title: Valsartan improves arterial stiffness in type 2 diabetes independently of blood pressure lowering.
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 (n=66), an ARB, with that of amlodipine (n=65), a calcium channel blocker on Ao-PWV in 131 T2DM patients with pulse pressure (PP) >or=60 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), -0.9 m/s (-1.4 to -0.3) for valsartan/HCTZ compared to amlodipine (P=0.002). AER fell significantly only with Val/HCTZ from 30.8(20.4, 46.5) to 18.2(12.5, 26.3) mcg/min, (P=0.01) with between treatment difference in favor of Val/HCTZ of -15.3mcg/min (P<0.001). 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.
authors.affiliation: Cardiovascular Division, King's College London School of Medicine, United Kingdom. j.karalliedde@kcl.ac.uk
authors.forename: Janaka
authors.initials: J
authors.lastname: Karalliedde
authors.forename: Andrew
authors.initials: A
authors.lastname: Smith
authors.forename: Lorenita
authors.initials: L
authors.lastname: DeAngelis
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mirenda
authors.forename: Albert
authors.initials: A
authors.lastname: Kandra
authors.forename: Jaco
authors.initials: J
authors.lastname: Botha
authors.forename: Philippe
authors.initials: P
authors.lastname: Ferber
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000419:Albuminuria / Q000188:drug therapy; D017311:Amlodipine / Q000008:administration & dosage; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001158:Arteries / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000008:administration & dosage*; D016896:Treatment Outcome; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D013777:Tetrazoles; D006852:Hydrochlorothiazide; D017311:Amlodipine; D000068756:Valsartan; D014633:Valine