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...

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Aims OUTSTEP‐HF compared the effect of sacubitril/valsartan vs. enalapril on 6‐min walk test (6MWT) distance, non‐sedentary daytime physical activity and heart failure (HF) symptoms in patients with HF with reduced ejection fraction (HFrEF). Methods and results Ambulatory patients (n = 621) with stable symptomatic HFrEF were randomised 1:1 to sacubitril/valsartan (n = 310) or enalapril (n = 311). Changes in physical activity and mean daily non‐sedentary daytime activity from baseline to Week 12 were measured using 6MWT and a wrist‐worn accelerometer device, respectively. After 12 weeks, 6MWT improved by 35.09 m with sacubitril/valsartan [97.5% confidence interval (CI) 27.85, 42.32] and by 26.11 m with enalapril (97.5% CI 18.78, 33.43); however, there was no significant difference between groups [least squares means treatment difference: 8.98 m (97.5% CI −1.31, 19.27); P = 0.0503]. Mean daily non‐sedentary daytime activity decreased by 27 min with sacubitril/valsartan and by 21 min with enalapril [least squares means treatment difference: −6 min (97.5% CI −25.7, 13.4), P = 0.4769] after 12 weeks. 6MWT improved by ≥30 m in 51% of patients in the sacubitril/valsartan group vs. 44% of patients treated with enalapril (odds ratio 1.251, 95% CI 0.895, 1.748). At Week 4, non‐sedentary daytime activity increased by ≥10% in 58% of patients treated with sacubitril/valsartan vs. 64% with enalapril; 58% of patients treated with sacubitril/valsartan reported improved HF symptoms as assessed by patient global assessment vs. 43% with enalapril. However, these differences did not persist at Week 12. Conclusion After 12 weeks of treatment, there was no significant benefit of sacubitril/valsartan on either 6MWT or daytime physical activity measured by actigraphy compared with enalapril.