Abstract
Ambulatory blood pressure (BP) and central systolic BP (cSBP) are superior to brachial office BP measurements in predicting cardiovascular end organ damage. The authors aimed to analyze the effect of olmesartan 80 mg (OLM 80) vs 20 mg (OLM 20) vs amlodipine 5 mg (AML 5) on central hemodymamics and ambulatory BP in patients with metabolic syndrome (MetS).In a double‐blind, three‐phase crossover study comprising 69 untreated patients with MetS defined by the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults guidelines, the effects of OLM 80 on central hemodynamics (cSBP), central pulse pressure), pulse wave velocity (PWV), and 24‐hour ambulatory BP were compared with OLM 20 and AML 5, given for 6 weeks each. In 69 patients (47 men, 22 women) (51.5±9.75 years), reduction in cSBP was the highest with OLM 80 and significantly greater than the reduction with AML 5 (−14.1 mm Hg vs −9.7 mm Hg, P=.0117). All three substances significantly reduced 24‐hour ambulatory systolic (OLM 80 and OLM 20 P<.0001; AML 5 P=.0105). BP and 24‐hour diastolic BP (OLM 80 and OLM 20 P<.0001; AML 5 P=.0126). PWV was significantly reduced by OLM 80 (−0.58 m/s, P=.0088) and by OLM 20 (−0.48 m/s, P=.0362) but not by AML 5 (−0.28 m/s, P=.2065). For PWV, no significant differences were detected between the three groups. OLM significantly improves arterial stiffness as demonstrated by the reduction in PWV and in cSBP. In addition, 24‐hour ambulatory BP was reduced to a greater extent with OLM 80 than with AML 5.
The metabolic syndrome (MetS) is a cluster of adverse metabolic parameters with an increasing prevalence in the Western world. Based on data from the National Cholesterol Educational Program (NCEP), an estimated 34% of men and 35% of women are affected by MetS in the United States. In Europe, about 20% to 25% of the population have MetS. Several studies clearly demonstrate that patients with MetS are at increased risk for cardiovascular mortality and morbidity.1, 2 Data from the Hoorn study shows that MetS—independent of the definition applied—is associated with a two‐fold increase of cardiovascular morbidity and mortality.1
If arterial hypertension coexists with adverse metabolic patterns of the MetS, such as abdominal obesity, hyperlipidemia, and insulin resistance, both conditions exaggerate the detrimental effects on the vasculature by altered hemodynamic and biochemical processes, consecutively resulting in severe cardiovascular end organ damage. Thus, strict control of both blood pressure (BP) and metabolic parameters is essential in preventing or reducing cardiovascular risk in patients with MetS. In the face of the evidence that different antihypertensive classes have been demonstrated to act differently on the vasculature, finding a therapeutic approach that not only reduces high BP but simultaneously exerts beneficial effects on the vasculature might be seminal in patients with MetS.
Several experimental and clinical studies have reported beneficial effects of the angiotensin receptor blockers (ARBs) such as olmesartan (OLM) on vascular pathologies.3, 4, 5 Similarly, in the Conduit Artery Functional Endpoint (CAFE) study, the calcium channel blocker amlodipine (AML) was shown to be superior to the β‐blocker atenolol in reducing central systolic BP (cSBP) despite comparable impact on brachial BP.6
In this study we aimed to investigate the effect of OLM 80 mg—a dose above the approved maximum daily dose—compared with OLM 20 mg and the calcium channel blocker AML 5 mg on arterial stiffening determined by pulse wavy velocity (PWV) and on 24‐hour ambulatory BP or brachial and central BP.
The OLM dose of 80 mg was chosen since BP‐independent beneficial effects have been observed above the maximum BP dose and because the observation that very high doses of ARBs, such as OLM, are not related to higher incidence of side effects, ie, there is no dose dependency of side effects with ARBs.
Methods
Study Population
Sixty‐nine patients were enrolled in the study in our clinical research center in Erlangen‐Nürnberg (www.crc-erlangen.de). All patients had MetS according to the classification of the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) panel of the NCEP.7 Men and women aged 18 years or older were included if they met the following key inclusion criteria: systolic/diastolic BP ≥130/85 mm Hg or pretreated for primary arterial hypertension plus two additional metabolic parameters according to the ATP III panel: waist circumference >102 cm in men or >88 cm in women, triglycerides ≥150 mg/dL, high‐density lipoprotein <40 mg/dL in men or <50 mg/dL in women, fasting blood glucose ≥100 mg/dL, or pretreated type 2 diabetes mellitus.
Main exclusion criteria were insulin‐dependent diabetes mellitus, systolic BP ≥180 mm Hg and/or diastolic BP ≥110 mm Hg, or any secondary form of arterial hypertension. In addition, patients were excluded if they had a history or any present clinical sign of cardiovascular or cerebrovascular disease, estimated glomerular filtration rate (by Modified Diet in Renal Disease equation) <60 mL/min/1.73 m2, hepatic or hematologic disease, acute or chronic inflammatory disease, malignant disease, intake of lipid‐lowering drugs starting within 3 months before inclusion into the study, history of allergy or contraindications to calcium antagonists or ARBs, pregnant or lactating women or women planning to become pregnant, or women not using appropriate birth control.
Before enrollment in the study, written informed consent was obtained from each participant. The study protocol was approved by the ethics committee of the University of Erlangen‐Nürnberg. The study was performed in adherence to the principles of the Declaration of Helsinki and according to good clinical practice standards. This study was registered at www.clinicaltrials.gov (NCT00891267).
Study Design
The study was performed according to a double‐blind, three‐phase crossover design. After inclusion, patients taking direct renin inhibitors, ARBs, or angiotensin‐converting enzyme (ACE) inhibitors entered a 6‐week washout period, and patients taking any other antihypertensive substance entered a 4‐week washout period, respectively. After the washout period and before patients were randomly assigned to the first of the three treatment phases, as well as after completion of each of the three treatment phases, brachial office BP, 24‐hour ambulatory BP, and PWV were measured and pulse wave analysis adopted in each patient. In parallel, inflammatory and safety laboratory measurements were performed. Each of the three treatment phases had a duration of 6 weeks. At the end of each treatment phase, compliance was checked by pill counting, and medication for the following phase was dispensed.
All measurements were performed according to predefined standard operating procedures after an overnight fast and after a 15‐minute rest.
BP Measurements
The brachial office BP was measured noninvasively in a sitting position using the validated DINAMAP Pro 100 V2 device (GE Healthcare, Little Chalfont, United Kingdom) with an appropriately sized cuff. Three measurements were made at intervals of 2 minutes and the means were considered for analysis.
Twenty‐four–hour ambulatory BP was measured by the validated Spacelabs 90207 system (Spacelabs Healthcare, Snoqualmie, WA), with an appropriately sized cuff. BP was recorded every 15 minutes during daytime (7 am–10 pm) and every 30 minutes during nighttime (10 pm–7 am). Conductance of 24‐hour ambulatory BP was not mandatory as to avoid an increased dropout rate caused by intolerance of the measurements, a critical quality aspect in a three‐phase crossover study. Indeed, many study participants refused ambulatory BP measurements, which were therefore performed in only 44% of overall study participants.
Pulse Wave Analysis
The central aortic pressure waveform can be used to determine cSBP, central pulse pressure (PP), and augmentation pressure (AP). The central arterial waveform was derived by using the SphygmoCor system (AtCor Medical, Sydney, Australia). The radial artery waveform was recorded from the radial artery at the wrist using high‐fidelity applanation tonometry (Millar Instruments, Houston, TX). The SphygmoCor system automatically generates the corresponding central (aortic) waveforms from an averaged radial artery waveform. From the central waveform, information on cSBP were derived.
Pulse Wave Velocity
PWV is a direct measure of the arterial stiffness of large arteries. For the determination of aortic PWV, waveforms of the common carotid artery and the femoral artery were obtained again using the SphygmoCor system. PWV was calculated as the distance between the suprasternal notch and the femoral artery recording site, and divided by the time interval between the feet of the pressure waves.
Statistical Analysis
Statistical analysis of this three‐way crossover study was performed using Statistical Analysis Software version 9.2 (SAS Institute Inc, Cary, NC). An analysis of variance model with sequence, treatment, and period as factors and subject nested within sequence as random effect was performed on the changes after 6 weeks of double‐blind treatment. The analysis was performed on the full analysis set applying the last‐observation‐carried‐forward (LOCF) approach within the respective treatment phases. Since there were no missing values in the full analysis set, the results of the LOCF approach were identical to the observed case approach. There was no statistically significant period effect in this crossover trial for all key parameters. The three hypotheses (1) OLM 80 mg vs OLM 20 mg, (2) OLM 80 mg vs AML, and (3) OLM 20 mg vs AML were tested in hierarchical order with significance level α=5%.
Qualitative efficacy variables were analyzed by means of the chi‐square test.
Results
Sixty‐nine patients with MetS were included in the analysis (47 men and 22 women). Mean age was 51.5±9.75 years, mean body mass index was 32.9±4.64, and brachial systolic and diastolic office BPs at baseline without antihypertensive medication was 148.4±10.96 mm Hg and 87.7±9.90 mm Hg, respectively. Baseline characteristics of the study population are demonstrated in Table 1.
Table 1.
Baseline Characteristics of the Study Population (N=69)
| Mean±SD | |
|---|---|
| Age | 5.15±9.75 |
| Male/female | 47/22 |
| Waist, cm | 111.4±10.36 |
| BMI, kg/m2 | 32.9±4.64 |
| Office systolic BP, mm Hg | 148.4±10.96 |
| Office diastolic BP, mm Hg | 87.7±9.90 |
| Triglycerides, mg/dL | 215.7±110.11 |
| HDL, mg/dL | 46.8±9.55 |
| LDL, mg/dL | 156.6±29.63 |
| Fasting blood glucose, mg/dL | 104.1±19.02 |
Abbreviations: BMI, body mass index; BP, blood pressure; HDL high‐density lipoprotein; LDL, low‐density lipoprotein; SD, standard deviation.
The majority of patients in this study took medications prior to the start of the study (84%): 34 patients (49.3%) were taking ACE inhibitors or ARBs at the time of study entry (and before the washout phase), 15 (21.7%) were taking β‐blockers, 8 (11.6%) were taking calcium channel blockers, and 7 (10.1%) were taking diuretics. Furthermore, 7 patients (10.1%) were taking oral antidiabetic agents. The compliance rate to the study medication during the study was 98.9±2.
Office BP
Brachial systolic and diastolic office BPs at baseline and after each treatment phase are shown in Table 2.
Table 2.
Office BP Measurements of the Study Population (N=69) at Baseline and After 6 Weeks of Treatment and Change From Baseline
| OLM 80 mg | OLM 20 mg | AML 5 mg | |
|---|---|---|---|
| At baseline | |||
| Office BP, mm Hg | (n=69) | (n=68) | (n=69) |
| Systolic | 148±11 | 148±11 | 148±11 |
| Diastolic | 88±10 | 88±10 | 88±10 |
| After 6 weeks of treatment | |||
| Office BP, mm Hg | (n=69) | (n=68) | (n=69) |
| Systolic | 131±15a | 134±16a | 136±12a |
| Diastolic | 77±8a | 79±9a | 82±9a |
| Change From Baseline | mm Hg | P Value | mm Hg | P Value | mm Hg | P Value |
|---|---|---|---|---|---|---|
| Office BP, mm Hg | ||||||
| Systolic | −17.2 | <.001 | −14.4 | <.001 | −12.2 | .010 |
| Diastolic | −10.8 | <.001 | −8.3 | <.001 | −5.6 | .012 |
Abbreviations: AML, amlodipine; BP, blood pressure; OLM, olmesartan.
Indicates significant reduction compared with baseline values. P<.05 is considered statistically significant.
All three treatment regimens significantly reduced brachial systolic and diastolic office BPs compared with baseline (Table 2). The reduction of systolic office BP with OLM 80 mg was significantly greater than with AML 5 mg (−17.2 mm Hg vs −12.2 mm Hg, P=.0045) and numerically higher than with OLM 20 mg (−17.2 mm Hg vs −14.2 mm Hg, P=.0883).
The reduction of diastolic office BP with OLM 80 mg was significantly greater compared with the reduction achieved with OLM 20 mg (−10.8 vs −8.3 mm Hg, P=.0237) as well as AML 5 mg (−10.8 vs −5.6 mm Hg, P<.0001). The reduction in diastolic office BP was also greater with OLM 20 mg than with AML 5 mg (−8.3 mm Hg vs −5.6 mm Hg, P=.0120) (Table 2).
Ambulatory BP Measurement
Twenty‐four–hour daytime and nighttime ambulatory BP values of the three groups at baseline and after treatment are shown in Table 3. A total of 31 patients in the OLM 80, 26 in the OLM 20, and 31 in the AML 5 group had complete ambulatory BP data at baseline and after respective treatment.
Table 3.
24‐Hour BP Measurements of the Study Population (N=69) at Baseline and After 6 Weeks of Treatment and Change From Baseline
| OLM 80 mg | OLM 20 mg | AML 5 mg | |
| At baseline | |||
| 24‐hour ABPM, mm Hg | (n=31) | (n=26) | (n=31) |
| Systolic | 138±11 | 139±11 | 139±12 |
| Diastolic | 84±9 | 84±10 | 85±9 |
| Daytime ABPM, mm Hg | |||
| Systolic | 143±12 | 144±13 | 144±13 |
| Diastolic | 87±10 | 88±11 | 88±10 |
| Nighttime ABPM, mm Hg | |||
| Systolic | 129±12 | 129±11 | 128±13 |
| Diastolic | 75±9 | 76±9 | 76±9 |
| After 6 weeks of treatment | |||
| 24‐hour ABPM, mm Hg | (n=31) | (n=26) | (n=31) |
| Systolic | 127±14a | 130±14a | 134±8a |
| Diastolic | 76±9a | 77±9a | 81±7a |
| Daytime ABPM, mm Hg | |||
| Systolic | 131±14a | 135±16a | 138±9a |
| Diastolic | 80±9a | 81±10a | 85±7a |
| Nighttime ABPM, mm Hg | |||
| Systolic | 118±15a | 119±12a | 125±12 |
| Diastolic | 68±9a | 68±8a | 74±9 |
| Change From Baseline | mm Hg | P Value | mm Hg | P Value | mm Hg | P Value |
|---|---|---|---|---|---|---|
| 24‐hour ABPM, mm Hg | ||||||
| Systolic | −11.6 | <.001 | −7.3 | <.001 | −4.0 | .01 |
| Diastolic | −7.8 | <.001 | −5.3 | <.001 | −2.5 | .01 |
| Daytime ABPM, mm Hg | ||||||
| Systolic | −11.9 | <.001 | −7.8 | <.001 | −4.7 | .005 |
| Diastolic | −7.8 | <.001 | −5.6 | <.001 | −3.1 | .006 |
| Nighttime ABPM, mm Hg | ||||||
| Systolic | −11.2 | <.001 | −6.5 | .004 | −3.8 | .054 |
| Diastolic | −7.8 | <.001 | −5.4 | .002 | −1.8 | .132 |
Abbreviations: ABPM, ambulatory blood pressure monitoring; AML, amlodipine; BP, blood pressure; OLM, olmesartan.
Indicates significant reduction compared with baseline values. P<.05 is considered statistically significant.
Twenty‐four–hour Ambulatory BP
Twenty‐four–hour systolic and diastolic BPs were reduced significantly in all three treatment groups as shown in Table 3. The effect of lowering 24‐hour systolic BP with OLM 80 was significantly greater compared with the effect with OLM 20 and AML 5 (Figure 1). The reduction in lowering 24‐hour diastolic BP was significantly greater with OM 80 than with AML 5. Only numerical differences were found between OLM 20 and AML 5.
Figure 1.
Bar chart showing the reduction of 24‐hour systolic blood pressure (BP) and central systolic BP in the three groups (olmesartan 80 mg, olmesartan 20 mg, amlodipine 5 mg). Least‐squares means are given and P<.05 is considered statistically significant.
Daytime BP
Daytime systolic and diastolic BPs were significantly reduced in all three treatment groups (Table 3). OLM 80 was significantly more effective compared with OLM 20 and with AML 5 in reducing daytime systolic BP (Figure 1). Likewise, the decrease in daytime diastolic BP was greater with OM 80 than with AML 5 (P=.0023). There was a numerical difference between OLM 20 compared with AML 5, which did not reach statistical significance.
Nighttime BP
Only OLM 80 and OLM 20 but not AML 5 significantly reduced nighttime systolic and diastolic BPs (Table 3). OLM 80 reduced nighttime systolic as well as diastolic BP (nighttime systolic BP: P=.0082; nighttime diastolic BP: P=.0007) to a greater extent than AML 5.
Central Systolic BP
Median cSBP at baseline was 134 mm Hg. Six‐week treatment with OLM 80 reduced cSBP by −14.0 mm Hg, treatment with OLM 20 reduced cSBP by −12.1 mm Hg, and treatment with AML 5 reduced cSBP by −9.7 mm Hg (all P<.0001 vs baseline) (Figure 2).
Figure 2.
Bar chart showing the reduction of pulse pressure in the three groups (olmesartan 80 mg [OLM 80], olmesartan 20 mg [OLM 20], amlodipine 5 mg [AML 5]) (a). Bar chart showing the reduction of pulse wave velocity in the three groups (olmesartan 80 mg, olmesartan 20 mg, amlodipine 5 mg) (b). Least‐squares means are given and P<.05 is considered statistically significant.
The reduction in cSBP with OLM 80 was significantly greater than with AML 5 (P=.0117). Only numerical differences in the reduction of cSBP were found between OLM 80 and OLM 20 (P=.1490) and between OLM 20 and AML 5 (P=.2796), respectively.
Central PP
Mean central PP (cPP) at baseline was 60.7±12.9 mm Hg. Six‐week treatment with OLM 80 reduced cPP by −6.4 mm Hg, treatment with OLM 20 reduced cPP by −5.9 mm Hg, and treatment with AML 5 reduced cPP by −6.6 mm Hg (P<.0001) (Figure 2). There were no significant differences between the three treatment groups.
Pulse Wave Velocity
PWV at baseline was 8.90±2.147 m/s. OLM 80 (n=63) and OLM 20 (n=61) significantly reduced PWV by −0.58 m/s (P=.0088) and −0.48 m/s (P=.0362), respectively. AML 5 (N=61) did not significantly reduce PWV (−0.28 m/s, P=.2065) compared with baseline. The reduction of PWV with OLM 80 was not significantly greater compared with the one with OLM 20 (−0.58 vs −0.48 m/s, P=.7358) and with AML 5 (−0.58 m/s vs −0.28 m/s, P=.3397) in reducing PWV (Figure 2).
Correlation Analyses of PWV and Mean Arterial Pressure
Absolute values of mean arterial pressure (MAP) were strongly associated with absolute PWV values for the treatment groups OLM 80 and OLM 20 (R=0.338, P=.007 and R=0.238, P=.027, respectively) but not for AML 5 (R=0.176, P=.174). However, the change in PWV throughout the study was not associated with the change in MAP with OLM 80 (R=0.142, P=.267) or OLM 20 (R=0.111, P=.393) and with AML 5 mg (R=0.067, P=.610) (Figure 3).
Figure 3.
Scatter blot showing the association of pulse wave velocity (PWV) with mean arterial pressure (MAP) (upper part). The regression equations are for OLM 80 mg: PWV = 0.0735 + 0.088*MAP; OLM 20: PWV = 1.095 + 0.077*MAP; AML: PWV = 4.448 + 0.042*MAP, and the change of PWV with the change in MAP (lower part) regression equation are for OLM 80: PWV = −0.134 + 0.033*MAP; OLM 20: PWV = −0.205 + 0.018*MAP; and AML: PWV = −0.141 + 0.0151*MAP). OLM 80 indicates olmesartan 80 mg; OLM 20, olmesartan 20 mg; AML, amlodipine.
Neither with OLM 80 (R=0.142, P=.267) or OLM 20 (R=0.111, P=.393) and AML 5 (R=0.067, P=.610) was change in MAP associated with change in PWV.
Safety
Of the patients included in the safety population, 90.4% had at least one treatment‐emergent adverse event (TEAE). Of these, 45.2% were assessed as being a drug‐related TEAE, with a similar pattern and distribution among the OLM and AML treatments for the most common drug‐related TEAEs, which were headache, dizziness, vertigo, and abdominal pain. The second most common drug‐related TEAE (peripheral edema) was seen only in the AML treatment group. Only two patients experienced serious TEAEs, and none were assessed as being drug‐related. No clinically relevant changes over time or differences between treatments in laboratory assessments, vital signs, electrocardiographic findings, or physical examination were observed. All study treatments were generally safe and well tolerated, which corresponds to the known good safety profiles of OLM medoxomil and AML.
Discussion
Inhibition of the RAS with either ACE inhibitors or ARBs has been shown to reduce BP and exert additional nonhemodynamic beneficial effects.8 Results of our study show that in patients with MetS, treatment with OLM significantly reduces PWV, brachial and central BPs, and 24‐hour ambulatory systolic BP, with OLM 80 being significantly greater and OLM 20 numerically better compared with AML 5.
The ARB OLM is characterized by a fast onset of action, prolonged duration with a strong BP‐lowering effect, and good safety and tolerability. Data from our study confirmed that all three regimens, ie, OLM 80, OLM 20, and AML 5 significantly reduced systolic and diastolic brachial office BP as well as 24‐hour and day/night BP compared with baseline. OLM 80 also led to the greatest reduction in cSBP.
In our study, we observed that both daytime systolic BP and cSBP were significantly and comparably reduced by all three treatment strategies (OLM 80, OLM 20, and AML 5), with OLM 80 being superior to AML 5 but not to OLM 20 and with OLM 20 being numerically better compared with AML 5. It is currently well recognized that central BP, compared with brachial BP, better reflects the BP load imposed on the heart and brain. Its association with cardiovascular mortality and morbidity has been clearly demonstrated in numerous large‐scale studies and in different study populations.9, 10, 11 As a result, the guidelines of the European Society of Hypertension/European Society of Cardiology acknowledged that central BP is predictive of outcome in specific populations.12 In addition, the guidelines also acknowledge that central BP may be differently affected by antihypertensive treatments.12 This statement is supported by the results from the CAFE study. Despite similar impact of the β‐blocker atenolol (±thiazide) and AML (+ACE inhibitors) on brachial BP, differences in clinical outcome and cSBP were observed between the two treatment groups in the CAFE study.6 Whether the similarities of brachial and central BP reduction in our study population are attributed to the drugs applied or are an effect of factors, such as sample size, study duration, or characteristics of the study population remains unclear.
However, despite significant reduction of cSBP in all three study groups, only OLM 20 and OLM 80 but not AML 5 significantly reduced PWV, a validated measurement of arterial stiffness. PWV is known to be dependent on BP and it is thus likely to assume that changes of PWV might be attributed to changes in BP. Ong and colleagues recently addressed this issue in a group of untreated hypertensive patients. After long‐term antihypertensive treatment, they found a reduction in PWV that was independent of the change in MAP. In our crossover study, we found a strong correlation of absolute values of PWV and MAP. However, the changes in PWV observed in the different treatment groups were not associated with the changes in MAP. Thus, OLM but not AML reduced PWV independent of BP reduction.
As already discussed, there is evidence from experimental and clinical studies showing that the ARB OLM exerts effects on the vasculature beyond mere BP lowering. Recently, Chuang and colleagues13 reported from an animal study in 5/6 nephrectomized rats that treatment with the OLM ameliorated arterial stiffness through the reduction of oxidative stress in the aortic wall. Zhang and colleagues14 found in cultured endothelial cells that OLM attenuates the impairment of endothelial cell via downregulation of the increased lectin‐type oxidized low‐density lipoprotein receptor expression induced by oxidized low‐density lipoprotein receptor 1. These effects might account for the reduction in PWV observed in our study population with OLM 80 as well as OLM 20. AML, however, despite not being inferior to OLM 20 in lowering brachial and cSBP, did not affect PWV. In patients with mild to moderate essential hypertension, Rajzer and colleagues15 investigated the effect of AML 10 mg, the ACE inhibitor quinapril, and the ARB losartan on PWV. AML, even in a dose twice as high as applied in our study, did not affect PWV.15 In contrast, in clinical studies, OLM proved to be beneficial beyond BP control by reducing the development of microalbuminuria in patients with diabetes and at least one cardiovascular risk factor (Randomized Olmesartan and Diabetes Microalbuminuria Prevention [ROADMAP] trial), to improve vascular structure abnormalities in the microcirculation (Vascular Improvement With Olmesartan Medoxomil Study [VIOS]), and to reduce cardiovascular risk in patients with atherosclerosis (Multicentre Olmesartan Atherosclerosis Regression Evaluation [MORE]).4, 16, 17
PWV is the gold standard for determining arterial stiffness.18 Numerous studies have clearly demonstrated that PWV is a predictor for cardiovascular events and is associated with cardiovascular morbidity and mortality.19, 20, 21 Protogerou and colleagues22 analyzed PWV in patients with MetS. They showed that in treated hypertensive patients with MetS, PWV is increased compared with controls without MetS of the same age, sex, and MAP. Likewise, in a study with patients with MetS, Kim and colleagues.23 found that compared with patients with essential hypertension, PWV and thus arterial stiffening in the group with MetS was increased. Furthermore, regression analysis showed that METS was associated with increased risk of high arterial PWV.
Reduction of PWV implies reduced vascular stiffness and increased vascular compliance and thus reflects an important therapeutic strategy in patients at increased cardiovascular risk, such as our study population with MetS. OLM proved effective in our study population to reduce PWV. Our results are supported by results from Mediavilla and colleagues as well as recently by Laurent and coworkers who analyzed the effect of OLM on PWV in patients with essential hypertension.24, 25 Mediavilla and colleagues showed that after 16 weeks of treatment with OLM, PWV was significantly reduced from 10.50 m/s to 9.26 m/s and this seemed to be independent of the BP‐lowering effect.24 Laurent and coworkers could also demonstrate that high‐dose OLM significantly reduced PWV in a BP‐independent manner, leading to a beneficial remodeling and destiffening of the arterial wall material.25
Study Limitations
Our study has some limitations. The short duration of the study does not allow any predictions on the impact of those benefits on the long‐term effects of OLM on cardiovascular morbidity or mortality in patients with MetS. The therapeutic effects of OLM 80 have been observed in a hypertensive study population of MetS. These effects cannot be extrapolated to other hypertensive populations.
Conclusions
This study demonstrates that in patients with MetS, OLM 20 and OLM 80 significantly improve arterial stiffness as demonstrated by the reduction in PWV. Furthermore, it reduces cSBP as well as 24‐hour ambulatory BP, with OLM 80 to a greater extent than AML. Thus, our results add to the evidence that OLM exerts beneficial effects on the vasculature in patients with increased cardiovascular risk.
Sources of Funding
This study was supported by Daiichi‐Sankyo Europe.
Acknowledgments and Disclosure
The expert technical assistance of D. Bader‐Schmieder, I. Biermann, I. Fleischmann, U. Heinritz, and S. Pejkovic is greatly appreciated. Ulrike Raff, Stefanie Walker, Christian Ott, and Markus P. Schneider have no conflicts of interest to disclose. Roland E. Schmieder has received grants from the university and advisory and speaker honorarium from Daiichi Sankyo and other ARB‐producing companies.
J Clin Hypertens (Greenwich). 2015;17:98–104. DOI: 10.1111/jch.12458. © 2014 Wiley Periodicals, Inc.
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