Valsartan Improves Arterial Stiffness in Type 2 Diabetes Independently of Blood Pressure Lowering

Abstract

Abstract-Increased arterial stiffness, as estimated from aortic pulse wave velocity (Ao-PWV), and albuminuria are independent predictors for cardiovascular disease in type 2 diabetes mellitus (T2DM). Whether angiotensin receptor blockers (ARBs), drugs with cardio-renal protective effects, improve Ao-PWV to a greater extent than other equipotent antihypertensive medications remains unclear. After a 4-week washout phase, we compared the effects of valsartan (nϭ66), an ARB, with that of amlodipine (nϭ65), a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure (PP) Ն60 mm Hg and raised albumin excretion rate (AER) in a 24-week randomized, double-blind, parallel group study. Hydrochlorothiazide (HCTZ) 25 mg/d was added to valsartan 160 mg and amlodipine 5 mg/od uptitrated to 10 mg/od after 4 weeks to ensure equivalent BP control. After 24 weeks brachial and central aortic PP had fallen to a similar extent with attained mean (SD) brachial and central PP of 61.6 (13.6) and 47.3 (14.1) mm Hg in the valsartan/HCTZ group and 61.5 (12.2) and 47.3 (9.9) mm Hg in the amlodipine group, respectively. Ao-PWV showed a significantly greater reduction, mean (95% CI), Ϫ0.9 m/s (Ϫ1.4 to Ϫ0.3) for valsartan/HCTZ compared to amlodipine (Pϭ0.002). AER fell significantly only with Val/HCTZ from 30.8(20.4, 46.5) to 18.2(12.5, 26.3) mcg/min, (Pϭ0.01) with between treatment difference in favor of Val/HCTZ of Ϫ15.3mcg/min (PϽ0.001). Changes in AER and Ao-PWV were not correlated. Valsartan/HCTZ improves arterial stiffness and AER to a significantly greater extent than amlodipine despite similar central and brachial BP control. These 2 effects, which appear independent of each other, may explain the specific cardio-renal protective properties of ARBs. Key Words: type 2 diabetes Ⅲ hypertension Ⅲ arterial stiffness Ⅲ albuminuria Ⅲ angiotensin receptor blockers C ardiovascular disease (CVD) is the main cause of death in patients with type 2 diabetes mellitus (T2DM). 1 In T2DM angiotensin type 1 (AT 1 ) receptor blockers (ARB) reduce albumin excretion and prevent the progression of diabetic renal disease, 2,3 and inhibition of the renin angiotensin system (RAS) may also provide cardio-protective benefits. 4,5 These effects would appear independent of the brachial blood pressure lowering action of these drugs. [2][3][4][5] However, some authors have questioned whether antihypertensive drugs offer cardio-renal protection beyond blood pressure lowering. 6,7 In T2DM systolic hypertension is often associated with albuminuria, and both are strong predictors of CVD mortality and morbidity and progressive renal failure. 8 Recent evidence indicates that increased arterial stiffness, involving accelerated vascular aging of the aorta, is a powerful and independent risk factor for early mortality and provides prognostic information above and beyond traditional CVD risk factors such as blood pressure itself, age, gender, diabetes, smoking, and cholesterol. 9,10 As arterial stiffness is the principal determinant of pulse pressure (PP), a...

Pravastatin and Olmesartan Synergistically Ameliorate Renal Failure-Induced Vascular Calcification

“…Strong renoprotection by ARBs, but not other antihypertensive drugs, via a reduction in proteinuria is well known, in addition to direct BPlowering effects 31,32) . In addition, several reports have shown that ARBs improve the arterial stiffness, as assessed by the pulse wave velocity 33,34) . Especially in CKD patients, superior preventive effects for olmesartan on nocturnal hypertension and proteinuria have been suggested compared to other ARBs 35,36) .…”

Correlates of Aortic Stiffness Progression in Patients With Type 2 Diabetes: Importance of Glycemic Control

“…However, what determines progression or regression of aortic stiffness over the long-term, which is critical to planning long-lasting interventions to reducing arterial stiffness, remains unsettled. Indeed, most prospective studies evaluated the effects of pharmacological or nonpharmacological interventions in the short-term of few months up to a year (11,12) or only measured cf-PWV once at the end of follow-up (13,14). Few prospective studies evaluated serial changes in cf-PWV and their correlates over the long-term of at least 2-3 years (15)(16)(17)(18)(19).…”

2013 Esh/Esc Guidelines for the Management of Arterial Hypertension

“…Однако из-за нехватки качественных РКИ с достаточной статистической мощностью остается неясным, превосходят ли эти препараты по своему влиянию на жесткость артерий другие антигипертензивные средства. Способность блокаторов РАС уменьшать жесткость артерий, о кото-рой судят по СПВ, по-видимому, не зависит от их спо-собности снижать АД [582][583][584]. Однако несмотря на то, что комбинация амлодипина с валсартаном снижала центральное САД более эффективно, чем комбинация амлодипина с атенололом, в исследова-нии EXPLOR обе комбинации уменьшали СПВ на 0,95 м/сек, без значимых различий на протяжении 24 недель [399].…”