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J Clin Hypertens (Greenwich). 2012;14:773–778. ©2012 Wiley Periodicals, Inc.
Postmenopausal women are at greater risk for hypertension-related cardiovascular disease. Antihypertensive therapy may help alleviate arterial stiffness that represents a potential modifiable risk factor of hypertension. This randomized controlled study investigated the difference between an angiotensin receptor blocker and a calcium channel blocker in reducing arterial stiffness. Overall, 125 postmenopausal hypertensive women (age, 61.4±6 years; systolic blood pressure/diastolic blood pressure [SBP/DBP], 158±11/92±9 mm Hg) were randomized to valsartan 320 mg±hydrochlorothiazide (HCTZ) (n=63) or amlodipine 10 mg±HCTZ (n=62). The primary outcome was carotid-to-femoral pulse wave velocity (PWV) changes after 38 weeks of treatment. Both treatments lowered peripheral blood pressure (BP) (−22.9/−10.9 mm Hg for valsartan and −25.2/−11.7 mm Hg for amlodipine, P=not significant) and central BP (−15.7/−7.6 mm Hg for valsartan and −19.2/−10.3 mm Hg for amlodipine, P<.05 for central DBP). Both treatments similarly reduced the carotid-femoral PWV (−1.9 vs −1.7 m/s; P=not significant). Amlodipine was associated with a higher incidence of peripheral edema compared with the valsartan group (77% vs 14%, P<.001). BP lowering in postmenopausal women led to a reduction in arterial stiffness as assessed by PWV measurement. Both regimens reduced PWV to a similar degree after 38 weeks of treatment despite differences in central BP lowering, suggesting that the effect of valsartan on PWV is mediated through nonhemodynamic effects.
Cardiovascular disease is the most frequent cause of death in women, with the risk rising exponentially with age.1,2 Postmenopausal women with hypertension significantly outnumber hypertensive men and show a steep age-related increase in arterial stiffness3–5 leading to increases in systolic blood pressure (SBP) and left ventricular hypertrophy.6,7 Arterial stiffness measured by pulse wave velocity (PWV) is an independent risk factor for cardiovascular events and is a strong predictor of cardiovascular disease–associated mortality in hypertensive patients.8–10 Drugs that have the potential to reduce arterial stiffness in addition to lowering blood pressure (BP) can effectively reduce the risk of cardiovascular outcomes in postmenopausal women.
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are both effective antihypertensive agents with similar effects on the renin-angiotensin system (RAS) and both have potential in reducing arterial stiffness in hypertensive patients. Several clinical studies have demonstrated that both ACE inhibitors and ARBs increase arterial compliance and distensibility, thereby reducing arterial stiffness even independent of BP lowering.11–13 The present study assessed the differential effects of valsartan (RAS antagonist) vs amlodipine (a calcium channel blocker [CCB] or non-RAS antagonist) on PWV changes as a marker of large artery stiffness in postmenopausal women. Data suggest that CCBs and, more specifically, amlodipine treatment, increase peripheral sympathetic basal tone as well as RAS activity.14 Thus, the purpose of this study was to compare the effects of two antihypertensive agents with similar BP reductions on changes in PWV. To our knowledge, this study is the first to compare the efficacy of a RAS vs a non-RAS antihypertensive agent on arterial stiffness in postmenopausal women with hypertension.