Abstract 20622: Effect of Angiotensin Receptor Blockade on Carotid Artery Atherosclerosis
Background: Angiotensin II plays a key role in the pathogenesis of atherosclerosis at least partly by promoting oxidative stress (OS) and inflammation.
Objectives: We investigated the effects of Angiotensin II type-1 receptor (AT1R) blockade with Valsartan on carotid wall atherosclerosis, with the hypothesis that Valsartan will reduce progression of atherosclerosis, OS, and inflammation.
Methods: Subjects (n= 120, 60±9 years, 51% male) with carotid intima-media thickness >0.65 mm by ultrasound were randomized (2:1) in a double-blind manner to receive either Valsartan (n=80), titrated up to 320 mg daily, or placebo (n=40) for 2 years. Bilateral T2-weighted black-blood carotid magnetic resonance imaging (MRI) was performed at baseline, 12 and 24 months. Changes in the carotid bulb vessel wall area (VWA) and wall thickness (WT) were primary endpoints. Secondary endpoints included changes in carotid plaque thickness, plasma levels of aminothiols, C-reactive protein, fibrinogen, and endothelium-dependent and -independent brachial artery vasodilation. Statistical comparisons between groups were performed using a linear mixed-effects model to account for multiple measurements within subject.
Results: Over 2 years, the carotid bulb VWA decreased with valsartan (p=0.008) but not with placebo (p=0.28); p=0.01 between groups. Similarly, mean WT increased with placebo (p=0.0035) but remained unchanged with Valsartan (p=0.31); p=0.009 between groups. Importantly, plaque thickness decreased with Valsartan (p= 0.014) but was unchanged with placebo (p=0.16); p=0.01 between groups. These findings were independent of statin therapy and changes in blood pressure. Furthermore, there were significant improvements in the aminothiol cysteineglutathione disulfide and fibrinogen levels and in endothelium-independent vasodilation with Valsartan.
Conclusions: AT1R blockade with Valsartan is associated with significant carotid arterial remodeling manifested as regression in carotid atherosclerosis, changes that may be secondary to improvement in OS, inflammation, and vascular function.
Author Disclosures: R. Ramadan: None. S. Dhawan: None. A. Alkhoder: None. J.N. Binongo: None. J. Oshinski: None. A.A. Quyyumi: None.
- © 2014 by American Heart Association, Inc.