Ronnie Ramadan1, Saurabh S Dhawan2, José Nilo G Binongo3, Ayman Alkhoder2, Dean P Jones2, John N Oshinski4, Arshed A Quyyumi2. 1. Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA. Electronic address: rramadan@bidmc.harvard.edu. 2. Emory Clinical Cardiovascular Research Institute, Department of Medicine, Emory University School of Medicine, Atlanta, GA. 3. Department of Biostatistics & Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, GA. 4. Department of Radiology and Imaging Sciences, Emory University School of Medicine and Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA.
Abstract
BACKGROUND: Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis. METHODS:Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function. RESULTS: Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function. CONCLUSIONS: In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation.
RCT Entities:
BACKGROUND: Progression of atherosclerosis is associated with a greater risk for adverse outcomes. Angiotensin II plays a key role in the pathogenesis and progression of atherosclerosis. We aimed to investigate the effects of angiotensin II type-1 receptor blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis. METHODS: Subjects (n = 120) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan or placebo for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area and wall thickness were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent vascular function. RESULTS: Over 2 years, the carotid bulb vessel wall area decreased with Valsartan (-6.7, 95% CI [-11.6, -1.9] mm(2)) but not with placebo (3.4, 95% CI [-2.8, 9.6] mm(2)), P = .01 between groups. Similarly, mean wall thickness decreased with Valsartan (-0.18, 95% CI [-0.30, -0.06] mm), but not with placebo (0.08, 95% CI [-0.07, 0.23] mm), P = .009 between groups. Furthermore, plaque thickness decreased with Valsartan (-0.35, 95% CI [-0.63, -0.08] mm) but was unchanged with placebo (+0.28, 95% CI [-0.11, 0.69] mm), P = .01 between groups. These findings were unaffected by statin therapy or changes in blood pressure. Notably, there were significant improvements in the aminothiol cysteineglutathione disulfide, and trends to improvements in fibrinogen levels and endothelium-independent vascular function. CONCLUSIONS: In subjects with carotid wall thickening, angiotensin II type-1 receptor blockade was associated with regression in carotid atherosclerosis. Whether these effects translate into improved outcomes in subjects with subclinical atherosclerosis warrants investigation.
Authors: Donald Lloyd-Jones; Robert J Adams; Todd M Brown; Mercedes Carnethon; Shifan Dai; Giovanni De Simone; T Bruce Ferguson; Earl Ford; Karen Furie; Cathleen Gillespie; Alan Go; Kurt Greenlund; Nancy Haase; Susan Hailpern; P Michael Ho; Virginia Howard; Brett Kissela; Steven Kittner; Daniel Lackland; Lynda Lisabeth; Ariane Marelli; Mary M McDermott; James Meigs; Dariush Mozaffarian; Michael Mussolino; Graham Nichol; Véronique L Roger; Wayne Rosamond; Ralph Sacco; Paul Sorlie; Véronique L Roger; Randall Stafford; Thomas Thom; Sylvia Wasserthiel-Smoller; Nathan D Wong; Judith Wylie-Rosett Journal: Circulation Date: 2009-12-17 Impact factor: 29.690
Authors: A Prasad; T Tupas-Habib; W H Schenke; R Mincemoyer; J A Panza; M A Waclawin; S Ellahham; A A Quyyumi Journal: Circulation Date: 2000-05-23 Impact factor: 29.690
Authors: A Mauriello; G Sangiorgi; G Palmieri; R Virmani; D R Holmes; R S Schwartz; R Pistolese; A Ippoliti; L G Spagnoli Journal: Circulation Date: 2000-02-22 Impact factor: 29.690
Authors: B Schieffer; E Schieffer; D Hilfiker-Kleiner; A Hilfiker; P T Kovanen; M Kaartinen; J Nussberger; W Harringer; H Drexler Journal: Circulation Date: 2000-03-28 Impact factor: 29.690
Authors: Raymond Q Migrino; Mark Bowers; Leanne Harmann; Robert Prost; John F LaDisa Journal: J Cardiovasc Magn Reson Date: 2011-08-03 Impact factor: 5.364
Authors: Alexander Balatskiy; Ilia Ozhimalov; Maria Balatskaya; Alexandra Savina; Julia Filatova; Natalia Kalinina; Vladimir Popov; Vsevolod Tkachuk Journal: Int J Mol Sci Date: 2022-02-03 Impact factor: 5.923
Authors: Anastasia V Poznyak; Dwaipayan Bharadwaj; Gauri Prasad; Andrey V Grechko; Margarita A Sazonova; Alexander N Orekhov Journal: Int J Mol Sci Date: 2021-06-22 Impact factor: 5.923