2022 NATIONAL CONGRESS OF THE ITALIAN SOCIETY OF HYPERTENSION (SIIA)

METABOLIC ASPECTS AND RELATED RISK FACTORS

URIC ACID RELATIONSHIP WITH LIPIDS AND ADIPOSITY INDICES: ROLE OF DIFFERENT HYPERURICEMIA CUT-OFF

Alessandro Maloberti^1,2, Jennifer Vanoli^2,3, Elia Gelfi^2,3, Alessandra Annaloro^2,3, Rita Facchetti^2,3, Giuseppe Mancia², Guido Grassi^2,3

¹ Cardiology 4, “A. De Gasperis” Cardio Center, ASST GOM Niguarda Ca’ Granda, Milan, Italy; ² School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; ³ Internal Medicine Department, San Gerardo Hospital, Monza, Italy

Introduction: The studies published so far on the relationship between Uric Acid (UA) and lipids have found an association mainly with triglycerides. Furthermore, studies on adiposity indices and have been based on the evaluation principally of the Visceral Adiposity Index (VAI).

Aim: To provide in the same population a systematic evaluation of lipids and adiposity indices with UA. Furthermore, we test both the classic cut-off for hyperuricemia (6/7 mg/dL for females/males) and the newly one identified in the URRAH study (5.1/5.6 mg/dL for females/males).

Methods: We analysed data from 1892 subjects of the PAMELA study with available UA, lipids (total cholesterol, HDL, LDL, non-HDL, triglycerides) and variables needed to calculate VAI, Cardio-Metabolic Index (CMI) and Lipid Accumulation Product (LAP).

Results: at linear regression model (corrected for age, sex, systolic blood pressure, diabetes, body mass index, glomerular filtration rate, statins and antihypertensive therapies) UA correlates with all the lipids values (with the strongest beta for triglycerides) and adiposity indices (VAI beta:0.26; CMI beta: 0.24; LAP beta 0.29). When the two different cut-offs were compared the URRAH one is significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non-HDL, p < 0.001) while this was not the case for the classic one. Regarding adiposity indices the classic cut-off present highest OR (1.82, 1.73 and 2.50 for VAI, CMI and LAP respectively, p < 0.001) in comparison to the URRAH one (1.61, 1.53 and 1.99 respectively, p < 0.001).

Conclusions: Newly reported URRAH cut-off for hyperuricemia better relate to atherogenic lipoprotein (LDL and non-HDL) when compared to the classic one. The opposite has been found for adiposity indexes where the classic cut-off seems to present highest performance. Among adiposity indexes, LAP present the highest OR for the relationship with hyperuricemia. We can speculate that hyperuricemia can determine cardiovascular events at lower cut-offs mainly through pro-atherogenic lipoprotein while, when UA further increase, also adiposity and general metabolic derangement concurs.

SERUM URIC ACID, LEFT VENTRICULAR MASS AND CARDIOVASCULAR DEATH. THE URIC ACID RIGHT FOR HEART HEALTH (URRAH) STUDY

Maria Lorenza Muiesan, Massimo Salvetti, Anna Paini, Claudia Agabiti-Rosei, Agostino Virdis, E. Casiglia, Valerie Tikhonoff, C.M. Barbagallo, M. Cirillo, Giovambattista Desideri, Claudio Ferri, Ferruccio Galletti, Cristina Giannattasio, Guido Iaccarino, Francesca Mallamaci, Stefano Masi, A. Mazza, Paolo Palatini, Roberto Pontremoli, Paolo Verdecchia, Massimo Volpe, Guido Grassi, Claudio Borghi, on behalf of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension

Introduction: A relationship between serum uric acid (UA) and CV events has been documented in the URRAH study. The association between UA and left ventricular mass index (LVMI) has been investigated with heterogeneous results.

Aim: To investigate the association between UA and LVMI and whether UA and LVMI or they combination may predict the incidence of death for CV disease (CVM) in a large Italian cohort in the frame of the Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)

Methods: URRAH study is a nationwide, multicentre, observational cohort study involving data on subjects aged 18 to 95years,recruited on a community basis from all regions of Italy under the patronage of the SIIA.CVM was defined as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. Multivariate Cox regression models having CVM as dependent variables, adjusted for age, sex, BMI, SBP, glycemia, total cholesterol, triglycerides, HDL-cholesterol, smoking and estimated glomerular filtration rate (eGFR) were used to search for an association between UA and LVMI as a continuous variable and CVM.LVH was defined as LVMI > 95g/m² in women and 115 g/m² in men

Results: 10733 subjects (mean age, 54 years; 51% female) with echocardiographic LVMI measurements were included in the analysis study. A significant association between UA and LVMI was confirmed in multiple regression analysis in both sexes (men: beta 0,095, F 5.47, P < 0.001; women: beta 0.069, F 4.36, P < 0.001).During follow-up(median 130 months), 319 subjects died for a CV event, including myocardial infarction, angina pectoris, congestive heart failure and cerebrovascular disease. Previously identified sex specific cut off values (5.6 mg/dl men, 5.1 mg/dl women) and LVH were used to define 4 different groups (normal UA and LVMI, increased UA and no LVH, normal UA and LVH, increased UA and LVH). Kaplan–Meier curves showed a significantly poorer survival rate in the group with higher UA and LVMI (log-rank chi-square 298.105; P < 0.0001).Multivariate Cox regression analysis showed that in women LVH alone [HR 2.25 (1.076 to 4.721); P = 0.03]and the combination of higher UA and LVH [HR 3.785 (1.789 to 8.008); P = 0.001],but not hyperuricemia alone, were associated with a higher risk of CVD, while in men hyperuricemia without LVH [HR 2.338 (1.292 to 4.232); P = 0.005], LVH without hyperuricemia [HR 3.008 (1.750 to 5.449); P = 0.001]and their combination [HR 5.273 (3.044 to 9.135); P = 0.001] were all associated with a higher incidence of CVM.

Conclusions: Our findings demonstrate that UA is independently associated with LVMI and suggest that the combination of hyperuricemia with LVH is an independent and powerful predictor for CVM both in men and women. The association between UA and CVD events may be explained in part because of a direct association of UA with LVMI.

URIC ACID RELATIONSHIP WITH LIPIDS AND ADIPOSITY INDICES: ROLE OF DIFFERENT HYPERURICEMIA CUT-OFF

Alessandro Maloberti^1,2, Jennifer Vanoli^2,3, Elia Gelfi^2,3, Alessandra Annaloro^2,3, Rita Facchetti^2,3, Giuseppe Mancia², Guido Grassi^2,3

¹Cardiology 4, “A.De Gasperis” Cardio Center, ASST GOM Niguarda Ca’ Granda, Milan, Italy; ² School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; ³ Internal Medicine Department, San Gerardo Hospital, Monza, Italy

Introduction: The studies published so far on the relationship between Uric Acid (UA) and lipids have found an association mainly with triglycerides. Furthermore, studies on adiposity indices and have been based on the evaluation principally of the Visceral Adiposity Index (VAI).

Aim: To provide in the same population a systematic evaluation of lipids and adiposity indices with UA. Furthermore, we test both the classic cut-off for hyperuricemia (6/7 mg/dL for females/males) and the newly one identified in the URRAH study (5.1/5.6 mg/dL for females/males).

Methods: We analyzed data from 1892 subjects of the PAMELA study with available UA, lipids (total cholesterol, HDL, LDL, non-HDL, triglycerides) and variables needed to calculate VAI, Cardio-Metabolic Index (CMI) and Lipid Accumulation Product (LAP).

Results: At linear regression model (corrected for age, sex, systolic blood pressure, diabetes, body mass index, glomerular filtration rate, statins and antihypertensive therapies) UA correlates with all the lipids values (with the strongest beta for triglycerides) and adiposity indices (VAI beta:0.26; CMI beta: 0.24; LAP beta 0.29). When the two different cut-offs were compared the URRAH one is significantly related to atherogenic lipids profile (OR 1.207 for LDL and 1.33 for non-HDL, p < 0.001) while this was not the case for the classic one. Regarding adiposity indices the classic cut-off present highest OR (1.82, 1.73 and 2.50 for VAI, CMI and LAP respectively, p < 0.001) in comparison to the URRAH one (1.61, 1.53 and 1.99 respectively, p < 0.001).

Conclusions: newly reported URRAH cut-off for hyperuricemia better relate to atherogenic lipoprotein (LDL and non-HDL) when compared to the classic one. The opposite has been found for adiposity indexes where the classic cut-off seems to present highest performance. Among adiposity indexes, LAP present the highest OR for the relationship with hyperuricemia. We can speculate that hyperuricemia can determine cardiovascular events at lower cut-offs mainly through pro-atherogenic lipoprotein while, when UA further increase, also adiposity and general metabolic derangement concurs.

SERUM ACID URIC PREDICTS ALL-CAUSE AND CARDIOVASCULAR MORTALITY INDEPENDENTLY FROM FASTING TRIGLYCERIDES LEVELS: A SUB-ANALYSIS OF THE URIC ACID RIGHT FOR HEART HEALTH (URRAH) STUDY

Alessandro Mengozzi^1,2, Nicola Riccardo Pugliese¹, Stefano Taddei¹, Stefano Masi^1,3, Claudio Borghi⁴, Agostino Virdis¹, Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension (SIIA)

¹Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italia, ²Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italia, ³Institute of Cardiovascular Science, University College London, Londra, UK, ⁴Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italia

Introduction: Serum urate acid (SUA) and serum fasting triglycerides (fTG) have been acquiring relevance as cardiovascular risk factors.

Aim: To evaluate their relative role in terms of all-cause (AcM) and cardiovascular mortality (CVM).

Methods: To pragmatically evaluate the predictive values of SUA and fTG, we tested the cut-offs of Uric Acid Right for Heart Health study (URRAH) study for all-cause mortality (AcM; SUA > 4.7 mg/dL) and cardiovascular mortality (CVM; SUA > 5.6 mg/dL) on subjects without chronic end-stage diseases. Population was stratified according to normal (nTG) and high (fTG > 150 mg/dL) serum triglycerides (hTG) and classified according to their cardiometabolic disease: hypertension (HT), obesity (Ob) or type 2 diabetes (T2D). Cut-offs were then tested on two different models of cardiometabolic disease, one independent and the other cumulative (according to an arbitrary chosen HT ObT2D progression), comparing nTG vs hTG.

Results: In patients (n = 13,381) from URRAH study, fTG and SUA were related, even after adjustment for age, sex, BMI (p < 0.001). Multivariate Cox regression analyses, after adjustment for confounders (age, sex, BMI, smoking, blood pressure, total cholesterol, HDL, glycaemia, creatinine and diuretics) showed an independent association of both SUA and fTG with AcM (HR 1.22 [1.10–1.34] and 1.14 [1.02–1.27]) and CVM (1.48 [1.29–1.69] and 1.14 [1.01–1.34]). Association between fTG and SUA was confirmed for both nTG and hTG (p < 0.001). In the exploratory analysis across the cardiometabolic spectrum, SUA > 5.6 mg/dL confirmed its predictive power in CVM (Figure).

Conclusions: Uric acid and triglycerides independently affect cardiovascular risk. URRAH cut-offs show consistency in CVD prediction in patients with different levels of fTG, confirming the relevance of including uric acid in the cardiovascular risk stratification. The different trends observed in AcM require further investigation as they might be justified by the hyperactivation of synergic noxious pathways affecting mortality.

Figure 1 Trend of all-cause mortality and cardiovascular mortality across different models using URRAH study cut-offs: SUA > 4.7 mg/dL for AcM e SUA > 5.6 mg/dL for CVM. A-B: independent model: each disease is an independent risk factor, without taking into account other comorbidities; C-D: cumulative model: each cardiometabolic disease is added to the antecedent according to a progression HT → Ob → T2D.

ASSOCIATION BETWEEN METABOLIC SYNDROME AND LOW BONE MINERAL DENSITY IN FREE-LIVING WOMEN AT RISK FOR OSTEOPOROSIS

Veronica Abate¹, Alfonso Giaquinto¹, Domenico Rendina¹, Domenico Prezioso², Gaetano Piccinocchi³, Marco Evangelista¹, Gianpaolo De Filippo⁴, Biagio Barone², Lanfranco D’Elia¹, Pasquale Strazzullo¹

¹Department of Clinical Medicine and Surgery, Federico II University Hospital, Naples, Italy. ²Department of Neuroscience Reproductive Sciences and Dentistry, Federico II University, Naples, Italy. ³“COMEGEN” Medical Cooperative, 80126, Naples, Italy. ⁴Assistance Publique—Hôpitaux de Paris, Hôpital Robert-Debré, Service d’Endocrinologie et Diabétologie, Paris, France

Introduction: Osteoporosis (Op) and metabolic syndrome (MetS) are two common disorders showing common pathogenic patterns.

Aim: This cross-sectional study was performed to evaluate if MetS and its constitutive elements are associated to an increased risk of low bone mineral density (BMD) in free-living women examined by Dual-energy X-ray absorptiometry (DXA) for suspected Op.

Methods: 13,182 free-living Caucasian women, referring to "COMEGEN" general practitioners cooperative operating in Naples, Italy, performed a contextual evaluation of BMD by DXA and all MetS constitutive elements (systolic and diastolic blood pressure, waist circumference, serum levels of triglycerides, high-density lipoprotein cholesterol, and fasting glucose) between June 1st 2008 and May 31st 2018. Subjects aged less than 40 years or with signs or symptoms suggestive of secondary Op were excluded from the study.

Results: MetS is associated to an increased risk of low BMD (Odds Ratio 1.19; 95% Confidence Interval 1.08–1.31). Among MetS constitutive elements, hypertension was associated to increased risk of low BMD, whereas high fasting glucose level/diabetes were associated to reduced risk of low BMD.

Conclusions: The significant association between Op and MetS in free-living women examined by DXA for suspected Op suggests the advisability of a contextual evaluation of both disorders in this setting.

METABOLIC CONTROL AMELIORATES LEFT VENTRICULAR MECHANO-ENERGETIC EFFICIENCY IN HYPERTENSIVE PATIENTS

Maria Lembo, Costantino Mancusi, Maria Virginia Manzi, Maria Assunta Elena Rao, Giovanni De Simone, Carmine Morisco, Giovanni Esposito, Raffaele Izzo, Bruno Trimarco

Department of Advanced Biomedical Sciences, University of Naples, Italy

Introduction: Arterial hypertension, especially when associated with additional cardiovascular risk factors, could determine an imbalance between myocardial demand and altered energetic efficiency, leading to early left ventricular (LV) systolic dysfunction, even in terms of mechano-energetic efficiency indexed for myocardial mass (MEEi).

Aim: To analyse clinical, metabolic and therapeutic determinants of LV MEEi improvement in hypertensive patients with a long-term follow up.

Methods: The study population included 6687 hypertensive patients followed-up for 5.3 ± 4.5 years, enrolled in the Campania Salute Network, undergoing both echocardiographic and clinical evaluation. MEEi was obtained as the ratio between stroke work and oxygen consumption indexed for LV mass. ΔMEEi was calculated as the difference between follow-up and baseline MEEi and ΔMEEi quartiles were derived. Patients in the highest ΔMEEi quartile (≥ 0.0454 mL/s/g) (group 1) were compared to the ones of merged first, second and third quartiles (< 0.0454 mL/s/g) (group 2). LV mass index reduction was defined for a decrease of at least of 5g/m2.7 from baseline. METS-IR was calculated as {ln[2*Fasting-plasma-glucose(mg/dL)+Triglycerides(mg/dL)]*BMI(kg/m2)/ln[HDL-Cholesterol(mg/dL)]}.

Results: Patients in group1 were younger (p < 0.0001), less often diabetic (p = 0.001) and obese (p = 0.035). Despite comparable values of both mean systolic and diastolic blood pressure during the follow-up, group1 experienced more frequently LV mass index reduction and had a better metabolic control in terms of METS-IR (both p < 0.0001), lower mean serum triglycerides(p = 0.005) and fasting glucose plasma levels(p = 0.005) and higher mean HDL cholesterol values (p = 0.001) during the follow up. Beta-blockers were more often used in group 1 (p < 0.0001) than group 2.

A logistic regression analysis showed that younger age, better metabolic control in terms of METS-IR, higher LV mass index reduction, therapy with beta blockers were significantly associated with LV MEEi improvement, independently on the presence of diabetes and obesity.

Conclusions: Metabolic control and therapy with beta-blockers contribute to improvement of left ventricular mechano-energetic efficiency over time in hypertensive patients.

ASSOCIATION BETWEEN BERLIN QUESTIONNAIRE INDEX, HYPERTENSION AND METABOLIC PROFILE IN TREATED AND UNTREATED HYPERTENSIVE PATIENTS

Jennifer Vanoli¹, Michele Bombelli², Raffaella Dell’Oro¹, Rita Facchetti¹, Miriam Nava¹, Cecilia Cappellini¹, Beatrice Scali¹, Guido Grassi¹

¹ Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; ² University of Milano-Bicocca, ASST-Brianza, Pio XI Hospital, Internal Medicine, Desio, Italy

Introduction: Essential hypertension and sleep disorders are closely related and increase risk of major cardiovascular outcomes.

Aim: To evaluate the association between the Berlin questionnaire (BQ) index and hypertension and metabolic profile both in treated and untreated hypertensive patients.

Methods: This is a cross-sectional study performed on 598 subjects enrolled in the PAMELA study (Pressioni Arteriose Monitorate E Loro Associazioni), a cohort recruited to be representative of the general population, for which a validated questionnaire, antihypertensive drug history, metabolic profile, blood pressure (BP) and heart rate (HR) measurements were available.

Results: Mean age was 66 ± 10 years and the 48.5% was men. 211 subjects (35%) had a positive BQ with 2 or more positive categories of the inquiry. These selected subjects compared to those without sleep disorders showed a greater male prevalence (55.9%), worse serum glucose and triglycerides profile, greater BMI (28.9 ± 4.9 vs 24.9 ± 3.4) and higher both office systolic (S) and diastolic (D) BP (139.6 ± 17.6 and 84.5 ± 9.3 vs 134.5 ± 17.7 and 82.7 ± 8.8 for SBP and DPB, respectively) and HR values (72.4 ± 10.7 vs 69.5 ± 9.5). Furthermore, these subjects exhibited organ damage with elevated serum creatinine values and a greater rate of echocardiographic left ventricular (LV) hypertrophy (25% vs 13% for LV mass indexed for height2.7). Untreated subjects with anti-hypertensive therapy exhibited these same characteristics, while in treated patients, no significant difference was observed among those with positive BQ when compared to those with negative BQ.

Conclusions: BQ identifies among naïf subjects those with worse hypertensive and metabolic control and with higher cardiovascular risk because of organ damage. Instead, among subjects under anti-hypertensive treatment, the findings of our study showed no difference between those affected by sleep disorders and who were not, suggesting a control achievement of BP and metabolic assessment in both conditions.

COFFEE CONSUMPTION RELATES TO A REDUCTION OF VASCULAR AND HEART DAMAGE IN WELL-CONTROLLED HYPERTENSIVES

Miriam Di Trani¹, Marialuisa Svevamarozzi¹, Antonio Vacca², Gabriele Brosolo²,Cristiana Catena^{2, G}iuseppe Ranieri¹, Leonardo Albertosechi², Sebastiano Cicco¹

¹Unit of Internal Medicine “Guido Baccelli”, Department of Biomedical Sciences and Human Oncology, University of Bari "Aldo Moro", Bari, Italy; ²Division of Internal Medicine, Department of Medicine, Building 8, University of Udine, I-33100 Udine (UD),Italy

Introduction: Nutritional interventions that could prevent hypertension-related organ damage are far from being fully defined. Coffee is one of the most used beverages all over the world. Many studies have tried to define the optimal amount of coffee in order to understand whether coffee has a role in cardiovascular prevention.

Aim: Thus, we evaluated heart and vascular damage in well controlled hypertensives according to coffee consumption.

Methods: We evaluated 316 patients (150F, 166M, aged 62.22 ± 10.76) with essential hypertension. All patients were checked for organ damage screening. The number of coffee cups per day was asked during the visit. The median coffee consumption was 2 cups per day.

Results: Patients were subdivided into three groups according to tertiles of cups consumed: Group 1, 0-1 cups 112 patients (57F, 55M; 64.21 ± 10.91), Group 2, 2 cups, 101 patients (53F; 48 M; 61.95 ± 10.10), Group 3, > 2 cups, 103 patients (40F; 63M; 60.32 ± 10.95). No differences were seen in weight and BMI, nor in blood pressure (both systolic and diastolic). Group 1 had an increased left ventricular mass compared to the other two groups (p = 0.0008 and p = 0.019 respectively). Similarly, Group 1 had a significant reduction in E/e’ ratio (p = 0.042 and p = 0.019, respectively). No significance was found between Group 2 and 3 for left ventricular mass and diastolic function. Group 3 had an increased intima-media thickness (p = 0.004 and p = 0.005 vs Group 1 and 2, respectively). Prevalence of carotid stenosis was lower in Group 3 (p = 0.011 and p = 0.039, respectively) and was comparable in Group 1 and 2.

Conclusions: Coffee consumption may have a role in prevention of heart remodelling. Consumption of at least 2 cups of coffee per day reduces left ventricular mass and diastolic dysfunction.

CARDIOVASCULAR RISK AND DAMAGE IN PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY

Alessandro Bressan¹, Elisabetta Faggin¹, Francesco Cinetto², Carla Felice², Maristella Donato³, Chiara Nardin², Riccardo Scarpa², Anna Spada², Patrick Bez², Alessandro Dell’edera², Carlo Agostini², Marcello Rattazzi²

¹Department of Medicine, University of Padua, Padua, Italy; ²Medicina Generale I^, Ca' Foncello Hospital, 31100 Treviso, Italy; ³ Department of Pharmaceutical and Pharmacological Sciences, University of Padua, Padua, Italy

Introduction: Although the immune system is involved in vascular disorders, the actual role of B cells in atherosclerotic cardiovascular disease (ASCVD) remains unclear (Pattarabanjird et al., 2021). Common Variable Immunodeficiency (CVID) is a rare primary immunodeficiency of adulthood and represents a pathological condition suitable for studying the role of B cells in ASCVD (Bonilla et al., 2016). The cardiovascular risk profile of patients affected by this rare disease is unexplored and it is unclear whether CVID patients are protected towards atherogenesis.

Aim: We investigated the prevalence of cardiovascular risk factors and the presence of subclinical ASCVD in CVID patients.

Methods: We enrolled 123 CVID patients divided by clinical phenotype in patients presenting only infection and patients with complications (autoimmunity, polyclonal lymphoproliferation, enteropathy). Clinical and biochemical data were collected. Vascular structural and functional investigation was performed evaluating the presence of atherosclerotic plaques, arterial elastic properties, intima media thickness and endothelial function.

Results: patients with complicated clinical phenotype showed increased inflammatory markers like CRP (6.0 ± 4.3 vs 3.6 ± 1.2 mg/L) and more often requiring steroidal (30.6% vs 11.6%, p = 0.017) and immunosuppressive treatment (23.5% vs 0%, p < 0.001), presented lower total cholesterol (182 ± 36 vs 204 ± 41 mg/dl, p = 0.009) and LDL cholesterol (112 ± 33 vs 129 ± 42 mg/dl, p = 0.04), as well as lower blood glucose (89 ± 14 vs 98 ± 17 mg/dl, p = 0.011) and glycosylated haemoglobin levels (33 ± 4 vs 38 ± 6 mmol/mol, p < 0.001) as compared to uncomplicated cohort. FMD and IMT were no different between groups in a sub-cohort of 45 patients.

Conclusions: Our data suggest that clinical phenotypes of CVID may be associated with different cardiovascular risk profiles, possibly based on the different underlying immunological alterations.

IMPORTANCE OF URIC ACID THRESHOLD IN ITS CORRELATION WITH METABOLIC SYNDROME

Alessandro Maloberti, Ilaria Garofani, Stefano Fumagalli, Claudio Mario Ciampi, Ossola Paolo, Marco Carbonaro, Monticelli Massimiliano, Giovanni Tavecchia, Michele Bombelli, Cristina Giannattasio

Cardiologia 4, ospedale Niguarda, Milano, Italia; Scuola di medicina e chirurgia, Università Milano-Bicocca, Milano, Italia; Medicina Interna, Ospedale di Desio, Desio, Italia

Introduction: The relationship between Hyperuricemia and Cardiovascular risk has been established, but whether or not a correlation between Serum Uric Acid (SUA) and Metabolic Syndrome (MS) exists is still a matter of debate. Indeed, whether SUA level is part of MS diagnosis or just a pure marker of an unfavourable metabolic profile has not been demonstrated. Besides it’s unknown whether SUA’s addition to MS definition makes a difference in terms of prognosis.

Aim: To evaluate in a group of hypertensive patients, the correlation between MS diagnosis and SUA defined with two different cut-off: (1) ≥6 mg/dL for women and ≥7 for men (classic cut-off); (2) > 5.6 mg/dL for both sexes (recently proposed by the URRAH Project).

Methods: We enrolled 473 Hypertensive patients followed by the Hypertension Unit of San Gerardo Hospital (Monza, Italy), in which SUA was measured. Patients with Hyperuricemia were identified according to the two different thresholds. NCEP-ATP-III criteria were used for diagnosis of MS.

Results: MS was diagnosed in 33.6% while Hyperuricemia was found in 14.8% of subjects according to the traditional cut-off and 35.9% according to URRAH study’s cut-off. Hyperuricemia and MS coexist in 9.7% (traditional cut-off) and 17.3% (URRAH’s threshold) of the population. Hyperuricemia was more frequent in MS than in non-MS subjects (29 vs 7.6%, p value < 0.0001 for cut-off 6/7 mg/dL and 51.6 vs 28.0%, p-value < 0.0001 for cut-off 5.6 mg/dL). Linear regression models showed that SUA is related to MS diagnosis (β = 1.597, p value < 0.0001). At logistic analysis Hyperuricemia was strongly related to MS when defined by the HURRAH's cut-off (OR = 0.303, p value < 0.0001). The same relation is weak, although significant, when Hyperuricemia was defined by the classic cut-off (OR = 0.182, p value < 0.0001).

Conclusions: Hyperuricemia is related with MS diagnosis especially when defined by the recently defined cut-off of 5.6 mg/dL.

RENAL RESISTIVE INDEX IS ASSOCIATED WITH MICROVASCULAR REMODELLING IN PATIENTS WITH OBESITY

Alessandro Mengozzi^1,2, Diego Moriconi¹, Rosa Maria Bruno³, Stefano Masi¹, Monica Nannipieri¹, Agostino Virdis¹

¹Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italia; ²Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italia; ³INSERM U970, Cardiovascular Research Center-PARCC, Paris, France

Introduction: Though renal haemodynamics is supposed to be impaired since the early stage of cardiometabolic disease, its non-invasive indices still fail to provide pathophysiologic and clinical meaningfulness in patients with severe obesity.

Aim: Explore the relationship between systemic and renal-specific non-invasive hemodynamic indices and gold-standard microcirculatory assessment in patients with severe obesity.

Methods: We enrolled patients with obesity (n = 50) referring to our outpatient obesity clinic with an indication for bariatric surgery. Patients underwent an extensive metabolic and renal examination, paired with abdominal color Doppler ultrasound and the renal resistive index (RRI) measurement. eGFR was calculated according to EPI cys-cr formula. Visceral fat biopsies were collected on the day of the surgery to perform an ex-vivo complete (structural and functional) microcirculatory assessment. In detail, media-to-lumen ratio (M/L) and vascular response to acetylcholine (ACh) alone or co-incubated with L-NAME (to assess the nitric oxide contribution to vasodilation) were measured.

Results: The study population was 45 ± 13 years old, 72% females, BMI of 45.1 ± 7.0 Kg/m², 128 ± 10/81 ± 7 mmHg systolic/diastolic blood pressure. 20% were type 2 diabetics, 42% hypertensive, 12% albuminuric. eGFR mean was 100 ± 24 ml/min/1.73m², RRI 0.64 ± 0.04, M/L 0.09 ± 0.02, vasorelaxation to ACh 66.8 ± 9.3% and L-NAME inhibition 15.2 ± 9.0%. M/L was related to RRI (p = 0.003, St.β 0.41) (Figure 1A). Vasodilation to ACh and L-NAME inhibition were associated with mean arterial blood pressure (p = 0.001, St.β = − 0.44 and p = 0.001, St.β = − 0.40, respectively) (Figure 1B-C). Notably, all these correlations were consistent also after adjustment for confounding factors.

Conclusions: The RRI relationship with the microvascular remodelling in patients at the very early stage of cardiometabolic derangement supports the hypothesis of a profound tight pathophysiologic connection of the renal haemodynamic with microcirculatory disruption. As small pilot studies have shown the rescuing potential of treatments (such as bariatric surgery) on RRI, our data endorse early addressing of the cardiometabolic disease.

Figure 1 Relationship between M/L and RRI (A), vasodilation to acetylcholine and mean arterial pressure (B), L-NAME inhibition and mean arterial pressure (C).

SERUM MYOSTATIN IS ASSOCIATED WITH PULSE WAVE VELOCITY RATIO IN HEALTHY ADOLESCENTS. THE MACISTE STUDY

Marco D’Abbondanza², Rosa Curcio^1,2, Luisa Nunziangeli³, Francesca Battista⁴, Fabio Anastasio⁵, Tommaso Campanella^1,2, Lorenzo Chiatti^1,2, Leandro Sanesi², Stefano Ministrini^6,5, Gaetano Vaudo^1,2, Giacomo Pucci^1,2

¹ Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia, Italy; ² Struttura Complessa di Medicina Interna, Azienda Ospedaliera “Santa Maria”, Terni, Italy; ³ Polo d’innovazione Genomica Genetica e Biologica, Terni, Italy; ⁴ Divisione di Medicina dello Sport e dell’Esercizio Fisico, Dipartimento di Medicina, Università di Padova, Padova, Italy; ⁵ Divisione di Cardiologia, Ospedale “Regina Montis Regalis”, Mondovì, Cuneo, Italy; ⁶ Centro di Cardiologia Molecolare, Università di Zurigo, Zurigo, Svizzera

Introduction: Serum myostatin (sMSTN) is a protein that regulates muscle growth and extracellular matrix production, also able to exert profibrotic and antihypertrophic effects on smooth muscle cells. Aortic-brachial pulse wave velocity ratio (PWVr) is a measure of arterial stiffness gradient between the aorta and peripheral arteries, known to reflect early arterial ageing.

Aim: Aim of the present study was to explore the association between sMSTN and arterial stiffness gradient, measured through the PWVr, in a cohort of healthy adolescents.

Methods: 128 healthy subjects (mean age 17 ± 2 years, 59% men) were randomly recruited among participants of the Metabolic And Cardiovascular Investigation at School, TErni (MACISTE) study. sMSTN was measured through enzyme-linked immunosorbent assay. PWV was measured through applanation tonometry (SphygmoCor) along the carotid-femoral (cf-PWV, aortic) and the carotid-radial (cr-PWV, brachial) pathways. PWVr was expressed as the ratio between cf-PWV and cr-PWV. BP was recorded simultaneously, and also expressed as systolic/diastolic BP percentiles (z-score).

Results: Mean BP was 126 ± 12/68 ± 8 mmHg (z-score 1.2 ± 0.9/0.3 ± 0.7). Mean Cf-PWV was 5.1 ± 0.9 m/s, cr-PWV was 6.9 ± 0.9 m/s. PWVr was 0.75 ± 0.12. PWVr increased linearly at increasing quartiles of sMSTN (0.71 ± 0.09, 0.74 ± 0.13, 0.75 ± 0.14, 0.78 ± 0.12, p for trend = 0.03, Figure 1). Subjects with higher than average PWVr had higher BMI (21.7 ± 2.6 kg/m² vs 20.8 ± 2.3 kg/m², p = 0.04) and SBP (1.39 ± 0.97 vs 0.97 ± 0.91, p = 0.01), whereas they did not differ in terms of age, sex, HR, adiposity and other CV risk factors. In a multivariate linear model, PWVr was independently predicted by SBP and sMSTN, both if expressed as continuous variable (beta = 0.21, p = 0.018) or in quartiles (beta = 0.26, p = 0.011).

Conclusions: In a cohort of healthy Italian adolescents, sMSTN was positively and independently associated to increased PWVr, a measure of arterial stiffness gradient. sMSTN might interfere with structural and functional components of the arterial wall, and might be a target of treatment to reduce early arterial ageing.

ANALYSIS OF CLINIC AND 24-HOUR AMBULATORY HEART RATE IN ADULT OUTPATIENTS WITH HYPERTENSION AND SEVERE OBESITY

Giuliano Tocci ¹, Guido Salvetti ², Barbara Citoni ¹, Ilaria Figliuzzi ¹, Francesca Miceli ¹, Giulia Nardoianni ¹, Barbara Pala ¹, Alessandro Basolo ², Ferruccio Santini ², Massimo Volpe ¹

¹ Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ² Obesity and Lipodystrophy Centre at the Endocrinology Unit, University Hospital of Pisa, Pisa, Italy

Introduction: Severe obesity, as defined by body mass index (BMI) ≥ 35 kg/m², has been associated to sustained blood pressure (BP) elevation and increased cardiovascular (CV) risk.

Aim: To evaluate clinic and 24-h, day-time and night-time ambulatory heart rate in adult outpatients with different degrees of obesity.

Methods: A single-centre, cross-sectional study was conducted in treated and untreated adult individuals (aged ≥ 18 years), who consecutively underwent full BP evaluation and global cardiovascular risk assessment at our Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy. All BP measurements were performed and BP thresholds were set according to European guidelines; cuff sizes and dimensions were adapted according to arm anatomy and diameters. Patients were then stratified into four categories according to BMI strata: (1) normal weight (BMI < 25 kg/m²); (2) overweight (BMI ≥ 25 and < 30 kg/m²); (3) class I obesity (BMI ≥ 30 and < 35 kg/m²); (4) class II/III obesity (BMI ≥ 35 kg/m²).

Results: We analyzed data from 9308 adult individuals (women 48.4%, mean age 57.6 ± 14.5 years, BMI 26.8 ± 4.5 kg/m², clinic BP 143.7 ± 20.0/90.0 ± 12.5 mmHg, 24-h BP 129.8 ± 13.7/79.2 ± 9.9 mmHg), among whom 37.3% had normal weight, 42.1% were overweight, 15.4% had class I, and 5.2% class II/III obesity. Clinic heart rate resulted significantly higher in patients with class II/III obesity than those with class I obesity or overweight (79.6 ± 13.7 vs. 75.9 ± 12.6 vs. 75.7 ± 15.6 bpm, respectively; P < 0.001). Similar trends were observed for 24-hour (76.6 ± 10.6 vs. 73.8 ± 9.7 vs. 72.5 ± 9.8 bpm; P < 0.001), day-time (78.7 ± 11.5 vs. 76.1 ± 10.4 vs. 74.9 ± 10.4 bpm; P < 0.001), and night-time (70.6 ± 10.7 vs. 67.0 ± 9.4 vs. 65.6 ± 9.2 bpm; P < 0.001) periods. BMI resulted significantly and positively related with both clinic (r = 0.028; P = 0.015), 24-h (r = 0.072; P < 0.001) (figure A), day-time (r = 0.058; P < 0.001) (figure B) and night-time (r = 0.103; P < 0.001) (figure C) heart rate. Patients with severe obesity also showed significantly lower nocturnal dipping of heart rate (9.1 ± 0.4%) compared to those with class I obesity (11.7 ± 8.4%) or overweight (12.1 ± 8.2%) (ANOVA P < 0.001).

Conclusions: Obesity was associated with higher heart rate during the entire 24-h period.

PREVALENCE OF WHITE-COAT HYPERTENSION, MASKED HYPERTENSION AND SUSTAINED HYPERTENSION IN ADULT OUTPATIENTS WITH DIFFERENT CLASSES OF OBESITY

Giuliano Tocci ¹, Guido Salvetti ², Ilaria Figliuzzi ¹, Barbara Citoni ¹, Francesca Miceli ¹, Giulia Nardoianni ¹, Priscilla Tifi ¹, Alessandro Basolo ², Ferruccio Santini ², Massimo Volpe ¹

¹ Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ² Obesity and Lipodystrophy Centre at the Endocrinology Unit, University Hospital of Pisa, Pisa, Italy

Introduction: It has been suggested that severe obesity, as defined by body mass index (BMI) ≥35 kg/m², may be associated to the occurrence of specific hypertension phenotypes, mostly including white-coat (WCHT) or masked (MHT) hypertension, rather than sustained hypertension (SHT).

Aim: To evaluate prevalence and clinical characteristics of WCHT, MHT and SHT in adult outpatients with different classes of obesity.

Methods: A single-centre, cross-sectional study was conducted in treated and untreated adult individuals (aged ≥ 18 years), who consecutively underwent full BP evaluation and global cardiovascular risk assessment at our Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy. All BP measurements were performed and BP thresholds were set according to European guidelines; cuff sizes and dimensions were adapted according to arm anatomy and diameters. The following definitions were applied: WCHT (clinic BP ≥ 140/90 mmHg; 24-h our BP < 130/80 mmHg), MHT (clinic BP < 140/90 mmHg; 24-h BP ≥130/80 mmHg), and SHT (clinic BP ≥ 140/90 mmHg; 24-h BP ≥ 130/80 mmHg). Patients were also stratified into four BMI categories: (1) normal weight (BMI < 25 kg/m²); (2) overweight (BMI ≥ 25 and < 30 kg/m²); (3) class I obesity (Bmi ≥ 30 and < 35 kg/m²); (4) class II/III obesity (BMI ≥ 35 kg/m²).

Results: We analyzed data from 9308 adult individuals (women 48.4%, mean age 57.6 ± 14.5 years, BMI 26.8 ± 4.5 kg/m², clinic BP 143.7 ± 20.0/90.0 ± 12.5 mmHg, 24-h BP 129.8 ± 13.7/79.2 ± 9.9 mmHg), among whom 37.3% had normal weight, 42.1% were overweight, 15.4% had class I, and 5.2% class II/III obesity. Obese patients were more frequently treated (P < 0.001) and received significantly more antihypertensive drugs (P < 0.001) than normal weight individuals. They also showed significantly higher values of day-time (P = 0.004) and night-time (P < 0.001) systolic BP levels than control groups. Only 12.5% of patients with class II/III obesity had WCHT, and 12.3% had MHT, having the majority (54.6%) a SHT profile (Figure A). In particular, in untreated individuals MHT tended to reduce, while SHT tended to increase according to BMI strata (Figure B).

Conclusions: Our findings support the hypothesis that subjects with severe obesity frequently have sustained BP elevation, rather than transient or late BP rise, thus suggesting the need for full BP evaluation and proper antihypertensive treatment to reduce the risk of CV outcomes.

STRENGTHENING OF BALANCE-WALK IN OCCUPATIONAL THERAPY IN FRAIL ELDERLY WOMEN WITH METABOLIC SINDROME

Ferdinando D’Amico^1,2, Rosetta Grasso¹, Rossella D’Amico³

¹Department of Geriatrics - Long Term Care, Center of Hypertension, Hospital of Patti; ²School of Medicine, University of Messina; ³IRCCS of Troina

Aim: This study assessed reduced homeostatic reserves connected with frailty through balance-walk markers in elderly women affected by Metabolic Syndrome.

Methods: We examined 16 men (mean age 73 ± 3) and 14 women (mean age 69 ± 2) with Metabolic Syndrome. The design of the study included: 1) blood tests; 2) clinical measurement of blood pressure; 3) Short Physical Performance Battery (SPPB). Patients with a reported SPPB score comprised between 5 and 9 can be considered frail.

Results: Among all subjects 12 (7 men and 5 women) had a <9 SPPB score (group A); while 18 had a > 9 score (group B). Prevalence of uncontrolled hypertension (SBP 154 ± 3 and DBP 90 ± 4 mmHg, p < 0.005) was observed in group A. A substantial connection between reduced physical performance (SPPB < 9) and uncontrolled hypertension in group A (p < 0.01) was noted. Those 12 frail elderly patients were administered a 6-month occupational therapy program aimed at balance-walk strengthening with a 2-month check.

Conclusions: In elderly women affected by Metabolic Syndrome, the study assesses a relationship between uncontrolled hypertension and a reduced physical performance. Evaluation through SPPB was able to assess a reduced physical performance in balance-walk markers thus proving frailty. A combination of pharmacological and occupational therapy can empower physical performance in frail elderly patients affected by metabolic syndrome.

ATHEROSCLEROSIS AND INFLAMMATION

ATHEROSCLEROSIS ESTABLISHES ARTERY-BRAIN-CIRCUITS THAT MODULATE SPLENIC NERVOUS ACTIVITY

Lorenzo Carnevale¹, Sarajo Mohanta^2,3, Marialuisa Perrotta^1,4, Raimondo Carnevale¹, Fabio Pallante¹, Andreas Habenicht^2,3, Giuseppe Lembo^1,4, Daniela Carnevale^1,4

¹Department of AngioCardioNeurology and Translational Medicine, IRCCS Neuromed, Pozzilli, Italy; ²Institute for Cardiovascular Prevention, LMU Munchen, Munich, Germany; ³German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany; ⁴Department of Molecular Medicine, University of Rome “La Sapienza”, Rome, Italy

Introduction: The sympathetic nervous system hyperactivity is a known pathological processes involved in cardiovascular diseases. Recent findings have demonstrated the formation of arterial tertiary lymphoid organs on the adventitia of arteries with ongoing atherosclerosis, and the existence of artery-brain-circuits (ABC) with nerve fibers innervating these organs and projecting to the brain.

Aim: In this work we will evaluate how the peripheral nervous system reacts to pathological stimuli evoked from ABC during the atherosclerotic process.

Methods: Apoe Knock-out (KO) mice and matched Wildtype (WT) controls were evaluated by ultrasound imaging to evaluate the plaque volume in aortic arch and abdominal aorta. Young (3 months), adult (8 months) and old (12 months) mice underwent splenic nerve recording, while adult and old mice underwent coeliac vagus nerve recording.

Results: Young Apoe KO mice did not show atherosclerotic plaques in any aorta segment, and splenic nervous activity was similar to matched WT mice. KO adult and old mice shown atherosclerotic plaques in both analyzed aorta segments, showing a parallel increase in nervous activity on the splenic nerve, with firing frequency significantly correlated to the volume of plaques in both aortic arch and abdominal aorta. (Fig. A). Finally, coeliac vagus nerve activity was unaltered in adult KO mice, while was found to be increased in old KO mice (Fig. B).

Conclusions: The atherosclerotic plaque formation establishes ABC that in turn recruit a nervous drive towards the splenic district, favouring its pathological progression.

HEART

PROGNOSTIC IMPACT OF RENIN ANGIOTENSIN ALDOSTERONE SYSTEM INHIBITION IN HYPERTENSIVE PATIENTS UNDERGOING TRANSCATHETER AORTIC VALVE IMPLANTATION

Christian Basile, Costantino Mancusi, Anna Franzone, Marisa Avvedimento, Domenico Angellotti, Domenico Simone Castiello, Andrea Mariani, Rachele Manzo, Plinio Cirillo, Giovanni de Simone, Giovanni Esposito

University of Naples “Federico II”, Department of Advanced Biomedical Science

Introduction: Aortic Stenosis (AS) is a very common heart disease, with a prevalence that is increasing. Tissue renin-angiotensin-aldosterone system (RAAS) activation participates to fibrosis and worse outcomes.

Aim: We determine the impact of pre-procedural treatment with RAAS inhibitors (RAASi) on all-cause mortality, in a series of patients with severe AS who underwent transcatheter aortic valve implantation (TAVI).

Methods: We retrospectively examined 373 patients with AS who had undergone TAVI. Analyses were undertaken in the subgroup of hypertensive individuals (n = 327) with 2-year follow-up. Univariable and multivariable Cox regression models were built according to baseline RAASi therapy status [RAASi (n = 222) vs non-RAASi (n = 151)]. A second analysis was undertaken by categorizing patients in angiotensin II receptor blockers (ARBs) (n = 110) vs non-ARBs (n = 217) or angiotensin-converting enzyme inhibitors (ACEi) (n = 112) vs non-ACEi (n = 215) recipients.

Results: Among hypertensive TAVI patients, RAASi administration at baseline was significantly related to female gender (56.8%), heart failure (25.7%), chronic kidney disease (25.7%), atrial fibrillation (19.4%), use of calcium-channel blocker (26.6%) or anti-platelet therapy (68.5%) (all p < 0.05). All-cause mortality occurred in 23 (10.4%) patients on RAASi (9 on ARBs and 14 on ACEi), and in 21 of 151 patients not taking RAASi (13.9%).

In univariable COX regression model, overall, treatment with RAASi was associated with 54% reduction in 2-year all-cause mortality (HR = 0.46, 95% CI 0.25–0.84 p = 0.011). After multivariable control for significant confounders, this association was not statistically significant (95% CI 0.31-1.11 p 0.1). Analyzing pre-procedural ACEi and ARBs separately vs non RAASi recipients, ARB therapy was associated with 58% reduction in all-cause mortality (95% CI 0.18–0.95 p = 0.038) (Figure) that was confirmed in multivariate analysis whereas no impact of baseline ACEi was observed (Table).

Conclusions: ARBs, but not ACEi, are independently associated with decreased risk of 2-year all-cause mortality in a series of hypertensive patients with severe AS, who underwent TAVI.

Figure. Survival of patients on ARBs

Table.

Multivariate Cox regression model

	HR	95.0% CI for HR		p
		Lower	Upper
Angiotensin II receptor blockers (n/y)	0.416	0.182	0.952	0.038
ACE-inhibitor (n/y)	0.775	0.372	1.614	0.495
Calcium channel blocker (n/y)	1.13	0.544	2.347	0.744
Anti-platelets therapy (n/y)	0.813	0.408	1.622	0.557
Sex female	1.645	0.825	3.28	0.157
Age (years)	0.995	0.952	1.040	0.840
Systolic blood pressure (mmHg)	0.996	0.98	1.012	0.617
Heart failure (n/y)	2.462	1.318	4.602	0.005
Atrial Fibrillation (n/y)	1.87	0.941	3.714	0.074
Chronic kidney disease (n/y)	1.645	0.871	3.107	0.125

NURSING CARE MODEL USING TELEPHONE COUNSELING TO ASSESS AND IMPROVE ADHERENCE IN PATIENTS RECENTLY ADMITTED FOR ACUTE HF, A PILOT STUDY.

Filomena Attanasio, Ilaria Fucile, Maurizio Conte, Francesco Rozza, Nicola De Luca, Costantino Mancusi

¹Azienda Unità Sanitaria Locale di Modena, Ospedale Ramazzini Carpi (MO), Modena, Italy; ²Università Federico II di Napoli, Naples, Italy

Introduction: The progressive increase in chronic pathologies has determined the need for structuring new treatment strategies aimed at creating an initiative healthcare model. Heart failure (HF) is the leading cause of hospitalization in over 65 years old and is considered a major public health problem.

Aim: To validate a nursing care model using telephone counseling to assess and improve adherence to pharmacological and non-pharmacological prescription in patients recently admitted for acute HF.

Methods: A prospective study included 51 patients enrolled at Cardiac Rehabilitation Unit of the Federico II Hospital of Naples. All patients at the time of discharge received detailed prescription of drugs, nutritional and physiotherapy plans, self-monitoring of parameters such as weight and blood pressure. During the telephone interviews performed 15 and 30 days after discharge assessment and counseling on pharmacological and non-pharmacological prescription was done. Adherence to pharmacological therapy was assessed using Morisky Medication Adherence Scale (MMAS).

Results: 45 patients completed the study. Mean age of participant was 66.49 ± 12.8 years. Adherence to pharmacological therapy did not change during the study (MMAS score 7.52 ± 0.8 vs 7.64 ± 0.8) After the first phone call we demonstrated a significant improvement in self-monitoring of blood pressure (62.2% vs 100%) and body weight (37.8% vs 86.4%). Practice of exercise prescribed by physiotherapy at discharge improve from 40% to 65.9% at second phone call.

Conclusions: Our study demonstrate that a strategy based on phone call performed by nurse lead to improvement in non-pharmacological prescription with better adherence to self-monitoring of body weight, blood pressure and exercise prescription.

ASSOCIATION OF NON-ALCOHOLIC FATTY LIVER DISEASE WITH LEFT VENTRICULAR CHANGES IN TREATMENT-NAIVE PATIENTS WITH UNCOMPLICATED HYPERTENSION

Gabriele Brosolo, Cristiana Catena, Andrea Da Porto, Debora Donnini, Luca Bulfone, Antonio Vacca, Giorgio Soardo, Leonardo Sechi

Hypertension Unit, Liver Unit, Department of Internal Medicine, University of Udine, Italy

Introduction: Cardiac structural and functional changes have been demonstrated in patients with nonalcoholic fatty liver disease (NAFLD).

Aim: Because of the frequent association of NAFLD with hypertension, we examined the relationship of liver steatosis with left ventricular (LV) changes in patients with hypertension.

Methods: In a cross-sectional study, we included 360 treatment-naive, essential hypertensive patients who were free of cardiovascular and renal complications. Liver steatosis was assessed by 3 different clinical/biochemical scores (NAFLD Liver Fat Score, LFS; Fatty Liver Index, FLI; Hepatic Steatosis Index, HSI). Echocardiography was performed with standard B-mode and tissue-Doppler imaging.

Results: LV hypertrophy was present in 19.4% and LV diastolic dysfunction in 49.2% of patients who had significantly higher body mass index (BMI), blood pressure (BP), and HOMA-index and higher frequency of the metabolic syndrome and liver steatosis that was defined by presence of 2 or more positive scores. LV mass index increased progressively across patients who had none, 1, or 2 or more liver steatosis scores with associated progressive worsening of LV diastolic function. LV mass index was highly significantly and positively correlated with age, BMI, BP, HOMA-index, LFS and HSI. Logistic regression analysis showed that age, blood pressure, and liver steatosis scores independently predicted both LV hypertrophy and diastolic dysfunction. Liver steatosis predicted LV dysfunction but not LV hypertrophy even after inclusion in analysis of the HOMA-index.

Conclusions: NAFLD is associated with LV hypertrophy and diastolic dysfunction in untreated patients with hypertension. In hypertension, NAFLD could contribute to LV diastolic dysfunction with factors unrelated to insulin resistance.

CARDIOMEMS MONITORING SYSTEM IMPROVES PROGNOSIS OF PATIENTS WITH ADVANCED HEART FAILURE IN THE REAL-WORLD

Valeria Visco¹, Paola Di Pietro¹, Cristina Esposito², Antonella Rispoli¹, Nicola Virtuoso², Michele Manzo², Albino Carrizzo^1,3, Gennaro Galasso¹, Carmine Vecchione^1,3, Michele Ciccarelli¹

¹Department of Medicine, Surgery and Dentistry, University of Salerno, Italy; ²Department of Cardiology, "San Giovanni di Dio e Ruggi D'Aragona" Hopital-University, Salerno, Italy; ³Vascular Pathophysiology Unit, IRCCS Neuromed, Pozzilli, Italy

Introduction: Despite several pharmacological advances, the morbidity and mortality in heart failure (HF) remain high, posing a problem for both patients and the National Health System. The natural history of this disease alternates phases of stability and phases of exacerbation; this has led to the development of remote monitoring systems.

Aim: Specifically, in this study we have investigated a new therapeutic approach.

Methods: We enrolled 6 patients with end-stage HF, who received the combined CardioMEMS/Levosimendan strategy to reduce the number of hospitalizations and optimize both tailored adjustment of home therapy and infusions of Levosimendan. Specifically, CardioMEMS is a wireless sensor that can be implanted in the pulmonary artery, where it detects cardiac filling pressures, an objective measure of the patient's “hemodynamic congestion”; these pressures increase two weeks before the onset of symptomatic congestion.

Results: The 6 patients (72.25 ± 4.60 years; 33.33% female) who received the device did not have any complications related to the procedure. Patients were monitored daily by CardioMEMS; if the cardiologist detected a tendency for pulmonary artery diastolic pressure (PAPd) to rise, patients were contacted for home therapeutic changes. If no further changes were possible, the patient was hospitalized for the infusion of Levosimendan. In particular, following the implantation of CardioMEMS, a significant reduction in HF hospital admissions was recorded (hospitalizations/month: pre-CardioMEMS 0.657 ± 0.303 vs post-CardioMEMS 0.029 ± 0.021, p 0.0313). In addition, lower pulmonary arterial pressures were recorded at 6-months FU on CardioMEMS monitoring (pre vs post: PAPs: 51.25 ± 2.56 vs 42.75 ± 2.46 mmHg, p 0.0168; PAPd: 26.25 ± 0.85 vs 20.25 ± 0.85 mmHg, p 0.0034), a reduction in the echocardiographic E/e' (20.86 ± 1.77 vs 14.13 ± 2.02, p 0.0057), an improvement in the quality of life (EQ5D 75.17 ± 2.06 vs 108.60 ± 8.70, p 0.0078) and a reduction in IL-6 levels (p 0.0211).

Conclusions: In this study we present the first experience of serial infusions of Levosimendan guided by CardioMEMS. Our results support the usefulness of this device in remote management of the HF patient, especially during this pandemic.

THE POTENTIAL ROLE OF ECHOCARDIOGRAPHY IN PREDICTING SACUBITRIL/VALSARTAN MAXIMUM DOSE TOLERABILITY

Valeria Visco¹, Ilaria Radano¹, Alfonso Campanile², Amelia Ravera², Angelo Silverio¹, Daniele Masarone³, Giuseppe Pacileo³, Michele Correale⁴, Pietro Mazzeo⁴, Giuseppe Dattilo⁵, Francesco Giallauria⁶, Alessandra Cuomo⁶, Valentina Mercurio⁶, Carlo Gabriele Tocchetti⁶, Paola Di Pietro¹, Albino Carrizzo^1,7, Rodolfo Citro², Gennaro Galasso¹, Carmine Vecchione^1,7, Michele Ciccarelli¹

¹Department of Medicine, Surgery and Dentistry, University of Salerno, Italy; ²Department of Cardiology, "San Giovanni di Dio e Ruggi D'Aragona" Hopital-University, Salerno, Italy; ³Heart Failure Unit, AORN Colli, Naples, Italy; ⁴Cardiology Department, Ospedali Riuniti University Hospital, Foggia, Italy’; ⁵Department of Clinical and Experimental Medicine, Operative Unit of Cardiology, University of Messina, Messina, Italy; ⁶Department of Translational Medical Sciences, Federico II University, Naples, Italy; ⁷Vascular Pathophysiology Unit, IRCCS Neuromed, Pozzilli, Italy

Introduction: Sacubitril/Valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all-cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up-titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes.

Aim: to determine which echocardiographic index best predicts the up-titration success.

Methods: From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1-72.8]years; 15.8%females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a p value < 0.1 in the univariate analyses.

Results: A significant improvement in NYHA functional class was reported (NYHA II: from 58% to 74%; NYHA III from 41% to 14%). After 6 months, LVEF significantly increased from 28.8% [22.2–33] to 35% [29–40]; LVESV significantly decreased from 135 [108–180] to 114 ml [83–166] (p < 0.001), and sPAP decreased from 35 [28.7–48.5] to 31.5 mmHg [23–42.2]. After the multivariate analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% CI 0.794–0.954) to predict maximum Sac/Val dose tolerability.

Conclusions: Our study is the first to analyze the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. From a clinical point of view, patients with RV dysfunction (baseline TAPSE<16 mm, in our cohort) might benefit from a different strategy during the follow-up, in order to maximize the benefit of the treatment with Sac/Val.

PLGF MEDIATES A CARDIAC-NEURO-IMMUNE AXIS THAT CONTROLS ADAPTATION TO CARDIAC STRESS THROUGH CARDIAC MACROPHAGES

Sara Perrotta¹, Raimondo Carnevale², Lorenzo Carnevale², Marialuisa Perrotta^1,2, Francesco Mastroiacovo², Fabio Pallante², Giuseppe Lembo^1,2, Daniela Carnevale^1,2

¹ Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy; ² Department of Angiocardioneurology and Translational Medicine, IRCCS Neuromed, Pozzilli, Italy

Introduction: Cardiac remodeling to pressure overload is a process of adaptation of the left ventricle (LV) that involves immune cells, mainly macrophages. We found that Placental Growth Factor (PlGF) is required for the adaptive remodeling to pressure overload induced by transverse aortic constriction (TAC).

Aim: To investigate the role of PlGF as an immunomodulator during cardiac remodeling in response to TAC.

methods: We induced pressure overload by transverse aortic constriction and we analyzed the process of cardiac remodeling by echocardiography. We analyzed the cardiac monocyte/macrophage populations by flow cytometry and PlGF levels in the spleen and blood by immunohistochemistry and/or immunoenzymatic ELISA assay.

Results: After TAC, WT mice, but not PlGF KO mice, showed cardiac adaptive hypertrophy and a significant increase of resident macrophages, suggesting that PlGF is involved in the expansion of immune cells. To discriminate resident and recruited macrophages, we subjected to TAC CCR2 KO mice that are unable to recruit pro-inflammatory monocytes to the inflammatory site and we observed a LV adaptive remodeling similar to that of WT mice. Since TAC induced the expression of PlGF in the spleen, we subjected splenectomized mice to TAC, observing that they exhibited early heart failure and reduced accumulation of monocytes/macrophages in the LV. To investigate the pathway through which PlGF modulates this response, we induced pressure overload by TAC in mice with a selective deletion of Neuropilin-1 (Nrp1), a receptor for PlGF, in the myeloid lineage. These mice developed an early phenotype of heart failure and a lack of expansion of monocytes/macrophages in the LV similarly to splenectomized mice and PlGF KO mice.

To study the involvement of a neuroimmune mechanism, we performed a selective denervation of the splanchnic district through the surgical removal of the celiac ganglion (CGX). Mice subjected to CGX and TAC recapitulated the phenotypes observed in splenectomized and PlGF KO mice.

Conclusions: Pressure overload activates a neuroimmune mechanism in the spleen where it induces PlGF release that, in turn, is able to modulate the cardio-immune response through its receptor Nrp1. In particular, PlGF/Nrp1 induces the expansion of cardiac resident macrophages contributing to the establishment of an adaptive remodeling to pressure overload, preventing heart failure development.

MACROPHAGES ARE A KEY DETERMINANT IN CARDIOTOXICITY

Jessica Gambardella^1,2 Gaetano Santulli^1,2,3, Antonella Fiordelisi¹, Federica Andrea Cerasuolo¹, Xujun Wang³ MD, Nella Prevete^1,2, Eduardo Sommella⁴, Roberta Avvisato¹, Antonietta Buonaiuto¹, Giovanna Giuseppina Altobelli¹, Laura Rinaldi¹, Michele Ciccarelli⁴, Carmine Morisco^1,2, Junichi Sadoshima⁵ Guido Iaccarino^1,2, Daniela Sorriento^1,2

¹ Federico II University, Napoli, Italy, ² Hypertension Research Center (CIRIAPA), Napoli, Italy. ³ Albert Einstein College of Medicine, New York (USA); ⁴University of Salerno, Baronissi (SA), Italy; ⁵Rutgers New Jersey Medical School, Newark-USA

Introduction: The functional contribution of non-myocyte cardiac cells, such as inflammatory cells, in the setup of heart failure in response to doxorubicin (Dox) is recently becoming of growing interest.

Aim: to evaluate the role of macrophages in cardiac damage elicited by Dox treatment.

Methods: C57BL/6 mice were treated with one intraperitoneal injection of Dox (20 mg/kg) and followed up for 5 days by cardiac ultrasounds (CUS), histological, and flow cytometry evaluations. Murine cardiomyoblasts were directly treated with Dox (D-Dox) or with conditioned medium from cultured murine macrophages treated with Dox (M-Dox).

Results: Dox-induced cardiac dysfunction was detectable by CUS 5 days after treatment while macrophages infiltration in the heart occurred earlier, indicating that inflammation precedes cardiac damage. In cardiomyoblasts, cell vitality was lower and apoptosis was higher in response to M-Dox compared with D-Dox. These events were linked to p53-induced alterations of mitochondria morphology, function, and autophagy. Mechanistically, Dox-activated macrophages release catecholamines leading to mitochondrial apoptosis of cardiac cells through b-AR stimulation.

Conclusions: Taken together, our data indicate that crosstalk between macrophages and cardiac cells participates in cardiac damage in response to Dox.

ASCENDING AORTA DILATION IS ASSOCIATED TO HARD CARDIOVASCULAR ENDPOINTS, FOLLOW-UP FROM MULTICENTRIC ARGO-PERSPECTIVE PROJECT

Lorenzo Airale¹, Francesco Borrelli¹, Alessio Arrivi², Alessandro Baracchi³, Fabio Bertacchini⁴, Iside Cartella⁵, Nicola De Luca⁶, Daniela Degli Esposti³, Cristina Giannattasio⁴, Raffaele Izzo⁶, Maria Lembo⁶, Costantino Mancusi⁶, Maria Virgina Manzi⁶, Martina Milani⁵, Antonella Moreo⁵, Maria Lorenza Muiesan⁴, Anna Paini⁴, Giacomo Pucci², Federico Ruscelli³, Massimo Salvetti⁴, Mario Soldati³, Gaetano Vaudo², Alberto Milan¹

¹ Department of Medical Sciences-Hypertension Center-University of Torino-AOU Citta` della Salute e della Scienza di Torino, Turin, Italy; <sup>2</sup> SC Medicina Interna, Azienda Ospedaliero-Universitaria di Terni, Terni, Italy; <sup>3</sup> Cardiothoracic and Vascular Department, S. Orsola-Malpighi University Hospital, Bologna, Italy; <sup>4</sup> Department of Internal Medicine, ASST Spedali Civili di Brescia, Brescia, Italy; <sup>5</sup> Echo Lab, Cardiologia IV, De Gasperis Dep, ASST Niguarda Ca granda e Dip Medicina e Chirurgia, Universita` Milano Bicocca, Milan, Italy; ⁶ Hypertension Research Center, Federico II University Hospital, Naples, Italy

Introduction: The latest ESC/ESH 2018 guidelines¹ emphasized that hypertension can be associated with dilatation of the proximal aorta. Furthermore, one study observed that the presence of dilatation of the ascending aorta (AAD) was associated with increased rate of cardiovascular (CV) events in a population with essential hypertension².

Aim: Assessing whether the presence of aortic dilatation is associated with strong cardiovascular (CV) events (MACE: heart failure, CV death, stroke, acute coronary syndrome)

Methods: 450 hypertensive patients from 6 Italian hospitals were recruited as part of ARGO-SIIA study³. For all centres, follow-up was obtained by re-contacting all patients by telephone and through the hospital's computer system. Aortic dilatation (AAD) was obtained through absolute parameters obtained by ROC analysis, in order to maximize specificity.

Results: Median follow-up was 60 months. AAD was found to be associated with the occurrence of MACE both in univariate cox regression (HR [95%CI] = 4.40 [1.80–10.00], p < 0.001) and after adjustment for age, sex, and left ventricular hypertrophy (LVH) (HR [95% CI] = 2.76 [1.15–6.66], p = 0.023). Among patients with LVH, the presence of AAD was associated with the occurrence of MACE both at univariate cox regression (HR [95% CI] = 4.04 [1.56–10.46], p = 0.004) and after adjustment for age and sex (HR [95%CI] = 3.21 [1.23–8.42], p = 0.017).

Conclusions: The presence of AAD was found to be associated with an increased risk of MACE even after correction for major confounders. Furthermore, the presence of AAD in addition to LVH appears to be associated with greater CV risk than the presence of LVH alone.

RELATIONSHIP BETWEEN MYOCARDIAL MECHANO-ENERGETIC EFFICIENCY AND 24-HOUR AMBULATORY BLOOD PRESSURE PROFILE

Giuliano Tocci¹, Massimo Salvetti², Anna Paini², Ilaria Figliuzzi¹, Barbara Citoni¹, Francesca Miceli¹, Marialudovica Carducci¹, Giulia Nardoianni¹, Maria Lorenza Muiesan², Massimo Volpe¹

¹Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ²Medicina ASST, Spedali Civili di Brescia, and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

Introduction: A non-invasive approach for estimating left ventricular myocardial mechano-energetic efficiency index (MEEi) has been recently proposed in the diagnostic work-up of hypertension.

Aim: To evaluate the correlation between MEEi and 24-hour ambulatory blood pressure (ABPM) levels.

Methods: A single-centre, cross-sectional study was conducted in treated and untreated adult individuals (aged ≥ 18 years), who consecutively underwent full BP evaluation and global cardiovascular risk assessment at our Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy. ABPM was performed by an oscillometric device (Spacelabs 90207, Spacelabs Inc., Redmond, Washington, USA). All BP measurements were performed and BP thresholds were set according to European guidelines. MEE was calculated as the ratio between SV and HR, where HR for convenience can be divided by 60. Then, MEEi was obtained as MEE divided by LVM, and expressed as ml/s per g.

Results: We considered an overall sample of 563 adult outpatients with valid clinic and ABPM data and concomitant (± 14 days) echocardiographic assessment of LV mass and function (women 34.3%, mean age 53.3 ± 15.6 years, BMI 27.0 ± 4.5 kg/m², clinic BP 147.4 ± 19.4/90.0 ± 12.4 mmHg, 24-h our BP 132.6 ± 14.5/82.1 ± 10.9 mmHg), among whom the vast majority were treated (67.3%) or untreated (24.3%) hypertensive outpatients. MEEi resulted significantly higher in female than in male individuals (0.43 ± 0.1 vs. 0.38 ± 0.1; P < 0.001) and significantly lower in hypertensive outpatients than in normotensive individuals (0.39 ± 0.1 vs. 0.46 ± 0.2; P < 0.001). MEEi resulted significantly and inversely related with 24-hour systolic (r = − 0.161; P < 0.001) and diastolic (r = − 0.133; P < 0.001), day-time systolic (r = − 0.124; P < 0.001) and diastolic (r = − 0.100; P < 0.001), and night-time systolic (r = − 0.206; P < 0.001) and diastolic (r = − 0.195; P < 0.001) BP levels.

Conclusions: In our sample of adult outpatients with and without hypertension, we firstly observed an inverse relationship between MEEi and day-time and, mostly, night-time BP levels, thus suggesting a lower degree of LV efficiency in those patients with sustained BP elevations.

RELATIONSHIP BETWEEN MYOCARDIAL MECHANO-ENERGETIC EFFICIENCY AND PLASMA ALDOSTERONE LEVELS IN ADULT OUTPATIENTS WITH ESSENTIAL HYPERTENSION

Giuliano Tocci ¹, Massimo Salvetti ², Anna Paini ², Ilaria Figliuzzi ¹, Barbara Citoni ¹, Francesca Miceli ¹, Marialudovica Carducci ¹, Giulia Nardoianni ¹, Maria Lorenza Muiesan ², Massimo Volpe ¹

¹ Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ² Medicina ASST, Spedali Civili di Brescia, and Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy

Introduction: It has been recently reported an inverse correlation between high plasma aldosterone (PA) levels and left ventricular myocardial mechano-energetic efficiency index (MEEi) in patients with primary aldosteronism.

Aim: To evaluate the potential correlation between MEEi and PA levels in adult outpatients with essential hypertension

Methods: A single-centre, cross-sectional study was conducted in treated and untreated adult individuals (aged ≥ 18 years), who consecutively underwent full BP evaluation and global cardiovascular risk assessment at our Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy. All BP measurements were performed and BP thresholds were set according to European guidelines. MEE was calculated as the ratio between SV and HR, where HR for convenience can be divided by 60. MEEi was obtained as MEE divided by LVM, and expressed as ml/s per g. Blood samples were then obtained to test PA concentration (ng/ml) and plasma renin activity (PRA). Any drugs able to interfere with PA, PRA or aldosterone-renin ratio (ARR) was stopped at least 4-6 weeks before samples and replaced by calcium channel blockers and/or alpha-blocker, if needed.

Results: From an overall sample of 197 adult outpatients with available PA levels, we considered 162 individuals with valid and concomitant (± 2 days) echocardiographic assessment of LV mass and function (women 34.3%, mean age 44.7 ± 14.5 years, BMI 26.8 ± 4.9 kg/m2, clinic BP 146.3 ± 18.3/94.1 ± 12.9 mmHg), among whom the vast majority were treated (61.9%) or untreated (28.9%) hypertensive outpatients. MEEi resulted significantly and inversely related with PA (r = − 0.178; P = 0.024) (Figure A) and ARR (r = − 0.228; P = 0.004), but not with PRA (r = 0.007; P = 0.927). This correlation maintained statistical significance even after correction for age, gender and BMI.

Conclusions: In our sample of adult outpatients with and without essential hypertension, we firstly demonstrated an inverse relationship between MEEi and PA, thus supporting the potential role increased PA levels in the pathogenesis of LV dysfunction also in patients without primary hyperaldosteronism.

DYSLIPIDEMIA AND ARTERIAL HYPERTENSION

PLASMA LEVELS OF PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 ARE INVERSELY ASSOCIATED WITH N-TERMINAL PRO B-TYPE NATRIURETIC PEPTIDE IN AN OLDER POPULATION

Francesco Spannella^1,2, Federico Giulietti ^1,2, Chiara Di Pentima ^1,2, Massimiliano Allevi ^1,2, Serena Re ^1,2, Beatrice Ortensi ^1,2, Roberta Galeazzi ³, Anna Passarelli ⁴, Paolo Magni ^4,5, Riccardo Sarzani ^1,2

¹ Internal Medicine and Geriatrics, IRCCS INRCA, Ancona, Italy; ² Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy; ³ Clinical Laboratory and Molecular Diagnostic, IRCCS INRCA, Ancona, Italy; ⁴ Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; ⁵ IRCCS MultiMedica, Sesto S. Giovanni, Milan, Italy

Introduction: Cardiac natriuretic peptides (NPs) exert several metabolic effects, including some on lipid metabolism. Higher NPs levels are likely to be associated with a favorable lipid profile. In vitro, NPs have been found to modulate the low-density lipoprotein receptor (LDLR), preventing proprotein convertase subtilisin/kexin type 9 (PCSK9) overexpression.

Aim: to investigate a possible association between plasma levels of PCSK9 and N-terminal pro B-type natriuretic peptide (NT-proBNP) in vivo.

Methods: We performed a cross-sectional study on 160 older patients hospitalized for medical conditions. Patients taking lipid-lowering drugs and patients with an admission diagnosis of acute heart failure were excluded. Fasting blood samples were collected after clinical stabilization of the acute illness, the day before discharge.

Results: Mean age was 87.8 ± 6.4 years with female prevalence (62.5%). A history hypertension was present in 69.7% of the study population. Median NT-proBNP was 2340 (814–5397) pg/ml. Mean plasma PCSK9 was 275.2 ± 113.2 ng/ml. We found an inverse correlation between plasma PCSK9 and NT-proBNP (r = − 0.280; p = 0.001). This association was confirmed even after taking into account NT-proBNP tertiles (Figure 1) and even after adjustment for confounding factors [beta = − 0.361, p = 0.001 for ln(NT-proBNP); beta = − 0.330, p = 0.001].

Conclusions: The inverse association found between PCSK9 and NT-proBNP in our “real-life” clinical study supports the hypothesis that NPs play a role on cholesterol metabolism, also through a probable inhibitory action on PCSK9, thus increasing the availability of LDLR.

Figure 1 PSK9 levels according to NT-proBNP tertiles.

COST-EFFECTIVENESS OF POLYPILL TREATMENT IN HIGH-RISK HYPERTENSIVE SUBJECTS WITH HYPER-CHOLESTEROLAEMIA

Giuliana Autiero², Enrico Cavazzin², Giulio Sasso², Eliana Miozzo^1,2, Gioia Torin^1,3, Antonella Paola Sacco¹, Marta Milan¹, Stefano Cuppini¹, Alberto Mazza^1,3

¹UOC Medicina Interna, Osp. Santa Maria della Misericordia, Rovigo, AULSS5 Polesana, Italy; ² Università degli studi di Padova, Scuola di Specializzazione in Medicina Interna, Padua, Italy; ³ UOS Ipertensione, Centro di Eccellenza ESH per l’Ipertensione

Introduction: Hypertension and hyper-cholesterolaemia is a dangerous combination frequently found in clinical practice. Despite a wide range of medications available for these both conditions, a large proportion of treated patients remain uncontrolled.

Aim: We aimed to evaluate the cost-effectiveness treatment of a polypill in high-risk hypertensive and hyper-cholesterolemic subjects.

Methods: Design and Method—46 subjects (mean age 67.4 ± 11.5 years, 69.6% men) treated a with free-combination (FCT) of statins (atorvastatin 63.1%, simvastatin 19.6%, rosuvastatin 8.7%, other 8.6%), renin-angiotensinsystem blockers (ramipril 37.1%, perindopril 28.2%, enalapril 11%, zofenopril 4.4%, candesartan 6.5%, valsartan, losartan and telmisartan 4.3%) and calcium-channel blockers (amlodipine 61%, lacidipine and lercanidipine 15.2%, manidipine 6.6%), were switched to once-daily therapy with a polypill containing atorvastatin/perindopril/amlodipine at different doses. The monthly cost for treating patients with FCT and polypill was estimated using pharmacy dispensing records. Blood pressure (BP) and low-density cholesterol (LDL-C) targets values to reach were <130/80mmHg and <70mg/dL, respectively. Categorical variables were compared using the Pearson’s chi-squared test. The change of systolic BP (SBP), diastolic BP (DBP), LDL-C levels and the costs of treatments were compared from baseline to the follow-up (FW, 3.5 ± 1.5 months) by the analysis of variance for repeated measures using the Fisher’s (F) test.

Results: From baseline to the FW, polypill significantly decrease SBP (141.3 ± 10.1 vs. 133.9 ± 10.5, F = 33.8, p < 0.0001), DBP (81.8 ± 5.3 vs. 77.8 ± 4.1, F = 9.3, p < 0.004) and LDL-C values (99.3 ± 31.5 vs. 70.9 ± 18.5, F = 60.6, p < 0.0001), respectively. The BP and LDL-C targets significantly increased from 24.1 to 56.5% (p < 0.05) and 21.7 to 63.1% (p < 0.05), respectively. The average cost of polypill is lower than the FCT one (13.5 ± 0.7 vs. 23.2 ± 5.3 €, p < 0.0001, difference -9.8 ± 5.2 €). No adverse event was observed during the polypill treatment.

Conclusions: In high-risk hypertensive and hyper-cholesterolemic subjects, the polypill treatment is cost-effective. National and regional epidemiological data show a prevalence of high-risk hypertensives of about 12%. In perspective, in the local public health-unit 5 Polesana, which gathers about 235 thousand inhabitants, using polypill compared to the FCT could result in annual cost savings of about 3.2 million € (Figure). However, for definite conclusions, further studies including a wider number of subjects in this setting are needed.

FREE OR FIXED COMBINATION OF CALCIUM CHANNEL BLOCKER AND STATIN: A SPONTANEUS OBSERVATIONAL STUDYIN HYPERTENSIVE DYSLIPIDEMIC PATIENTS

G. Baldini¹, R. Del Pinto¹, G.B .Zito², C. Ferri¹

¹Department of Life, Health, and Environmental Sciences, University of L'Aquila, S. Salvatore Hospital, L'Aquila, Italy; ² President, Regional Associations of Ambulatory Cardiologists

Introduction: Hypertension and LDL hypercholesterolemia often coexist, and their effective treatment has favourable implications for cardiovascular health.

Aim: To define the impact of amlodipine and rosuvastatin as free or fixed combination on blood pressure (BP) and LDL-cholesterol, and the satisfaction with treatment, in hypertensive individuals with LDL hypercholesterolemia.

Methods: A spontaneous longitudinal observational study was conducted at Italian cardiology outpatients clinics. Eligible individuals (age > 18y, informed consent, stable 5 or 10 mg amlodipine therapy in addition to a RAAS inhibitor, stable 10 or 20 mg rosuvastatin therapy) underwent home and officeBP and LDL-cholesterol assessment at 12 and 24 weeks. Satisfaction with the fixed versus the free combination was assessed.

Results: 285 participants were enrolled (51%M; 67 ± 10y; 94 on the free combination). Baseline BP and LDL-cholesterol were higher in the fixed combination group. At 12 weeks, they were reduced without between-groups differences; at 24 weeks they were further reduced, and home systolic BP was lower in the fixed than the free combination group (121.9 ± 17.6 vs 129.4 ± 8.5 mmHg; p = 0.03). Patients in the fixed combination reported higher satisfaction with this regimen than with the free combination.

Conclusions: The fixed combination of calcium channel blocker and statin appears to have advantages in terms of clinical efficacy and patients satisfaction.

IMPACT OF SIMULTANEOUS MANAGEMENT OF HYPERTENSION AND HYPERCHOLESTEROLEMIA WITH ACE INHIBITORS AND STATINS ON CARDIOVASCULAR OUTCOMES IN THE BRISIGHELLA HEART STUDY: A 8-YEAR FOLLOW-UP

Arrigo F.G. Cicero,^1,2 Federica Fogacci,¹ Elisabetta Rizzoli,^1,2 Marina Giovannini,¹ Sergio D’addato,^1,2 Claudio Borghi,^1,2

¹ Hypertension and Cardiovascular Risk Research Group, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; 2 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Introduction: In the last decades, there has been significant progress in concomitant hypertension and hypercholesterolemia control.

Aim: To evaluate the long-term effect of simultaneous treatment of hypertension and hypercholesterolemia with angiotensin-converting enzyme (ACE) inhibitors and statins on the incidence of major cardiovascular events (MACE) and other clinical outcomes.

Methods: We considered data from a subset of Brisighella Heart Study (BHS) participants who were consecutively evaluated in three epidemiological surveys between 2012 and 2020. We excluded normotensive subjects and individuals with a low calculated 10-year CVD risk, hypertensive patients treated with antihypertensive drugs different from ACE inhibitors and patients who changed antihypertensive medications during follow-up. The remaining participants were divided into four groups depending on whether they were treated with (I) perindopril ± amlodipine without statin treatment (N. 132), (II) perindopril ± amlodipine and atorvastatin (N. 132), (III), an ACE inhibitor other than perindopril ± a calcium-channel blocker without statin therapy (N. 133), (IV) an ACE inhibitor other than perindopril ± a calcium-channel blocker and statin therapy (N. 145). The long-term (8 years) effects of the different combined treatment were compared among the pre-defined groups.

Results: Over the follow-up period of 8 years, the proportion of subjects who developed MACE were 8 (6.1%), 6 (4.5%), 10 (7.5%) and 8 (5.5%) among patients taking respectively perindopril (± amlodipine) without statin therapy, perindopril (± amlodipine) and atorvastatin, an ACE inhibitor (± CCBs) other than perindopril without statin treatment, and an ACE inhibitor (± CCBs) other than perindopril with statin treatment. These differences in incidence were statistically significant among groups (P < 0.05).

Conclusions: Combined treatment with ACE inhibitors and statins (especially atorvastatin) in hypertensive patients seems to significantly reduce the risk of developing CVD in comparison with treatment with ACE inhibitors alone.

URICEMIA LEVELS AND ECHOCARDIOGRAPHIC PARAMETERS ARE ASSOCIATED WITH THE RISK OF PREECLAMPSIA IN A COHORT OF 258 PREGNANT WOMEN

Carmine Verde, Daniela Degli Esposti, Federica Piani, Davide Agnoletti, Claudio Borghi

Cardiovascular Internal Medicine, IRCCS Policlinico S.Orsola, Bologna, Italy

Introduction: Uric acid is a relevant molecule in the pathogenesis of numerous cardiovascular diseases. In recent decades, increasing attention has been paid to its role in hypertensive pathologies of pregnancy and in particular in preeclampsia (PE). The latter is a serious pathology of pregnancy characterized by a high rate of evolution that has a huge impact on both maternal and fetal outcomes and for which there are no simple and at the same time effective tools to stratify the risk of patients and their prognosis.

Aim: To evaluate the impact of echocardiography and uricemia (sUA) in the prognostic stratification of women with hypertensive disorders of pregnancy, focusing on PE. Finally, in pregnant women with PE, the possible presence of linear correlations between sUA values and echocardiographic parameters was evaluated.

Methods: To this end, we prospectively followed 258 pregnant women, visited on several occasions during and after the end of pregnancy and divided into healthy pregnancies, complicated by gestational / chronic hypertension or complicated by PE (Figure 1). At each visit, a complete echocardiographic examination with Tissue Doppler imaging was performed and we took note of the values of sUA, creatininemia, sodiemia, potassium and vital parameters.

Results: It was found that during pregnancy of women with PE the value of sUA increase to a greater extent than other pregnant women. They are significantly superior as early as the 2nd trimester of pregnancy and also in the 3rd trimester when standardized for renal function (sUA/creatininemia) (Figure 2). Echocardiography performed in the early stages of pregnancy was able to intercept early hemodynamic, morphological and systo-diastolic alterations in women with PE, in accordance with the literature. Finally, it emerges that the hearts of women with PE when evaluated within one year of the end of childbirth show a decrease in longitudinal contractility and an increase in cavity volumes to probably express an impact on the cardiovascular profile of these patients after PE. In addition, in these women, it was found that some echocardiographic alterations correlate in a linear manner with the sUA values of the 2nd and 3rd trimester.

Conclusions: In conclusion, in a cohort of pregnant women the echocardiographic evaluation and uricemia values suggest a prognostic role in identifying pregnant women at greater risk of evolution into PE.

CONTROL OF SERUM TRIGLYCERIDES LEVELS AND CARDIOMETABOLIC RISK: A CROSS-SECTIONAL, NATION-WIDE STUDY

Giuliano Tocci ¹, Barbara Citoni ¹, Ilaria Figliuzzi ¹, Francesca Miceli ², Giulia Nardoianni ¹, Marialudovica Carducci ¹, Arrigo F.G. Cicero ², Federica Fogacci ², Claudio Borghi ², Massimo Volpe ¹, on behalf of the EFFECTUS Steering Committee

¹ Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ² Medical and Surgical Sciences Department, University of Bologna, Sant’Orsola-Malpighi Hospital, Bologna Italy

Introduction: Triglycerides (TG) play a major role in development and progression of atherosclerotic diseases, yet they are marginally considered in global cardiovascular (CV) risk stratification.

Aim: To evaluate distribution of serum TG levels in a large cohort of adult outpatients’ representative of general population in Italy, stratified according to presence or absence of CV events or diabetes.

Methods: Data from large cohort of outpatients, followed by general practitioners, cardiologists and diabetologists in Italy, were stratified according to presence or absence of either diabetes or previous CV events, including coronary artery (CAD), cerebrovascular (CVD) and peripheral artery (PAD) diseases. Predefined therapeutic TG goals were set according to European guidelines: <150 mg/dl for diabetic patients in primary prevention and for those in secondary prevention; <200 mg/dl for non-diabetic patients in primary prevention.

Results: We analysed data from 9641 adult outpatients with available serum TG levels (45.9% female, age 65.8 ± 9.8 years, BMI 28.1 ± 4.8 kg/m2), among whom 66.7% in primary and 33.3% in secondary prevention; proportions of diabetic patients were 33.0% and 44.6%, respectively. Patients in secondary prevention showed significantly higher TG levels (159.8 ± 80.4 vs. 154.0 ± 73.3 mg/dl; P < 0.001) and lower values of all other lipid parameters than those in primary prevention, including apolipoprotein B (107.6 ± 28.0 vs. 109.7 ± 27.1 mg/dl; P < 0.001), despite both statins and omega3 were more commonly prescribed in the former than in the latter group. About 47% of diabetic patients in primary prevention and 50% of non-diabetic patients in secondary prevention showed TG levels above the target of <150 mg/dl. At multivariate analysis, low CV risk [OR 0.937 (95% CI 0.924–0.950)], low BMI [OR 0.933 (95% CI 0.922–0.943)], and age [OR 1.046 (95% CI 1.037–1.055)] resulted independent predictors for having TG <150 mg/dl.

Conclusions: In our population sample, about half of the population showed above normal TG levels, mostly patients in secondary prevention with or without diabetes.

DIAGNOSTIC-THERAPEUTIC WORKUP OF HYPERTENSION IN NEUROFIBROMATOSIS TYPE I: A CASE REPORT

Massimiliano Quici, Maddalena A. Wu, Luciana Scandiani, Chiara B. Cogliati

Hypertension Center" U.O.C. General Medicine H. Sacco Milan, Italy

Introduction: Neurofibromatosis is a genetic disease with autosomal dominant transmission due to mutations in the NF gene. There are two forms, of which type I is secondary to mutations of the NF1 gene on chromosome 17 and type II to mutations of the NF2 gene on chromosome 22. Type I (Von Recklinghausen's disease) has a prevalence of 1/3000 and is associated with the development of café-au-lait spots of variable diameter located throughout the trunk which may also be present at birth, cutaneous or subcutaneous neurofibromas that arise from adolescence, arterial hypertension (possibly secondary to renal artery stenosis or pheochromocytoma), bone abnormalities, gliomas of the optic nerve, iris Lisch nodules, possible learning disabilities (from autism to ADHD), short stature.

Two of the following 7 diagnostic criteria are required for diagnosis: at least 6 café-au-lait spots or hyperpigmented macules greater than 5 mm, axillary or inguinal freckles, 2 or more neurofibromas or at least one plexiform neurofibroma, optic nerve glioma, at least 2 Lisch nodules, pseudarthrosis of the long bones or sphenoid dysplasia, a first degree family member affected by neurofibromatosis type I. Type II is characterized by a lower prevalence of skin manifestations with a greater tendency to develop multiple neoplasms (neurofibromas, schwannomas, gliomas, meningiomas), hearing loss, cranial nerve palsy. For the diagnosis, the presence of at least 1 criterion is required among: bilateral schwannomas, first degree family member with type II neurofibromatosis and unilateral schwannoma or at least 2 neoplasms including meningioma, schwannoma, glioma, neurofibroma, subcapsular cataract, multiple meningiomas and unilateral vestibular schwannoma or multiple neoplasms.

Aim: to illustrate the clinical-diagnostic workup of a patient suffering from neurofibromatosis with newly detected grade 1 arterial hypertension.

Methods: Blood tests (potassium, thyroid function, hypothalamic-pituitary-adrenal axis evaluation) and urinary tests (24-hour urinary metanephrines) were performed.

Serum renin and aldosterone with the patient lying down and in the upright position were measured 24-h ambulatory blood pressure monitoring was performed.

Echocolordoppler of the renal arteries was performed to exclude stenosis of the renal arteries, as well as abdominal CT scan with contrast medium, which was also useful to assess pheochromocytoma.

In consideration of the newly discovered arterial hypertension, Doppler echocardiography was also performed, with no remarkable findings (especially, no signs of left ventricular hypertrophy).

Results: A 22-year-old patient presented to our outpatient clinic for thorough evaluation after the fortuitous finding of arterial hypertension in known type I neurofibromatosis. Blood tests highlighted mild hypokalaemia (serum potassium 3.3 mEq/l). Serum cortisol was within normal range (19.9 mcg/dl at 8:00 performed as a evaluation not associated with dexamethasone suppression test) and thyroid function was not altered (TSH: 2.3 mIU/ml). Ambulatory blood pressure monitoring revealed increased systolic-diastolic arterial blood pressure values. To further assess organ involvement in a case of newly diagnosed arterial hypertension, Doppler echocardiography was also performed, with no signs either of hypertensive heart disease or of other neurofibromatosis-related alterations (e.g. septal defect).

In the suspicion of pheochromocytoma, 24-h our urinary metanephrines were measured, with normal results (57.6 mch/24 h) and contrast-enhanced abdominal CT scan was performed, showing normal adrenal features bilaterally and excluding kidney neoplasms (e.g. clear cell carcinoma or hypernephroma) bilaterally.

Mild hyperreninaemia was detected (serum renin of 48.9 mcUI/ml in supine position and 74.2 mcIU/ml in standing position), with normal levels of serum aldosterone (138 pg/ml in supine position and 251 pg/ml in standing position).This finding can be interpreted as non-specific in the light of the echocolordoppler of the renal arteries, which excluded stenosis bilaterally.

From the therapeutic point of view, doxazosin 4 mg was initially suspended for renin/aldosterone dosage in upright and supine position, replacing it with 10 mg amlodipine and oral potassium supplementation.

Due to poor blood pressure control with the above-mentioned calcium channel blocker, we chose to optimize the treatment strategy withdrawing amlodipine and opting for a combination therapy with an ARB (olmesartan 20 mg OD) and an alpha-blocker (doxazosin 4 mg OD), with clinical benefit.

A 6-month follow-up has been planned, with a 24-h ambulatory blood pressure monitoring to check the blood pressure profile.

Conclusions: The case presented serves as reminder that arterial hypertension may be associated to neurofibromatosis, even in the absence of renal artery stenosis or pheocromocytoma. The underlying pathophysiological mechanisms may involve activation of the RAAS system, as suggested also by the patient’s favourable response to low dose ARB therapy, after suboptimal response to a full dose calcium channel blocker.

HYPERTENSION EMERGENCY AND URGENCY

PULSELESS HYPERTENSIVE EMERGENCY: FROM THEORY TO PRACTICE

Gioia Torin,^1,3 Milan Marta,¹ Giuliana Autiero,² Eliana Miozzo,^1,2, Stefano Cuppini¹, Alberto Mazza^1,3

¹Department of Internal Medicine, Santa Maria della Misericordia General Hospital, Rovigo, Italy; ²School of Internal Medicine, University of Padua, Padua, Italy; ³ Unit of Hypertension and ESH Excellence Hypertension Centre, Department of Internal Medicine, Santa Maria della Misericordia, General Hospital, Rovigo, Italy

Introduction: The main factors involved in the arterial pulse assessment are cardiac output and wall vessel elasticity. The absence of arterial pulse can be acute or chronic and sometimes paucisymptomatic and in this respect for therapeutic purposes a differential diagnosis is mandatory. A hypertensive emergency with absence of femoral pulse and anasarcatic state is described.

Case report: A 58-year-old male, of Moroccan nationality, was hospitalized for hypertensive emergency (PA 200/100 mmHg) and worsening dyspnea. He was an active smoker (20 cigarettes/daily) and having an intermittent claudication at 500 m diagnosed 3 months earlier; drug history was negative.

Physical examination revealed the absence of femoral pulses, anasarcatic state and dyspnea requiring low flow of oxigen therapy. Blood tests showed an increase in D-dimer (6.46 mcg/mL) and Nt-pro-BNP (21.166 ng/mL); serum hemoglobin, creatinine, HbA1c and thrombophilic screening were normal. CT-scan (Figure) showed a left segmental pulmonary embolism and a complete occlusion of the juxta-renal abdominal aorta up to the common femoral arteries, thrombosis of the superior mesenteric artery and deep femoral arteries with collateral circulation downstream, left renal infarction; no evidence of deep venous thrombosis was found. ECG showed sinus tachycardia and repolarization abnormalities, while echocardiogram revealed increased volumes of heart chambers with reduced FE (34%); a single-vessel critical stenosis (Cx) on coronary angiography was observed. After therapy with amlodipine 15mg, bisoprolol 2.5mg, doxazosin 2mg, furosemide 125mg, spironolactone 50mg and sacubitril/valsartan 49/51mg bid, blood pressure normalized (128/74 mmHg). Therapies with Edoxaban 30 mg, acetylsalicylic acid 100 mg, atorvastatin 40 mg and dapaglifozin 10 mg were also started. The patient was than discharged 25 days later, with diagnosis of” Heart failure with reduced EF in ischemic-hypertensive heart disease with Leriche syndrome type-III”.

Conclusion: Arterial hypertension is a well-known risk factor for peripheral arterial vascular diseases and when associated with the absence of the femoral pulse must raise the suspicion of the Leriche syndrome. This latter, if not promptly identified and treated, has a poor prognosis.

HYPERTENSIVE EMERGENCIES AND URGENCIES IN EMERGENCY DEPARTMENT: A SINGLE CENTRE EXPERIENCE

Costantino Mancusi ¹, Ilaria Fucile ¹, Maria Virginia Manzi ¹, Maria Lembo ¹, Biagio Migliaccio ¹, Guido Iaccarino¹, Raffaele Izzo ¹, Nicola De Luca ¹, Fiorella Paladino ², Filomena Liccardi ², Stefania Auciello ²

¹Hypertension Research Center & Department of Advanced Biomedical Science, Federico II University Hospital, Naples, Italy; ²Cardarelli Hospital Naples, Italy

Introduction: Hypertensive emergencies and urgencies represent a frequent challenge for physicians in Emergency Department. Rapid and careful assessment of the clinical presentation is crucial in order to allow prompt recognition of Hypertensive Emergencies that require appropriate treatment targeted to the affected organ(s).

Aim: to evaluate the prevalence, clinical presentation and treatment of patients admitted for hypertensive emergencies or hypertensive urgencies in ED.

Methods: Medical records of consecutive patients aged at least 18 years, admitted to the ED of “Antonio Cardarelli” hospital in Naples (Italy) over a one month period and presenting with SBP at least 180 mmHg and/or DBP at least 110 mmHg were prospectively analyzed.

Results: We screened 3500 patients and enrolled 63 (1.8%). The mean age of the participants was 65 ± 13 and 65% were men. 73% of the patients had hypertension, 25% had coronary heart disease and 19 % diabetes. Overall, 31 had hypertensive emergency and 32 had hypertensive urgency. Five patients (8%) tested positive for Covid 19 infection, all hospitalized for hypertensive emergency.

Among hypertensive emergencies, the different forms of organ damage were: acute coronary syndrome (39%), abdominal aorta fissure (3.2%), acute heart failure (23%), hemorrhagic stroke (16%) and ischemic stroke (19%).

SBP values and heart rate (HR) were higher in patients with emergencies than in those with urgencies (BP 195 ± 17 vs 186 ± 24 mmHg and 93 ± 20 vs 83 ± 22 bpm), but the analysis showed no statistically significant differences between the two groups. (p = 0.12 and p = 0.087 respectively).

Chest pain was the most common presenting symptom in hypertensive emergency (42%) followed by neurological deficit (35%) and dyspnoea (22.6%).

Patients with hypertensive urgencies were prevalently asymptomatic (29%) o presented headache (28%).

Twelve patients with hypertensive emergency (38.7%) were assigned a yellow code.

Mortality was 8%; they were admitted for hypertensive emergency and 3 of the 5 deceased patients were affected by SARS COVID 19 infection.

Conclusions: The high prevalence of hypertensive emergency can be explained as our hospital is a reference center for percutaneous coronary intervention and stroke. Covid infection may have adversely affected the prognosis of patients with hypertensive emergency.

EPIDEMIOLOGY AND CLINICAL ASPECTS

CAROTID PLAQUE OFFSETS THE SEX DIFFERENCE IN CARDIOVASCULAR RISK IN YOUNG TO MIDDLE AGE HYPERTENSIVE PATIENTS: THE CAMPANIA SALUTE NETWORK

Costantino Mancusi, Ilaria Fucile, Maria Lembo, Maria Virginia Manzi, Christian Basile, Eva Gerdts, Carmine Morisco, Giovanni de Simone, Nicola De Luca, Raffaele Izzo

Introduction: Although women have in general lower risk for cardiovascular disease, presence of left ventricular hypertrophy (LVH) in hypertension offsets the female sex-protection in cardiovascular risk.

Aim: To assess whether presence of carotid artery plaque (CP) has a similar impact on the sex difference in risk for future cardiovascular events.

Methods: We studied 5209 women and men <65 years old with hypertension and free from prevalent cardiovascular disease enrolled in the prospective Campania Salute Network registry were followed over a mean of 5.9 years. Subjects were grouped according to the absence or the presence of CP identified by Doppler ultrasound (intima-media thickness > 15mm). Main outcome was major cardiovascular events (MACE; combined acute coronary syndromes, stroke, hospitalization for heart failure and incident atrial fibrillation).

Results: Among patients without CP (n = 3139), women were older, with higher systolic BP, cholesterol level and prevalent LVH but lower triglycerides and eGFR, compared to men (all p < 0.001). Among patients with CP (n = 2070), women were older, taking higher number of antihypertensive drug, with higher cholesterol level and prevalent LVH but lower triglycerides and eGFR compared to men (all p < 0.001). In Cox regression analysis adjusting for cardiovascular risk factors, LVH and antihypertensive treatment during follow up women without CP had lower hazard rate (HR = 0.41) for MACE (n = 107) than men (95% confidence interval [CI] 0.39–0.89, p = 0.01). In contrast, among patients with CP, women had similar HR for MACE (n = 132) as men (HR 0.79 [95% CI 0.54–1.14], p = 0.203).

Conclusions: This study demonstrates that presence of carotid organ damage in hypertension contributes to offset the female sex-protection in cardiovascular risk. Thus, expanding previous finding, young to middle-age women and men with hypertension and carotid organ damage have comparable cardiovascular risk.

PROGNOSTIC IMPACT OF FRAILTY ON FUNCTIONAL AUTONOMY IN OLDER ADULTS WITH HYPERTENSION

Ludovica Ceolin¹, Giulia Rivasi², Giada Turrin², Virginia Tortù², Marco Capacci², Diego Gentileschi², Carolina Corsi², Enrico Mossello², Andrea Ungar²

¹ Referral Centre for Hypertension Management in Older Adults, Division of Geriatric and Intensive Care Medicine, Careggi Hospital and University of Florence and Azienda Ospedaliero Universitaria Careggi, Florence, Italy; ² Referral Centre for Hypertension Management in Older Adults, Division of Geriatric and Intensive Care Medicine, Careggi Hospital and University of Florence and Azienda Ospedaliero Universitaria Careggi, Florence, Italy

Introduction: To date, few studies have evaluated frailty in older adults with hypertension and the most appropriate tool to quantify frailty in this population has yet to be identified.

Aim: to investigate the prognostic impact of frailty on decline of functional autonomy in a sample of hypertensive older adults.

Methods: We performed a longitudinal observational study including patients aged 75 or older evaluated at the Hypertension Clinic and Memory Clinic of the Division of Geriatric and Intensive Care Medicine, Careggi Hospital, Florence. Participants underwent a multidimensional geriatric assessment including frailty evaluation using three frailty scales (Fried Frailty Phenotype, Clinical Frailty Scale [CFS], Frailty Index) and two physical performance measures (gait speed and Short Physical Performance Battery [SPPB]). The primary outcome was reduction of autonomy in daily activities according to the Barthel Index ("functional decline"). The predictive performance of different frailty measures was evaluated based on ROC curve analysis, sensitivity, specificity and accuracy.

Results: Among 99 hypertensive older adults (mean age 81 years, 59% women, follow-up 13 months), functional decline occurred in 39% of patients. Participants with functional decline had a higher prevalence of cognitive impairment and frailty according to all the frailty scales used and a worse physical performance. Frailty Index and CFS showed the best predictive performance (AUC 0.715 and 0.708, respectively), followed by physical performance measures (AUC 0.691). All frailty measures showed good specificity (66–79%) and moderate sensitivity (54–70%). Gait speed showed the highest accuracy (71%) and achieved 57% sensitivity and 79% specificity, resulting in better predictive performance than the SPPB.

Conclusions: The CFS and gait speed—easily applicable even in non-geriatric settings—may represent useful instrument to detect frailty and predict functional decline in hypertensive older adults.

PREVALENCE, CLINICAL CHARACTERISTICS OF PERIPHERAL ARTERY DISEASE: A CROSS-SECTIONAL, NATION-WIDE STUDY

Giuliano Tocci¹, Francesca Miceli¹, Ilaria Figliuzzi¹, Barbara Citoni¹, Marialudovica Carducci¹, Giulia Nardoianni¹, Giovan Battista Desideri², Massimo Volpe¹, on behalf of the EFFECTUS Steering Committee

¹ Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ² Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy

Introduction: Diagnosis of peripheral artery disease (PAD) is frequently underestimated in clinical practice.

Aim: To evaluate prevalence, clinical characteristics and factors predicting the presence of PAD in a large cohort of adult outpatients representative of general population in Italy.

Methods: We collected data from a large sample of outpatients, followed by general practitioners, cardiologists and diabetologists in Italy. All data were centrally analysed for global CV risk stratification and rates of control of major CV risk factors. Study population was stratified according to presence or absence of previous CV events, including coronary artery (CAD), cerebrovascular (CVD) and PAD. In particular, PAD was defined by the presence of carotid or peripheral atherosclerosis, or both, as defined by Doppler Ultrasound examination of carotid or lower limb arteries. Multivariate analysis was set for identifying predictive factors of PAD.

Results: We analysed data from an overall population sample of 16,645 individuals (44.3% females, age 65.6 ± 10.3 years, BMI 28.0 ± 4.8 kg/m²), among whom 14,412 (86.6%) did not have and 2233 (13.4%) had evidence of PAD; in this latter group, 320 (14.3) had carotid, 1592 (71.3%) had peripheral and 321 (14.4%) had combined atherosclerosis. Patients with PAD had significantly higher prevalence of all risk factors and comorbidities. At multivariate analysis, CVD [OR 4.687 (95% CI 3.677–5.974)], CAD [OR 1.798 (95% CI 1.528–2.115)], smoking [OR 1.934 (95% CI 1.652–2.263)], dyslipidaemia [OR 1.809 (95% CI 1.528–2.141)], and eGFR [OR 0.992 (95% CI 0.988–0.996)], emerged, among others, as independent predictors for the presence of PAD.

Conclusions: Though its prevalence was relatively low, patients with PAD, mostly those with combined atherosclerosis, were characterized by very high CV risk profile. In the absence of ABI, presence of additional risk factors, CVD and CAD resulted strongly and independently predictors of the presence of PAD.

PROGNOSTIC ROLE OF ORTHOSTATIC BLOOD PRESSURE IN HYPERTENSIVE OLDER ADULTS

Giada Turrin, Giulia Rivasi, Marco Capacci, Ludovica Ceolin, Diego Gentileschi, Carolina Corsi, Virginia Tortu’, Martina Rafanelli, Enrico Mossello, Andrea Ungar

Hypertension Clinic, Division of Geriatric and Intensive Care Medicine, Careggi Hospital and University of Florence, Italy

Introduction: in older adults, orthostatic hypotension (OH) represents a recognized risk factor for adverse outcomes such as falls, syncope and cardiovascular events, while its prognostic impact on functional autonomy remains currently unknown.

Aim: to investigate the association between orthostatic blood pressure (BP) response and functional decline in hypertensive older adults.

Methods: the study involved hypertensive patients aged 75+ from the Hypertension Clinic and Memory Clinic of the Geriatric Department of Careggi Hospital, Florence, Italy. Participants underwent multidimensional geriatric assessment and measurement of BP within 3 minutes of standing. Decline in functional autonomy was defined according to the Barthel Index assessed during phone interviews. Cox regression analysis was applied to investigate the association of functional decline with standing systolic BP (sBP) and orthostatic systolic BP drop (ΔBP), expressed as a percentage of supine systolic BP.

Results: Among 99 patients (mean age 81 years, 56% female), prevalence of OH was 44%, with a mean immediate BP drop of 14.8 ± 14.2% (ΔBP-t0), a mean drop of 10.6 ± 16.3% at the first minute (ΔBP-t1) and 8.0 ± 14.4% at the third minute (ΔBP-t3).

After a median follow-up of 13 months, 37 patients reported functional decline. sBP and ΔBP were comparable in patients with and without functional decline. In a sex- and age-adjusted Cox regression analysis, sBP was not associated with functional decline. A greater systolic BP drop at 1 minute within standing was associated with an increased risk of functional decline in frailer subjects (HR 1.048, 95% CI 1.003–1.095), but not in fit ones (HR 0.969, 95% CI 0.918–1.022).

Conclusions: a greater systolic BP drop at 1 minute within standing predicts 1-year functional decline in older adults with hypertension and frailty.

APPLICABILITY OF THE SPRINT STUDY IN A "REAL WORLD" SAMPLE OF HYPERTENSIVE OLDER ADULTS

D. Gentileschi, G. Rivasi, G. Turrin, M. Capacci, L. Ceolin, C. Corsi, V. Tortù, E. Mossello, A. Ungar

Hypertension Clinic, Division of Geriatric Medicine and Intensive Care Medicine, University of Florence and Azienda Ospedaliera Universitaria Careggi, Florence, Italy,

Introduction: The SPRINT study demonstrated the benefits of intensive blood pressure (BP) control in older hypertensive adults, including frailer patients (1). However, the applicability of these results in the geriatric population remains doubtful, due to very selective inclusion criteria and low levels of frailty of the SPRINT study population.

Aim: This study assessed the applicability of SPRINT in a "real world" sample of hypertensive older adults and analysed the association between BP and functional decline by SPRINT eligibility.

Methods: We applied SPRINT inclusion/exclusion criteria in a sample of hypertensive patients ≥ 75 years evaluated at the Hypertension and Memory clinics of the Geriatric Department of Careggi Hospital, Florence. The Cox analysis was applied to analyse the association between BP and functional decline (according to Barthel Index) by SPRINT eligibility.

Results: Among 123 patients (mean age 81), only 39 (31.7%) complied with the SPRINT inclusion criteria. Ineligible patients showed higher prevalence of frailty (46% vs 26%, p = 0.028) and disability in basic (25% vs 5%, p = 0.009) and instrumental activities of daily living (61% vs 33%, p = 0.005) and worse physical performance (reduced walking speed 43% vs 22%, p = 0.027). Moreover, they had a higher comorbidity burden (median Charlson Index 5 [4–6] vs 4 [3–5], p < 0.001). BP values were similar in the two subgroups. At 13 months, incidence of functional decline was higher in ineligible subjects (48% vs 21%, p = 0.012). In age- and sex-adjusted Cox analysis, ambulatory BP was associated with functional decline only in eligible subjects (24h-systolic BP HR 1.193, 95% CI 1.009–1.411).

Conclusions: In a "real world" sample of hypertensive older adults, only one third of subjects complied with the SPRINT inclusion criteria. Higher levels of frailty and disability were observed in ineligible subjects, in whom BP values seem to have a limited prognostic impact.

PRESCRIPTIVE APPROPRIATENESS IN PRIMARY CARDIOVASCULAR PREVENTION: DATA FROM NIGUARDA HOSPITAL

Alessandro Maloberti, Davide Ceruti, Elena Gualini, Valentina Colombo, Valentina Giani, Martina Milani, Jinwei Sun, Marta Alloni, Cristina Giannattasio

Cardiologia 4, Niguarda Hospital, Milan, Italy; School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

Introduction: The main cause of waste of health resources is represented by overuse of diagnostic and therapeutic procedures. Given its high prevalence and the importance of identifying hypertensive-mediated organ damage, management of patients with arterial hypertension can lead to a lack of appropriateness.

Aim: to evaluate the prescriptive appropriateness of non-invasive diagnostic tests (Echocardiography, Carotid ultrasound, ECG exercise testing, 24h Ambulatory blood pressuremonitoring) in outpatients referring to an ambulatory of primary cardiovascular prevention.

Methods: 559 specialistic ambulatory visits were retrospectively analysed and appropriateness of every prescription was evaluated. An integration of different Italian and European guidelines was used todefine appropriateness. Moreover, we evaluated the correlation between prescriptions, appropriateness and clinical characteristics of the population.

Results: During the 559 ambulatory visits analysed, 449 prescriptions were made, including 198 echocardiographies, 148 carotid ultrasound, 85 24h ABPM and 18 ECG exercise testing. The global percentage of appropriate prescriptions was 40.3%. Focusing on each test, appropriateness rate was 49.4% in 24h ABPM, 43.9% in echocardiography, 38.9% in ECG exercise testing and 30.4% in carotid ultrasound. A significant correlation was identified between the age and cardiovascular risk category of patients and the appropriateness of echocardiography, 24h ABPM and carotid ultrasound, and a correlation between appropriateness of echocardiography and the duration of hypertension and the presence of valvular heart disease.

Conclusions: Our study shows a relevant percentage of inappropriate prescriptions of non-invasive cardiologic exams; moreover, there might be a greater lack of appropriateness in young and low risk patients.

ANALISYS OF CENTRAL BLOOD PRESSURE AND HYPERTENSION-MEDIATED ORGAN DAMAGE IN A COHORT OF YOUNG PATIENTS WITH ISOLATED SYSTOLIC HYPERTENSION

Giuliano Tocci ¹, Giulia Nardoianni ¹, Ilaria Figliuzzi ¹, Barbara Citoni ¹, Francesca Miceli ¹, Marialudovica Carducci ¹, Giacomo Pucci ², Massimo Volpe ¹

¹ Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ² Department of Medicine and Surgery, University of Perugia, Perugia, Italy, and Unit of Internal Medicine, Santa Maria University Hospital, Terni, Italy

Introduction: Recent studies suggested a potential role of high levels of central blood pressure (BP) in the pathophysiology of isolated systolic hypertension (ISHT) in young individuals.

Aim: To estimate brachial and central systolic BP and pulse pressure (PP), pulse wave velocity (PWV), augmentation index (AI) and peripheral vascular resistances (PVR) in young adults undergoing a diagnostic work-up for essential hypertension at an ESH excellence centre in Italy.

Methods: A single-centre, cross-sectional study was conducted at Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy by including outpatients aged 18-50 years, who consecutively underwent full BP evaluation and global cardiovascular risk assessment. Clinic brachial and central BP and pulse wave velocity (PWV) were measured in seated position after 5–10 min of rest by using an automated, oscillometric device (Mobil-O-Graph PWA Monitor, I.E.M. GmbH, Stolberg, Germany). Study population was stratified according to different hypertension phenotypes: normotension (NT), clinic brachial BP <140/<90 mmHg; ISHT, > = 140/<90 mmHg; isolated diastolic hypertension (IDHT), <140/ > = 90 mmHg; systo-diastolic hypertension (SDHT), > = 140/ > = 90 mmHg.

Results: We analysed 259 young individuals (39.2% female, 39.7 ± 7.6 years, BMI 26.7 ± 5.3 kg/m²), among whom 38.6% had NT, 15.1% IDHT, 11.6% ISHT, and 34.7% SDHT. ISHT patients showed significantly higher cSBP (126.5 ± 10.0 vs. 116.5 ± 10.6 mmHg; P < 0.001) and cPP (37.7 ± 10.1 vs. 32.5 ± 8.2 mmHg; P = 0.022) than NT individuals. cSBP (126.5 ± 10.0 vs. 135.7 ± 14.2 mmHg; P = 0.002) and PVR (1652.5 ± 239.7 vs. 1830.2 ± 348.1 dyn*sec/cm⁵; P = 0.013) resulted significantly lower in ISHT than in SDHT patients. No significant differences were observed between these two groups for cPP, indexes of left ventricular function and other markers of cardiac and vascular HMOD, including LVMi, LVMh^2.7, AI and PWV.

Conclusions: Our findings support the hypothesis that ISHT in young individuals should not be viewed as an innocent phenomenon, being characterized by increased cSBP, cPP, and reduced PVR compared to other hypertension phenotypes.

PREVALENCE AND CLINICAL CHARACTERSITICS OF WHITE-COAT HYPERTENSION IN YOUNG PATIENTS WITH ISOLATED SYSTOLIC HYPERTENSION

Giuliano Tocci, Giulia Nardoianni, Ilaria Figliuzzi, Barbara Citoni, Francesca Miceli, Marialudovica Carducci, Massimo Volpe

Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy

Introduction: Several studies suggested that isolated systolic hypertension (ISHT) in young adults may be related to transient clinic blood pressure (BP) elevation with normal 24-hour ambulatory BP levels, namely white-coat hypertension (WCHT).

Aim: To estimate prevalence and clinical characteristics of WCHT in young adults with ISHT compared to that of other hypertension phenotypes.

Methods: A single center, prospective, cohort study was conducted at Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy. We evaluated clinic, 24-h, day-time and night-time systolic/diastolic BP levels in outpatients aged 18–50 years, who consecutively underwent full BP evaluation and global cardiovascular risk assessment. ISHT was defined as clinic systolic/diastolic BP ≥ 140/< 90 mmHg, and WCHT as clinic BP ≥ 140/≥ 90 mmHg and 24-h BP < 130/< 80 mmHg.

Results: We analyzed data from an overall sample of 2967 individuals (female 45.4%, mean age 40.4 ± 7.4 years, mean BMI 26.6 ± 4.9 kg/m²), among whom 6.8% had ISHT. ISHT patients were significantly younger than those in other hypertension phenotypes (P < 0.001), whilst no significant differences were found for distribution of major risk factors and comorbidities. They also showed significantly higher home (P < 0.001) and 24-hour ambulatory (P < 0.001) systolic BP and SCORE risk (P < 0.001) levels than those of other groups. Patients with ISHT were more frequently males than females (61.1% vs. 38.9%; P < 0.001) and treated for hypertension (P = 0.033) and dyslipidaemia (P = 0.046) than other groups. WCHT was detected in 33.5% of patients with ISHT. The majority of ISHT patients showed sustained (24-h) systolic BP elevation (66.5%), both in the presence (72.2%) or in the absence (62.9%) of antihypertensive medications.

Conclusions: Our findings support the hypothesis that ISHT in young individuals should be viewed as an innocent phenomenon, being frequently associated with sustained BP elevation during the 24-h period and high cardiovascular risk profile.

PREVALENCE AND CLINICAL CHARACTERSITICS OF “SPURIOUS HYPERTENSION” IN YOUNG PATIENTS WITH ISOLATED SYSTOLIC HYPERTENSION

Giuliano Tocci ¹, Giulia Nardoianni ¹, Ilaria Figliuzzi ¹, Barbara Citoni ¹, Francesca Miceli ¹, Marialudovica Carducci ¹, Giacomo Pucci ², Massimo Volpe ¹

¹ Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy; ² Department of Medicine and Surgery, University of Perugia, Perugia, Italy, and Unit of Internal Medicine, Santa Maria University Hospital, Terni, Italy

Introduction: Recent clinical studies suggested that isolated systolic hypertension (ISHT) with normal central systolic blood pressure (BP), a condition defined “spurious hypertension” (sHTN), may have better cardiovascular outcomes than “true” ISHT.

Aim: To estimate prevalence and clinical characteristics of sHTN in young adults with ISHT undergoing a diagnostic work-up for essential hypertension at an ESH excellence centre in Italy.

Methods: A single center, prospective, cohort study was conducted at Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy, by including outpatients aged 18–50 years, who consecutively underwent full BP evaluation and global cardiovascular risk assessment. Clinic brachial and central BP and pulse wave velocity (PWV) were measured in seated position after 5–10 min of rest by using an automated, oscillometric device (Mobil-O-Graph PWA Monitor, I.E.M. GmbH, Stolberg, Germany). ISHT was defined as clinic brachial systolic/diastolic BP ≥ 140/< 90 mmHg. Once identified, ISHT patients were further stratified according to the presence or the absence of sHTN, as defined as cBP above or below the median value in our population sample (± 125 mmHg).

Results: We identified 30 young patients with ISHT (female 45.4%, mean age 39.0 ± 7.3 years, mean BMI 27.1 ± 6.9 kg/m², systolic/diastolic brachial BP 150.2 ± 9.6/84.4 ± 4.1 mmHg, central BP 126.5 ± 10***.0/88.8 ± 7.1 mmHg), among whom 43.3% had sHTN and 56.7% had true ISHT. Patients with sHTN showed significantly lower BMI (23.7 ± 4.3 vs. 29.7 ± 7.4 g/m²; P = 0.014), cPP 31.1 ± 6.6 vs. 42.8 ± 9.5 mmHg; P < 0.001), LVMi (74.3 ± 20.9 vs. 94.9 ± 24.3 g/m²), LVMh^2.7 (31.0 ± 9.7 vs. 42.4 ± 12.4 gr/m^2.7), and PVW (6.1 ± 0.6 vs. 6.9 ± 0.5 m/s) than those with true ISHT. There was no significant difference between groups for the distribution of gender, major cardiovascular risk factors and antihypertensive therapies.

Conclusions: Our findings support the hypothesis that sHTN in young adults with ISHT may represent a condition associated with lower cardiovascular risk profile and lower incidence of cardiac and vascular HMOD than true ISHT.

CORRELATION BETWEEN PLASMA ALDOSTERONE LEVELS AND PULSE WAVE VELOCITY IN A LARGE SAMPLE OF ADULT OUTPATIENTS WITH ESSENTIAL HYPERTENSION

Giuliano Tocci, Vivianne Presta, Barbara Citoni, Ilaria Figliuzzi, Francesca Miceli, Giulia Nardoianni, Marialudovica Carducci, Massimo Volpe

Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy

Introduction: Asymptomatic vascular hypertension-mediated organ damage (HMOOD) related to arterial stiffening has an important role in cardiovascular (CV) risk stratification. Its correlation with hormone levels has not been fully elucidated.

Aim: To evaluate the potential correlation between plasma aldosterone (PA) levels and parameters of vascular stiffness.

Methods: A single-centre, cross-sectional study was conducted in treated and untreated adult outpatients aged > 18 years, who consecutively underwent full BP assessment and global CV risk assessment at our Hypertension Unit, Division of Cardiology, Sant’Andrea Hospital, Rome Italy. Clinic blood pressure (BP) and pulse wave velocity were measured in seated position after 5-10 minutes of rest by using an automated, oscillometric device (Mobil-O-Graph PWA Monitor, I.E.M. GmbH, Stolberg, Germany). Blood samples were then obtained to test PA concentration (ng/ml) and plasma renin activity (PRA). Any drugs able to interfere with PA, PRA or aldosterone-renin ratio (ARR) was stopped at least 4–6 weeks before samples and replaced by calcium channel blockers and/or alpha-blocker, if needed.

Results: We analysed BP data from an overall sample of 131 adult outpatients with valid clinic BP and PA levels (36.6% females, mean age 42.2 ± 13.6 years, mean BMI 26.2 ± 4.6 kg/m², clinic BP 144.7 ± 17.5/94.6 ± 12.6 mmHg), among whom 57.3% were untreated, 23.7% were on monotherapy, and 19.1% were on dual combination therapy. PWV was significantly higher in treated hypertensive outpatients than in untreated individuals (7.5 ± 19 vs. 6.7 ± 1.1 m/sec; P < 0.001), while no significant difference was found for PA, PRA and ARR between groups. PWV resulted significantly and positively correlated with PA (r = 0.219; P = 0.012) (Figure A), even after correction for covariates. No significant correlations were observed between PWV and either PRA (P = 0.577) or ARR (P = 0.075).

Conclusions: Our analysis demonstrated positive and independent correlation between increased PWV and high levels of PA, thus suggesting a potential role of this hormone in the pathogenesis of vascular HMOD in essential hypertension.

GENETIC, PHARMACOGENOMYC, PROTEOMIC AND METABOLOMIC

THE CAUSAL ROLE OF SERUM CALCIUM, PTH AND FGF23 ON BLOOD PRESSURE: A TWO-SAMPLE MENDELIAN RANDOMIZATION

Alice Giontella^1,2; Luca A. Lotta³; John D. Overton³; Aris Baras³; Regeneron Genetics Center³, Pietro Minuz¹; Dipender Gill^4,5,6,7; Olle Melander^2,8; Cristiano Fava^1,2

¹Department of Medicine, University of Verona, Verona, Italy; ²Department of Clinical Sciences, Clinical Research Center, Lund University, Malmö, Sweden; ³Regeneron Genetics Center, Tarrytown, NY, USA; ⁴Department of Epidemiology and Biostatistics, Imperial College London, London, UK; ⁵Novo Nordisk Research Centre Oxford, Old Road Campus, Oxford, UK; ⁶Clinical Pharmacology Group, Pharmacy and Medicines Directorate, St George’s University Hospitals NHS Foundation Trust, London, UK; ⁷Clinical Pharmacology and Therapeutics Section, Institute for Infection and Immunity, St George’s, University of London, London, UK; ⁸Department of Emergency and Internal Medicine, Skåne University Hospital, Malmö, Sweden

Introduction: Vitamin D (Vit-D), Parathyroid hormone (PTH) and Fibroblast Growth Factor 23 (FGF23) are the major calciotropic hormones involved in the regulation of blood calcium levels from the intestine, kidney, and bone through a tight endocrine feedback loop system. Altered levels of calcium per se or through the effect of its regulatory hormones could affect blood pressure (BP), but the exact mechanisms remain unclear.

Aim: To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a Two-Sample Mendelian Randomization (MR) study.

Method: From four large genome-wide association studies (GWAS) we obtained independent (r^2<0.001) single nucleotide polymorphisms (SNPs) associated with serum calcium (119 SNPs), Vit-D (78 SNPs) PTH (5 SNPs), and FGF23 (5 SNPs), to investigate through MR their association with Systolic BP (SBP) and Diastolic BP (DBP) in a Swedish urban-based study, the Malmö Diet and Cancer (n = 29,298). Causality was evaluated by the Inverse Variance Weighted Method (IVW) and weighted median, while MR Egger and MR-PRESSO were used as sensitivity analyses.

Results: Genetically predicted serum calcium level was found to be associated with DBP (IWV: beta = 0.10, SE = 0.04, p = 0.007) and SBP (IWV: beta = 0.07, SE = 0.04, p = 0.04). Genetically predicted Vit-D and PTH didn’t show any association with the traits, while FGF23 was inversely associated with SBP (IWV: beta = − 0.11, SE = 0.04, p = 0.01), although this association lost statistical significance in sensitivity analysis.

Conclusions: Our study shows a direct association between genetically predicted calcium level and DBP, and a weaker association with SBP. No such clear association was found for genetically predicted calciotropic hormones levels. It is of interest to detect which target genes involved in calcium homeostasis mediate the effect of calcium on BP, particularly for improving personalized intervention strategies.

ASSOCIATION OF NDUFC2 POLYMORPHIC VARIANTS WITH LEFT VENTRICULAR HYPERTROPHY IN HUMAN HYPERTENSION

Giovanna Gallo¹, Maurizio Forte², Giuliano Tocci¹, Maria Cotugno², Simona Marchitti², Rosita Stanzione², Franca Bianchi², Sara Palmerio², Sebastiano Sciarretta³, Massimo Volpe¹, Speranza Rubattu ^1,2

¹ Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy; ² IRCCS Neuromed, Pozzilli (IS), Italy; ³ Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, 04100 Latina, Italy

Introduction: Previous experimental studies showed that a dysfunction of the NADH dehydrogenase (ubiquinone), the mitochondrial Complex I (CI), is associated with the development of left ventricular hypertrophy (LVH). A deficiency of Ndufc2 (a subunit of CI) impairs CI activity and causes severe mitochondrial dysfunction. The NDUFC2/rs11237379 polymorphic variant is associated with reduced gene expression and impaired mitochondrial function, contributing to increased susceptibility to vascular diseases.

Aim: We examined the association of NDUFC2/rs11237379 and another NDUFC2 polymorphic variant (rs641836) with the development of LVH in hypertensive patients.

Methods: Two-hundred-fourty-six hypertensive subjects (147 male, 59.7%) with a mean age of 59 ± 15 years were studied. Seventy-nine individuals (32%) presented LVH. Genomic DNA was isolated from venous peripheral blood by using the FlexiGene kit (Qiagen). The two polymorphic variants were characterized by Taqman methodology.

Results: The association analysis for both SNPs showed that hypertensive patients carrying the TT genotype at the NDUFC2/rs11237379 had a significant increase of echocardiographically assessed septal thickness (p = 0.001), posterior wall thickness (p = 0.003), relative wall thickness (RWT) (p = 0.01), LV mass/BSA (p = 0.012) and LV mass/height^2.(p = 0.0033) compared to subjects carrying either CC or CT genotypes. To better dissect out the genetic effect, a covariate ANOVA was performed for each cardiac variable, considering age, gender, body mass index (BMI), office blood pressure (BP), antihypertensive treatment with a combination of 2 or more drugs and the number of BP-lowering agents as covariates. The adjustment for covariates revealed significant differences for septal thickness (p = 0.07), posterior wall thickness (p = 0.008), RWT (p = 0.021), LV mass/BSA (p = 0.03). With regard to NDUFC2/rs641836, hypertensive subjects carrying the mutant A allele had a significant increase of septal thickness (p = 0.001), posterior wall thickness (p = 0.001), RWT (p = 0.005), LV mass (p = 0.001), LV mass/body surface area (BSA) (p = 0.001), LV mass/height^2.7(p = 0.002) compared to wild-type homozygotes. After adjustment for covariates, the results were significant for septal thickness (p = 0.017), posterior wall thickness (p = 0.011), LV mass (p = 0.003), LV mass/BSA (p = 0.002) and LV mass/height^2.7(p = 0.010).

Conclusions: Our results demonstrate for the first time a significant association of NDUFC2 variants with LVH in hypertensive patients and highlight a novel role of CI dependent mitochondrial dysfunction on increased susceptibility to cardiac damage in human hypertension. This study paves a way of a new pathophysiological mechanism of LVH in humans which may lead to new clinical strategies.

CORONAVIRUS, HYPERTENSION AND CARDIOVASCULAR RISK

ONGOING ACE-INHIBITOR OR ATII-ANTAGONIST TREATMENT DOESN’T IMPACT ON OUTCOME NOR ON SEQUELAE OF PATIENTS WITH MODERATE TO SEVERE COVID-19 PNEUMONIA

Gianluca E.M. Boari ², Francesca Salvotti ^1,2, Thelma Geneletti ^1,2, Eleonora Carlotti ^1,2, Elena Maria Fusco ^1,2, Giulia Gazzina ^1,2, Alessandro Salvini ^1,2, Pietro Volpe ^1,2, Federico Tosoni ^1,2, Erika Borghi ², Daniele Turini ², Giancarlo Pasini ², Vittoria Guarinoni ², Sara Viola ², Francesca Manzoni ², Daniele Turini ², Paolo Malerba ^1,2, Carolina De Ciuceis ¹, Claudia Agabiti Rosei ¹, Damiano Rizzoni ^1,2

¹ University of Brescia, Brescia, Italy; ² Division of Medicine, Spedali Civili di Brescia, Montichiari, Brescia, Italy

Introduction: COVID-19 pandemic still represents a major clinical problem worldwide. Many studies are actively being carried out to better understand prognostic factors of outcome as well as optimal treatment.

Aim: ACE-2 receptor is highly expressed on the surface of cardiac and pulmonary cells, and it is used by coronaviruses to enter host cells; this makes the role of ACE-inhibitors and Angiotensin Receptor Blockers (ARBs) drugs controversial. Moreover, it is still unclear whether these drugs may have any impact on sequelae.

Methods: In this retrospective study, we analysed a group of 244 hypertensive unvaccinated patients (134 on ACE-inhibitors, 110 on ARBs) admitted for moderate to severe COVID-19 pneumonia.

As shown in Table 1, the two groups were homogeneous.

Of these patients, 46 (20 treated with ACE-I and 26 treated with ARBs) came to a follow-up visit after a mean of 260 days; they underwent a quality-of-life assessment, laboratory and radiologic tests and spirometry (with DLCO).

Table 1 Main comparisons between groups

Results: A total of 20 of 110 (18%) patients under treatment with ARBs and 23 of 134 (17%) died during hospitalization (p = 0.8, NS).

At discharge, biochemical, radiological and respiratory data were not significantly different.

We did not find any significant difference in terms of radiological alterations, lung fibrosis, spirometry data, DLCO, persisting effort dyspnea.

Biochemical data were substantially super-imposable in the two groups.

Conclusions: In conclusion, we could not detect any difference in outcome nor in complications type or number in the two groups of hypertensive patients undergoing treatment with ACE-inhibitor or ARBs. This result seems to support and to strengthen the idea that ACE-inhibitors and ARBs do not play a significant role in onset, evolution and outcome of moderate to severe COVID-19 pneumoniae. Although the number of follow-up patients is small, we did not find any difference in follow-up sequelae in both groups.

MODERATE TO SEVERE SARS-COV2 AND CARDIOVASCULAR EVENTS AT ONE YEAR: A DESCRIPTIVE RETROSPECTIVE ANALYSIS

Francesca Salvotti ^1,2, Gianluca E.M. Boari ², Carolina De Ciuceis ¹, Claudia Agabiti Rosei ¹, Erika Borghi ^1,2, Federico Tosoni ^1,2, Elena Maria Fusco ^1,2, Pietro Volpe ^1,2, Thelma Geneletti ^1,2, Eleonora Carlotti ^1,2, Giulia Gazzina ^1,2, Alessandro Salvini ^1,2, Michele Saottini ², Valeria Brami ², Bianca Bonzi ², Paolo Desenzani ², Paolo Malerba ², Luca Trombetta ², Maria Claudia Tusi ^1,2, Eros Zanotti ², Giulia Ferrari-Toninelli ², Damiano Rizzoni ^1,2

¹ University of Brescia, Brescia, Italy; ² Division of Medicine, Spedali Civili di Brescia, Montichiari, Brescia, Italy

Introduction: The Coronavirus disease 2019 (COVID-19), doesn’t affect only respiratory system, but it also involves other organs including cardiovascular system, possibly causing acute or chronic cardiovascular events. Preexisting cardiovascular diseases enhance COVID-19 morbidity, as well.

Aim: In this retrospective analysis we investigated the onset of cardiovascular events during a time-span of more than one year since hospitalization (384 days).

Methods: The analysis included 43 patients, who were hospitalized in Internal Medicine Department of Montichiari Hospital (ASST Spedali Civili of Brescia) for moderate to severe SARS-CoV2 related pneumonia treated with high-flow oxygen support (ranging from 40% fraction of inspired oxygen to non-invasive ventilation)

Results: Mean age was 63 years, 28% (12/43) were female and 72% (31/43) were male. Thirty-five percent of the patients suffered from heart diseases, 56% of them were hypertensives and 23% had type 2 diabetes; 12% had chronic kidney disease (CKD) and 5% an active neoplasm. 49% of the sample was obese. Nineteen percent took ACE inhibitors and 19% was on ARBs. Statins were taken by 37% of the patients; an antiaggregant by 21%, and an anticoagulant by 2% (see table)

Table 1: Main demographic data, comorbidities and ongoing therapies

The follow-up visit included the evaluation of post-covid infection quality-of-life, standard laboratory tests, chest computed tomography, spirometry with evaluation of DLCO. The onset of cardiovascular events during the average period of 384 days was evaluated. None of the 43 patients had major cardiovascular events: coronary heart disease, cerebrovascular disease, peripheral arterial disease, deep vein thrombosis and pulmonary embolism.

Conclusions: Even if this study failed to demonstrate new-onset CV events, longer follow-up studies performed to evaluate cardiovascular risk following SARS-CoV1 infection showed persistent hyperlipidemia, cardiovascular system abnormalities, and glucose metabolism disorders in a very high number of patients.

Future analyses are needed to further investigate longer term cardiovascular consequences of SARS-CoV2 infection.

RENIN-ANGIOTENSIN-SYSTEM INHIBITORS ARE ASSOCIATED WITH LOWER IN-HOSPITAL MORTALITY IN COVID-19 PATIENTS AGED 80 AND OLDER

Francesco Spannella ^1,2, Giorgia Laureti ^1,2, Federico Giulietti ^1,2, Chiara Di Pentima ^1,2, Piero Giordano ¹, Massimiliano Allevi ^1,2, Samuele Scorcella ^1,2, Paola Schiavi ^1,2, Caterina Garbuglia ^1,2, Riccardo Sarzani ^1,2

¹ Internal Medicine and Geriatrics, IRCCS INRCA, Ancona, Italy; ² Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy

Introduction: Older adults are at higher risk of morbidity and mortality for COVID-19. Renin angiotensin-system-inhibitors (RASi) were found to have neutral or protective effect against mortality in COVID-19 adult patients.

Aim: We investigated whether this association was confirmed also in COVID-19 older patients.

Methods: Prospective observational study on 337 hospitalized older adults (aged 80 years and older). We classified the study population according to RASi use before and during hospitalization.

A propensity score analysis was also performed to confirm the findings.

Results: Mean age was 87.4 ± 6.1 years. Patients taking RASi at home were 147 (43.6%). During hospitalization, 38 patients (11.3% of the entire study population) discontinued RASi, while 57 patients (16.9% of the entire study population) started RASi. In-hospital mortality was 43.9%. Patients taking RASi during hospitalization (patients who maintained their home RASi therapy + patients who started RASi during hospitalization) had a significant lower in-hospital mortality than untreated patients [HR 0.48 (95% CI 0.34–0.67)], even after adjustment for required respiratory support, functional status, albumin, inflammation and cardiac biomarkers. The association between RASi and in-hospital mortality has been found to be more evident in patients with NT-proBNP ≥ 1800 pg/ml. The analysis on the groups derived from the ‘propensity score matching’ (58 patients in each group) confirmed these results [HR 0.46 (95% CI 0.23–0.91)].

Conclusions: Despite the high risk of death in older COVID-19 patients, RASi therapy during hospitalization was associated with clinically relevant lower in-hospital mortality, likely due to the benefit of RAS modulation on cardiopulmonary system during the acute phase of the disease. Our findings confirm the protective role of RASi even in COVID-19 patients aged 80 years and older.

MONOCENTRIC COHORT RETROSPECTIVE OBSERVATIONAL STUDY ON COVID-19 PATIENTS AIMED AT EXPLORING THE FACTORS OF CARDIOVASCULAR DEATH

Chiara Grasselli, Lucia Salvi, Riccardo Simoni, Maicol Baldini, Angelo Ghirarduzzi

Hypertension Center of Cardiovascular Medicine - AUSL of Reggio Emilia, Italy

Introduction: Several factors have been proposed to explain the high mortality rate of the Covid-19, including hypertension and treatment with renin-angiotensin-aldosterone (RAAS) system inhibitors. Age and multimorbidity could be confounding factors.

Methods: Our Hypertension Center enlisted 462 Covid-19 patients, admitted from March 2020 to April 2021 at our Cardiovascular Medicine Unit (males 61.7%, 71 ± 0.5 years), of which 338 patients (73.2%) had comorbidity. The 65.5% of patients had previous cardiovascular diseases, of which hypertension was the most represented (61.7%). At the onset the most frequent symptom is fever, followed by dyspnoea/tachypnea and cough and frequently associated dyslipidaemia, diabetes mellitus and obesity. Among the main cardiovascular complications, 12 pulmonary embolism, 10 deep venous thrombosis, 7 acute coronary syndrome, 9 strokes and 1 peripheral acute ischemia.

Results: One hundred and then people have died (24.9%). The main causes of deaths were ARDS (12.3%) and sepsis and MOF (9.2%). The population that did not survive had an average age of almost 80 years, significantly higher than the group of living, and different comorbidities, mainly cardiovascular, that configured a greater degree of fragility. Treatment with RAAS inhibitors in the group of deceased has been more frequently suspended.

Conclusions: The stop of therapy was found to be attributable to either erroneous beliefs borrowed from early Chinese reports or sepsis hypotension, and arterial hypertension or therapy with RAAS blockers cannot be considered risk factors due to the onset or to the manhood of COVID-19.

RAAS blockers certainly do not hurt, indeed it is hypothesized that their use is associated with protective effects on the prognosis of Covid-19, in line with what is stated in the Literature.

MONOCENTRIC COHORT RETROSPECTIVE OBSERVATIONAL STUDY ON COVID-19 PATIENTS AIMED AT EXPLORING THE FACTORS OF CARDIOVASCULAR DEATH

Chiara Grasselli, Lucia Salvi, Riccardo Simoni, Maicol Baldini, Angelo Ghirarduzzi

Hypertension Center of Cardiovascular Medicine-AUSL of Reggio Emilia, Italy

Introduction: Several factors have been proposed to explain the high mortality rate of the COVID-19, including hypertension and treatment with renin-angiotensin-aldosterone (RAAS) system inhibitors. Age and multimorbidity could be confounding factors.

Methods: Our Hypertension Center enlisted 462 Covid-19 patients, admitted from March 2020 to April 2021 at our Cardiovascular Medicine Unit (males 61.7%, 71 ± 0.5 years), of which 338 patients (73.2%) had comorbidity. The 65.5% of patients had previous cardiovascular diseases, of which hypertension was the most represented (61.7%). At the onset the most frequent symptom is fever, followed by dyspnoea/tachypnoea and cough and frequently associated dyslipidaemia, diabetes mellitus and obesity. Among the main cardiovascular complications, 12 pulmonary embolism, 10 deep venous thrombosis, 7 acute coronary syndrome, 9 strokes and 1 peripheral acute ischemia.

Results: One hundred and then people have died (24.9%). The main causes of deaths were ARDS (12.3%) and sepsis and MOF (9.2%).

The population that did not survive had an average age of almost 80 years, significantly higher than the group of living, and different comorbidities, mainly cardiovascular, that configured a greater degree of fragility. Treatment with RAAS inhibitors in the group of deceased has been more frequently suspended.

Conclusions: The stop of therapy was found to be attributable to either erroneous beliefs borrowed from early Chinese reports or sepsis hypotension, and arterial hypertension or therapy with RAAS blockers cannot be considered risk factors due to the onset or to the manhood of COVID-19. RAAS blockers certainly do not hurt, indeed it is hypothesized that their use is associated with protective effects on the prognosis of COVID-19, in line with what is stated in the Literature.

ANALYSIS OF PROGNOSTIC FACTORS IN COVID-19 HOSPITALIZED PATIENTS: AN ITALIAN SINGLE-CENTER PROSPECTIVE STUDY

Antonio Concistrè^1,2, Cecilia Lina Pugliano², Fabio Vinci¹, Monia Celi², Elio Pietro Perrone¹, Silvia Rella¹, Francesco Iannazzo¹, Alberta Angheloni¹, Lucia Coraggio¹, Francesco Di Rienzo¹, Daniela Maggi¹, Maurizio Muscaritoli^1,3, Claudio Letizia^1,2

¹ Internal Medicine COVID-19 Unit, Policlinico Umberto I University Hospital, Rome, Italy; ² Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, University of Rome “Sapienza”, Italy; ³ Department of Translational and Precision Medicine, University of Rome “Sapienza”, Italy

Introduction: COVID-19 clinical presentation ranges from asymptomatic infection to an inflammatory cytokine storm with multi-organ failure and fatal outcomes. The identification of high-risk patients for severe disease is crucial in order to plan an early treatment and intensive follow-up.

Aim: we aimed at investigating negative prognostic factors in a group of patients hospitalized for COVID-19.

Methods: 181 patients (83 men and 98 women, age 69.50 ± 15.75 years) were enrolled. Each patient received a work-up including medical history, clinical examination, arterial blood gas analysis, laboratory blood tests, feasible ventilatory support required during hospital stay, intensive care setting required, duration of illness and length of hospital stay (> or<25 days). For the assessment of the severity of COVID-19, four main indicators were considered: (1) the intensive care unit (ICU) admission (2) the hospitalization length > 25 days; (3) the need of non-invasive ventilation (NIV); (4) death.

Results: The independent risk factor associated with the ICU admission were: male gender (p = 0.02), gamma glutamyl transpeptidase elevation (p = 0.014), C reactive protein elevation (p = 0.09) at hospital admission and direct oral anticoagulant home therapy (p = 0.048); for hospital length > 25 days: early corticosteroid therapy (p = 0.026) d-dimer elevation at hospital admission (p = 0.009), the presence of at least three comorbidities (p = 0.038); for NIV treatment: ferritin and C reactive protein elevation at hospital admission (p = 0.006 and p = 0.008 respectively), body overweight (p < 0.01) and early corticosteroid therapy (0.018); for in-hospital death: body overweight (p = 0.012), age (p = 0.047), antiplatelet therapy (p = 0.03), creatinine values elevation (p = 0.025).

Conclusions: The presence of the above factors may be useful to identify patients at high risk of developing a severe COVID-19 that need an early treatment and intensive follow-up.

COVID-19 AND CARDIOVASCULAR SYSTEM: NOT ONLY HEART BUT ALSO VASCULAR. THE EFFECTS OF THE INFECTION ON ARTERIAL STIFFNESS

Elena Gualini, Alessandro Maloberti, Sara Scarpellini, Michela Algeri, Marco Biolcati, Enzo Grasso, Chiara Tognola, Antonella Moreo, Cristina Giannattasio

Cardiology 4, Niguarda Hospital, Milan, Italy; School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

Introduction: SARS-CoV-2 determines a framework of multi-organ dysfunction that can involve the cardiovascular system creating damages of different nature. Among these, endothelial damage could play a key role in increasing arterial stiffness and thus the cardiovascular risk of infected patients.

Aim: to evaluate the Pulse Wave Velocity (PWV) of a population of patients after recovery from infection and to compare them with those of a group affected by arterial hypertension.

Methods: This prospective observational monocentric study involved 143 patients with previous diagnosis of Covid-19 who undergone PWV measurement during the follow-up at a median time of 3.8 months after the infection. These patients were compared to a population of 143 patients with hypertension matched by age, sex, Systolic Blood Pressure values and Body Mass Index.

Results: PWV values were higher in Covid-19 group comparing to hypertension group (10.5 ± 3.0 m/s VS 8.9 ± 2.5 m/s). Furthermore, there is a correlation between higher PWV values and lower values of SpO₂% at time of admission at the Emergency Department. (R = − 0.302; p < 0.001).

Conclusions: SARS-CoV-2 infection seems related to increased PWV values. Moreover, higher arterial stiffness seems correlated to a worse oxygen saturation in Emergency Department. More studies with longer follow-up time are necessary to establish whether the vascular damage is reversible and whether it correlates with an increase of long-term cardiovascular risk.

ATRIAL FIBRILLATION INCIDENCE IN SARS-CoV-2 INFECTED PATIENTS: PREDICTORS AND RELATIONSHIP WITH IN-HOSPITAL MORTALITY

Alessandro Maloberti^a,b, Cristina Giannattasio^a,b, Paola Rebora^c, Giuseppe Occhino^c, Nicola Ughi^d, Jacopo RIZZO^b, Saverio Fabbri^b, Filippo LEIDI^b, Iside Cartella^b, Michela Algeri^a, Claudio Rossetti^e, Oscar Massimiliano Epis^d, Giulio Molon^f, Paolo Bonfanti^g, Maria Grazia Valsecchi^b, and Simonetta Genovesi^b,h

^a Cardiology 4, “A.De Gasperis” Cardio Center, ASST GOM Niguarda Ca’ Granda, Milan, Italy; ^b School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; ^c Bicocca Bioinformatics, Biostatistics and Bioimaging Centre-B4, School of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; ^d Rheumatology, Multispecialist Medical Department, ASST GOM Niguarda Ca’ Granda, Milan, Italy; ^e Nuclear Medicine, ASST GOM Niguarda Ca’ Granda, Milan, Italy; ^f Cardiology Department, IRCCS Sacro Cuore Don Calabria Hospital, Negrar, Italy; ^g Infectious Disease Department, San Gerardo Hospital, Monza, Italy; ^h Cardiology Unit, Istituto Auxologico Italiano, IRCCS, Milan, Italy

Introduction: Among the different CardioVascular (CV) manifestation of the COronaVIrus-related Disease (COVID) particular attention has been paid to arrhythmia and particularly to Atrial fibrillation (AF).

Aim: To assess the incidence of AF episodes in patients hospitalized for COVID and to evaluate its predictors and its relationship with in-hospital all-cause mortality.

Methods: We enrolled 3435 cases of SARS-CoV2 infection admitted in four hospitals in Northern Italy. We collected data on clinical history, vital signs, Intensive Care Unit (ICU) admission, laboratory tests and pharmacological treatment. AF incident and all-cause in-hospital mortality were considered as outcomes.

Results: 145 (4.2%) patients develop AF during hospitalization, with a median time of 3 days (IQR: 0, 11.5) from admission. Incident AF patients were older and had lower eGFR, lower platelet and lymphocytes count and higher C-Reactive Protein (CRP), were admitted more frequently to ICU and more frequently died compared to subjects that didn’t present AF. At the Cox regression model significant determinants of incident AF were older age (HR 1.070; 95% CI: 1.048, 1.092), history of AF (HR 2.800; 95% CI: 1.465, 5.351), ischemic heart disease (HR 0.324; 95% CI: 0.130, 0.811) and ICU admission (HR 8.030; 95% CI: 4.511, 14.292). Incident AF was a predictor of all-cause mortality (HR 1.679; 95% CI: 1.170, 2.410), together with age (HR 1.053; 95% CI: 1.042, 1.065), dementia (HR 1.553; 95% CI 1.151, 2.095), platelet count (HR 0.997; 95% CI: 0.996, 0.999) higher CRP (HR 1.004; 95% CI: 1.003, 1.005) and eGFR (HR: 0.991; 95% CI: 0.986, 0.996)

Conclusions: AF present as the main arrhythmia in COVID-19 patients and its development during the hospitalization strongly relates with in-hospital mortality.

EVALUATION OF A NEW MULTI-PARAMETER NON-INVASIVE TELEMONITORING SYSTEM TO IMPROVE THE HOME MANAGEMENT OF SUBJECTS POSITIVE FOR COVID 19 AND WITH A DIFFERENT DEGREE OF CARDIOVASCULAR RISK

Valerio Pecchioli¹, Nazzareno Lomartire², Lucia Valente², Arik Eisenkraft⁴, Lorenzo Pecchioli¹, Giuseppe I. W. Germanò⁵

¹ Cardiovascular Prevention Unit, Hospital Department ASL Frosinone, Italy; ² Anaesthesiology and Intensive Care Unit, ASL, Frosinone, Italy; ³ Cardiology and Cardiological Intensive Care Unit, ASL Frosinone, Italy; ⁴ The Institute for Research in Military Medicine, The Hebrew University of Jerusalem, Israel; ⁵ Policlinico Umberto I° University “La Sapienza”, Rome, Italy

Introductions: The coronavirus pandemic has created the need to redesign new methods of care delivery to address clinical impact in real time, also seeking to address the long-term implications for COVID 19 patients. Connected health makes it possible to monitor COVID 19 patients discharged from hospital and residents at home with the aim of quickly identifying those who require higher care treatment.

Several data have shown a link between infection and the onset of new heart diseases and in the seven days following a diagnosis of COVID 19 infection, the probability of having a myocardial infarction is 6 times higher than in a non-positive ill. A new connected device, the BioBeat^®, in the two “watch” and “patch” versions that use Photoplethysmography (PPG) technology, allows to detect parameters such as Oxygen Saturation; Respiratory Rate for monitoring respiratory function; as well as Heart Rate, Blood Pressure, Systemic Vascular Resistance, Stroke volume and Cardiac Output for monitoring the cardiovascular function.

The temperature measurement allows to monitor the inflammatory and septic state.

The "patch" device applied to the patient's chest continuously records the ECG in one lead. The Cloud-based software platform dedicated to the two devices allows you to manage a constant monitoring service of the conditions of COVID-19 patients on a daily basis and decide on the most appropriate therapeutic solutions the National Early Warning (NEWS) score has been introduced on the BioBeat platform.

AIM: To validate the digital system for home multiparametric control of patients with COVID-19 infection in order to monitor specific parameters of cardiac function, with a particular focus on changes in blood pressure.

METHODS: We enrolled 18 patients of which 8 treated at home (group A) and 10 with previous SARS-COV2 disease in hospital discharge after hospitalization (group B).

Results: Figure 1 shows the results of the study

Conclusions: The device proved to be easy to use. The data can be accessed from any web platform and is displayed interactively even in graphical form. Its use has allowed the accurate home management of patients with high cardiovascular risk associated with COVID 19 infection.

IMPACT OF POST-COVID MENTAL STRESS DISORDERS ON BLOOD PRESSURE RESPONSE TO EXERCISE

Mordeglia Lorenzo*^1,2, Morgana Giovanni*^1,2, Caparvi Camilla^1,2, Sanesi Leandro², Cavallo Massimiliano², Santoni Edoardo^1,2, Dominioni Irene^1,2, Sicari Francesco³, Curcio Rosa^1,2, Santuro Emanuela², Meloni Sara⁴, Bartoli Stefano⁴, Pasticci Maria Bruna^1,3, Vaudo Gaetano^1,2, Pucci Giacomo^1,2

¹Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia; ² Struttura Complessa di Medicina Interna, Azienda Ospedaliera “Santa Maria”, Terni; ³ Clinica delle Malattie Infettive, Azienda Ospedaliera “Santa Maria”, Terni; ⁴ Unità di Psicologia Ospedaliera, Azienda Ospedaliera “Santa Maria”, Terni

Introduction: Patients recovered from COVID-19 are at high risk of developing mental stress disorders over the long-term. Post-traumatical stress disorders (PTSD) are associated with increased BP and hypertension incidence.

Aim: We tested the hypothesis that PTSD, occurring in patients after hospital discharge for severe COVID-19, is associated with an impaired BP response to exercise.

Methods: 108 patients previously hospitalized for severe COVID-19 were evaluated after 5 months from hospital discharge. A Revised Impact of Event Scale (IES-r) score > 33 indicated probable COVID-related PTSDs All subjects underwent maximal cardio-pulmonary exercise test on a cycle ergometer with incremental ramp protocol. Submaximal BP was recorded after 4 minutes, at a workload threshold of 75W.

Results: 95 subjects (mean age 58 ± 10 years, 71% men) had complete data. Mean baseline BP was 128/82 ± 12/11 mmHg. 51% were hypertensive. 32% had a IES-r score > 33 (PTSD group). These patients were more frequently women (45% vs 20%, p = 0.01), whereas no differences in terms of age, BMI, hypertension history, other CV risk factors or diseases were found compared to non-PTSD group. Baseline BP did not differ between PTSD and non-PTSD groups (127/82 ± 10/8 mmHg vs 129/82 ± 15/9 mmHg, p = 0.43/0.88). By contrast, submaximal exercise SBP (eSBP) was increased in PTSD vs non-PTSD group (155 ± 16 mmHg vs 146 ± 14 mmHg, p < 0.05). A strong sex-specific effect was found, being eSBP higher in PTSD vs non-PTSD women, but not in PTSD vs non-PTSD men (p for sex interaction = 0.01). Intrusion symptoms, such as unwanted and upsetting memories, nightmares and flashbacks, were more markedly associated with increased BP response to exercise.

Conclusions: In women with mental stress disorders related to previous COVID-19 hospitalization, we showed increased submaximal BP during exercise, whereas this finding was not observed in men. Mental stress disorders could negatively impact on future CV risk in post-COVID-19 women through an exaggerated BP response to physical stressors.

HYPERTENSIVES WHO UNDERWENT COVID 19 INFECTION SHOW AN INCREASED ARTERIAL STIFFNESS BUT NOT A BLODD PRESSURE ELEVATION

Pietro Nazzaro, Adele Nardecchia, Gianfranco Amodio, Maura Buttiglione, Gabriella Schirosi, Maria Contini, Lorenzo Debenedittis, Gabriella Aceto, Valentina Gasparre, Mariarita Marvulli, Cesare De Virgilio Suglia, Linda Lopez, Mila Consiglio

Dip. Scienze Biomediche e Oncologia Umana, U.O.S.D. di Ipertensione Arteriosa “AM. Pirrelli”, Università di Bari “Aldo Moro”, Bari, Italy

Introduction: Recent studies showed that, during the pandemia, the psychological and cognitive health in hypertensives is associate to the preserved arterial compliance.

Aim: To highlight the medium-long term vascular consequences in Covid-19 negativized grade-1 hypertensives.

METHODS: After 8.6 ± 4.2 months of negative test (POST-Covid), 80 adult male (61 ± 12), hypertensives, treated only by ACEi or ARB, within 12-15 months since the previous out-patients clinical control (PRE-Covid), with similar metabolic assessment and hypertensive state, underwent ABPM to recognize individualized awake (d) and sleep (n) SBP/DBP and BP fall during sleep (dipping), central SBP (SBPcar) and arterial stiffness (PWVcf) by carotid-femoral arterial tonometry, LVMi by echocardiogram and cognitive assessment (COGN) by multiple choice 18 items questionnaire.

Results: Patients did not modify smoke habit (7 ± 10 vs 8 ± 10), BMI (29.1 ± 4.9 vs 28.4 ± 5.3) and drug compliance (Morisky) but further significant characteristics occrred. (m ± s.d.: *:p < .05,**:p < .01, ***:p < .001 vs PRE-Covid).

pts/var	SBPoff	DBPoff	SBP/DBPd	SBP/DBPn	dipping%
PRE-Covid	130 ± 15	79 ± 8	131 ± 7/82 ± 9	116 ± 12/71 ± 9	11.6 ± 8
POST-Covid	132 ± 15	78 ± 8	132 ± 13/83 ± 10	118 ± 16/72 ± 10	10.2 ± 14.9
	Morisky	LVMi	SBPcar	PWVcf	COGN
PRE-Covid	38.1 ± 5.1	54.5 ± 13	122 ± 14	9.5 ± 1.9	24.2 ± 5.7
POST-Covid	39.1 ± 2.6	58.4 ± 16	130 ± 13***	10.9 ± 1.4***	29.1 ± 4.9**

Pearson analysis showed the association (0.286*) between PWVcf and COGN during the first months after the infection.

Conclusions: The findings show that, during the first stages following the Covid-19 infection, the hypertensives treated by SRA antagonists, present an arterial compliance impairment apparently associated with an initial cognitive decline.

The long-term cardiovascular consequences of Covid-19 infection (long Covid) are obviously still to be recognized.

RESISTANT HYPERTENSION

RENAL CIRSOID ANEURYSM AS A RARE CAUSE OF RESISTANT HYPERTENSION: A CASE REPORT

Emanuele Citi¹, Chiara Buono¹, Javier Rosada¹, Agostino Virdis², Alberto Camaiti¹, Alessandro Mengozzi^2,3

¹ Ospedali Riuniti di Livorno, Azienda USL Toscana Nord Ovest, Pisa, Italia, emanueleciti89@gmail.com; ² Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italia, ³ Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italia

Introduction: Renal arteriovenous malformations (RAVMs) as cirsoid aneurysms are abnormal communications between the renal arterial and venous systems. Although generally asymptomatic, they could induce a local hyperdynamic circulation leading to secondary hypertension.

Aim: We aim to report a case of secondary hypertension driven by a cirsoid aneurysm describing how its treatment led to a partial resolution of arterial hypertension.

Methods: We report a case showing its clinical pathway from emergency department (ED) admission to outpatient clinic diagnosis and subsequent treatment by interventional embolisation.

Results: A. B., a 36-year-old male, presented to ED for a single hypertensive peak. After dismission, he was administered a benzothiazepines calcium-channel blocker (tildiem 300 mg/day) and referred to our outpatient clinic. After the first visit, his anti-hypertensive therapy was implemented by adding doxazosin 2 mg/day, and a subsequent visit to rule-out secondary hypertension was prioritised. The outpatient abdomen Doppler ultrasound of the right renal artery showed a peak systolic velocity of 346 cm*sec-1 and a renal/aortic ratio of 2.1, suggestive of non-hemodynamically significant stenosis in the context of hyperdynamic circulation (Figure 1A–C). As blood pressure was still poorly controlled, therapy was progressively increased by adding perindopril 10 mg/day and spironolactone/hydrochlorothiazide 25/25 mg/day. Even if MRI did not detect any RAVMs, angiography identified a right lower polar intraparenchymal arterio-venous fistula (Figure 1D), treated with microcoils embolisation. Post-procedure blood pressure control was improved, and the patient dismissed any chronic therapy but perindopril.

Conclusions: The importance of employing color flow Doppler ultrasound from the early screening for secondary hypertension proved fundamental to detect a rare but targetable cause of resistant hypertension. The earlier treatment was as well crucial to avoid late persistent consequences.

Figure 1.

Imaging of abdominal aorta and renal arteries. Color Doppler flow of the abdominal aorta (A), left renal artery (B) and right renal artery (C). Despite the elevated PSV values, the RAR was below the benchmark for diagnosing haemodynamically significant renal artery stenosis. (D) Angiographic examination of the right renal arteries. The angiographic examination showed the presence of an intraparenchymal arterio-venous fistula at the right lower polar site with two afferents arteries and a convoluted morphology compatible with a cirsoid aneurysm.

PREVALENCE AND CLINICAL CORRELATES OF POOR THERAPEUTIC ADHERENCE IN PATIENTS WITH APPARENT RESISTANT ARTERIAL HYPERTENSION

Nicolò De Biase, Giulia Mori Ubaldini, Maria Grazia Grosso, Lavinia Del Punta, Nicola Riccardo Pugliese, Simona Buralli, Stefano Taddei, Stefano Masi, Alessandra Violet Bacca

Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Introduction: Renal denervation (RDN) represents an important interventional approach to lower blood pressure (BP) values in patients with difficult-to-control arterial hypertension (DTC-HTN), which is defined as BP not effectively controlled by medical therapy, often due to intolerance to multiple classes of antihypertensive medications. A most common cause of poor BP control is the lack of therapeutic adherence.

Aim: In this study, we sought to objectively evaluate medication adherence in patients eligible for RDN, by quantifying serum concentrations of prescribed antihypertensive drugs.

Methods: We evaluated the prevalence of cardiovascular risk factors and subclinical or overt hypertension-mediated organ damage in a population of consecutive patients with DTC-HTN, and we excluded the presence of secondary causes of arterial hypertension, according to Current Guidelines [1]. Furthermore, we obtained a venous blood sample to measure serum concentrations of the antihypertensive medications taken by each patient, by means of high-performance liquid chromatography-tandem mass spectrometry.

Results: 43 patients were enrolled; their demographic and clinical characteristics are presented in Table 1. In this sample (mean age 62 ± 10 years, males 53%), 20/43 (46%) patients were found to be non-adherent to treatment. In particular, in 13/43 patients (30%) none of the prescribed antihypertensive medications had detectable serum concentrations, whereas in 7/43 patients (16%) serum concentrations were much lower than expected, suggesting only partial therapeutic adherence.

Conclusions: Poor therapeutic adherence is common in hypertensive patients eligible for RDN. This study suggests that about half of patients with DTC-HTN may prefer to undergo an interventional procedure rather than adhere to medical therapy. Considering the limited risks inherent to RDN, such a procedure could be regarded as a valuable therapeutic option also in the early stages of the disease.

Table 1.

Demographic and clinical characteristics of the study population

	Whole population (n = 43)
Age, years	68 ± 12
Males, n (%)	23 (53%)
Systolic BP, mmHg	165 ± 19
Diastolic BP, mmHg	93 ± 13
Heart rate, bpm	71 ± 11
Prescribed medications, n	3 ± 1
Patients reporting adverse reactions to therapy, n (%)	22 (51%)
Current smokers, n (%)	19 (44%)
Overweight/obesity, n (%)	18 (42%)
Diabetes mellitus, n (%)	15 (35%)
Dyslipidaemia, n (%)	17 (40%)
OSAS, n (%)	8 (19%)
Microalbuminuria, n (%)	15 (35%)
Left ventricular hypertrophy, n (%)	24 (56%)
Chronic kidney disease, n (%)	15 (35%)
TIA/stroke, (%)	10 (23%)
CAD, n (%)	9 (21%)
Carotid artery atherosclerosis, n (%)	25 (58%)
PAD, n (%)	5 (12%)

Data are presented as mean ± standard deviation or n (%) as appropriate.

Dyslipidaemia: LDL cholesterol > 116 mg/dL or lipid-lowering therapy.

Microalbuminuria: ACR > 30 mg/g e <300 mg/g in a spot urine sample.

Left ventricular hypertrophy: LVMi > 95 g/mq (women) or > 115 g/mq (men) at transthoracic echocardiography.

ACR: urine albumin to creatinine ratio; BP: blood pressure; CAD: coronary artery disease; LDL: low-density lipoprotein; LVMi: left ventricular mass index; OSAS: obstructive sleep apnoea syndrome; PAD: peripheral artery disease; TIA: transient ischaemic attack.

CEREBROVASCULAR DISEASE

THE CORRELATION BETWEEN SUBCLINICAL LEFT VENTRICULAR DYSFUNCTION ASSESSED BY GLOBAL LONGITUDINAL STRAIN AND MILD COGNITIVE IMPAIRMENT IN HYPERTENSIVE PATIENTS

Germano Junior Ferruzzi ¹, Valeria Visco¹, Francesco Loria¹, Gennaro Galasso¹, Guido Iaccarino², Carmine Vecchione¹ and Michele Ciccarelli¹

¹ University of Salerno, Department of Medicine, Surgery and Dentistry, Salerno, Italy; ² Federico II University of Naples, Department of Advanced Biomedical Sciences, Naples, Italy

Introduction: Global longitudinal strain (GLS) has emerged as a more precise myocardial function measure than left ventricular ejection fraction (LVEF). GLS detects subtle systolic abnormalities in various cardiovascular disease, which represent significant risk factors for cognitive impairment and cerebrovascular disease.

Aim: This study examines the relationship between subclinical cardiac dysfunction assessed by GLS and mild cognitive impairment (MCI) in hypertensive patients.

Methods: Complete clinical characteristics, laboratory analyses and echocardiographic data were collected. Hypertensive patients without severe carotid artery stenosis (> 50%), anticoagulation drugs, atrial fibrillation, cerebrovascular and/or neurodegenerative diseases were enrolled. Finally, MCI was defined by accurate the Quick Mild Cognitive Impairment (QMCI) Screen corrected for age and education. This score assesses spatial and temporal orientation, registration, delayed recall, clock design, logical memory and verbal fluency in a brief time (5 min - score 0-100).

Results: 81 hypertensive patients [66 ± 7.27 years; 9 (11 %) females] were included in the study. LVEF was 50.47 ± 9.95% and mean GLS was − 16.00 ± 3.66. Mean QMCI corrected for age and education was 56.45 ± 9.37, and MCI was detected in 21 patients (26%). When comparing the patients with MCI (QMCItot < 49.4) and without MCI (QMCItot > 49.4), a statistically significant difference of GLS values was detected (no MCI: − 16.52 ± 3.66 vs MCI − 14.18 ± 3.23; p 0.032); on the other hand, the two groups did not differ in LVEF (no MCI: 50.58 ± 9.70 vs MCI 48.86 ± 11.93; p 0.864). When patients with LVEF ≥ 45% were excluded from the analysis, a statistically significant linear regression was observed between QMCI (corrected for age and education) and the GLS (p 0.014). Figure 1.

Conclusions: Compromised GLS, but not LVEF, is associated to MCI in hypertensive patients. Furthermore, our study demonstrates for the first time the existence of a significant correlation between the QMCI and GLS.

Figure 1.

ANTI-HYPERTENSIVE THERAPY EFFECTS ON CEREBRAL FUNCTIONAL NETWORKS AND CONNECTIVITY

Lorenzo Carnevale¹, Angelo Maffei¹, Alessandro Landolfi¹, Giovanni Grillea¹, Daniela Carnevale ^1,2, Giuseppe Lembo^1,2

¹Department of AngioCardioNeurology and Translational medicine, IRCCS Neuromed, Pozzilli, Italy; ²Department of Molecular Medicine, University of Rome “La Sapienza”, Rome, Italy

Introduction: In this work we investigated the impact of different antihypertensive therapies on brain functional connectivity, a main feature measurable by resting-state functional MRI.

Aim: This characterization let us analyse how pathological conditions influence the cognitive processes and the spontaneous organization of brain activity.

Methods: 42 hypertensives with controlled BP levels (SBP < 140mmHg e DBP < 90mmHg) underwent resting-state functional MRI. Functional connectivity measurements were elaborated by CONN, according to an analysis pipeline to build functional connectivity networks calculating the cross-correlation of BOLD signal among different brain regions. The obtained network has been analyzed by general linear model regression to highlight differences in functional connectivity in patients treated with different antihypertensives.

Results: The application of regression models with age, sex, BMI, alcohol, smoke, SBP and DBP levels, heart rate we evidenced that treatment with diuretics modulates a large connectivity network among Salience network, Default Mode Network and Language Network (Fig. A). Ace-inhibitors treatment is associated with a significant modulation of connection between Default Mode Network and FrontoParietal Network (Fig. B), while ARBs are associated to the modulation of connections between Cerebellar and Language Networks (Fig. C). Finally, beta-blockers are associated with connections centered in Dorsal Attention Network and projected to Language and FrontoParietal Networks (Fig. D).

Conclusions: Functional MRI let us investigate the differential contribution of antihypertensive drugs on brain functional organization. With this approach, we will be able to take into account the central and cognitive effects of different antihypertensive treatments on the choice of pharmacological treatments.

HORMONAL MECHANISMS AND ENDOCRINE HYPERTENSION

TRANSCRIPTOMIC ANALYSIS OF URINARY EXOSOMES IN HYPERTENSIVE PATIENTS: VOLTAGE-GATED CALCIUM/SODIUM CHANNELS OVEREXPRESSION IN PATIENTS WITH PRIMARY ALDOSTERONISM

Mariangela Veneri¹, Gabriele Mango¹, Annalisa Castagna¹, Francesca Ambrosani¹, Patrizia Pattini^1, Paolo Brazzarola², Domenica De Santis¹, Simonetta Friso¹, Oliviero Olivieri¹, Francesca Pizzolo¹

¹ Department of Medicine, Unit of Internal Medicine, Verona, Italy; ² Department of Surgery and Oncology, Unit of Endocrine Surgery, Verona, Italy

Introduction: In Primary Aldosteronism, the most frequent form of endocrine hypertension, genomic and, more recently, transcriptomic studies on the adrenal gland, characterized some molecular mechanisms involved in the disease. Scant data are available about gene expression in the kidney, that is the main target tissue of aldosterone action.

Aim: To analyze RNA-Seq data from urinary exosomes of 5 patients with aldosterone-producing adrenal cortex adenoma (APA), before and after adrenalectomy, and 8 patients with essential hypertension (EH). Then, compare the differentially expressed genes to evaluate gene expression differences between APA and EH, and after adrenalectomy within APA patients.

Methods: Urinary exosomes were purified using precipitating reagent and differential centrifugations. RNA libraries were prepared according to the TruSeq Stranded Total RNA protocol and sequenced by NextSeq System (Illumina).

Results: Gene set enrichment analysis on differentially expressed genes detected 7 significantly over-expressed transcripts involved in the activity of voltage-dependent calcium channels in patients with APA compared to EH subjects: 3 transcripts encoding for calcium channel subunits (CACNA2D1, CACNA2D4 and CACNG2) and 4 transcripts encoding for sodium channel subunits (SCN3A, SCN5A, SCN9A and SCN11A). In patients with APA the gene expression of these channels was only partially reduced after adrenalectomy.

Conclusions: This study contributes to a more precise characterization of the molecular mechanisms underlying the differences between APA and EH. It is well known that ion channels mutations in the adrenal adenoma tissue genetically characterize subjects with APA, and a different expression of some ion channel in APA adrenal tissue was demonstrated. To our knowledge, it is the first time that a differential expression of ion channels has been documented in renal tissue urinary exosomes.

PROFILING CIRCULATING EXTRACELLULAR VESICLE SURFACE ANTIGENS IN PRIMARY ALDOSTERONISM

Jacopo Burrello^1,2, Martina Tetti¹, Vittorio Forestiero¹, Vanessa Biemmi^2,3, Sara Bolis², Margherita Alba Carlotta Pomatto⁴, Martina Amongero⁵, Dario Di Silvestre⁶, Pierluigi Mauri⁶, Giuseppe Vassalli², Giovanni Camussi⁴, Tracy Ann Williams^1,7, Paolo Mulatero¹, Lucio Barile^2,3, and Silvia Monticone¹.

¹ Division of Internal Medicine 4 and Hypertension Unit, Department of Medical Sciences, University of Turin, Italy; ² Laboratory for Cardiovascular Theranostics and Laboratory of Cellular and Molecular Cardiology, Cardiocentro Ticino Institution, Lugano, Switzerland; ³ Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland; ⁴ Molecular Biotechnology Center, Department of Medical Sciences, University of Turin, Italy; ⁵ Department of Mathematical Sciences G. L. Lagrange, Polytechnic University of Turin, Italy; ⁶ Proteomic and Metabolomic Laboratory, Institute for Biomedical Technologies-National Research Council (ITB-CNR), Segrate (Milan), Italy; ⁷ Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany.

Introduction: Chronic aldosterone excess in patients with primary aldosteronism (PA) determines detrimental effects on cardiovascular system. Circulating extracellular vesicles (EVs) have a fundamental role in the crosstalk between endothelium and inflammatory cells, and they may be involved in the development of organ damage in patients with PA.

Aim: We aimed to assess the potential role of EVs in aldosterone-related vascular injury by evaluating a panel of 37 EV surface antigens through an innovative flow cytometry multiplex bead-based platform.

Methods: Serum EVs were isolated by immuno-capture from 32 patients with PA, 29 patients with essential hypertension (EH) and from 22 normotensive (NT) controls. EVs were characterized by nanoparticle tracking analysis, transmission electron microscopy, western blotting, and flow cytometry.

Results: EV concentration was higher in patients with PA compared to patients with EH and NT controls and the number of particles decreased after unilateral adrenalectomy. Nineteen EV surface antigens, including markers from activated platelets, endothelial and immune/inflammatory cells, were differentially expressed in patients with PA compared to controls. Supervised learning was used to combine the expression levels of single EV markers in a specific molecular signature which discriminated patients with PA from controls (EH and NT), whereas after specific treatment the profile became similar to EH. Stimulation of human endothelial cells with PA patient derived EVs resulted in the overexpression of 5 selected genes (AKT1, CALR, CSNK2A1, FN1, and PIK3R1), previously identified by bioinformatics analysis as potential targets of differentially expressed EV antigens. Notably, the effect was specifically dependent on EV surface antigens, since it was abolished by removal of EV membrane associated proteins.

Conclusions: Our data suggest that EVs represent biomarkers of vascular inflammation and endothelial dysfunction in patients with PA, and also potential biovectors contributing to endothelial dysfunction, vascular inflammation, and accelerated organ damage by multiple signalling processes.

EXCLUSION TESTS FOR THE DETECTION OF UNILATERAL PRIMARY ALDOSTERONISM (EXCLUPA) STUDY. A SYSTEMATIC REVIEW AND META‐ANALYSIS

Rui Zhu^1,2, Tungalagtamir Shagjaa^1,3, Giacomo Rossitto⁴, Brasilina Caroccia⁴, Teresa Maria Seccia⁴, Dario Gregori ⁶, Gian Paolo Rossi ⁴

¹ International PhD Program in Arterial Hypertension and Vascular Biology (ARHYVAB), Department of Medicine-DIMED, University of Padua, Padua, Italy; ² Department of Endocrinology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China; ³ Department of Neurology, Mongolian National University of Medical Sciences, Ulaanbaatar, Mongolia; ⁴ Internal & Emergency Medicine Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy; ⁵ Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy

Introduction: Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Current guidelines recommend one or more tests in patients tested by means of the aldosterone-to-renin ratio to avoid costly and invasive lateralization procedures in those who tested false-positive. To date the diagnostic gain provided by these tests over aldosterone-to-renin ratio was examined only in few studies. Therefore, it stands on a weak level of evidence.

Aim: To assess the accuracy of exclusion tests in the work-up of primary aldosteronism (PA) using the diagnosis of unilateral PA as reference.

METHODS: Design: Systematic review and meta-analysis.

Data Sources: PubMed, EMBASE, Web of Science, and Cochrane Library databases.

Eligibility criteria for study selection: Studies of exclusion tests that met tight quality criteria published from January 1st, 1970 to December 31st, 2021.

Data extraction and synthesis: Data were extracted following the PRISMA methodology. We performed a two-stage meta-analysis that entailed an exploratory and a validation phase based on a “golden” or “gold” diagnostic standard, respectively. Pooled specificity, negative likelihood ratio, diagnostic odds ratio, and summary area under the ROC curve (sAUC) were calculated.

Results: The accuracy of exclusion tests compared to a golden and a gold reference. 31 datasets comprising a total of 4242 patients fulfilling the predefined inclusion criteria were meta-analyzed. Pooled accuracy estimates (sAUC) showed no differences between the aldosterone-to-renin ratio (ARR) (0.95, 95% CI 0.92–0.98), the captopril challenge test (CCT) (0.92, 95% CI 0.88–0.97), and the saline infusion test (SIT) (0.96, 95% CI 0.94–0.99). Solid information could not be obtained for the fludrocortisone suppression test and the furosemide upright test, which were assessed in only one study each.

Conclusions: Both the CCT and the SIT showed high diagnostic accuracy, which was expected because of the selection of patients with a high pre-test probability of PA. However, as neither test furnished a diagnostic gain over the ARR, no evidence supporting their systematic use in clinical practice could be found.

DEVELOPMENT OF A CLINICAL SCORE AND MACHINE LEARNING-BASED MODELS TO PREDICT PRIMARY ALDOSTERONISM IN PATIENTS WITH ARTERIAL HYPERTENSION

Fabrizio Buffolo¹, Jacopo Burrello¹, Alessio Burrello², Daniel Heinrich³, Christian Adolf³, Lisa Marie Müller³, Rusi Chen¹, Vittorio Forestiero¹, Elisa Sconfenza¹, Martina Tetti¹, Franco Veglio¹, Tracy Ann Williams^1-3, Paolo Mulatero¹, Silvia Monticone¹

¹ Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy; ² Department of Electrical, Electronic and Information Engineering “Guglielmo Marconi” (DEI), University of Bologna, Bologna, Italy; ³Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany

Introduction: International guidelines recommend to screen for primary aldosteronism (PA) patients with arterial hypertension on the basis of individual risk factors. Following current recommendations more than 50% of patients with hypertension should be screened. Some experts propose to further expand the screening for PA to all patients with hypertension.

Aim: We designed a study to develop prediction models to define the risk of PA in patients with hypertension.

Methods: We developed and validated a clinical score and supervised machine learning algorithms in a retrospective internal cohort of 4059 patients with hypertension. We then validated our results in an external cohort of 584 patients with hypertension. PA diagnosis and subtype definition were achieved in agreement with major international guidelines.

Results: We developed a conventional scoring system (SToP-PA score) and 308 machine learning based models, based on 6 widely available parameters: sex, systolic blood pressure, antihypertensive treatment, body mass index, lowest potassium, and organ damage. Among 308 machine learning models we selected a random forest regressor model, that showed the highest diagnostic performances. At the internal validation, we obtained high predictive performance with SToP-PA score (optimized sensitivity of 90.7% for PA and 92.3% for unilateral PA) and even higher with random forest regressor (optimized sensitivity of 96.6% for PA, and 100.0% for unilateral PA). Applying these models to the whole internal cohort and the external cohort, we identified a subgroup of patients with very low probability of having PA and null probability of having unilateral PA.

Conclusions: The SToP-PA score and the machine learning model accurately predict the individual risk of PA in patients with arterial hypertension, avoiding unnecessary screening in up to 32.7% of patients using a random forest regressor algorithm, without omitting patients with unilateral UPA.

LONG-TERM EFFECTS OF ADRENALECTOMY OR MEDICAL TREATMENT ON CARDIAC STRUCTURE AND CARDIOVASCULAR OUTCOME IN PATIENTS WITH PRIMARY ALDOSTERONISM

Claudia Agabiti-Rosei, Anna Paini, Carlo Aggiusti, Fabio Bertacchini, Deborah Stassaldi, Sara Capellini, Chiara Arnoldi, Marco Cacciatore, Giulia Arenare, Carolina De Ciuceis, Massimo Salvetti, Maria Lorenza Muiesan

Internal Medicine, University of Brescia & ASST Spedali Civili di Brescia,Brescia, Italy

Introduction: In patients with primary aldosteronism (PA), a higher prevalence and degree of severity of left ventricular hypertrophy (LVH) have been demonstrated, possibly influencing an excess rate of CV events. Available evidence indicates that reduction of LV mass does not differ in PA patients treated with adrenalectomy or medical therapy with antihypertensive drugs, including mineralocorticoid receptor antagonists. Therefore, we assessed the outcome of PA patients with a baseline and follow-up echocardiogram, performed after adrenalectomy and/or medical treatment

Results Among 185 PA patients 140 received medical therapy (76 %) and 40 adrenalectomy (22 %). At follow-up (mean 13 years, range 2–24 years) BP was lowered (P < 0.0001 versus baseline) to similar values in adrenalectomized or medically treated PA patients. LVH was diagnosed at baseline in 62 patients, of whom 20 underwent adrenalectomy and 42 received medical treatment and at follow-up in 24 patients (7 surgically and 17 medically treated). A first major CV event occurred in 28 patients. Kaplan-Meier survival curves did not differ between surgically and medically treated patients (Mantel-Cox p = 0.38). In patients who suffered a CV event age, body mass index (BMI), glycemia and LV mass index were higher, with a lower estimated glomerular filtration rate (eGFR). By multivariate Cox regression analysis regression of LVH from baseline to follow-up (β 0.218 CI 0.049–0.974, p = 0.046) and development of LVH (β 14.9 CI 1.65–134.63, p = 0.016), were associated to the risk of CV events, as compared to patients with persistence of LVH and normal LV mass at baseline and follow-up, while age, BMI and eGFR changes did not enter the statistical model.

Conclusions: This study indicates that in PA patients changes in LV mass measured after adrenalectomy or medical treatment may influence the occurrence of CV events during the follow-up.

ASSOCIATION OF RENOVASCULAR HYPERTENSION AND PRIMARY ALDOSTERONISM

Chiara Grasselli, Lucia Salvi, Riccardo Simoni, Maicol Baldini, Angelo Ghirarduzzi

Hypertension Center of Cardiovascular Medicine-AUSL of Reggio Emilia, Italy

Introduction: Renal artery stenosis is rarely associated with Conn adenoma.

Aim: To analyze all the causes of hypertension.

Methods: We report a 63-year-old female patient who presented with a severe high blood pressure associated with cramps and nocturia. Physical examination was indifferent. Laboratory studies revealed low serum potassium level at 3.3 mmol/L associated with high aldosterone/renin ratio (60). Abdominal CT scan demonstrated aortic calcification involved ostia renal arteries and right adrenal globosity. Canrenone was started. Angiography confirmed left renal artery stenosis, then performed angioplasty with stenting. Patency of the renal arteries on Doppler, but blood pressure values not at target. Positive saline load, therefore adrenal vein sampling with right lateralization (see Table 1). Right laparoscopic adrenalectomy.

Results: Hystology compatible with Conn adenoma. Clinical and biochemical recovery at 6 months (see Table 2).

Conclusions: Based on prevalence studies, the coexistence of primary aldosteronism and renal artery stenosis can be statistically evaluated as involving 10 out of 10,000 patients. We discussed whether the association between these two entities is merely fortuitous or conversely based on a causal relationship.

Table 1.

Adrenal vein sampling with right lateralization

	Aldosterone (A), ng/dl	Cortisol (C), mcg/dl	A/C
Right adrenal vein	3700	1500	2.47
Left adrenal vein	204	650	0.31
Inferior cava vein	37	32	1.16

Bilateral selectivity with [C]adrenal vein/[C]i.c.v.≥5 on both sides;

High lateralization ratio: [A/C]r/[A/C]l = 8;

Contralateral suppression: [A/C]l/[A/C]i.c.v. = 0.3.

Table 2.

Clinical and biochemical recovery at 6 months

Characteristics	Before surgery	After surgery
ABPM, mmHg	156/94	129/82
N. drugs	1	0
Serum potassium, mmol/L	3.3	4.4
Urinary potassium, mmol/24 ore	49	83
Renin, mUI/L	3.44	38.9
Aldosterone, pmol/L	573	422
Aldosterone after-saline load, pmol/L	408	219

ABPM = Ambulatory Blood Pressure Measurement.

ANALYSIS OF MIRNA EXPRESSION FROM THE ADIPOSE TISSUE SURROUNDING THE ADRENAL NEOPLASIA

Antonio Concistrè¹, Luigi Petramala², Francesco Circosta¹, Priscilla Romagnoli¹, Maurizio Soldini¹, Marco Bucci³, Domenico De Cesare³, Giuseppe Cavallaro⁴, Giorgio De Toma⁴, Francesco Cipollone³, Claudio Letizia¹

¹ Department of Clinical, Internal Medicine, Anesthesiology and Cardiovascular Sciences, “Sapienza” University of Rome, Rome, Italy; ² Department of Translational and Precision Medicine, “Sapienza” University of Rome, Rome, Italy; ³ Department of Medicine and Aging Sciences, University "G. d'Annunzio" of Chieti-Pescara, Chieti, Italy; ⁴ Department of Surgery "P. Valdoni", “Sapienza” University of Rome, Rome, Italy

Introduction: Primary aldosteronism (PA), is characterized by several metabolic changes as insulin resistance, metabolic syndrome, and adipose tissue (AT) inflammation. Mi(cro)RNAs (miRNAs) are a class of noncoding small RNA molecules representing critical regulators in several cellular process associated with adipose tissue dysfunction.

Aim: To evaluate the expression of some miRNAs in visceral and subcutaneous AT in patients undergoing adrenalectomy for aldosterone-secreting adrenal adenoma (APA), respect samples of AT obtained in patients undergoing adrenalectomy for non-functioning adrenal mass (NFA).

Methods: Quantitative expression of selected miRNA using PCR real time was analyzed in surrounding adrenal neoplasia, peri-renal and subcutaneous AT samples of 16 adrenalectomized patients (11 patients with APA and 5 patients with NFA).

Results: Real-time PCR cycles for miRNA 132, miRNA 143 and miRNA 221 in fat surrounding adrenal neoplasia and in peri-renal AT were significantly higher in APA than in NFA patients. Unlike NFA patients, miRNA 132, miRNA 143, miRNA 221 and miRNA 26b were less expressed in surrounding adrenal neoplasia AT compared to subcutaneous AT in APA patients.

Conclusions: This study, conducted on tissue expression of miRNAs, highlights the possible pathophysiological role of some miRNAs in determining the metabolic alterations in PA patients.

SERUM PARATHORMONE, VITAMIN D AND CARDIOVASCULAR RISK FACTORS AND MARKERS

Ilaria Fucile, Maria Virginia Manzi, Maria Lembo, Biagio Migliaccio, Guido Iaccarino, Raffaele Izzo, Nicola De Luca, Costantino Mancusi

Hypertension Research Center & Department of Advanced Biomedical Science, Federico II University Hospital, Naples, Italy

Introduction: Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. There are conflicting reports in the literature regarding whether 25 OHD and PTH may play a role in atherosclerosis.

Aim: to evaluate the associations of serum 25-OHD and PTH concentrations with blood pressure and carotid intima-media thickness (IMT).

Methods: This observational retrospective study included 81 patients admitted at Hypertension Research Center of Federico II University Hospital in Naples with GFR > 60 mL/min. We collected serum 25-OHD, PTH, creatinine, BMI, lipid profile, blood glucose and office blood pressure. All patients underwent carotid doppler ultrasound and echocardiography.

Results: Mean age of the participants was 55 ± 18 years and 74% were men. Mean (SD) 25-OHD and PTH were 21 ± 9 ng/mL and 82 ± 41 pg/mL, respectively. 69% of the patients had hypertension, 43% dyslipidaemia and 12 % diabetes.

Pearson's correlation analysis indicated that PTH levels correlated directly with age, diabetes, dyslipidaemia, hypertension, fasting glucose, and inversely with the GFR and vit D level (all p < 0.05). Vit. D levels correlated inversely with PTH and diastolic blood pressure. No significant association of PTH and vit D were found with carotid IMT or left ventricular mass (both p > 0.05).

Multivariate regression models were built to assess main determinant of PTH and Vit. D. PTH was significantly associated with higher fasting glucose (p = 0.002), with no effect of age, GFR, diabetes, dyslipidaemia, hypertension. Vit D was associated with lower GFR(p = 0.007) and PTH level (p = 0.04)

Conclusions: In a population at high cardiovascular risk, PTH level was associated with higher fasting glucose while Vit D was associated with lower renal function. Vit. D and PTH are not directly associated with carotid atherosclerosis but might influence association with other cardiovascular risk factors and markers

SKIN-SPECIFIC MECHANISMS OF BODY FLUID REGULATION IN HYPERTENSION

G. Rossitto^1,2, J.Y. Chen², S. Mary², P. Boder², G.P. Rossi¹, R.M. Touyz³, C. Delles²

¹ UOC Medicina d’Urgenza-Ipertensione, DIMED, Università degli Studi di Padova, Italia; ² Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; ³ Department of Family Medicine, McGill University, Montreal, Canada

Introduction: Increasing evidence suggests excess skin Na+ accumulation in hypertension, but skin-specific mechanisms of local Na+/water regulation have largely been ignored.

Aim: To investigate the association between measures of sweat and transepidermal water loss (TEWL), skin Na+ content (surrogate of total body Na+) and clinical parameters in hypertensive patients.

Methods: An iontophoretic pilocarpine-induced sweat sample, measures of TEWL (Tewameter^®) and a skin punch biopsy were collected from adult, non-pregnant hypertensive patients. Sweat and skin Na+ and K+ content was assessed by flame photometry. Vascular Endothelial Growth Factor-c (VEGFc) was measured in serum (ELISA, R&D).

Results: In our cohort (n = 90; age range 21–86 years; females = 48.9%; BMI: 29.8 [26.9–35.2] kg/m²), sweat Na+ concentration ([Na+]SWEAT) was inversely correlated with [K+]SWEAT. Patients who took ACEIs/ARBs had higher [Na+]SWEAT compared to those who did not (33 [26–46] vs 26 [18–40] mmol/l, p < 0.05), whereas sweat composition was independent of sex and BMI. We observed a positive association between [Na+] in epidermis/superficial dermis (ESD) and [Na+]SWEAT, independent of sex, BMI and use of ACEi/ARBs (padjusted = 0.025); both [Na+]ESD and [Na+]SWEAT closely correlated with age (p < 0.01). Office DBP but not SBP inversely correlated with [Na+]SWEAT (r = − 0.312, p = 0.006), independent of age and other potential confounders (padjusted = 0.02). Total sweat volume and excreted Na+, but not [Na+]SWEAT, were lower in patients with uncontrolled office BP (p < 0.01 for both; padjusted<0.005); sweat volume also positively correlated with TEWL and serum-VEGFc (p < 0.05 for both).

CONCLUSIONS: Sweat and TEWL appear to participate in the systemic regulation of total body Na+ in hypertension, with potential therapeutic implications.

BLOOD PRESSURE MEASUREMENT

PREDICTION OF MASKED UNCONTROLLED HYPERTENSION DETECTED BY AMBULATORY BLOOD PRESSURE MONITORING

Francesca Coccina¹, Paola Borrelli², Anna M. Pierdomenico³, Jacopo Pizzicannella¹, Maria T. Guagnano³, Chiara Cuccurullo³, Marta Di Nicola², Giulia Renda⁴, Oriana Trubiani¹, Francesco Cipollone³, Sante D. Pierdomenico¹

¹ Department of Innovative Technologies in Medicine & Dentistry; ² Department of Medical, Oral and Biotechnological Sciences, Laboratory of Biostatistics; ³ Department of Medicine and Aging Sciences; ⁴ Department of Neurosciences, Imaging and Clinical Sciences; all Departments of the University “Gabriele d’Annunzio”, Chieti-Pescara, Chieti, Italy

Introduction: Masked uncontrolled hypertension (MUCH), that is normal clinic but high out-of-office blood pressure (BP) in treated patients, is at increased cardiovascular risk. Though factors associated with MUCH have been described, few reports have attempted to provide prediction models.

Aim: To provide prediction models for MUCH detected by ambulatory BP monitoring in a Caucasian population.

Methods: We studied 738 treated hypertensive patients with normal clinic BP. Subjects were classified as having controlled hypertension (CH) or MUCH if daytime BP < or ≥135/85 mmHg regardless of night-time BP, respectively, or CH or MUCH if 24-h BP < or ≥130/80 mmHg regardless of daytime or night-time BP, respectively.

Results: We detected 215 (29%) and 275 (37%) patients with MUCH using daytime and 24-hour BP threshold, respectively. Multivariate logistic regression analysis showed that male sex, smoking habit, left ventricular hypertrophy (LVH), clinic systolic BP between 130-139 mmHg and/or clinic diastolic BP between 85-89 mmHg were associated with MUCH. The area under the receiver operating characteristic curve showed good accuracy. Specifically, the area under the curve was 0.78 (95%CI 0.75-0.81, p < 0.0001) and 0.77 (95% CI 0.73-0.80, p < 0.0001) for MUCH defined by daytime BP and for MUCH defined by 24-hour BP, respectively. Internal validation suggested a good predictive performance of the models.

Conclusions: Male sex, smoking habit, LVH, high-normal clinic systolic and/or diastolic BP are capable to predict MUCH and models including these factors provide good diagnostic accuracy in identifying this ambulatory BP phenotype.

ANTIHYPERTENSIVE DRUG TREATMENT IN WHITE-COAT HYPERTENSION: DATA FROM THE PLAQUE HYPERTENSION LIPID-LOWERING ITALIAN STUDY (PHYLLIS)

Fosca Quarti Trevano¹, Jennifer Vanoli¹, Raffaella Dell’oro¹, Gino Seravalle², Rita Facchetti¹, Giuseppe Mancia³, Guido Grassi¹

¹ Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; ² Istituto Auxologico Italiano, Milan, Italy; ³ Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy

Introduction: No trial-based evidence is available on whether antihypertensive treatment lowers cardiovascular risk in white-coat hypertension (WCH). Protection may be indirectly inferred, however, from the blood pressure (BP) effects of treatment, because in trials outcomes decrease is linearly related to BP reduction.

Aim: We analyzed the effect of antihypertensive treatment on office and out-of-office BP in WCH using data from the Plaque HYpertension Lipid-Lowering Italian Study (PHYLLIS).

Methods: Office and ambulatory BP were measured in 470 hypertensive patients randomized to an ACE-inhibitor or a diuretic alone or combined with a statin before treatment and at yearly intervals during a 3-year follow-up. Patients were divided into two groups according to whether baseline data obtained before randomization to treatment showed that (1) office and 24-h mean BP were elevated (sustained hypertensive, SH) or (2) office BP was elevated but 24-hour BP values were normal (WCH).

RESULTS: Antihypertensive treatment was associated with an early marked BP reduction, which persisted virtually unchanged throughout the treatment period and was only slightly and usually not significant different in SH and WCH (− 18.9 ± 11.1/− 12.7 ± 5.9mmHg for SBP/DBP in SH and − 18 ± 10***.4/− 12.3 ± 6.2 mmHg for SBP/DBP in WCH, p = 0.43/p = 0.52). This was not the case, however, for 24-h BP which fell consistently in SH while showing no change in WCH (− 10.7 ± 10***.8/1.0 ± 8.3mmHg for SBP/DBP in SH and − 7.4 ± 7.2/0.1 ± 4.8 mmHg in WCH, p < 0.001/p < 0.001). In SH but not in WCH antihypertensive treatment consistently reduced either the higher daytime and the lower night-time BP values.

Conclusions: In WCH antihypertensive treatment can effectively and durably reduce office BP. This reduction is accompanied by the inability to lower ambulatory BP from the normal values characterizing this condition at baseline.

ASSOCIATION BETWEEN HYPOTENSION DURING 24-HOUR AMBULATORY BLOOD PRESSURE MONITORING AND REFLEX SYNCOPE: THE SYN-ABPM 1 STUDY

Giulia Rivasi¹, Antonella Groppelli², Michele Brignole², Davide Soranna³, Antonella Zambon³, Grzegorz Bilo², Martino Pengo², Bashaaer Sharad⁴, Viktor Hamrefors⁴, Martina Rafanelli¹, Giuseppe Dario Testa¹, Ciara Rice⁵, Rose Anne Kenny⁵, Richard Sutton⁶, Andrea Ungar¹, Artur Fedorowski⁷, Gianfranco Parati²

¹Division of Geriatric and Intensive Care Medicine, University of Florence and Azienda Ospedaliero Universitaria Careggi, Florence, Italy; ²IRCCS, Istituto Auxologico Italiano, Cardiology Unit and Department of Cardiology, S.Luca Hospital; Milan, Italy; ³IRCCS Istituto Auxologico Italiano, Biostatistics Unit, Milan, Italy; ⁴Department of Clinical Sciences, Lund University, and Skåne University Hospital, Malmö, Sweden; ⁵Falls and Syncope Unit, St James’s Hospital, Dublin, Ireland; ⁶Department of Cardiology, Imperial College, Hammersmith Hospital Campus, London. UK; ⁷Department of Cardiology, Karolinska University Hospital, and Department of Medicine, Karolinska Institute, Stockholm, Sweden

Introduction: Although ambulatory blood pressure monitoring (ABPM) has been used to identify hypotension, diagnostic criteria for ABPM use in patients with reflex syncope are lacking. The study hypothesis was that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM.

Aim: To investigate the diagnostic role of ambulatory systolic blood pressure (SBP) drops in reflex syncope and the SBP cut-off values allowing identification of patients with hypotensive susceptibility.

Methods: ABPM data from reflex syncope patients and controls, matched by average 24-hour SBP, age, sex and hypertension were compared. Patients with constitutional hypotension, orthostatic hypotension, predominant cardio-inhibition during carotid sinus massage or prolonged electrocardiogram monitoring or competing causes of syncope were excluded. Daytime and night-time SBP drops (< 110, 100, 90, 80 mmHg) were assessed. Findings were validated in an independent sample.

Results: In the Derivation sample, daytime SBP drops were significantly more common in 158 syncope patients than 329 controls. One or more daytime drop < 90 mmHg achieved 91% specificity, 32% sensitivity, Odds Ratio [OR] = 4.6, p = 0.001. Two or more daytime drops <100 mmHg achieved 84% specificity and 40% sensitivity (OR = 3.5, p = 0.001). Results were confirmed in the Validation sample of 164 syncope patients and 164 controls: one or more daytime SBP drop <90 mmHg achieved 94% specificity and 29% sensitivity (OR = 6.2, p < 0.001), while two or more daytime SBP drops <100 mmHg achieved 83% specificity and 35% sensitivity (OR = 2.6, p < 0.001)

Conclusions: SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope.

REPRODUCIBILITY OF BLOOD PRESSURE PHENOTYPES IDENTIFIED BY OFFICE AND AMBULATORY BLOOD PRESSURE IN TREATED HYPERTENSIVE PATIENTS. DATA FROM THE PHYLLIS STUDY

Michele Bombelli¹, Jennifer Vanoli², Rita Facchetti², Viola Dolfini², Giuseppe Mancia³ and Guido Grassi²

¹ University of Milano-Bicocca, ASST-Brianza, Pio XI Hospital, Internal Medicine, Desio, Italy; ² Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; ³ University of Milano-Bicocca, Milan, Italy

Introduction: Previous studies have shown that white-coat and masked uncontrolled hypertension (WUCH and MUCH, respectively) are clinical conditions with a very poor reproducibility over time. This is the case also for the different night-time blood pressure (BP) patterns (dipping, non-dipping, reverse dipping or extreme dipping).

Aim: To assess whether and to what extent the phenomenon might depend on the type of antihypertensive treatment.

Methods: We analyzed data collected in the Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS), in which office and ambulatory BP were measured three times during an almost three-year treatment period.

Results: The results showed that a limited number of WUCH or MUCH patients at an initial office and 24 h systolic (S) BP measurements maintained the same status at a second set of measurements one or more years later. This was the case also for all dipping patterns, and only a minimal number of patients exhibited the same phenotype throughout all on-treatment SBP measurements. Results were similar for treatment with a thiazide diuretic or an ACE-inhibitor and in line with those of the European Lacidipine Study on Atherosclerosis (ELSA) trial, i.e. the only other available trial with multiple on-treatment office and ambulatory BP measurements, in which patients were treated with a calcium channel blocker or a beta-blocker.

Conclusions: Thus, all the BP patterns identified in treated hypertensive patients by joint office and ambulatory BP measurements display a poor reproducibility and that this is unrelated to the type of antihypertensive treatment used.

PREVALENCE AND CLINICAL CORRELATES OF HYPOTENSIVE EPISODES DURING 24-H AMBULATORY BLOOD PRESSURE MONITORING IN HYPERTENSIVE OLDER ADULTS

Marco Capacci, Giulia Rivasi, Giada Turrin, Ludovica Ceolin, Diego Gentileschi, Carolina Corsi, Virginia Tortu’, Martina Rafanelli, Enrico Mossello, Andrea Ungar

Centro di Riferimento Regionale per l'Ipertensione dell'Anziano, SOD di Geriatria e Terapia Intensiva Geriatrica, Università di Firenze e AOU Careggi, Firenze, Italy

Introduction: Ambulatory blood pressure monitoring (24h-ABPM) represents a useful diagnostic tool to detect hypotension. Hypotensive episodes have a recognized negative prognostic impact in older adults, being associated with adverse outcomes such as falls and injuries.

Aim: To assess the prevalence and the clinical variables associated with hypotensive episodes on 24h-ABPM in older hypertensive adults.

Methods: Hypertensive patients aged 75 or older evaluated at the Hypertension Clinic and Memory Clinic of Careggi Hospital, Florence, were enrolled and underwent geriatric multidimensional assessment and 24h-ABPM. Hypotensive episodes were defined as single systolic blood pressure (SBP) measures <90 mmHg. Clinical variables associated with hypotension were investigated using multivariable logistic regression.

Results: Among 123 participants (mean age 81 years, 59% female), prevalence of hypotensive episodes on ABPM was 16%. Patients with hypotensive episodes were older (84 ± 5 vs 81 ± 4, p = 0.002), had significantly higher prevalence of dementia (50% vs 26%, p = 0.034) and received a higher number of daily medications (8[6-10] vs 6 [5-9], p = 0.036). Moreover, they showed lower 24h-SBP (139 ± 15 vs 149 ± 15, p = 0.008), daily SBP (141 ± 15 vs 151 ± 15, p = 0.005) and night-time SBP (129 ± 18 vs 140 ± 20, p = 0.005) and a higher prevalence of white coat effect (30% vs 12%, p = 0.034). At multivariable analysis, hypotensive episodes were associated with angiotensin-receptor blockers (ARBs, OR 24.325, p = 0.002), independently of age, sex, dementia, 24h-SBP and number of medications. By contrast, use of ACE-inhibitors (OR 0.719, p = 0.013) and thiazide diuretics (OR 0.978, p = 0.048) was inversely associated with hypotension on ABPM.

Conclusions: Hypotensive episodes are a common finding in older adults undergoing ABPM. Hypotensive episodes more frequently occurred in patients with lower SBP and white coat effect and were independently associated with ARBs use. By contrast, ACE-inhibitors and thiazides were inversely associated with hypotensive episodes on ABPM.

HYPERREACTIVITY TO STANDING IS ASSOCIATED WITH INCREASED AMBULATORY BP A RELATIONSHIP AMPLIFIED BY ENHANCED SYMPATHOADRENERGIC ACTIVITY

¹ Cardiology Unit, Cittadella Town Hospital, Cittadella, Padua, Italy; ²Department of Medicine, University of Padua, Padua, Italy; ³Cardiology Unit, San Daniele Del Friuli Town Hospital, San Daniele del Friuli, Udine, Italy; ⁴ Medicine I^, Ca’ Foncello Hospital, Treviso; ⁵ Medicine Unit, Vittorio Veneto Town Hospital, Vittorio Veneto, Treviso, Italy

Introduction: Previous research showed that elevated systolic blood pressure (SBP) reaction to standing (RS), a condition that may be accompanied by sympatho-adrenergic hyperactivity, is a predictor of cardiovascular events. This might be due to the influence of RS on ambulatory BP (ABP).

Aim: we investigated whether RS is a determinant of ABP and if this putative relationship is stronger in a milieu of hyperadrenergic activity.

Methods: We studied 630 young-to-middle-age (mean age 33.6 ± 8.5 years), stage I untreated hypertensives from the HARVEST study. RS was defined as difference between 6 SBP measurements in orthostatic and supine posture. Participants were divided into tertiles of SBP RS (<− 5.34, − 5.34 to 0.30 and > 0.30 mmHg, respectively) and of 24 h urinary epinephrine (UE) (< 8.3, 8.3–14 and > 14 mcg/24 h, respectively). The relationship with 24h average SBP was tested in a two-way ANCOVA adjusting for age, sex and office SBP.

Results: Mean RS was − 3.0 ± 7.4 mmHg and median UE was 10.5 (IQR 7.0–16.0) mcg/24 h. Subjects in the highest UE tertile had a higher (mean ± SEM) 24 h SBP (132.2 ± 0.8 mmHg) than the lower tertiles (129.9 ± 0.7 mmHg and 129.8 ± 0.7 mmHg, p = 0.041). The same trend was observed for the RS tertiles: 24h SBP was 134.3 ± 0.7 mmHg in the highest tertile vs 129.5 ± 0.7 in the intermediate and 128.3 ± 0.7 mmHg in the lowest tertile (p < 0.001). 24h SBP was positively and significantly correlated with both RS (r = 0.16 p < 0.001) and UE (r = 0.10, p = 0.028). In a two-way ANCOVA analysis a significant interaction was observed between RS and UE (p = 0.033): 24h SBP was 136.5 ± 1.2 mmHg among participants with the highest RS and UE levels and 127.2 ± 1.2 mmHg among those with the lowest RS and UE levels.

Conclusions: RS was a significant determinant of average 24h SBP, an association amplified by sympatho-adrenergic hyperactivity. This can account for the increased risk of cardiovascular events previously found in hypertensives hyperreactive to standing.

BLOOD PRESSURE RESPONSE TO STANDING IS A STRONG PREDICTOR OF MASKED HYPERTENSION

Francesca Saladini^1-2, Marcello Rattazzi^2-3, Lucio Mos⁴, Guido Garavelli⁵, Claudio Fania², Giuseppe Zanata⁶, Paolo Spinella², Paolo Palatini²

¹ Cardiology Unit, Cittadella Town Hospital, Cittadella, Padua, Italy; 2Department of Medicine, University of Padua, Padua, Italy; 3Medicine I^, Ca’ Foncello Hospital, Treviso, Italy; ⁴ Cardiology Unit, San Daniele Del Friuli Town Hospital, San Daniele del Friuli, Udine, Italy; ⁵ Medicine Unit, Cremona Town Hospital, Cremona; Medicine Unit, SacileTown Hospital, Sacile Pordenone, Italy

Aim: to clarify the role of the blood pressure (BP) response to the upright posture (OrthoResp) as a potential mechanism for the development of masked hypertension in young subjects screened for stage 1 hypertension.

METHODS: We studied 1078 (mean age 33.2 ± 8.5 years) subjects untreated at baseline. OrthoResp was the difference between 6 systolic BP measurements in the orthostatic and supine posture. People with OrthoResp > 6.5 mmHg (upper decile) were defined as Hyperreactors. After 3 months of follow-up, according to 24-h ambulatory BP, participants were classified as Normotensives (N = 120), White-coat hypertensives (N = 168), Masked hypertensives (N = 166), and Sustained hypertensives (N = 624) using the 140/90 and 130/80 mmHg cutoffs for office BP and 24-hour BP, respectively. In 591 participants, 24h urinary epinephrine was measured and patients were divided into four groups according to BP reactivity (> 6.5 mmHg or ≤6.5 mmHg) and 24-hour urinary epinephrine/creatinine (> 10.5 mcg/g or ≤10.5 mcg/g). The risk of developing masked hypertension was explored in a logistic regression model.

Results: Mean ± SEM OrthoResp was − 3.8 ± 0.7 mmHg in the Normotensives, − 3.1 ± 0.6 mmHg in the White-coat hypertensives, − 0.9 ± 0.6 mmHg in the Masked hypertensives, and − 2.6 ± 0.3 mmHg in the Sustained hypertensives. OrthoResp was an independent predictor of masked hypertension after 3 months (p = 0.001). Odds ratio for the Hyperreactors was 2.5 (95% CI 1.5–4.0, p < 0.001). In the participants stratified by OrthoResp and urinary epinephrine, the risk of masked hypertension was 4.2 (95% CI 1.8–9.9, p = 0.001) in the hyperreactors with epinephrine above the median and 2.6 (95% CI 0.9–7.3, p = 0.069) in those with epinephrine below the median.

Conclusions: Hyperreactivity to standing is a significant predictor of masked hypertension. This risk of masked hypertension was even quadrupled in people with an OrthoResp > 6.5 mmHg and high urinary epinephrine suggesting a role of sympatho-adrenergic activity in the pathogenesis of masked hypertension which may be partly mediated by hyperreactivity to standing.

ASSOCIATION BETWEEN RETINAL DAMAGE AND INTER-BRACHIAL BLOOD PRESSURE DIFFERENCE IN A POPULATION OF HYPERTENSIVE PATIENTS WITH TYPE 2 DIABETES MELLITUS

Adriano Massacesi ^1,2, Francesco Spannella ^1,2, Beatrice Ortensi ^1,2, Federica Verdecchia ², Alessia Ferraioli ², Riccardo Sarzani ^1,2

¹ Internal Medicine and Geriatrics, IRCCS INRCA, Ancona, Italy; ² Department of Clinical and Molecular Sciences, University “Politecnica delle Marche”, Ancona, Italy

Introduction: The systolic interbrachial blood pressure difference (IADs) is an independent predictor factor of vascular damage and cardiovascular events as well as cardiovascular death.

Aim: We investigated whether there was an association between hypertensive retinopathy and systolic interbrachial blood pressure difference (IADs), as early as 5 mmHg, in a population of hypertensive patients with type 2 diabetes mellitus (T2DM).

Methods: Cross-sectional observational study on 350 patients with T2DM and a history of arterial hypertension, to whom blood pressure (BP) was simultaneously measured on both arms with dedicated device and retinopathy was assessed with image of the fondus oculi using a non-mydriatic retinal camera.

Results: Mean age: 68.9 ± 10.7 years. BP at left arm: 140.7 ± 18.4/ 77.2 ± 10.1 mmHg. BP at right arm: 141.9 ± 19.8/76.9 ± 9.9 mmHg. IADs was 4 (2-7) mmHg, while the diastolic IAD was 3 (1-5) mmHg. The prevalence of IADs ≥5 mmHg was 44.6%, while the prevalence of IADs ≥10 mmHg was 15.1%. Hypertensive retinopathy was present in a 8.3% of patients: cottony nodules (100%), hard exudates (58.6%), microaneurysms (58.6%) and flame haemorrhages/microhaemorrhages (55.2%). Patients with IADs ≥5 mmHg had more than 2-fold greater probability of having retinopathy compared to those with IADs <5 mmHg (9.1% vs 6.1%, p = 0.048, OR = 2.2). After adjustment for glycosylated haemoglobin levels and systolic BP values on the arm with the highest BP, this latter variable was the only one that maintained statistical significance (OR = 1.02; p = 0.040).

Conclusions: Our study shows that there is a possible association also between IADs, already starting from 5 mmHg, and retinal microvascular damage, probably driven by high BP values, identified thanks to bilateral BP measurement. Our data therefore support interbrachial BP measurement in the diabetic patient, for an appropriate patient management.

PILOT STUDY ON THE DEGREE OF SATISFACTION IN THE MEASUREMENT OF AMBULATORY BLOOD PRESSURE WITH A CUFFLESS WEARABLE DEVICE: THE BIOBEAT PATCH ABPM®

Valerio Pecchioli¹, Nazzareno Lomartire², Lucia Valente², Arik Eisenkraft³, Lorenzo Pecchioli¹, Giuseppe I. W. Germanò⁴

¹ Cardiovascular Prevention Unit, Hospital Department ASL Frosinone, Italy; ² Anaesthesiology and Intensive Care Unit, ASL, Frosinone, Italy; ³ The Institute for Research in Military Medicine, The Hebrew University of Jerusalem, Israel; ⁴ Policlinico Umberto I° University “La Sapienza”, Rome, Italy

Introductions: Outpatient blood pressure measurement is a widely used method for the diagnosis and management of hypertension. In order to obtain a better assessment of BP levels, numerous automatic measuring instruments have been developed. In the era of telemedicine, the creation of wearable wireless devices can overcome the technical difficulties and procedural complexity that limit the application of these devices.

Aim: to validate the accuracy of the BIOBEAT PATCH ABPM wearable system through, first of all, the estimation of customer satisfaction. The satisfaction of the methodology will also be tested among the health professionals who provide the service.

Methods: We enrolled 12 patients, divided into two groups; in Group A we have grouped patients already subjected on other occasions to continuous monitoring of the BP and had to perform a check to verify the effectiveness of the antihypertensive treatment and Group B consisting of patients who for the first time carried out the measurement of BP. For both groups, the BP was monitored for 24 hours with traditional and wearable wireless systems and simple satisfaction questionnaires were administered. Subsequently, subgroups of analysis will be extrapolated by isolating the group of obese, i.e. patients who have used the "larger" pressure cuff, compared to normal weight. In addition, further study will also be addressed to operators questioned on the applicability of calibrated devices vs the non-calibrated and self-wearable by the patient independently compared to those who must necessarily go to the clinic. The clinical data and variables measured in the study groups were compared using Bland Altman's plot to indicate the level of agreement between the different measurement methods and between observers measuring the same phenomenon. At the end of the procedure we administered a simple customer satisfaction questionnaire for users and operators.

Results: the analysis of the data showed an adequacy of the wearable Patch for the number of valid measurements performed in the 24 hours. It emerged that the wearable system was more accurate in detecting values that exceed 130 mmHg for SBP and 89 mmHg for DBP. Also significant was satisfaction with the wearability of the BioBeat Patch ABPM system.

Conclusions: The extremely encouraging results obtained with this preliminary pilot study allows us to continue enrolling other subjects to have a significant sample number.

HOME AND OFFICE BLOOD PRESSURE DISCREPANCY AND HYPERTENSION-MEDIATED ORGAN DAMAGE: PERSONALIZED DAYTIME AND NIGHT-TIME AMBULATORY MEASUREMENTS AND GLOBAL BLOOD PRESSURE LOAD

Pietro Nazzaro, Maura Buttiglione, Adele Nardecchia, Gianfranco Amodio, Gabriella Schirosi, Maria Contini, Lorenzo Debenedittis, Gabriella Aceto, Serena Calò, Mariangela Lisena, Flavio Castigliego, Doriana Bici

Dip. Scienze Biomediche e Oncologia Umana, U.O.S.D. di Ipertensione Arteriosa “AM. Pirrelli”, Università di Bari “Aldo Moro”, Bari, Italy

Introduction: Blood pressure values during medical visit (off) often differ from those taken at home (hom). ABPM, then, is critical to aim a correct diagnosis but very few studies compared different measures, resulted by the individual recognized awake (day) and sleep (night) time.

Aim: To recognize the association of these different BP measures to cardiovascular damage.

Methods: We studied 100 hypertensives, in monotherapy by ACEi or ARB, consecutively enrolled with a hom-off SBP discrepancy > ± 10%, similar metabolic assessment, compliance to the treatment and hypertensive state, subdivided in tertiles, 33 with lower (L), 37 with medium (M) and 30 with higher (H) arterial stiffness measured by arterial tonometry (PWVcf). Then, they compiled a 18-items multiple choice cognitive questionnaire and underwent ABPM. By the individual personalized (per) awake and sleeptime, the % of measurements (load%SBP) exceeding the SBP normal values (ESC-ESH2018) and the “area-under-the-curve” (AUC: SBP*time in m’/100), as measure of global SBP load by every measurement along the entire ABPM duration.

RESULTS: Patients presented similar smoke habit, BMI (28.6 ± 5.6 vs 29.4 ± 4.4 vs 27.9 ± 4.5), age (55 ± 12 vs 59 ± 13 vs 60 ± 10) and SBP/DBPoff (139 ± 16/83 ± 11 vs 143 ± 17/84 ± 11 vs 141 ± 14/87 ± 9), but they showed further significant characteristics. (m ± s.d.:*:p < .05,**:p < .01, ***:p < .001 vs PWV-L; ^:p < .05, ^^:p < .01,^^^:p < .001 vs PWV-M).

paz/var	PWVcf	day (min)	night (min)	SBP/DBPd	SBP/DBPn
PWV-L	9.2 ± 1.4	991 ± 81	448 ± 83	141 ± 19/84 ± 10	119 ± 19/71 ± 10
PWV-M	12.9 ± 1.3***	1004 ± 61	435 ± 58	148 ± 18/86 ± 8	129 ± 23/75 ± 10
PWV-H	18.8 ± 5.4***^^^	1047 ± 76***^^	388 ± 69***^^^	147 ± 16/90 ± 8	125 ± 12/75 ± 9
	COGN	load%SBPd	load%SBPn	AUC-SBPd	AUC-SBPn
PWV-L	24.8 ± 6.5	58.3 ± 28.23	47.1 ± 31.9	1395 ± 188	542 ± 164
PWV-M	27.1 ± 6.8	65.5 ± 23.9	59.8 ± 29.9	1497 ± 184*	578 ± 137
PWV-H	30.1 ± 7.1**	66.8 ± 23.1	58.8 ± 25.6	1558 ± 171***	479 ± 107*^^^

Conclusions: The findings show that the analysis of individual duration of awake and sleep time, along ABPM, and the measure of the global load of all the BP values along the entire examination, more than the mean values of the awake-sleep standardized interval, might be significantly associated to arterial stiffness, particularly in hypertensives with BP values discrepancy between home and medical office.

NUTRACEUTICALS

EFFECTS OF CARDIOL FORTE ON THE INFLAMMATORY STATE IN PATIENTS WITH MILD TO MODERATE HYPERCHOLESTEROLEMIA: CHANGES IN ARTERIAL STIFFNESS

Nazzareno Lomartire¹, Valerio Pecchioli², Lucia Valente¹, Maria Paola Gemmiti³, Maria Pia Corsi³, Giuseppe I. W. Germanò⁴

¹ Anaesthesiology and Intensive Care Unit, ASL, Frosinone, Italy; ² Cardiovascular Prevention Unit, Hospital Department ASL Frosinone, Italy; ³Cardiology and Cardiological Intensive Care Unit, ASL Frosinone, Italy; ⁴Policlinico Umberto I° University “La Sapienza”, Rome, Italy

Introduction: High arterial stiffness is associated with a higher prevalence and incidence of target organ damage and is associated with an increased risk of cardiovascular events. Carotid-femoral pulse wave velocity (PWV) has emerged as the gold standard method for assessing arterial stiffness thanks to the numerous evidence demonstrating its association with cardiovascular disease regardless of traditional risk factors.

Aim: to evaluate the effects on endothelial function for the nutraceutical compound Cardiol forte^® by studying the correlation between inflammatory biomarkers and PWV values.

Methods: A cohort of 80 consecutive outpatients with mild to moderate hypercholesterolemia were enrolled in a single-center, double-blind, placebo-controlled study: 40 patients were assigned to the NC group and received active nutraceuticals for 16 weeks associated with a low-fat diet and 40 subjects treated with dietary regimes only (control group C). At Time 0 (T0) and every 4 weeks PWV measurements were performed by arteriograph and hsPCR values were determined to evaluate the anti-inflammatory effect.

Results: The comparison between the two groups shows a statistically significant difference in the reduction of hs-PCR values being 29.6% in the nutraceutical group and minimal variation recorded in the control group. From the data analysis we found a reduction in PWV in the NC group equal to 37.6% compared to 5.3% in the control group. The decrease in CRP values correlated significantly with the decrease in PWV.

Conclusions: The use of Cardiol forte^® can significantly reduce LDL-C levels and improve endothelial function by stopping the inflammatory process.

A NEW NATURALLY-DERIVED PEPTIDE ABLE TO CONTROL BLOOD GLUCOSE LEVELS THROUGH INTERACTION WITH DPP-IV

Albino Carrizzo^1,2, Eduardo Sommella¹, Paola Di Pietro¹, Antonio Damato², Marina Sala¹, Eleonora Venturini², Massimiliano De Lucia², Pietro Campiglia¹, Carmine Vecchione^1,2

¹ University of Salerno, Baronissi, Italy; ² IRCCS Neuromed, Pozzilli, Italy

Introduction: Recently, we showed that administration of SP6 was able to exert an antihypertensive effect by enhancing endothelial vasodilation by promoting increased serum nitrite levels. New computational data revealed that SP6 is able to interact with the dipeptidylpepdase IV (DPP-IV) enzymeprompting us to hypothesize its possible involvement in the control of diabetes mellitus.

Aim: To investigate the anti-diabetic role of the peptide SP6 isolated from gastro-intestinal-simulated in vitro digestion of spirulina platensis matrix.

Methods: We used an experimental mouse model of type 2 diabetes. A 4-week treatment by gavage administration of SP6 was performed. By molecular biology studies and the use of mass spectrometry imaging (MALDI-MSI), the expression of GLUTs levels, DPP-IV activity and GLP-1 levels, and oxidative stress were evaluated.

Results: We were able to show that daily oral admministration with SP6 peptide was able to protect against hyperglycemia-induced endothelial dysfunction. Its effect was mediated by the regulation of gene expression of GLUT1, GUT2, GLUT4 and SGLT2. In parallel, SP6 treatment was able to inhibit DPP-IV activity by promoting an increase in circulating levels of glucagon-like-peptide 1 (GLP1) without evoking any side effects. Measurement of glycated hemoglobin levels after a 5-week treatment period showed that peptide treatment was able to normalize HbA1c levels, bringing its levels back below 6%. SP6 treatment was able to reduce oxidative stress at the pancreatic level.

Conclusions: In conclusion, our data support the beneficial role of SP6 on the pathophysiology of diabetes and lay the foundation for being able to develop a possible new therapeutic approach to control pre-diabetes condition.

EFFECT OF DIETARY SUPPLEMENTATION WITH EUFORTYN^® COLESTEROLO PLUS ON SERUM LIPIDS, ENDOTHELIAL FUNCTION, INDEXES OF NON-ALCOHOLIC FATTY LIVER DISEASE AND SYSTEMIC INFLAMMATION IN HEALTHY SUBJECTS WITH POLYGENIC HYPERCHOLESTEROLEMIA: THE ANEMONE STUDY

Arrigo F.G. Cicero,^1,2 Federica Fogacci,¹ Elisabetta Rizzoli,^1,2 Marina Giovannini,¹ Sergio D’addato,^1,2 Maddalena Veronesi,^1,2 Claudio Borghi,^1,2

¹Hypertension and Cardiovascular Risk Research Group, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; ²IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Introduction: Recently, artichoke and bergamot standardized flavonoids extracts have been suggested as safe lipid-lowering nutraceuticals.

Aim: To evaluate if dietary supplementation with a nutraceutical compound (Eufortyn^® Colesterolo Plus) containing standardized bergamot polyphenolic fraction phytosome (Vazguard^®), artichoke extract (Pycrinil^®), artichoke dry extract (Cynara scolymus L.), Q10 phytosome (Ubiqosome^®) and zinc, could positively affect serum lipids concentration, systemic inflammation and indexes of non-alcoholic fatty liver disease (NAFLD) in 60 healthy subjects with polygenic hypercholesterolemia.

Methods: Participants were adhering to a low-fat low-sodium Mediterranean diet for a month before being randomly allocated to 8-week treatment with 1 pill each day of either Eufortyn® Colesterolo Plus or placebo.

Results: Dietary supplementation with Eufortyn^® Colesterolo Plus was associated with significant improvement in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), high-sensitivity C-reactive protein (hs-CRP) and endothelial reactivity (ER) in comparison with baseline, and with significant reductions in waist circumference TC, LDL-C, LDL-C/HDL-C, lipid accumulation product and fatty liver index compared to placebo. TC and LDL-C improved with Eufortyn® Colesterolo Plus versus both baseline and placebo.

Conclusions: The study shows that dietary supplementation with standardized bergamot polyphenolic fraction phytosome, artichoke extracts, Q10 phytosome and zinc safely exerts significant improvements in serum lipids, systemic inflammation, indexes of NAFLD and endothelial reactivity in healthy subjects with moderate hypercholesterolemia.

EFFECT OF DIETARY SUPPLEMENTATION WITH DIURIPRES® ON BLOOD PRESSURE, VASCULAR HEALTH AND METABOLIC PARAMETERS IN INDIVID-UALS WITH HIGH-NORMAL BLOOD PRESSURE OR STAGE I HYPERTENSION: THE CONDOR STUDY

Arrigo F.G. Cicero,^1,2 Federica Fogacci,¹ Daniela Degli Esposti,^1,2 Antonio Di Micoli,^1,2 Giulia Fiorini,^1,2 Stefano Bacchelli,^1,2 Claudio Borghi^1,2

¹Hypertension and Cardiovascular Risk Research Group, Medical and Surgical Sciences Department, University of Bologna, Bologna, Italy; ²IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

Introduction: In the last decades there has been a growing interest in natural compounds targeting multiple biochemical pathways. This effort -together with a drive for innovative non-pharmacological treatments of hypertension- has recently resulted in remarkable advances in the field of cardiovascular disease prevention.

Aim: We aimed to evaluate if dietary supplementation with a nutraceutical compound (Diuripres^®) containing magnesium, standardized extract of orthosiphon, hawthorn and hibiscus could positively affect blood pressure (BP), vascular health and metabolic parameters in individuals with high-normal BP or stage I hypertension.

Methods: Participants were adhering to a low-fat low-sodium Mediterranean diet for a month before being randomly allocated to 8-week treatment with 2 pills each day of either Diuripres® or placebo.

Results: Diuripres^® significantly decreased systolic BP compared to placebo after 4 weeks and more consistently after 8 weeks. At 8-week follow-up, dietary supplementation with Diuripres^® was associated with significant improvements in diastolic BP, aortic BP, waist circumference, visceral adiposity index, high-density lipoprotein cholesterol and high-sensitivity C-reactive protein (hs-CRP) in comparison with baseline. The reductions in aortic BP and hs-CRP were also significant compared to placebo.

Conclusions: Our study show that dietary supplementation with Diuripres^® may be useful in individuals with high-normal BP or stage I hypertension.

PRIMARY PREVENTION AND CARDIOVASCULAR RISK

SINGLE CENTER EXPERIENCE IN MANAGEMENT OF PATIENTS WITH CARDIOVASCULAR ADVERSE EVENTS DURING CARFILZOMIB THERAPY

Giulia Mingrone¹, Anna Astarita¹, Anna Colomba¹, Cinzia Catarinella¹, Marco Cesareo¹, Lorenzo Airale¹, Dario Leone¹, Fabrizio Vallelonga², Sara Bringhen³, Francesca Gay³, Franco Veglio¹ and Alberto Milan¹

¹ Department of Internal Medicine and Hypertension Division, “Città della Salute e della Scienza” Hospital, University of Turin, Turin, Italy; ² Acceptance and Emergency Medicine and Surgery, San Giovanni Bosco Hospital, Turin, Italy; ³ Myeloma Unit, Division of Haematology, “Città della Salute e della Scienza” Hospital, University of Turin, Turin, Italy

Introduction: Carfilzomib (CFZ) improves the prognosis of multiple myeloma(MM) patients, but has shown cardiotoxicity[1]. The risk stratification of cardiovascular adverse events (CVAE) now appears fairly accurate [2], while little is known about the fate of patients with high cardiovascular(CV) risk or presenting CVAEs. No recommendations can be made regarding further continuation or discontinuation of MM-therapy in patients with evidence of cardiac dysfunction during treatment.

Aim: To evaluate the single centre experience in terms of decision-making regarding patients having high risk of CVAE due to CFZ or after cardiovascular major events.

Methods: 180 patients with MM and hematologic indication to CFZ treatment performed a baseline CV evaluation to assess the risk of CVAEs during CFZ. In patients with high baseline CV risk or suspected CVAEs during therapy several diagnostic investigations have been carried out to confirm/rule out clinical conditions that could contraindicate the administration of haematologic therapy. All patients were clinically followed-up during CFZ to early identify and manage the occurrence of CVAEs.

Results: After the baseline CV evaluation 11.6% of patients were considered at high risk of CVAE, 46% at intermediate risk, 22.7% at low risk. 6.6% of patients performed inducible myocardial ischemia test and 2.2% of these could not perform CFZ because of CV contraindications. 95.6% patients started the CFZ therapy: 39% experienced arterial hypertension-related events and 20% major CVAEs (Table 1). In 9.9% of patients the CFZ therapy had to be suspended/remodulated.

CONCLUSIONS: In MM patients with indication to CFZ, the baseline CV risk stratification and the clinical/diagnostic follow-up are critical to identify or rule out clinical condition that could contraindicate the hematologic therapy.

Table 1.

Cardiovascular adverse events (CVAEs) incidence during Carfilzomib therapy

Cardiovascular adverse events*	Population, n = 172
Events related to arterial hypertension, (%)	67 (39)
Arterial hypertension, (%)	54 (31)
Arterial hypertension before Carfilzomib infusion, (%) -with subsequent administration, (%) - without subsequent administration, (%)	37 (21.5) 26 (15.1) 18 (10.5)
Arterial hypertension after Carfilzomib infusion, (%)	17 (10)
Uncontrolled arterial hypertension (> 180/100) with symptoms, (%)	6 (3.5)
Hypertensive emergency, (%)	0 (0)
Major cardiovascular events, (%)	34 (20)
Dyspnoea, (%)	6 (3.5)
Arrythmia, (%)	11 (6.4)
Severe hypotension, (%)	4 (2.3)
Cardiac failure, (%)	7 (4.1)
Typical chest pain, (%)	8 (4.7)
STEMI, (%)	1 (0.6)
NSTEMI, (%)	6 (3.5)
Syncope, (%)	1 (0.6)
Cardiac-related sudden death, (%)	1 (0.6)
Both major and hypertensive events, (%)	19 (11)

*Defined according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events)

THE RATIO BETWEEN SERUM URIC ACID AND SERUM CREATININE PREDICTS CARDIOVASCULAR EVENTS IN A NATIONWIDE COHORT OF 21,349 SUBJECTS. THE URRAH (URIC ACID RIGHT FOR HEART HEALTH) PROJECT

Valerie Tikhonoff ³, Edoardo Casiglia ³, Agostino Virdis ⁴, Carlo M Barbagallo ⁵, Massimo Cirillo ⁶, Giovambattista Desideri ⁷, Claudio Ferri ⁷, Ferruccio Galletti ⁸, Cristina Giannattasio ⁹, Guido Iaccarino ¹⁰, Alessandro Maloberti ¹⁹, Alberto Mazza ¹¹, Maria L Muiesan ¹², Paolo Palatini ³, Gianfranco Parati ¹³, Roberto Pontremoli ¹⁴, Marcello Rattazzi ³, Paolo Verdecchia ¹⁵, Francesca Viazzi ¹⁴, Massimo Volpe ¹⁶, Andrea Ungar ¹⁷, Arrigo Fg Cicero ², Guido Grassi ¹⁸, Claudio Borghi ²

¹ Department of Medicine- DIMED, University of Padua, Padova, Italy, ² Department of Medical and Surgical Science, Alma Mater Studiorum University of Bologna, Bologna, Italy, ³ Department of Medicine- DIMED, University of Padua, Padova, Italy, ⁴ Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy, ⁵ Biomedical Department of Internal Medicine and Specialistics, University of Palermo, Palermo, Italy, ⁶ Department of Public Health, “Federico II" University of Naples, Napoli, Italy, ⁷ Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy, ⁸ Department of Clinical Medicine and Surgery, “Federico II" University of Naples Medical School, Napoli, Italy, ⁹ School of Medicine and Surgery, Milano-Bicocca University, Milano, Italy, ¹⁰ Department of Advanced Biomedical Sciences, “Federico II" University of Naples, Napoli, Italy, ¹¹ Department of Internal Medicine, Hypertension Unit, General Hospital, Rovigo, Italy, ¹² Department of Clinical and Experimental Sciences, University of Brescia,, Brescia, Italy, ¹³ Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital,, Milano, Italy, ¹⁴ Department of Internal Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino,, Genova, Italy, ¹⁵ Hospital S. Maria della Misericordia,, Perugia, Italy, ¹⁶ Hypertension Unit, Division of Cardiology, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psycho, Roma, Italy, ¹⁷ Department of Geriatric and Intensive Care Medicine, Careggi Hospital and University of Florence, Firenze, Italy, ¹⁸ Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Milano, Italy, ¹⁹ Cardiology IV, “A.De Gasperi’s" Department, Niguarda Ca’ Granda Hospital, Milano, Italy

Introduction: Serum Uric acid (SUA) depends on renal clearance function and increased SUA often occurs as a consequence of renal dysfunction. The SUA to serum creatinine (SCr) ratio, considered as a renal function-normalized SUA, has emerged as a new biomarker and evidence on its effect on CVD is limited.

Aim: Searching for a prognostic cut-off value of the SUA/SCr ratio in predicting cardiovascular (CV) outcome in a large regional-based Italian database of men and women.

Methods: A nationwide multicentre database collects data on subjects aged 18–95 years recruited on a regional community basis from all the territory of Italy with at least 1 measure of SUA and SCr and a mean follow-up of 110.1 ± 64.3 months. A total of 21,596 subjects were included in the analysis. Total CV outcome was defined on the basis of ICD10 codes and double-checked with general practitioners and hospital files. Multivariate dichotomic Cox regression models having total CV outcome as dependent variable, adjusted for age, sex, body mass index, LDL-cholesterol, arterial hypertension, diabetes, use of alcohol were preliminarily used to search for an association between SUA/SCr ratio as a continuous variable and total CV outcome. In the whole cohort and in men and women separately, the prognostic cut-off values of the SUA/SCR ratio identified by means of receiver operating characteristics (ROC) curves, able to discriminate between subjects developing a CV event, were used as independent predictors in further multivariate Cox models adjusted for the confounders listed above.

Results: Both SUA and SCr as continuous variables predicted 20-year cardiovascular (CV) events (OR 1.115, 95% CI 1.136–1.715, p < 0.0001, and OR 1.267, 95% CI 1.267–1.399, p < 0.0001, respectively). Diabetes (p < 0.0001), body mass index (p < 0.01), arterial hypertension (p < 0.0001) and ethanol consumption (p < 0.0001) were significant covariables in Cox model. The SUA/SCr ratio as a continuous variable was a significant predictor (OR 1.027, 95% CI 1.007–1.048, p = 0.007). By means of ROC curve method, prognostic cut-off values of SUA/SCR were found for the whole cohort (> 5.35, 95% CI 4.76–5.53), for the 10,347 men (> 5.35, 95% CI 3.20–6.17) and for the 11,596 women (> 5.56, 95% CI 5.28–6.60). Subjects were then stratified into those being until the cut-off and over the cut-off of SUA/SCr, using cut-off as a categorical variable in multivariate Cox models adjusted for age, sex, diabetes, body mass index, arterial hypertension, LDL-cholesterol and ethanol consumption. The hazard ratio of being over the cut-off was 1.291 (95% CI 1.1661.431, p < 0.0001) for the whole cohort, 1.191 (95% CI 1.025–1.383, p = 0.02) for men and 1.380 (95% CI 1.197–1.590, p < 0.0001) form women. Kaplan-Meier curves were created (those concerning the whole cohort are reproduced below in figure 1). They clearly separated subjects who were until and those who were over the cut-off (p = 0.013 for men, p < 0.0001 for women).

Conclusions: In conclusion, the SUA/SCr ratio, both used as a continuous variable and through calculate cut-off values, is a good predictor of CV events having the advantage of making SUA independent of SCr.

ROLE OF THE ELECTROCARDIOGRAM IN DETECTING LEFT VENTRICULAR MASS INCREASES AND NEW ONSET LEFT VENTRICULAR HYPERTROPHY OVER TIME

Jennifer Vanoli¹, Cesare Cuspidi¹, Alessandro Maloberti¹, Simone Maggioni¹, Rita Facchetti¹, Giuseppe Mancia², Guido Grassi, Michele Bombelli³

¹ Clinica Medica, Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy; ² University of Milano-Bicocca, Milan, Italy; ³ University of Milano-Bicocca, ASST-Brianza, Pio XI Hospital, Internal Medicine, Desio, Italy

Aim: We assessed the value of 3 electrocardiographic (EKG) voltage criteria in detecting variations of left ventricular mass (LVM) over time, taking echocardiographic (ECHO) LVM as reference, in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study.

Methods: For 927 subjects (age 47 ± 13 years on entry, 49.9% men) an ECHO evaluation of LVM and EKG suitable for measurement of EKG-LVH criteria (Sokolow-Lyon voltage, Cornell voltage and R-wave voltage in aVL) were available at baseline and at a second evaluation performed 10 years later. Δ (delta) LVM, Δ LVMI and Δ EKG parameters values were calculated from second evaluation to baseline.

Results: The sensitivity of the EKG criteria in the diagnosis of LVH, poor at baseline (at best 28% for R in aVL), becomes even worse after 10 years, reaching very low values, 0.64% for Sokolow-Lyon. Only the sensitivity of R-wave amplitude exhibited slight increase over time but with unsatisfactory absolute values. Indeed, despite the prevalence of ECHO-LVH at the second evaluation was threefold increased compared to baseline (29.3% and 33.7% for LVM indexed to BSA and height2.7, respectively), the prevalence of EKG-LVH was unchanged when evaluated by Sokolow-Lyon criteria, significantly reduced when assessed by Cornell voltage index, while significantly increased using R-wave voltage in aVL criteria. No significant correlation was found between changes in ECHO-LVM and variations of voltages of the three EKG criteria. Despite an ECHO-LVM increase over the time, mean EKG changes were of opposite sign, except for R-wave amplitude in aVL.

Conclusions: Our study highlights the discrepancy between ECHO and EKG in monitoring LVM changes over the time, especially for commonly-used criteria in detecting LVH, such as Sokolow-Lyon and Cornell voltage. Thus EKG is an unsuitable method for the longitudinal evaluation of LVM variations.

URIC ACID AND CREATININE RATIO IS ASSOCIATED WITH THE DEVELOPMENT AND SEVERITY OF PREECLAMPSIA IN A COHORT OF 258 PREGNANT WOMEN

Federica Piani, Davide Agnoletti, Carmine Verde, Daniela Degli Esposti, Claudio Borghi

Cardiovascular Internal Medicine, IRCCS Policlinico S. Orsola, Bologna, Italy

Introduction: Preeclampsia (PE) is the leading cause of maternal and fetal morbidity and mortality. PE presents with new-onset hypertension and increased levels of protein in the urine after 20 weeks of gestation that can progress rapidly leading to serious complications for both the mother and the fetus. Furthermore, the development of PE represents a recognized life-long cardiovascular risk factor. Thus, it is of crucial importance to identify biomarkers associated with PE development and its associated complications, to strictly follow-up patients at high-risk and implement management and therapeutic strategies. In recent studies, serum uric acid concentrations have been associated with the development of PE and its complications. However, there are still few large studies on the predictive value of serum uric acid in women with hypertensive disorders of pregnancy vs. PE, and with PE vs. normotensive pregnancies. Additionally, since during pregnancy lot of hemodynamics and renal adaptations occur, it would be of crucial importance to consider uric acid/creatinine ratio instead of serum uric acid alone.

Aim: In this study we aimed to assess the prognostic value of uric acid/creatinine ratio in the assessment of PE risk in women at their third trimester of pregnancy.

Methods: We collected clinical history, vital signs, and laboratory results of 258 pregnant women, 201 with hypertensive disorders of pregnancy and 57 healthy controls, from our Hypertensive disorders of Pregnancy Clinic. Of the 201 women with hypertensive disorders of pregnancy, 111 were diagnosed with PE. All samples were analyzed in the Metropolitan Laboratory Unit of Bologna (LUM), Italy, a certified laboratory that meets all European standards and requirements. We performed logistic regression analysis to assess the associations between serum uric acid concentrations and uric acid to creatinine ratio at the third trimester of pregnancy, development of PE, and the need for Intensive Care Unit (ICU) transfer.

Results: Main characteristics of the study population are summarized in Table 1. Women with hypertensive disorders of pregnancy (n = 201) had significantly higher Body Mass Index before pregnancy (BMI) (p = 0.018) and delivered around two weeks earlier (p = 0.001) compared to women with normotensive pregnancy. Serum uric acid concentration at the third trimester of pregnancy was significantly higher in women with hypertensive disorders of pregnancy (5.6 ± 1.6 vs. 4.4 ± 0.9, p = 0.001). Compared to women with normotensive pregnancies, women with hypertensive disorders of pregnancy had a significantly lower rate of spontaneous deliveries (p = 0.042) and a higher proportion of early deliveries (before 37 weeks of gestation) (p = 0.017).

The ratio of uric acid to creatinine at the third trimester of pregnancy was associated with an increased risk of the composite outcome of PE development and need for ICU transfer (OR 1.26, CI 1.09 to 1.47, p = 0.0016), after adjustment for age, BMI before pregnancy, hypertensive therapy during pregnancy, gestational diabetes, first pregnancy, and acetylsalicylic acid therapy (Table 2).

Conclusions: In our study, elevated uric acid/creatinine ratio at the third trimester of pregnancy were associated with an increased risk of PE development and ICU admission in women with hypertensive and normotensive pregnancies, highlighting a significant prognostic role of uric acid/creatinine during pregnancy.

Table 1

	Normotensive pregnancies (n = 57)	Hypertensive disorders of pregnancy (n = 201)	p value
Age (years)	35 ± 5	36 ± 6	0.252
BMI (kg/m2)	25.7 ± 4.8	27.9 ± 6.3	0.018
Creatinine 3rd trimester (mg/dl)	0.56 ± 0.10	0.62 ± 0.15	0.015
Uric acid 3rd trimester (mg/dl)	4.4 ± 0.9	5.6 ± 1.6	0.001
Gestational Diabetes	13/57 (22.8%)	48/201 (23.9%)	0.866
First pregnancy	22/57 (38.6%)	91/201 (45.3%)	0.352
Delivery timing (weeks)	38 ± 2	36 ± 3	0.001
Early delivery (before 37 weeks of gestation)	4.7%	29.6%	0.017
Spontaneous delivery	55.5%	36.9%	0.042
Antihypertensive therapy during pregnancy	0/57 (0%)	161/201 (80.1%)	<0.001
Acetylsalicylic acid therapy during pregnancy	4/57 (7%)	60/201 (29.8%)	<0.001
ICU admission	1/57 (1.7%)	5/201 (2.5%)	0.678

Table 2

	O.R.	95% CI		P value
Uric acid/Creatinine ratio 3rd Trimester	1.26	1.09	1.47	0.001
Age	0.99	0.93	1.07	0.906
BMI	0.96	0.90	1.012	0.126
Antihypertensive therapy during pregnancy	5.30	2.30	12.93	<0.001
Gestational diabetes	1.74	0.79	3.93	0.172
First pregnancy	0.89	0.68	1.15	0.369
Acetylsalicylic acid therapy during pregnancy	0.30	0.14	0.65	0.002

M1/M2 RATIO PREDICTS CARDIAC SYSTOLIC FUNCTION AFTER MI WITH ST ELEVATION (STEMI)

Maria Rosaria Rusciano¹, Elena De Angelis¹, Ilaria Radano², Angelo Silverio¹, Rodolfo Citro², Amelia Ravera², Paola Di Pietro¹, Albino Carrizzo¹, Anna Laura Toni¹, Gennaro Galasso¹, Carmine Vecchione¹, Michele Ciccarelli¹

¹ University of Salerno, Department of Medicine, Surgery and Odontoiatry, Salerno, Italy; ² University Hospital San Giovanni di Dio e Ruggi d’Aragona, Salerno, Italy

Introduction: In response to myocardial infarction (MI), cardiac monocytes and macrophages regulate inflammation and scar formation playing a crucial role in infarct healing and subsequent LV remodelling. In humans, two different monocyte subsets are identified: classical CD14++CD16– so-called M1 monocytes and nonclassical CD14+CD16++ or M2 monocytes; these two populations show a different pro-inflammatory activity. The prognostic post-STEMI impact of monocyte subsets remains, nonetheless, unknown.

Aim: In this study, we sought to examine the dynamic changes of the 2 monocyte subsets in a contemporary population with anterior STEMI and correlate these changes with the short-term cardiovascular outcome.

Methods: We enrolled prospectively 64 patients with a diagnosis of acute myocardial ischemia with ST-elevation (STEMI), defined by typical chest pain and persistent ST-segment elevation on electrocardiography with total ischemic time inferior to 4 hours. Levels of peripheral monocytes were evaluated by FACS analysis at hospital admission (time 0), 48 and 96 hours post-admission. After 96 h from admission all patients underwent a cardiac echography for the evaluation of cardiac volumes, left ventricular ejection fraction (LVEF) and left ventricular global longitudinal strain; patients were divided into two groups according to the LVEF (<45% and ≥45%).

Results: Baseline characteristics, pharmacological treatment, total ischemia time and post-PCI TIMI flow did not show significative differences with the exceptions of diuretics use that was prevalent in the LVEF<45% population (20% n = 4 in LVEF<45%; n = 0 in LVEF > 45%; p = 0,001), cardiac arrest (20% n = 4 in LVEF<45%; n = 0 in LVEF > 45%; p = 0,001), and ventricular fibrillation (20% n = 4 in LVEF<45%; n = 0 in LVEF > 45%; p = 0,001). Total peripheral monocyte counts were not different between the two populations at the three timepoint (p = 0,486 a T0; p = 0,213 a T48; p = 0,456 a T96). However, M1 monocytes were significantly increased at T0, T48 and T96 in the FE<45% (T0: 63,8%, T48: 60%, T96: 55,8%) than the FE ≥45% population (T0: 37%, T48: 43,7%, T96: 62%; p < 0,000). Also M2 monocytes were significantly increased at T0, T48 and T96 in the FE<45% (T0: 85%, T48: 98%, T96: 91%) than the FE ≥45% (T0: 67%, T48: 44,9%, T96: 36,9%; p = 0,005 for T0, P = 0,002 for T48, P < 0,000 for the T96). The T48 and T96 M1/M2 ratio was reduced in the LVEF<45% group (Fig. 1). Moreover, the M1/M2 ratio at 48 and 96 h presented a significant positive linear correlation with the LVEF (R = 0,063 at T0, p = 0,272; R = 0,128 at T48, p = 0,016; R = 0,316 at T96, p = 0,001) confirmed by the logistic regression (OR = 1,646 at T0, p = 0,419; OR = 4,339 at T48, p = 0,035; OR = 4,635 at T96, p = 0,014) (Fig.2).

Conclusions: Elevation of M2-monocytes and a lower M1/M2 ratio are related to a reduced LVEF possibly due to a pronounced pro-fibrotic state thus demonstrating that M1 and M2 monocytes expression can predict the outcome of the systolic cardiac function in a short time after STEMI

Figure 1 M1/M2 ratio correlates with FE

Figure 2 Linear correlation M1/M2 ratio and LVEF

EFFECTS OF THE KETOGENIC DIET AND INTERMITTENT FASTING ON SYSTEMIC BLOOD PRESSURE AND VASCULAR REACTIVITY IN A COHORT OF WOMEN WITH OBESITY AND ARTERIAL HYPERTENSION (DIET-TO-HTN)

Barbara Pala, Priscilla Tifi, Sara Di Marzio, Giuliano Tocci, Massimo Volpe

Division of Cardiology, Faculty of Medicine and Psychology, University of Rome Sapienza, Sant’Andrea Hospital, Rome, Italy

Introduction: ISTAT reported that in 2021 46.2% of the Italian adult population has not normal weight (34.2% overweight, 12.0% obese). The constant and continuous increase of unfavorable lifestyle habits and metabolic risk factors makes necessary to promote healthy eating patterns; mostly in postmenopausal when hormonal changes increase the incidence of cardiovascular disease in women.

Aim: To evaluate the effects of either free diet, Ketogenic or Intermittent Fasting diet on postmenopausal obese hypertensive outpatients.

Methods: We conduct a single-center, prospective, case-control, clinical study, which included outpatients followed at the Hypertension Unit, Sant'Andrea Hospital, Rome, Italy. The following inclusion criteria will be considered: (1) postmenopausal women aged between 48 and 60 years; (2) BMI ≥30 kg/m²; (3) treated essential hypertension. Clinic Blood Pressure (BP) and pulse wave velocity will be measured in seated position after 5-10 minutes of rest by using an automated, oscillometric device (Mobil-O-Graph PWA Monitor, I.E.M. GmbH, Stolberg, Germany). Conventional 12-lead electrocardiogram, cardiac eco-color-Doppler and a nutritional visit with Body Mass Index (BMI) assessment will be also performed. Once included, patients will be randomly divided into three homogenous groups with different dietary regimen for 6 months (free diet, ketogenic diet, intermittent fasting).

Results: We will firstly evaluate the effects of different diets on the clinic BP levels and cardiac and vascular parameters of organ damage. Then, we will correlate BMI changes with different measures of cardiovascular prevention.

Conclusions: The assessment of the biological changes obtained with dietary regimens will allow to establish other preventive interventions and to provide a tool to reduce the morbidity and mortality burden related to menopause.

EFFECTS OF PRESCRIBING ICT-SUPPORTED ADAPTED PHYSICAL ACTIVITY IN SEDENTARY PATIENTS

Antonio Bianco, Luca Allocca, Rosita Mottola, Vincenza Notarangelo, Antonia Buonaiuto, Rocco Santarone, Giuseppe Iadicicco, Guido Iaccarino

Centro Interdipartimentale di Ricerca in Ipertensione Arteriosa e Patologie Associate, Università Federico II di Napoli, Italy

Introduction: The ESC guidelines for the prevention and management of heart failure reinforce the prescription of physical activity as a powerful tool for improving the quality of life. However, it is not easy to induce in sedentary patients the adoption of a healthy lifestyle that also includes physical activity. For this reason, at the Prescription Clinic for Adapted Physical Activity (AFA) of the AOU Federico II we have developed an APP (Telerevalidatie) to be installed on the patients' mobile phones that allows them to remember to perform the AFA and offers videos of the exercises, prescribed for the day, at the end of which the patient confirms the execution.

Aim: We evaluated the effectiveness of this support in inducing the adoption of a healthy lifestyle, and the impact on physical health parameters, and exercise tolerance, as well as the effects on hemodynamic parameters.

Methods: We enrolled 61 sedentary patients from January 2021 who were prescribed AFA with alternating programs of muscle strengthening and flexibility and aerobic physical activity at 60% of the maximum theoretical heart rate; of these, 37 patients completed a minimum FU of 3 months (mean 213 + 31 days, median 141 days). Of these, 20 were hypertensive on drug treatment. Patients had a mean age of 61.6 + 2.3 years, 49% women. At each FU visit, patients underwent bioimpedance analysis (Akern), strength tests (dynamometer and chair test), balance (walking blindfolded in place), flexibility and exercise tolerance (Bruce's Cycle ergometer Protocol).

Results: Adherence to the AFA program, assessed by counting APP accesses with respect to the prescribed program, was about 55 + 7%. By comparing the parameters measured at the time of enrollment with those at the last available FU, we observed an improvement in anthropometric parameters, strength of the lower limbs and tolerance to effort. It is interesting to note that the haemodynamic parameters of diastolic arterial pressure assessed in supine position were also improved, although no changes had been made on the pharmacological therapy of hypertensive patients.

Conclusions: The prescription of the AFA with technological support through APP represents an interesting therapeutic aid to be promoted for the implementation of the guidelines.

	Base	Follow-uUp	P VALUE
Weight (kg)	73.2 ± 2.3	71.1 ± 2.9	n.s.
Total Water (L)	41.2 ± 1.4	38.4 ± 1.4	p < 0.05
Line Mass (% peso)	74.9 ± 1.3	71.2 ± 2.5	n.s.
Flexibility (cm)	-5.6 ± 1.3	-2.5 ± 1.1	p < 0.05
Upper arms strength (kg)	25.7 ± 1.4	26.2 ± 1.5	n.s.
Chair test (repetitions)	14.3 ± 0.6	17.1 ± 0.8	p < 0.05
Stress time (min)	6.1 ± 0.4	7.6 ± 0.4	p < 0.05
Recovery time (min)	4.7 ± 0.5	3.5 ± 0.2	p < 0.05
Systolic BP (mmHg)	133 ± 2.0	129 ± 2.7	n.s.
Diastolic BP (mmHg)	81 ± 1.8	76 ± 1.9	p < 0.05

KIDNEY

PREVALENCE AND DISEASE SPECTRUM OF FIBROMUSCULAR DYSPLASIA IN PATIENTS WITH SPONTANEOUS CEREBROVASCULAR ARTERY DISSECTION

Marco Pappaccogli¹, Martina Mangeruga¹, Elisabetta Eula¹, Elvira Fanelli¹, Giovambattista Bosco², Fabio Verzini³, Paolo Cerrato², Alessandro Depaoli⁴, Franco Rabbia¹, Franco Veglio¹.

¹Division of Internal Medicine and Hypertension Unit, Department of Medical Sciences, University of Turin, Turin, Italy; ²Stroke Unit, Città della Salute e della Scienza – Molinette, Turin, Italy; ³Vascular Surgery Unit, Department of Surgical Sciences, University of Turni, A.O.U. Città della Salute e della Scienza, Molinette Hospital, Turin, Italy; ⁴Radiology Unit, Department of Surgical Sciences, University of Turin, Turin, Italy

Introduction: Fibromuscular Dysplasia (FMD) is an idiopathic, segmental, noninflammatory and nonatherosclerotic disease of the musculature of arterial walls, leading to stenosis of small- and medium-sized arteries. FMD phenotype also includes aneurysms, arterial dissections and tortuosity and should be always suspected in case of spontaneous arterial dissection occurring in young patients without other risk factors.

Aim: to assess the prevalence of extra-cervical FMD in patients with a diagnosis of spontaneous cerebrovascular artery dissection (CeAD).

Methods: All patients discharged from the Stroke Unit of A.O.U. Città della Salute e della Scienza of Turin from 2016 to 2020 with a diagnosis of CeAD underwent a contrast-enhanced CTA from chest to pelvis to look for FMD-related lesions (multifocal stenosis, aneurysms, dissections and/or arterial tortuosity). Written informed consent was retrieved from all participants. FMD diagnosis was assessed in the presence of at least a multifocal stenosis in one of the vascular beds explored.

Results: Among 40 patients with spontaneous CeAD (77.5% male; 51.4 ± 8.5 y.o.), 36.1% of patient had hypertension and 51.5% were past or current smokers. According to radiological findings, 90.9% of patients showed extra-cervical arterial lesions, with a prevalence of FMD (defined as the presence of at least a multifocal stenosis) reaching 81.8% of the studied sample and affecting renal (45.5%), visceral (54.5%), iliac (45.5%) and coronary arteries (9.1%) respectively. Renal involvement included multifocal renal stenosis in 27.3% of patients and renal artery aneurysms in 18.2%. Visceral involvement (splenic, inferior and superior mesenteric, and hypogastric arteries, celiac trunk) included multifocal stenosis in 27.3% of patients, visceral aneurysms in 18.2% of patients, and silent mesenteric artery dissection in the superior mesenteric artery in 9.1% of patients. Iliac involvement included tortuosity (18.2%), and common iliac and/or internal/external iliac arteries ectasia (30%). Furthermore, a spontaneous dissection of the left external iliac artery, clinically asymptomatic, was reported in a young male with no other multifocal stenosis or arterial lesions. Nine% of patients (9.1%), all women, suffered also from SCAD. Finally, mild lesions, such as arterial profile irregularities, were reported in 9.1% of patients. Two or more extra-cervical vascular beds were involved in almost half of the patients (45.5%) with sever lesions (multifocal high degree stenosis and/or arterial dissections) affecting 27.3% of the population.

Conclusions: According to our results, we demonstrated that FMD is a common cause of spontaneous CeAD and that silent FMD-related lesions, even severe as arterial dissections, may coexist in such patients. Therefore, FMD should always be taken in consideration in the differential diagnosis of spontaneous arterial dissection or aneurysm rupture, especially if occurring in young subjects without major cardiovascular risk factors.

VESSELS AND ENDOTHELIUM

INCIDENT AORTIC ROOT DILATATION IN THE GENERAL POPULATION: FINDINGS FROM THE PAMELA STUDY

Raffaella Dell’Oro¹, Jennifer Vanoli¹, Gino Seravalle², Fosca Quarti-Trevano¹, Rita Facchetti¹, Cesare Cuspidi¹, Giuseppe Mancia¹, Guido Grassi¹

¹ Department of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy; ² Istituto Auxologico Italiano, Milan, Italy

Introduction: Aortic remodelling is frequently observed in hypertensive patients.

Aim: to assess the long-term changes in aortic root (AR) diameter in a population-based sample, focusing on new onset AR dilatation, as well as on the demographic and clinical variables independently related to this dynamic process.

Methods: A total of 1,122 participants with measurable echocardiographic parameters at baseline and after a ten-year follow-up were included in the analysis. Sex-specific upper limits of normality for absolute AR diameter, AR diameter indexed to body surface area (BSA) and to height were derived from 712 healthy normotensive PAMELA participants.

Results: Over the 10-year follow-up new AR dilatation occurred in 3.4% (AR/BSA), 4.4% (AR/height) and 7.3% (absolute AR), respectively. No substantial relationship was observed between baseline office and ambulatory BP or their changes over time and incident AR/BSA and AR/height dilatation. Baseline AR diameter and left ventricular mass index (LVMI) emerged as important predictors of AR dilation, regardless of the diagnostic criteria used. This was also the case for the 10-year change in LVMI. The strength of association between non-hemodynamic variables and new onset AR dilatation was variable, depending on the definition of the aortic phenotype.

Conclusions: The incidence of AR dilatation in a general middle-aged population is a relatively infrequent but not so rare event and scarcely influenced by both office and out-office BP. On the contrary, it is strongly related to LVMI (and its variations over time). From a clinical perspective, this underlines that LVH prevention and regression can reduce the risk of AR dilatation in the community.

TARGETING GRK2 TO PREVENT AORTIC VALVE CALCIFICATION

Maria Rosaria Rusciano¹, Daniela Sorriento², Valeria Valerio³, Anna Laura Toni¹, Paola Di Pietro¹, Albino Carrizzo¹, Guido Iaccarino², Paolo Poggio³, Carmine Vecchione¹, Michele Ciccarelli¹

¹ University of Salerno School of Medicine, Department of Medicine, Surgery and Odontoiatry, Salerno, Italy ² Federico II University Hospital, Advanced Biomedical Sciences, Naples, Italy; ³ Centro Cardiologico Monzino, IRCCS, Unità per lo Studio delle patologie Aortiche, Valvolari e Coronariche, Milan, Italy

Introduction: Calcific aortic valve stenosis (CAVS) is a clinically relevant issue due to the lack of drugs for prevention or treatment. CAVS is driven by endothelial dysfunction and inflammation. A novel therapeutic strategy should target specific molecules involved in the regulation of both endothelial function and immune responses. G protein-coupled receptor kinase 2 (GRK2) regulates desensitization and downregulation of G protein-coupled receptors, but more recently, it has been shown to interact with an extensive repertoire of proteins. We previously demonstrated that the lack of this protein in the endothelium promotes vascular inflammation and atherosclerosis in mice due to increased mitochondrial reactive oxygen species (ROS).

Aim: To evaluate the role of GRK2 in Aortic Valve Calcification (AVC) by in vivo and in vitro studies.

Methods: To reach our purpose we evaluated GRK2 expression in mitochondria isolated from the valve of patients with calcified (CAVS) aortic valve leaflets vs control ECs. We also performed histological analysis by using 12 months old mice with selective endothelial knock-out of GRK2 (Tie2CRE-GRK2fl/fl) in EC compared to control (GRK2fl/fl) to evaluate the presence of microcalcification in the aortic valve. Finally, we cloned a small sequence of the PH domain of ßARKct into the pcDNA3 to induce GRK2 localization into mitochondria.

Results: In vitro, we observed a significant downregulation of GRK2 expression into the mitochondria of CAVS VECs than control VECs (fig 1), which associates to an increased ROS production. Histological analysis revealed that GRK2fl/fl mice of 12 months-old display presence of microcalcification, as expected (fig. 2). However, this phenotype is significantly more pronounced in the Tie2CRE-GRK2fl/fl (fig. 2), demonstrating that the lack of GRK2 in the EC accelerates the calcific degeneration of the aortic valve in mice. A previous report demonstrated that ßARKct transfection in macrophage increases mitochondrial biogenesis and reduces ROS production. Here, we cloned several small sequences of the PH domain of ßARKct into the pcDNA3.1 plasmid, named as PH#1-4 (fig 3a). We found that the transfection into HEK293 cells of the PH#3 potently increased GRK2 localization into the mitochondria as compared to ßARKct, PH4, and pcDNA3.1 as control (fig 3b). PH3 also determined increased biogenesis (fig 3c) and reduced ROS production after AngII stimulation (Fig 3d). These data support the concept that a smaller portion of the PH domain of ßARKct can reproduce its biological effect

CONCLUSIONS. In conclusion, our data suggest a direct involvement of GRK2 expression/localization in the pathogenesis of CAVS. Intracellular re-localization of GRK2 could be a novel strategy to prevent AVC in a pathophysiological condition such as ageing

URIC ACID STIMULATES CYTOSKELETON PATHWAYS IN VASCULAR SMOOTH MUSCLE CELLS THROUGH F-ACTIN POLYMERIZATION AND ATROGIN, ΑSMA AND SM22 UP REGULATION

Elisa Russo,¹ Daniela Verzola,² Maria Bertolotto,² Valentina Zanetti,² Daniela Picciotto,² Francesca Cappadona,² Pasquale Esposito,² Federico Carbone,² Fabrizio Montecucco,² Francesca Viazzi²

¹ San Luca Hospital, Lucca, Italy; ² Department of Internal Medicine, IRCCS Policlinico San Martino, Genoa, Italy

Introduction: Hyperuricemia (HU) has been identified as a risk factor for hypertension and renal disease. The most widely documented pathogenetic mechanisms for the uric acid (UA) mediated vascular and renal damage are vascular inflammation and remodeling. Vascular smooth muscle cells (VSMCs) possess a distinctive property of plasticity that allows the phenotypic transition and contributes to vascular remodeling.

Aim: to investigate UA effects on VSMC cell line, focusing on phenotypic transition and searching for possible signals involved in this process.

Methods: MOVAS, a mouse VSMC cell line, was exposed for short (0–6 hrs) or long time (24–48 h) to 0 (No Treated cells: NT), 6, 9 and 12 mg/dl of UA, respectively. We evaluated cell viability by MTT test, migration property in a 48-well microchemotaxis chamber (using an 8 μm pore size, polycarbonate polyvinylpyrrolidone-free filters) and by phalloidin staining. Changes in cytoskeleton proteins [moothelin (SMT), alpha-Smooth Muscle Actin (αSMA), Smooth Muscle 22 Alpha (SM 22α)] were detected by real time polymerase chain reaction (rt-PCR) and Western blot. In addition, we evaluated angiotensin receptor 1 (AT1) and atrogin 1 expression by rt-PCR, and Map kinase activation (Erk 1,2) by western blot. Lastly, we tested the UA effects on cellular changes through a prior treatment with angiotensin receptor blockers, Valsartan (V) and Losartan (L) 10 µmol.

Results: A small increment in cell proliferation was observed at 24 h (+11–15%, p < 0.05). UA promoted an increased migratory rate in UA treated VSMCs at 24 and 48 hrs respect to untreated cells (p < 0.001). These results were confirmed by F-actin intracellular distribution: the AlexaFluor 594-conjugate-phalloidin staining revealed a compact polymerization of F-actin in stress fibers along the major cell axis in untreated cells, while a re-arrangement in thinner and poorly oriented fibers localized at cortical level were found in UA treated cells (Figure 1). When we evaluated cytoskeleton components, we found out that 24 hrs UA exposition rose up, SMT (2.5-3.4 fold, p < 0.05), αSMA (1.3-1.5 fold, p < 0.05), and SM 22α levels (1.3-2.5 fold p < 0.05). Conversely, we found a 48 hrs UA treatment caused them to drop (SMT = −20 to 40 %, p < 0.05; αSMA = − 20 to 40 %, p < 0.05; SM 22α = − 30 to 43%, p < 0.05). Atrogin-1 was 2-fold up regulated at 48 hrs in UA treated VMSCs compared to NT (p = 0.04), suggesting a possible role for UA in cytoskeleton remodeling (Figure 2). Furthermore, we observed a significant increase in VSMC area (+30%, p < 0.001) regardless of UA concentration and time exposition. Supposing a key role of Angiotensin involvement in UA induced VSMCs changes, AT1 expression was assessed. We found AT1 was up regulated in UA treated VSMCs compared to NT (p = 0.04). As expected, V and L had inhibitory effects on AT1 upregulation. Moreover, the two angiotensin receptors blockers inhibited all the phenotypic changes induced by UA. Lastly, UA induced a time dependent Erk 1,2 phosphorylation (1.5–2.5 fold vs T0, p < 0.05–0.01), which was reversed by both L and V.

Conclusions: The results of this study show for the first time as UA-induced cytoskeletal changes involve polymerization of F-actin, Atrogin, αSMA and up-regulation of SM22.These results reveal the pathways by which UA induces an increase in VSMC area and in migratory rate, suggesting UA as a key player in vascular remodeling.

Figure 1.

UA triggers F-actin polymerization in MOVAS. UA treatment induced cortical F-actin distribution (magnification 40x).

THE IMPACT OF TRANSCATHETER AORTIC VALVE IMPLANTATION (TAVI) ON THE FUNCTIONAL ADAPTATIONS OF RESISTANCE ARTERIES AFTER THE PROCEDURE AND AT SIX MONTH FOLLOW-UP

Carlo Barsali, Armando Ferrera, Massimo Volpe, Carmine Savoia

Clinical and Molecular Medicine Department, Cardiology Unit, Sant’Andrea Hospital, Sapienza University of Rome, Rome, Italy

Introduction: We showed that early hemodynamic adaptations after TAVI are characterized by vasodilation in resistance arteries.

Aim: To evaluate whether these early adaptations are maintained in mid-term follow-up after TAVI.

Methods: Patients were studied before TAVI (T0), 48 h (T1) and 6 months (T6) later. We completed a six-month follow-up in 7 patients (age 81.9 ± 3.6 years, 14% male, 86% female) out of 30 patients previously studied. Patients had hypertension (100%), diabetes (57%), dyslipidaemia (29%) and were on therapy with: beta-blockers (71%), diuretics (86%), RAS-blockers (86%), calcium-channel blockers (57%), statins (29%), oral hypoglycaemic agents (57%). By applanation tonometry (Sphygmocor) we evaluated: (1) ejection duration (ED); (2) parameters of aortic stiffness: pulse wave velocity (PWV) and pulse pressure (PP); (3) parameters of functional adaptation of peripheral vascular resistance: central (cAI@75%) and peripheral (pAI@75%) Augmentation Index, Reflection Index (RI). By oscillometric device and tonometry we measured Peripheral and central systolic/diastolic blood pressure (BP) respectively. By echocardiography we evaluated aortic size (bulb and ascending aorta), aortic transvalvular gradient (Gmed) and parameters of systolic/diastolic left ventricular function.

RESULTS: Gmed was reduced at T1 vs pre-TAVI (46.6 ± 2.5 mmHg vs 7.3 ± 1.3 mmHg, p < 0,0001), and maintained reduced at T6 (6.5 ± 0.8 mmHg.). ED was reduced at T1 vs T0 (332.3 ± 4.85 mmsec vs 292.8 ± 6.8 msec, p < 0,0001), and significantly increased at T6 (T6:341.5 ± 12.5 mmsec vs T1:292.8 ± 6.8 mmsec, p < 0.0001) to a similar extend as in T0. At T1 the following parameters were reduced as compared to T0: cAI@75 (33.9 ± 1.5%, vs 25.8 ± 1.7%, p < 0.005), pAI@75 (− 0.6 ± 1.7% vs – 13.8 ± 3.4%, p < 0.05), RI (81.6 ± 2.9% vs 68.2 ± 3.2%, p < 0.005). At T6 these parameters increased to values similar to T0, suggesting that the early vasodilatory adaptations in resistance arteries were not maintained after six months.

Conclusions: These findings suggest that after TAVI early vasodialtion may occur in resistance arteries. However this adaptation is not maintained after 6-months, suggesting that it is time dependent and might be influenced by variations of the hemodynamic load.

PI3K REGULATES THE CROSS TALK OF CD8 T CELL AND THE VASCULATURE IN HYPERTENSION

Marialuisa Perrotta^1,2, Sara Perrotta¹, Fabio Pallante², Lorenzo Carnevale², Agnese Migliaccio², Stefania Fardella², Giuseppe Lembo ^1,2 and Daniela Carnevale^1,2

¹ Department of Molecular Medicine “Sapienza” University of Rome, Rome, Italy; ² Department of Angiocardioneurology and Translational Medicine “IRCCS Neuromed”, Italy

Introduction: CD8 effector T cells colonize target organs of hypertension. Phosphatidylinositol 3 kinase gamma (PI3K is a lipid kinase mainly distributed in immune and cardiovascular systems. It regulates many cellular functions, of whom the differentiation of CD8 in effector cells is of particular interest in hypertension, since we have previously described a crucial role of PI3K in blood pressure regulation.

Aim: Aim of this work is to identify, the signaling pathways involved in the acquisition of effectors functions that is still unknown.

Methods: Here, by taking advantage of a knock in mouse model expressing a constitutively active PI3K isoform (PI3K CX/CX), we tested the hypothesis that PI3K regulates CD8 T cell trafficking in hypertension.

Results: First, we found that PI3K CX/CX mice were spontaneously hypertensive and displayed a significant infiltration of activated CD8 in perivascular spaces of kidneys. Further demonstrating a critical role of PI3K in adaptive immunity, the crossbreeding of PI3K mice on a genetic background null for lymphocytes (RAG 1 KO) brought back BP to normal levels. To test the direct role of PI3K CX/CX CD8, we purified this subset of T cells from PI3K spleens and performed an adoptive transfer in WT mice The recipient mice increased BP and accumulated activated CD8 in kidneys. To test the interaction of these cells with the vasculature, we co-cultured CD8 PI3K with pressurized resistance arteries from WT mice for 3 days, finding that the activated immune cells significantly increased myogenic tone (an important regulator of BP).

Conclusions: Taken together these data show that PI3K signaling in CD8 T cells is crucial for priming of immune response in hypertension. These results also suggest that PI3K inhibitors could be beneficial in modulating the immune response involved in hypertension.

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CAROTID ELASTICITY IS IMPAIRED IN STAGE 1 HYPERTENSIVE PATIENTS EVEN IF WITH WELL-CONTROLLED BLOOD PRESSURE

Francesca Saladini,^1-2 Marcello Rattazzi,^2-3 Elisabetta Faggin, ² Paolo Palatini, ² Massimo Puato⁴

¹ Cardiology Unit, Cittadella Town Hospital, Cittadella, Padua, Italy; ² Department of Medicine, University of Padua, Padua, Italy; ³ Medicine I^, Ca’ Foncello Hospital, Treviso, Italy; ⁴ Medicina, Mirano Town Hospital, Mirano, Venezia, Italy

Introduction: Whether impaired arterial elasticity in stage 1 hypertension can be brought back to normal by antihypertensive treatment is unknown.

Aim: To evaluate the impact of long-term well-controlled blood pressure (BP) on carotid artery elasticity and endothelial function in stage 1 hypertensive patients.

Methods: We studied 40 hypertensives (mean age 49.7 years) with BP at target by pharmacological treatment and/or lifestyle modifications for a mean of 7.5 years. Carotid compliance coefficient (CC) and distensibility coefficient (DC) were measured by B-mode ultrasound system. Endothelial function was evaluated by post-occlusion flow mediated dilation (FMD). 40 normotensives, matched for age and sex, served as controls.

Results: In hypertensive subjects, BP was well controlled throughout period (mean office BP 133.7 ± 9.0/81.2 ± 7.0 mmHg; mean 24hours BP 124.2 ± 10***.4/78.2 ± 7.5 mmHg). Compared to controls, significantly higher office BP levels and waist circumference were present. Compared to normotensives, carotid elasticity (DC 24.5 ± 9.0 vs 37.0 ± 8.5 10-3/kPa, and CC 0.92 ± 0.34 vs 1.28 ± 0.36 mm2/kPa, p < 0.0005 for both) and endothelial function (FMD 5.7 ± 2.4% vs 9.2 ± 2.9%, p < 0.0005) were significantly impaired in hypertensives. Among inflammatory markers, hs-CRP and OPG were higher in hypertensives than in normotensives (1.41 ± 1.07 vs 0.97 ± 0.65 mg/L, p = 0.030; 1246 ± 560 vs 936 ± 148 pg/ml p = 0.001). In a logistic regression, hypertensive status was a significant predictor of local carotid vascular stiffness, odds ratio of 14.98 (95%CI, 2.60-18.55) p < 0.0005 for crude data; when data were adjusted for age, FMD, OPG, and BMI, the odds ratio only slightly decreased (13.04 (2.27-74.96), p = 0.004). Hypertensive status remained a significant predictor also after the adjustment for systolic and diastolic BP or mean BP.

Conclusions: Hypertensive patients with long term well-controlled BP according to current standards, exhibited increased local arterial stiffness, endothelial dysfunction and increased markers of inflammation. Whether an earlier and more aggressive intervention could be useful to reduce arterial stiffening and improve endothelial function in hypertension should be explored.

OBESITY-RELATED MICROVASCULAR DYSFUNCTION BEGINS AT EARLY AGE AND IS ASSOCIATED WITH REDUCED NITRIC OXIDE AVAILABILITY

Silvia Armenia¹, Alessandro Mengozzi^1,2, Emiliano Duranti¹, Stefano Masi¹, Agostino Virdis¹

¹ Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Pisa, Italia; ² Istituto di Scienze della Vita, Scuola Superiore Sant'Anna, Pisa, Italia

Introduction: Obesity-related microvascular dysfunction plays a key role in defining the individual cardiovascular risk profile, being the first step of the transition from a healthy to a cardiometabolic impaired phenotype.

Aim: To explore whether, and to what extent, obesity-related microvascular damage is present in early life, and which are the main pathophysiologic mechanisms involved.

Methods: Fifteen patients undergoing elective surgery referring to our Hospital Paediatric Surgery Unit were enrolled. Visceral fat biopsies were collected during the surgical procedure and small vessels were extracted and mounted in a pressurized myograph. Endothelium-dependent relaxation was assessed by acetylcholine (Ach). This was repeated after the addiction of L-NAME to assess nitric oxide (NO) bioavailability. In a subpopulation (n = 3) overnight incubation with RVX-208, a strong epigenetic modulator of vascular inflammation, was performed.

Results: The study population was 10 [4; 18] years old; people were healthy except that for their weight status. Ach response and BMI percentiles showed a negative correlation (St.β -0.515; p = 0.049). Subjects were stratified for CDC growth chart percentiles and divided in two groups, respectively controls (≥ 5th percentile and < 85th percentile) and overweight/obese (O/O; ≥ 85th percentile). Age did not differ between the two groups. Controls (n = 9) median percentile was 62.3 [39.2; 81.3] while O/O (n = 6) was 98.6 [97.7; 99.0]. Controls’ response to Ach was greater (95 ± 0.1% vs 82.4 ± 0.1%); after the addition of L-NAME, both groups showed superimposable vasodilation (Figure). After incubation with RVX-208, a +17% improvement in relaxing response to Ach was observed.

Conclusions: Microvascular dysfunction related to obesity is already present at an early age. It is strongly related to NO availability with vascular inflammation also playing a major role. Our findings support the importance of very early lifestyle intervention to prevent the onset of a cardiometabolic damaged phenotype, ultimately reducing the cardiovascular risk. Further studies are needed to completely unravel the putative mechanisms of this impairment.

Figure. Vasodilatory response to acetylcholine and inhibition of L-NAME in a cohort of very young healthy or overweight/obese (O/O) subjects.

RESTING HEART RATE AND ARTERIAL STIFFNESS: A LONGITUDINAL PROSPECTIVE STUDY IN A POPULATION OF HYPERTENSIVE PATIENTS

Alessandro Maloberti, Stefano Fumagalli, Ilaria Garofani, Ghidini Simone, Ruzzenenti Giacomo, Michele Bombelli, Cristina Giannattasio

Cardiologia 4, ospedale Niguarda, Milano, Italia; Scuola di medicina e chirurgia, Università Milano-Bicocca, Milano, Italia; Medicina Interna, Ospedale di Desio, Desio, Italia

Introduction: The role of resting Heart Rate on the progression of arterial stiffness has not yet been extensively evaluated.

Aim: to investigate the relationship between resting HR and baseline arterial stiffness (evaluated by cfPWV) as well as its progression in a population of hypertensive patients over a 3.7 years follow-up period.

Methods: We enrolled 572 hypertensive outpatients 18–80 aged, followed by the Hypertension Unit of St. Gerardo Hospital (Monza, Italy). Anamnestic, clinical and laboratory data, BP and cfPWV (complior) were assessed at baseline and after a median follow-up time of 3.7 ± 0.5 years

Results: At baseline the mean age was 53.9 ± 12.7 years, SBP and DBP were 141.2 ± 17.8 and 86.5 ± 10.5 mmHg, HR was 65.6 ± 10.9 bpm and PWV was 8.6 ± 2.0 m/s. Despite an improvement in BP values (from 141.2/86.5 to 132.6/79.2 mmHg, p < 0.001), during follow-up, PWV increased (ΔPWV 0.5 ± 2.2 m/s). In patients with a ΔHR above as compared to those under the median value (9 bpm), ΔPWV was significantly higher (0.82 ± 2.22 vs. 0.27 ± 2.25 m/s, p = 0.003). At multivariate analysis, HR was among the significant determinants of both baseline PWV and its progression (β = 0.031, p < 0.001). Furthermore, ΔHR was a significant determinant of ΔPWV (β = 0.019; p = 0.017).

Conclusions: In hypertensive patients there is a significant relationship between basal resting HR and basal PWV as well as between the increase of HR and the increase of PWV during the follow-up period. Beyond age and BP, resting HR must be considered as an independent determinant of arterial stiffness. This represents a possible mechanism through which HR contributes to the increase in CV risk.

CONSISTENT SMOKING AND DEVELOPMENT OF ARTERIAL STIFFENING IN ADULT MEN: RESULTS OF AN EIGHT-YEAR FOLLOW-UP STUDY – THE OLIVETI HEART STUDY

Anita Vergatti, Lanfranco D’Elia, Maria Masulli, Alfonso Giaquinto, Ilaria L. Pizzulo, Antonella Fiore, Veronica Abate, Domenico Rendina, Pasquale Strazzullo, Ferruccio Galletti

Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy

Introduction: Cigarette smoking is a major modifiable risk factor for cardiovascular disease. Several studies evaluated the association between chronic smoking habit and vascular damage, but with not univocal results.

Aim: To estimate the role of chronic cigarette smoking on the incidence of arterial stiffening (pulse pressure > 60 mmHg) (AS) in an 8-year follow-up of a sample of adult men (The Olivetti Heart Study).

Methods: The analysis included 427 men that did not change their cigarette smoking habit during follow-up, without AS at baseline and antihypertensive treatment both at baseline and at follow-up.

Results: After 8-year-follow-up, there was an incidence of 7.3% in AS. According to the smoking habit, the sample was stratified by two groups, one including never smokers and other one with smokers at baseline and at follow-up visit. The percentage of participants that developed AS was significantly greater in the smoker group in comparison with never smokers (10.5% vs 5.1%). The direct association between smoke and development of AS over time was confirmed also after adjustment for confounders. Furthermore, separate analyses on smokers showed that the number of cigarettes smoked per day was not associated with risk of AS, while a direct and significant trend was detected for duration of smoking (p < 0.05).

Conclusions: The results of this prospective study indicate a predictive role of chronic and consistent cigarette smoking on AS, independently of main potential confounders. Moreover, the effect of smoking seems be more related to duration of smoking than the number of cigarettes smoked.

ASCENDING AORTA PROFILE CHANGES IN RELATION TO TYPE OF NORMALIZATION FOR BODY SIZE IN HYPERTENSIVE PATIENT: THE CAMPANIA SALUTE NETWORK

Costantino Mancusi, Maria Virginia Manzi, Ilaria Fucile, Maria Lembo, Christian Basile, Carmine Morisco, Giovanni de Simone, Nicola De Luca, Raffaele Izzo

Introduction: In hypertensive patients dilatation of the sinus of Valsalva (SoV) is associated with increased cardiovascular risk but less is known about the remodeling of ascending aorta (AscAo).

Methods: 1634 hypertensive patients > 18 years old with available data on AscAo were included. AscAo was measured at end-diastole with leading edge to leading edge method. Pearson correlation analysis was used to asses main correlates of AscAo and AscAo indexed for body surface area (AscAo/BSA) and height (AscAo/HT). Multivariable regression models were built to assess possible determinants of AscAo, AscAo/BSA and AscAo/HT.

Results: AscAo measured 33 ± 4.3 mm, AscAo/BSA was 17.6 ± 2.7 mm/m² and AscAo/HT 19.7 ± 2.6 mm/m. Correlation with age, eGFR, systolic BP and HR were similar in the 3 aortic measurements. Male gender was associated with grater AscAo and smaller AscAo/BSA and AscAo/HT. Obesity was associate grater aortic dimension using AscAo and AscAo/HT while was associated with lower AscAo/BSA. Diabetes and triglycerides level were associated with greater AscAo and AscAo/HT, not with AscAo/BSA. In multivariable regression, both AscAo and AscAo/HT were independently associated with older age, lower systolic BP and higher diastolic BP, lower heart rate and presence of obesity; AscAo/BSA was greater in women and smaller with obesity (Table).

Conclusions: Our study demonstrated that age and sex influence AscAo dimension but the correlation of sex varies differently according to the normalization for BSA or HT. Diabetes, obesity and triglycerides level are associated with increased AscAo and AscAo/HT as expected but using indexation of BSA lead to an unexpected inverse correlation.

Table.

Multivariable regression model for main determinats of AscAo (panel A), AscAo/BSA (panel B) and AscAo/HT (panel C)

Panel A
Dependent Variable AscAo	Standardized Coefficients	p	95,0% Confidence Interval for B
	Beta		Lower Bound	Upper Bound
Age (years)	0.432	0.0001	0.121	0.151
Sex (Men/Women)	− 0.272	0.0001	− 2.626	− 1.891
Systolic BP (mmHg)	− 0.095	0.001	− 0.030	− 0.008
Diastolic BP (mmHg)	0.239	0.0001	0.061	0.101
Heart rate (beats/min)	− 0.085	0.0001	− 0.045	− 0.014
Obesity (n/y)	0.093	0.0001	0.450	1.243
Triglycerides (mg/dl)	0.001	0.756	− 0.002	0.003

Panel B
Dependent Variable: AscAo/BSA	Standardized Coefficients	p	95,0% Confidence Interval for B
	Beta		Lower Bound	Beta
Age (years)	0.474	0.0001	.086	.105
Sex (Men/Women)	0.171	0.0001	.681	1.133
Systolic BP (mmHg)	− 0.046	0.097	− .013	.001
Diastolic BP (mmHg)	0.157	0.0001	.022	.046
Heart rate (beats/min)	− 0.052	0.016	− .021	− .002
Obesity (n/y)	− 0.242	0.0001	− 1.642	− 1.159
Triglycerides (mg/dl)	− 0.019	0.389	− .002	.001

Panel C
Dependent Variable: AscAo/HT	Standardized Coefficients	p	95,0% Confidence Interval for B
	Beta		Lower Bound	Beta
Age (years)	0.516	0.0001	.090	.108
Sex (Men/Women)	0.002	0.912	− .210	.235
Systolic BP (mmHg)	− 0.083	0.004	− .017	− .003
Diastolic BP (mmHg)	0.219	0.0001	.033	.057
Heart rate (beats/min)	− 0.064	0.005	− .023	− .004
Obesity (n/y)	0.094	0.0001	.277	.754
Triglycerides (mg/dl)	0.013	0.551	− .001	.002

RELATIONSHIP BETWEEN AORTIC AND CAROTID STIFFNESS WITH MEASURES OF ADIPOSITY IN ADOLESCENTS. THE MACISTE STUDY

Rosa Curcio^1,2, Mariella Martina³, Elisabetta Bianchini³, Marco D’Abbondanza^1,2, Francesca Battista⁴, Fabio Anastasio⁵, Leandro Sanesi², Gaetano Vaudo^1,2, Giacomo Pucci^1,2

¹ Dipartimento di Medicina e Chirurgia, Università di Perugia, Perugia; ² Struttura Complessa di Medicina Interna, Azienda Ospedaliera “Santa Maria”, Terni; ³ Istituto di Fisiologia Clinica, Centro Nazionale delle Ricerche, Pisa; ⁴ Divisione di Medicina dello Sport e dell’Esercizio Fisico, Dipartimento di Medicina, Università di Padova, Padova; ⁵ Divisione di Cardiologia, Ospedale “Regina Montis Regalis”, Mondovì, Cuneo

Introduction: In the present study, we aimed at evaluating the differential association between arterial stiffness, taken at different arterial segments (aortic and carotid), with measures of adiposity, accounting for the effect of BP as a mediator of the relationship between fat accumulation and increased arterial stiffness.

Methods: 322 healthy Italian adolescents attending the Liceo Donatelli High school, Terni, taking part to the MACISTE Study (Metabolic and Cardiovascular Investigation at School, TErni), were evaluated. BMI, waist, hip and neck circumferences, and their ratio (waist-to-hip) were taken as measures of adiposity. Laboratory parameters related to adiposity were also collected. Arterial stiffness was measured at the aortic level through carotid-femoral pulse wave velocity (applanation tonometry, SphygmoCor), and at the carotid level (Cardiovascular suite, Quipu).

Results: 322 participants (mean age 17 ± 1.4 years, 56% boys) had complete data. 40 (12%) were overweight. All central and peripheral measures of BP were higher in overweight vs normal-weight (all p < 0.01), excluding peripheral and central DBPs, which were lower in overweight, and brachial PP, which was similar between groups. The aortic-to-brachial pulse pressure amplification was reduced in overweight vs normal-weight (1.51 ± 0.13 vs 1.58 ± 0.13, p < 0.01). Carotid and aortic stiffness were positively correlated with anthropometric and laboratory measures of adiposity. After adjustment for mean arterial pressure, only neck circumference remained associated with carotid (β = 0.24, p < 0.01) and aortic stiffness (β = 0.16, p = 0.02). After adjustment for central PP, only carotid stiffness (β = 0.15, p = 0.04), but not aortic stiffness (β = 0.12, p = 0.07) was associated with neck circumference.

Conclusions: Arterial stiffness, when assessed at different levels of central arteries, showed site-specific associations with measures of body fat adiposity. Neck circumference was the only measure of adiposity to show a BP-independent association with carotid stiffness. Carotid stiffness is a promising marker of pressure-independent vascular damage promoted by overweight status.

THE ARTERY-VEIN RATIO BY RETINOGRAPHY MAY PRECEED THE FUNCTIONAL AND STRUCTURAL DAMAGE IN THE LARGER ARTERY DISTRICTS

Pietro Nazzaro, Gianfranco Amodio, Adele Nardecchia, Maura Buttiglione, Gabriella Schirosi, Maria Contini, Lorenzo Debenedittis, Gabriella Aceto, Simona Di Bari, Anna De Cataldo, Francesca Zotti, Girolamo Zangara

Dip. Scienze Biomediche e Oncologia Umana, U.O.S.D. di Ipertensione Arteriosa “AM. Pirrelli”, Università di Bari “Aldo Moro”, Bari, Italy

Introduction: The hypertension research was always dedicated to distinguish early and predictive markers of hypertensive disease and related organ damage. Among these, the funduscopy, reliable to highlight the later and severe injuries.

Aim: To highlight if the technique might offer through a further index, the artery-vein ratio (AVR), an employable marker since the early stages of the disease.

Methods: In order of artery stiffness, by pulse wave velocity (PWVcf), (carotid-femoral tonometry), a cohort of adult hypertensives, treated with ACEi or ARB as monotherapy, with similar age, metabolic assessment and history of hypertension, were grouped in 42 with normal compliance (PWV-N), 33 with normal-high (PWV-NH) and 32 with values of high stiffness (PWV-H). Central SBP (SBPcar) and ankle-brachial index (ABI) were also taken. Then, patients, underwent ABPM to recognize the individual SBP/DBP during awake hours (d) and sleep (n), related BP fall during sleep (dipping %), cognitive state (COGN) by an 18-multiple choice questionnaire and amydriatic funduscopy.

Results: Patients showed similar smoke habit (12.6 ± 10.8 vs 11.1 ± 11.7 vs 10.6 ± 10.9) and BMI (29.5 ± 4.8 vs 30.3 ± 4.8 vs 28.9 ± 4.9) but further significant findings. (m ± s.d.: *:p < .05,**:p < .01, ***:p < .001 vs PWV-N; ^:p < .05, ^^:p < .01,^^^:p < .001 vs PWV-NH ).

pts/var	SBPoff	DBPoff	SBP/DBPd	SBP/DBPn	dipping%
PWV-N	132 ± 15	79 ± 10	130 ± 6/83 ± 7	117 ± 10/74 ± 12	10.1 ± 7.6
PWV-NH	135 ± 15	80 ± 11	132 ± 9/80 ± 9	116 ± 8/75 ± 10	11.8 ± 6.2
PWV-H	136 ± 13	79 ± 11	133 ± 11/81 ± 9	118 ± 13/73 ± 8	10.7 ± 12.7
	ABI	SBPcar	PWVcf	AVR	COGN
PWV-N	0.95 ± 0.05	116 ± 13	8.6 ± 0.8	0.85 ± 0.04	24.5 ± 5.6
PWV-NH	0.93 ± 0.05	121 ± 15	9.8 ± 0.2***	0.81 ± 0.04**	26.8 ± 6.3*
PWV-H	0.89 ± 0.03***^^^	123 ± 14*	11.8 ± 0.9***^^^	0.72 ± 0.06***^^^	28.5 ± 5.6***

Partial Pearson analysis showed a significant association between AVR and both PWVcf (−.615***) and COGN (−.242**).

Conclusions: The findings show that, by a different approach of funduscopy, the small artery impairment may occur before that functional and structural damages of larger caliber arteries arise and that this measure may be associated, since the early phases, to cognitive decline.

THE ROLE OF SORTILIN IN WARFARIN-INDUCED VASCULAR CALCIFICATION

Paola Di Pietro,¹ Paola Iesu,¹ Maria Rosaria Rusciano,¹ Valeria Visco,¹ Augusto Di Castelnuovo,² Licia Iacoviello,³ Angela Abate,¹ Carmine Izzo,¹ Michele Ciccarelli,¹ Albino Carrizzo,^1,3 Carmine Vecchione^1,3

¹Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy; ²Mediterranea Cardiocentro, Napoli, Italy; ³Vascular Physiopathology Unit, I.R.C.C.S. Neuromed Mediterranean Neurological Institute, Pozzilli, Italy

Warfarin, a vitamin K antagonist (VKA), is known to accelerate vascular calcification (VC) both in rodents and in humans. Increasing evidence suggests that vascular endothelium contributes to vascular calcification via endothelial-mesenchymal transition. However, additional research is warranted to elucidate the signaling mechanisms involved. In the last decade, a prominent role for sortilin has been demonstrated in VC. Moreover, we previously demonstrated that the increase of sortilin in the endothelium promotes endothelial dysfunction.

Thus, we aim to investigate a potential contribution of sortilin in vascular calcification induced by warfarin. For this purpose, endothelial cells and aortic rings from wild type C57BL/6J mice were cultured in promineralization medium in the presence of therapeutic levels of warfarin. Plasma sortilin levels were measured in 19 patients under VKA therapy who were stratified into short-term (3-12 months) or long-term group (24–45 months) based on VKA treatment duration.

Warfarin treatment increased calcium levels in human endothelial cells, a process prevented by the sortilin inhibitor AF38469. In ex vivo cultures, warfarin treatment induced a significant loss of the endothelial marker von Willebrand Factor (vWF), and increased protein expression of sortilin both in the endothelial and in the medial smooth muscle layers of aortic rings. Interestingly, sortilin immunostaining was found to co-localize with α-SMA in the endothelium of warfarin-treated aortic rings, a hallmark of endothelial-to-mesenchymal transition. Along with elevated plasma calcium levels, patients receiving long-term VKA showed increased circulating sortilin levels when compared to short term VKA-treated patients.

Our data suggest a potential role for endothelial-derived sortilin in regulating vascular calcification induced by warfarin.

SORTILIN INDUCES ARTERIAL HYPERTENSION THROUGH SPHINGOSINE 1-PHOSPHATE SIGNALLING-MEDIATED VASCULAR OXIDATIVE STRESS

Paola Di Pietro,¹ Eduardo Sommella,² Augusto Di Castelnuovo,³ Licia Iacoviello,⁴ Fabrizio Merciai,² Paola Iesu,¹ Michele Ciccarelli,¹ Albino Carrizzo,^1,4 Carmine Vecchione^1,4

¹Department of Medicine, Surgery and Dentistry, University of Salerno, Baronissi, Italy; ²Department of Pharmacy, School of Pharmacy, University of Salerno, Fisciano, Italy; ³Mediterranea Cardiocentro, Napoli, Italy; ⁴Vascular Physiopathology Unit, I.R.C.C.S. Neuromed Mediterranean Neurological Institute, Pozzilli, Italy

Introduction: Sortilin, a member of vacuolar protein sorting domain family Vps10, has been positively correlated with vascular disorders in humans. However, no study has yet evaluated the direct vascular effect of sortilin.

Aim: to investigate the role of sortilin in the modulation of vascular function and blood pressure. Vascular reactivity of mesenteric arteries was assessed by using pressure myography.

Methods: To mimic an in vivo condition of sustained high circulating sortilin levels, osmotic pumps were subcutaneously implanted into WT, sphingosine-1-phosphate receptor 3 (S1P3) and NADPH oxidase 2 (gp91phox/NOX2) knockout mice for the continuous release of sortilin for 14 days. Blood pressure was determined in conscious mice by radiotelemetry. Sortilin, acid sphingomyelinase (ASMase) activity and NOX2 soluble derived peptide were quantified in plasma of hypertensive and normotensive individuals from two prospective Italian studies, The Campania Salute Network Study and the Moli-Sani Study.

Results: Sortilin evoked endothelial dysfunction and ROS overproduction through NOX2 activation, dysfunction that was prevented by knockdown of ASMase or sphingosine kinase 1 (SphK1). These effects were also abolished by gene silencing of the S1P3 receptor. In vivo, administration of recombinant sortilin increased arterial blood pressure in WT mice, an effect that was completely counteracted by S1P3 or gp91phox deficiency. Plasma levels of sortilin, ASMase activity, S1P and soluble NOX2 derived peptide were higher in hypertensive than normotensive subjects, but even higher in uncontrolled hypertensive ones. Finally, we found positive correlations between plasma levels of sortilin and S1P, and the latter with soluble NOX2 derived peptide in hypertensive patients.

Conclusions: Our results have unmasked a novel molecular mechanism underpinning the role of sortilin in sphingolipid dysregulation, oxidative stress and endothelial dysfunction in the pathophysiology of hypertension. Moreover, these results may add new clinical perspectives aiming at improving the ability to predict and monitor the progression of hypertension.

ASSOCIATION BETWEEN RETINAL MICROCIRCULATION AND INCIDENCE OF CARDIOVASCULAR AND TOTAL EVENTS IN A POPULATION OF HYPERTENSIVE AND NORMOTENSIVE PATIENTS

Paolo Malerba¹, Claudia Agabiti Rosei¹, Carolina De Ciuceis¹, Claudia Rossini¹, Giulia Chiarini¹, Andrea Gaggero¹, Matteo Nardin², Francesca Famà¹, Enzo Porteri¹, Enrico Agabiti Rosei¹, Maria Lorenza Muiesan¹, Damiano Rizzoni^1,3

¹ Department of Clinical and Experimental Sciences, University of Brescia; ² Terza Medicina, ASST Spedali Civili of Brescia; ³ Medicina Generale, ASST Spedali Civili di Brescia P.O. Montichiari (BS)

Introdutcion: The media-to-lumen ratio (MLR) of small subcutaneous arteries is an independent prognostic indicator of fatal and non-fatal cardiovascular events, particularly in the high cardiovascular (CV) risk population. Adaptive optics (AO) represents to date one of the most innovative and non-invasive methods for studying the wall-to-lumen ratio of retinal arterioles (WLR), which directly correlates with the MLR of subcutaneous small arteries.

Aim: we evaluated the WLR in a population of hypertensive and normotensive subjects and its association with the occurrence of cardiovascular and/or total events.

Methods: A total of 245 subjects, 90 normotensive and 155 hypertensive, with a mean age of 59 ± 16 years, who underwent assessment of retinal microcirculation morphology with OA (RTX-1, Imagine Eyes; Orsay, FR) between 2015 and 2017 were included in this study. The occurrence of cardiovascular events (atrial fibrillation, heart failure, stroke and ischemic heart disease) and total (CV disease, cancer or other) was assessed. The average follow-up period was 5 ± 2 years.

Results: In these 245 subjects we observed 49 events, 25 of which were cardiovascular events; there were furthermore 14 deaths from non-CV causes. Subjects were divided into increasing tertiles of WLR; using the chi-square test a statistically significant difference in the distribution of CV events was observed between the 2nd (n.82, WLR 0.27-0.32) and the 1st tertile (n.81,WLR <0.27,p = 0.02) and between the 3rd (n.82, WLR 0.32-0.54) and 1st tertile (p = 0.05).

Conclusions: A WLR value above 0.27 is associated with a significant increase of incidence of cardiovascular events in a population of hypertensive and normotensive subjects. WLR assessment through adaptive optics could be useful for a better cardiovascular risk stratification and potentially for a more accurate evaluation of the effects of antihypertensive therapy. Further studies in a larger population are needed in order to confirm these data.