization exerts a positive influence on cardiac function and structure, but does not modify significantly peripheral vascular stiffness, which is probably responsible for the progression of coronaropathy.

5.3 Indexation of Left Ventricular Mass to Body Surface Area and Height to Allometric Power of 2.7: is the Difference Limited to Obese Hypertensive Patients?

F. Negri,¹ V. Giudici,² S. Meani,³ C. Valerio,⁴ C. Sala,⁵ A. Zanchetti,⁶ G. Mancia⁷ and C. Cuspidi¹

1 DipartimentoClinica Med. e Prevenzione Univ.Milano-Bicocca e Un.Ricerca Clinica Ist.Auxologico Italiano, Milan, Italy; 2 Unità di Ricerca Clinica, Istituto Auxologico Italiano, Milan, Italy; 3 Divisione di Cardiologia, Ospedale di Rho, Milan, Italy; 4 Istituto Auxologico Italiano, Meda, Italy; 5 DipartimentoToraco-Polm. eCardiocirc. Policlinico e Centro interuniv. Fisiologia Clinica Univ. Milan, Milan, Italy; 6 Un.Ricerca Clinica Ist.Auxologico Italiano e Centro interuniv. Fisiol.Clinica e Ipert., Univ. Milan, Milan, Italy; 7 DipartimentoCl.Med., Un.Ricerca Clinica Ist.Auxologico Italiano e C.Interuniv.Fisiol.Clinica Univ. MI-Bicocca, Milan, Italy

Introduction: Whether left ventricular mass (LVM) should be normalized to different indexes in relation to body size is still debated.

Aim: We sought to evaluate the prevalence of left ventricular hypertrophy (LVH) defined by different indexation criteria in a cohort of hypertensive subjects categorized according to body mass index (BMI).

Methods: A total of 2213 essential hypertensive subjects included in the Evaluation of Target Organ Damage in Hypertension (ETODH) were divided in three groups according to BMI thresholds (<25, 25–29.9 and ≥30 kg/m²). All patients underwent extensive investigations including quantitative echocardiography. LVH was defined as an LVM index equal to or higher than (1) 125 g/m² in men and 110 g/m² in women, (2) 51 g/m^2.7 in men and 47 g/m^2.7 in women.

Results: Overall, 687 out of 2213 patients (31.0%) were found to have LVH when LVM was indexed to body surface area (BSA) and 1030 (46.5%) when indexed to height^2.7. A total of 845 patients (38.2%) had normal BMI, 954 patients (43.1%) were overweight and 414 (18.7%) were obese. Prevalence rates of LVH in the three groups were 25.1, 31.6, 41.2% by indexation to BSA and 29.9, 50.5, 71.8% by indexation to height2.7, respectively.

Conclusions: LVM indexed to BSA markedly underestimates LVH prevalence in obese as well as overweight hypertensive patients. To avoid a systematic misclassification of cardiovascular risk, LVM should be routinely indexed to height2.7 in overweight and obese patients representing a large percentage of the hypertensive population.

5.4 Improving Cardiovascular Risk Stratification by Indexing Left Ventricular Mass to Both Body Surface Area and Height 2.7

V. Giudici,¹ F. Negri,² S. Meani,³ C. Sala,⁴ A. Zanchetti,⁵ G. Mancia⁶ and C. Cuspidi²

1 Unità di Ricerca Clinica, Istituto Auxologico Italiano, Milan, Italy; 2 DipartimentoClinica Med. e Prevenzione Univ.Milano-Bicocca e Un.Ricerca Clinica Ist.Auxologico Italiano, Milan, Italy; 3 Divisione di Cardiologia, Ospedale di Rho, Milan, Italy; 4 DipartimentoToraco-Polm. e Cardiocirc. Policlinico e Centro interuniv. Fisiologia Clinica Univ. Milan, Milan, Italy; 5 Un.Ricerca Clinica Ist.Auxologico Italiano e Centro interuniv. Fisiol.Clinica e Ipert., Univ. Milan, Milan, Italy; 6 DipartimentoCl.Med., Un.Ricerca Clinica Ist.Auxologico Italiano e C.Interuniv.Fisiol.Clinica Univ.MI-Bicocca, Milan, Italy

Introduction: Limited information is available about the burden of hypertension on echo-lab activity in current practice.

Aim: To investigate in present nation-wide survey in out-patient echo-labs the prevalence rates of:

1. echo examinations performed for the evaluation of hypertensive cardiac damage;

2. reports providing quantitative data on left ventricular (LV) structure and geometry;

3. LV hypertrophy (LVH) in hypertensive patients referred to echo labs.

Methods: The study was carried out in 14 out-patient echo-labs across Italy. Prescriptions written by general practitioners were used to identify the indications for the examinations. Estimates of LVH were derived from original echo reports or were calculated from LV primary measures, when available, with Devereux’s formula in a post-analysis.

Results: Echo examination was performed in 2449 subjects (1245 men and 1201 women); hypertension was the indication for echo in 745 (30.4%) cases. In this subgroup, LV mass (LVM), LVM indexed to body surface area, LVM indexed to height^42.7 and RWT ratio were reported in 58%, 59%, 54%, and 52%, respectively. LVH was present in 53% of untreated hypertensive patients and, among treated patients, in 45 and 65 percent of those with and without BP control, respectively.

Conclusions: Our findings show that:

1. hypertension accounts for approximately one third of echo examinations performed in clinic practice;

2. a large fraction of echo reports do not provide quantitative data on LVM and LV geometry,

3. LVH is highly prevalent in hypertensive patients referred to echo labs for the search for cardiac damage.

5.5 Home Telemonitoring in the Management of Chronic Heart Failure

M. Benvenuto,¹ L. Beltrami,¹ A. Esposito,² G. Rossetti,² D. Solari,¹ C. Redaelli,¹ A. Pernigotti³ and S. Carugo²

1 IMMeS e PAT, I UOC Cardiologia, Milan, Italy; 2 Dipart. toraco-polmonare e cardiocircolatorio, Università di Milan; IMMes e PAT, I UOC Cardiologia, Milan, Italy; 3 Università degli Studi, Milan, Italy

Introduction: Chronic Heart Failure (CHF) is one of the leading causes of hospitalization and health costs for CHF are increasing.

Aim: We sought to identify whether a new approach of home management of these patients with HTM improves outcomes cutting hospitalization and death.

Methods: We enrolled 60 patients with a recent clinic admission for CHF with left ventricular ejection fraction (LVEF) <40% or diastolic dysfunction. Patients sent and received data via Internet with the telematic support. Home telemonitoring (HTM) consisted of 6 months weekly remote monitoring of vital signs and ECG, with feed-back instructions for the management of drug therapy and way of life. Quality of life was measured by means of Minnesota Living with Heart Failure Questionnaire (MLHFQ).

Results: We enrolled 60 patients from 50 to 94 years (mean 74, median 74, mode 61), 33 males (55%), 27 females (45%). The aetiology of heart disease was: post-ischemic 35 (58%), valvular 11 (18%), idiopathic 5(8%), hypertensive 6 (11%), post-myocardial inflammation 1 (2%), post-ischemic associated with immunologic disease 2 (3%). Mean LVEF at the beginning was 32% and after 6 months became 38% (T1 vs T0 p < 0.0001). After 6 months patients in NYHA Class IV underwent: 48% in III, 37% in II–III, 5% in II and 5% remained stable in IV; patients in NYHA Class III became II (18%), II–III (18%) and 64% remained stable. Mean MLHFQ score at the beginning was mean 54 and after 6 months became 24 (T1 vs T0 p < 0.0001). Considering titration, beta-blockers use increased from 67% to 88%, ACEI from 50% to 68%, AT1 from 47% to 80% and diuretics from 90% to 98%; the use of digitalis glycosides lowered from 78% to 10% (T1 vs T0 p < 0.001). The rate of mortality and hospitalization for clinic instability at 6 months was extremely low (5%).

Conclusions: The results of this study support the compliance, effectiveness and appropriateness of HTM for the management of CHF in the early months after heart failure admission. In particular we obtained a successful optimization of the therapy according to Guidelines, a significant increase in LVEF and a sensible decrease in III–IV NYHA patients and MLHFQ score as an index of the sensible improvement of the quality of life of these patients.

5.6 Echocardiography in Clinical Practice: the Burden of Arterial Hypertension: a Multicenter Italian Survey

C. Cuspidi, F. Negri, V. Giudici, M.L. Muiesan, G. De Simone, N. De Luca, L. Lonati, A. Morganti, G. Tocci, A. Capra, A. Milan, A. Vaccarella, M. Longo, G. Macca and G. Mancia on behalf of Gruppo di Studio Cuore e Ipertensione della SIIA

Gruppo di Studio Cuore e Ipertensione della SIIA, Milan, Italy

Introduction: Little information is available about the burden of hypertension on echo-lab activity in current practice.

Aim: To investigate the prevalence rates of:

1. echo examinations performed for the evaluation of hypertensive cardiac damage;

2. reports providing quantitative data on left ventricular (LV) structure and geometry;

3. left ventricular hypertrophy (LVH) in hypertensive patients referred to echo labs.

Methods: The study was carried out in 14 out-patient echo-labs across Italy. Prescriptions written by general practitioners were used to identify the indications for the examinations. Estimates of LVH were derived from original echo reports or were calculated from LV primary measures, when available, with Devereux’s formula in a post-analysis.

Results: Echo examination was performed in 2449 subjects (1245 men and 1201 women); hypertension was the indication for echo in 745 (30.4%) cases. In this subgroup, LV mass (LVM), LVM indexed to body surface area, LVM indexed to height 2.7 and RWT ratio were reported in 58%, 59%, 54%, and 52%, respectively. LVH was present in 53% of untreated hypertensive patients and, among treated patients, in 45 and 65 percent of those with and without BP control, respectively.

Conclusions: Our findings show that:

1. hypertension accounts for approximately one third of echo examinations performed in clinic practice;

2. a large fraction of echo reports do not provide quantitative data on LVM and LV geometry;

3. LVH is highly prevalent in hypertensive patients referred to echo labs for the search for cardiac damage.

5.7 Cardiac Remodelling in Visceral Obesity: Role of the Metabolic Syndrome

A.M. Maresca, G. Martegani, E. Nicolini, A. Lippi, C. Mongiardi, L. Montalbetti, L. Mellana, A.M. Grandi and A. Venco

Dipartimento di Medicina Clinica-Università degli Studi dell’Insubria, Varese, Italy

Introduction: In general population and hypertensive patients the presence of metabolic syndrome (MetS) is associated to a greater left ventricular (LV) remodeling. Moreover visceral obesity is also a well-known risk factor for LV hypertrophy and diastolic dysfunction. Few studies investigated the impact of MetS on cardiac remodeling in patients with visceral obesity.

Aim: To evaluate the influence of MetS on LV morpho-functional characteristics in patients with visceral obesity.

Methods: We enrolled 64 (39 males, mean age 54 + 11 years) overweight-obese patients (BMI > 25 kg/m², waist circumference >88 cm for women and >102 cm for men), without known cardiovascular diseases or diabetes. MetS was defined by AHA-NHLBI (2005) criteria. Each patient underwent ambulatory blood pressure (BP) monitoring and LV echocardiographic examination (M-mode, B-mode, trans-mitral Doppler and tissue Doppler).

Results: MetS was present in 39 patients (MetS+) [61%]. MetS+ patients were older than MetS— (57 + 12 vs 51 + 12 years, p < 0.05) whereas there was no difference between groups in gender, BMI, waist circumference, smoke habit, 24 h systolic and diastolic BP. End-diastolic LV diameter was normal in all patients and not different between the two groups. LV mass index was greater in MetS+ (57.9 + 17.5 kg/m²,7) than in MetS— (47.4 + 8.6 kg/m²,7, p = 0.003) due to greater wall thickness. LV diastolic indices from tissue Doppler evaluation were lower in MetS+ than in MetS— (Em/Am 0.9 ± 0.06 vs 1.1 ± 0.06, p < 0.04, E’/A’ 0.87 ± 0.05 vs 1.05 ± 0.06, p < 0.02). These results didn’t change after adjustment for age. LV ejection fraction was normal in all patients and not different between the two groups.

Conclusions: In patients with visceral obesity MetS appears to significantly influence LV remodeling, inducing greater myocardial hypertrophy and subclinic impairment of diastolic function.

5.8 Left Ventricular Remodelling in Obstructive Sleep Apnea: Influence of CPAP Treatment and Weight Changes

A.M. Maresca,¹ E. Laurita,¹ F. Solbiati,¹ F. Colombo,² C. Salina,³ E. Nicolini,¹ L. Montalbetti,¹ A.M. Grandi¹ and A. Venco¹

1 Dipartimento di Medicina Clinica-Università degli Studi dell’Insubria, Varese, Italy; 2 Pneumologia-Ospedale di Circolo e Fondazione Macchi, Varese, Italy; 3 Pneumologia Riabilitativa-Ospedale di Somma Lombardo, Somma Lombardo, Italy

Introduction: Left ventricular (LV) remodelling has been described in obstructive sleep apnea (OSA). Continuous positive airways pressure (CPAP) ventilation is an effective therapy in OSA. Few data are available about CPAP effects on LV remodelling.

Aim: To evaluate the effects of CPAP treatment and weight changes on LV morpho-functional features in OSA patients with abdominal obesity.

Methods: We enrolled 41 OSA patients. Selection criteria were: apnea-hypopnea index >20 events/hour of sleep; abdominal obesity (BMI >27 kg/m² and waist circumference >102 cm for men and >88 cm for women); no previous CPAP treatment, no known cardiovascular diseases, diabetes, COPD or thyroid diseases. Each patient underwent 24 h ambulatory blood pressure (BP) monitoring and LV echocardiographic examination before and after at least 12 months of CPAP treatment. No changes in antihypertensive drugs were made during study time.

Results: Mean length of CPAP treatment was 23 + 7 months. After CPAP we found: significant (p < 0.001) improvement of all the respiratory parameters, significant decrease of weight, BMI, waist circumference, 24 h, day-time, night-time heart rate and diastolic BP, night-time systolic BP and LV mass index (59.7 + 2.2 to 56.4 + 1.9 kg/m²,7, p = 0,04); mild increase of transmitral E/A ratio (0.94 + 0.04 to 1.03 + 0.04, p = 0.04). We subdivided patients on the basis of weight changes: in 20 patients weight was decreased >2kg (W−), in 21 patients weight was unchanged or increased >2kg (W+). Mean length of CPAP treatment and the extent of respiratory improvement was similar between the two groups. In W− we found a significant reduction in heart rate, 24 h BP and LV mass index (64.7 + 3.3 to 56.6 + 3.2 kg/m²,7 p < 0.001) and a significant increase (p < 0.02) of LV diastolic indices. In W+ there was no change in all BP and LV morpho-functional parameters.

Conclusions: In OSA patients with abdominal obesity, CPAP treatment is effective in improving respiratory function, whereas LV remodeling seems to be mainly influenced by weight reduction. Indeed, despite the similar improvement of respiratory performance, only in the group of patients with weight reduction there was BP reduction, LV hypertrophy regression and improvement of diastolic function.

5.9 Left Ventricular Mass Index in Children According to Blood Pressure and Body Weight

F. Pieruzzi,¹ M. Giussani,² P. Brambilla,² V. Tono,¹ V. Barbieri,¹ V. Sala,¹ A. Stella,¹ L. Antolini¹ and S. Genovesi¹

1 Università degli Studi di Milan Bicocca, Monza, Italy; 2 FIMP, Milan, Italy

Introduction: To study left ventricular mass index in relation to different body weight and blood pressure classes in children.

Methods: Body weight, height, blood pressure (BP) and left ventricular mass (LVM) were measured in 361 children of similar age (9.8 + 2.2 years, 201 males), and divided according to the National High Blood Pressure Education Program in normotensives: systolic (SBP) and diastolic BP (DBP) <90th percentile; pre-hypertensives: SBP and/or DBP >90th and <95th; hypertensive patients: SBP and/or DBP >95th. Children with casual SBP and/or DBP >90th were considered casual hypertensive patients. Normal weight (NW), overweight (OW) and obese (OB) children were defined according to the International Obesity Task Force. LVM was calculated according to the ASE formula and indexed to the height 2.7.

Results: NW children were 78 (21.5%),OW 127 (35.1%) and OB 156 (43.4%). BP class distribution was: normotensives: 52 (14.5%); pre-hypertensive patients: 81 (22.4%); hypertensive patients: 133 (36.8%) and subjects with casual hypertension: 95 (26.3%). In all the subjects with elevated blood pressure values (>90th) the percentage of OW and OB children was significantly higher than in NW subjects (p < 0.001). The values of left ventricular mass index are reported in the table. LVM values change according to blood pressure classes. Multiple analysis shows a significant difference between normotensives and the other blood pressure classes (p < 0.001). Body weight class stratification shows that LVM distribution changes (p < 0.001) with a significant increase among all body weight classes (NW: 32.9 + 5.4, OW 37.3 + 5.6, OB 41.5 + 5.0, p < 0.001). Both absolute values of SBP and DBP are significantly and directly correlated to LVM values (p < 0.05).

Conclusions: In children BP values above the 90th percentile are associated with greater LVM values as compared to normotensives subjects. Body weight class is strongly linked to both elevated BP values and increased LVM. This study suggests that target organ damage should be assessed not only in children with hypertension but also with pre-hypertension and casual hypertension, in particular when body weight excess is present.

5.10 Impact of Diabetes on Left Ventricular Geometry in Hypertensive Patients with Chronic Kidney Disease

A. Palermo, E. Nardi, P. Cusimano, G. Mulè,G. Bonanno, T. Bellavia, S. Cottone and G. Cerasola

Dipartimento di Medicina Interna, Malattie Cardiovascolari e Nefrourologiche-Università di Palermo, Palermo, Italy

Introduction: In hypertensive patients the presence of chronic kidney disease (CKD) is associated with higher prevalence of left ventricular hypertrophy (LVH). In this study we evaluate the impact of diabetes (DM) on left ventricular geometry in a group of hypertensive patients with CKD.

Methods: 93 hypertensive patients with CKD and DM and 165 non diabetic hypertensive patients with CKD were enrolled. The two groups did not differ with regard to age, distribution of sex, BMI, blood pressure, duration of hypertension, GFR and hemoglobin. All patients underwent echocardiographic examination (Acuson Sequoia 512). Patients with heart failure, coronary artery disease, valvular diseases, and obesity were excluded.

Results: Patients with DM, when compared with those without DM, had higher septum thickness (p < 0.0001), posterior wall thickness (p = 0.01), LVMI (p < 0.05), LVMH 2 7 (p < 0.03), and relative wall thickness (p < 0.0001). No differences about LV diameters were observed. The difference of prevalence of LVH (59.6% in group with DM and 47.6% in patients without DM) did not reach statistical significance. (p = 0.85). However, the prevalence of the different patterns of LVH was significantly different between the two groups: in the group with DM, 55.35% of patients had concentric LVH, 30.35% had eccentric LVH, and 14.3% had mixed LVH [characterized by LVMI >125 g/m² in men and >110 g/m² in women, RWT >0.45, and LV end-diastolic diameter indexed by body surface area (LVEDD/m²) >3.2 in men and >3.1 in women]. In the group without DM, 44.3% of patients had concentric, 48.1% had eccentric and 7.6% had mixed LVH (p = 0.026 vs group with DM).

Conclusions: Our data show that diabetes is associated with an increase of LV mass and wall thicknesses in hypertensive patients with CKD. In our sample the prevalence of LVH was similar in patients with and without, but DM was found to be associated with higher prevalence of concentric and mixed LVH. It is likely that such influence on LV geometry may contribute to explain the unfavourable prognosis of hypertensive patients who have CKD and diabetes. In these patients a global and aggressive therapeutic approach is necessary to reduce cardiac damage and improve the prognosis.

5.11 Determining Factors of Left Ventricular Hypertrophy (LVH) in Hypertensive Patients

A. Belfiore, V.O. Palmieri, M. Lucariello, E. Lella and G. Palasciano

Policlinico, Bari, Italy

Introduction: Many factors, besides the high pressure load, are involved in the development of LVH in hypertensive patients.

Aim:

1. to evaluate the prevalence of LVH and the remodeling pattern of LV in a population of on therapy hypertensive patients;

2. to evaluate the correlation between indexed LV mass (iLVM) and several clinic and laboratory variables.

Methods: 302 patients have been recruited (M:F = 153–149; aged 55 + 11 years, range 23–81 years). Each patient underwent to a complete clinic and functional evaluation, including echocardiographic study of iLVM.

Results: On the basis of the pre-fixed cut-off value of iLVM for LVH (> 50g/m2.7), patients have been divided into two groups (table).

Conclusions: LVH is largely represented in our study population; concentric remodeling is the more frequent form of remodeling; LVH is positively correlated to clinic SBP, duration of hypertension, frequency of Metabolic Syndrome; diastolic dysfunction is early and may be observed even in absence of LVH. Patients with concentric hypertrophy had a more serious hypertensive disease, characterized by higher BP values, number of hypotensive drugs and prevalence of obesity.

5.12 Impact of Hormonal Factors in the Evolution of Cardiac Geometry in Hypertension

Elena Colli, Chiara Cerutti, Francesca Corlianò, Elisa Cornetti,Gian Paolo Fra, Gian Piero Carnevale and Ettore Bartoli

Università del Piemonte Orientale Amedeo Avogadro, Ospedale Maggiore della Carità , Clinica Medica, Novara, Italy

Introduction: The increase in relative wall thickness (RWT) in hypertensive subjects identifies concentric left ventricular remodeling. Both hypertension and hormonal factors, such as insulin resistance, hyperinsulinemia and the renin-angiotensin-aldosterone system, cause the evolution of cardiac damage which, in turn, leads to the occurrence of cardiovascular events.

Aim: To define whether the increased RWT is associated to the above-mentioned hormonal factors and chromogranine-A, suggestive of the activation of adrenergic system.

Methods: We enrolled 338 hypertensive subjects (male 152, female 186), aged 50.7 ± 13.4, normo-gluco-tolerant (NGT) by oral-glucose-tolerance-test (OGTT). We classified these subjects into two groups based on RWT, normal or high, using Ganau’s classification, which stratifies this echocardiographic index according to age. We considered anthropometric parameters, such as BMI, waist circumference (WC), glucose and insulin plasma concentrations at time 0’ and 120’ (G0, G120, Ins0 and Ins120), insulin-resistance index (HOMAIR), insulin-sensitivity index (EISI), aldosterone (Ald) and chromogranine-A (ChromoA).

Results: Hypertensive subjects with elevated RWT (n. 197) have BMI, WC, Ins0, HOMAIR, Ald and ChromoA significantly higher than those with normal RWT. Male subjects with elevated RWT (n. 98) exhibit levels of Ald higher than those with normal RWT, while BMI, WC, HOMAIR and EISI are not different between the two groups. This same analysis in female subjects demonstrates that BMI, WC and chromoA are higher when RWT is increased (n. 99). Male and female subjects with increased RWT show no difference in hormonal factors with respect to normals, except for Ins120 which is higher in females.

Conclusions: We conclude that hormonal factors play a role in the worsening cardiac geometry of hypertension: aldosterone is important in males, chromogranine-A in females. Female hypertensive subjects exhibit an impaired insulin action even though still in the normal glucose tolerance range.

5.13 Diastolic Function in Arterial Hypertension: Impact of Different Echocardiographic Criteria on Diagnosis

A. Milan, M. Caserta, D. Naso, C. Magnino, E. Puglisi, F. Tosello, E. Avenatti, S. Abram, S. Totaro, D. Tizzani, A. Viola, V. Milazzo and F. Veglio

Università di Torino-ASO San Giovanni Battista-Cattedra di Medicina Interna, Torino, Italy

Introduction: Diastolic dysfunction is usually associated and often precedes left ventricular hypertrophy in hypertensive patients.

Aim: To evaluate the sensitivity of different echocardiographic parameters in order to estimate diastolic dysfunction prevalence in arterial hypertension.

Methods: We studied 308 essential hypertensive patients (mean age ± standard deviation 49.8 ± 11 years; SBP/DBP 140.4 ± 15/84.9 ± 10 mmHg). Every subject underwent clinic evaluation, echocardiography with ultrasound systems (ATL 5000) equipped with multiple frequency phased array transducers (2 to 4 MHz) to study left ventricular morphology and function. Transmitralic Doppler (Dopp mitr), Doppler of pulmonary veins (PVarD, Adur) flow, tissue Doppler of mitral annulus (E’ sep, E’ lat) and left atrial volume (LAV ind) were acquired for each patient.

Results: Transmitralic Doppler alone (figure), allows the detection of diastolic dysfunction in 34% of hypertensive patients. When this parameter was combined with Tissue Doppler, Pulmonary veins Doppler and LAV ind, about 40% of subjects previously classified as normal, resulted affected by diastolic dysfunction (p < 0.001). Left atrial volume, indexed for body surface area, appears to be the most sensitive criteria.

Conclusions: Prevalence of diastolic dysfunction changes according to limits and criteria used for its detection. Systematic use of recent parameters (e.g. atrial volume or TDI) represents a sensitive tool to identify diastolic dysfunction in hypertensive patients.

5.14 Metabolic Syndrome is an Independent Risk Factor for Left Ventricular Hypertrophy in Overweight/Obese Hypertensive Patients

R. Sarzani, F. Guerra, F. Salvi, L. Mancinelli, M. Fortunati, L. Angelini, P. Dessì-Fulgheri and A. Rappelli

Clinica di Medicina Interna, Univ. Politec. Marche, Ancona, Italy

Introduction: Overweight and obesity influence blood pressure (BP) and left ventricular mass (LVM). It is unclear whether the presence of metabolic syndrome (MetS) affects BP and echocardiographic parameters in overweight/obese hypertensive patients.

Methods: We studied 365 overweight/obese hypertensive patients (age ≤65 years) presenting to our Centre for BP control-related problems. Patients who underwent recent changes of antihypertensive therapy were excluded. MetS was defined according to NCEP III/ATP with AHA modifications. Left atrium diameter (LAD), ejection fraction (EF), relative wall thickness (RWT) and LVM, indexed by either body surface area (LVMi) or height 2.7 (LVM/h 2.7) were evaluated by echocardiography. Left ventricular hypertrophy (LVH) was defined as LVMi ≥125 g/m² for males and ≥110 g/m² for females and LVM/h2.7 ≥49.2 g/m2.7 for males and ≥46.7 g/m2.7 for females. Concentric remodeling was defined as RWT ≥0.42.

Results: Two hundred and forty patients (65.8%) had MetS. Hypertensive patients with MetS had significantly higher systolic (SBP), diastolic (DBP) and mean BP (MBP) and BMI than those without MetS. No difference in LVMi was found between patients with or without MetS. Hypertensive patients with MetS had higher LAD (40.3 ± 5.8 vs 38.9 ± 6 cm; p = 0.033) and LVM/h2.7 (58.6 ± 15.5 vs 53.7 ± 14.3 g/m2.7; p = 0.012), as well as reduced EF than those without MetS. Hypertensive patients with MetS have a near 2-fold higher risk to have LVH/h2.7 (unadjusted OR 1.77; 95% CI 1.12, 2.81; p = 0.01). The OR changed to 1.6 when the model was adjusted by age and MBP (OR 1.6; 95% CI 1.01, 2.56; p = 0.05). Similarly, patients with MetS had a 2-fold higher risk to have concentric remodeling (OR 1.95 95% CI 1.16, 3.29, p = 0.01) also when the model was adjusted by age, sex, and MBP (OR 1.89; 95% CI 1.11, 3.22; p = 0.02). MetS lost its independent effect when BMI was included in the model.

Conclusions: MetS influences BP levels, LVM and cardiac dimensions and remodeling. MetS maintains its role of risk factor for LVH and concentric LV remodeling independently of age, sex and MBP, making it a useful predictor of target organ damage in clinic practice. However, MetS loses its independent effect when BMI or obesity are taken into account, suggesting that BP and cardiac remodeling are mainly driven by the degree of adiposity.

5.15 Early Left Ventricular Remodeling in Normotensive Male Offspring of Essential Hypertensive Parents Independent of Blood Pressure

G. Pelà, P. Pattoneri, M. Passera, G. Tirabassi, M. Goldoni and A. Montanari

Università di Parma, Parma, Italy

Introduction: Left ventricle (LV) abnormalities, including variations in LV geometry and/or mass and diastolic function, may be detected early in normotensive offspring of hypertensive parents (EH+) when compared to matched offspring of normotensive families (EH−). Since EH+ subjects also show consistently a slightly higher blood pressure (BP), the relative contribution to such LV abnormalities of BP levels and of other BP-independent LV primary changes developing early in the prehypertensive age remains unknown.

Methods: Twenty-three normotensive sedentary male EH+ (age 25 ± 3 years) and 20 age-matched male EH− participated in the study. All of them underwent clinic BP measurement, 24-hour ambulatory BP monitoring (ABPM), measurements of the frequency-domain parameters of autonomic heart rate control and conventional and Doppler Tissue Echocardiographic study of both ventricles. LV Relative Wall Thickness (RWT, i.e. the ratio between the sum of inter-ventricular septum and posterior wall thickness to LV diameter) was used as a measure of LV remodeling. EH+ subjects had higher office systolic and diastolic (p < 0.05), average 24-hour systolic (p < 0.001), diastolic (p < 0.01) and mean (p < 0.05) BP.

Results: No between-group differences were detected for heart rate variability, systolic and diastolic function in both ventricles and left ventricular mass. A greater LV RWT (0.38 + 0.05 vs 0.34 + 0.03 SD; p < 0.01) was observed in EH+. At the univariate statistical analysis, RWT showed a highly significant correlation to the condition of EH+ (p < 0.004), but also it was related to: clinic systolic BP (p < 0.05), average 24-hour systolic (p < 0.01), diastolic (p < 0.0) and mean (p < 0.0) BP. Stepwise multiple regression analysis, performed assuming RWT as the dependent variable and all other variables, including age, BMI, clinic systolic and diastolic BP, ABPM-derived BP levels, HR variability and type of subjects (EH+ or EH−) as the independent variables, showed that only the condition of EH+ was independently associated with RWT (p<0.006). Receiver Operating Characteristic (ROC) curves analysis showed that RWT, with a cut-off point of 0.369, predicted the condition of EH+ with a 90% specificity and a 65% sensitivity (AUC = 0.759, 95% CI = 0.61, 0.91).

Conclusions: Our data show that a trend towards LV concentric remodeling, as indicated by a higher RWT, may be detected in EH+. Since RWT was independently associated only with the condition of EH+, and not with BP, EH+ condition is a strong predictor of early changes in LV geometry in such subjects independent of BP. This suggests that early changes in LV geometry in the prehypertensive age are paralleled, but not caused by a slightly higher BP. In addition, RWT measurement may be a quite specific tool to detect early LV alterations due to the condition of EH+.

5.16 Left Ventricular Myocardial Performance in Normotensive Offspring of Hypertensive Parents

P. Pattoneri, M. Passera, L. Musiari, A. Biggi, A. Montanari and G. Pelà

Università di Parma, Parma, Italy

Introduction: Offspring of hypertensive parents are at increased risk of developing hypertension. Abnormalities in morphology and function of the left ventricle (LV) may occur very early in the development of essential hypertension and even in the pre-hypertensive period.

Aim: To evaluate the influence of genetic predisposition to essential hypertension on LV function by the use of Myocardial Performance Index (MPI), a relatively new parameter of both systolic and diastolic functions.

Methods: The study included 15 healthy normotensive, non-obese male offspring of hypertensive parents (EH+, mean age 28 ± 5 years). They were compared to 10 aged-matched normotensive subjects without any family history of hypertension (EH−). All subjects were sedentary and no-smoker. None of them received any pharmacological treatment. Each subject underwent office blood pressure (BP) measurement and a conventional Doppler Echocardiography including the assessment of MPI defined as the sum of LV isovolumic contraction time and isovolumic relaxation time, divided by LV ejection time. Doppler Tissue Echocardiography (DTE) also was performed at the mitral and tricuspidal anulus, at the lateral site, to evaluate the systolic and diastolic function of both ventricles. LV Relative Wall Thickness (RWT, i.e. the ratio between the sum of interventricular septum and posterior wall thickness to LV diameter) was used as a measure of LV remodeling.

Results: Office BP was higher in EH+ than in EH−, with a statistical significance for diastolic BP (85 ± 9.2 SD vs 71.7 ± 2.9 mmHg; p < 0.02). A trend towards an increase in the LV relative wall thickness (RWT) was observed in EH+ compared to EH− (0.37 ± 0.04 vs 0.31 ± 0.02; p = 0.05), whilst LV mass was unchanged (84.3 ± 13.8 vs 80.1 ± 6.6 gr/m²; p = NS). Systolic and diastolic function of both ventricles were the same in the two groups. MPI was higher in EH+ than in EH− subjects, although with no statistical significance (0.48 ± 0.10 vs 0.41 ± 0.04; p = NS), mainly due to a statistically significant prolongation of isovolumic contraction time (61.9 ± 9.2 msecs vs 51.0 ± 10.0; p < 0.04). MPI was significantly related to RWT (r = 0.44, p < 0.05).

Conclusions: This study shows in offspring of hypertensive parents: a higher office BP, a trend to a LV concentric remodeling and a different myocardial performance. MPI seems attractive and useful to identify those subjects with genetic predisposition to future hypertension who develop early morphological and functional changes of the cardiovascular system.

5.17 C-Reactive Protein, Metabolic Syndrome and the Appropriateness of Left Ventricular Mass in Untreated Essential Hypertension

F. Paneni, S. Sciarretta, G. Tocci, G.M. Ciavarella, L. De Biase, J. Passerini, M. Gregori, F. Palano, A. Ferrucci and M. Volpe

Università “La Sapienza”-II° Facoltà di Medicina e Chirurgia-Cardiologia — Ospedale S.Andrea, Rome, Italy

Introduction: Metabolic syndrome (MS) seems to increase left ventricular mass (LVM) beyond the potential contribution of blood pressure (BP) and body size.

Aim: To evaluate the appropriateness of LVM in a cohort of untreated hypertensive patients according to the presence of obesity and MS. In addition, to evaluate in these patients the relation between the appropriateness of LVM and levels of high sensitivity c-reactive protein (CRP), a marker of systemic inflammation.

Methods: 176 untreated hypertensive patients underwent their first evaluation for hypertension. In all subjects routine blood chemistry including CRP, echocardiographic examination (conventional and TDI) and 24-h ambulatory BP monitoring were performed. Inappropriate LVM (ILVM) was defined as observed/predicted ratio (OPR) of LVM >128%. On the basis of the presence of obesity (defined as BMI> 30 Kg/m²) and ATPIII criteria for MS, the population was divided in 4 groups:

1. obese with MS;

2. obese without MS;

3. non obese with MS;

4. non obese without MS.

Results: Obese with MS displayed an higher prevalence of LVH (63.6% vs 57.7%, p < 0.001) and ILVM (59.1% vs 38.5%, p < 0.01), as compared with subjects without MS; similarly, higher values of LVH (42.9% vs 19.8%, p < 0.001) and ILVM (19% vs 15.1%, p < 0.001) were found among non obese with MS than without MS. CRP was higher in patients with MS independently of body size (group 1 to 4: 0.35 ± 0.23 vs 0.24 ± 0.16 vs 0.27 ± 0.23 vs 0.14 ± 0.14 mg/dL, p < 0.001) and significantly correlated with OPR at univariate analysis (Pearson, r = 0.29, p < 0.001). In patients with MS, ILVM was also associated with lower indexes of systolic and diastolic function evaluated both conventionally and with TDI. Multiple regression analysis showed that age (beta = 0.17, p < 0.05), waist circumference (beta = 0.43, p < 0.001), diastolic BP (beta = 0.20, p < 0.05) and CRP (beta = 0.11, p < 0.05) were significant predictors for OPR of LVM (p < 0.001).

Conclusions: ILVM is higher among patients with MS and is correlated with higher levels of CRP, thus suggesting that inflammation may increase LVM considered not appropriate for cardiac work load and body size.

5.18 Left Ventricular Diastolic Function in Different Ventricular Geometries in Hypertensive Patients with or without Left Ventricular Hypertrophy

A. Nardecchia, G. De Pergola, E. Dolce, R. Ria and F. Silvestris

Medicina Interna Universitaria, Bari, Italy

Introduction: Arterial hypertension is responsible for myocardial ultrastructural modifications such as left ventricular hypertrophy (LVH), interstitial fibrosis, and diastolic and systolic dysfunction.

Aim: To investigate whether:

1. an impaired left ventricular diastolic function is already apparent in hypertensive patients without LVH, and

2. an impaired left ventricular diastolic function is associated to a particular ventricular geometry in patients with LVH.

Methods: 88 patients (45 men and 43 women), aged 32–50 years, having a very recent onset of essential hypertension (140–179 mmHg as systolic blood pressure and 90–109 mmHg as diastolic blood pressure), and not treated by antihypertensive drugs, were consecutively enrolled into the study. Patients underwent a standard echo 2D M-mode echocardiography, and indexed left ventricular mass (ILVM) has been measured either per body surface or per height to correct data for the influence of overweight and obesity, with a cut-off of 51 g/h. Ventricular geometry has been measured by the RWT parameter ([interventricular septum + behind wall]/telediastolic diameter of left ventricle), with a cut-off of 0.45. Diastolic function has been evaluated by standard doppler imaging (E peak velocity, e deceleration time, A peak velocity, E/A ratio) and by tissue doppler imaging (TDI), placed on the lateral and on the septum wall of the mitral annulus.

Results: 22 patients (25%) showed a normal ILVM, 25 subjects (28.5%) had a left ventricular concentric remodeling, 27 individuals (30.6%) had a concentric LVH, and 14 patients (16.0%) had an eccentric LVH. Diastolic function was normal in hypertensive subjects with normal ILVM, whereas it was impaired in hypertensive subjects with LVH, showing the longest E-DT and the shortest E/A ratio in subjects with concentric LVH. TDI was similar to that obtained by the traditional method, showing the lowest Em/Am ratio measured either on the lateral or on the septum wall of the mitral valve, and the highest E/Em in concentric LVH.

Conclusions: Our data confirm the importance to identify different left ventricular geometries in hypertensive patients with LVH, since they may influence the prognosis and the therapy. Diastolic function, as measured by the traditional method or by the TDI, has shown a more compromised left ventricular compliance in concentric LVH.

5.19 Intima-Media Thickness and Left Ventricular Dysfunction: a Tissue-Doppler Echographic Study

C. Catena, Gl. Colussi, C. Petri, A. Chiuch, M. Valeri, A. Di Fabio and L.A. Sechi

Clinica Medica, Univarsità di Udine, Udine, Italy

Introduction: Thickening of the inner layer of the carotid arteries is an early indicator of organ damage in patients with hypertension. The intima-media thickness (IMT) has been demonstrated to be related with structural and functional abnormalities of the heart in hypertensive patients.

Aim: In this study, we have investigated the relationships of the IMT with parameters of cardiac function as assessed by pulsed wave tissue-Doppler echocardiography.

Methods: In 301 patients with grade I–II essential hypertension (age 60 ± 13 years; 165 males, 136 females) we performed ultrasound carotid scan and echocardiography both with standard methodology and with pulsed wave tissue Doppler imaging (TDI). Patients with an ejection fraction of less than 50% and relevant cardiac valve disease were excluded. The carotid scan and echocardiography were performed according to current guidelines; in TDI myocardial systolic and diastolic velocities were measured at the lateral and septal corner of the mitral annulus.

Results: An IMT of more than 900 mm was found in 124 (41%) of 301 patients. The IMT was correlated directly with left atrial diameter, left ventricular mass index, relative wall thickness (RWT), and early deceleration time (all p < 0.001), and inversely with the E/A velocity ratio (p < 0.001). The IMT was also directly related with parameters of diastolic (septal E/Em, p < 0.001 and lateral E/Em, p = 0.007) and systolic function (septal Sm, p = 0.004 and lateral Sm, p < 0.001) as assessed by TDI. Multiple regression analysis that was performed with inclusion of demographic and anthropometric variables showed statistically significant correlations only between the IMT and intraventricular septum thickness (p = 0.015), posterior wall thickness (p = 0.021), and RWT (p = 0.011). Inclusion of age in the multivariate model eliminated the relationship between IMT and diastolic parameters.

Conclusions: Thickening of the inner carotid layer is independently related with left ventricular mass in patients with hypertension, whereas the relationship with diastolic dysfunction is dependent on the age of patients.

5.20 Assessment of Left Ventricular Mass and Function in Patients with Apolipoprotein A-I Amyloidosis (LEU75PRO)

M. Salvetti,¹ M.L. Muiesan,¹ A. Paini,¹ E. Belotti,¹ C. Agabiti Rosei,¹ C. Aggiusti,¹ C. Monteduro,¹ M. Nardi,² L. Obici,³ A. Negrinelli,⁴ F. Scolari,⁴ G. Gregorini,⁴ G. Cancarini⁴ and E. Agabiti Rosei¹

1 Clinica Medica, Università di Brescia, Brescia, Italy; 2 Cardiologia, Università di Brescia, Brescia, Italy; 3 Centro per l’amiloidosi, Laboratori di Biotecnologia, Pavia, Italy; 4 Nefrologia, Università di Brescia, Brescia, Italy

Introduction: Hereditary amyloidosis are late-onset autosomal dominant disorders characterized by amyloid deposition in various tissues. Among them, Apolipoprotein A-I amyloidosis (Leu75Pro) is a rare, autosomal dominant condition in which renal, hepatic, and testicular involvement has been demonstrated. Few data are available about cardiac involvement in this condition.

Aim: To evaluate cardiac structure and function in patients with Apolipoprotein A-I amyloidosis (APO A-I amyloidosis).

Methods: In 104 patients with Apolipoprotein A-I amyloidosis [Leu75Pro] (mean age 52 ± 16 years, 56 F, 57% hypertensive patients) and in 104 subjects matched for age, sex, body mass index (BMI) and clinic blood pressure (BP), left ventricular (LV) structure and function were evaluated by echocardiography (Mono-bidimensional + conventional and tissue Doppler analysis).

Results: By definition no differences were observed for age, sex, BMI, BP and heart rate. LV mass index was significantly greater in patients with APO A-I amyloidosis than controls (35.6 ± 12.8 vs 32.7 ± 7.3 g/m2.7, p < 0.05). Relative wall thickness was similar in the two groups (0.32 ± 0.07 vs 0.30 ± 0.05, p = ns). The absolute value of mitral annular e velocity (Em) was significantly lower in patients with APO A-I amyloidosis (8.6 ± 3.4 vs 9.7 ± 2.2, p < 0.05), and the ratio of transmitral e velocity (E) to Em, (E/Em ratio) a sensitive index of LV filling pressure, was significantly greater (9.7 ± 4.2 vs 8.0 ± 2.1, p < 0.005). Ejection fraction, fractional shortening and midwall fractional shortening were significantly lower in amyloidosis as compared to controls (64.0 ± 7.0 vs 66.3 ± 5.9, p < 0.05; 37.2 ± 8.3 vs 40.2 ± 7.4, p < 0.005 and 19.2 ± 3.8 vs 20.8 ± 3.0, p < 0.001, respectively).

Conclusions: In patients with Apolipoprotein A-I amyloidosis (Leu75Pro) a significant increase in LV mass associated with an impairment of systolic and diastolic function has been observed. These results, obtained in a wide sample of patients, may add significant information to the clinic features of this rare genetic disorder.

5.21 Study of Cardiopulmonary Testing Response in Hypertensive Patients: Analysis Before and After Aerobic Physical Training

M. Vicenzi, V. Rossi, A. Dallacìa, M. Antelmi and M. Guazzi

Centro per la Cura e lo Studio dell’Ipertensione Arteriosa,Università di Milan, Ospedale S. Paolo, Milan, Italy

Introduction: Cardiorespiratory response during maximal exercise provides important pathophysiological information in patients with left ventricular failure. Few studies have investigated the cardiopulmonary testing response of hypertensive patients whose better characterization could help to improve the therapeutic approach.

Methods: 45 patients with arterial hypertension [mean age: 40 ± 9 years] underwent cardiopulmonary exercise testing before (T0) and after aerobic physical training period (T1, mean duration: 99 ± 16 days). We considered peak oxygen consumption (VO₂), aerobic efficiency (VO₂/WR), the ventilatory efficiency slope during exercise (VE/VCO₂ slope), heart rate and oxygen consumption ratio (HR/VO₂), and systolic arterial pressure (SAP) at peak of exercise.

Results: All variables considered improved significantly after aerobic physical training period (table; T0 vs T1: # p < 0.01; * p = 0.03). A statistically significant decrease in exercise SAP was observed (−5.9 ± 17.7 mmHg, p = 0.02), which correlated with VO2 change (p < 0.01).

Conclusions: Hypertensive patients exhibit exercise cardiopulmonary features that are similar to those observed in physical deconditioning, as indicated by a low VO₂ percent predict value and normal aerobic inefficiency (low VO₂/WR ratio). Aerobic physical training improves all the cardiopulmonary variables considered, and modulates SAP during exercise. Changes observed in VE/VCO2 slope and HR/VO₂ suggest a potential putative role of an improved neuromediated control. Our results indicate that the variables investigated could be considered as additional target of anti-hypertensive treatment targets.

5.22 Development of Systolic Dysfunction not Related to Myocardial Infarction in Treated Hypertensive Patients with Left Ventricular Hypertrophy: the LIFE Echo Substudy

M. Chinali,¹ G.P. Aurigemma,¹ W.H. Gaasch,¹ E. Gerdts,² K. Wachtell,³ P.O. Okin,⁴ S.E. Kjeldsen,⁵ S. Julius,⁶ B. Dalhof,⁷ G. de Simone⁸ and R.B. Deereux⁴

1 University of Massachusetts Medical School, Worcester, MA, USA; 2 Haukeland University Hospital, Bergen, Norway; 3 Rigshospitalet, Copenhagen, Denmark; 4 Weill-Cornell Medical College, New York, NY, USA; 5 University of Oslo, Oslo, Norway; 6 University of Michigan, Ann Arbor, MI, USA; 7 Sahlgrenska University Hospital/Östra, Gothenburg, Sweden; 8 Università di Napoli “Federico II”, Napoli, Italy

Introduction: While it is commonly thought that left ventricular (LV) systolic function might insidiously deteriorate in hypertensive patients, few prospective data are available to support this notion.

Methods: We evaluated 703 hypertensive patients (66 + 7 years; 45% women) with ECG-LV hypertrophy enrolled in the LIFE echo-substudy. Only patients free of prevalent cardiovascular disease and with baseline ejection fraction (EF) >55% were included. Echocardiographic exams were performed annually for 5 years during antihypertensive treatment. Development of reduced systolic function was defined as incident EF>50%.

Results: Main findings of our study are shown in the table. During a mean follow up of 4.8 + 1 years, 37 patients developed reduced EF without an intercurrent myocardial infarction (5.3%). Patients who developed reduced EF were more often men (p < 0.05). In analysis of covariance, patients who developed reduced EF had greater baseline LV diameter and LV mass, lower mean EF (all p < 0.05), and similar diastolic function indices. As shown in the table below, at last available exam before EF reduction, independently of covariates, patients with reduced EF showed a significant increase in LA size, LV diameter, end-systolic stress and mitral E/A ratio, as compared to those who did not develop reduced EF (all p < 0.05). In time-varying Cox regression analysis, controlling for baseline EF, predictors of developing reduced EF were higher in-treatment LV diameter (HR = 5.19; 95% CI: 2.58, 10.41; p < 0.001) and higher in-treatment mitral E/A ratio (HR = 2.37; 95% CI: 1.58, 3.56; p < 0.001).

Conclusions: We provide the first evidence of significant changes in cardiac geometry and function preceding incident reduced EF, in the absence of intercurrent MI, in treated hypertensive patients. Higher in-treatment LV diameter and mitral E/A ratio are the strongest echocardiographic predictors of reduced EF.

5.23 Cardiac Modifications Related to Incident Heart Failure in Treated Hypertensive Patients: the LIFE Echo Substudy

M. Chinali,¹ G.P. Aurigemma,¹ W.H. Gaasch,¹ E. Gerdts,² K. Wachtell,³ P. Okin,⁴ S.E. Kjeldsen,⁵ S. Julius,⁶ B. Dalhof,⁷ G. de Simone⁸ and R.B. Devereux⁴

1 University of Massachusetts Medical School, Worcester, MA, USA; 2 Haukeland University Hospital, Bergen, Norway; 3 Rigshospitalet, Copenhagen, Denmark; 4 Weill-Cornell Medical College, New York, NY, USA; 5 University of Oslo, Oslo, Norway; 6 University of Michigan, Ann Arbor, MI, USA; 7 Sahlgrenska University Hospital/Östra, Gothenburg, Sweden; 8 Università di Napoli “Federico II”, Napoli, Italy

Introduction: Hypertensive patients with left ventricular (LV) hypertrophy (H) have increased risk of developing heart failure (HF). Little is known on whether acute HF is associated with significant variations in echocardiographic parameters, nor whether these variations are independent of intercurrent myocardial infarction (MI).

Methods: We evaluated 926 hypertensive patients (66 + 7 years; 45% women) with ECG-LV hypertrophy enrolled in the LIFE echo-substudy, without history of heart failure. Echocardiographic exams were performed annually for 5 years during anti-hypertensive treatment. Data from baseline examination, last examination before HF, and first examination after HF event are reported.

Results: During follow-up, 23 patients developed HF (2.5% of study population; 14 women) and 38 MI events occurred. Patients who developed HF were older (72 vs 54 years), had higher baseline heart rate (76 vs 67 bpm) and higher rate of pre-existing ischemic heart disease (47.8% vs 14.5%; all p < 0.01), as compared to patients that did not develop HF. Higher rate of intercurrent MI was observed in patients who subsequently developed HF (13.2% vs. 2% in non-HF; p = 0.002). Echocardiographic data of patients that developed HF during the study are displayed in the table, dichotomized by the presence (N = 5) or absence (N = 17) of incident MI.

Conclusions: In our group of treated hypertensive patients at high-risk because of LV hypertrophy, less than one in four (22%) HF events were related to intercurrent MI. In all patients development of HF was associated with more dilated LV geometry (reduction in RWT) and signs of increased LV filling pressures (increased mitral E/A ratio and/or IVRT shortening). A mild reduction in EF was observed only in patients with MI-related HF.

5.24 Cardiac Mechanics in Mild Hypertensive Heart Disease by Speckle Strain Imaging

M. Chinali, A. Narayanan, G.P. Aurigemma, J.C. Hill and D.A. Tighe

University of Massachusetts Medical School, Worcester, MA, USA

Introduction: Speckle strain imaging, a 2D ultrasound based technique, permits measurement of cardiac strain (S) in all three planes: circumferential (Sc), radial (Sr) and longitudinal (Sl) and can potentially provide insight into systolic mechanics in hypertensive patients.

Methods: Standard 2D Doppler echocardiography, tissue Doppler imaging (TDI), and 2D speckle strain imaging were performed in 104 subjects [52 HTN (53 + 12 years) and 52 controls (49 + 13 years; p = 0.82)] with a normal ejection fraction. Peak systolic (S’), and diastolic (E’) annular velocities were obtained by TDI, while longitudinal myocardial systolic velocity (Vl) was obtained by speckle tracking. Circumferential, longitudinal, and radial strains (Sc, Sl, Sr), obtained by speckle tracking, were used as indices of global LV function. FSmw and peak basal longitudinal strain (basal Sl) were used as indices of regional function.

Results: Hypertensive patients had lower velocities: TDI E’ and S’, as well as Vl. However, strains — Sc, Sl, and Sr — were similar. E/E’ ratio, an index of LV filling pressure, was higher among hypertensive patients. Both E’ and E/E’ correlated with RWT (r = 0.34, r = 0.21, p < 0.05). Hypertensive patients showed reduced regional systolic function (FSmw and basal Sl), and impaired diastolic function; while global strain was not different among study groups. However among hypertensive patients, significant inverse associations were found between LV mass and global longitudinal (r = −0.51) and circumferential S (r = −0.21; both p < 0.05; figure).

Conclusions: Mild hypertensive heart disease with normal EF is associated with reduced myocardial velocities, but normal global S. In hypertensive patients, lower global strain are found only in the presence of higher LV mass and thus may represent more severe systolic dysfunction.

5.25 Increased Left Ventricular Mass in Hypertensive Men is More Strongly Related to Central than to Brachial Blood Pressure Control

M. Chinali, A. Narayanan, G.P. Aurigemma, J.C. Hill, A. McNamee, D.A. Tighe and R.A. Phillips

University of Massachusetts Medical School, Worcester, USA

Introduction: Cardiovascular risk in hypertension (HTN) has been shown to be more strongly related to central systolic blood pressure (c-SBP) than to brachial (cuff) systolic blood pressure (b-SBP).

Aim: We examined the relation of left ventricular (LV) mass and LV hypertrophy (H) with BP control defined by both b-SBP and c-SBP.

Methods: Ninety-one patients without diabetes or prevalent cardiovascular disease (42% men, 57 + 15 years), underwent standard 2D echocardiography and blood pressure measurement using a commercially available device (HEM-9000AI, Omron Healthcare Co., Kyoto, Japan). Central SBP was derived from the SBP2 peak according to a previously invasively validated equation. Nine patients were excluded due to sinus arrhythmia or suboptimal BP curve recording. The remaining 82 patients (56 + 15 years, 27.7 + 4.6 kg/m²; 65 HTN of which 72% treated) were dichotomized according to the presence of uncontrolled HTN (SBP > 140 mmHg) by b-SBP and by c-SBP.

Results: Higher prevalence of uncontrolled HTN was found when classification was made according to c-SBP (52.4%) as compared to b- SBP (41.5%; p < 0.001), with poor agreement between the two methods (kappa score = 0.54). Analysis of the whole population showed that uncontrolled HTN (by b-SBP or c-SBP) was associated with higher values of LV mass index and relative wall thickness (p < 0.01). In men, classification by b-SBP was unable to identify differences among group with controlled vs. uncontrolled HTN in either LV mass or LVH prevalence. In contrast, classification based on c-SBP showed significantly higher values of LV mass index in patients with uncontrolled BP (43 + 11g/m2.7) compared to those with controlled BP (37 + 8g/m2.7) [figure]. Accordingly, prevalence of LVH was significantly higher in uncontrolled HTN when the classification was based on c- SBP (30 vs 6% p = 0.05).

Conclusions: Compared to b-SBP, c-SBP better identifies hypertensive men with increased LV mass and LVH, and may be of incremental value in risk stratification.

5.26 Combination of Left Atrial Size and Function Improves Prediction of Incident Heart Failure: the Strong Heart Study

M. Chinali,¹ G. de Simone,¹ J.R. Kizer,² M.J. Romen,² A. Barac,³ J. Panza,³ J.N. Bella,² E.T. Lee,⁴ L.G. Best,⁵ B.V. Howard³ and R.B. Devereux²

1 Università di Napoli “Federico II”, Napoli, Italy; 2 Weill-Cornell Medical College, New York, NY, USA; 3 Medstar, Washington, DC, USA; 4 University of Oklahoma, Oklahoma City, OK, USA; 5 Missouri Breaks Industries, Timber Lake, MO, USA

Introduction: This study was designed to assess whether combination of left atrial (LA) systolic function (SF) with LA size improves prediction of incident heart failure (HF).

Methods: Doppler echocardiography was performed on 2808 participants in the Strong Heart Study (age 59.3 ± 8.0 years, 62.5% women, 43.0% hypertension, 46.7% diabetes, and 54.1% obese) without valvular abnormalities or prevalent CV disease. LASF was estimated from mitral orifice area and mitral peak A velocity, as previously reported. Increased LASF was categorized by the prognostically validated cut- point of 14.33 Kdynes. LA dilatation was defined using prognostically validated gender-specific partition values (>3.8cm for women and >4.2cm for men).

Results: During a mean follow-up of 8 ± 2 years, 209 participants (2.7%) had incident HF. At baseline, 617 participants (21.9%) had high LASF alone, 286 (14.2%) had LA dilatation alone and 186 participants (6.6%) had both, with similar LA diameter to participants with isolated LA dilatation (4.16 ± 0.30 vs. 4.17 ± 0.27; p = NS). When analyzed as continuous variables in separate models, both LA diameter and LASF were associated with increased risk of HF (both p < 0.001). In multivariate Cox regression adjusting for age, gender, presence of diabetes, hypertension, obesity, left ventricular mass index, ejection fraction and E/A ratio class, isolated LA dilatation (HR = 1.26; 95% CI = 0.78, 2.02) and increased LASF (HR = 1.33; 95% CI = 0.92, 1.93) were not significantly associated with higher risk of incident HF, whereas the concomitant presence of both abnormalities was significantly and independently associated with higher risk of future HF (HR = 1.94; 95% CI = 1.18, 3.18; p = 0.009).

Conclusions: Concomitant presence of LA dilatation and increased LASF is associated with increased risk of incident HF, independently of CV risk factors, demographic variables and LV geometry and function.

5.27 Possibility of Quantitative Evaluation of Left Ventricular Structure using M-Mode and B-Mode Echocardiography in a Hypertension Echolab

D. Degli Esposti, F. Santi, L. Laghi, V. di Gregori, A. Dormi, S. Bacchelli, E.R. Cosentino, E.R. Rinaldi,M. Pombeni, D. Maione, M. Veronesi and C. Borghi

S.Orsola-Malpighi-Università di Bologna, Bologna, Italy

Introduction: M-mode echocardiography in the evaluation of left ventricular (LV) mass (M) can be performed only in a limited number of subjects because of technical difficulty in obtaining ultrasonic beam (UB) correct alignment (really perpendicular to left ventricular structures) and a good quality of the image. This last, on the contrary, is more often available with a non optimal UB alignment, by which sometimes LV quantitative assessment is performed. Bidimensional long axis (B) LV walls and dimensions measurement gives LVM evaluation similar to the M-mode one, when the last one is not technically available.

Aim: To assess in how many patients (pts) B-mode long axis and M-mode quantitative LV evaluation can be performed, in how many LV measurement can be performed with optimal alignment of UB (L-opt) and in how many it can be performed only with a non optimal alignment of UB (LQ), however excluding an UB/LV structures angle >110° or a not adequately circular short axis image.

Methods: We therefore considered 4 kinds of measurements: 1 B and 3 M-mode guided by LQ, short axis (T), or L-opt. In one month we evaluated by echocardiography 148 consecutive subjects (63 M, 85 F, mean age 67.7 years, range 14–92, 58% hypertensive patients), assessing LV end diastolic walls thickness and internal diameter. M-mode evaluation of LV structure was not possible in 32 patients (No M-mode), of which 18 did not consent any quantitative evaluation at all.

Results: Number and characteristics of patients in each group are represented in the table (* p < 0.05 vs LQ, B, No M-mode; ** p < 0.05 vs LQ, B, T, L-opt).

Conclusions: M-mode evaluation with UBcorrectly aligned is possible only in a little percentage of pts, whilst adequate measurements can be performed by B in most pts, without excluding the oldest ones.

5.28 Echocardiographic Ultrasonic Beam Alignment and Left Ventricular Geometric Patterns Prevalence

D. Degli Esposti, L. Laghi, F. Santi, V. di Gregori, A. Dormi, S. Bacchelli, E.R. Cosentino, M. Pombeni, E.R. Rinaldi, M.G. Prandin, M. Rosticci and C. Borghi

S.Orsola-Malpighi-Università di Bologna, Bologna, Italy

Introduction: M-mode echocardiography for quantitative evaluation of left ventricular (LV) mass (M) can be performed only in a limited number of subjects because of technical difficulty in obtaining ultrasonic beam (UB) correct alignment (really perpendicular to left ventricular structures) and a good quality of the image, which, on the contrary, is more often available with a non optimal UB alignment. Bidimensional long axis LV walls and dimensions measurement (B) gives LVM evaluation similar to the M-mode one, when the last one is not technically available.

Aim: To assess how UB alignment could influence LV structural measurements and LV geometric patterns prevalence.

Methods: In one monthwe evaluated 116 consecutive subjects (41 M, 75 F, mean age 61.4 years, range 14–92, 56.9% hypertensive patients) with an echocardiography of adequate technical quality to assess quantitative evaluations of LVM. Interventricular septum (IVS), posterior wall (PW) and LV end diastolic dimensions (D) were measured in Band M-mode with UB derived from: long axis best quality image, but without optimal UB alignment (LQ), short axis [T] (excluding an alignment with an angle >110° or a short axis image not adequately circular), and long axis with optimized UB alignment (L-opt). We assessed LVM index (LVMI) and relative wall thickness [RWT = (ISV + PW)/D].

Results: LVMI and LVD were significantly different in L-opt and B (94.2 ± 27.3 g/m², 4.6 ± 0.5 cm; 89.8 ± 27.1, 4.6 ± 0.5) respect to LQ and T (110.6 ± 36.1, 5.1 ± 0.8; 104.1 ± 33.5, 5.1 ± 0.7; p < 0.0001). In the table, are represented the numbers of subjects in the 4 geometric patterns (N = normal, CR = concentric remodelling, CH = concentric hypertrophy, EH = eccentric hypertrophy) with the different kinds of measurements (* p < 0.001 vs LQ, T).

Conclusions: LQ and T, often used in quantitative evaluations of LV, overestimating D, make EH more prevalent, which is, on the other hand, less represented with L-opt and B. This observation suggests how a different UB alignment could give a different clinic evaluation of patients with consequent different prognostic assessment.

5.29 Left Ventricular Mass, Left Ventricular Pump Performance and Cardiovascular Events: the Strong Heart Study

M. De Marco,¹ G. de Simone,¹ M. Chinali,¹ E.T. Lee,² M. Russell,³ L.G. Best,⁴ M.J. Romen,⁵ B.V. Howard⁶ and R.B. Devereux⁵

1 Università Federico II, Napoli, Italy; 2 University of Oklahoma, Oklahoma City, OK, USA; 3 MedStar Research Phoenix, Phoenix, AZ, USA; 4 Missouri Breaks Industries Research, Timber Lake, MI, USA; 5 Weill Cornell Medical College, New York, NY, USA; 6 Medstar Research Institute, Washington, DC, USA

Introduction: Ejection-phase indices of LV function such as ejection fraction (EF) are good prognostic indicators. However, at given level of EF and assuming normal mitral valve closure, LV pump performance (stroke volume [SV]) may differ, depending on Starling reserve and LV diastolic volume. Symptoms of heart failure (HF) may depend more on SV than on EF. Evaluation of low SV as a prognostic marker might be difficult because of its strong biological co-linearity with high LV mass (LVM).

Aim: We prognostically compared and assessed the interaction among EF, SV and LVM in a large population free of cardiovascular disease.

Methods: We analyzed 8-year survival curves of quintiles of EF, SV (z-derived method) and LV mass (LVM) in 2323 participants of the Strong Heart Study (58 ± 7 years; 62% women, 39% hypertensive patients, 45% diabetics and 54% obese) without valvular heart diseases or prevalent coronary heart diseases, stroke or heart failure.

Results: Risk of composite fatal or non-fatal cardiovascular (CV) events progressively increased from the highest to the lowest quintiles of EF (log rank = 21.7; p = 0.0002) and from the lowest to the highest quintiles of LVM (log rank = 40.8; p < 0.00001). In contrast, SV did not show significant predictive value. LVM was negatively related to EF (r = −0.37), but was positively correlated with SV (r = 0.66), (both p < 0.0001). Thus, the level of LVM, could confound evaluation of the association of SV with subsequent CV events. Thus, we evaluated LV pump performance per gram of LVM (SV/LVM). Kaplan Meier curves revealed a progressively higher rate of CV events from the highest to the lowest quintiles of SV/LVM (log rank = 36.3; p < 0.0001). Cox regression, adjusting for age and sex and including EF, SV and LVM showed that hazard of incident CV events increased with higher LVM (HR = 1.1/10 g, CI = 1.05, 1.12, p < 0.0001) and lower SV (HR = 0.90/10 mL, CI = 0.80, 0.98; p < 0.01), with no independent effect of EF (HR = 0.90/10%, CI = 0.70, 1.03, p = 0.11).

Conclusions: Evaluation of LV pump performance is influenced by the amount of myocardial muscle pumping blood into the arterial tree. When LV mass is taken into consideration, indices of LV pump performance are useful and may improve identification of subjects at risk of incident CV events.

5.30 Cardiovascular Predictors of Incident Heart Failure in Diabetes: the Strong Heart Study

G. de Simone,¹ R.B. Devereux,² M. Chinali,¹ M.J. Romen,² A. Barac,³ J. Panza,³ E.T. Lee,⁴ J.M. Galloway⁵ and B.V. Howard³

1 Università di Napoli Federico II, Napoli, Italy; 2 Weill Cornell Medical College, New York, NY, USA; 3 Medstar Research Institute, Washington, DC, USA; 4 University of Oklahoma, Oklahoma City, OK, USA; 5 University of Arizona, Tucson, AZ, USA

Introduction: We have previously shown that diabetes is a strong predictor of heart failure (HF) independent of prevalent coronary heart disease, hypertension and obesity, and intercurrent myocardial infarction. The association of diabetes with incident HF might be at least in part due to coexistent diabetes-associated abnormalities of left ventricular (LV) geometry and function that might favor the progression to HF.

Methods: We analyzed incidence of HF (8.91 ± 2.76 years) in relation with echocardiographic phenotypes in 2 757 diabetic (DM) or non diabetic (ND) participants (1777 women) of the 2nd exam of the Strong Heart Study (SHS), without prevalent HF, coronary heart disease or severe kidney disease. We evaluate hazard of incident HF (defined by the SHS Mortality and Morbidity Committee), adjusting for covariates, and also after censoring incident myocardial infarction as a competing risk event.

Results: Diabetes was present in 1278 participants (46%, 69% women) and was associated with higher prevalence of obesity (63% vs. 46% in ND), central fat distribution (87% vs. 69%) and hypertension (53% vs. 34%, all p < 0.0001). Incident HF was about 3-times higher in DM (156 cases, or 12%) compared to ND (68 cases or 5%; OR = 2.89 [2.15−3.88], p < 0.0001). After adjusting for age, gender, body mass index (BMI) and presence of hypertension, DM had LV mass index (LVMi) similar to ND, higher relative wall thickness, lower LV stroke index (SVi) and lower end-systolic stress, but greater cardiac output (due to higher heart rate) and pulse pressure/stroke index ratio (PP/SVi; all p from <0.04 to <0.001).No differences between DM and ND were found in endocardial and midwall shortening, also when controlling for end-systolic stress. Doppler transmitral E/A ratio and isovolumic relaxation time (IVRT), were lower in DM then ND (both p < 0.001), also after normalization for heart rate. After adjusting for the competing risk of incident myocardial infarction, HF was predicted by LVMi and greater atrial dimensions, lower systolic shortening, longer Doppler transmitral e deceleration time, lower IVRT and greater PP/SVi (from p < 0.02 to p < 0.0001), independent of effect of age, gender, BMI, systolic blood pressure, heart rate, and C-reactive protein. However presence of diabetes was still associated with more then two-times higher risk of HF, compared to ND, independent of all echocardiographic variables considered in the Cox model (p < 0.0001). Lower IVRT and higher PP/SVi were main characteristics associated with development of HF in DM participants.

Conclusions: The broad spectrum of echocardiographic abnormalities associated with incident HF not due to coronary artery disease do not completely explain the greater risk of HF associated with DM. LV delayed relaxation and greater arterial stiffness are important predictors of HF in DM, but other reasons of the residual association between DM and HF remain to be clarified.

5.31 Reproducibility of Doppler Indices of Left Ventricular Diastolic Function: the Red Trial

M. Galderisi,¹ A Grandi,² C. Palombo,³ M.L. Muiesan,⁴ C. Giannattasio,⁵ D. Degli Esposti⁶ and G. De Simone¹

1 Università Federico II, Napoli, Italy; 2 Università dell’Insubria, Varese, Italy; 3 Università di Pisa, Pisa, Italy; 4 Università di Brescia, Brescia, Italy; 5 Università di Milano-Bicocca, Milan, Italy; 6 Università di Bologna, Bologna, Italy

Introduction: To investigate the biological variability of test-retest measurements of parameters of left ventricular (LV) diastolic function in single patients.

Methods: Transmitral Doppler spectral signals, pulsed Tissue Doppler of mitral anulus and colour M-mode flow propagation velocity (Vp) were recorded in the same session and 3-to-10 days apart in 98 participants (42.2 ± 14 years, 47 normotensive, 51 hypertensive) in 6 centres in Italy. Myocardial early diastolic velocity (Em) of septal and lateral mitral annulus were measured and averaged. The ratio between transmitral e velocity and septal Em or lateral Em or average Em were calculated as estimate of LV filling pressure. The two tracings were read by two observers in each centre. The variability of test-retest measurements were assessed in both readers by computing single measurements intra-class correlations and Bland-Altman tests. Several percentiles of absolute and percent differences were also computed.

Results: The 90% of the interval of agreement was −10.4–+13.7% for systolic blood pressure, −14.4–17.7% for diastolic blood pressure and −20–+16.5% for heart rate. For day-to-day test-retest intra-observer variability (average of three cardiac cycles), the 90% interval of agreement for the main diastolic parameters were the following: e velocity deceleration time = −39.4–+40.2 msec (−18–+25%), atrial filling fraction = −9.34–8.17% (−41–25.8%), transmitral e velocity = −0.16–+0.22 cm/sec (−28–+25%), average Em = −3.5–+3.13 cm/sec(−32–+25%), Vp = −19.4–24 cm/sec (−72–42%), E/septal Em = −2.45–2.62 (−46–27%), E/lateral Em = 2.72–2.82 (−37–+38%), E/average Em = −2.89–2.18 (−39–27%).

Conclusions: The test-retest variability of indices of diastolic function is substantially greater than, and can be only partially explained by, the variability of blood pressure and heart rate. Among different diastolic parameters transmitral e velocity, Tissue Doppler derived Em velocity (average of septal and lateral annulus) and E/average Em ratio show a lower day-to-day variability in comparison with colour M-mode flow propagation velocity. Based on these results E/Em ratio appears as a more stable, and possibly reliable, index of LV filling pressure than Vp.

5.32 Hypertension is the Parameter that Explains the Association Between Metabolic Syndrome and Left Ventricular Mass in a Population of Obese Women

G. Salvetti,¹ A. Pucci,¹ A. Virdis,² G. Scartabelli,¹ P. Fierabracci,¹ V. Di Bello,³ C. Palagi,³ D. Versari,² A. Pinchera,¹ F. Santini¹ and A. Salvetti²

1 Dipartimento di Endocrinologia e Rene-Azienda Ospedaliero-Universitaria Pisa, Pisa, Italy; 2 Dipartimento di Medicina Interna, Azienda Ospedaliero-Universitaria Pisa, Pisa, Italy; 3 Dipartimento Cardio-Toracico-Azienda Ospedaliero-Universitaria Pisa, Pisa, Italy

Introduction: Obesity is frequently associated with an increase of left ventricular mass (LVM).

Aim: To evaluate the parameters that influence LVM in a group of obese women.

Methods: 166 obese women, age 41 ± 12 years (19–67), weight 111.6 ± 18 kg (78–185), body mass index kg/m² 43.1 ± 6.3 (32.1–66.3), waist circumference 123 ± 14.6 cm (93–178), waist-to-hip ratio (WHR) 0.94 ± 0.09 (0.65–1.31), intra abdominal fat (IAF) 82.7 ± 24.3 mm (25–160), duration of obesity 22.7 ± 11.1 years (3–55); 58 women (35%) with hypertension [HT] (41 treated), 43 (25%) with diabetes mellitus [DM] (32 on treatment) and 94 (56.6%) with Metabolic Syndrome (MS). LVM was 200.2 ± 42.7 grams, or 56.5 ± 12.9 gr/h2.7 or 95.9 ± 12.2 gr/m². IAF was measured by ultrasound technique and LVM by echocardiography with standard method. HT was defined as BP >140 or 90 mmHg or antihypertensive drug treatment, DM according to ADA and MS was defined according to ATPIII criteria. Data are reported as mean ±SD and range values. The influence of various parameters on LVM was assessed by multivariate analysis using LVM as dependent variable and parameters showing a significant correlation with LVM in univariate analysis ad independent variables, including the presence of HT as dichotomous values.

Results: In the multivariate analysis, the following parameters were independently and directly correlated to the LVM: Age (r² = 0.042), Duration of obesity (r² = 0.044), HT (r² = 0.034), WHR (r² = 0.044), Weight (r² = 0.11). Overall these parameters predict around 36% (r² = 0.36) of LVM values. The presence of MS was associated with significantly (p < 0.01) greater LVM (MS+ 206.1 gr. MS− 192.3 gr.) in the overall population but not in the group of normotensive women (LVM: MS+ 194.1 gr. vs MS— 189.3 gr.).

Conclusions: In obese women the main determinant of LVM are age, duration of obesity, weight, fat distribution, expressed as WHR, and hypertension. The association of MS with LVM seems to be determined (caused) by the presence of HT.

Hormonal Mechanisms

6.1 Euroadrenergic Function in Insulin-Resistant Acromegalic Patients

G.L. Seravalle,¹ L. Lonati,¹ M. Scacchi,² C. Carzaniga,² L. Fatti,² R. Attanasio,³ M. Montini,³ S. Buzzi,⁴ R. Cozzi,⁵ F. Cavagnini,² G. Grassi⁴ and G. Mancia⁴

1 Ospedale San Luca, Milan, Italy; 2 Divisione di Endocrinologia, Università di Milan, Milan, Italy; 3 Divisione di Endocrinologia, Ospedale Riuniti di Bergamo, Bergamo, Italy; 4 Clinica Medica, Università Milano-Bicocca, Monza, Italy; 5 Divisione di Endocrinologia, Ospedale di Niguarda, Milan, Italy

Introduction: Growth hormone-deficient adults (GHDA) display an increased sympathetic activity, a condition widely considered as an important cardiovascular risk factor. In these patients GH replacement is followed by only partial correction of this sympathetic alteration. In acromegaly old data obtained with indirect measurement of adrenergic tone have shown a normal sympathetic outflow while more recently power spectral analysis of heart rate documented a sympatho-vagal imbalance due to parasympathetic hyperactivity.

Aim: To assess the adrenergic tone in a homogeneous group of acromegalic patients through direct measurement of muscle sympathetic nerve activity (MSNA).

Methods: We studied three groups of subjects: (a) 12 patients (5 men; age 52.6 ± 13.6 years, mean ± SD) with untreated active acromegaly (mean baseline serum GH 10.8 ± 11.86 mg/L, mean serum IGF-I 691.2 ± 207.95 mg/L, normal serum prolactin), all characterized by short disease duration; (b) 8 healthy normotensive subjects matched for age, sex and body mass index (BMI); (c) 7 acromegalic patients controlled by somatostatin analogue (SSA) treatment. In all subjects a M- and B-mode echocardiography, an anthropometric evaluation, a study of glucose and lipid metabolism and calculation of HOMA index were performed. MSNA was recorded via the microneurographic technique, together with continuous recording of blood pressure (BP, Finapres), respiratory rate (RR, Respitrace) and heart rate (HR,EKG).

Results: BMI, waist-to-hip ratio, waist circumference and lipid profile were superimposable in the three groups. The HOMA index was significantly (p < 0.05) increased in untreated acromegalic patients. No echocardiographic signs of left ventricular hypertrophy were detected in patients, presumably because of the short duration of the disease. For superimposable mean BP, RR and HR values, mean MSNA was significantly lower in untreated patients than in controls (17.9 ± 9.4 vs 39.5 ± 8.9 bs/min, p < 0.05) while in the group of SSA-controlled patients mean MSNA (31.1 ± 4.9 bs/min) shows the tendency toward a normalization of these values.

Conclusions: Our study demonstrates that recently diagnosed acromegalic patients display a central sympathetic inhibition which is detectable despite the presence of hyperinsulinemia and insulin-resistance. This finding, together with the tendency to normalization of adrenergic tone in medically-controlled acromegalic patients and with the sympathetic hyperactivity reported in GHDA, suggests that GH/IGF-I axis has a relevant action on sympathetic neural function.

6.2 Correlation among Cardiac and Vascular Structural Alterations and A/R Ratio in Hyperaldosteronism

A.C.M. Capra,¹ F. Bianchi,² M. Rigoldi,² F. Citterio,² M. Galbiati,² M. Alloni,² D. Dozio,² G. Grosso,² M. Pozzi,² M. Betelli,² P. Sartori,³ R. Caprotti,³ C. Giannattasio¹ and G. Mancia⁴

1 Clinica Medica, ospedale San gerardo e Università Milan Bicocca, Monza, Italy; 2 Università degli studi Milan Bicocca, Monza, Italy; 3 Clinica Chirurgica, Ospedale san Gerardo, Monza, Italy; 4 Centro Auxologico Italiano, Milan, Italy

Introduction: Several studies have shown that aldosterone may cause cardiovascular fibrosis, but there is little evidence in humans.

Aim: To investigate the correlation between cardiac and vascular structure in terms of vascular wall thickness or left ventricular mass index (LVMI), aldosterone plasma levels and aldostron/renin ratio (A/R) in patient with Conn syndrome or bilateral adrenal hyperplasia and to study the effect of treatment.

Methods: We studied 12 patients with diagnosed PH (age 46.2 ± 5.5, means ± SE), 7 patients underwent surgical adrenalectomy, while 5 were medically treated with an aldosterone antagonist, and for each we measured A/R. 17 age and sex matched subjects affected by essential hypertension (EH) were used as control group (age 43.9 ± 3.1 years, means ± SE). Each subject underwent an echocardiogram to measure LV structure, LVMI, LV diastolic function (E/A ratio) and an echoDoppler to measure the carotid intima-media thickness (IMT) both at baseline (B), and in PH also 6 months after surgical intervention or initiation of medical therapy (T).

Results: At B, in PH vs EH BP was 142/85 ± 4.0/2.0 vs 146/92 ± 4.9/2.0 mmHg, LV mass index was 123 ± 12 vs 103 ± 5.3 g/mq, IMT was 0.62 ± 0.06 vs 0.55 ± 0.02 and E/A 1.0 ± 0.1 vs 1.2 ± 0.08. Moreover in PH, LVMI and IMT showed a highly significant positive correlation with A/R ratio (r = 0.74 and r = 0.73 respectively, p < 0.01). After T, BP was significantly reduced (134/80 ± 5.3/4.0 mmHg, p < 0.05 vs B) and the same thing was observed in the EH group, while other variables did not change. On the contrary, in PH we observed a not significant trend towards a reduction of LV mass (T: 110 ± 15 g/mq) IMT (0.5 ± 0.04 mm), and increase in E/A (1.1 ± 0.1).

Conclusions: Cardiovascular structure and function is related to aldosterone levels in PH. Both surgical or medical treatment of PH may improve such alteration, and this seems to be not related to changes in BP.

6.3 Angiotensin II Signaling via Type 2 Receptors in a Human Model of Vascular Hyporeactivity: Implications for Hypertension

L.A. Calò, S. Schiavo, E. Pagnin, P. Mormino and A.C. Pessina

Università di Padova, Padova, Italy

Introduction: Angiotensin II (Ang II) signaling via type 1 receptor (AT1R) has been extensively characterized, while Ang II signaling via type 2 receptors (AT2R), although counteracts actions mediated by AT1R, remains incompletely understood. Bartter’s/Gitelman’s patients (BS/GS) have intrinsically blunted AT1R signaling making them a good model to examine Ang II signaling via AT2R with particular emphasis on mitogen-activated protein kinase phosphatase 1 (MKP-1) that interacts with the Ang II stimulated ERK pathway of cell signaling.

Methods: BS/GS and healthy controls fibroblasts AT1R and AT2R level and the time course were of Ang II’s effect on MKP-1 levels and ERK1/2 phosphorylation over 1 hour time course were assessed by western blot. The time course of Ang II’s effect on MKP-1 levels and ERK1/2 phosphorylation alone or in the presence of either PD123319, an AT2R blocker, or Losartan, an AT1R blocker or in combination was characterized.

Results: AT1R and AT2R levels did not differ between BS/GS and healthy controls. Ang II induced ERK1/2 phosphorylation in BS/GS fibroblasts but peak ERK1/2 phosphorylation declined more rapidly than control and BS/GS fibroblasts also exhibited increased MKP-1 levels at 30 minutes incubation. PD123319, an AT2R blocker in BSGS fibroblasts abolished the increased MKP-1 and ERK1/2 phosphorylation time course became the same as control. Losartan, an AT1R blocker alone altered the time course of control fibroblast MKP-1 to mimic the increase seen in BS/GS fibroblasts while ERK1/2 declined concomitantly. Treatment with Losartan plus PD123319 in controls reduced MKP-1 and elevated ERK1/2 phosphorylation to those observed in BS/GS plus PD123319.

Conclusions: ERK1/2 phosphorylation time course found in BS/GS fibroblasts tracked changes in MKP-1 levels and incubation with an AT2R blocker, PD123319 abrogated those responses. Losartan, an AT1R blocker, reproduced these changes in healthy controls while the presence in controls of both AT1R and AT2R inhibitors abolished these changes. These data strongly suggest that MKP-1 is a major effector in altering ERK1/2 phosphorylation status. Moreover the results explain the blunted responses in BS/GS reported for Ang II short and long term effects, provide insight into the mechanisms responsible and thereby yield additional support for the role of AT2R signaling in the proposed effects of Ang II AT1R blockers beyond AT1R blockade.

6.4 ACE2 and Angiotensin 1-7 are Increased in a Human Model of Cardiovascular Hyporeactivity: Pathophysiological Implications

L.A. Calò, S. Schiavo, E. Pagnin and A.C. Pessina

Università di Padova, Padova, Italy

Introduction: ACE and ACE2 produce angiotensin II (Ang II), vasopressor, inducer of cardiovascular remodeling and Ang 1–7, vasodilator and antiremodeling factor. In addition, while Ang 1–7 has antiarrhythmic properties, at higher concentration it may induce ventricular tachycardia and sudden death. ACE2, therefore, may play essential role in blood pressure homeostasis, hypertension long term complications (cardiovascular remodeling) and in the induction of cardiac electric abnormalities.

Aim: This study evaluated in Bartter’s/Gitelman’s patients (BS/GS), who have elevated Ang II level and endogeneous blockade of Ang II type 1 receptor signaling, the levels of ACE2 and Ang 1–7 compared with healthy subjects and essential hypertensive patients. BS/GS were also considered given their not completely clarified predisposition to cardiac arrhythmias.

Methods: Mononuclear cell ACE2 and Ang 1–7 were evaluated using western blot.

Results: Both ACE2 (1.59 ± 0.63) and Ang 1–7 (2.26 ± 1.18) were significantly elevated in BS/GS compared with either normotensive controls (0.98 ± 0.45; p = 0.021; 1.12 ± 0.48, p = 0.018 respectively) and hypertensive patients (1.06 ± 0.24; p = 0.022; 0.72 ± 0.28; p = 0.005, respectively). ACE2 and Ang 1–7 directly correlated only in BS/GS (r = 0.914, p = 0.001).

Conclusions: The increases of ACE2 and Ang 1–7 in BS/GS mirror those in hypertensive patients and are in line with the clinic, haemodynamic and pathophysiological characteristics of BS/GS patients, likely contributing to them and further strengthen the importance of ACE2/Ang 1–7 system in cardiovascular biology.

6.5 Renin-Angiotensin-Aldosterone System and Erythrocyte Tyr-Phosphorylation of 3 Band Endometriosis

S. Garelli,¹ C. Fiore,¹ M. Gjergji,² L. Bordin,³ C. Cosma,⁴ A. Andrisani,² G. Ambrosini,² F. Manganello,² R. Favero,² G. Clari³ and D. Armanini¹

1 Dipartimento di Scienze Mediche e Chirurgiche — Endocrinologia, Padova, Italy; 2 Dipartimento di Scienze Ginecologiche e della Riproduzione Umana, Padova, Italy; 3 Dipartimento di Chimica Biologica, Padova, Italy; 4 Dipartimento diMedicinadi Laboratorio-Università di Padova, Padova, Italy

Introduction: Aldosterone (A) is involved in oxidative stress and inflammation, particularly at the cardiovascular level. The prooxidative action of aldosterone has been associated both to genomic and non genomic effects. We have recently showed that the inflammatory process can also be evaluated in erythrocytes analyzing biochemical parameters of the erythrocyte membranes, as in the case of Tyr-phosphorylation of 3 band. Moreover, the analysis of this protein could provide further material for evaluating the inflammatory status associated with endometriosis, a gynaecological situation associated with inflammatory status and cardiovascular complications.

Aim: To evaluate the renin aldosterone axis in these patients and to evaluate the non genomic oxidative status in erythrocytes of these patients.

Methods: 15 patients affected by ovarian endometriosis and 15 healthy controls matched for BMI and age were studied. Diagnosis was made by the usual exams and laparoscopy. The following plasma parameters were measured: A, PRA, sodium, potassium. Erythrocytes were isolated to measure total glutathione, oxidized glutathione, the analysis of the Tyr-phosphorylation levels in band 3 of the erythrocyte membranes and of its modifications/alterations at the membrane level.

Results: Plasma aldosterone in sitting position was significantly higher in endometriosis (509 ± 198 pmol/L) than control group (206.83 ± 129.04 pmol/L), p < 0.05. In all patients, after surgery A levels were lower (315 ± 81.5 pmol/L, p < 0.05). PRA and electrolytes did not change after surgery while aldosterone/PRA ratio was normal. The in vitro data of the erythrocytes isolated from the patients showed an increase of the Tyr-phosphorylation of the band 3 of the erythrocyte membrane and a minor concentration of glutathione reduced in oxidative stress conditions.

Conclusions: Endometriosis is associated with an increase of aldosterone and with Tyr-phosphorylation at the level of erythrocyte membrane and all these abnormalities are reversed after surgery. We hypothesize that aldosterone plays an important role in the inflammatory state of endometriosis. The analysis of the Tyr-phosphorylation of band 3 of this protein could be related to a non genomic effect of aldosterone on plasma membrane as reported by other studies.

6.6 Effects of Female Sex Hormones and Contraceptive Pill on the Diagnostic Work-Up for Primary Aldosteronism

F. Pizzolo, R. Raffaelli, C. Pavan, P. Guarini, A. Castagna, A. Memmo, A. Bassi, L. Chiecchi, R. Corrocher and O. Olivieri

Università di Verona, Verona, Italy

Introduction: At present Primary Aldosteronism (PA) is recognized as the most frequent cause of secondary hypertension. The change in the estimated prevalence has been mainly due to the widespread use of the aldosterone to renin ratio (ARR) as screening tool. Once the result of screening test is positive, PA diagnosis needs further confirmation by means of an inhibitory test such as iv saline load (SLT).

Aim: To investigate the role of female hormones in the work-up of patients suspected for having PA; by both evaluating possible differences by gender on the rate of saline loading inhibitory tests response and analysing the influence of free and pill-induced menstrual cycle on orthostatic ARR determination.

Method: We retrospectively examined the folders of 85 hypertensive patients who underwent iv SLT after a positive ARR screening. The screening test was considered to be positive when plasma aldosterone concentration was >150 pg/mL and orthostatic ARR was >32 pg/mL (ratio of aldosterone, expressed as pg/mLl-1, to direct active renin, expressed as pg/mL-1). We enrolled also 33 healthy fertile women, and analyzed ARR during free menstrual cycle (in the mid-cycle and luteal phase) and after two months of oral contraceptive (OC) therapy.

Results: In 46 out of 85 hypertensive patients diagnosis of PA was confirmed by iv SL test. Patients with positive SLT and patients with negative SLT differed only for gender distribution and ARR values: 85.2% of males with an elevated ARR at the initial screening had the PA diagnosis confirmed, compared with only 39.7% of females. In the healthy women population, an increase of renin and aldosterone concentrations occurred in the first to the second phase of menstrual period, with a substantially unchanged ARR. By contrast, after OC therapy renin values were nearly halved, aldosterone only slightly decreased and ARR doubled with mean values over the cut-off for PA screening.

Conclusions: ARR screening fails to predict the diagnosis of PA in the majority (60.3%) of hypertensive women as compared with 14.8% of hypertensive men. Variations of ARR during menstrual phases and after oral contraceptives may contribute to such diagnostic inaccuracy in females.

6.7 Nitric Oxide and Aldosterone Secretion in Human Hypertension

C. Sala, M. Rescaldani, L. Turolo, E. Oggiano, R. Famiani, GB. Bolla and F. Magrini

Università di Milan, Fondazione Policlinico IRCCS, Milan, Italy

Introduction: Nitric oxide (NO) inhibits aldosterone (Aldo) secretion from adrenal glomerulosa cells. Experimental hypertension induced by chronic NO-synthase inhibition is associated with increased plasma Aldo and interstitial fibrosis, which is reversed by spironolactone. In order to investigate the relationship between NO and Aldo secretion in human hypertension, we examined whether platelet cGMP, as a marker of NO activity, is related to plasma Aldo in essential hypertensive patients (EH).

Methods: In 103 untreated EH males (age 43.4 ± 1.4 yr, K + 4.2 ± 0.04 mEq/L), systolic, diastolic blood pressure (SBP, DBP, sphygmo) and heart rate (HR, pulse rate) were measured after a 60 min supine rest and venous blood was sampled for determination of plasma Aldo, renin activity (PRA), atrial natriuretic peptide (ANP) and platelet cGMP (PLTcGMP; RIA on acid extracts of washed platelets).

Results: The main findings of our study are shown in the table (mean ± S.E). In a univariate analysis, Aldo was directly related to PRA (r = 0.57, p < 0.01) and inversely to ANP (r = −0.20, p < 0.05) and PLT cGMP (r = −0.22, p < 0.05); this last parameter was unrelated to PRA (r = −0.11, ns) and to ANP (r = −0.12, ns). In a multiple regression analysis, plasma Aldo was predicted by PRA (beta = 0.53, p < 0.001), by PLT cGMP (beta = −0.17, p < 0.05) and not by ANP (beta = −0.13, p = 0.12).

Conclusions: In a population of EH, the marker of NO activity PLT cGMP is inversely related to plasma Aldo; among the multiple factors controlling Aldo secretion, PLT cGMP, after PRA, is the best predictor of the circulating levels of Aldo. Thus, our data are compatible with an inhibitory effect of the NO/cGMP system on Aldo secretion in human hypertension; this effect is apparently independent from a negative modulation of the circulating renin-angiotensin system.

6.8 Adrenal Endothelin-1 Levels are not Associated with Aldosterone Secretion in Primary Aldosteronism

F. Morello, C. Bertello, D. Schiavone, D. Tizzani, S. Totaro, S. Abram, E. Avenatti, P. Mulatero and F. Veglio

Università di Torino, Torino, Italy

Introduction: Endothelins (ET-1, ET-2 and ET-3) are potent vasoactive peptides with biological activity in several cardiovascular diseases. Several evidence have suggested tha there is a functional link between ETs and aldosterone. ETs have been show to act via ET(A and ET(B) receptors as aldosterone secretagogues in vitro and in vivo and may promote activation and proliferation of adrenal cells. Recent studies have also shown that aldosterone can, in turn, up-regulate ET-1 expression. In the present study, we sought to examine ET- secretion from the adrenal glands in patients with Primary Aldosteronism (PA).

Methods: We determined ET-1 levels in adrenal vein blood of 17 patients with confirmed PA undergoing AVS [7 adenomas (APA) and 10 bilateral adrenal hyperplasia (BAH)]. Only samples obtained from successful and diagnostic adrenal vein cannulation were used. To account for cannulation variability, raw ET-1 concentrations in adrenal bloo samples were normalized by local cortisol concentrations. Plasma ET-1 was measured by radioimmunoassay. We also examined the mRNA expression of the ET system in tissue samples from aldosterone-producing adenomas (APAs, n = 9) and control normal adrenal (n = 3).Tissue mRNA expression of the ET system was assayed with Affymetrix microarrays.

Results: ET-1 levels did not differ between inferior vena cava and adrenal vein blood in both bilateral adrenal hyperplasia and APA patients. Even after normalization for local cortisol levels (to account for sampling variability related to adrenal vein cannulation), normalize adrenal blood ET-1 levels did not differ ipsilaterally and contralaterally to the APA (4.3 ± 2.5 vs 7.2 ± 3.4 pg ET-1/μg cortisol). Through gene expression profiling with microarray, n significant difference was observed between ET-1 mRNA levels in APAs and in normal adrenal samples (fold change −1.06, p = 0.84). Similarly, ECE-1, ECE-2, ET(A) and ET(B were all similarly expressed in APA samples as compared with normal adrenals (p > 0.05) Microarray findings were further confirmed by quantitative real time PCR.

Conclusions: The present data argue against the hypothesis that adrenal gland ET-1 secretion is enhanced in PA and do not support a general role for adrenal ETs in the vascula pathophysiology of PA.

6.9 Impact of Accessory Hepatic Veins on the Selectivity Index during Adrenal Vein Sampling for Identification of Surgically Curable Primary Aldosteronism

G.P. Rossi,¹ G. Pitter,¹ T.M. Seccia,¹ R. De Toni,¹ M. Vincenzi,² G Feltrin,² D. Miotto² and A.C. Pessina¹

1 Clinica Medica 4, Padova, Italy; 2 Dipartimento di Scienze Medico-Diagnostiche e Terapie Speciali, Padova, Italy

Introduction: Adrenal vein sampling (AVS) is the ‘gold standard’ for identification of the surgically curable subtypes of primary aldosteronism (PA). Nevertheless, 15% of AVS are not selective at the right side, presumably because of the blood dilution from accessory vein blood.

Aim: To investigate the impact of accessory veins on the assessment of AVS selectivity.

Methods: In 73 consecutive PA patients undergoing AVS we prospectively determined at phlebography the presence of accessory veins draining into adrenal veins. The selectivity index (SI) was calculated as the ratio between plasma cortisol concentration (PCC) in the right or left adrenal vein and the infrarenal inferior vena cava (IVC). The diagnosis of APA was based on the ‘four corner’ approach.

Results: On the right side the venous anatomic pattern could be conclusively determined in 93% of the cases: we detected hepatic accessory veins in 12.1%, no accessory veins in 42.4%, and capsular veins in 45.5%. On the left side the anatomic venous pattern entailed phrenic veins in 89.1% of the cases and capsular accessory veins in the remaining 10.9%. On either side we found no effect of capsular and phrenic accessory veins on the SI. By contrast, on the right side the presence of hepatic accessory veins was associated with SI values about ten-fold lower as compared to the absence of such accessory veins (12.72 ± 2.41 vs 1.26 ± 0.32, p = 0.01), even when adrenal catheterization was judged to be selective at phlebography. Superselective adrenal catherization resulted into high values of the SI (34.2 ± 18.76, range 4.8–84.2) in these cases.

Conclusions: Hepatic accessory veins sharing common egress into the inferior vena cava with the right adrenal vein occur in about 12% of the patients and imply a low SI, likely because of adrenal blood dilution by hepatic blood carrying a low cortisol concentration. Super-selective catheterization of the right adrenal vein is necessary in these conditions, as bilaterally selective AVS data are required to accurately attribute lateralization of aldosterone secretion to the APA side.

6.10 Within-Patient Reproducibility of the ARR for the Screening of Primary Aldosteronism

G.P. Rossi,¹ C. Maniero,¹ T.M. Seccia,¹ A.C. Pessina¹ and F. Mantero² on behalf of PAPY Investigators

1 Clinica Medica 4, Padova, Italy; 2 Endocrinologia, Padova, Italy

Introduction: The plasma aldosterone (PAC) to plasma renin activity (PRA) ratio (ARR) is the most popular test for the screening of primary aldosteronism (PA). However, scant data on its reproducibility exist.

Aim: To investigate the within-patient reproducibility of the ARR using the PAPY study dataset.

Methods: In the PAPY study, a large prospective multicenter study that enrolled 1125 consecutive hypertensive patients referred to specialized centers for Hypertension in Italy, the ARR was determined at the baseline screening in all patients, and repeated before the saline infusion test, after on average 4 weeks, in the patients with an ARR >40 and in one every four of those with an ARR <40 according to a predefined protocol. The patients were carefully prepared from the pharmacologic standpoint, as previously described. The diagnosis of aldosterone-producing adenoma (APA), based on the ‘four corner criteria’, was used as referent. The Bland-Altman plot and coefficient of repeatability were used to determine the reproducibility of the ARR.

Results: Data for within-patients comparison of the ARR were available in 262 patients, of which 43 were conclusively diagnosed as APA. The ARR showed a highly significant within—patient correlation (r = 0.51, p < 0.0001) and repeatability. By Bland & Altman plot we found no evidence for proportional, magnitude- related, and absolute systematic error between the two ARR; moreover, only 4.3% of the values, e.g. the proportion that was predicted by chance, fell out of the 95% confidence interval for the between test difference. Finally, the overall concordance rate of the two ARR for pinpointing APA patients was 85%. Most discordant or false negative results could be accounted for by obvious protocol violations.

Conclusions: Albeit being performed under different conditions in a large multicenter study, the ARR showed a good within-patient repeatability. Thus, while challenging the claimed poor reproducibility of the ARR, these data support the use of this simple test for the screening of PA, provided that strict adherence to a predefined protocol is followed.

6.11 Expression Profiles of Aldosterone Producing Adenoma MicroRNA Revealed By Oligo-Micro-Array Analysis

L. Lenzini, T.M. Seccia, B. Caroccia and G.P. Rossi

Clinica Medica 4, Padova, Italy

Introduction: Primary aldosteronism is the most common endocrine cause of hypertension but its underlying mechanisms remain unknown. Aldosterone Producing Adenomas (APAs) were found to be heterogeneous at both the clinic and the molecular level. They respond differently in vivo to stimuli as ACTH and angiotensin II and despite featuring aldosterone overproduction they exhibited a heterogeneous expression of the steroidogenic enzymes when assessed with a whole transcriptome approach. Thus, the mechanisms leading to hyperaldosteronism and APA development are by far more complex than increased aldosterone synthase gene expression.

Aim: To disentangle this complexity we investigated the expression profile of microRNAs (miR), a number of short nucleotide RNA molecules that regulate gene expression for which no data in APAs are currently available.

Methods: The miR expression profile was measured by an oligomicroarray technique in APAs (N = 20) for which whole transcriptome data were already available, using the normal adrenal cortex (N = 3) as referent. Seven hundred twenty-three human and seventy six human viral miR sequences were quantified, using the Human miRNA Microarrays platform (Agilent Technologies). Results were analyzed using the Rosetta Resolver™ statistical software. Significant differences of miR expression were validated by real time RT-PCR, using RNU48 as housekeeping sequence.

Results: Overall there were no significant changes of miR sequences across APAs. However, as compared to the normal adrenal cortex a significant under-expression of miR199b and miR199a, which was validated by real time PCR was found. MiR 199b (mean expression fold change = −6.5 ± 5.0) and miR199a (−4.8 ± 13.9) were under-expressed in 95% and 75% of the APAs, respectively. A search of miR199a and miR199b targets by bioinformatics tools and its matching to the whole transcriptome data revealed some unexpected pathways that are currently investigated by functional experiments.

Conclusions: This homogeneous miR199b and miR199a under-expression contrasts markedly with the heterogeneous transcriptome profile in APAs; moreover, by involving these miR sequences in the physiopathology of APA, these findings mandate experiments aimed at defining the functional pathways associated with miR199 under-expression.

6.12 ‘Ether-À-Go-Go Like’ (ELK)-1 Expression in he Aldosterone Producing Adenoma (APA)

T.M. Seccia,¹ B. Caroccia,¹ L. Lenzini,¹ A.S. Belloni,² C. Recarti,¹ R. De Toni,¹ W.E. Rainey,³ A.C. Pessina¹ and G.P. Rossi¹

1 Clinica Medica 4, Padova, Italy; 2 Anatomia Umana e Fisiologia, Padova, Italy; 3 Department of Physiology, Medical College of Georgia, Augusta, GA, USA

Introduction: We previously identified with adrenal vein sampling (AVS) and ACTH stimulation ACTH-responsive (ACTH-R) and ACTH non-responsive (ACTH-NR) aldosterone producing adenomas (APA). However, the molecular mechanisms underlying this divergent responsiveness to ACTH are unknown.

Aim: To investigate if: (1) ACTH-R and ACTH-NR APA are characterized by different gene profiles, and (2) cultured cells isolated from ACTH-R or ACTH-NR APA maintain the responsiveness to ACTH in vitro and therefore can be useful to explore the mechanisms of the responsiveness to ACTH.

Methods: APA were diagnosed by the ‘four corner’ criteria developed in the PAPY Study (JACC 2006;48:2293). RNA from APA (n = 16) and pooled control RNAs from normal adrenocortical tissues (n = 8) were hybridized to Whole Human Genome Oligo Microarray. The microarray results were analysed with Feature Extraction and Rosetta Resolver and results were confirmed with quantitative real time RT-PCR (Q RT-PCR). Cells isolated from APA were incubated with 10–8 M ACTH and aldosterone secretion in the medium (RIA) and CYP11B2 gene expression was analyzed (Q RT-PCR). APA cells were also cultured and examined with electron microscopy (EM) at day 2, 4, and 6.

Results: We identified 24 genes that differed between ACTH-R and ACTH-NR APA, of which four code for K+ channel subunits. The 24 gene subset allowed correct classification of APA as ACTH-R or ACTH-NR with an overall accuracy greater than 80%, when applied retrospectively. KCNH8, which encodes for the ‘ether-à-go-go like’K+ channel (elk)-1, exhibited the most marked expression differences between ACTH-R and ACTH-NR APAs. Q-RT-PCR and immunoblot analysis confirmed the elk-1 gene expression in APAs. EM showed that the cultured cells maintained their original features only up to day 4. Noteworthy, after ACTH stimulation aldosterone production and CYP11B2 mRNA expression in the isolated and cultured cells at day 4 did not differ between ACTH-R and ACTH-NR.

Conclusions: This study evidences (1) different molecular signatures of ACTH-R and ACTH-NR APAs; (2) the presence of elk-1 in adrenocortical and APA cells. Elk-1, being differently expressed in ACTH-R and ACTH-NR APAs,might account for their divergent ACTH responsiveness. The dissociation between the in vivo and in vitro responsiveness to ACTH of APA cells indicates that freshly isolated or cultured APA cells cannot be a useful tool for investigating the mechanisms underlying the in vivo responsiveness to ACTH.

6.13 Expression of HE Adipokine CTRP-1 in the Human Adrenal Gland and The Arterial Wall: a Link Between Hyperaldosteronism and Vascular Remodelling?

G. Skander,¹ T.M. Seccia,¹ A. Belloni,² L. Lenzini,¹ A.C. Pessina¹ and G.P. Rossi¹

1 Clinica Medica 4, Padova, Italy; 2 Anatomia Umana e Fisiologia, Padova, Italy

Introduction: CTRP1 (Complement-C1q TNFα-related protein) is a novel recently identified adipokine. Since it was found to stimulate aldosterone production in the adrenocarcinoma- derived cell line H295R, we hypothesize that CTRP-1 may represent a patho-physiologic link between hyperaldosteronism and arterial hypertension in overweight-obese patients.

Aim: (1) To investigate whether CTRP-1 is expressed in the human adrenal gland and/or the arterial wall, and (2) to identify the cell type that synthesizes CTRP-1.

Methods: CTRP-1 gene expression was measured with quantitative real-time RT-PCR (Light-Cycler 480, Roche). RNA was extracted following a standard protocol (RNAeasy kit, Qiagen) from human adrenal tissue (incidentaloma, n = 2, pheochromocitoma, n = 5, aldosterone producing adenoma (APA), n = 8), omental and periadrenal adipose tissue (n = 4), and fibroblasts, vascular muscle cells (VSMCs), endothelial cells and H295. Expression levels were calculated with ΔΔCt method. CTRP-1 protein expression was investigated with immunohistochemistry (IHC) in paraffin-included sections from adrenal tissue, adipose tissue, aorta, and pulmonary, tibial, and mammary arteries. The presence of CTRP-1 protein was then confirmed with immunoblot.

Results: CTRP-1 gene was found to be expressed in the adipose tissue (expression level: 181 ± 105) and all adrenal tissues examined. Higher expression levels were found in pheocromocitomas (50 ± 22) as compared to both APA (30 ± 10) and incidentalomas (33 ± 23). All the examined cell types express CTRP-1, with higher expression levels in VSMCs than in endothelial cells and fibroblasts. IHC showed CTRP-1 protein expression in the adrenal gland and the adipose tissue. Immunoreactivity was markedly positive in the media layer of the small periadrenal arteries, less intense in the mammary, pulmonary and tibial arteries, and barely detectable in the aorta.

Conclusions: CTRP-1 expression is not restricted to the adipose tissue, but occurs also in the adrenal tissue and the arterial wall. The high CTRP-1 expression levels in the APA and pheochromocitoma suggest that CTRP-1 may modulate the aldosterone synthesis in the zona glomerulosa by autocrine/paracrine effects. The marked CTRP-1 expression in the media of the small arteries and the VSMCs suggest a role of CTRP-1 in the vascular remodelling associated with hyperaldosteronism.

6.14 Anti-Inflammatory Anti-Fibrotic Effect of Angiotensin AT2 Receptor Stimulation or AT1 Receptor Blockade in Scleroderma

F. Santi,¹ K. Ströder,² F. Rompe,² A. Wieland,² M. Artuc,³ C. Thöne-Reineke,² T. Unger² and U.M. Steckelings²

1 Università di Bologna, Ospedale S. Orsola Malpighi, Bologna, Italy; 2 CCR-Center for Cardiovascular Disease, Berlin, Germany; 3 Department of Dermatology, La Charité Hospital, Berlin, Germany

Introduction: Skin harbours a complete renin-angiotensin-system (RAS). There is evidence for an upregulation of RAS in Scleroderma lesions.

Aim: To investigate whether pharmacological interference with the RAS (angiotensin AT1 receptor blockade or AT2 receptor stimulation) may be effective in reducing inflammation and fibrosis in a scleroderma murine model.

Methods: Female C3/H mice were treated with bleomycin injection (100 μL of a 100 μg/mL solution s.c.) every second day over a period of 4 weeks. Animals were randomised in 4 treatment groups (n = 6 each): (i) control group, (ii) Bleomycin; (iii) Bleomycin + AT1R blocker, Candesartan (0.1 mg/kg bw, s.c. every day); (iv) Bleomycin + AT2R agonist, Compound21 (0.3 mg/kg bw, s.c. every day). Subsequently, tissue samples were collected and analysed for markers of inflammation and fibrosis by real time RT-PCR, Western Blotting and conventional histological staining (HE).

Results: After 4 weeks of Bleomycin injection, histological analysis showed an increased in extracellular matrix primarily within the subdermal layers. This fibrotic reaction was ameliorated both by Compound21 and Candesartan treatment. Histological reduction of fibrosis as a result of Compound21 or Candesartan treatment coincided with a reduced expression of precollagen IáI and TGFα as estimated by Western Blot. Furthermore, Bleomycin elicited an increase in IL-6 and MCP-1 mRNA expression, which could be significantly reduced by Compound21 and Candesartan. Experiments in vitro on human fibroblasts show results similar to our murine model.

Conclusions: Our data indicate that pharmacological interference with the cutaneous RAS by AT1R blockade or by AT2R stimulation could be a potential therapeutic approach to reduce inflammation and fibrosis in scleroderma and, potentially, in other pathological settings with similar pathomechanism.

6.15 Adrenal Gland Surgery in Hypertensive Patients: a Follow-Up Evaluation

A. Nardecchia, G. De Pergola, E. Dolce, R. Ria and F. Silvestris

Medicina Interna Universitaria, Bari, Italy

Introduction: In the last two years, we have started a collaboration with the University Clinic of Urology to examine patients affected by adrenal incidentalomas, independently of the presence of arterial hypertension.

Aim: To identify new predictive parameters of reappearance of hypertension in patients who underwent adrenal gland removal.

Methods: 70 patients (37 men and 33 women), aged 26–78 years, 59 hypertensive and 11 normotensive. The hypertensive group had patients with recent onset of hypertension or old diagnosis of the disease, but with recently developed resistance to drug therapy. Only 10 of hypertensive patients them had not family history of hypertension. All of patients had performed a adrenal gland MRI or TC before surgery, with the aim of defining the volume of the tumors. Spongiocytic adenomas (n = 9) had a volume of 1.0–7.0 cm, micronodular hyperplasias (n = 4) were 0.5–3.0 cm, pheochromocytomas (Pheo) (n = 8) were 3–5 cm, 1 haemorrhagic lesion had a volume of 12 cm, 1 mielolipoma 5 cm, 1 mixoid liposarcoma 17 cm, and 1 adenocarcinoma 6 cm.

Results: Concerning hormone evaluation, 1 adenocarcinoma, 2 of 4 cases of micronodular hyperplasia, and 8 of 9 cases of spongiocytic adenomas were characterized by high 24-hour urine cortisol. Only 2 of 8 cases of Pheo had high 24-hour urine catecholamines. Plasma aldosterone/PRA ratio was high in all cases of micronodular hyperplasias and in 6 of 9 cases of spongiocytic adenomas. Plasma DHEAS was high only in the patient with adenocarcinoma. High blood pressure (BP) was normalized after 1 month of adrenal gland removal in all patients with Pheo, in all subjects with micronodular hyperplasias, and in 7 of 9 cases of spongiocytic adenomas. After 6 months from surgery, BP had increased in 2 of 8 patients with Pheo, in 2 of 4 subjects with micronodular hyperplasias, and in 5 of 9 cases of spongiocytic adenomas.

Conclusions: Hypertensive patients who underwent adrenal gland removal have not actually solved their problem of hypertension. Whether this result is due to a pre-existing essential hypertension, it is difficult to explain by the BP changes after 6 months from surgery.We would like to suggest that it is very important the clinic evaluation in patients with adrenal gland alterations, to decide whether and when to address the patient to the surgeon and what to wait for after adrenal gland removal.

6.16 Assessment of Various Forms of Organ Damage in Patients with Primary Aldosteronism

M.L. Muiesan, C. Agabiti Rosei, M. Salvetti, A. Paini, D. Stassaldi, C. Aggiusti, L. Micheletti, C. Monteduro, E. Porteri, D. Rizzoni and E. Agabiti Rosei

Clinica Medica, Università di Brescia, Brescia, Italy

Introduction: In primary aldosteronism, target organ damage is greater than in age-, sex- and blood pressure-matched controls, reflecting the ability of elevated aldosterone to produce structural and functional changes over and above those produced by high blood pressure. Several studies have separately reported that complications are more evident in the cardiovascular system, and lesser in the kidney, although substantial.

Aim: To evaluate the whole spectrum of cardiac, vascular and renal complications in patients with PA.

Methods: In 76 patients with PA (n = 55 with adrenal hyperplasia AHA and n = 21 with adrenal adenoma APA), (mean age 51 ± 11 years, 25 F) echocardiography, carotid ultrasound and pulse wave velocity (PWV, Complior) were performed. All subjects underwent laboratory examinations, including PRA and plasma aldosterone, and both clinic and 24 hours blood pressure (BP) measurement.

Results: No significant differences were observed for clinic BP and heart rate values, total cholesterol and triglycerides plasma concentration, while 24 hours systolic BP and glycemia were higher in APA than in AHA. The prevalence of traditionally defined LVH (LVMI >47 and 50 g/m2.7 in males and women, respectively), carotid plaques (IMT >1.3 mm), increased arterial stiffness (PWV >12m/sec) and impaired renal function (estimated glomerular filtration rate MDRD formula <60mL/min/1.73m2) were respectively 44%, 61%, 28% and 13%. The prevalence of LVH was greater in APA than in AHA (62 vs 37% chi square = 0.05), although this difference lost statistical significance after considering differences in 24 hours SBP and glycemia. No significant differences between APA and AHA were observed in the prevalence of carotid plaques, increased arterial stiffness or renal function impairment, even after adjusting for 24 hours SBP and glycemia.

Conclusions: In this large group of patients with PA the prevalence of cardiac and vascular alterations is greater, followed by a lesser impairment of renal function, possibly explaining the adverse cardiovascular outcome observed in these patients. No differences are observed between APA and AHA in different TOD prevalence.

Hypertension during Pregnancy

7.1 Left Ventricular Remodelling during Gestational Period in Normotensive Rats

F. Giofrè,¹ G. Acquistapace,¹ R. Paliotti,¹ G. Busca,¹ I. Zucca,² F. Magrini³ and M. Ciulla¹

1 Dipartimento Toraco Polmonare e Cardiocircolatorio, Università di Milan, Milan, Italy; 2 Fondazione IRCCS IstitutoNeurologico “Carlo Besta”, Direzione Scientifica, Milan, Italy; 3 Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy

Aim: To investigate the effects of volume overload in pregnancy on left ventricular (LV) geometry and function using cine-MRI, by comparing non pregnant (NP) with late 3rd week pregnant normotensive (LP) rats.

Methods: 14 female CD rats, 9 weeks old, were investigated, 7 NP and 7 normotensive LP. In vivo heart dimensions and function were evaluated by MRI (isoflurane anesthesia; 20 phases/cycle, slice thickness 1 mm, matrix size 192 × 192; TE/TR = 2.9/8.3 ms) on images obtained at the same level used for standard 2D-echo (12.5 Mhz linear array). LV geometry was assessed according to Relative Wall Thickness (RWT) and Left Ventricular Mass Index (LVMI) ratio as follows: normal (N), concentric (CH) and eccentric (EH) hypertrophy, concentric remodeling (CR).

Results: An increase in heart rate was found in LP if compared to NP (Δ + 8%; p = 0.024); LV wall thicknesses (interventricular septum and posterior wall) at end-diastole/systole were higher in LP, while LV diameters, even if slightly greater, and Ejection Fraction were not significantly different in the studied groups. Cardiac Output was increased in LP (Δ + 30%; p = 0.03) mainly due to the combined increase in Stroke Volume and Heart Rate (HR). Furthermore, LV mass was increased in LP (Δ + 23%; p = 0.04) with a high prevalence of LV hypertrophy (n = 3; 43%), classified as EH in 2 cases, and as CH in 1 case. Some differences were found when comparing MRI and 2D-echo linear measurements, especially in LV wall thicknesses, that were generally underestimated by 2D-echo if compared with MRI. Moreover, geometric differences were found in geometric patterns assignment, where 2D-echo misclassified a case of CH.

Conclusions: LV hypertrophy, mainly eccentric (28%), is a frequent process of adaptation during normal late pregnancy also in rats, nevertheless it is not the main phenotype, since 57% of LP rats were characterized by a normal LV geometry; measurements obtained by MRI were not always concurrent with those obtained by 2D-echo, reflecting the better definition in MRI evaluations of LV dimension and geometry.

7.2 An Uncomplicated Case of Primary Aldosteronism in Pregnancy

G. Giacchetti,¹ F. Turchi,¹ V. Ronconi,¹ M. Scarpelli² and M. Boscaro¹

1 Clinica di Endocrinologia-Università Politecnica delle Marche, Ancona, Italy; 2 Anatomia Patolgica-Università Politecnica delle Marche, Ancona, Italy

Introduction: Primary aldosteronism (PA) has been shown to follow a variable course in pregnancy, characterized by an high prevalence of preterm delivery, placental abruption, intrauterine fetal death and fetal distress. In a small number of patients (n = 3 cases reported in literature) blood pressure decline spontaneously.

Clinic Case: In May 2007 our patients with idiopathic hyperaldosteronism expressed the willing to get pregnant. She was referred to our clinic for the first time in 2005, when she is 28 years old, with palpitation and severe hypertension. After hormonal evaluation, CT scan of adrenal glands and the adrenal venous sampling, PA due to bilateral aldosterone oversecretion was diagnosed. She started treatment with MR antagonist (potassium canrenoate, 100 mg/day) and calcium channel antagonist (amlodipine 10 mg/day) with good control of high blood pressure (130/80 mmHg) and maintenance of normokalemia. Planning a pregnancy, the MR antagonist was withdrawn due to the concern of causing possible feminization of male infant, while calcium channel blocker was continued and oral potassium supplementation was started (40–48 mEq/day). In July 2007 she got pregnant. During pregnancy, despite higher aldosterone levels (219 pg/mLat 11a week, 561 pg/mL at 24a week and 860 pg/mL at 36a week) with arising in progesterone (42.5 ng/mL at 11a week, 95 ng/mL at 24a week and 232 ng/mL at 36a week), blood pressure decline to normal values so that she gradually discontinued antihypertensive treatment and continued only potassium supplementation. The patient was tightly followed by clinic and biochemical evaluations during pregnancy which course was uncomplicated. She had a vaginal delivery at term (38 weeks of gestation), and gave birth to a healthy boy. Pathological examination of the placenta showed a normal vascular structure without signs of damage due to aldosterone excess. 24 hour after the delivery, supine plasma aldosterone levels were 299 pg/mL while plasma progesterone values were 31 ng/mL. The post-delivery course was characterized by normotension until 4 days after delivery, then blood pressure began to rise again and she had to reintroduce antihypertensive treatment, while the aldosterone levels started to decreased.

Conclusions: We conclude that a previous planning of pregnancy, an early and appropriate medical therapy and vigilance regarding the occurrence of possible complications are recommended in the not rare condition of PA in pregnancy, in order to reduce both the maternal and fetal risks associated with this disease.

7.3 Pregnancy in Women with Chronic Hypertension: Outcome and Complications

Francesca Vettore,¹ Grazia Guzzetta,¹ Anna Realdi,¹ Giulia Inverso,¹ Luisa Macchini,¹ Paola Caielli,¹ Giacomo Strapazzon,¹ Martino Pengo,¹ C. Leprotti² and A. Semplicini²

1 Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Padova, Italy; 2 Dipartimento di Medicina Clinica, ULSS 12 Veneziana, Venezia, Italy

Introduction: Hypertension during pregnancy is common and a major cause of maternal, foetal and neonatal morbidity. The choice of antihypertensive drugs in women who want to conceive must be prudent as some antihypertensive drugs are not safe for the infant and the pharmacological treatment of hypertension during pregnancy only limits progression to severe hypertension.

Aim: To correlate pregnancy outcome, complications with antihypertensive treatment and blood pressure control in patients with chronic hypertension.

Methods: We identified 49 pregnant hypertensive patients attending the hypertension outpatient clinic of Padua between 1983 and 2008 with 54 pregnancies. Aetiology of hypertension, antihypertensive treatment before, during and after pregnancy, number and type of drugs, office blood pressure control during pregnancy, risk factors for pre-eclampsia, laboratory findings suggestive of pre-eclampsia, course and outcome of pregnancy were assessed.

Results: Forty five patients (92%) had essential hypertension and 38 (73%) had been taking antihypertensive drugs before pregnancy. During pregnancy, 30 patients were treated with two or more antihypertensive drugs. Blood pressure control was good in 31 patients (59%). Twenty nine patients (56%) had maternal or foetal complications with 10 terminations of pregnancy and 84% caesarean section delivery. Risk factors for pre-eclampsia were not different between pregnant women with or without complications. Twenty eight out of 29 (97%) pregnant women with complications had been taking antihypertensive drugs. The incidence of complications was higher in treated (28/48, 58%) than in untreated patients (1/4, 25%), but the difference was not statistically significant. Beta blockers, alone or in combination, were significantly associated with complications. Upon multivariate linear regression analysis, low birth weight was independently associated with beta blocker treatment (beta = −0.218, p < 0.05) and duration of pregnancy (beta = 0.791, p < 0.001), but duration of pregnancy did not differ in patients treated with or without beta-blockers.

Conclusions: Women with chronic hypertension who begin a pregnancy are at high risk of maternal and foetal complications, and above all those with severe hypertension. Antihypertensive treatment and blood pressure control during pregnancy do not reduce the risk of complications, with beta-blocker administration linked to the largest incidence, especially low birth weight. Hypertensive women need a close follow-up, before, during and after pregnancy to plan the best diagnostic and therapeutic work up.

7.4 Left Ventricular Structure and Function and Blood Pressure Values in Women with Previous Pre-Eclampsia

M. Salvetti,¹ F. Prefumo,² A. Paini,¹ G. Gatti,² E. Belotti,¹ C. Agabiti Rosei,¹ C. Aggiusti,¹ E. Agabiti Rosei,¹ T. Frusca² and M.L. Muiesan¹

1 Clinica Medica, Università di Brescia, Brescia, Italy; 2 Clinica Ostetrica e Ginecologica, Università di Brescia, Brescia, Italy

Introduction: It has been reported that women with a history of pre-eclampsia (PE) may have an increased risk for cardiovascular events or chronic kidney disease in later life. Most studies analysed the prevalence of cardiovascular risk factors or the occurrence of CV events in the long term (9–14 years after delivery). Very few data are available on the time course of blood pressure (BP) increase and of cardiovascular target organ damage development in these patients.

Aim: To evaluate arterial blood pressure and cardiovascular structural changes in patients with a previous first pregnancy complicated by pre-eclampsia as compared to subjects with a previous first uncomplicated pregnancy, 2 years after delivery.

Methods: 15 women with previous PE (defined as SAP ≥ 140 and/or DAP ≥ 90 mmHg and proteinuria >0.3 gr/24-hour) and 15 women with a previous uncomplicated pregnancy, matched for demographic and anthropometric variables, underwent a follow up visit 30 ≥ 7 months after delivery. In all patients echocardiography (Mono-bidimensional+conventional and tissue Doppler analysis) was performed for the evaluation of left ventricular structure and function.

Results: The two groups were comparable for age, weight, BMI and duration of follow up. Mean age was 36 ± 10 years, gestational age at diagnosis of PE was 29.6 ± 2.6 W. Systolic BP was similar in the two groups, while diastolic BP was significantly higher in patients with previous pre-eclampsia (114 ± 10 vs 112 ± 7 mmHg, p n.s and 67 ± 8 vs 72 ± 6 mmHg, p < 0.05). Left ventricular (LV) mass index and relative wall thickness were not different in the two groups (24.5 ± 7 vs 26 ± 5 gr/h2.7 and 0.27 ± 0.03 vs 0.26 ± 0.03, respectively, p = NS), as were indices of LV systolic function. Left atrial diameter was significantly greater in patients with previous PE (3.3 ± 0.3 vs 3.0 ± 0.3, p < 0.05). The ratio of mitral annular e velocity (Em) to annular A velocity (Am) was significantly lower in PE (1.7 ± 0.5 vs 2.1 ± 0.5 respectively, p < 0.05) and the ratio of transmitral e velocity (E) to annular e velocity (Em), a reliable marker of LV filling pressures, was significantly higher in patients with previous PE in comparison to controls (7.01 ± 1.3 vs 6.2 ± 1.0 respectively, p < 0.05).

Conclusions: Our findings suggest that, in patients with previous PE, an early increase in BP values may be observed associated with structural and functional changes of diastolic filling and relaxation indexes. These results may give further insights into the mechanisms underlying the increased CV risk observed in subjects with previous pre-eclampsia.

7.5 Cytochrome P-450 Derived Metabolites of Arachidonic Acid in Pregnancy and Pre-Eclampsia

P. Minuz,¹ G. Amen,¹ H. Jiang,² C. Fava,¹ A. Meneguzzi,¹ G. Zanconato,¹ A. Lechi,¹ J.C. McGiff² and P. Patrignani³

1 Università di Verona, Verona, Italy; 2 New York Medical College, New York, NY, USA; 3 Università di Chieti, Chieti, Italy

Introduction: Pre-eclampsia is characterized by reduced generation of angiogenic factors and coexisting metabolic risk factors, which may independently contribute the development of the disease. Experimental data indicate that P-450 (CYP)-derived metabolites of arachidonic acid, implicated in the control blood pressure and renal excretion of sodium, may have a role in altered placental vascularization, as well as the development of hypertension and renal dysfunction in pre-eclamptic women.

Methods: We set up a cross-sectional study in which women with pre-eclampsia (hypertension after the 20th week of pregnancy plus proteinuria >300 mg/day) were compared with normotensive pregnant women of the same gestational age (30–39 weeks) and non-pregnant women. The three groups were pair-matched for age (22–38 years), pre-gravidic BMI (below 26 in all the pre-eclamptic women) and the absence of metabolic risk factors (obesity, diabetes, pre-existing arterial hypertension). Plasma concentrations of epoxyeicosatrienoic acid (EETs) and their metabolites (DHETs, also measured in urine), together with plasma concentration and urinary excretion of 20-hydroxyeicosatetraenoic acid (20-HETE) were measured by mass-spectrometry.

Results: A preliminary analysis of the data showed that EETs are significantly higher in normotensive pregnant (median 11.5 ng/mL; range: 5.9–25.2; n = 11) and pre-eclamptic women (13.7 ng/mL; 6.8–48.0; n = 8), compared to non-pregnant controls (7.4 ng/mL; 3.7–10.3; n = 8, p < 0.05), with no significant differences in DHETs, data indicating a possible reduction in epoxide hydrolase activity in late pregnancy. Similarly to what observed in other hypertensive conditions, the urinary excretion of 20-HETE was lower in pre-eclamptic women (1.3 ng/h; 0.2–2.6, n = 8, p < 0.05), compared to normotensive pregnant (3.1 ng/h; 0.5–30.8; n = 11) and non-pregnant women (3.3 ng/h; 0.8–28.3; n = 11). In pre-eclamptic women blood pressure was higher, although treated, as was arterial stiffness, measured by means of a pulse wave analyzer (Stiffness Index 8.3; 6.8–10.7; non-pregnant women: 6.8; 4.4–7.3; p < 0.05).

Conclusions: Our data indicate that CYP-dependent arachidonic acid metabolism is altered during pregnancy and suggest a role for CYP-derived metabolites of arachidonic acid in the pathogenesis of pre-eclampsia, independently of any pre-existing risk factor.

Imaging Techniques

8.1 Evaluation of the Relationship between Carotid Arterial Stiffness, Assessed with E-Tracking, and Left Ventricular Diastolic Function in Diabetics and Hypertensive Patients with Coronary Microcirculation Disease

F. Natale, L. Aronne, G.M Di marco, A. Siciliano, M. Cardaropoli, E. Lo priore, P. Calabrò, L. Scotto di vetta, C. Granato, C. Cirillo, P. Golino and R. Calabrò

Seconda Università di Napoli, Napoli, Italy

Introduction: In diabetic and hypertensive patients increased arterial stiffness and diastolic dysfunction are early expression of organ damage and are related with a higher cardiovascular risk. Subjects with increased arterial stiffness PWV is high, and the backward waves from the periphery return earlier to the ascending aorta. Since this backward waves coming from the periphery arrive during the LV ejection, they raise the central systolic blood pressure and the LV afterload and decrease the central diastolic pressure and the coronary perfusion pressure. These changes may cause ischaemia particularly in the subendocardium, which if chronic is associated with left ventricular interstitial fibrosis.

Aim: We assessed the arterial stiffness by a non-invasive new tool known as ‘e-tracking, Aloka, Japan’ and the diastolic function with tissue Doppler imaging in patients with coronary micro-circulation disease proved by typical anginous synthomatology, negative coronary angiography, positive myocardial scintigraphy stress test.

Methods: We have observed 40 consecutive patients with angina, proved by typical clinic history, positive myocardial scintigraphy stress test and negative coronary angiography. We compared the data of arterial stiffness with the measurements of 50 healthy volunteers. We performed e-tracking on the left carotid with ALOKA alfa 10 ultrasound system. Arterial compliance (AC), pulse wave velocity (PWV), elastic pressure (Ep) stiffness parameter (Beta) and augmentation index (AI) were measured.

Results: Pwv (m/s) 7 ± 2, AC (mm²/Kpa) 1 ± 0.4, Ep (Kpa) 102 ± 31, Beta 7.53 ± 2, AI (%) (17 ± 8), normalized for age, were increased when compared with healthy subjects. Stiffness parameters correlate significantly with Tissue Doppler imaging diastolic parameters : pwv (r = 0.56, p < 0.05), Ep (r = 0.55, p < 0.05) and AI (r = 0.75, p < 0.01).

Conclusions: These results suggest that increased arterial stiffness could be involved in the pathogenesis of the left ventricle microcirculation disease. The positive correlation between Em and arterial stiffness parameters show that diastolic disfunction may be also linked to health status of artery.

8.2 Relationship between Carotid Artery Stiffness, Assessed with E-Tracking, and Carotid Plaque Echogenicity in Hypertensive Patients

F. Natale, C. Cirillo, E. Lo Priore, L. Aronne, M. Cardaropoli, F. Allocca, P. Calabrò, G.M. Di Marco, L. Scotto Di Vetta, A. Siciliano, P. Golino and R. Calabro

Seconda Università di Napoli, Napoli, Italy

Introduction: Plaques that appear echolucent on B-mode ultrasound are lipid-rich, whereas echogenic plaques have a higher content of fibrous tissue and calcification.

Aim: To evaluate carotid artery stiffness parameters in patients with echogenic plaque and patients with echolucent plaques.

Methods: We have observed 40 hypertensive patients with carotid plaque. Carotid artery stiffness parameters were assessed by e-tracking on the left carotid (in free plaque area) with ALOKA alfa 10 ultrasound system. Elastic pressure (Ep) and stiffness parameter (Beta) were measured. Carotid plaque echogenicity was graded from 1 (plaque appearing black or almost black) to 4 (plaque appearing white or almost white) according to the Gray-Weale classification. Plaques of grades 1 and 2 were defined as echolucent plaques, and plaques of grades 3 and 4 were defined as echogenic plaques. Patients were divide in two groups (A or B) according plaque echogenicity.

Results: Themain findings of our study are shown in the table. Ep (Kpa) 110 ± 31, Beta 8.5 ± 2, of group A (echogenic plaque), were increased when compared with group B (echolucent plaque) p < 0.05.

Conclusions: Carotid arterial stiffness assessed by e-tracking was increased in hypertensive patients with echogenic plaques. Probably it depend by the same systemic pathophysiological process leading to connective tissue extracellular matrix accumulation.

8.3 Association between Carotid Artery Stiffness, Estimated With E-Tracking, and Diastolic Dysfunction, Assessed with Tissue Doppler Imaging in 80 Patients with Masked Hypertension

F. Natale, A. Siciliano, G.M. Di Marco, C. Cirillo, C. Granato, L. Aronne, M. Cardaropoli, E. Lo Priore, L. Scotto di Vetta, P. Calabrò, P. Golino and R. Calabro

Seconda Università di Napoli, Napoli, Italy

Introduction: A normal blood pressure, in the clinic, but an elevated blood pressure out of the clinic is defined as masked hypertension. It may occur in as many 10% of the general population. Increased arterial stiffness directly increases end-diastolic left ventricular pressure and compromise myocardial relaxation properties.

Aim: To evaluate the role of carotid artery stiffness parameters on diastolic function in patients with masked hypertension.

Methods: We observed 80 consecutive patients with masked hypertension (proved by 24 h- ambulatory blood pressure monitoring). Diastolic early (E’) and late (A’) velocities were recorded by pulse wave tissue doppler performed on the lateral mitral anulus in the apical 4-chamber view. Carotid artery stiffness parameters were valued by e-tracking on the left carotid with ALOKA alfa 10 ultrasound system. Pulse wave velocity (PWV), elastic pressure (Ep) and stiffness parameter (Beta) were measured.

Results: PWV (m/s) 8 ± 2, Ep (Kpa) 134 ± 23, Beta 12 ± 2, normalized for age, were increased when compared with healthy subjects. Stiffness parameters correlate significantly with Tissue Doppler imaging diastolic parameters in particularly with E’: PWV (r = 0.68, p < 0.05), Ep (r = 0.60, p < 0.05) and Beta (r = 0.68, p < 0.01).

Conclusions: Patients with masked hypertension increased arterial stiffness and abnormal left ventricular diastolic function (particularly with E’), was associated with arterial stiffness, expression of a greater contribution of atrial contraction to left ventricular filling for increased left ventricular end-diastolic pressure due to an high afterload.

Kidney

9.1 Role of Sympathetic Activation and Methylarginies Accumulation in Mild-To-Moderate Renal Failure

F. Arenare,¹ F. Quarti,¹ G. Seravalle,² C. Mineo,¹ L. Magni,¹ C. Zoccali,³ F. Mallamaci,³ G. Grassi¹ and G. Mancia¹

1 Università Milan-Bicocca, Monza, Italy; 2 Istituto Auxologico Italiano, Milan, Italy; 3 Unità Operativa di Nefrologia, Dialisi e Trapianto Renale Ospedali Riuniti e IBIM-CNR, Reggio Calabria, Italy

Introduction: End-stage renal failure is characterized by a profound sympathetic activation coupled with an endothelial dysfunction, as documented by the marked increase in circulating plasma norepinephrine and asymmetric dimethylarginine (ADMA) values. Whether this is the case in mild renal failure is unknown, however. It is also unknown which of the two alterations has an earlier appearance in the clinic course of the disease.

Methods: In 22 mild-to-moderate renal failure patients belonging to stage 2–3 of the National Kidney Foundation Classification, due to nephrosclerosis or chronic interstitial nephritis (15 males, 7 females; age: 61.7 ± 2.1 years; creatinine clearance: 46.6 ± 3.3 mL/min, mean ± SEM), we measured beat-to-beat blood pressure (Finapres), heart rate (EKG), plasma norepinephrine (HPLC) and muscle sympathetic nerve traffic during a 30 min resting period (MSNA, microneurography, peroneal nerve). Measurements, which included ADMA and symmetric dimethylarginine SDMA (Enzyme-Linked Immunosorbent Assay), were performed also in 12 age-matched healthy control subjects.

Results: In renal failure patients MSNA values were significant increased as compared to controls (68.4 ± 3.3 vs 36.8 ± 5.7 bursts/100 hb, p < 0.01), this being the case for plasma norepinephrine (323.3 ± 73 vs 210.8 ± 29, p < 0.05) and, although to a lesser extent, for heart rate (73.1 ± 2.8 vs 68.6 ± 1.9 beats/min, p = 0.07). In contrast, both ADMA and SDMA were still in the normal range with values similar to controls (0.72 ± 0.03 vs. 0.68 ± 0.08 and 1.03 ± 0.1 vs 0.94 ± 0.2 μmol/L, p = NS). No significant relationship was found between ADMA, SDMA and direct (MSNA) or indirect (heart rate, norepinephrine) indices of adrenergic cardiovascular tone.

Conclusions: These findings provide evidence that in mild to moderate renal failure two markers of adrenergic drive such as plasma NE and MSNA display a substantial increase well before any significant raise in ADMA and SDMA. This suggests that sympathetic activation (1) precedes methylarginines accumulation in the development and progression of the renal disease and (2) may be responsible for the more advanced appearance of the endothelial alteration.

9.2 Frequency and Co-Frequency of Cardiac, Renal and Vascular Damage in a Group of Treated Hypertensive Patients

L. Boffi, R. Facchetti, F. Cesana, A. Salvioni, G. Grosso, D. Dozio, P. Canova, P. Campadello, M. Galbiati, M. Rigoldi, A. Capra, M. Failla, C. Giannattasio and G. Mancia

Clinica Medica, Univ-Milan Bicocca e Ospedale San Gerardo di Monza, Monza, Italy

Introduction: Current European hypertension guidelines emphasize the importance of assessing organ damage in order to accurately define the total cardiovascular risk of hypertensive patients.

Aim: To define in a large series of hypertensive patients, prevalence of organ damage in the different vital organs subjected to the effects of hypertension as well as their correlation.

Methods: We investigated 511 consecutive outpatients with essential hypertension and in apparently adequate control treatment. Organ damage was assessed in the kidney by the presence of microalbuminuria (spot urine), a glomerular filtration rate <60 mL/min/1.73 m² (MDRD) or a creatinine clearance <60 mL/min (CrCl-Cockroft-Gault equation) in the hearth by the presence of left ventricular hypertrophy (LVH, echocardiography) and left ventricular mass index (LVM, M ≥ 125 g/m²; W ≥ 110 g/m²) and in large arteries by the presence of a common carotid intima-media thickness > 0.9 mm (ecocolordoppler, IMT).

Results: Average (±SD) blood pressure was 142.1 ± 18.6 (SBP) and 86.4 ± 10.3(DBP) mmHg in the wall population. LVH was present in 241 (48%) of the patients, the prevalence was 5%, 14% and 10% for reduced GFR, reduced CrCl and increased IMT, respectively. There was a highly significantly correlation (p < 0.01) between all measure of organ damage although their values were never high (between 0.15 and 0.36). The relation of CrCl with LVH survived in a multiple regression model considering all risk factors measured. Organ damage in one organ was present in 39% of patients, the prevalence of two and three organ damage was 13% and 3% respectively.

Conclusions: In essential hypertension organ damage is common even when blood pressure is close to or near normal values. Multiorgan damage is more rarely. CrCl seems to be the most sensible predictor of the cardiovascular target organ; CrCl is also the most related one to LVMI which is the most frequent organ damage in Hypertensive patients.

9.3 Intrarenal Resistance Indices are Related to Arterial Stiffness and Other Subclinic CV Risk Factors

A. Salvioni, C. Zazzeron, L. Boffi, R. Facchetti, F. Citterio, F. Cesana, G. Grosso, C. Nicoli, M. Pozzi, A. Capra, M. Failla, C. Giannattasio and G. Mancia

Clinica Medica, Univ-Milan Bicocca e Ospedale San Gerardo di Monza, Monza, Italy

Introduction: ColorDoppler duplex ultrasound of renal artery is used to measure intrarenal vascular resistance, the increase of which (mean resistance index, mRI > 0.7) is believed to represent an element in favour of a form of renal cause of hypertension. Limited information exists however on whether and to what extend intrarenal vascular resistance reflect generalized rather than specific vessel alteration.

Aim: We hypothesize the association of intrarenal vascular resistance with cardiovascular risk factors and subclinic systemic damage in mild to moderate essential hypertensive patients.

Methods: We studied 58 consecutive (30 men and 28 women, age 53 ± 13 years, mean ± SD) treated essential hypertensive patients (blood pressure 145 ± 21/88 ± 11 mmHg, SBP/DBP) seen as outpatients in our Hospital. Patients with diabetes mellitus, obesity and chronic renal diseases or pathology were excluded. Measurements included metabolic risk factors, estimated glomerular filtration rate (MDRD), creatinine clearance (Cockroft-Gault formula), spot urine microalbuminuria, left ventricular mass index and diastolic function (LVMI and E/A, echocardiogram), common carotid intima-media thickness (IMT), aortic stiffness (pulse wave velocity, PWVcf). Total Cardiovascular risk was determined by the Framingham risk score and by SCORE. Renal resistance index was calculated by echoDoppler as the average of peak systolic velocity minus diastolic velocity/peak systolic velocity at nine representative locations of the renal artery.

Results: The mRI was always <0.7 and the average value was 0.59 ± 0.09. As expected, the mRI was significantly related with age (r = 0.41, p < 0.001) and SBP (r = 0.31, p = 0.01). There was a significantly correlation with several other variables: PWVcf (r = 0.36, p = 0.004), IMT (r = 0.39, p = 0.002), E/A (r = 0.29, p = 0.03), glomerular filtrate rate (r = −0.32, p = 0.03) and creatinine clearance (r = −0.42, p < 0.001). There was also a high significant correlation with total cardiovascular risk as quantified by the Framingham and the SCORE method.(r = 0.42; p < 0.001). The PWVcf value and the SCORE quantification of total risk, remained the only selected variables significant in a multivariate analysis.

Conclusions: In mild to moderate uncomplicated hypertension, mRI reflects the general arterial characteristics as measured by arterial stiffness.

9.4 Burden of Chronic Renal Insufficiency in the General Population and Added Predictive Power of Glomerular Filtration Rate to Brain Natriuretic Peptide (BNP) and NT-ProBNP in Detection of Altered Ventricular Structure and Function

A. Cataliotti,¹ D.W. Mahoney,¹ R.J. Rodeheffer,¹ C.S.P. Lam,¹ M.M. Redfield,¹ J.C. BurnettJr¹ and L.S. Malatino²

1 Division of Cardiovascular Diseases, Mayo Clinic and Foundation, Rochester-USA; 2 Dipartimento di Medicina Interna e Patologie Sistemiche, Catania, Italy

Introduction: Chronic renal insufficiency (CRI) is a strong predictor of increased mortality in the presence of congestive heart failure (CHF) and its prevalence has been increasing in the US. In addition, CRI is a major contributing factor to the progression of CHF as it is associated with chronic volume overload, accelerated atherosclerosis and hypertension (HTN).

Aim: The first aim of the current study was to evaluate the prevalence of CRI in an adult general population. The second aim was to address whether calculated glomerular filtration rate (cGFR) adds value to the cardiac biomarkers BNP and NT-proBNP in detecting early cardiac structural and functional impairments in the general population.

Methods: From 1997 to 1999 medical history, physical examination, echocardiography, BNP (Biosite) and NT-proBNP (Roche) and serum creatinine (SCr) were obtained in 1982 randomly selected residents of Olmsted County, MN ≥45 years (range 45–96 years). GFR was calculated using the Cockroft Gault equation adjusting for age, gender, body weight and surface area in which CRI was defined as a GFR <60 mL/min. Cardiac structure and function were evaluated by in- depth echocardiographic examination.

Results: In this random adult cohort, the prevalence of cardiovascular comorbidities was coronary atherosclerosis 12%, HTN 29.5% and diabetes mellitus 7.5%. The prevalence of CRI was 22.8% when cGFR was used for its detection. Importantly, cGFR significantly increased the ability of BNP in detecting left ventricular hypertrophy (LVH) (p = 0.0044), increased relative wall thickness (RWT) (p = 0.0036), diastolic dysfunction (DDF) (p = 0.0001) and HTN (p = 0.0002). Similarly, when combined with NT-proBNP, cGFR increased the predictive power of detecting DDF (p = 0.0001) and HTN (p = 0.0366).

Conclusions: This study reports a higher than predicted prevalence of CRI in this general adult US population equal to 23% and closely associated with the prevalence of HTN (29.5%). Importantly, this study also demonstrates that cGFR has additive predictive power when used in combination with two important cardiac biomarkers of cardiac dysfunction and remodeling which are BNP and NT-proBNP. These studies underscore the increasing burden of CRI in the general population and the utility of assessing cardiorenal function by combining renal and cardiac biomarkers in assessment of cardiac structure and function.

9.5 Microalbuminuria is a Predictor of Chronic Renal Insufficiency in Non-Diabetic Hypertensive Patients: the Magic Study

F. Viazzi, G. Leoncini, N. Conti, E. Baratto, G. Storace, R. Pontremoli and G. Deferrari

Azienda Ospedale Università San Martino, Genova, Italy

Introduction: Increased urinary albumin excretion is a known risk factor for cardiovascular events (CVE) and clinic nephropathy in diabetic patients. Whether microalbuminuria predicts long term development of chronic renal insufficiency (CRI) in non diabetic patients with primary hypertension remains to be documented.

Methods: We conducted an 11.8 year follow-up of 917 hypertensive, non diabetic patients enrolled in the MAGIC cohort between 1993 and 1997. Urinary albumin to creatinine ratio (ACR) was assessed at baseline in untreated patients in a core laboratory. Microalbuminuria was defined as ACR ¡Ỳ 22 mg/g in men and ACR ¡Ỳ 31 mg/g in women.

Results: A total of 10 268 person-years of follow-up, revealed that baseline microalbuminuria was associated with an increased risk of developing CRI (RR 7.61, 95% CI 3.19, 8.16, p < 0.0001), CVE (composite of fatal and non fatal cardiac and cerebrovascular events) with an RR of 2.11 (95% CI 1.08, 4.13, p < 0.028), and cardio- renal events (composite of former end-points) with an RR of 3.21 (95% CI 1.86, 5.53, p < 0.0001). Microalbuminuria remained significantly related to CRI (RR 12.75, 95% CI 3.62, 44.92, p < 0.0001) and cardio-renal events (RR 2.58, 95% CI 1.32, 5.05, p = 0.0056) even after adjusting for several baseline covariates such as age, gender, body mass index, systolic blood pressure, serum glucose, uric acid, LDL-cholesterol, and estimated glomerular filtration rate.

Conclusions: Microalbuminuria is an independent predictor of renal and cardiovascular complications in non diabetic patients with primary hypertension.

9.6 The Combined Effect of Albuminuria and Reduced Estimated Glomerular Filtration Rate on Cardiovascular Events and All-Cause Mortality in Low-Risk Hypertensive Patients

F. Viazzi, G. Leoncini, N. Conti, E. Baratto, G. Storace, R. Pontremoli and G. Deferrari

Azienda Ospedale Università San Martino, Genova, Italy

Introduction: Decreased GFR and microalbuminuria (MA) have been shown to predict mortality and CV events in the general population, and in high risk patients. However, their combined prognostic power in non diabetic patients with primary hypertension without overt renal damage has not been previously investigated.

Aim: We assessed the prognostic role of glomerular filtration rate (GFR) and albuminuria, for cardiovascular (CV) morbidity and all cause mortality in non diabetic patients with primary hypertension.

Methods: We conducted a 11.2 year follow-up of 837 hypertensive non diabetic patients enrolled from 1993 to 1997 in the MAGIC (Microalbuminuria: A Genoa Investigation on Complications) cohort. Urinary albumin to creatinine ratio (ACR) and estimated GFR (eGFR) were assessed in untreated patients at baseline. Renal dysfunction was defined as the inclusion in the most unfavourable gender specific decile of eGFR (< 50.5 mL/min in females, <69.5 mL/min in males) or of ACR (>1.7 mg/mmoL in females, >2.4 mg/mmoL in males). The primary endpoints were the occurrence of non fatal cerebrovascular and cardiac events (CVE), composite of all cause death and CVE (CEP), and composite of CVE and chronic renal insufficiency (CRE).

Results: During 9374 person-years of follow-up, the incidence rate for CVE, CRE, and all cause mortality was 6.3, 7.8, and 3.1/1000 person-years, respectively. Renal dysfunction was associated with increased risk for CVE (RR 2.21, 95% CI 1.20, 4.01, p = 0.011), CEP (RR 1.86, 95% CI 1.07, 3.23, p = 0.027), and CRE (RR 2.56, 95%CI 1.48, 4.40, p<0.001), even after adjustment for several baseline covariates such as gender, duration and severity of BP, and total-cholesterol.

Conclusions: Renal dysfunction is a risk factor for cardiorenal complications and all cause mortality independent of traditional confounders in non diabetic patients with primary hypertension.

9.7 N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Reduces Albuminuria and Renal Fibrosis in Diabetic Rats: a Proteomic Approach

G. Castoldi,¹ C. Galbusera,² C.R.T. di Gioia,³ C. Bombardi,¹ C. Sarto,² M. Mancini,³ M. Leopizzi,³ P. Brambilla,² B. Corradi,¹ G. Zerbini,⁴ F. Magni,² M. Galli-Kienle² and A. Stella¹

1 Clinica Nefrologica. Az. Osp. San Gerardo. DIMEP. Univ. Milano-Bicocca, Monza, Italy; 2 Dipartimento Medicina Sperimentale. Univ.Milano-Bicocca, Monza, Italy; 3 Ist. Anatomia Patologica. Dipartimento Med. Sperim.La Sapienza Univ. di Rome, Rome, Italy; 4 Unita’ di Complicanze del Diabete. Ist. San Raffaele, Milan, Italy

Aim: To evaluate the effect of Ac-SDKP, physiological tetrapeptide hydrolyzed by ACE on albuminuria, renal fibrosis and renal protein expression profiles in streptozotocin-induced diabetic rats.

Methods: Diabetes was induced in 26 Sprague Dawley rats by streptozotocin injection. Control rats (n = 12) underwent only buffer injection. Out of 26 diabetic rats, 12 were chronically treated with insulin. Two months after the onset of diabetes, Ac-SDKP (1 mg/kg/die s.c.) was administered for 8 weeks to 5 control rats, 7 diabetic rats, and 6 insulin treated diabetic rats by osmotic mini-pumps. To evaluate the effect of chronic Ac-SDKP administration on whole kidney protein expression profile, we performed a multiple comparative proteomic analysis using 2-DE combined with MALDI-TOF.

Results: Main findings of our study are shown in the table. At the end of the experimental period, diabetic rats had a significant increase in blood glucose level, that was absent in those treated with insulin. Albumin excretion rate and renal fibrosis were significantly increased in diabetic rats, but not in insulin treated diabetic rats. Ac-SDKP administration in diabetic rats prevented the increase in albumin excretion rate and significantly reduced renal fibrosis. A total of 19 proteins, differently modulated by Ac-SDKP in the kidney of diabetic rats, were identified by PMF analysis. Eight proteins were detectable only in diabetic rats and, conversely, 11 proteins were absent.

Conclusions: Metabolic pathway investigation of the differentially modulated proteins, using Ingenuity Pathway Analysis tool, showed that Ac-SDKP interferes with multiple pathways involved in cellular growth and cytoskeleton organization. These data demonstrate a renal protective effect of Ac-SDKP and suggest the proteins modulated by this peptide as potentially involved in the pathogenesis of diabetic nephropathy.

9.8 Role of the Aldosterone on the Control of Glomerular Function

B. Fabris,¹ P. Losurdo,¹ B. Toffoli,¹ C. Zennaro,¹ S. Bernardi,¹ M. Carraro,¹ N. Sabato,¹ P. Mulatero,² R. Candido,³ F. Veglio² and R. Carretta¹

1 Dipartimento di Medicina Clinica e Sperim. e Neuroscienze Cliniche e Sperim., Università di Trieste, Trieste, Italy; 2 Dipartimento di Medicina e Oncologia Sperimentale, Università di Torino, Torino, Italy; 3 Centro antidiabetico, A.S.S. 1 Triestina, Trieste, Italy

Introduction: Recent studies have demonstrated that aldosterone (Aldo) can play a role in the progression of renal pathology.

Aim: To evaluate the effects of in vivo administration of Aldo in the presence or absence of a high salt diet on glomerular function and on the expression of proinflammatory and prosclerotic genes.

Methods: 128 Wistar uninephrectomized rats were studied for 28 days. Animals were randomized to receive the following treatment: vehicle (control group) high salt diet at 1% (NaCl-1%) and 8% (NaCl-8%), Aldo at the doses of 40 (Aldo 40) and 72 μg/kg/die (Aldo 72), Aldo in association with high salt diet at 1 or 8% and Aldo 72 plus saline at 8% in association with eplerenone (E) at the dose of 100 mg/kg/die. At 2-week intervals, body weight and systolic blood pressure (SBP) were measured. At the end of the study glomerular filtration rate and albuminuria (Alb-U) were evaluated. The rats have been then decapitated, the blood collected for determination of Aldo, creatininemia and azotemia, their abdomen opened and the left kidney rapidly excised and weighed. In each group the kidneys from half of the animals have been used for determination of glomerular area (GA), glomerular sclerotic area (SGA) and glomerular albumin permeabilitry (P-alb) determination. The kidneys from the other half of the animals have been employed for gene expression studies.

Results: In the NaCl-8% and in the Aldo 72 groups there were a significant and comparable increase in the SBP, kidney weight, GA and SGA. These changes were further increased in the animal treated with Aldo 72 and high salt diet both at 1 and 8%. A significant increase in Alb-U and Palb was present both in the group treated with high salt diet and in group receiving Aldo 72 and high salt diet. In these groups were also evident a gene hyperexpression of CTGF (Connective tissue growth factor) and MCP-1 (Monocyte chemoattractant protein-1). The increase in SBP, GA, SGA and the alteration in Alb-U and P-alb were prevented by treatment with E.

Conclusions: Aldo may induce an alteration of glomerular function only when it is administered together with a high salt diet which can independently affect glomerular function. In the presence of hyperaldosteronism the control of P-alb and of the proinflammatory and prosclerotic gene expressions is an important target of the treatment with E.

9.9 Sodium Proximal Fractional Reabsorption and Incidence of Hypertension: Olivetti Heart Study

L. D’Elia,¹ F. Galletti,¹ D. De Palma,¹ R. Ippolito,¹ G. Barba,² R. Iacone,¹ G. Rossi¹ and P. Strazzullo¹

1 Università di Napoli Federico II, Napoli, Italy; 2 Istituto di Scienze dell’Alimentazione- CNR, Avellino, Italy

Introduction: It has been postulated that higher proximal sodium reabsorption could be involved in the high BP of obese hypertensive patients. However no data are so far available in prospective analysis.

Aim: To evaluate the predictive role of the sodium proximal reabsorption in the development of HPT, during 8 years of follow-up, in the participants of the Olivetti Heart Study.

Methods: We selected, at baseline subjects without anti-hypertensive therapy and with normal renal function (creatinine clearance-CrCl> 60 mL/min) who were visited also after 8 years (n = 314). Sodium proximal reabsorption was calculated through the esogenus-litio clearance.

Results: The baseline characteristics of the population sample were: age 49.3 ± 6.8 years, BMI 26.4 ± 2.8 kg/m², CrCl 90.9 ± 18.2 mL/min, SBP/DBP 119.8 ± 9.6/78.9 ± 6.4 mmHg (M ± SD). The prevalence of HPT, after 8 years, was 52%. We compared the subjects who did not develop HP (group A) vs those who developed HPT during the follow-up (group B). At baseline there was a significant difference in SBP and DBP (A vs B: 117.0 ± 10.0 vs 122.4 ± 8.4 mmHg; p < 0.0001), DBP (77.1 ± 6.7 vs 80.6 ± 5.6 mmHg; p < 0.0001), BMI (25.9 ± 2.6 vs 27.0 ± 2.9 kg/m²; p< 0.0001) and proximal reabsorption of sodium (73.8 ± 7.3 vs 75.8 ± 6.3%; p = 0.01). In a logistic regression model (variables expressed as z-score), proximal Na reabsorption predicted a greater risk of HPT, in 8 years (OR: 1.44, IC 95%: 1.13, 1.84; p = 0.003), independently by basal SBP (OR: 1.88, I.C. 95%: 1.43, 2.47; p < 0.001), BMI (OR: 1.51, IC 95%: 1.16, 1.95; p = 0.002), age and basal GFR.

Conclusions: In this sample of untreated male adult subjects, the proximal sodium reabsorption was an independent predictor of HPT development: for an increase of 1 standard deviation in the sodium proximal reabsorption, the risk to develop hypertension increased of 44% in 8 years.

9.10 Renal Artery Stenosis is Associated with Elevated Fasting Plasma Insulin and Elevated Lipoprotein(A) in Hypertensive Patients

C. Catena,¹ Gl. Colussi,¹ F. Capobianco,¹ A. Chiuch,¹ M. Valeri,¹ A. Casanova-Borca,¹ A. Di Fabio,¹ L. Marzano,¹ D. Gasparini² and L.A. Sechi¹

1 Clinica Medica, Univarsità di Udine, Udine, Italy; 2 Radiologia Interventistica, Udine, Italy

Introduction: The role of the ‘emergent’ cardiovascular risk factors in the development of atherosclerotic renal artery stenosis is not completely elucidated.

Aim: To assess the levels of plasma fibrinogen, D-dimer, homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, prothrombin fragment 1 + 2 and C reactive protein in a group of hypertensive patients with angiographically documented renal artery stenosis and hypertension.

Methods: Fifty patients (age 67 ± 10 y; M, 36; F,14), with angiographically confirmed renal artery stenosis were included in this study. Patients were suspected to have secondary hypertension on a clinic ground (resistant hypertension, abdominal bruit, hypokalemia) and had a positive screening test (angio-CT scan or angio-MRI) for renovascular disease. These patients were compared with 56 hypertensive patients (age 64 ± 9 y;M, 34; F, 22) who had comparable clinic characteristics, had a negative screening test for renovascular disease, and were matched for the cardiovascular risk profile.

Results: As compared to patients without renal artery stenosis, patients with renal artery stenosis had longer duration of hypertension (16 ± 11 vs 12 ± 11 y; p = 0.048), heavier anti-hypertensive treatment (2.7 ± 1.6 vs 1.7 ± 1.6 drugs; p = 0.003), lower 24-h creatinine clearance (37 ± 16 vs 47 ± 15 mL/min/m²; p = 0.001), greater serum lipoprotein(a) levels (27 ± 29 vs 12 ± 9 mg/dL; p = 0.003), and greater insulin response to the oral glucose load (area under the curve 895 ± 713 vs 516 ± 612 pmol.L-1.min; p = 0.016). The multivariate logistic analysis showed that serum lipoprotein(a) levels and the insulin response to the oral glucose load were associated with the presence renal artery stenosis independent of renal function.

Conclusions: Thus, this association study suggests that elevated serum lipoprotein(a) and hyperinsulinemic response to glucose challenge might contribute to the development of renal artery stenosis.

9.11 Biomarkers of Left Atrial Volume: a Longitudinal Study in Patients with End Stage Renal Disease (ESRD)

G. Tripepi,¹ F. Mallamaci,¹ F.A. Benedetto,² L. Malatino³ and C. Zoccali¹

1 CNR-Az. Osp., Reggio Calabria Italy; 2 Servizio di Cardiologia Osp., Reggio, Calabria; 3 Dipartimento Di Medicina Interna, Ospedale Civile di Ragusa, Italy

Introduction: Left atrial volume (LAV) has recently emerged as an useful biomarker for risk stratification and risk monitoring in patients with end stage renal disease (ESRD).

Aim: We investigated the relationship between cardiac natriuretic peptides (ANP and BNP) and norepinephrine (NE) with LAV and LAV changes over time in 199 ESRD patients.

Methods: At baseline, LAV was directly related to BNP (r = 0.60), ANP (r = 0.59) and NE (r = 0.28) (p < 0.001) and these relationships held true in multiple regression models adjusting for potential confounders (p < 0.003).

Results: In the longitudinal study (17 ± 2 months) LAV increased from 9.8 ± 4.6 mL/m2.7 to 10.9 ± 5.4 mL/m2.7 (+11%). In a multiple linear regression model, BNP (beta = 0.28, p = 0.003), ANP (beta = 0.22, p = 0.03) and NE (beta = 0.27, p = 0.003) predicted LAV changes. The area under the ROC curve (AUC) for predicting LAV changes (>3 mL/m2.7/years) of a risk score based on standard risk factors was 0.72. Plasma BNP (+12%, p = 0.004), ANP (+8%, p = 0.03), NE (+8%, p = 0.05) and midwall fraction shortening (+8%, p = 0.05) increased to a significant extent the AUC while LV mass did not (+5%, p = 0.18). Predictive models including BNP, ANP and NE maintained a satisfactory discriminatory power for LAV and LAV changes also when tested by a bootstrap re-sampling technique BNP and ANP are strongly related to LAV in the ESRD patients and predict LAV changes over time in these patients.

Conclusions: Because an increased LAV underlies diastolic dysfunction and/or volume overload, i.e. potentially modifiable risk factors, the measurement of the plasma concentration of these compounds.

9.12 Dynamic Renal Resistive Index Evaluation after Sublingual Nitroglycerine Administration: a Simple and Non Invasive Tool to Evaluate Renal Haemodynamics

R.M. Bruno, E. Daghini, L. Ghiadoni, D. Versari, A. Magagna, S. Taddei and A. Salvetti

Università di Pisa, Pisa, Italy

Introduction: Dynamic renal resistive index (RI) evaluation after a vasodilating stimulus might reveal early renal vascular alterations.

Aim: To evaluate the effect of two different NO-donors, intravenous sodium nitroprusside (SNP) and sublingual nitroglycerine (GTN) on renal vasodilation, blood pressure (BP) and sympathetic nervous system in essential hypertensive patients.

Methods: In sixteen essential hypertensive patients we administered SNP, at a dose ranging from 0.4 to 1.2 mcg/kg/min iv, in order to obtain about 10% reduction in BP, and low dose (25 mcg) sublingual GTN. RI was obtained by duplex ultrasound, with three consecutive samples for each kidney, at baseline, 5’ after GTN and during SNP when target BP was reached. Heart rate (HR), non invasive beat-to-beat BP (Portapres) and muscle sympathetic nerve activity (MSNA, microneurography) were recorded at baseline and during drug administration. Total peripheral resistance (TPR) were derived by Portapres BP waveforms through Modelflow algorithm.

Results: RI was similar at baseline in the two kidneys (right 0.60 ± 0.07, left 0.60 ± 0.05) and was similarly reduced after SNP (0.54 ± 0.07, p < 0.001 vs baseline, −10.5%) or GTN (0.53 ± 0.08, p < 0.001 vs baseline, −10.1%). Mean BP decrease was −9.9% after SNP infusion (from 110.7 ± 10.5 to 99.8 ± 12.8 mmHg, p < 0.001 vs baseline) and −3.2% after GTN sublingual administration (from 111.5 ± 9.5 to 107.9 ± 8.6 mmHg, p < 0.01 vs baseline). SNP caused a +11.4% increase in HR (from 67.8 ± 10.3 to 74.9 ± 10.9, p < 0.001 vs baseline), while GTN did not affect HR (from 63.8 ± 6.9 to 63.0 ± 7.2, p = ns vs baseline). As expected, SNP determined an increase of MSNA expressed both in bursts frequency and incidence (from 34.1 ± 8.2 to 46.0 ± 10.2 bursts/min, p < 0.001 vs baseline, +37.4%; from 53.0 ± 14.0 to 63.6 ± 10.1 bursts/100 hb, p < 0.001 vs baseline, +22.3%), while a slight and not significant increase in MSNA was achieved with sublingual GTN (from 32.9 ± 7.5 to 36.7 ± 11.6 bursts/min, p = ns, +10.3%; from 53.2 ± 11.6 to 60.5 ± 18.7 bursts/100 hb, p = ns, +12.9%). TPR were decreased during SNP infusion (from 1.21 ± 0.23 to 0.99 ± 0.27, p < 0.001 vs baseline) and unchanged during GTN administration (from 1.15 ± 0.31 to 1.23 ± 0.43, p = ns vs baseline).

Conclusions: Compared to SNP infusion, low dose sublingual administration of GTN achieved a similar significant renal vasodilatory effect without affecting total body haemodynamics and without determining baroreflex-mediated sympathoexcitation. Thus, sublingual GTN could be a feasible and non invasive test to study renal haemodynamics in essential hypertensive patients.

Metabolic Aspects and Mechanisms

10.1 Non-Alcoholic Fatty Liver Disease is Associated with Left Ventricular Diastolic Dysfunction in Essential Hypertension

F. Fallo,¹ A. Dalla Pozza,¹ N. Sonino,² M. Lupia,³ F. Tona,³ C. Catena,⁴ S. Bernardi,⁵ B. Fabris⁵ and L.A. Sechi⁴

1 Dipartimento di Scienze Mediche e Chirurgiche,Università diPadova, Padova, Italy; 2 Dipartimento di Scienze Statistiche, Università di Padova, Padova, Italy; 3 Dipartimento di Scienze Cardiache, Toraciche e Cardiovascolari, Università di Padova, Padova, Italy; 4 Dipartimento di Patologia e Medicina Sperimentale e Clinica, Università di Udine, Udine, Italy; 5 Dipartimento di Medicina Clinica e Neurologia, Università di Trieste, Trieste, Italy

Introduction: Insulin resistance is recognized as the pathophysiological hallmark of non-alcoholic fatty liver disease (NAFLD). A relation between insulin sensitivity and left ventricular morphology and function has been reported in essential hypertension, where a high prevalence of NAFLD has been recently found.

Aim: We investigated the inter-relationship between left ventricular morphology/function, metabolic parameters and NAFLD in hypertensive patients with no major risk factors for liver steatosis.

Methods: Eighty-six never treated patients with essential hypertension were selected as having (n = 48) or not having (n = 38) NAFLD at liver ultrasonography (criteria of Saadeh, 2002). The two groups were similar as to sex, age and blood pressure levels. No subject had diabetes mellitus, obesity, hyperlipidemia, or other risk factors for liver disease.

Results: Body mass index, waist circumference, triglycerides, glucose, insulin, homeostasis model of assessment index for insulin resistance (HOMA-IR), AST and ALT were higher and adiponectin levels were lower in patients with NAFLD than in patients without NAFLD (p < 0.001), and were associated with NAFLD at univariate analysis (p < 0.001). Patients with NAFLD had similar prevalence of left ventricular hypertrophy compared to patients without NAFLD, but a higher prevalence of diastolic dysfunction (75.0 vs 36.8%, p< 0.001), as defined by E/A ratio <1 and E-wave deceleration time >220 ms. Diastolic dysfunction (p = 0.032) and HOMA-IR (p = 0.021) remained independently associated with NAFLD at backward multivariate analysis. Prevalence of diastolic dysfunction progressively increased according to the degree of NAFLD from patients without liver steatosis (n = 8/39, 21.0%) to patients with mild (n = 12/26, 46.1%), moderate (n = 16/20, 80%) and severe steatosis (n = 2/2, 100%).

Conclusions: Non-alcoholic fatty liver disease was associated with insulin resistance and abnormalities of left ventricular diastolic function in a cohort of patients with essential hypertension, suggesting a concomitant increase of metabolic and cardiac risk in this condition.

10.2 Neuroadrenergic Alterations in Patients with Iron Overload and Hemocrometosis

F. Quarti-Trevano,¹ G. Seravalle,² R. Dell’Oro,¹ F. Arenare,¹ S. Buzzi,¹ R. Mariani,¹ G. Brambilla,¹ A. Rozzoni,¹ A. Piperno,¹ G. Grassi¹ and G. Mancia¹

1 Università Milano-Bicocca, Ospedale San Gerardo, Monza, Italy; 2 Istituto Auxologico Italiano, Milan, Italy

Introduction: Previous studies have shown that sympathetic activation and insulin resistance are closely related each other, suggesting that this metabolic disarray represents the driving force for the adrenergic overdrive seen in different cardiometabolic disease. Frequently, however, the presence of conditions that “per se” exert sympathoexcitation, such as hypertension and obesity, did act as confounders, preventing definite conclusions to be drawn.

Aim: In the present study we thought to overcome the above limitations by studying a selected group of hemochRometosis patients as a model of iron-induced alteration of insulin sensitivity and/or secretion.

Methods: In 12 untreated male hemochRometosis patients without metabolic confounders (age 45.5 ± 3.2 years), we measured during a 30-minute resting period beat-to-beat blood pressure (Finapres), heart rate (EKG), and postganglionic muscle sympathetic nerve traffic (MSNA) via microneurography at a peroneal nerve. Data, which also included HOMA index, were compared with those obtained in 8 age-matched healthy controls. In 4 patients with hemochRometosis, measurements were repeated after phlebotomy-induced iron depletion.

Results: Patients with hemochRometosis had blood pressure, heart rate, waist circumference and body mass index values in the normal range and superimposable to those seen in controls. HOMA index was significantly higher than in controls (2.1 ± 0.2 vs 0.9 ± 0.2 a.u., p < 0.01). This was the case also for MSNA, whose values were substantially increased in patients with iron overload (62.2 ± 2.4 vs 47.8 ± 4.2 bursts/100 heart beats, p < 0.02). Iron depletion was associated with an improvement in insulin sensitivity with an average HOMA reduction of about 20%. This was accompanied by a sustained reduction in MSNA, amounting on average to 30%.

Conclusions: These data demonstrate that a reduced insulin sensitivity insulin resistance, even when blood pressure is normal and no overweight or obese state is present, is associated with a sympathetic activation. They also show that improvement in insulin sensitivity is coupled with a sympathetic inhibition, suggesting the cause-effect relationship between the two phenomena.

10.3 Regional Sympathetic Activation in the Metabolic Syndrome

R. Dell’Oro,¹ G. Seravalle,² A. Dubini,² S. Buzzi,¹ M. Volpe,¹ C. Mineo,¹ V. Vella,¹ G. Grassi¹ and G. Mancia¹

1 Clinica Medica, Università Milano-Bicocca, Monza, Italy; 2 Istituto Auxologico Italiano, Milan, Italy

Aim: The present study was designed at determining whether and to what extent the activation of the sympathetic activation reported in the metabolic syndrome has a generalized or rather a regional distribution over the cardiovascular system.

Methods: In 16 untreated patients with metabolic syndrome, 12 essential hypertensive patients, 12 obese and 14 lean healthy normotensive controls, we measured blood pressure (Finapres), heart rate (EKG), venous plasma norepinephrine (HPLC) and postganglionic sympathetic nerve traffic in the skeletal muscle and in the skin areas (microneurography at peroneal nerve). The muscle and skin nerve traffic measurements were made in randomized sequence and included evaluation of skin sympathetic responses to arousal (acoustic stimulus).

Results: The four groups of subjects had superimposable ages (49.4 ± 2.8, mean ± SEM). Compared with controls muscle sympathetic nerve traffic values were significantly higher in subjects with hypertension and in those with obesity (37.2 ± 3.3 vs 51.2 ± 2.8 and 52.0 ± 3.0 bursts/100 heart beats, respectively, p < 0.01), a further significant increase being detected in subjects with the metabolic syndrome (61.0 ± 3.2 bursts/100 heart beats, p < 0.05). In contrast, skin sympathetic nerve traffic was not significantly different in the four groups (15.4 ± 1.0 vs 13.0 ± 0.7, 14.3 ± 1.3 and 12.5 ± 0.8 bursts/minute, respectively, p = NS), this being the case also for the skin sympathetic responses to the acoustic stimulus. In the population as a whole, resting MSNA, but not SSNA, significantly and directly correlated with mean finger arterial pressure (MSNA: r = 0.30, p < 0.05 and SSNA: r = 0.04, p = NS) and body mass index values (MSNA: r = 0.53, p < 0.001; SSNA: r = 0.05, p = NS). Plasma norepinephrine was also directly and significantly related to MSNA (r = 0.37, p < 0.02), but not to SSNA (r = 0.07, p = NS).

Conclusions: The present data provide the first direct evidence that in the metabolic syndrome the sympathetic activation is not uniformly distributed over the cardiovascular system. The different behaviour of skin and muscle sympathetic neural drive is likely to depend on the different impact of the metabolic syndrome components on the reflex and non-reflex mechanisms modulating muscle and skin adrenergic neural drive.

10.4 Relationship between Obesity and Plasma Aldosterone in Essential Hypertension: Influence of Gender

Giuseppe Mule’, Santina Cottone, Raffaella Riccobene, Paola Cusimano, Anna Carol Foraci, Emilio Nardi, Alessandro Palermo, Tania Bellavia, Giuseppe Andronico and Giovanni Cerasola

Università di Palermo, Palermo, Italy

Introduction: Increased adiposity has been associated with an augmented secretion of aldosterone, independently of angiotensin II, in several experimental investigations. However, clinic studies exploring the relationship between obesity and plasma aldosterone (PAC) yielded conflicting results. Moreover, little is known about the potential influence of gender on this relationship.

Aim: To evaluate the relationships between PAC, body mass index (BMI) and waist circumference (WC), in a wide group of non diabetic essential hypertensive subjects, attending our Hypertension Centre, initially in the overall population and subsequently separately by sex.

Methods: We enrolled 590 hypertensive patients (mean age: 43.8 ± 12.5 years; 61% males), with a PAC/plasma renin activity ratio <400 and free from renal and cardiovascular complications. In all patients, 24-h urinary sodium and potassium excretion, serum sodium and potassium levels, PAC, and plasma renin activity ratio (PRA) were determined, with the subjects kept in the supine position for one hour. All the subjects underwent also a 24-h ambulatory blood pressure (BP) monitoring.

Results: In the overall population we observed direct and statistically significant correlations of PAC (logarithmically transformed) with both BMI (r = 0.13; p = 0.002) and WC (r = 0.14; p = 0.001). These associations held (p < 0.01) in stepwise multiple regression models, in which PAC was considered dependent variable, and age, sex, urinary sodium, clinic or 24-h, BP values, (log) PRA, and BMI (or WC) were included as explanatory variables. Even if the interaction factor “BMI (o W) x gender” was not statistically significant when added to the multivariate models ran in the overall population, the multiple regression analyses separately performed in men and women, showed that the relationships of BMI and of WC with PAC remained significant only in men (beta = 0.11; p = 0.02 and beta = 0.10; p = 0.03, respectively). Moreover, when we grouped the study population in normal weight, overweight and obese subjects, PAC disclosed a stepwise significant increase in men, but not in women.

Conclusions: Our results seems to suggest that obesity is positively associated with PAC, even if this association seems to be significant only in men.

10.5 Comparison of the Relationships among Different Definitions of Metabolic Syndrome and Left Ventricular Hypertrophy in Essential Hypertension

Giuseppe Mule’, Emilio Nardi, Paola Cusimano, Giovanna Bonanno, Alessandro Palermo, Calogero Geraci, Miriam Costanzo, Anna Carol Foraci, Santina Cottone and Giovanni Cerasola

Università di Palermo, Palermo, Italy

Introduction: Several studies documented that metabolic syndrome (MetS), defined according to the ATPIII or IDF criteria, is associated with an increased left ventricular (LV) mass in essential hypertension. Limited information is available about the different ability of these two diagnostic criteria to identify LV hypertrophy (LVH). Moreover, one of the potential limitations of the MetS concept is the dichotomous nature of the current definitions of MetS, that would limit the power to correctly assess the cardiovascular risk in every patient.

Aim: To compare the ability of different definitions of the MetS to identify LVH in a wide group of patients with essential hypertension.

Methods: We recruited 724 non diabetic hypertensive subjects (mean age 45.3 ± 11.7 years; 63% males), free from cardiovascular complications. In all subjects, routine blood chemistry, echocardiographic examination and 24-hour ambulatory blood pressure (BP) monitoring were performed. We adopted 4 definitions of MetS, two dichotomous (ATPIII e IDF) and two ‘quantitative’. Of these latter, one was defined on the basis of the mean value of the sex-specific Z score for every component (MetS Z score) and the other as the average of the percent deviation from the cut-off values used in the ATPIII criteria (‘MetS D %’).

Results: The areas under the ROC curves for every definition of the MetS, with respect to the diagnosis of LVH (= LVMH2.7 > 51 g/m2.7), were higher when we used the quantitative definitions (MetS Z score: 0.645 ± 0.023; MetS D %: 0.636 ± 0.023), in comparison to the ATPIII definition (0.597 ± 0.023; p = 0.008 and p = 0.02, respectively) and to the IDF definition (0.574 ± 0.023; p = 0.001 and p = 0.008, respectively). In stepwise logistic multiple regression models, taking into account various confounding factors, LVH was more closely associated with quantitative definitions of Mets (MetS Z score, p < 0.0001; MetS D %, p = 0.007) than it was with the categorical definitions (ATPIII, p = 0.01 and IDF, p = 0.03).

Conclusions: Our results seem to suggest that in hypertensive patients the adoption of ‘quantitative’ definitions of MetS allows to better identify subjects with left ventricular hypertrophy than the traditional dichotomous definitions.

10.6 Impact of Hypertension and Role of Fibrinogen in the Metabolic Syndrome

F. Corlianò, C. Cerutti, E. Colli, E. Cornetti, G.P. Fra, G.P. Carnevale Schianca and E. Bartoli

Università del Piemonte Orientale A. Avogadro-Osp. Maggiore della Carità — Clinica Medica Generale, Novara, Italy

Introduction: The diagnosis of the Metabolic Syndrome (MS), according to ATP III, requires three out of five of the following criteria: elevated blood pressure (EP); abdominal circumference (AV) ≥102 cm in males (M) and 88 in females (F); triglycerides (TG) ≥150 mg/dL; high-density lipoprotein-cholesterol (HDL) <40 mg/dL inM(<50 in F); fasting blood glucose (G) ≥100 mg/dL. The present study examines the impact of each of these factors on the cardiovascular risk of outpatients affected by MS.

Methods: We studied 482 subjects (197 M), with a median age of 54.2 years, performing OGTT with measurement of blood glucose and insulin concentrations at time 0 ‘and after two hours (G, G-2h, Ins and Ins-2h). We calculated BMI, AV and as, indexes of insulin resistance and sensitivity, HOMAIR and EISI respectively. We evaluated, as cardiovascular risk factors (CRF), total cholesterol (CT), TG, HDL, LDL and fibrinogen (Fb).

Results: The prevalence was 92.3% for EP, 60.2% for TG, 61.1% for HDL, 62.1% for G and 80.7% for AV. Normotensive subjects (n = 37) exhibited significantly lower values for HDL e Fb, while TG was increased compared to hypertensive patients (n = 445). In subjects with normal AV (n = 93), BMI, Ins, Ins-2h, HOMAIR, HDL and FB were significant lower while EISI e TG were higher compared to subjects with increased AV (n = 389). In subjects with normal TG (n = 192), CT and LDL were significant lower, while BMI, AV and HDL were increased as compared to subjects with increased TG (n = 290). In subjects with normal HDL (n = 188), G, CT and LDL were significant increased compared with subjects with low HDL (n = 294). In subjects with normal G (n = 183), G-2 h, HOMAIR and HDL were significant reduced, while EISI was increased compared with subjects with G ≥100 mg/dL (n = 299).

Conclusions: These results confirm that the combination of criteria is the major determinant of the overall CVR. This overwhelms the risk contributed by individual criteria. It is very important the high prevalence of EP in the subjects with MS (92.3%). Fibrinogen, significantly higher in hypertensive patients and in subjects with increased AV, seems particularly relevant to account for the increased thrombogenic risk.

10.7 Newly Diagnosed Arterial Hypertension in Male and Female Subjects

C. Cerutti, E. Cornetti, F. Corlianò, E. Colli, G.P. Fra, G.P. Carnevale Schianca and E. Bartoli

Università del Piemonte Orientale A. Avogadro-Osp. Maggiore della Carità-Clinica Medica Generale, Novara, Italy

Introduction: Arterial hypertension (AH) leads to metabolic alterations which cause an increased cardiovascular risk (RCV). In this study we examined the risk connected to AH at its onset in both sexes.

Methods: We recruited 382 subjects (172 males) aged 44.1 ± 14.3 years, 163 of whom with a newly diagnosed AH. The inclusion condition was normal glucose tolerance at OGTT. None of the subjects studied was affected by hypercolesterolemia and/or familiar hypertrigliceridemia. In each subject, in addition to anthropometric indices, as waist circumference (WC) and BMI, we measured glycaemia and insulin concentration at time 0 f and 120 f (G0,G120,Ins0 and Ins120) of OGTT, cholesterol (CT), triglicerids (TG), HDLcholesterol (HDL), LDLcholesterol (LDL) and fibrinogen (Fb). We also calculated the HOMAIR and the EISI as insulin-resistance and insulin-sensibility indices, respectively. Three independent comparisons were made: two between hypertensive and normotensive subjects in both sexes, the third one between male and female hypertensive subjects.

Results: The comparison between the male groups disclosed a significant rise in BMI, CV, G0, Ins0, HOMAIR and Fb, and a significant reduction of EISI in hypertensive (n = 82) compared to normotensive subjects. We obtained similar results in the comparison between females, where, in addition, Ins120, CT and LDL were also found to be significantly increased (n = 81). When comparing male to female hypertensive subjects we found a significant increase in Fb and HDL, with concomitant reduction of TG in females.

Conclusions: Our study confirms that AH confers an unfavourable metabolic profile in both sexes. These alterations are more evident in females: when a woman becomes hypertensive, she discloses profound alterations of her blood lipids together with increased fibrinogen, and she exhibits insulin-resistance if compared to non hypertensive females. Furthermore, it is very significant that fibrinogen is more elevated than in hypertensive males, who, in turn, show values higher than normotensive subjects. These findings contribute to the increased RCV associated to arterial hypertension. Females exhibit an overall risk significantly more pronounced than males.

10.8 Evaluation of Candesartan Compared to Olmesartan on Insulin Sensitivity-Related Parameters in Type 2 Diabetic Hypertensive Patients

G. Derosa, P. Maffioli, S. Salvadeo, I. Ferrari, A. Gravina, R. Mereu, I. Palumbo and R. Fogari

Università di Pavia, Pavia, Italy

Introduction: The correlation among retinol-binding protein-4 (RBP-4), visfatin, vaspin and markers on insulin sensitivity and glucose metabolism is unclear. Few studies considered the actions of sartans on these parameters. Our study aimed to compare the effect of Candesartan (C) vs Olmesartan (O) on insulin-sensitivity related-parameters, before and after antihypertensive therapy.

Methods: After 4 week washout placebo period, 118 hypertensive (DBP ≥80 mmHg and SBP ≥130 mmHg) patients with well controlled type 2 diabetes (HbA1c <7%) were randomised to C 16 mg o.d. or O 20 mg o.d. and titrated after 1 month to C 32 mg o.d. or O 40 mg o.d.; the treatment period had a 1 year duration. We evaluated SBP, DBP, and collected plasma samples of RBP-4, visfatin, and vaspin at baseline, and after 1 year.

Results: One hundred and nine patients completed the study (58 in C and 51 in O group). SBP and DBP were significantly reduced by both treatments [from 144 ± 8/88 ± 6 mmHg to 124 ± 5/76 ± 4 by C (p < 0.001) and from 144 ± 9/88 ± 7 mmHg to 127 ± 7/78 ± 5 mmHg by O (p < 0.001)] without any difference between them. The RBP-4 was reduced by 20.7 ± 7.6 mg/mL in C group (p < 0.01), and by 4.5 ± 1.4 mg/mL in O group (ns vs baseline, p < 0.05 vs C). Visfatin increase was 7.9 ± 4.8 ng/mL in C group (p < 0.05), and 3.3 ± 1.9 ng/mL in O group (ns vs baseline, p < 0.05 vs C), and vaspin reduction was 0.3 ± 0.1 ng/mL in C group (p < 0.05), while was unchanged in O group (ns).

Conclusions: Candesartan therapy compared to Olmesartan therapy improved insulin-sensitivity, beyond the same reduction in blood pressure.

10.9 Effects of Valsartan Compared to Losartan on Insulin-Resistance Parameters in Overweight Hypertensive Patients

R. Fogari, A. Zoppi, P. Lazzari, A. Mugellini, P. Preti, L. Corradi and G. Derosa

Università di Pavia, Pavia, Italy

Introduction: The link between insulin resistance and the two adipocytokines retinol-binding protein-4 (RBP-4), and visfatin is not well determined and no study verified whether antihypertensive drugs modify their plasma levels.

Aim: To compare the effect of Valsartan (V) vs Losartan (L) on insulin resistance, RBP-4, and visfatin in overweight hypertensive patients.

Methods: After 4 week washout placebo period, 96 mild to moderate hypertensive (SBP >140 ≤ 160 mmHg and/or DBP >90 ≤ 100 mmHg) patients with BMI ≥ 25 Kg/m² and <30 Kg/m² were randomised to V 80 mg o.d. or L 50 mg o.d. and titrated after 1 month to V 160 mg o.d. or L 100 mg o.d.; the treatment period had a 1 year duration. Their blood pressure was checked every month. An euglycemic hyperinsulinemic clamp, and an evaluation of plasma RBP-4, and visfatin was performed at baseline, and after 1 year.

Results: Ninety-two patients completed the study (48 in V and 44 in L group). SBP and DBP were significantly reduced by both treatments [from 149 ± 10/96 ± 7 mmHg to 128 ± 6/79 ± 4 by V (p < 0.001) and from 148 ± 9/99 ± 8 mmHg to 129 ± 7/81 ± 5 mmHg by L (p < 0.001)] without any difference between them. M value was increased by 1.07 ± 0.09 mmoL/min/Kg in V group (p < 0.01) and by 0.38 ± 0.01 mmoL/min/Kg in L group (ns vs baseline, p < 0.05 vs V). The RBP-4 reduction was 13.8 ± 3.9 mg/mL in V group (p < 0.01), and 2.9 ± 0.6 mg/mL in L group (ns vs baseline, p < 0.05 vs V); visfatin increased by 6.5 ± 1.1 ng/mL in V group (p < 0.05), and by 2.1 ± 0.3 ng/mL in L group (ns). There was a significant correlation between M value increase and RBP-4 decrease (r = −0.58, p < 0.001).

Conclusions: Valsartan improved insulin resistance as well as RBP-4, and visfatin, while L did not change them, despite a similar blood pressure reduction. The RBP-4 reduction seems to be related to insulin sensitivity improvement.

10.10 Lipolysis and Uncoupling Protein 1 (UCP1) Expression in ex vivo Human Visceral Adipocytes are Induced by Nebivolol

R. Sarzani,¹ M. Bordicchia,¹ P. Marcucci,¹ E. Giannini,¹ L. Scappini,¹ W. Siquini,² A. Fianchini,³ M. Emanuelli,² P. Dessì-Fulgheri¹ and A. Rappelli¹

1 Clinica di Medicina Interna, Univ. Politec. Marche, Ancona, Italy; 2 Dipartimento di Biochimica, Univ. Politec. Marche, Ancona, Italy; 3 Clinica di Chirurgia Generale, Univ. Politec. Marche, Ancona, Italy

Introduction: Selective β1 blockers have a decreasing reputation in the treatment of hypertension also because metabolic side effects such as increasing adiposity, dyslipidemia, and dysglycemia. Nebivolol (a racemic mixture of D- and L-enantiomers) is a third-generation β1 blocker with vasodilatatory activity mediated through the β3 adrenergic receptor (ADRB3) because of ADRB3 agonist activity of the L-enantiomer. Available clinic data suggest that nebivolol lacks the adverse metabolic side effects of other β1 blockers.

Aim: In this study we examined whether nebivolol was able to induce ADRB3-mediated lipolysis and UCP1 expression, key steps in the use of fatty acids for thermogenesis.

Methods: Human visceral mature adipocytes were isolated from omental adipose tissue obtained during elective abdominal surgery. Gene expression of ADRB1, ADRB2, ADRB3, UCP1 receptors, and adipocyte markers were analysed by RealTime PCR-TaqMan assay. ADRB3 were also investigated by western blotting. The effects of isoproterenol, ADRB3 agonists (CL316243, BRL37344), nebivolol (D and L mixture as well as both pure enantiomers), atenolol, and metoprolol on lipolysis (free glycerol production) and UCP1 expression (evaluated by Real Time PCR-TaqMan assay) were studied in vitro.

Results: Isolated unilocular adipocytes expressed all ADRB receptors, hormone sensitive lipase, and adipocyte markers (adiponectin and leptin). ADRB3 mRNA and protein were expressed in variable amounts in human omental adipose tissue and in isolated adipocytes (n = 10). As expected, isoproterenol and ADRB3 agonists induced frank lipolysis whereas non-vasodilating β1 blockers did not. Nebivolol induced significant lipolysis (about 2.8-fold, p = 0.026) that was mediated by the L-enantiomer (about 50% of the isoproterenol-induced lipolysis at same concentrations). Only nebivolol was able to induce UCP1 gene expression (about 3-fold, p = 0.032).

Conclusions: Nebivolol activates ADRB3-mediated lipolysis and induces UCP1 gene expression in human visceral adipocytes, a pathway known to lead to thermogenesis and weight loss. Treatment of hypertensive-overweight patients with nebivolol induced blood pressure control but also could be induced positive metabolic effect acting on visceral adipose tissue.

10.11 Human Endocannabinoid CB1 Receptor 3813a/G Variant in Obese-Hypertensive Patients and Adipose CB1 Gene Expression in Relation to Fat Depots, Endocannabinoid Levels and Microvascular Damage

R. Sarzani,¹ M. Bordicchia,¹ I. Battistoni,¹ L. Mancinelli,¹ E. Giannini,¹ G. Refi,¹ D. Minardi,² G. Muzzonigro,² R. Mazzucchelli,³ R. Montironi,³ F. Piscitelli,⁴ S. Petrosino,⁴ P. Dessì-Fulgheri,¹ V. di Marzo⁴ and A. Rappelli¹

1 Clinica di Medicina Interna, Univ. Politec. Marche, Ancona, Italy; 2 Clinica Urologica, Univ. Politec. Marche, Ancona, Italy; 3 Dipartimento Anatomia Patologica, Univ. Politec. Marche, Ancona, Italy; 4 Ist. di Chimica Biomolecolare, CNR-Pozzuoli, Napoli, Italy

Introduction: Overactivity of the endocannabinoid system (ECS) in human visceral adipose tissue (VAT) appears to be involved in the cardiovascular and metabolic complications of obesity. Endocannabinoid CB1 receptor gene (Cnr1) 3813A/G alleles may influence CB1-mediated ECS activities.

Aim: Obese-hypertensive patients (OH), who are at higher risk of metabolic syndrome (MetS), were studied to evaluate the frequency of the 3813A/G SNP and its correlation with clinic parameters. We also analyzed Cnr1 alleles in relation to different levels of CB1 expression in VAT. Moreover, we studied VAT endocannabinoid (EC) levels and CB1 receptor expression in relation to anthropometry, VAT area, plasma adiponectin, and microvascular damage (MVD) in human kidney.

Methods: Cnr1 3813A/G alleles were evaluated in 280 OH (age <=65 years) excluding diabetics in drug therapy. Perirenal VAT and kidney samples were obtained from 30 patients undergoing renal surgery. In these subjects we determined total VAT and perirenal VAT areas, quantitative CB1 expression and EC levels in perirenal VAT, and total and high molecular weight (HMW) circulating adiponectin. MVD was evaluated in healthy portions of kidney cortex.

Results: OH with the 3813G allele had lower prevalence of MetS in both unadjusted (OR.0.385, 95% IC 0.2, 0.7, p = 0.003) and adjusted models (OR. 0.398, 95% IC 0.2, 0.9, p = 0.032). A significant lower (about 40%) CB1 expression in perirenal VAT was found in patients with the 3813G allele in comparison with 3813A carriers. A positive correlation was found between CB1 mRNA levels in perirenal VAT and the perirenal and total VAT areas. Anandamide levels in the perirenal VAT correlated with CB1 expression (r = 0.750, p = 0.008). A near 2-fold higher CB1 expression was found in patients with more advanced (arteriolar sclerosis) MVD (p = 0.047). HMW adiponectin was negatively correlated with glomerular sclerosis.

Conclusions: Genetics (Cnr1 3813A/G alleles) influence perirenal VAT CB1 expression and the prevalence of MetS in OH. Increased visceral adiposity is associated with increased perirenal VAT CB1 expression, which is accompanied by elevated anandamide levels. CB1 overexpression is also related to MVD, which instead is negatively correlated with adiponectin levels. CB1-mediated ECS overactivity appears to be involved in human visceral obesity and its complications.

10.12 Serum Uric Acid Levels and Incidence of Hypertension in a Sample of Adult Male Population with Normal Blood Pressure

L. D’Elia,¹ R. Ippolito,¹ D. De Palma,¹ G. Rossi,¹ G. Barba,² O. Russo,¹ F. Galletti¹ and P. Strazzullo¹

1 Università di Napoli Federico II, Napoli, Italy; 2 Istituto di Scienze dell’Alimentazione- CNR, Avellino, Italy

Introduction: The relationship between serum uric acid levels (SUA) and hypertension (HPT) have already been evaluated cross-sectionally and prospectively.

Aim: To evaluate the role of SUA on the development of HPT in a sample of adult male subjects with normal BP according to the ESH guidelines (Systolic/Diastolic BP <130/85 mmHg).

Methods: The population sample was composed by 253 subjects (age 49.5 years, range 26–71), without diabetes and any pharmacological treatment, with normal renal function (creatinine clearance-CrCl> 60 mL/min) and BP levels, examined both at baseline (1994–95) and at follow-up examination (2002–04).

Results: The basal SUA were directly correlated with BMI (r = 0.27; p < 0.0001), Diastolic BP (r = 0.22; p < 0.0001) and HOMA index (r = 0.28; p < 0.0001), while was inversely related to CrCl (r = −0.14; p = 0.02). After 8 years, the incidence of HPT (BP> = 140 and/or 90 mmHg or RX) was of 45%. Participants who developed HPT had higher basal SUA than participants who did not develop HPT (M ± SE: 5.76 ± 0.11 vs 5.36 ± 0.09 mg/dL; p = 0.006). The logistic regression analysis showed that basal SUA (expressed as z-score) significantly predicted the risk of developing HPT in the 8 years of follow-up (OR = 1.40, CI 95% 1.060, 1.860, p = 0.018), after adjustment for age, basal BMI, Systolic BP, CrCl and HOMA index.

Conclusions: In a sample a healthy subjects with normal BP serum uric acid predicted the development of hypertension during an 8 years follow-up.

10.13 Non-HDL Cholesterol and Target Organ Damage in Essential Hypertension

F. Paneni, S. Sciarretta, G. Tocci, F. Palano, B. Ponziani, L. De Biase, A. Ferrucci and M. Volpe

Università “La Sapienza”-II° Facoltà di Medicina e Chirurgia-Cardiologia — Ospedale S.Andrea, Rome, Italy

Introduction: Non-HDL cholesterol (non-HDL-C) includes VLDL cholesterol (VLDL-C), LDL cholesterol (LDL-C), IDL cholesterol (IDL-C) and triglycerides (TG). Prospective studies and meta-analysis have shown that non-HDL-C is an independent predictor of cardiovascular events. However, it is still not clear the value of non-HDL-C, as compared with the traditional lipid indexes, in predicting the presence and the extension of target organ damage (TOD) in arterial hypertension.

Methods: 174 hypertensive patients (98M, 73W, mean age 60 ± 11 years), underwent standard blood pressure (BP) measurement, 12-leads EKG and blood chemistry including fasting glycaemia, total cholesterol (TC), LDL-C, HDL-C and TG. Non-HDL-C was obtained as the difference between TC and HDL-C. Successively, the following lipid ratios were calculated: non-HDL-C/HDL-C, LDL-C/HDL-C, TG/HDL-C. All patients underwent trans-thoracic echocardiogram and left ventricular hypertrophy (LVH) was defined as left ventricular mass indexed to height2,7 (LVM/h2,7) >47 g/m² in women and >50 g/m² in men. Ultrasound Doppler evaluation of carotid arteries for the measurement of intima-media thickness (IMT) and urinary spot microalbuminuria (MAU) were also performed. Basing on the presence or the absence of TOD, the population was divided in 127 and 47 subjects, respectively.

Results: Patients with and without TOD significantly differed for HDL-C (47.8 ± 13.2 vs 59.5 ± 14.8 mg/dL, p < 0.01), TG (156.2 ± 106.6 vs 93.9 ± 66.9 mg/dl, p < 0.01), non-HDL-C/HDL-C (3.6 ± 1.3 vs 2.21 ± 0.8, p < 0.01), TG/HDL-C (3.8 ± 3.4 vs 1.8 ± 2.5, p < 0.01), fasting glycaemia (102.2 ± 20.2 vs 95.2 ± 15 mg/dl, p < 0.01). Groups also differed regarding the prevalence of metabolic syndrome (MS) (37% vs 14.9%, p < 0.001) and the prevalence of subjects taking calcium channel blockers (39.6% vs 19.1%, p< 0.05). Conversely, no differences were found regarding statin treatment among patients with and without TOD (23.4% vs 24.4%,p = 0.53). After performing logistic regression analysis adjusted for age, gender, systolic and diastolic BP and the presence of MS, non-HDL-C and TG/HDL-C resulted to be independently associated with TOD [respectively, adjusted OR 1.97 (95% IC 1.08, 2.24); 1.71 (95% IC 1.19, 2.29); p < 0.01]. Interestingly, non-HDL/HDL-C was independently and more strongly associated with the extension of TOD (defined as the coexistence of MAU, LVH and increased IMT): adjusted OR non-HDL-C vs TG/HDL, respectively: 2.4 (95% IC 1.23, 3.90, p < 0.01) and 2,02 (95% IC 1.66, 2.98, p < 0.01).

Conclusions: In a population of hypertensive patients, non-HDL-C/HDL-C ratio resulted to be strongly associated the presence and the extension of TOD, as compared with LDL-C/HDL-C and TG/HDL-C, independently from TG levels and the presence of MS.

10.14 Olivetti Heart Study: Circulating Leptin Levels Predict the Decrease of Renal Function in a Sample of Adult Men

F. Galletti,¹ L. D’Elia,¹ D. De Palma,¹ R. Ippolito,¹ O. Russo,¹ A. Barbato,¹ F.P. Cappuccio² and P. Strazzullo¹

1 Università di Napoli Federico II, Napoli, Italy; 2 Warwick Medical School, Coventry, UK

Introduction: Although the relationship between serum leptin levels (LPT) and progression to end-stage kidney disease has been investigated in patients with impaired renal function, the possible association between LPT and decline of renal function has not been evaluated prospectively in a population-based setting. Aim of the present study was to evaluate the predictive role of LPT on the decrease of renal function during an 8 year follow-up period in the participants of the Olivetti Heart Study.

Methods: 362 normotensive and otherwise unselected men with normal renal function (creatinine clearance/body surface area, GFR >60 mL/min), examined in 1994–95, were included in the analysis (age: 49.7 ± 0.35 years; SBP:119 ± 0.53, DBP:78 ± 0.34 mmHg; BMI: 26.4 ± 0.15 kg/m²; LPT: 3.2 ± 0.12 ng/mL; GFR 91.7 ± 0.97 mL/min-mean ± SE).

Results: After an average follow-up period of 8 years, the incidence of hypertension was 50%. There were significant changes in BMI (+0.5 ± 0.09 kg/m²−p < 0.001), SBP (+14.1 ± 0.75 mmHg−p < 0.001), DBP (+8.8 ± 0.48 mmHg-p < 0.001) and GFR (-3.03 ± 1.25 mL/min-p < 0.02). At baseline LPT was significantly related to BMI (r = 0.53, p < 0.001), SBP (r = 0.16, p = 0.002), DBP (r = 0.28, p < 0.001), but not to GFR (r = 0.02, p: n.s.). An inverse association with GFR was apparent however at follow-up examination (r = −0.14, p = 0.007). At multivariate regression analysis, LPT (expressed as Z score) was an independent predictor of the rate of decline in GFR, 1-standard deviation positive difference in LPT being associated with 3.95 ± 1.11 decrease in GFR (p < 0.001), after adjustment for age, baseline BMI and GFR and hypertensive status at follow-up examination.

Conclusions: In an initially normotensive sample of adult male population with normal renal function, plasma leptin concentration was a significant predictor of the decline in GFR during an average follow-up period of 8 years, independently of age, BMI and development of HP.

10.15 Daily Physical Activity, Blood Pressure and Adiponectin — Olivetti Heart Study

L. D’elia, F. Galletti, D. De Palma, R. Ippolito, R. Iacone, A. Barbato and P. Strazzullo

Università di Napoli Federico II, Napoli, Italy

Introduction: The relationship between regular physical activity and plasma adiponectin levels has not yet been investigated in population-based studies.

Aim: To evaluate the predictive role of habitual daily physical activity (PA) on blood pressure (BP), anthropometric indices and adiponectin plasma levels in a selected sample of the Olivetti Heart Study (OHS) population.

Methods: We used the OHS database of 1994–95 and 2002–04 examinations. The study population was made of 303 men (age 48.6 ± 5.9 years in 1994,M ± SD), who did not practice any PA in 1994, for whom plasma adiponectin and information about PA (walking or cycling, investigated by a standardized questionnaire) were available in both occasions. The sample was stratified into 3 subgroups with reference to PA reported at the 2002–04 follow-up examination (group A: PA < 15 min/day (n = 113), group B: 15C: PA > 30 (n = 105).

Results: The 3 groups were not different for principal characteristics at baseline, while, in 2002–04 follow-up, there was a significantly difference for changes (Δ) of BMI (A: 0.69 ± 1.78, B: 0.23 ± 1.9, C: 0.13 ± 1.6 kg/m²; p = 0.04) and D adiponectin (A: 1.76 ± 2.6, B: 2.07 ± 2.4, C: 2.74 ± 3.0 mcg/mL; p = 0.027). BP difference was significantly and directly associated to (AMP;)DELTA; BMI, after adjustment of antihypertensive therapy (β = 2.15, p < 0.001). At the multivariate regression analysis, PA is a significant and independent predictor of Δ adiponectin, over 8 years (adjusted for age, BMI difference, BP difference and basal adiponectin — β = 0.91, p = 0.014); besides Δ adiponectin, among the three groups, was significantly different (A: 1.81 ± 0.25, B: 2.02 ± 0.28, C: 2.72 ± 0.26 mcg/mL; p = 0.036), after adjustment for the same confounder factors.

Conclusions: This study shows that daily physical activity is associated with higher adiponectin level 8 years later, independently of basal adiponectin plasma levels, BMI and blood pressure.

10.16 Plasma Adiponectin Levels, Body Mass Index and Cornell Voltage-Duration Product in a Sample of Adult Male Population — Olivetti Heart Study

L. D’Elia, P. Schiattarella, S. Avallone, D. De Palma, R. Ippolito, F. Farina, V. Liguori, F. Galletti and P. Strazzullo

Università di Napoli Federico II, Napoli, Italy

Aim: To evaluate the relationships between blood pressure, anthropometric indices, metabolic variables and Cornell voltage-duration product (C-P), as LVH indices, both in cross-sectional and prospective investigations.

Methods: 606 participants of the Olivetti Heart Study visited both in 1994–1995 and in 2002–2004 examination were included in the analysis. C-P was calculated through the following formula: ((SV3 + RaVL) * QRS) and expressed in mm*ms.

Results: At baseline the characteristics of our sample were: age 51.8 ± 7.3 years, Systolic BP 129.9 ± 16.8 and Diastolic BP 84.3 ± 9.7 mmHg (prevalence of hypertension: 40%), BMI 27.1 ± 2.9 kg/m², abdominal circumference (AC) 95.0 ± 7.9 cm, Adiponectin levels 4.7 ± 2.3 mcg/mL, HOMA-index 2.4 ± 1.7 Units (M ± SD). At the basal examination, C-P was directly and significantly related to BMI (r = 0.15, p < 0.001), SBP (r = 0.23, p < 0.001) and HOMA index (r = 0.10, p < 0.02). After 8 years, we found the following changes (Δ): SBP +8.8 ± 16.8 mmHg (p < 0.001), BMI +0.49 ± 1.7 kg/m² (p < 0.001), AC +3.3 ± 4.7 cm (p < 0.001), Adiponectin levels +2.2 ± 3.1 mcg/mL (p < 0.001), HOMA +0.1 ± 1.9U (p = ns), C-P +40.1 ± 450 mm*ms (p = 0.029) (M ± SD). While the relationship between C-P with BMI (r = 0.13, p < 0.001) and SBP (r = 0.23, p < 0.001) was confirmed, in addition an inverse relationship was detected with Adiponectin levels (r = −0.09, p = 0.03). This association was confirmed also adjusting for age, BMI, SBP and HOMA-index (β = −0.09 0.04, p = 0.03).

Conclusions: In our sample of adult male population, the Cornell voltage-duration product, is directly associated, both cross-sectionally and prospectively, with blood pressure and body mass index; while, it was inversely associated with plasma adiponectin levels only after 8 years of follow up.

10.17 Is Glomerular Hyperfiltration a Correlate of the Metabolic Syndrome in Never-Treated Essential Hypertension?

G. Pucci, M. Pirro, M.R. Mannarino, R. Hijazi, R.S. Helou, E. Mannarino and G. Schillaci

Università di Perugia, Perugia, Italy

Introduction: The metabolic syndrome (MetSyn) is considered an emerging risk factor for chronic kidney disease. However, its relationship with glomerular filtration rate (GFR) in the early phases is controversial. On the one hand, MetSyn predicts the future occurrence of low GFR on the other hand, an association has been described between MetSyn and glomerular hyperfiltration.

Methods: The relation between MetSyn and renal function was examined in 669 patients with newly diagnosed, never treated essential hypertension (men 57%, age 49 ± 10 years, blood pressure 151/93 ± 16/10 mmHg). We excluded from the study all subjects with overt cardiovascular disease or serum creatinine ≥1.5 mg/dL. MetSyn was defined according to the AHA-NHLBI modification of the NCEP-ATPIII criteria. Creatinine clearance was estimate according to the Cockcroft-Gault (CG) formula. GFR was calculated on the basis of the quadratic Mayo equation and the 4-variable Modified Diet in Renal Disease (MDRD) equation.

Results: The prevalence of MetSyn in the examined population was 30% (n = 198). According to the CG formula, the patients with the MetSyn had a higher estimated creatinine clearance than those without MetSyn (108 ± 23 vs 95 ± 21 mL/min, p < 0.001). Estimated GFR was not different in the groups with vs without the MetSyn (81 ± 10 vs 80 ± 11 mL/min/1.73 m² according to the MDRD equation, p = n.s.; 103 ± 13 vs 104 ± 13 mL/min/1.73 m² according to the Mayo formula, p = n.s.). We also tested the association between GFR and single MetSyn components. After adjusting for the effects of age and sex, eGFR was higher in the subjects with low HDL-cholesterol (MDRD equation, 83 ± 10 vs 80 ± 10 mL/min/1.73 m², p = 0.009).

Conclusions: In untreated hypertensive subjects, glomerular hyperfiltration, estimated through methods which do not produce overestimation of GFR in obese subjects, is not associated with the diagnosis of MetSyn. However, an association was found between hyperfiltration and some of the components of MetSyn (low HDL-cholesterol), possibly reflecting the relation between insulin resistance and glomerular filtration.

10.18 Gene Expression in Subcutaneous and Visceral Adipose Tissue of Obese Women with or without Metabolic Syndrome

R. Tosini, L. Mori, M.C. Tacchetti, C. Corbellini, M. Giacchè, C. Cappelli, F. Mittempergher, B. Salerni, E. Agabiti Rosei and M. Castellano

Università di Brescia, Brescia, Italy

Aim: To compare the expression of genes involved in inflammation (endoplasmic reticulum stress, proinflammatory cytokines) and in other different molecular pathways (pro-angiogenic and antioxidant factors, glucose transport, lipolysis, insulin signalling, adipogenesis) in subcutaneous (SAT) and visceral adipose tissue (VAT) of obese subjects with or without metabolic syndrome (MS).

Methods: Anthropometric and biochemical parameters of 16 obese women, aged 18–65 years (MS− n = 8; MS+ n = 8), were evaluated. Quantitative mRNA expression of forty-four genes was measured by RT-PCR on VAT and SAT samples obtained from the same subject at the time of bariatric surgery (restrictive or malabsorptive).

Results: When considering groups of genes related to specific pathways, such as inflammation (14 genes) and insulin resistance (5 genes), a multivariate analysis showed significant difference (p < 0.05, at least) in relation to the different depots and the presence of MS. Moreover, considering the whole group of patients, we found increased expression of TNF-alpha (+2.4 fold change), JUN (+2.1), ERN1 (+2.0), PRKCϴ (+2.7), angiotensinogen (+2.4), methallothionein-3 (+5.3) and decreased expression of WISP2 (−3.7) and leptin (−2.4) in VAT as compared to SAT. As compared to MS−, MS+ patients had lower expression of IRS1, both in VAT and SAT, coupled to increased plasma insulin). MS+ patients also showed higher expression of PRKCϴ in VAT vs. SAT, whereas C reactive protein (CRP) gene expression was more increased in SAT as compared to VAT, with concomitantly higher plasma CRP levels.

Conclusions: The results of our study (higher activation of adipogenesis in VAT, as highlighted by decreased WISP2 expression, and insulin resistance related to increased PRKC and IRS1 expression levels, more evident in MS+) support the hypothesis than VAT and/or the metabolic syndrome play an important role in the pathogenesis of metabolic and cardiovascular complications associated to obesity. Furthermore, the increased CRP gene expression in SAT, but not in VAT of MS+ subjects, suggest that also subcutaneous depot may be involved in the activation of inflammatory processes.

Nervous System

11.1 Role of Heart Rate as Marker of Sympathetic Activity in Metabolic Syndrome

F. Quarti-Trevano,¹ F. Arenare,¹ A. Rozzoni,¹ V. Vella,¹ R. Dell’Oro,¹ L. Magni,¹ M. Volpe,¹ G. Seravalle,² G. Grassi¹ and G. Mancia¹

1 Università Milan-Bicocca, Ospedale San Gerardo, Monza, Italy; 2 Istituto Auxologico Italiano, Milan, Italy

Introduction: Metabolic syndrome (MS) is characterized by a peripheral sympathetic activation, as documented by the marked increase in muscle sympathetic nerve traffic (MSNA) as well as in systemic norepinephrine spillover reported in this condition. Whether and to what extent, however, cardiac sympathetic drive is also increased is unknown. It is also unknown (1) whether in this condition heart rate represents a faithful marker of the adrenergic overdrive and (2) which MS definition is the one more sensitive in detecting the adrenergic overdrive.

Methods: In 79 patients with MS (ATPIII criteria, 66 males and 13 females) aged 56.5 ± 1.3 years (mean ± SEM) we assessed mean arterial pressure (Finapres), heart rate (HR, EKG), venous plasma norepinephrine (NE, high-performance liquid chromatography) and MSNA (microneurography at a peroneal nerve) during a 30-minute resting period. The same measurements were made in a age-and gender-matched group of 28 healthy controls.

Results: Both male and female MS subjects displayed MSNA and NE values which were, as expected, significantly greater than those found in controls (59.6 ± 1.7 vs 39.8 ± 2.9 bs/100 hb, p < 0.01). This was the case for plasma NE (315.2 ± 15 vs 220.5 ± 28 pg/mL, p < 0.05) and HR (78.2 ± 1.4 vs 69.8 ± 2.4 b/min). In the MS group as a whole HR was significantly correlated with both plasma NE (r = 0.22, p < 0.05) and MSNA (r = 0.33, p < 0.01). The correlation was (1) detectable in both genders and (2) independent on the central or peripheral type of the obese state. MSNA was significantly related to HOMA index (r = 0.56, p < 0.01), plasma insulin levels (r = 0.42, p < 0.01), body mass index (r = 0.42, p < 0.01) as well as waist circumference (r = 0.33, p < 0.01). No significant correlation was found between NE or HR and the above mentioned metabolic and anthropometric indices. ATPIII, AHA and IDF definition displayed a similar sensitivity in detecting the MS-dependent sympathetic activation, independently on the direct or indirect approach used to assess adrenergic function.

Conclusions: These data provide evidence that in MS not only peripheral but also cardiac sympathetic drive is enhanced and that the adrenergic overdrive is similarly detectable when different MS definitions are employed. They also show that HR can be regarded as a sensitive marker of the inter-individual difference in sympathetic drive. The sensitivity of the approach is limited, however, because HR was unable to reflect the main metabolic and anthropometric abnormalities of the disease.

11.2 Reduced Heart Rate Variability and Prolonged QT Interval in Patients with Uncomplicated Essential Hypertension

S. Maule, V. Milazzo, S. Totaro, D. Tizzani, S. Abram and F. Veglio

SCDU Medicina 4, Centro Ipertensione Arteriosa, Università di Torino, Torino, Italy

Introduction: Heart rate variability (HRV) represents both an index of the autonomic function and an important prognostic factor in several diseases. An abnormal HRV, characterised by a sympathetic predominance, has been shown in patients with essential hypertension, even in the early stages of the disease and in association with left ventricular hypertrophy. QT interval prolongation has been associated with an increased risk of ventricular arrhythmias and sudden death in the general population and in several medical conditions. An abnormal ventricular repolarisation has been described in patients with hypertensive heart disease and a prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects.

Aim: To evaluate the relation between autonomic nervous system function, measured with heart rate variability (HRV), and QT interval in patients with untreated uncomplicated essential hypertension.

Methods: 215 untreated patients with essential hypertension underwent an ECG Holter recording with a software dedicated to HRV and QT analyses.

Results: 9% of the patients showed a corrected QT (QTc) >440 ms. HRV indexes in time-domain (SDNN, SDNN index, RMSSD, and pNN50) were significantly reduced in patients with prolonged QTc compared to normal QTc (SDNN 24h: 126.4 ± 29.9 vs 143.9 ± 35.4 ms, p = 0.02; SDNN index night-time: 85.9 ± 32.4 vs 115.5 ± 36.7 ms, p = 0.0006; RMSSD 24h: 22.2 ± 7.7 vs 31.2 ± 13.0 ms, p = 0.0007; pNN50 24h: 4.4 ± 4.9 vs 9.7 ± 8.4%, p = 0.0006). Linear correlation analysis between QTc length and HRV parameters showed a significant negative correlation with all time-domain indexes. Such a correlation was maintained for RMSSD, pNN50 and SDNN index nighttime after correction for gender and age.

Conclusions: The present study shows that, even prior to the development of cardiac hypertensive disease, a prolongation of QTc and a reduced HRV, both markers of cardiovascular risk, coexist in a percentage of patients with untreated essential hypertension. Follow-up studies are warranted to evaluate the potential role of the association of abnormal ventricular repolarisation and reduced HRV in predicting life-threatening arrhythmias and increased mortality rates in hypertensive patients.

11.3 Hypertension and Cognitive Impairment in Very Old People

F. Scapellato,¹ L. Beltrami,² A. Esposito,³ C. Redaelli,² D. Solari,² A. Pernigotti,⁴ M. Muzio,⁴ C. Negri¹ and S. Carugo³

1 Unità Alzheimer, IMMeS e PAT, Milan, Italy; 2 IMMeS e PAT, I UOC Cardiologia, Milan, Italy; 3 Dipart. toraco-polmonare e cardiocircolatorio, Università di Milan; IMMes e PAT, I UOC Cardiologia, Milan, Italy; 4 Università degli Studi, Milan, Italy

Introduction: One of the most feared consequences of aging is dementia, a deterioration of acquired cognitive ability that involves not only a diminution of quality of life for the patient, but also a significant impact on families and public expense. Therefore, many are the measures to prevent this deficit.

Aim: To evaluate a possible association between cardiovascular risk factors and dementia.

Methods: We retrospectively evaluated 124 patients (107 females, 17 males), mean age 82 years (range 59–99 ys) referring to Alzheimer’s Unit of Pio Albergo Trivulzio of Milan, with a history of hospitalization for at least 2 months between 2006 and 2008. During admission to hospital, patients underwent to thorough clinic, laboratory and instrumental investigation: (1) visit, (2) routine examination, (3) sphygmomanometric blood pressure (3 successive measurements) and heart rate, (4) EKG, (5) CT brain, (6) screening for dementia and assessment of cognitive function based on cognitive test UCLA.

Results: The etiology of dementia was 39% vascular, 27% Alzheimer’s disease, 28% mixed, 6% mild cognitive. Cardiovascular diseases were absent in 48% of patients, 7% were suffering from coronary heart disease and 2% congestive heart failure. Considering the factors of cardiovascular, hypertension was found in 43% of patients, with a mean duration of 8 years and 34% of theirs had developed multifactorial dementia, 30% an Alzheimer’s dementia, 30% a mixed and 6% mild cognitive impairment. During hospitalization, both cardiological therapy than neurological were optimized and we found to discharge a statistically significant decrease of the UCLA score (T1 vs T0, p < 0.0001). There were not observed significant changes in the BP (T0 126/75 mmHg vs T1 128/75, p = NS).

Conclusions: Hypertension is confirmed to be the main cardiovascular risk factor and it is vital to act on prevention rather than control in old age; while the optimization of neurological therapy is strictly related with the improvement of the degree of dementia measured by UCLA score.

11.4 Blood Pressure Control Status and Cognitive Decline: a Longitudinal Study

G. Inverso,¹ A. Realdi,¹ M. Maraffon,¹ L. Macchini,¹ P. Amodio,¹ S. Schiff,¹ D. Mapelli,² S. Cantatore,² M. Puato,¹ M. Zanardo,¹ C. Tirrito,¹ R. Manara³ and A. Semplicini¹

1 Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Padova, Italy; 2 Dipartimento di Psicologia, Università di Padova, Italy; 3 Dipartimento di Neuroscienze, Università di Padova, Padova, Italy

Introduction: Hypertension induced cerebrovascular damage is a known determinant of age related cognitive decline, but the role of blood pressure control in slowing or reversing cognitive decline is still debated.

Aim: To assess the correlation of cognitive decline with blood pressure control and cerebrovascular organ damage.

Methods: 60 patients (age 63 ± 6 years, 41 males) with long-standing (17 ± 7 years), treated hypertension, attending our hypertension outpatient clinic, underwent 24 hr ambulatory blood pressure monitoring (ABPM), intima-media thickness (IMT) measurement by carotid ultrasonography, cerebrovascular reactivity (CVR) study by transcranial Doppler, brain magnetic resonance imaging and neuropsychological tests. After 6 ± 1 years follow up, 46 patients (32 males) underwent a second evaluation by ABPM, IMT measurement and neuropsychological tests.

Results: Patients with poor blood pressure control (n = 29; ABPM > 125/80 mmHg) had larger white matter lesions, reduced CVR and higher IMT at enrolment. Cognitive performance was unrelated to blood pressure control, but higher diastolic blood pressure was associated with better scores in attention tests. Upon logistic regression, worse performance in executive tests was predicted by higher IMT and worse attention, but not by blood pressure. IMT increased at follow up and it was predicted by diabetes and blood pressure, while attention and executive functions improved (from −0.36 ± 1.7 to 0.18±1.1, p < 0.05 and from −1.63 ± 3.4 to −0.27 ± 4.1, p < 0.05) and memory declined (from 0.25 ± 2.7 to −0.45 ± 2.5, p < 0.05).

Conclusions: Undemented patients with long-standing hypertension have cognitive decline involving the executive functions. Cognitive impairment is related to IMT and attention and unrelated to blood pressure control, at baseline. Better attention is related to higher blood pressure. Both attention and executive functions improve at follow up, despite IMT increase. Short term blood pressure lowering has a negative effect on attention that worsens cognitive performance and masks any correlation between blood pressure control and executive functions. Long-term antihypertensive treatment improves cognitive functions despite IMT progression through adaptation to lower blood pressure levels. Gradual blood pressure lowering and steady blood pressure control are required to prevent hypertension induced cognitive decline.

11.5 Effect of Sympathetic Inhibition on Renal Resistive Index in Essential Hypertensive Patients

R.M. Bruno, E. Daghini, L. Ghiadoni, A. Magagna, D. Versari, S. Taddei and A. Salvetti

Università di Pisa, Pisa, Italy

Introduction: In essential hypertension renal sympathetic nervous system activity is increased, with consequences on renal haemodynamics, sodium balance, renin production.

Aim: To determine whether an acute administration of the sympathomodulator clonidine can influence renal haemodynamics and SNS activity in essential hypertensive patients.

Methods: Thirteen never treated, essential hypertensive patients were included. ECG, non invasive beat-to-beat blood pressure values (BP, Portapres) and muscle sympathetic nervous activity (MSNA, microneurography) were monitored in basal conditions and during a low dose infusion of clonidine (0.5 ìg/kg iv in 15 minutes). Venous samples for assessment of norepinephrine (NE), epinephrine (E), plasma renin activity (PRA), were obtained before and at the end of recording. Renal intraparenchimal resistive index (RI) was obtained by duplex ultrasound in basal conditions and at the end of the infusion.

Results: Clonidine infusion determined a significant reduction in mean BP (from 111.7 ± 13.6 to 107.4 ± 16.4 mmHg, p = 0.03 vs baseline) and in RI (from 0.56 ± 0.02 to 0.52 ± 0.06, p = 0.001 vs baseline, −8.3%). Plasma NE was significantly reduced by clonidine,(from 304 ± 99 to 232 ± 81, p = 0.002 vs baseline), while MSNA (from 33.3 ± 9.2 to 31.0 ± 9.3 bursts/min, p = 0.09 vs baseline, −6.7%; from 48.9 ± 12.7 to 46.5 ± 12.9 bursts/100 heart beats, p = 0.08 vs baseline, −4.6%) and heart rate (from 68.3 ± 10.4 to 66.8 ± 10.4 bpm, p = 0.12 vs baseline) only tended to decrease. PRA and E were unchanged. RI changes were directly related to NE changes (r = 0.865, p < 0.001), but not to MSNA (r = 0.256, p = ns).

Conclusions: Low dose clonidine significantly reduced intrarenal vascular resistances and circulating NE without affecting MSNA. These data suggest that the renal effect of clonidine could be mediated mainly by a prejunctional action on NE release.

11.6 Sleep Disordered Breathing and High Altitude Hypoxia: Gender Related Differences: the HIGHCARE Project

C. Lombardi,¹ P. Meriggi,² M. Bartesaghi,³ G. Caldara,³ K. Styczkiewicz,⁴ G. Bilo,¹ A. Giglio,¹ E. Colamartino,³ P. Mazzoleni,² A. Giuliano,³ M. Revera,¹ M. DiRienzo,² G. Mancia¹ and G. Parati¹ on behalf of a nome dei ricercatori HIGHCARE

1 Univ. Milano-Bicocca, Ist. Auxologico It IRCCS, Milan, Italy; 2 Polo Tecnologic, Biomedical Technology Department, Fondazione Don Carlo Gnocchi Onlus, Milan, Italy; 3 Istituto Auxologico Italiano, Milan, Italy; 4 Istituto Auxologico Italiano IRCCS and I Department of Cardiology and Hypertension, Jagiellonian Univeristy, Milan, Italy

Introduction: Respiratory periodicity during night at high altitude is frequently reported in patients with cardiovascular disease and it is due to alternance between respiratory center stimulation by hypoxia and its subsequent inhibition by hyperventilation-induced hypocapnea. This respiratory pattern may be influenced also by sex hormones. In fact estrogens and progesterone have been suggested to protect from sleep-related breathing disorders (SRBD) at sea level. Aim of our study was to explore whether a different ventilatory pattern during night sleep might characterize women and men during acute exposure at high and very high altitude hypoxia.

Methods: In 27 healthy subjects, 23 male (mean age 40 years) and 14 female (mean age 36 years) participating in the HIGH altitude Cardiovascular Research project (HIGHCARE), we performed nocturnal portable polysomnography with a new wearable system (MAGIC vest) and with a standard portable system (Embletta) in the following conditions: (1) at sea level (SL), (2) during the first or second night at Namche Bazaar (3500 m above SL) and (3) during first or second night at Mt Everest Base Camp (5400 mt slm). During the recording we monitored (1) air flow, (2) thoraco-abdominal movements; (3) finger pulse oximetry (SpO₂), (4) body position, (5) ECG, (6) snoring. Mean and minimum SpO₂ during night, number of central and obstructive apneas, oxygen desaturation index (ODI), apnea-hypopnea index (AHI) were measured.

Results: During night at Namche Bazar (3500 slm) AHI was 57.7 ± 33.4 in male and 4.68 ± 2.7 in female (p < 0.05) the difference being due to a strikingly higher number of central sleep apneas and hypopneas in male than in female subjects (central AHI: 54.1 ± 33 vs 4.68 ± 2.7, p < 0.01), leading to a corresponding difference in oxygen desaturation index (ODI, 49.14 ± 25 vs 9.1 ± 7 respectively, p < 0.01). At Base Camp AHI was 92 ± 41 in male and 53.6 ± 45 in female. The difference was still referred to central sleep apneas. ODI values were 75.12 ± 28 vs 49.1 ± 25 respectively, p < 0.05.

Conclusions: Under exposure to high and very high altitude hypoxia periodic breathing at night affects more frequently male than female subjects. Females started to present a significant number of central sleep apnea only at the highest hypobaric hypoxia level achieved. This data highlight the presence of a gender-related difference in respiratory center stimulation by hypoxia, which leads to trigger periodic breathing in males earlier and more frequently than in females. This data may also have important implications for pathogenesis and cardiovascular consequences of SRBD at sea level which are reported to be significantly more frequent in males than in females.

11.7 Emotional (Dys)regulation and Blood Pressure Levels

A. Mingarelli,¹ M. Casagrande,¹ A. Muggianu,¹ G. Germanò² and M. Bertini¹

1 Dipartimento di Psicologia-“La Sapienza” Università di Rome, Rome, Italy; 2 Dipartimento di Scienze dell’Invecchiamento-“La Sapienza” Università di Rome, Rome, Italy

Introduction: Neurophysiologic, motor/expressive and cognitive domains of emotions appear to be central factors in the integration processes between psyche and soma. The Emotional Regulation (ER) consist of the synergetic integration of these domains. As many recent studies pointed out, a deficit in the cognitive processing of the emotion (alexithymia) could lead to a dysregulation of the Autonomic Nervous System (ANS), that can be considered as one of the causes explaining the relationship between alexithymia and Hypertension. In order to make clear this link, two different models have been proposed: a hypoarousal and a hyperarousal model. Authors have suggested an Autonomic Nervous System hypoactivation, as a reaction to emotional situations, in the alexithymic subjects. On the other hand they proposed an hyperactivation during the physiologic parameter recovery.

Aim: On the basis of this model we can hypothesize that alexythymic subjects, compared to non alexythymic subjects, present blood pressure levels: (a) higher on a baseline condition, (b) lower during the report of an emotional story (c) higher during a recovery phase.

Methods: Fifty subjects (Man/Women = 22/28; mean age = 23.54 ± 2.38), selected from a larger sample of 300 university students (18–30 age), participated in this study. They were selected on the basis of extreme scores obtained on the 20 items of the Toronto Alexithymia Scale. After a baseline phase of 14 minutes, the researcher asked subjects to think, imagine and verbally report an event, coming from the own life and characterized by either positive, negative, or neutral emotional valence. The three verbal reports were generated in three different moment of the experimental setting, in a counter-balanced order. Each stage of narration was followed by a (physiologic) recovery phase, in which the subject rested quietly without speak. Blood pressure was measured through the experiment every 90 seconds.

Results: Alexithynic subjects compared to controls showed higher level of Diastolic blood pressure (DBP) (p < 0.05) in the baseline condition and higher level of both Systolic blood pressure (SBP) (p < 0.05) and DBP (p < 0.04) in the experimental conditions. Furthermore an ER × Event (neutral, positive, negative) × Modality (imagination, narration, recovery) interaction was observed, which showed higher blood pressure levels in alexithymic subjects, compared to controls, during the narration of emotional events (p < 0.03). Moreover alexithymic, compared to non alexithymic subjects, presented higher DBP levels (p < 0.02) in the recovery stage, which were not extended to SBP (p < 0.09).

Conclusions: Our results showed that alexithymic subjects presents higher blood pressure levels in each experimental condition (baseline, emotional, physiological recovery), supporting the Hyperarousal model and suggesting that a deficit in the ER can be a risk factor, also for young people.

11.8 Promoting the Ability of Emotional Self-Regulation in People Affected by Hypertension

A. Mingarelli,¹ M. Casagrande,¹ M. Benevento,² E. Stella,¹ G. Germanò,³ A. Muggianu,¹ L. Maccari¹ and M. Bertini¹

1 Dipartimento di Psicologia-“La Sapienza” Università di Rome, Rome, Italy; 2 Dipartimento di Psicologia Clinica e Dinamica-“La Sapienza” Università di Rome, Rome, Italy; 3 Dipartimento di Scienze dell’Invecchiamento-“La Sapienza” Università di Rome, Rome, Italy

Introduction: Among the competences of living, considered as fundamental in the health support by the World Health Organization (WHO), there are: the management of emotion and stress, the empathy and the self-awareness. All these competences are strictly related to the emotional area. Based on studies highlighted how people affected by Hypertension show a deficit in the emotional elaboration (Alexithymia).

Aim: To evaluate the efficacy of a psychological intervention for Promoting Emotional Regulation Skills (PERS) in both reducing the level of blood pressure and improving the supervision of health in patients affected by hypertension.

Methods: Ninety patients with high blood pressure, selected at the Center for the cure of hypertension in the 1st Medical Clinic Umberto 1 in Rome, participated in this study. Five Groups of 12 people were part of the PERS groups and 30 people were included in a waiting list, that formed the control groups. The two types of groups were homogeneous for the consumption of hypertensive drugs and balanced for gender and alexithymia level. The medical and psychological history has been assessed after an evaluation of psychological (Alexithymia e Locus of control health) and physiological (Measuring of high blood pressure) characteristics before and after the treatment and upon a follow up at three months. The PERS groups participated to 12 sessions of 2 hours each on a weekly basis. Within the PERS groups, game activities took place, focused on some emotional aspects and on the elaboration of emotional experiences of the day life. At the end of the treatment the patients have been interviewed for plain how to use, in the daily life, the emotional competences developed within the PERS groups.

Results: Main results showed in the PERS groups, compared to the control group, a reduction of pressure parameters (systolic p < 0.0004 and diastolic p < 0.000001) and an increase in health Locus of control (p < 0.02).

Conclusions: Although these are just preliminary results, they seem to demonstrate that a psychological intervention can facilitate the development of emotional competences, that helps people to improve physical health by reducing the level of blood pressure.

11.9 Alexithymia and Hypertension: the Role of the Affective Factors and Cognitive Elaboration

A. Mingarelli,¹ M. Casagrande,¹ M. Benevento,² G. Germanò,³ M. Vernamonte,¹ I. Saponaro¹ and V. Giordano¹

1 Dipartimento di Psicologia-“La Sapienza” Università di Rome, Rome, Italy; 2 Dipartimento di Psicologia Clinica e Dinamica-“La Sapienza” Università di Rome, Rome, Italy; 3 Dipartimento di Scienze dell’Invecchiamento-“La Sapienza” Università di Rome, Rome, Italy

Introduction: Alexithymia is a deficit including the difficulty in identifying, describe and elaborate emotions. Some studies showed that Hypertensive people have higher alexithymic level compared to normal people. However, this relation should seem to be evident only in people who present levels of blood pressure so high to require a Pharmacological Antihypertensive Treatment (PAT). Some Neuropsychological studies have proved that subcortical areas (such as the amygdala) are involved in the perception of the emotions, while cortical regions are involved in the cognitive elaboration of the emotions. The most utilized questionnaire for evaluating the alexithymia is the Toronto Alexithymia Scale. The last version of this instrument, including 20 items (TAS-20), presents a good psychometric properties, but it lost in part his sensibility for evaluating the emotional perception. Recently, the Bermond-Vorst Alexithymia Questionnaire (BVAQ) was developed in order to evaluate two big-factors: an affective dimension of emotions, related to the emotional perception, and a cognitive dimension of emotions, related to the emotional elaboration.

Aim: To evaluate if Hypertensive people following a PAT have higher deficit in both affective and cognitive dimensions of emotions compared to Hypertensive people who do not follow a PAT.

Methods: In this study 97 patients participated (Man/Woman = 44/53; mean age = 54.46 ± 12.76) affected by Essential Hypertension, who completed the Italian version of the BVAQ.

Results: An ANCOVA, considering as independent factor the PAT (yes/no), the age as covariate, and the BVAQ scores as dependent variables, indicated higher alexithymic levels in patients undergoing PAT compared to controls (p < 0.001). Both the affective and the cognitive dimensions of emotions are involved in this result (p < 0.001). Furthermore, within the cognitive elaboration’s dimensions, both analyzing (p < 0.02) and verbalizing (p < 0.01) were also significant.

Conclusions: These results confirmed that hypertensive patients who underwent to a PAT, compared to controls, present higher levels of alexithymia, which appears specifically characterized by difficulties in the cognitive elaboration of emotions. These results have important clinic implications for planning interventions, aimed to ameliorate the abilities to elaborate and communicate the emotions in people with essential Hypertension.

11.10 Blood Pressure and Risk of Haemorrhagic Transformation and Cerebral Edema after Intravenous Thrombolysis in Ischaemic Stroke

L. Macchini,¹ E. Parotto,² L. Bolognani,² G. Magagnotti,² A. Realdi,² M. Leoni,² G. Strapazzon,² F. Vettore,² P. Caielli,² M. Pengo,² L. Calò,² R. Manara,³ F. Tosato⁴ and A. Semplicini¹

1 Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Ospedale SS Giovanni e Paolo Venezia, Venezia, Italy; 2 Dipartimento di Medicina Clinica e Sperimentale, Università di Padova, Padova, Italy; 3 Dipartimento di Neurologia, Università di Padova, Azienda Ospedaliera, Padova, Italy; 4 Dipartimento di Pronto Soccorso e Medicina d’Urgena, Azienda Ospedaliera, Padova, Italy

Introduction: Haemorrhagic transformation (HT) is considered the most unfavorable complication after thrombolytic treatment in ischemic stroke, and is often attributed to uncontrolled high blood pressure.

Aim: We sought to (1) assess the incidence rate of both early and late HT in patients with acute ischemic stroke who received intravenous thrombolysis, (2) identify variables and risk factors associated with HT, (3) assess the clinic course and outcome associated with HT.

Methods: 63 patients with ischemic stroke received intravenous rt-PA within 3h of symptom onset. Brain CT scan was performed before treatment, 24–36h after rt-PA administration and later when needed according to the clinic course. Stroke severity was assessed with NIHSS score at baseline; neurological status was then reassessed 2h, 24h and 7 days after rt-PA administration. The modified Rankin Scale was used to evaluate outcome three months after acute stroke. HT was categorized according to the criteria published by Fiorelli et al for the ECASS I cohort and distinguished in early (<36 hours from thrombolysis) or late HT.

Results: HT occurred in 18 (30%) patients within 36h. Control CT scan after 36h revealed worsening of HT in 4 (10%) and new HT in 10 (25%). The only variables associated with risk of HT were the medical history of hypertension (p = 0.002) and high platelet count on admission (p = 0.008). HT was not associated with worse clinic outcome at 7 days and 3 months after acute stroke. Cerebral edema (CE) was reported in 20 (33%) patients at 24–36h and in 16 (40%) patients at the follow up CT scan and associated with hypotension at onset (p = 0.04). Odds of a favorable 3-month outcome were lower in patients who presented late cerebral edema (p = 0.001). At baseline, 24 (39,3%) patients showed hyperdense middle cerebral artery sign (HMCAS); MCA occlusion resolved in 12 (50%) patients after intravenous thrombolysis. NIHSS score was lower at 24h in recanalized vs nonrecanalized patients (5.8 ± 4.3 vs 12.2 ± 5.0; p = 0.003).

Conclusions: HT is associated with a history of hypertension, and doesn’t affect outcome neither in terms of disability, nor of mortality. CE after 36h is associated with low blood pressure at stroke onset. CE and failure of arterial recanalization emerge as the most important predictors of disability in patients with ischemic stroke treated with intravenous thrombolysis.

11.11 Changes in Neuropsychological and Psychological Performance at High Altitude: Data from the HIGHCARE2008 Project

B. Poletti,¹ F. Maringelli,² C. Lombardi,³ P. Meriggi,⁴ A. Lafronza,¹ V. Silani¹ and G. Parati³ on behalf of Ricercatori HIGHCARE

1 Dipartimento di Neurologia e Lab. di Neurosc.-Univ. degli Studi di Milan-IRCCS Istituto Auxologico Italiano, Milan, Italy; 2 Srlabs, Milan, Italy; 3 Dipartimento di Prev. e Med. Clinica, Univ. di Milano-Bicocca — Dipartimento di Cardiol., IRCCS Istituto Auxologico It., Milan, Italy; 4 Polo Tecnologico — Biomedical Technology Department, Fondazione Don Carlo Gnocchi Onlus, Milan, Italy

Introduction: Exposure to high altitude reduces oxygen supply to the central nervous system and may cause a variety of neuropsychological and psychological impairments. Cognitive alterations following high altitude exposure have been variously described in literature for both ecological and simulated conditions. Neuropsychological performance modifications during high altitude exposure include quantitative and qualitative changes, positively correlated with altitude conditions.

Aim: To analyze neuropsychological and psychological profiles of normal subjects at sea level and when exposed to high and very high altitude (3500 and 5400 m), the latter conditions being considered as a model of cognition functioning in clinic conditions such as chronic obstructive pulmonary disease (COPD), obstructive sleep apnea (OSA) or cerebrovascular diseases complicating hypertension, all characterized by poor brain oxygen supply.

Methods: Forty-five normal subjects participating in the Himalaya’s HIGHCARE expedition underwent an extensive neuropsychological and psicodiagnostic assessment in normoxia condition, at 3500 m, at 5400 m and 3 month after expedition end. Different cognitive domains had been investigated with both paper and pencil tools as well as computerized tests. This battery included: computerized measures of reaction time and eye-movements (PVA test — Visuo-Attentional Performance Evaluation), Digit span test, Corsi’s Test, Tapping Test, Stroop Colour-Word Test, Symbol digit modalities test, Trail Making Test, Verbal Fluency Test, Visual cancellation tasks, Wechsler Memory Scale. Eye movements were measured using an × 50 eye-tracker. Clinic tools for assessing psychological and emotional were administered.

Results: Our data show quantitative and qualitative differences in cognitive performances between study conditions, with higher scores in normoxia and at 3500 m than at 5400 m. Significant differences and paradigmatic patterns of data emerge on different eye-movements/reaction times measures, while a general cognitive slowliness occurred at 5500 m condition. Subjects differed significantly for the presence of depressive/anxious symptoms. Neuropsychological and psychological data were correlated with cardiovascular and respiratory parameters.

Conclusions: High altitude exposure induces specific cognitive and psychological patterns, as well as peculiar alterations of eye-movements patterns. Computerized neuropsychological assessment seems more sensitive than usual tests to minimal changes observed in cognitive functions under hypoxia conditions. This assessment seem to be ideal in detecting small cognitive changes frequently observed in hypertensive patients affected by mild vascular cognitive impairment (mVCI). These findings have clinic implications for the neuropsychological management of patients affected by diseases associated with hypoxemia.

11.12 Patients with Coronary Artery Disease Have a Marked Impairment of the Baroreflex Function Even in the Absence of a Myocardial Infarction

A. Radaelli,¹ C. De Carlini,² P. Castiglioni,³ F. Soriano,² S. Bonfadini,² C. Accorsi,² M. di Rienzo,³ G. Paolini² and G. Mancia²

1 Divisione di Riabilitazione Cardiologica, Ospedale S.Gerardo Monza, Biassono, Italy; 2 Università Milan-Bicocca, Monza, Italy; 3 Dipartimento di Tecnologia Biomedica, Ospedale S. Maria Nascente, Fondazione Don Gnocchi, Milan, Italy

Introduction: Evidence exists that the baroreflex is impaired in patients with and without myocardial infarction. The extent of baroreflex impairment in these two conditions is nevertheless not known.

Methods: Patients with coronary artery disease and normal left ventricules (CAD, n = 29) had their R-R interval and arterial blood pressure (BP) continuously monitored, and were subjected to carotid baroreceptor stimulation by neck suction (−10, −20 and −40 mmHg). Age-matched controls (n = 29) and heart failure patients (CHF, n = 31) were identically studied. Baroreflex function was assessed by (i) the slope of the regression of R-R interval and BP responses to stimulus intensity, (ii) the slope of the progressive bradycardic and tachycardic responses to spontaneous changes of systolic blood pressure (sequence analysis), (iii) the baroreflex efficiency index.

Results: In CAD patients carotid baroreflex control of R-R interval and BP was reduced by −33% and −43%, respectively (both p < 0.01). Similar reductions were observed by the sequence analysis (−35%) and by the baroreflex efficiency index (−33%, all p < 0.01). Results in CHF patients were similar to those in CAD patients.

Conclusions: In CAD patients baroreflex function is severely impaired both in the heart rate response and in the control of blood pressure. The extent and the degree of baroreflex impairment observed in CAD patients are similar to those of CHF patients.

11.13 Impaired Blood Pressure Control in Grade 1 Hypertensive Patients Induces a Deficit in Cognitive and Attentive Functions

P. Nazzaro, M.F. De Caro, O. Todarello, G. Schirosi, C. Spinelli, A. Losignore, F. Fiorentino, V. Affatati, G. Grandolfo and F. Federico

DipartimentoScienze Neurologiche e Psichiatriche-Stroke Unit-Univerità di Bari, Bari, Italy

Introduction: Different studies showed that cognitive and vascular functions may decline along hypertension.

Aim: To highlight changes in cognitive profile and pre-clinic vascular damage in mild hypertensive patients, poorly controlled by antihypertensive therapy.

Methods: As assessed by medical visit (off) and ambulatory blood pressure monitoring (day-night), 20 normotensives (NTN), 63 hypertensive patients with adequately (AC-HTN) and 61 with inadequately (UC-HTN) lowered blood pressure, with similar age, sex, metabolic assessment and history of hypertension (156 ± 2/90 ± 2 vs 154 ± 1/88 ± 3 mmHg, n.s.) underwent a neuropsychological evaluation by tests for executive functions (FAB, STROOP), selective attention (MATRIX), verbal short memory (DIGITSPAN), working memory or ability of monitoring of learned information (SPANBACK) and lexical fluency (FAS). The SBPoff-day% served as surrogate measure of ‘white-coat effect’ (WCeff) and carotid intima-media thickness (IMT) was used as index of vascular damage.

Results: Differences in hemodynamic and cognitive functions occurred, as shown in the table (data are expressed as mean ± SE: * p < 0.05, ** p < 0.01, *** p < 0.001 vs NTN; ^p < 0.05, ^^p < 0.01, ^^^p < 0.001 vs AC-HTN). Pearson analysis, adjusted for smoke, age, IMT, WCeff, metabolic and anthropometric assessment, showed, in hypertensive patients, an inverse association between with SBPoff and FAB (−0.329***), MATRIX (−0.324***) and FAS (−0.304***).

Conclusions: The results showed that an insufficient blood pressure control may worsen frontal/executive and attentive functions, while working memory seems to characterize the hypertensive patients independently by the blood pressure control.

11.14 Chronic Effects of Sino-Aortic Denervation in Rats

A. Radaelli,¹ C. De Carlini,² P. Castiglioni,³ F. Soriano,² A.U. Ferrari² and G. Mancia²

1 Divisione di Riabilitazione Cardiologica, Ospedale S.Gerardo Monza, Biassono, Italy; 2 Università Milan-Bicocca, Monza, Italy; 3 Dipartimento di Tecnologia Biomedica, Ospedale S. Maria Nascente, Fondazione Don Gnocchi, Milan, Italy

Introduction: Baroreflex impairment is a common future of cardiovascular disease. While the effects of acute baroreceptors removal on heart rate and blood pressure are well known, the effects of chronic baroreceptor deafferentation are still not clear.

Methods: Seven conscious unanesthetized WKY rats (11–12 week old) were studied three days (acute, A) and 7 months (chronic, C) after surgical sino aortic denervation. Mean arterial pressure (MAP) and pulse interval (PI) were continuously monitored for 10 minutes. Data were analyzed to calculate mean value and standard deviation (SD) of PI and MAP, and their coherence. Differences between groups were assessed by Wilcoxon test.

Results: MAP was significantly lower in C than in A (88 ± 8 vs 109 ± 5 mmHg, M ± SEM, p < 0.04), PI was significantly longer in C than in A (196 ± 4 vs 150 ± 3 ms, p < 0.01). SD of MAP was similar in the two conditions (10 ± 2 mmHg in C vs 12 ± 3 mmHg in A) while SD of PI increased significantly in C with respect to A (13 ± 2 vs 5 ± 1 ms, p < 0.01). Coherence between PI and SBP was similarly low in A and in C.

Conclusions: With respect to the acute phase, 7 months after sino-aortic denervation: (1) blood pressure decreases while blood pressure variability remains constant; (2) PI and PI variability increase. In absence of the baroreflex other mechanisms act to reduce blood pressure and to increase vagal outflow or decrease cardiac sympathetic outflow to the heart. These mechanisms, nevertheless, are not efficient in buffering blood pressure variability.

Therapy, Pharmacoeconomics and Pharmacovigilance

12.1 Does Blockade of the Angiotensin II Subtype 1 Receptors Improve Arterial Stenoses due to Fibromuscular Dysplasia?

A. Mazza, S. Cuppini, L. Schiavon, M. Marzolo, C. Rossetti, D. Montemurro and S. Zamboni

AULSS 18 Rovigo, Rovigo, Italy

Fibromuscular dysplasia (FMD) represents a group of non-atherosclerotic, non-inflammatory arterial diseases frequently incidental and asymptomatic, most commonly involving renal and carotid arteries. The etiology of FMD is not well understood and several mechanisms have been proposed. Pathophysiology and molecular biology of FMD are unknown, and this disease has been listed by the National Organization of Rare Diseases. Angiographic classification includes multiple stenoses and the string-of-beads pattern. There are no treatment protocols for FMD and it may be managed conservatively by antiplatelet or anticoagulant therapy as prophylaxis against complications. In this clinic case on a young hypertensive woman with FMD the olmesartan-based treatment improved arterial stenoses of the celiac tripod (CLT) and superior mesenteric artery (SMA) after 14 months of therapy (figure). The improvement of the endothelial dysfunction due to selective blockade of the angiotensin II subtype 1 receptors (AT1) and the effect of the AT1-blockers on the transforming growth factor-beta pathway, are the possible mechanisms explaining this finding. We hope that this case can be of help to stimulate further investigations about FMD, a disease that has been reported to be the cause of sudden deaths in young people.

12.2 24-Hour Antihypertensive Efficacy of the Association between Barnidipina and Ramipril in Hypertensive Patients Uncontrolled with Ramipril

G. Rossetti,¹ D. Solari,² B. Caimi,² A. Esposito,² A. Pernigotti,³ S. Omboni⁴ and S. Carugo²

1 Dipartimento toraco-polmonare e cardiocircolatorio-Università degli Studi di Milan, Milan, Italy; 2 IMMeS e PAT, Milan, Italy; 3 IMMeS e PAT, I UOC Cardiologia, Milan, Italy; 4 DOCLEADER SRL, Varese, Italy

Introduction: Several studies showed that in hypertensive patients, blood pressure values in MAP 24-hour are related with organ damage more than simply ambulatory blood pressure values.

Methods: In this open, randomized in parallel groups study, was compared the efficacy of ramipril 10 mg/day (R) with ramipril 5 mg/day associated at barnidipina 10 mg/day (R + B), for 24 weeks of treatment in hypertensive patients with blood pressure values uncontrolled (PAD 90–109 mmHg e/or PAS 140–179 mmHg) by monotherapy with ramipril 5 mg/day. After 6 weeks, in patients uncontrolled (PAD > 90 mmHg e/or PAS > 140 mmHg) was added hydrochlorothiazide 12.5 mg in group R and increased barnidipina dosage at barnidipina 20 mg/day in group R + B. Main goal of the study was to evaluate the efficacy of both treatments on 24 hours blood pressure monitoring.

Results: In this preliminary analysis are showed the results of first 12 weeks treatment in first 30 enrolled patients.(15 R e 15 R + B). Average age of patients was 54 ± 13 years (60% M). After 6 weeks of therapy, in group R, in 4 patients with blood pressure values uncontrolled was added hydrochlorothiazide 12.5 mg, in group A, in 1 patient barnidipina dose was doubled at 20 mg/die. Both therapies decreased 24h blood pressure values. The reduction of BP was greater for the association therapy although the difference between two treatments, adjusted at baseline, was not significant (table). We observed similar results also for day time and night time blood pressure values. Finally, after 12 weeks of treatment, also ambulatory blood pressure decreased; this reduction was larger in the association therapy group (12/5 mmHg for R+ B, vs 6/1 mmHg for R), although the difference between two treatments was not significant. 1 patient in group R stopped therapy at 12 weeks for cough, and in 2 patients in group R + B interrupted treatment for headache respectively at 6 and 12 weeks.

Conclusions: Preliminary dates of this compared study shows that an ACE inhibitor monotherapy at high dosage is equally effective as a low dosage combination therapy.

12.3 Persistence with Antihypertensive Treatment in Newly Treated Patients: Predicting Factors and Role of Drugs

L. Degli Esposti,¹ C. Cerra,² C. Veronesi¹ and F.V. Costa³

1 CliCon S.r.l. Health, Economics & Outcomes Research, Ravenna, Italy; 2 Dipartimento Programmazione, Acquisto e Controllo, ASL di Pavia, Pavia, Italy; 3 Università di Bologna, Bologna, Italy

Aim: To evaluate persistence with antihypertensive treatment in newly treated patients at the Local Health Unit (LHU) of Pavia from 01/01/2003 to 31/12/2006.

Methods: Administrative databases were used. The retrospective analysis evaluated all subjects with at least one prescription refill (n. 57 051) of antihypertensive drugs: diuretics (D) (n. 8647), beta-blockers (BB) (n. 9678), calcium channel-blockers (CCB) (n. 7153), ACE inhibitors (ACE-I) (n. 19 819), angiotensin II antagonists (ARB) (n. 10 197), or others (n. 1557). All evaluated patients had a 12-months follow-up period starting from the date of first prescription refill. ‘Persistent’ patients were defined those with at least one antihypertensive prescription refill during the last 3 months of observation and a mean daily dose equal or higher than 80% of the defined daily dose. All evaluated patients were defined as diabetics, hypercholesterolemics and ‘cardiopathics’ according to antidiabetic, lipid-lowering or ‘cardiac’ therapy prescription refills. The mean age was 56.6 ± 15 years and male percentage was 45.1%. Persistence at 1 year was very low, lowest with D and highest with ARB.

Results: The main findings of our study are shown in the table. Not-persistence risk, compared to ARBs (RR = 1.00), was 1.5 for ACE-I, 1.88 for CCB, 3.64 for BB, 3.69 for others and 7.71 for D. Higher age (61.8 ± 12.6 vs 57.4 ± 16.5), higher diabetes prevalence (7.7 vs 4.2%) and dyslipidemia (6.0 vs 4.6%) was observed in persistent patients compared to not persistent patients.

12.4 Blood Pressure Lowering Efficacy of ‘Fast Walking’ Physical Training Programme in Treated Hypertensive Patients

D. di Raimondo, A. Tuttolomondo, S. La Placa, S. Miceli, G. Milio, R. Di Sciacca, G. Licata and A. Pinto

Policlinico, Palermo, Italy

Introduction: Hypertension is one of the most important risk factors for cardiovascular disease and ischemic stroke. Several studies have demonstrated that physical exercise reduces blood pressure (BP) levels in hypertensive subjects and improves controls of several well-known risk factors for atherosclerosis such as diabetes mellitus, blood lipid profile and obesity.

Aim: To evaluate if an exercise program based on periodic controlled fast walking sessions would reduce blood pressure levels in hypertensive subjects already in therapy with antihypertensive drugs, evaluating BP variations through 24 hour ambulatory blood pressure monitoring (ABPM).

Methods: 189 hypertensive subjects were enrolled (101 men and 88 women, mean age 55.7 ± 10.8 years) already under pharmacological therapy, not suffering from obesity (Body Mass Index <30) and without any pathological condition resulting in reduced mobility. A main inclusion criterion was the evidence of stage I hypertension, according to the Guidelines for Hypertension Treatment of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC), as an average value obtained with a 24-hour ABPM performed on admission. These subjects underwent to a six weeks program of exercise, based on fast walking, supervised by experienced physiotherapists. The walking velocity was set on the “self-selected” speed, that is the walking speed considered comfortable for every subject, added to a mean of 40%, to obtain a value comparable to fast walking for every subject. 168 patients of 189 completed the training period.

Results: Mean 24h systolic blood pressure (SBP) changed from 143.1 to 135.5 mmHg (p < 0.001), mean 24h diastolic blood pressure (DBP) changed from 91.1 to 84.8 mmHg (p < 0.001). Statistically significance reductions were evident also in everyone of the three periods in which daytime was divided. No differences were found in BP values during sleep between baseline and after exercise. No differences were found on mean values of heart rate.

Conclusions: This significant reduction of SBP and DBP, yet evident after a short period of exercise therapy, evaluated with ABPM, confirms that physical exercise should be a main element in lifestyle changes for the management of hypertension both in untreated hypertensive patients or high-risk subjects for hypertension, and also in hypertensive patients in association with pharmacological therapy, especially when blood pressure targets are not reached. In our study, further, ABPM confirms its major role in providing useful information regarding therapeutic follow-up of hypertensive subjects.

12.5 Blood Pressure Lowering Efficacy of ‘Fast Walking’ Physical Training Programme and Nocturnal Blood Pressure Profile in Treated Hypertensive Patients

D. di Raimondo, A. Tuttolomondo, R. di Sciacca, G. Milio, S. Miceli, R. Di Sciacca, G. Licata and A. Pinto

Policlinico, Palermo, Italy

Introduction: Walking is a very acceptable form of aerobic exercise. Several trials have demonstrated significant benefits of fast walking on the risk factors of cardiovascular disease, particularly for hypertension. Importance of circadian rhythm of blood pressure (BP) in the management of hypertension is well established. In our knowledge only a few studies have assessed the response of hypertensive subjects to regular physical exercise in relation to the nocturnal dip of BP, and none of these has used fast walking protocols in addiction to antihypertensive therapy.

Aim: To assess whether physical activity obtained through fast walking might lead to a different reduction of BP levels in hypertensive patients in relation to different circadian profile of BP.

Methods: We have enrolled 84 hypertensive patients, with evidence of stage I hypertension and presence of non-dipper nocturnal profile as an average value obtained by two 24-hour ABPM performed at time of admission and after three weeks. All subjects underwent a six weeks physical intervention based on fast walking, three sessions a week. Data obtained have been compared with other collected by our group in a similar analysis already performed in dipper subjects. The two groups resulted matched for age, sex, BMI, mean BP diurnal values before becoming of physical exercise program, antihypertensive therapy.

Results: The dipper vs non-dipper analysis shows that there is a significant lower response of non-dipper in both SBP (135.5 ± 6.4 vs 141.0 ± 4.4) and DBP (84.8 ± 8.2 vs 90.1 ± 2.5) 24-hour data. The lower response of non-dipper hypertensive to exercise therapy can also be seen comparing ABPM data obtained during the three period of day-time. No differences in heart rate have been found between the two groups before and after physical activity. Analyzing ABPM data related to nighttime, after exercise therapy is maintained the difference of BP values between the two groups yet evident on admission due to the different nocturnal profile: neither dipper nor non-dipper show a significant response of nocturnal BP do not resulting in a reduction of both SBP and DBP mean values. At intra-group analysis regarding non-dipper hypertensive patients no significant change was found in 24-hour SBP and DBP values.

Conclusions: In non-dipper hypertensive patients physical activity is less effective in provide a hypotensive effect if compared with dipper ones. This the consequence, probably, of the different pathophysiologic background on which exercise operate, first of all the level of the systemic vascular resistance, in which a difference degree of the sympathetic nervous system and of the renin-angiotensin system activity appear to be involved.

12.6 New Onset Diabetes Mellitus in Randomized Clinic Trials Performed with ACE Inhibitors or Angiotensin II Receptor Blockers: an Updated Meta-Analysis versus Placebo

G. Tocci,¹ A. Ferrucci,¹ G. Mancia² and M. Volpe¹

1 Università Sapienza, II Facoltà Medicina Chirurgia, Rome, Italy; 2 Università di Milan- Bicocca, Ospedale San Gerardo, Monza, Italy

Introduction: New onset diabetes mellitus (NOD) represents an adverse complication in the long-term treatment of cardiovascular (CV) disease, including hypertension, being related to a significant increase in CV morbidity and mortality. Retrospective analyses suggested that the use of drugs that counteract Renin-Angiotensin System (RAS) may significantly reduce NOD incidence. The recent results of TRANSCEND and PROFESS trials, however, have questioned this issue.

Aim: To evaluate the efficacy of ACE Inhibitors and Angiotensin II Receptor Blockers (ARBs) in term of NOD incidence in international, randomized, placebo-controlled clinic trials.

Methods: We performed a comprehensive meta-analysis of all available clinic trials performed with ACE Inhibitors (SOLVD, HOPE, PEACE e DREAM) or ARBs (CHARM, SCOPE, TRANSCEND, PROFESS), published within March 31 2009 (8 trials, n = 63.715 patients, mean age 65.7 ± 6.3 years), which reported NOD incidence, either as predefined CV endpoint or as drug-related adverse event, as compared to placebo in different clinic conditions.

Results: During a mean follow-up of 3.7 ± 0.9 years, we recorded 886/10 540 cases in the ACE Inhibitor group, 740/17 552 cases in the ARB group and 1875/22 880 cases in the placebo group. Antihypertensive therapy based on ACE Inhibitors reduced NOD incidence (OR 0.7288; 95% IC 0.5438, 0.9768), although this reduction did not achieve statistically significance; at the same time, antihypertensive strategy based on ARBs significantly reduced NOD incidence as compared to placebo (OR 0.8395; 95% IC 0.7573, 0.9306) in clinic trials performed in high risk patients, with or without heart failure. Overall, RAS blocking agents significantly reduced NOD incidence as compared to placebo (OR 0.8498; 95% IC 0.7917, 0.9122).

Conclusions: The clinic use of RAS blocking agents significantly reduced NOD incidence in placebo-controlled clinic trials in high risk patients, with or without heart failure.

12.7 New Onset Atrial Fibrillation in Randomized Clinic Trials Performed with ACE Inhibitors and Angiotensin II Receptor Blockers: an Updated Meta-Analysis

G. Tocci,¹ A. Ferrucci,¹ G. Mancia² and M. Volpe¹

1 Università Sapienza, II Facoltà Medicina Chirurgia, Rome, Italy; 2 Università di Milan- Bicocca, Ospedale San Gerardo, Monza, Italy

Introduction: Atrial fibrillation significantly increases the risk of developing major cardiovascular events, mostly stroke, in hypertensive patients and worsens prognosis in patients with cardiomyopathies or congestive heart failure. Thus, new onset atrial fibrillation (NOAF) represents an unfavourable complication in the long-term treatment of cardiovascular (CV) disease.Clinic trials and meta-analyses have suggested that the use of drugs that counteract Renin-Angiotensin System (RAS) may significantly reduce NOAF incidence.

Aim: To evaluate the efficacy of ACE Inhibitors and Angiotensin II Receptor Blockers (ARBs) in term of NOAF incidence in international, randomised, controlled clinic trials.

Methods: We performed a comprehensive meta-analysis of all available clinic trials performed with ACE Inhibitors (SOLVD, TRACE, CAPPP, STOP2, GISSI-3) or ARBs (Val-HeFT, LIFE, VALUE, OPTIMAAL, CHARM, ONTARGET, TRANSCEND, PROFESS, GISSI-AF), published within April 30 2009 (14 trials, n = 108.722 patients, mean age 66.1 ± 5.3 years), which reported absolute incidence of NOAF, either as predefined CV endpoint or as drug-related adverse event, as compared to placebo or other active treatment strategies in different clinic conditions.

Results: During a mean follow-up of 3.8 ± 1.5 years, we recorded 1014/8520 cases in the ACE Inhibitor group, 1966/29 945 cases in the ARB group and 3278/38 385 cases in the placebo group. In the presence of heterogeneity among selected clinic trials, antihypertensive therapy based on ACE Inhibitors (OR 0.8998; 95% CI 0.7439, 1.0884) or ARBs (OR 0.8820; 95% CI 0.7695, 1.0109) significantly reduced NOAF incidence. In particular, this beneficial effect of RAS blocking agents has been observed in patients with coronary artery disease (OR 0.8906; 95% CI 0.8056, 0.9845) or congestive heart failure (OR 0.7352; 95% CI 0.6299, 0.8580), and seems to be independent by the comparator strategy (placebo, conventional or active treatment). Overall, RAS blocking agents significantly reduced NOAF incidence (OR 0.8861; 95% CI 0.7980, 0.9840) as compared to any other treatment strategy, including placebo.

Conclusions: The clinic use of RAS blocking agents significantly reduced NOAF incidence in clinic trials performed in high risk patients in different clinic settings.

12.8 Effectiveness of Telmisartan in Hypertension and Organ Damage in Elderly People

G. Lombardo and F. D’Amico

UOC Geriatria PO Patti-AUSL n. 5 Messina, Patti-Messina, Italy

Aim: To evaluate the effectiveness of angiotensin II antagonist Telmisartan therapy on blood pressure and organ damage in elderly subjects.

Methods: We evaluated 47 elderly subjects (M 21, F 26, mean age 71 + 5) with mild-moderate hypertension. All subjects were administered a Telmisartan 80 mg monotherapy and were studied for 12 months. Those who still did not have controlled blood pressure after 4 weeks were also prescribed a 80 mg dose of Telmisartan or were associated Idroclorotiazide or Ramipril. Design of the study included before and after follow-up:

1. measurement of blood pressure;

2. ambulatory blood pressure measurement (ABPM);

3. colordoppler echocardiogram;

4. epiaortic colordoppler.

Blood pressure measurement resulted from average of 3 measurements taken at 5 minutes intervals and every four weeks. Left ventricular hypertrophy (LVH) was assessed through the following criteria: MVSI >125/110 gr/m²; MVS/h >51/47 gr/h 2.7. Thickness of intima-media carotid was assessed through IM >1.0 <1.3 mm. Prevalence of LVS was found in 73% subjects. In the same group the mean thickness of carotid wall was 2.4 + 1.4 mm.

Results: After 4 weeks:

1. 11 subjects maintained the same dose of 80 mg Telmisartan;

2. 14 subjects assumed a 160 mg dose of Telmisartan;

3. 13 subjects were associated Idroclorotiazide 12.5 mg;

4. 9 subjects were associated Ramipril 5 mg.

There were non significant differences between the two genders. Before and after the follow-up period subjects treated with Telmisartan showed:

1. blood pressure: SBP 163 + 21 vs 134 + 13 mmHg (p < 0.01); DBP 97 + 11 vs 89 + 12 mmHg (p < 0.01);

2. PP: 78.16 + 4 vs 62.9 + 3 mmHg (p < 0.05); (3) LVH: 73% vs 57% (p < 0.01); SPA 2.4 + 1.4 mm. vs 1.8+1.2 mm.

Patients treated with Telmisartan 160 mg. (p < 0.01) and Idroclorotiazide 12.5 mg showed a better control of BP also in the prevention of organ damage. Therapy was more effective during morning hours. No significant differences in BP values or organ damage were detected between the 2 genders.

Conclusions: Angiotensin II antagonist Telmisartan demonstrated to be a good effectiveness on hypertension in elderly subjects and is able to check the evolution of cardiovascular organ damage. Patients administered a 160 mg Telmisartan combined to Idroclorotiazide 12.5 mg therapy showed better clinic results.

12.9 Follow-Up of Obese Hypertensive Patients: a Better Blood Pressure Control is Possible Independently of Weight Loss

R. Sarzani, F. Salvi, E. Espinosa, O. Zingaretti, L. Mancinelli, F. Guerra, L. Lancioni, E. Giannini, M. Fortunati, A. Giovagnoli, I. Battistoni, E. Nicolini, L. Roberti, P. Dessì-Fulgheri and A. Rappelli

Clinica di Medicina Interna, Univ. Politec. Marche, Ancona, Italy

Introduction: Obesity-related hypertension is an increasing common phenotype due to interaction between genetic predisposition and unhealthy lifestyle. Obese hypertensive patients frequently have a resistant form of hypertension, due to both difficulty in losing weight and inadequate therapeutic approach. In this field, a clinic follow-up may be useful in improving blood pressure (BP) control and understanding underlying clinic factors.

Methods: One hundred thirty nine patients aged less than 65 years with essential hypertension and body mass index (BMI) ≥25 kg/m² underwent basal examination and follow-up visit after 6–12 months. Anthropometric parameters [height, weight, BMI, and waist circumference], BP, labs (renal function, albuminuria, lipids profile; plasma renin and aldosterone), anti-hypertensive therapy (as therapy index and number of drug classes) were evaluated.

Results: Systolic BP fell from 145.8 ± 18.5 to 140.2 ± 17.8 mmHg (p = 0.001) and diastolic BP from 90.3 ± 12.1 to 87.8 ± 10.3 mmHg (p = 0.037), despite substantially unchanged BMI (p = 0.091) but in line with increased therapy (therapy index from 1.22 ± 0.94 to 1.67 ± 0.97; number of drug classes from 1.63 ± 1.19 to 2.08 ± 1.04). The percentage of subjects obtaining BP control (defined as BP <140/90 mmHg) raised from 24% to 31.7% at follow-up. It was easier to obtain BP control in overweight (51.4%) than obese patients (27.4%), although subjects who became controlled doubled among overweight and triplicate among obese patients. Indeed, anti-hypertensive therapy was increased more consistently in obese than overweight subjects (D therapy index 0.57 ± 1 vs 0.18 ± 0.73, p = 0.01; D drug classes 0.58 ± 1.2 vs 0.17 ± 0.91, p = 0.027).

Conclusions: In a non-elderly overweight/obese hypertensive population BP control appears strictly related to obesity degree but also to an appropriate therapeutic approach aimed to increase dosage and number of prescribed anti-hypertensive drugs. Actually, a better BP control is possible independently of weight loss. In this field, clinic follow-up of these kinds of patients in a Hypertension Center could be an useful strategy to improve BP control.

12.10 Treatment of Primary Aldosteronism: Short- and Middle-Term Effects of Medical and Surgical Therapy in Primary Hyperaldosteronism: Experience on 45 Cases

M.V. Cicala,¹ Maurizio Cesari,² Anna Patalano,¹ Maurizio Iacobone,³ Barbara Mariniello¹ and Franco Mantero¹

1 UO Endocrinologia, Dipartimenti di Scienze Mediche e Chirurgiche, Università degli Studi di Padova, Padova, Italy; 2 Dipartimento di Medicina Clinica e Sperimentale, Padova, Italy; 3 Unità di Endocrinochirurgia, Padova, Italy

Introduction: Primary Hyperaldosteronism (PA), the most common causes of secondary hypertension, may be associated with hypokalemia, cardiac and renal damage. Laparoscopic adrenalectomy is recommended in unilateral PA (APA or UHA), while medical treatment based on mineralocorticoid receptor antagonists (MRA) is indicated in patients with bilateral adrenal (idiopathic adrenal hyperplasia, bilateral APA, GRA) or those unable or unwilling to undergo surgery. MRA treatment appears to be effective for blood pressure lowering and seem to provide blood-independent target organ protection. The most used drugs are Spironolactone, Potassium nate or Canrenone, Eplerenone or less frequently Amiloride. We present here our recent experience in patients with PA.

Aim: To evaluate short and middle-term effects of medical and surgical treatment hypertensive state, hormonal parameters and cardiac function in 45 patients with PA referred to tre between 2005 and 2008.

Methods: In all patients after confirmation of PA, ECG and radiography were performed at baseline and after treatment with adrenalectomy (n = 22 or n = 23) every 12 months with a median follow-up of 36 months.

Results: At baseline 82% ed moderate or severe hypertension, 66% hypokalemia, 15.5% renal damage with buminuria and 22% presented atrial fibrillation. Echocardiography measurement shows left ventricular hypertrophy in 69% of patients, 93% with concentric geometry; 40% presents reduced c function and 4% reduced systolic function. After treatment both groups presented various s of blood pressure reduction (60% normalization after adrenalectomy, 82% on medical nt) and 100% normokaliemia. In adrenalectomized patients there was a significant reduction ma aldosterone concentration (PAC) and normalization of ARR ratio. In medically treated s we observed significant normalization of plasma renin activity (PRA) and consequently zation of ARR. In both there was a significant reduction of LVMI, greater in the 1 year in adrenalectomized patients, subsequently greater in medically treated patients. A ant reduction of RWT was seen only in adrenalectomized patients. Prevalence of ophy decreased in both treated groups, whereas diastolic parameters had only mild and no ant improvement. Changes of LVMI were significantly correlated with changes in diastolic pressure in both and with PAC reduction only in adrenalectomized patients.

Conclusions: In the short-middle term, both adrenalectomy and treatment with MRA are effective in zation of plasma potassium, reduction of BP, ARR and left ventricular mass in patients with ile they are less effective in improving systolic and diastolic function.

12.11 Age-Related Response to Antihypertensive Drug Therapy

F. Rabbia, G. Leotta, E. Testa, S. Totaro, D. Tizzani, E. Avenatti, S. Abram, V. Milazzo and F. Veglio

Dipartimento di Medicina e Oncologia Sperimentale-Cattedra di Medicina Interna-Centro Ipertensione, Torino, Italy

Introduction: Some authors suggest that antihypertensive treatment can be performed by choosing the best drug for each patient according to his age and race, so by giving to Caucasian and younger people drugs that inhibit the renin-angiotensin-aldosterone system (R type) and to older and black population drugs that reduce body sodium and water content (V type). However, a recent meta-analysis by Blood Pressure Lowering Treatment Trialists’ Collaboration doesn’t confirm this drugs classification.

Aim: In our study we examined hypertensive Caucasian patients belonging to our Clinic, investigating if the age factor could influence the antihypertensive drugs efficacy in reducing the blood pressure (BP) values.

Methods: The study was carried out on 846 patients (400 females) analyzing the data from two consecutive visits, which took place in the time span of 30–180 days. Patients were divided according to their age (<50 or ≥50 years old) and to the pharmacological treatment received in their first visit (wash out or monotherapy). All patients included in this study were treated by a physician from the Clinic with only one antihypertensive drug.

Results: Patients who were younger than 50 and in wash out at their first visit tended to have a major percentage reduction in systolic and diastolic blood pressure values if given a R type drug (p = 0.01), once corrected the BMI and the basal blood pressure value. On the contrary, in older people (more than 50 years) V drugs were not related to high efficacy in lowering BP value. Similar results were shown in hypertensive patient not in wash out at their first visit, to whom physicians prescribed a different drug. At the same time, the percentage of patients younger than 50 achieving BP control was significantly higher in those treated with aR drug (42.1% vs 23.9%) and the rate of BP control doubled after correction of the BMI and the basal systolic and diastolic BP values.

Conclusions: Also in older people the BP control tended to be more frequent when they were treated with a R drug, even if not significantly. On the one hand, this study supports the idea that R drugs give better results in hypertensive patients younger than 50, which is in accordance with the recommendations of the British Hypertension Society Guidelines and the evidence collected from preview studies. On the other hand, our research doesn’t highlight a greater efficacy of V drugs in older people, aswas expected. Also in this patients, in fact, drugs that inhibit renin angiotensin system are more effective as first line agents.

Vessels and Endothelium

13.1 Intimal Medium Thickness, Fetuin A, Endothelial Activation and Oxidative Stress in Hypertensive Patients with Different Grade of Chronic Renal Failure

S. Cottone, M. Guarneri, R. Arsena, C. Geraci, R. Riccobene, F. Tornese, F. Incalcaterra, A. Previti and G. Cerasola

Università degli Studi di Palermo, Palermo, Italy

Introduction: Carotid intima-media thickness (IMT) is a target organ damage and predicts atherosclerotic disease in hypertensive patients. Fetuin A, a negative acute phase glycoprotein reactant, has been demonstrated to be reduced and related inversely to cardiovascular mortality in uremic patients.

Aim: To evaluate the relationship between IMT and the biomarkers of endothelial dysfunction (ET-1, ICAM-1, VCAM-1), inflammation (IL-6, Fetuin A), and of oxidative stress (8-Iso-PGF2a) involved in the development of atherosclerosis in hypertensive patients with different grade chronic renal failure.

Methods: In 120 hypertensive patients (HT) with stage 1–4 chronic kidney disease and in 50 healthy Controls we assessed IMT and plasma levels of Fetuin A, endothelin 1, ICAM-1, VCAM-1, IL-6, 8ISOPG were assayed. Subsequently, HT were divided on the basis of eGFR >90 mL/min/1.73 m².

Results: Overall HT showed significantly higher plasma levels of IL-6, ICAM- 1, VCAM-1, ET-1, 8isopg (p < 0.001 respectively) than Controls, whereas Fetuin A plasma levels were significantly lower (p < 0.001). In the univariate analysis, maximal IMT directly correlated with ET-1, VCAM-1, ICAM-1, 8-Iso-PGF2a, IL-6, (p < 0.001 respectively) and inversely with Fetuin-A (p < 0.001). Similar results were found in the subgroup of HT with eGFR >90 mL/min/1.73 m². The univariate analysis showed direct correlations of maximal IMT with ET-1, VCAM-1, ICAM-1, 8-Iso-PGF2a, IL-6, (p < 0.001 respectively) and an inverse correlation with Fetuin-A.(p < 0.01).

Conclusions: Our study showed that IMT is strictly related to endothelial activation, oxidative stress and inflammation in hypertensive patients with different stage of CKD. Fetuin A seems to be lower and inversely related to IMT even in hypertensive patients with normal renal function.

13.2 Relationship between Fetuin-A, Glomerular Filtration Rate and Endothelial Dysfunction in Hypertensive Patients with Moderate to Severe Chronic Kidney Disease

M. Guarneri, R. Arsena, R. Riccobene, F. Tornese, C. Altieri, C. Canale, G. Mulè, A. Palermo, A. Previti, G. Cerasola and S. Cottone

Università degli Studi di Palermo, Palermo, Italy

Introduction: In end-stage renal disease Fetuin-A has been demonstrated to be reduced and inversely related to cardiovascular mortality. This study had two distinct aims. The first was to verify if circulating concentration of Fetuin-A may depend on renal function in patients with chronic kidney disease (CKD). Furthermore, we analyzed the correlation of Fetuin-A with the biomarker of endothelial dysfunction Endothelin-1 (ET-1), and with the inflammatory cytokine Interleukin-6 (IL-6).

Methods: In 108 subjects with stage 3–5 CKD plasma levels of Fetuin-A, ET-1, and IL-6 were assayed. Patients were studied first in overall, then were divided according to stages of CKD and Fetuin-A tertiles.

Results: Fetuin-A concentration decreased in parallel with the increase in ET-1 and IL-6 levels as renal function declined. Multiple regression analysis showed that Fetuin-A was independently associated with estimated glomerular filtration rate (β = 0.386; p < 0.001), IL-6 (β = -0.393; p = 0.001) and ET-1 (β = -0.219; p = 0.02), in a multivariable model including also gender, parathyroid hormone and the calcium x phosphorus product.

Conclusions: These results seem to indicate that in CKD, even not severe, inflammatory processes are increased and linked to endothelial dysfunction, worsening progressively with the decline of renal function.

13.3 VEGF And MCP-1 Plasma Levels are Increased in Essential Hypertension

I. De Rome, R. Ria and G. Ranieri

DIMO- Sezione di Medicina Interna, Bari, Italy

Introduction: Several studies indicate that inflammation plays a pivotal role in the pathophysiology of essential hypertension. Vascular endothelial growth factor (VEGF) is currently discussed as a possible mediator of inflammation. VEGF is one of the most potent angiogenic factors known and is thought to function as a endogenous regulator of endothelial integrity. Animal studies have revealed that VEGF promotes endothelial regeneration and induces migration and activation of monocyte through induction of chemokines such as monocyte chemoattractant protein (MCP)-1. However, there is still a debate over the vascuoloprotective vs pro-inflammatory effect of VEGF.

Methods: We performed this study to investigate the hypothesis that VEGF and MCP-1 play a role as inflammatory mediators in essential hypertension. Twenty never treated patients with mild hypertension and 20 healthy controls were examined; serum levels of VEGF and MCP-1 were measured via commercially available enzyme linked immunoassay (R & D System).

Results: Hypertensive patients showed increased plasma levels of VEGF (p < 0.05) and MCP-1 (p < 0.05).VEGF positively correlated with mean arterial pressure/r = 0.48, p < 0.05); multivariate analysis demonstrated VEGF to be an independent predictors of MCP-1 levels.

Conclusions: This study suggests that in mild hypertension, inflammatory pathway have already been activated. We observed increased plasma levels of VEGF and MCP-1; stepwise multivariate analysis suggests that elevated VEGF levels contribute to the elevated MCP-1 levels. In conclusion, the present study seems to suggest new insights into the pathophysiological mechanisms in essential hypertension linking inflammation and abnormal angiogenesis.

13.4 Small Arteries from Visceral Fat of Obese Patients are Characterized by a Reduced Nitric Oxide Availability due to Oxidative Stress: Role of Inflammation

A. Virdis,¹ E. Daghini,¹ D. Versari,¹ F. Santini,¹ G. Salvetti,¹ M. Anselmino,² E. Duranti,¹ A. Pinchera,¹ S. Taddei¹ and A. Salvetti¹

1 Università di Pisa, Pisa, Italy; 2 Azienda Ospedaliera Universitaria Pisana, Pisa, Italy

Introduction: Visceral obesity has been associated with impaired endothelium-dependent vasodilation (VD) in peripheral conduit arteries and forearm microcirculation, an alteration never documented in visceral fat small arteries. Moreover, a cross-talk between inflammatory cytokines and nitric oxide (NO) has been described, but whether this relationship is also detectable at the level of visceral small vessels is still unknown. Therefore, we assessed the NO-derived endothelium-dependent VD in small resistance arteries taken from the visceral fat of patients with severe obesity (Ob) and non obese controls (Ctrl).

Methods: 8 Ob patients (age 38.4 ± 14, BMI: 46.1 ± 6.7, waist to hip ratio (WHR) 0.98 ± 0.08) and 8 Ctrl (age 43.2 ± 6, BMI: 24.9 ± 2, WHR: 0.93 ± 0.03) were investigated. Each subject underwent a biopsy of the visceral fat during a surgical laparoscopic procedure. Small arteries were dissected and investigated on a pressurized micromyograph. Endothelium-dependent VD was assessed by acetylcholine (ACh, 0.001–100 μM)-induced relaxation. NO availability and reactive oxygen species (ROS) production were assessed by repeating Ach in the presence of the endothelial NO synthase inhibitor L-NAME (100 μM) or the superoxide dismutase mimetic tempol (1 mM), respectively. Inflammation was investigated by testing ACh under infliximab (100 μM), a monoclonal anti-TNF antibody.

Results: All individuals had normal lipid and glucose plasma values and normal blood pressure levels. Ob showed higher (p < 0.05) plasma levels of inflammatory cytokines as compared to Ctrl (TNF-α, 14.7 ± 6.2 vs 8.6 ± 6.5 pg/mL; IL-6, 8.8±4.4 vs 2.4 ± 3.8 pg/mL). In Ctrl, maximal VD to ACh (96.1 ± 0.7%) was blunted by L-NAME (57.9 ± 3.8%; inhibitory effect: 39 ± 4.7%; p < 0.001), and unmodified by tempol (97.3 ± 0.6%) or by infliximab (97.1 ± 0.6%). In Ob, VD to ACh was blunted (59.4 ± 2.1%; p< 0.001 vs Ctrl), less sensitive to L-NAME (51.6 ± 2.9%; 7.8 ± 1.4% inhibition; p < 0.001 vs Ctrl), and normalized by tempol (95.9 ± 1.4%; p< 0.001) or infliximab (96.6 ± 1.6%; p < 0.001). In Ob, under tempol administration, the inhibitory effect of L-NAME on Ach was restored (59.2 ± 1.6%; 36.1 ± 3.2% inhibition; p < 0.001 vs L-NAME + ACh alone). Similarly, during infliximab co-infusion the inhibition of L-NAME on ACh was restored (60.1 ± 2.1%; 36.5 ± 3.1% inhibition; p < 0.001 vs L-NAME + ACh alone). Response to sodium nitroprusside was similar in both groups.

Conclusions: Small resistance vessels from visceral fat of obese patients are characterized by a reduced NO availability due to ROS excess. Vascular inflammation greatly affects endothelial function, probably by modulating ROS production.

13.5 Prevalence of Primary Aldosteronism in Resistant Hypertension and its Association with Early Vascular Damage

E. Capello, L. Marafetti, B. Lucatello, A. Benso, E. Ghigo and M. Maccario

1 S.C.D.U. Endocrinologia, Torino, Italy

Introduction: Preliminary data of the Literature suggest that the prevalence of primary aldosteronism (PAL), 5–10% in hypertensive subjects, is even higher than in subjects affected by resistant hypertension (lack of pressure normalization during therapy with three full-dose drugs, included a diuretic). Moreover, although aldosterone is recognized to have an important role in the pathogenesis of the cardiovascular damage, few controlled clinic trials have addressed this topic.

Aim: To determine the prevalence of PAL in patients with resistant hypertension, admitted in our Hypertension Unit, and define the possible association with early cardiovascular damage.

Methods: Here we report the data on the first 57 patient recruited. Cardiovascular risk and indexes of early vascular damage (microalbuminuria and intima-media thickness of common carotid arteries) were assessed being blind for the ultimate diagnosis of PAL (plasma aldosterone (pg/mL)/PRA (ng/mL/h) ratio >400 AND plasma aldosterone >200 basally AND >100 pg/mL after acute NaCl infusion) performed after adequate pharmacological wash-out).

Results: PAL was diagnosed in 20 out of 57 subjects (35.1%, aged 55.1 ± 12.6), the remaining 37 were considered affected by essential hypertension (EI, 64.9%, aged 57.4 ± 9.5). Further diagnostic investigation (adrenal CT and selected sampling from adrenal veins) was considered in patients with PAL, aiming to differentiate subtypes: histological diagnosis of aldosterone-producing adenoma was obtained in 4 out of 20 subjects with PAL. The two groups did not differ for BMI, smoking habit, glycemia, LDL cholesterol, HDL cholesterol, and triglyceride levels, family history of hypertension, diabetes mellitus, premature CHD. Arterial pressure levels did not differ in the two groups (PAL vs. EI: SBP 175.0 ± 24.8 vs. 169.9 ± 23.7 mmHg; DBP 104.5 ± 10.9 vs. 98.0 ± 11.7 mmHg). 10 out of 20 patients with PAL (50%) and 2 out of 37 (5.4%) patients with EI showed hypokalemia (< 3.5 mEq/l). Potassium levels were significantly lower in PAL (3.5 ± 0.5 vs. 4.0 ± 0.5 mEq/L, p = 0.0005).The presence of microalbuminuria was statistically more frequent in the group with PAL (52.6% vs. 21%, p = 0.02); furthermore we found an intima-media thickness >0.9 mm more often in subjects with PAL (43.7% vs 20.7%), although this data was not statistically significant (p = 0.09).

Conclusions: The results of the present study suggest that primary aldosteronism is very frequent in the hypertensive subjects resistant to the pharmacological therapy. Resistant hypertensive patients with primary aldosteronism are more often connoted with early vascular damage than resistant hypertensive patients with normal mineralcorticoid function.

13.6 Allopurinol Improves Endothelial Resistance to Oxidative Stress in Patients with Peripheral Arterial Disease

S. De Marchi,¹ A. Rigoni,¹ M. Prior,¹ D. Bianchini,¹ P. Delva² and E. Arosio¹

1 UO Riabilitazione Vascolare-Università di Verona, Verona, Italy; 2 Medicina Interna C-Università di Verona, Verona, Italy

Introduction: Xanthine oxidase is one of the main enzymatic systems producing reactive oxygen species during ischemia-reperfusion; this phenomenon in our protocol is produced by walking exercise on treadmill till the onset of ischemic pain.

Aim: To observe if xanthine oxidase inhibition can prevent endothelial dysfunction induced by maximal exercise in patients affected with intermittent claudication or peripheral artery disease (PAD).

Methods: 14 patients with PAD with uric acid in normal range and ankle-brachial index between 0.62 and 0.81 underwent endothelial dependent dilation measurements at the brachial artery (EDD) and flux measurement of the femoral artery in the worse leg before and after maximal exercise on treadmill (speed 3.2 km/h; slope 10%). Allopurinol 600 mg was administered after the treadmill test and 600 mg the day after, 6 hours before the second treadmill test. Lactate was dosed to confirm the patients reached anaerobic phase.

Results: Maximal treadmill acutely reduced EDD (0.406 ± 0.06 vs 0.442 ± 0.06 cm; p < 0.005). Allopurinol improved EDD at rest (12.1 ± 2.3 vs 7.3 ± 1.2%; p< 0.05) and counteracted the reduction of EDD after maximal treadmill test (−0.92 ± 0.14 vs −2.5 ± 0.23%; p< 0.05). Femoral artery flux increased after base exercise (0.702 ± 0.012 vs 0.675 ± 0.102 L/min; p < 0.05); a further increment in femoral artery flux after exercise was measured during treatment with allopurinol (0.714 ± 0.011 vs 0.702 ± 0.012 L/min; p < 0.05). Absolute walking distance after treatment increased (342 ± 101 vs 228 ± 98 m; p < 0.05). Uric acid was normal at baseline and reduced after treatment (3.55 ± 1.22 vs 5.34 ± 0.66 mg/dL; p < 0.005). Lactate increased after treadmill test, before and after allopurinol (baseline: 3.5 ± 0.8 vs 1.3 ± 0.3 mmol/L; p < 0.05—allopurinol: 3.4 ± 1.1 vs 1.5 ± 0.5 mmol/L; p < 0.05).

Conclusions: Maximal treadmill test in PAD patients causes acutely endothelial dysfunction, it can be partially counteracted by administration of allopurinol. This drug can reduce the generation of reactive oxygen species through inhibition of xanthine oxidase, as a consequence it improves EDD. Furthermore our study shows that allopurinol can increase femoral flux during exercise and walking distance; these effect cannot be attributed to reduction of uric acid. In conclusion our study demonstrates that xanthine oxidase increases oxidative stress during maximal claudication and its inhibition improves peripheral haemodynamics, endothelial dysfunction and relieves symptoms.

13.7 Angiotensin II-Induced AT1 Receptor Stimulation Increases Transglutaminase 2 Expression in Rat Vascular Smooth Muscle Cells

C. Savoia,¹ T. Ebrahimian,² A. Alonzo,¹ C. Rossi,¹ V. Capuano,¹ E.L. Schiffrin² and M. Volpe¹

1 Sapeienza Università di Rome, II Facoltà Medicina, Rome, Italy; 2 Lady Davis Institute for Medical Research, SMBD-Jewish General Hospital, McGill University, Montreal, Canada

Introduction: Transglutaminase 2 (TG2) is a multifunctional protein that is ubiquitously expressed and induces transamidation and cross-linking among proteins. This process has an important impact on cell-matrix interactions and vascular remodeling which is modulated by activation of the renin-angiotensin system.

Aim: Here we hypothesized that angiotensin II (Ang II) through the angiotensin type 1 receptor (AT1R) differentially induces TG2 expression in vascular smooth muscle cells (VSMCs) from normotensive and hypertensive rats.

Methods: Mesenteric artery-derived VSMCs from Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats were studied. Cells were stimulated with Ang II (10–7 M) ± the AT1R blocker valsartan (Val 10–5 M). TG2 expression was evaluated by immunoblotting.

Results: Basal TG2 expression in SHR VSMCs was significantly higher compared to basal TG2 expression in WKY VSMCs (133.1 ± 14 vs 99.75 ± 0.25 respectively, p < 0.05). Ang II significantly increased TG2 expression in both WKY and SHR VSMCs compared to control (+19 ± 15% and +60 ± 25% respectively, p < 0.05). Ang II-induced TG2 expression in SHR VSMCs was moderately elevated with respect to WKY VSMCs (+36 ± 25%, NS). Val significantly reduced Ang II-induced TG2 expression in both WKY and SHR VSMCs.

Conclusions: Our findings suggest that Ang II positively regulates TG2 expression in rat VSMCs via AT1R. This effect is particularly evident in SHR VSMCs which presented high basal TG2 expression levels.

13.8 Relationship Between 24-Hour Arterial Pressure and Retinal Vascular Diameters

F. Brasca, C. Vecchiato, A. Solbiati, C. Gianni,G. Ponticelli, F. Giofrè, P. Broglia and F. Magrini

Centro Ipertensione-Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy

Aim: To evaluate the relationship between 24-hour arterial pressure and retinal microcirculation vascular diameters.

Methods: We carried out a cross-sectional study on a cohort of 107 hypertensive patients who were tested the same day with a fundus oculi photograph (through a non-mydriatic retinography, Topcon TRC-NW200) and a 24-hour ambulatory blood pressure monitoring (via met model 90207 Spacelabs ABPM). We excluded from the study patients with a known ophthalmopathy or grade III and IV hypertensive retinopathy. We performed a static analysis of retinal vessels with VesselMap II V.3.00, while blood pressure analysis with Spacelabs Medical software v 2.00. The data were statistically analyzed with SPSS software v. Statistics 17.0. We considered auxological parameters, 24-hour systolic blood pressure, diastolic and mean blood pressure (SBP, DBP and MBP respectively), central retinal artery equivalents (CRAE), central retinal vein equivalents (CRVE) and arteriolar-venular ratio (AVR).

Results: Our cohort of 107 patients comprised 63 men and 44 women (mean age 50 ± 13 years) with hypertension known since 5.5 ± 6.2 years. We found a statistically significant correlation between CRAE indexed to body surface area and values of 24-hour SBP (R2-0056 p = 0.015), DBP (R2 −0108 p = 0.001) and MBP(R2 −0084 p = 0.003) and between indexed CRVE and 24-hour SBP (R2 −0045 p = 0.03), DbP (R2 −0065 p = 0.009) and MBP (R2 = −0043 p 0033) of 24 hours. On the contrary, we couldn’t identify a significant correlation between blood pressure monitoring parameters and AVR.

Conclusions: There is an inverse relationship between systemic blood pressure and retinal vascular diameter (both arteriolare and venular) expressed by indexed CRAE and CRVE. This relation is more significant if we consider the relation between CRAE and DBP. According to these data, we can hypothesize the presence of an active vasoconstriction in the retinal microcirculation significantly related to the patient’s blood pressure. Only further studies will clarify if this relationship depends on self-regulation of retinal circulation or other mechanisms.

13.9 Endothelial Dysfunction Evaluation by Sub- and Supra- Anaerobic Threshold (AT) VO2 Kinetics in Constant Load Exercises

D. Maione, S. Bacchelli, E. Cosentino, S. D’Addato, D. Degli Esposti, F. Santi, E. Rinaldi, M. Rosticci, E. Ambrosioni and C. Borghi on behalf of Medicina Interna Università di Bologna Bologna Italy

Medicina Interna Università di Bologna, Bologna, Italy

Introduction: In constant load exercise sub-AT (in previous incremental test detected) VO₂ reaches steady-state describing exponential curve and its time constant (ô) measures the speed. Ô correlates with blood flow rapidity and entity in the active muscles microcircle at the beginning of exercise. Since this flow is in the endothelial function domain, ô reflects the endothelial function efficacy or dysfunction level. Physical training and/or cardiovascular therapy speed ô , which is load dependent, as we previously showed. Consequently, ô is often normal in young subjects, in trained ones, in mild dysfunction, or for therapy effects. On the other hand, in constant load exercise supra-AT, but sub 2nd ventilatory threshold, VO₂ kinetics are more complex because of another superimposition over the previous, which begins later and increases more slowly, named slow component (sc).

Methods: We measure the sc slope, like ô , and area between two exponentials, either in domain of endothelial function and reduced by physical training and therapy.

Results: Pathological increments in ô , sub and supra-AT directly correlate with hypertension during incremental test.

Conclusions: Both methods can be used in primordial prevention, before organ damage detected by echoDoppler technique, in drug effects on endothelial function, and in the physical training evaluation.

13.10 Changes in Arterial Properties during Acute Exposure to Hypobaric Hypoxia at High and Very High Altitude: the HIGHCARE2008 Project

M. Revera,¹ A. Giuliano,¹ F. Gregorini,¹ G. Bilo,¹ A. Faini,¹ S. Gautier,² E. Pretolani,³ P. Salvi,² A. Benetos,² C. Lombardi,¹ G. Caldara,⁴ A. Giglio,¹ G. Mancia¹ and G. Parati¹

1 Univ. Milano-Bicocca, Ist. Auxologico It IRCCS, Milan, Italy; 2 Dipartimento Medicina Interna e Geriatria-Università di Nancy, Nancy, France; 3 Ospedale Bufalini, Cesena, Italy; 4 Istituto Auxologico Italiano, Milan, Italy

Introduction: Exposure to hypobaric hypoxia at high altitude (HA) is responsible for complex changes in cardiovascular regulation, yet only partly explored. In particular little is known on the effects of this condition on arterial properties.

Aim: To assess the arterial properties of a group of healthy volunteers investigated both at sea level(SL) and during acute exposure to hypobaric hypoxia.

Methods: In 29 healthy normotensive volunteers (mean age 37.9 ± 8 years, 21 male), participating in a scientific expedition in the Himalayas, we performed a tonometric evaluation of arterial properties (PulsePen — DiaTecne) by assessing carotid-femoral pulse wave velocity (CF-PWV) and augmentation index (AIx) in the following conditions: (1) at SL; (2) during acute (1–3 days) exposure to HA (3500 m, HA1) and (3) during acute (1–3 days) exposure to very HA (>5000 m, HA2). AIx was corrected for heart rate (HR) = 75 beats/min (AIx75). Systolic and diastolic arterial pressure were measured by a validated oscillometric device (AND UA 767-PC). Mean arterial pressure (MAP) was calculated by PulsePen software. HR was derived from an ECG signal.

Results: Recorded parameters are shown in the table. After adjusting for changes in MAP the differences between HA2 and SL in CF-PWV and AIx75 remained significant.

Conclusions: This is the first demonstration that exposure to hypobaric hypoxia at HA induces an increase in CF-PWV and AIx, with a progressive increase from SL to High and to Very High altitude, indicating a progressive increase in arterial stiffness. The mechanisms behind these changes may include an increased adrenergic drive and elevation in total peripheral resistance accompanying an increase in the levels of plasma catecholamines, endothelin-1 and other vaso-constricting agents.

13.11 Changes in Arterial Properties during Prolonged Exposure to Hypobaric Hypoxia at Very High Altitude: the HIGHCARE2008 Project

M. Revera,¹ A. Giuliano,¹ F. Gregorini,¹ G. Bilo,¹ A. Faini,¹ G. Caldara,² C. Lombardi,¹ A. Giglio,¹ P. Salvi,³ G. Mancia¹ and G. Parati¹

1 Univ. Milano-Bicocca, Ist. Auxologico It IRCCS, Milan, Italy; 2 Istituto Auxologico Italiano, Milan, Italy; 3 Dipartimento Medicina Interna e Geriatria-Università di Nancy, Nancy, France

Introduction: Prolonged exposure to hypobaric hypoxia at very high altitude (HA) is responsible for complex and yet partly understood changes in cardiovascular parameters, including arterial properties.

Aim: To assess the arterial properties of a group of healthy volunteers both at sea level (SL) and repeatedly during prolonged exposure to hypobaric hypoxia at very high altitude.

Methods: In 20 healthy normotensive volunteers (mean age 37.6 ± 8.1 years, 13 male), participating in a scientific expedition in the Himalayas, we performed a tonometric evaluation of arterial properties (PulsePen — DiaTecne) by assessing carotid-femoral pulse wave velocity (CF-PWV), and augmentation index (AIx). This was done:

1. at SL;

2. 1–3 days after ascent to Everest Base Camp at 5400 m (BC1);

3. after 7–9 days’ permanence at BC (BC2);

4. within 5 days after return to SL (SLret).

AIx was normalized for heart rate(HR) = 75 beats/min (AIx75). Systolic and diastolic arterial pressure were measured by a validated oscillometric device (AND UA 767-PC); Mean arterial pressure (MAP) was calculated by PulsePen software. HR was derived from an ECG.

Results: Main results are shown in the table. After adjusting for changes in MAP, CF-PWV remained significantly higher at BC1 and BC2 than at SL, while AIx75 remained elevated only at BC1.

Conclusions: Carotid-femoral PWV and AIx75 increase acutely under hypobaric hypoxia at altitude and return almost completely to baseline values after return to SL. After several days permanence at very high altitude CF-PWV remained elevated, while AIx75 returned to SL values. Our results thus suggest that while arterial stiffness remains elevated under prolonged exposure to hypoxia at very high altitude, the concomitant reduction in AIx may reflect an adaptive response in terms of peripheral resistances. These data may be relevant to the management of patients with diseases associated with chronic hypoxemia.

13.12 Structural Alterations of Resistance-Sized Arteries Predict Long-Term Changes of the Renal Function in Hypertensive Patients

G.E.M. Boari,¹ D. Rizzoni,¹ E. Porteri,¹ C. De Ciuceis,¹ A. Brignani,² N. Rizzardi,¹ C. Platto,¹ C. Agabiti Rosei,¹ D. Avanzi,¹ M. Mazza,¹ L. Caimi² and E. Agabiti Rosei¹

1 Cattedra di Clinica Medica-Università di Brescia, Brescia, Italy; 2 Cattedra di Biochimica Clinica-Università di Brescia, Brescia, Italy

Introduction: We have previously demonstrated that structural alteration of subcutaneous small resistance arteries of hypertensive patients, as indicated by an increased media to lumen (M/L) ratio, has a strong prognostic significance. Among the predictors of M/L indicators of renal function are those more closely correlated.

Aim: To assess whether M/L ratio can predict subsequent changes in renal function in hypertensive patients.

Methods: Sixty patients (33 males; 27 females; 15 normotensives and 45 hypertensive patients) underwent a biopsy of subcutaneous fat at a mean age of 56 years. Resistance-sized arteries were dissected and mounted on a wire myograph according to Mulvany-Halpern technique, and M/L was measured. Patients were re-evaluated after a mean time period of 8.5 years; serum creatinine, blood urinary nitrogen (BUN) and uric acid were measured, and glomerular filtration rate (GFR) was calculated according to MDRD formula.

Results: At baseline, we observed significant correlations between M/L and serum creatinine (r = 0.32; p = 0.013), GFR (r = −0.26; p = 0.047), BUN (r = 0.37; p = 0.009), systolic (r = 0.45, p < 0.001), diastolic (r = 0.29, p = 0.02), mean blood pressure (r = 0.38, p = 0.002) and pulse pressure (r = 0.40, p = 0.002). In addition, we observed significant correlations between M/L and creatinine at follow up (r = 0.57; p < 0.001), percentage changes in serum creatinine (r = 0.46; p < 0.001), GFR at follow up (r = −0.43; p < 0.001); percentage changes in GFR (as ml/min r = −0.33; p = 0.008), as well as yearly changes (r = −0.34, p = 0.007), BUN at follow up, (r = 0.55; p < 0.001), as well as uric acid at follow up (r = 0.35; p = 0.026). A multivariate analysis in which all common cardiovascular risk factors were included, showed that M/L is the most potent predictor of changes in renal function.

Conclusions: Our data suggest that structural alterations of subcutaneous small resistance arteries (which may be present also in other vascular beds), may predict the time-course of changes of renal function during a follow-up period of about 9 years.

13.13 Effects of Telmisartan, Ramipril or their Combination on Subcutaneous Small Resistance Arteries Structure

E. Porteri, D. Rizzoni, M.L. Muiesan, M. Salvetti, E. Belotti, C. De Ciuceis, G.E.M. Boari, N. Rizzardi, C. Platto, S. Paiardi, A. Pilu and E. Agabiti Rosei

Cattedra di Clinica Medica-Università di Brescia, Brescia, Italy

Introduction: Structural alterations of subcutaneous small resistance arteries of hypertensive patients, as indicated by an increased media to lumen (M/L) ratio, have a strong prognostic significance. A complete normalization of small resistance artery structure was also demonstrated in hypertensive patients, after therapy with dihydropiridinic calcium antagonists, as well as with drugs interfering with the renin-angiotensin system. No improvement of vascular structure was observed, despite similar hemodynamic effects, after treatment with alpha-blockers or diuretics. However, no data are presently available about the effects of a combination between an ACE inhibitor and an angiotensin receptor blocker.

Aim: Therefore, we have investigated the effects of ramipril, telmisartan or their combination on subcutaneous small artery structure in 16 high-risk patients (diabetic patients, patients with coronary artery disease or cerebrovascular disease, etc).

Methods: All patients underwent a biopsy of subcutaneous fat after 3 years of treatment. Resistance-sized arteries were dissected and mounted on a wire myograph, according to Mulvany-Halpern technique, and M/L, media thickness, media cross-sectional area were measured. Systolic and diastolic blood pressure were evaluated by standard sphygmomanometric approach.

Results: The results obtained are summarized in the table.

Conclusions: The effect of the combination of ramipril and telmisartan was not different from that observed with ramipril or telmisartan alone, despite lower blood pressure, thus suggesting that, at least in this population, no additional improvement of microvascular structure should be expected by combining an ACE inhibitor and an angiotensin receptor blocker.

13.14 Effects on Structure and Function of Resistance-Sized Arteries of Spontaneously Hypertensive Rats of Melatonin and Pycnogenol

E. Porteri,¹ S. Paiardi,¹ R. Rezzani,² L.F. Rodella,² C. De Ciuceis,¹ G.E.M. Boari,¹ S. Tengattini,² F. Bonomini,² D. Rizzoni,¹ N. Rizzardi,¹ C. Platto,¹ A. Pilu¹ and E. Agabiti Rosei¹

1 Cattedra di Clinica Medica-Università di Brescia, Brescia, Italy; 2 Cattedra di Anatomia Umana-Università di Brescia, Brescia, Italy

Introduction: Oxidative stress has a key role in the development of endothelial dysfunction as well as of microvascular structural alterations. In animal models, the systemic infusion of angiotensin II, is associated with the development of vascular remodeling, as indicated by an increase in the media to lumen ratio (M/L) of mesenteric small resistance arteries.

Aim: Therefore, we have investigated the effect of two substances, which are known to possess antioxidant properties: a hormone produced by the pineal gland, melatonin (MEL), and a patented extract made from the bark of French maritime pine trees, pycnogenol (PYC).

Methods: We have treated 6 spontaneously hypertensive rats (SHR) with MEL, 6 with PYC, for 6 weeks, both groups at the dose of 10 mg/kg/day. We compared results obtained with those observed in 6 SHR and 6 Wistar-Kyoto normotensive control rats kept untreated. The animals were killed at 12 weeks of age. Mesenteric small resistance arteries were dissected and mounted on a wire myograph, and M/L, media thickness, media cross-sectional area were measured. In addition, a concentration-response curve to acetylcholine (10-9-10-5 Mol/L) was performed, in order to evaluate endothelial function.

Results: The results are summarized in the table (data are mean ± SD, * p < 0.05, ** p < 0.01, p < 0.001 vs. untreated SHR). A very small reduction in systolic blood pressure was observed. A significant improvement of endothelial function was observed in both groups of treatment; vascular structure improved mainly in rats treated with PYC.

Conclusions: In conclusion, our data suggest that treatment with PYC, and partly, also with MEL may protect the vasculature independently from blood pressure reductions, probably through their antioxidant effects.

13.15 Modifications of Collagen Subtypes in the Tunica Adventitia of Subcutaneous Small Resistance Arteries of Patients with Primary Aldosteronism

S. Paiardi,¹ L. Rodella,² C. De Ciuceis,¹ D. Rizzoni,¹ E. Porteri,¹ R. Rezzani,² G.E.M. Boari,¹ E. Borsani,² G. Favero,² N. Rizzardi,¹ C. Platto,¹ G. Bulgari,¹ G.A.M. Tiberio,³ S.M. Giulini³ and E. Agabiti Rosei¹

1 Cattedra di Clinica Medica-Università di Brescia, Brescia, Italy; 2 Cattedra di Anatomia Umana-Università di Brescia, Brescia, Italy; 3 Cattedra di Clinica Chirurgica-Università di Brescia, Brescia, Italy

Introduction: It was previously demonstrated that aldosterone may possess a strong profibrotic action in vitro and in animal models of genetic or experimental hypertension. We have also previously demonstrated that a marked fibrosis is present in the tunica media of subcutaneous small resistance arteries of patients with primary aldosteronism.

Aim: To investigate collagen subtypes in the tunica adventitia of patients with primary aldosteronism.

Methods: Six patients with primary aldosteronism (PA), 6 patients with essential hypertension (EH) and 6 normotensive controls (NT) underwent a biopsy of subcutaneous tissue. Small resistance arteries were mounted on an isometric myograph, and the tunica media to internal lumen ratio (M/L) were measured. In addition the collagen subtypes content within the adventitia was evaluated with Sirius red staining or immunohistochemistry.

Results: Main findings of our study are shown in ults are reported in the table (data are expressed as mean ± SD, ***=p < 0.001 vs normotensives, ###p < 0.0011 vs essential hypertension). Clinic blood pressure were similar in PA(142/89 ± 10/7 mmHg) and in EH (151/86 ± 8/10 mmHg), and greater than in NT (115/80 ± 11/6 mmHg, p< 0.05 al least in any case). The M/L was significantly increased in PA (0.095 ± 0.02) and in EH (0.101 ± 0.03) compared with NT (0.07 ± 0.02, p < 0.05 al least in any case), while no difference among groups was observed for adventitia thickness. Total collagen content was not different among groups. Type I collagen was markedly increased and type III collagen decreased in patients with PA and EH compared with NT; however, the concerned changes were clearly more pronounced in patients with PA than in patients with EH.

Conclusions: Our results indicate that, in small resistance arteries of patients with PA, pronounced changes in the ratio between type I and type III collagen may be observed. These changes are even more evident that in blood-pressure matched patients with EH.

13.16 Structural and Functional Alterations of Subcutaneous Small Resistance Arteries of Normotensive and Hypertensive Obese Patients

C. De Ciuceis,¹ E. Porteri,¹ D. Rizzoni,¹ C. Corbellini,¹ E. La Boria,² G.E.M. Boari,¹ S. Paiardi,¹ A. Pilu,¹ M. Castellano,¹ F. Mittempergher,² E. di Betta,² B. Salerni,² R. Tosini,¹ C. Agabiti Rosei¹ and E. Agabiti Rosei¹

1 Cattedra di Clinica Medica-Università di Brescia, Brescia, Italy; 2 Cattedra di Chirurgia Generale-Università di Brescia, Brescia, Italy

Introduction: Structural alterations of subcutaneous small resistance arteries of hypertensive patients, as indicated by an increased media to lumen (M/L) ratio, are frequently present in hypertensive and/or diabetic patients, and may represent the earliest alterations that may be observed. In addition, M/L of small arteries have a strong prognostic significance. However, no data are available about structure and endothelial function of small resistance arteries of obese patients.

Aim: Therefore, we have investigated 16 patients with severe obesity. Six of them were normotensive (NT), and 10 hypertensive (HT), according to 2007 European Guidelines, and only 3 of them had diabetes mellitus (DM).

Methods: We compared results obtained with those observed in 12 NT lean controls and in 12 HT lean patients. Systolic and diastolic blood pressure were measured. All patients underwent a biopsy of subcutaneous fat before or during surgical intervention of gastric banding or intestinal derivation. Subcutaneous small resistance arteries were dissected and mounted on a wire myograph and M/L, media thickness, media cross-sectional area were measured. A concentration-response curve to acetylcholine (10-9-10-5 Mol/l) was performed, in order to evaluate endothelial function.

Results: Main results are summarized in the table (data are expressed as mean ± SEM; * p < 0.05, ** p < 0.01, *** p < 0.001 vs. Lean NT; ^## p < 0.01, ^###p < 0.001 vs NT obese patients). Obese patients, independently from the presence of hypertension, diabetes and dyslipidaemia, show the presence of an increased M/L and of an increased media cross-sectional area. Preliminary data suggest the presence of endothelial dysfunction, as indicated by a reduced endothelium-dependent vasodilatation, especially in HT obese patients.

Conclusions: Our data suggest that the presence of obesity is associated to structural alterations of subcutaneous small resistance arteries, mainly characterized by hypertrophic remodeling.

13.17 Long-Term Blood Pressure Control: Effects on Endothelial Function and Arterial Stiffness in Patients with Essential Hypertension

L. Ghiadoni, F. Stea, Y. Plantinga, G. Lorenzini, A. Magagna, S. Taddei and A. Salvetti

Dipartimento Medicina Interna, Università di Pisa, Pisa, Italy

Introduction: Endothelial dysfunction and arterial stiffness are early vascular alterations characterizing essential hypertension and they are independent predictors of cardiovascular events. It has been shown that short term (<1 year) antihypertensive treatment is able to modify these vascular responses.

Aim: To evaluate the effect of blood pressure (BP) control (BP <140/90 mmHg) on indexes of vascular function and structure after long-term antihypertensive therapy.

Methods: Ninety-eight patients (69% males, age 50 ± 8 years, BP 152 ± 13/94 ± 9 mmHg) were recruited. Endothelial function was evaluated by Flow Mediated Dilation (FMD) of the brachial artery and compared to endothelial-independent dilation obtained with sublingual administration of 25 mcg of glyceryl trinitrate (GTN). FMD and response to GTN were calculated as % diameter change in diameter by a computerized system (FMD Studio, Institute of Clinic Physiology, CNR, Pisa). Aortic and peripheral arterial stiffness were measured as carotid-femoral and carotid-radial Pulse Wave Velocity (PWV), respectively. Aortic augmentation index (AIx) was obtained by radial applanation tonometry through a validated transfer function (Sphygmocor, AtCor Medical). These parameters were evaluated at baseline and after 3 years of therapy.

Results: Goal BP was achieved in 53% of patients (controlled patients: baseline 152 ± 12/94 ± 8; follow-up 127 ± 8/78 ± 7 mmHg, p < 0.01), while 47% did not reach BP target (uncontrolled patients: 154 ± 13/93 ± 9 to 147 ± 10/85 ± 8, p < 0.01). FMD was improved in the controlled patients (from 5.5 ± 3.4 to 6.5 ± 2.4%, p < 0.05), but not in uncontrolled patients (from 5.7 ± 4.2 to 6.2 ± 3.1, p = ns). Aortic PWV decreased in the group with controlled BP (9.0 ± 1.2 to 7.8 ± 1.3 m/s, p < 0.05), but not in uncontrolled group (9.3 ± 0.4 to 8.7 ± 0.2, p = ns). Response to GTN, AIx and peripheral PWV were not significantly modified in both groups.

Conclusions: An effective control of BP is associated with an improvement in endothelial function and aortic stiffness in essential hypertensive patients. These data suggest that effective BP control by antihypertensive therapy could exert positive effects on cardiovascular prevention also through a reversal of dysfunction and structural alterations of large arteries.

13.18 Comparison between Two Methods for Ultrasound Assessment of Intima-Media Thickness and Carotid Stiffness

E. Bianchini,¹ L. Ghiadoni,² F. Bozec,³ V. Gemignami,¹ F. Faita,³ C. Giannarelli,² M. Demi,¹ P. Boutouyearsie³ and S. Laurent³

1 Istituto di Fisiologia Clinica, CNR, Pisa, Italy; 2 Dipartimento Medicina Interna, Università di Pisa, Pisa, Italy; 3 Department of Pharmacology, G. Pompidou European Hospital, Paris, France

Introduction: Increased carotid Intima-Media Thickness (IMT) and arterial stiffness are important parameters for the assessment of vascular target organ damage in hypertensive patients. IMT can be assessed by standard ultrasonography. Local indices of carotid stiffness can be evaluated by measuring the diameter (D) and the stroke change in diameter (ΔD) from ultrasound data in conjunction with the local pulse pressure.

Aim: To compare a new system (Carotid Studio, Institute of Clinic Physiology, CNR, Pisa, Italy) for automatic evaluation of D, ΔD ed IMT on images from longitudinal B-mode scan of carotid arteries with the ArtLab (ESAOTE, Maastricht, NL), a referral radio-frequency (RF) based eco-tracking system.

Methods: A total of 90 scans of the right/left common carotid artery from 21 patients with various cardiovascular risk factors and 12 healthy volunteers were analysed. All measurements were performed in real-time by using the two systems sequentially. Different regions-of-interest (ROI) width were adopted on 60 scans for best performances (1 cm for Carotid Studio and 4 cm for Artlab). The remaining 30 scans were analyzed using the same ROI width for the two systems. Moreover, on the healthy volunteers the analysis was repeated twice with each device in order to evaluate the intra-observer variability. The agreement between the two systems was evaluated by Bland-Altman analysis. The variability for each device was presented as the coefficient of variation.

Results: The bias and the standard deviation of the data obtained with different ROI width were: 0.120 ± 0.220 mm for D, 0.008 ± 0.063 mm for IMT and −0.014 ± 0.044 mm for DΔ, respectively. Moreover, when the same ROI width was adopted the bias and the standard deviation were: 0.060 ± 0.110 mm for D, −0.006 ± 0.039 mm for IMT and −0.016 ± 0.039 mm for DΔ, respectively. The coefficients of variation of intra-observer measurements were: 2 ± 2% for D, 5 ± 5% for IMT and 6 ± 6% for ΔD with the ArtLab and 2 ± 1% for D, 6 ± 6% for IMT and 8 ± 6% for ΔD with the Carotid Studio.

Conclusions: Measurement obtained with the Carotid Studio showed good agreement with those by the ArtLab and a similar reproducibility. Hence, although it is common opinion that B-mode based devices have lower precision than the RF based ones, these data suggest that the Carotid Studio, measuring from standard ultrasound scans, can be a suitable device for the measurement of IMT and arterial stiffness parameters in clinic studies.

13.19 A Multicentre Study to AssessVariability of Endothelial Function in Brachial Artery

L. Ghiadoni,¹ F. Faita,² V. Gemignani,² L. Landini,¹ M.L. Muiesan,³ A. Biggi,⁴ F. Crea,⁵ G. Ambrosio,⁶ F. Cosentino⁷ and S. Taddei¹ on behalf of Gruppo di Studio “Endotelio” delle Società Italiana di Ipertensione Arteriosa e Società Italiana di Cardiologia

1 Università di Pisa, Pisa, Italy; 2 Istituto di Fisiologia Clinica, CNR, Pisa, Italy; 3 Università di Brescia, Brescia, Italy; 4 Università di Parma, Parma, Italy; 5 Università Cattolica del Sacro Cuore, Rome, Italy; 6 Università di Perugia, Perugia, Italy; 7 Università La Sapienza, Rome, Italy

Introduction: Flow-mediated dilation (FMD) of the brachial artery is the most commonly used method to assess endothelial function. A reduced FMD is associated with major cardiovascular risk factors and is an independent predictor of events. Despite the large effort to standardize the methodology, FMD evaluation is still characterized by problems of reproducibility and reliability.

Aim: To standardize the procedure for FMD assessment in different Units and evaluate FMD variability over time in healthy volunteers.

Methods: 101 healthy volunteers (age 20–60 years) were recruited in 6 Italyn Hypertension Units. FMD was assessed as dilation of the brachial artery secondary to 5 minutes forearm ischemia by trained operators using a clamp to held the ultrasound probe. Sequences of B-mode images of the brachial artery were VCR recorded for baseline FMD (time 0) and repeated 1 hour after baseline maintaining the probe in the same position (time 1) and 1 month apart (time 2). Endothelium independent vasodilation to glyceryl trinitrate (25 mcg, sublingual) was also evaluated at time 0 and 2. FMD and response to GTN were measured blindly as percentage brachial artery diameter changes by an automatic edge detection system (FMD Studio, Institute of Clinic Physiology, CNR, Pisa) in the coordinating Centre. The intra- (time 0 vs 1) and inter-session (time 0 vs 2) coefficients of variation were calculated for the 6 different research units and overall to assess FMD and GTN variability over time.

Results: All recordings were suitable for analysis. FMD was 7.4 ± 3.1% at time 0, 7.2 ± 3.3% at time 1 and 7.4 ± 2.9% at time 2. Overall, the intra-session FMD variability was 9.3 ± 10.1% ranging from 6.6% to 10.1% in the different Centres. Inter-session FMD variability was 13.9 ± 11.8%, ranging from 11.0% to 16.1% in the different Centres. GTN response was 12.8 ± 4.8% at time 0 and 12.6 ± 4.2% at time 2. Overall inter-session variability of GTN response was 15.9 ± 9.8%, ranging from 10.1% to 22.3%.

Conclusions: This multicenter study shows a similar variability in measuring FMD 1 month apart as compared 1 hour apart, an reliable index of intrinsic variability of endothelial response. Thus, a standardized procedure, including operator training, defined experimental settings and automatic brachial artery measurements, can ensure an adequate FMD reproducibility over time for the for the assessment of endothelial function in clinic studies.

13.20 Endothelial Dysfunction is Associated with Arterial Stiffness in Hypertensive Patients with Type 2 Diabetes Mellitus

R.M. Bruno, L. Ghiadoni, A.G. Daniele, G. Penno, F. Stea, L. Landini, S. Del Prato, S. Taddei and A. Salvetti

Università di Pisa, Pisa, Italy

Introduction: Both endothelial dysfunction and arterial stiffness have been considered as independent predictors of cardiovascular mortality, but their interrelationship has been poorly explored. Therefore we evaluated the relationship between endothelial function and pulse wave velocity (PWV) in essential hypertensive patients with (DM+) or without(DM−) diabetes mellitus, on chronic pharmacological treatment.

Methods: 50 DM+ patients (28 men; 57 ± 8 years, blood pressure, BP 142 ± 16/78 ± 11 mmHg; diabetes duration: 12 ± 8 years; HbA1c: 8.3 ± 0.7%) and 51 DM− patients (30 men; 55 ± 6 years; BP 138 ± 15/81 ± 9 mmHg) matched for age, gender and systolic BP (SBP) were included. Applanation tonometry (Sphygmocor®) was used to determine central BP and aortic (carotid to femoral) PWV. Brachial artery endothelium-dependent flow-mediated dilation (FMD), and endothelium-independent dilation by 25 μg sublingual glycerol trinitrate (GTN) were assessed by high resolution ultrasound and computerized edge detection system.

Results: DM+, compared to DM−, had higher BMI and blood glucose, and lower HDL cholesterol. Moreover in DM+ PWV was higher (9.9 ± 1.8 vs 8.4 ± 1.4 m/s, p = 0.0001) and FMD was lower (3.1 ± 1.7 vs 6.3 ± 3.5, p < 0.0001) than DM−. In DM+, PWV was related to BMI (r = 0.47, p = 0.002), fasting blood glucose (r = 0.39, p = 0.01), triglycerides (r = 0.41, p = 0.015), brachial (r = 0.59, p < 0.0001) and central SBP (r = 0.62, p<0.0001). Noteworthy, FMD was significantly and inversely correlated only with PWV (r = −0.456; p = 0.001). In multivariate analysis, only FMD (r2 = 0.20, p < 0.0001), brachial SBP (r² = 0.23, p < 0.0001), BMI (r² = 0.24, p = 0.005) and glycemia (r² = 0.06, p = 0.02) resulted significant independent predictors of PWV (full model r² = 0.73). Similar results were obtained when central SBP was included in the model instead of brachial SBP. On the contrary in DM−, PWV was related to age (r = 0.38, p = 0.01), brachial (r = 0.47, p < 0.0001) and central SBP (r = 0.53, p < 0.0001), but not to FMD. In multivariate analysis, only SBP (p = 0.01) was an independent predictor of PWV (r² = 0.24).

Conclusions: In hypertensive type 2 diabetic subjects on chronic pharmacological treatment, a decline in endothelial function seems to be independently associated with increased aortic stiffness, possibly suggesting a cause-effect mechanism. The association is not present in hypertensive euglycemic patients, who have lower aortic stiffness and endothelial dysfunction.

13.21 Increased Carotid Artery Stiffness is Associated with an Increased Echogenicity of Carotid Intima Media Complex in a Large Population of Hypertensive Patients with a Normal Intima-Media Thickness

F. Natale, L. Aronne, G.M. Di Marco, C. Cirillo, C. Granato, F. Allocca, E. Lo Priore, P. Calabrò, P. Golino and R. Calabrò

Seconda Università Di Napoli, Napoli, Italy

Introduction: The mechanisms linking arterial stiffness to atherosclerosis are not known at present. Atherosclerotic changes in the arterial wall could include smooth muscle cell proliferation, deposition of lipid and accumulation of collagen, elastin, and/or proteoglycans. However, it is not known whether intima-media complex with different contents are differentially related to carotid arterial stiffness.

Aim: To evaluate carotid stiffness in patients with different intima-media echogenity.

Results: Main findings of this study are shown in the table.

Conclusions: Intima-media echogenity is associated to lower flow-mediated dilation and increased carotid stiffness assessed with echo tracking (aloka a).

13.22 Vascular Remodelling in Patients with Psoriatic Arthritis: the Impact of Blood Pressure

M. Puato, M. Zanardo, C. Tirrito, G. Balbi, E. Faggin, M. Zanon, R. Ramonda, V. Modesti, A. Lo Nigro, A. Doria and P. Pauletto

Dipartimento di Medicina Clinica e Sperimentale, Padova, Italy

Introduction: Increased cardiovascular morbidity and mortality have been observed in several immune mediated rheumatic diseases, including psoriatic arthritis (PsA).

Aim: We evaluated subclinic atherosclerosis in PsA patients according with hypertensive status by studying non-invasively structural and functional properties of arteries.

Methods: We studied 41 consecutive patients with PsA (of whom, 48% hypertensive patients) attending hospital outpatient clinics. 40 normotensives healthy subjects (N-C) and 18 hypertensive patients (HT-C) served as controls. We evaluated by B-mode ultrasound the carotid intima media thickness (IMT). Measurements were expressed as mean-IMT (cumulative mean of mean IMT measured in each carotid segment, common, bulb, and internal carotid artery, bilaterally) and as M-MAX (cumulative mean of maximum IMT). Endothelial function was evaluated by post-occlusion flow mediated dilation (FMD) of the brachial artery using high-sensitivity brachial ultrasonography. NO-independent vasodilation was evaluated by the response to sublingual glyceryl trinitrate (GTN).

Results: PsA had a higher mean-IMT compared to N-C (normotensives PsA 0.69 mm, hypertensive patients PsA 0.71 mm vs N-C 0.60 cm, p = 0.005). Hypertensive PsA displayed higher M-MAX (0.91 mm) versus both HT-C (NC 0.71 mm and HT-C 0.77 mm, p = 0.007) and normotensive PsA (0.81 mm, p = 0.026). FMD was lower in PsA than in N-C (normotensives PsA 5.7%, hypertensive patients PsA 6.1% vs NC 8.9%, p < 0.0005), whereas there was no difference between hypertensive PsA, normotensive PsA, and HT-C. GTN response was similar in all groups.

Conclusions: Our data show that subclinic atherosclerosis is enhanced in PsA compared to N-C. In PsA, the hypertensive status proved to exert an additional effect on M-MAX, a parameter of advanced pro-atherogenic remodelling. FMD was reduced in PsA irrespective of hypertensive patients status. Thus, PsA per se implies a pro-atherogenic remodelling which is enhanced by the hypertensive status.

13.23 Blood Pressure Variability per se May Induce an Impaired Glomerular Filtration and a Microcirculatory Damage

P. Nazzaro,¹ G. Schirosi,¹ V. Lucivero,¹ G. Grandolfo,¹ V. Vulpis,² L. Pascazio,¹ M. Mingarelli³ and F. Federico¹

1 DipartimentoScienze Neurologiche e Psichiatriche-Stroke Unit-Univerità di Bari, Bari, Italy; 2 Medicina Generale-Policlinico Consorziale, Bari, Italy; 3 Dipartimento Fisiologia e Farmacologia- Università di Bari, Bari, Italy

Introduction: Hypertensive patients (HTN), since very initial stages of the disease, may show both a marked diurnal blood pressure variability and an early impaired glomerular filtration.

Aim: To recognize if these characteristics might be associated to the microvascular damage.

Methods: By medical visit (off), diurnal ambulatory blood pressure monitoring (day) and simultaneous actigraphy, the waking systolic blood pressure variability, as coefficient of variation (SBPcv), has been calculated in 180 hypertensive patients (139 ± 2/81 ± 1 mmHg), divided in tertiles as lower (L−), moderate (M−) and higher (H−) SBPcv. By routine blood chemistry and bioimpedance, the metabolic and anthropometric assessment have been identified. The glomerular filtration rate was also calculated (MDRD). By videocapillaroscopy of periungueal, phalangeal and forearm skin of the non-dominant arm the basal capillarity (CAP) and, by venous congestion, the maximized (CVC) and the recruited capillarity (GAIN), as indices of structural and functional microvascular damage, were measured.

Results: The main findings of the study are show in the table (data are expressed as mean ± SE: *p < 0.05, **p < 0.01, ***p < 0.001 vs L-SBPcv; ^p < 0.05, ^^p < 0.01, ^^^p < 0.001 vs M-SBPcv). Pearson analysis, adjusted for metabolic and anthropometric assessment, showed an inverse correlation of SBPcv with CAP (−0.300***), CVC (−0.212***) and MDRD (−0.440***).

Conclusions: Blood pressure variability, independently by blood pressure mean values, may induce structural microvascular rarefaction and impaired renal function since the early stages of hypertension.

13.24 Ultrasound Evaluation of Carotid Plaque Mechanical Properties and Composition

A. Paini,¹ M.L. Muiesan,¹ M. Salvetti,¹ P. Boutouyearsie,² M. Paterni,³ S. Laurent² and E. Agabiti Rosei¹

1 Clinica Medica, Università di Brescia, Brescia, Italy; 2 INSERM 652, Universitè Paris-Descartes, Paris, France; 3 Istituto di Fisiologia Clinica, CNR, Pisa, Italy

Introduction: Plaque rupture mechanisms are complex processes, which are dependent on plaque morphology and composition and mechanical characteristics. We have previously demonstrated that the higher risk of plaque complication reported in patients with diabetes and hypercholesterolemia may be due to a specific pattern of strain gradient between plaque and adjacent common carotid artery (CCA) (inward bending stress). In addition, previous studies have suggested that plaque echogenicity is related to the histological components of carotid plaques and that carotid plaque echolucency (low echogenicity) is associated with the development of neurological events.

Aim: To determine the difference in plaque composition according to the presence of an outward or an inward bending stress (ArtLab system).

Methods: We have used an in vivo noninvasive approach with a software for videodensitometry analysis, the MIP system (Medical Image Processing, CNR Pisa), which yields the gray levels distribution and second order parameters of a region of interest (ROI). The study included 24 patients with a recent cerebrovascular ischemic event and a plaque on the far wall of CCA. We divided the patients into two groups according to strain behaviour: pattern A (larger strain at the level of plaque than at the level of CCA, outward bending strain) and pattern B (plaque strain smaller than CCA strain, inward bending strain). In all patients digital images of plaques were analyzed offline with MIP.

Results: In 16 patients a pattern A and in 8 patients a pattern B strain behaviour were observed. Demographic and hemodynamic characteristics were similar in the two groups. The prevalence of hypercholesterolemia and diabetes were significantly higher in patients with a pattern B strain behaviour (respectively, 100% vs 56.3%, p = 0.03 and 62.5% vs 12.5%, p = 0.04). Mean gray levels were significantly lower in patients with an inward bending strain as compared to patients with an outward bending strain (65 ± 20 vs 95 ± 30, p = 0.018). As for strain gradient, in the whole group of patients, the mean gray level significantly decreased in parallel with the presence of dyslipidemia and/or type 2 diabetes (127 ± 20 vs 80 ± 21 and 59 ± 18, in the presence of none of them, one of them and both, respectively, p < 0.01). In addition, entropy, a second order parameter which may reflects plaque heterogeneity, was significantly higher in patients with pattern B (6.24 ± 0.78 vs 1.61 ± 1.43, p < 0.001).

Conclusions: These results suggest that the higher risk of plaque complication, reported in patients with diabetes and hypercholesterolemia, may be due both to a specific pattern of strain gradient between plaque and adjacent CCA and to a different plaque composition and homogeneity.

13.25 Brachial Artery Flow-Mediated Dilatation in Essential Hypertensive Patients: Effect of Therapy with Calcium-Channel Antagonist (Barnidipine) or Diuretic (Hydroclorotiazide)

A. Paini,¹ E. Belotti,¹ C. Aggiusti,¹ D. Stassaldi,¹ M. Salvetti,¹ A. Scotti,² M.L. Muiesan¹ and E. Agabiti Rosei¹

1 Clinica Medica, Università di Brescia, Brescia, Italy; 2 Direzione Scientifica Italfarmaco, Milan, Italy

Introduction: Flow-mediated dilatation (FMD) of a medium-size artery represents a non invasive method to determinate endothelial function. It has previously observed that in uncomplicated hypertensive patients brachial artery FMD is impaired and may improve with long term antihypertensive therapy.

Aim: To evaluate the effect of monotherapy with barnidipine (B) or with the diuretic hydroclorotiazide (H) on the FMD in 40 hypertensive patients.

Methods: The brachial artery diameter was measured by high resolution ultrasound (FMD studio software) in basal conditions, during reactive hyperaemia (5 minute occlusion) and after sublingual administration of nitroglycerine (40 μg). This procedure was repeated after 3 and 6 months of monotherapy with B or H.

Results: Preliminary results have been obtained in 28 patients (23 males, 5 females, age range 32–65 years). At baseline no significant differences between the groups of patient randomized to B (n = 14) or H (n = 14) were observed in age, clinic blood pressure (BP) plasma glucose, total and LDL cholesterol, and FMD. At 3 and 6 months a similar reduction of BP was observed in both groups (SBP/DBP: basal: 147 ± 11/97 ± 7, 3 months: 133 ± 9/86 ± 7, 6 months: 135 ± 13/86 ± 9 in B group; SBP/DBP: basal: 142 ± 12/93 ± 8, 3 months 127 ± 10/81 ± 6, 6 months: 132 ± 11/83 ± 6 in H group; p<0.001 one-way ANOVA for repeated measurements). At 3 and 6 months of treatment an increase of FMD was observed during therapy with B, while a reduction of FMD was observed in patients treated with H (+0.6% in B group and −0.9% in H group, p = 0.01 at 3 months and +0.6% in B group and −1.3% in H group, p = 0.008 at 6 months vs basal, one-way ANOVA for repeated measurements p = 0.04).

Conclusions: In essential hypertensive patients brachial artery FMD is altered in basal condition and it may improve with effective and long term reduction of blood pressure. Our results suggest that treatment with a dihydropiridinic calcium antagonist may be more favourable than diuretic therapy to this regard.

13.26 Arterial Stiffness According to Different Left Ventricular Geometric Patterns in a General Population

M. Salvetti, M.L. Muiesan, A. Paini, C. Monteduro, E. Belotti, C. Agabiti Rosei, C. Aggiusti, L. Micheletti, D. Stassaldi, M. Castellano and E. Agabiti Rosei

Clinica Medica, Università di Brescia, Brescia, Italy

Introduction: Increased left ventricular mass and concentric geometry have been found associated with reduced left ventricular (LV) systolic function, impaired diastolic relaxation, increased total peripheral resistances and a greater risk for cardiovascular (CV) events. An increase in arterial stiffness might contribute to the higher CV risk observed in patients with adverse LV remodeling.

Aim: To evaluate pulse wave velocity, currently considered the gold standard measure of aortic stiffness, as related to LV geometric patterns in a general population sample from Northern Italy (‘Vobarno Study’).

Methods: In 384 subjects (age 56 ± 10 years, 44% males, 64% hypertensive patients [HT], 32% treated) left ventricular structure and carotido-femoral PWV were measured. All subjects underwent laboratory examinations. Subjects were divided into 4 LV geometric patterns according to the presence of an increased LV mass index (LVM/h2.7 > 47 for women and >50 for men) and/or an increased relative wall thickness (RWT > 0.42).

Results: After the echocardiographic examination subjects were classified as follows: 70% with normal LV geometry (N), 11% LV with concentric remodelling (CR), 6% with concentric LV hypertrophy (C_LVH), 13% with eccentric hypertrophy (E_LVH). PWV was greater in patients with CR, C_LVH and E_LVH in comparison to N (12.5 ± 2.5, 13.9 ± 6, 11.9 ± 2.4 respectively, versus 10.8 ± 2.2, ANOVA p < 0.05). In addition, PWV was significantly greater in patients with C_LVH in comparison to E_LVH (p < 0.05). After correction for confounding variables (age, sex, BMI, glycemia, uric acid, and heart rate and mean BP measured during PWV assessment), PWV remained significantly higher in patients with C_LVH in comparison to N and E_LVH (p < 0.05).

Conclusions: In a general population sample patients with concentric LVH had increased arterial stiffness together with impaired systolic and diastolic function of the LV. Our results might give further insights into the mechanisms underlying LV remodelling in hypertension and on the CV risk associated with different geometric patterns.

13.27 Increased Pulse Wave Velocity in Patients with Apolipoprotein A-I Amyloidosis (LEU75PRO)

A. Paini,¹ M.L. Muiesan,¹ M. Salvetti,¹ E. Belotti,¹ C. Agabiti Rosei,¹ C. Aggiusti,¹ A. Negrinelli,² L. Obici,³ G. Gregorini² and E. Agabiti Rosei¹

1 Clinica Medica, Università di Brescia, Brescia, Italy; 2 Nefrologia, Università di Brescia, Brescia, Italy; 3 Centro per l’amiloidosi, Laboratori di Biotecnologia, Pavia, Italy

Introduction: Hereditary amyloidosis are late-onset autosomal dominant disorders characterized by amyloid deposition in various tissues. Among them, Apolipoprotein A-I amyloidosis (Leu75-Pro) is a rare, autosomal dominant condition in which renal, hepatic, and testicular involvement has been demonstrated. No data are available about vascular alterations in this condition.

Aim: To evaluate arterial stiffness, as assessed by pulse wave velocity (PWV), in patients with Apolipoprotein A-I amyloidosis (APO A-I amyloidosis).

Methods: In 104 patients with Apolipoprotein A-I amyloidosis (Leu75Pro) (mean age 52 ± 16 years, 56 F) and in 104 subjects matched for age, sex, body mass index (BMI) and clinic blood pressure (BP), PWV was measured (Complior SP).

Results: By definition no differences for age, sex, BMI, BP, heart rate were observed. PWV was significantly higher in patients with APO A-I amyloidosis than controls (11.5 ± 2.9 and 10.7 ± 2.3, p < 0.05), even after adjusting for plasma cholesterol, serum creatinine and mean BP and heart rate measured during PWV assessment. In patients with APO A-I amyloidosis the prevalence of increased arterial stiffness (defined as PWV >12m/sec) was significantly greater than in controls (31% vs 17% respectively, Chi square p < 0.05).

Conclusions: In patients with Apolipoprotein A-I amyloidosis (Leu75Pro) a significant increase in arterial stiffness is observed. These results, obtained in a wide sample of patients, may add significant information to the clinic features of this rare genetic disorder.

13.28 Effectiveness of Nebivolol on Blood Pressure Control and Endothelial Function in Hypertensive Post-Menopausal Women

M. Vicenzi, V. Rossi, A. Dallacìa, M. Antelmi and M. Guazzi

Centro per la Cura e lo Studio dell’Ipertensione Arteriosa,Università di Milan, Ospedale S.Paolo, Milan, Italy

Introduction: Arterial hypertension and endothelial dysfunction are closely related factors in determining a higher cardiovascular risk in postmenopausal women. Nebivolol is a selective beta1-blocker with additional peripheral vasodilating properties mediating an increase in nitricoxide (NO) bioavailability.

Aim: We tested the effectiveness of chronic nebivolol therapy in post-menopausal hypertensive women by monitoring the potential drug-induced effects on:

1. endothelial function,

2. physical performance and

3. systolic arterial pressure (SAP) control during maximal exertional test.

Methods: 13 hypertensive postmenopausal women (mean age: 53.2 ± 1.64 years), already treated with anti-hypertensive agents, underwent an in vivo evaluation of their endothelial function through a brachial artery flow-mediated dilation (FMD) test and performed a cardiopulmonary exercise testing to determine peak oxygen consumption (VO₂) before (T0) and after (T1) a treatment period with nebivolol (mean duration: 76.8 ± 22.6 days; daily dose: 4.5 ± 1.12 mg). Previous therapy was withheld between T0 and T1.

Results: Nebivolol treatment provided the same blood pressure control compared with standard treatment. Nebivolol also improved the FMD (p < 0.05; figure; T1 vs T0: @ = p < 0.01; # = p < 0.05) and promoted a significant increase in exercise tolerance as determined by peak VO₂ (delta VO₂ percent: 8.2 ± 4.55%, p< 0.02), without significant changes in exercise SAP control (delta PAS at peak exercise: −9.0 ± 15.17 mmHg, p = 0.2).

Conclusions: In this subset of hypertensive patients, nebivolol determined (i) a significant improvement of the endothelial function along with an optimal blood pressure control; (ii) an increased exertional performance very likely mediated by an improved endothelial mediated perfusion to working muscle. These results prospect the possibility that nebivolol should be considered as a first line anti-hypertensive therapy in postmenopausal women.

13.29 Endothelium-Dependent and -Independent Effects of Low Concentrations of Catechins on Vascular Tone in Rat Aortic Rings

D. Grassi, A. Aggio, L. Onori, A. D’Alessandro, S. Necozione, G. Desideri and C. Ferri

Università di L’Aquila, L’Aquila, Italy

Introduction: Ingestion of catechin-rich foods (tea, cocoa, red wine), results in low plasmatic concentration of catechin-derivatives (0.1–7 μM) associated with transient arterial vasodilatation. This effect is considered to be endothelium-dependent and mainly nitric oxide (NO) mediated. Conversely, experimental studies on isolated arteries, low concentrations of catechins induced conflicting results. Equivocal responses have sometime been associated to different catechin molecular structure, such as the presence of epigallol moiety (epigallocatechin, epigallocatechin gallate), confering contractile activity or cathecol group (epicatechin), eliciting relaxing response.

Aim: We investigated the effect of a low concentration of two structurally different catechins, (—)-epigallocatechin gallate (EGCG) and (—)-epicatechin (EC), on rat aortic rings in different experimental conditions. We hypothesised that effect of catechins could critically depend on basal muscular tone, and thus on the functional state of endothelial cells.

Methods: The isometric force recording technique was used to examine the response of endothelial intact or denuded aorta rings to cumulative concentrations of EGCG and EC (1 × 10−7 M to 1 × 10−5 M), on resting tension or phenylephrine (PE) submaximally precontracted preparations. The contractile responses were expressed as a percentage of the amplitude of contraction induced by PE in each preparation, and the relaxant responses as a percent decrease in the tension existing at the time of drug administration.

Results: On resting tension of endothelium- denuded preparations, EGCG and EC (1 × 10−7 M to 1 × 10−5 M) induced dose-dependent phasic contractions that were significantly larger than those induced in endothelium-intact tissues (p < 0.05). The contractile effect of EGCG was stronger than that induced by EC, in endothelium-denuded preparations (p < 0.05). On sustained active tension induced by PE in intact preparations, EGCG and EP induced a dose-dependent relaxation that was significantly larger than in endothelium-denuded tissues (p < 0.05); EGCG was still significantly stronger in potency than EC (p < 0.05). The vasorelaxant responses induced by EGCG and EC in PE contracted intact-aortic rings were significantly inhibited when tissues were preincubated with NwNitro-L-Arginine (L-NNA) (1 × 10−4 M), an inhibitor of endothelial NO-synthase (NOS) activity (p < 0.05). EGCG and EC on resting tension aortic rings induced a prevalent contraction through direct action on smooth muscle, which was significantly decreased by endothelial-mediated mechanisms. On precontracted tissues, they induced largely endothelium-dependent NO mediated relaxation. EGCG appeared to be more potent than EC in eliciting both effects.

Conclusions: Cumulatively, the present results indicate that catechin effects are critically dependent on smooth muscle tone, and consequently on the endothelial functional state. The hypothesis of a structure-activity relationship among catechin derivatives is not supported.

13.30 Relationship between Endothelial Function and Endothelial Biomarkers in Hypertensives with Chronic Kidney Disease

M. Guarneri, R. Riccobene, R. Arsena, C. Altieri, F. Tornese, A. Previti, G. Cerasola and S. Cottone

Università degli Studi di Palermo, Palermo, Italy

Introduction: Hypertension is characterized by a synergy between oxidative stress, inflammation and endothelial dysfunction. Endothelial dysfunction plays an important role in the patho-physiology of high blood pressure, atherosclerosis and cardiovascular diseases. In the last decade, was developed a technique for non-invasive assessment of flow mediated vasodilatation (FMD) into the brachial artery, an endothelium dependent function, which assess endothelial function in vivo.

Aim: To analyze the relationship between endothelial dysfunction, assessed through FMD, and biomarkers of endothelial dysfunction (ET-1, ICAM-1, VCAM-1) and inflammation (TNF-α) in patients with hypertension affected by chronic renal failure (CRF).

Methods: We enrolled 50 subjects with hypertension (HT), with various degrees of kidney function (CRF II–IV), and 50 healthy control subjects. In all the subjects were determined plasma concentrations of ET-1, ICAM-1, VCAM-1, E-SEL and TNF-α. In hypertensive patients endothelial function was assessed with the analysis of endothelium-dependent vasodilatation (FMD).

Results: Overall, the results showed HT plasma levels of ET-1, ICAM-1, VCAM-1, E-SEL and TNF-α significantly higher (p < 0.001) compared with control subjects. The average value of FMD% as assessed in the group of hypertensive subjects was of 6.57 ± 4.08. The linear correlation analysis, carried out in the group of hypertensive subjects, showed negative and significant correlations between FMD% and ET-1, ICAM-1, VCAM-1, E-SEL and TNF-α (p < 0.05 respectively). The analysis of correlation between FMD% and glomerular filtration rate, as estimated by the MDRD study equation at 4 variables, was not statistically significant.

Conclusions: Our study confirms the presence, in hypertensive patients with different degrees of renal function, of endothelial activation characterized by increased serum concentrations of adhesion molecules and markers of inflammation. This results are associated with reduced endothelium-dependent vasodilatation, regardless of the degree of renal function.

13.31 Daytime Ambulatory Arterial Stiffness Index and Aortic Pulse Wave Velocity

G. Schillaci,¹ G. Pucci,¹ M. Pirro,¹ M.R. Mannarino,¹ R. Hijazi¹ and G. Parati²

1 Università di Perugia, Perugia, Italy; 2 Università Milano-Bicocca, Milan, Italy

Introduction: Ambulatory arterial stiffness index (AASI), a measure based on the dynamic relation between 24-hour systolic and diastolic blood pressure (BP), has been suggested as a marker of arterial stiffness and a predictor of cardiovascular mortality. However, 24-hour AASI is intrinsically dependent on day-night diastolic BP changes; moreover, AASI obtained from daytime hours could theoretically be more closely related to office-based measures of arterial stiffness than 24-hour values.

Aim: We tested the relation between AASI calculated on the basis of daytime hours, after the exclusion of nocturnal readings, and aortic pulse wave velocity (PWV).

Methods: A total of 647 untreated hypertensive patients (58% men, age 48 ± 10 years) underwent 24-hour BP monitoring and determination of carotid-femoral PWV, a direct measure of aortic stiffness. 24-hour AASI (0.31 ± 0.17) was on average lower than either daytime AASI (0.48 ± 0.28, p < 0.001) or nighttime AASI (0.38 ± 0.26, p = 0.009). As expected, 24-hour AASI was inversely related with nocturnal systolic and diastolic BP reduction (r = −0.24 and −0.43, respectively; both p < 0.001). In contrast, daytime and nighttime AASI had no relation with nocturnal systolic/diastolic BP reduction (r = −0.04/−0.05 for daytime AASI; r = −0.04/−0.08 for nighttime AASI; all p = n.s.).

Results: Aortic PWV had a direct relationship with daytime AASI (r = 0.12, p = 0.008), but not with nighttime AASI (r = 0.05, p = n.s.). After adjustment for the effects of age, no significant association was found between aortic PWV and the different measures of AASI (r = 0.01 for daytime AASI; r = 0.00 for nighttime AASI; r = 0.00 for 24-hour AASI; all p = n.s.).

Conclusions: The relation between daytime AASI and a widely accepted measure of aortic stiffness, such as pulse wave velocity, is weak, and explained by age. These data suggest that AASI and aortic PWV might explore different physiological phenomena.

13.32 Reactive Oxygen Species Mediate Late Ischaemic Preconditioning-Induced Cell Protection against Hypoxia

A. Bellis, D. Castaldo, B. Trimarco and C. Morisco

Università Federico II, Napoli, Italy

Introduction: We have recently demonstrated that ischaemic preconditioning (PC) protects bovine aortic endothelial cells (BAECs) from hypoxia(12 hours)-induced apoptosis through the crosstalk between protein-kinase A (PKA) and Akt. However, the trigger event of this phenomenon is still unclear. Because both reactive oxygen species (ROS) and nitric oxide (NO) have been demonstrated to mimic PC-induced cell protection in some experimental models, we have hypothesized that ROS and NO production could be implicated in PC-mediated BAECs protection.

Aim: To evaluate ROS and NO role in ischemic PC of BAECs.

Methods: PC has been induced by exposing BAECs to 15 min of hypoxia (incubation in hypoxic chamber) followed by 15 min of reperfusion. First, we evaluated ROS and NO production during PC. ROS production has been measured through nitrated proteins quantization in cellular lysates obtained at different times since PC application. Early and late PC increased nitrated protein content in BAECs (3.2 vs control). Consistently, PC evoked NO production with two-peaks, detectable immediately and after 24 hours since PC-application through arginine-citrulline conversion assay (1.5 and 1.9 fold increase of citrulline in early and late PC vs control, respectively). Evaluation of PC-induced NO-production through GRIESS reaction showed the same biphasic trend. Then, we focused our attention on late PC and asked whether ROS and NO are needed for BAECs protection against apoptosis in this phase.

Results: The late PC-mediated inhibition of caspase-3-cleavage induced by 12 hours of hypoxia was abolished by cells pretreatment with a ROS scavenger (N-acetyl-cysteine), whereas it was unaffected by inhibition of NO- production (L-NAME+1400W). BAECs pretreatment with NOC-12 (a long term NO- donor) did not prevent the caspase-3-cleavage induced by 12 hours of hypoxia. To further exclude a role of iNOS and eNOS in late PC-induced cell protection, we assessed caspase-3-cleavage in late PC after pretreatment with 1400 W and silencing of eNOS expression. Both treatments did not affect late PC cytoprotective effect.

Conclusions: Our data show that late PC-induced cytoprotection in BAECs is mediated by ROS production, but not by NO synthesis.

13.33 Platelet and Endothelial Activation and Progression of Cognitive Impairment in Vascular Dementia

G. Desideri,¹ D. Grassi,¹ R. Bocale,² A. Raffaele,² M.C. Lechiara,² G. Mauti,² S. Necozione¹ and C. Ferri¹

1 Università degli Studi dell’Aquila, Dipartimento di Medicina Interna e Sanità Pubblica, L’Aquila, Italy; 2 Ospedale S. Rinaldi, Pescina, Italy

Introduction: Multi-infarct dementia, also known as vascular dementia, is the second most common form of dementia after Alzheimer disease in older adults in westernized countries where it represents a relevant clinic and socioeconomic problem due to its deep impact on quality of life and prognosis. Vascular dementia is caused by different mechanisms all resulting in vascular lesions in the brain. In this regard, current concept on atherogenesis identify in the proatherogenic activation of vascular endothelial cells and platelets a fundamental step in the onset and progression of atherosclerotic vascular damage.

Aim: Starting from these evidence we aimed to evaluate the role of patherogenic vascular inflammation in the progression of cognitive impairment in patients with vascular dementia.

Methods: We assessed circulating levels of soluble (s) CD40L and P-selectin, as indices of platelet activation, and of ICAM-1 and VCAM-1, as indices of endothelial activation in 78 patients (73.2 ± 4.2 years) with newly diagnosed vascular dementia (NINDS-AIREN criteria) and in 56 healthy sex and age-matched control subjects (75.2 ± 4.1 years). After baseline evaluations patients with vascular dementia were re-evaluated every six months up to 2 years.

Results: At baseline, circulating biomarkers of endothelial (sICAM-1: 345.5 ± 112.5 vs 188.2 ± 65.0 ng/mL, p < 0.0001; sVCAM-1: 634.2 ± 132.3 vs 443.2 ± 125.3 ng/mL, p < 0.002) and platelet activation (sCD40L: 7.2 ± 2.4 vs 2.9 ± 0.9 ng/L, p< 0.0001; sP-selectin: 67.3 ± 22.2 vs 54.1 ± 8.1 ng/mL, p< 0.003) were higher in demented patients than in controls. At the end of follow-up period, a progression of cognitive impairment was observed in demented patients with a mean decrement of MMSE score of 3.2 ± 1.0 (range 0.4–4.7). Spearman non-parametric correlation found significant relationships between changes of MMSE score at the end follow-up and baseline circulating levels of sCD40L (r= 0.452, p < 0.002) and sICAM-1 (r = 0.533, p< 0.001). In addition, by multivariate regression analysis baseline sCD40L and sICAM-1 levels were found to be independent predictors of MMSE score decrement after adjustment for potential confounders, explaining about 10% and 12% of MMSE score changes, respectively. In conclusion, our data demonstrated the existence of a tight relationship between the degree of proatherogenic activation of vascular endothelial cells and platelets and the progression of cognitive impairment in patients with vascular dementia.

Conclusions: These results, if confirmed in larger study population, could provide a useful tool to identify demented patients at high risk for disease progression and to evaluate the potential efficacy of intervention strategy aiming to least slow down the progression of dementia.

13.34 Role of CD40/CD40L System in the Pathophysiology of Cognitive Impairment in Old Hypertensive Patients with Non-Dipper Blood Pressure Profile

G. Desideri,¹ D. Grassi,¹ R. Bocale,² I. Petrella,¹ G. Croce,¹ B. Volpe,² S. Tiberti,¹ G. Mauti² and C. Ferri¹

1 Università degli Studi dell’Aquila, Dipartimento di Medicina Interna e Sanità Pubblica, L’Aquila, Italy; 2 Ospedale S. Rinaldi, Pescina, Italy

Introduction: Hypertension is a risk factor for cognitive impairment and dement. The evidence of a tight relationship between blood pressure and cognitive impairment which is already evident starting from high-normal blood pressure values, suggest the existence of a continuum of cognitive damage in hypertensive patients. According to this, a relationship between cognitive impairment and target organ damage has been described in hypertension.

Aim: To evaluate whether or not non-dipping blood pressure profile could be associated with impaired cognitive impairment in hypertensive patients. Furthermore, starting from previous evidence from our group of an involvement of CD40/CD40L in the pathophysiology of vascular damage in hypertensive patients and in cognitive impairment progression in Alzheimer disease, we also assessed the potential involvement of this system in the pathophysiology of cognitive impairment in non-dipper hypertensive patients.

Methods: We studied 2 groups or 25 never-treated old hypertensive patients (age >75 years), without additional cardiovascular risk factors, clinically evident cerebrovascular disease or overt dementia, differentiated on the basis of a nocturnal decrease of BP either of >10% (dippers) or <10% (non dippers) of daytime values, and in 25 matched normotensives. Cognitive function was assessed in all participants by MMSE, Trail Making Test A and B, Verbal Fluency Test. The result of these tests were logarithmically transformed and used to calculate a composite cognitive score.

Results: Circulating levels of soluble CD40L and the lipid peroxidation product 8-iso- prostaglandin( PG)F2alfa were also assessed. Cognitive performance were found to be worse in hypertensive patients in comparison to normotensive subjects (−0.26 ± 0.06 vs −0.13 ± 0.06, p < 0.001) especially in those with blunted nocturnal blood pressure fall (non-dipper: −0.30 ± 0.04, dipper: −0.23 ± 0.05, p < 0.001). Circulating levels of soluble CD40L (non-dipper: 4.7 ± 1.5 ng/mL; dipper: 4.0 + 1.3 ng/mL; controls: 3.0 ± 1.5 ng/mL) and 8-iso-PGF2alfa (non-dipper: 387 ± 123 pg/L; dipper: 314 ± 110 pg/L; controls: 271 ± 53 pg/L) were significantly higher in non-dipper than in dipper hypertensive patients and controls (p < 0.01). In the whole study population significant relationships between circulating soluble CD40L levels, cognitive score (r : 0.369, p< 0.001) and plasma levels of lipid peroxidation products (r : 0.557, p < 0.0001) were found. In a multivariate regression analysis sCD40L was found to be an independent determinant of cognitive impairment in the study population.

Conclusions: The results of our study suggest that non-dipping blood pressure profile is associated with cognitive dysfunction in hypertensive patients probably due to an overactivation of CD40/CD40L system.