Effects of Clopidogrel Therapy on Oxidative Stress, Inflammation, Vascular Function, and Progenitor Cells in Stable Coronary Artery Disease

• Type of Material: Article
• Authors: Ronnie Ramadan, Emory University; Saurabh S. Dhawan, Emory University; Hamid Syed, Emory University; F. Khan Pohlel, Emory University; Jose N Binongo, Emory University; Ziyad Bahjat Ghazzal, Emory University; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2014-04-01
• Publisher: SAGE Publications (UK and US)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2013 by Lippincott Williams & Wilkins.
• Final Published Version (URL): http://dx.doi.org/10.1097/FJC.0000000000000057
• Title of Journal or Parent Work: Journal of Cardiovascular Pharmacology and Therapeutics
• ISSN: 1074-2484
• Volume: 63
• Issue: 4
• Start Page: 369
• End Page: 374
• Grant/Funding Information: This work was supported by a grant from Sanofi Aventis; and in part by NIH grant UL1 RR025008 from the Atlanta Clinical and Translational Science Award program; NIH grant R01HL089650-02.
• Keywords: MYOCARDIAL-INFARCTION; CONTROLLED TRIAL; ST-SEGMENT ELEVATION; C-REACTIVE PROTEIN; oxidative stress; endothelial function; Life Sciences & Biomedicine; ANTIPLATELET THERAPY; antiplatelet; Science & Technology; Pharmacology & Pharmacy; HUMAN PLASMA; RISK-FACTORS; CARDIOVASCULAR-DISEASE; atherosclerosis; Cardiac & Cardiovascular Systems; progenitor cells; ENDOTHELIAL DYSFUNCTION; Cardiovascular System & Cardiology; AMERICAN-HEART-ASSOCIATION
• Research Categories: Biology, Biostatistics; Health Sciences, Medicine and Surgery

Abstract

Background:Traditional cardiovascular risk factors lead to endothelial injury and activation of leukocytes and platelets that initiate and propagate atherosclerosis. We proposed that clopidogrel therapy in patients with stable coronary artery disease imparts a pleiotropic effect that extends beyond antiplatelet aggregation to other atheroprotective processes. Methods: Forty-one subjects were randomized in a double-blind, placebo-controlled, crossover study to receive either clopidogrel 75 mg daily or placebo for 6 weeks and then transitioned immediately to the other treatment for an additional 6 weeks. We assessed (1) endothelial function as flow-mediated dilation of the brachial artery, (2) arterial stiffness and central augmentation index using applanation tonometry, (3) vascular function as fingertip reactive hyperemia index, (4) inflammation by measuring plasma CD40 ligand and serum high-sensitivity c-reactive protein levels, (5) oxidative stress by measuring plasma aminothiols, and (6) circulating progenitor cells, at baseline and at the end of each 6-week treatment period. Results: Clopidogrel therapy resulted in a significant reduction in soluble CD40 ligand (P = 0.03), a prothrombotic and proinflammatory molecule derived mainly from activated platelets. However, clopidogrel therapy had no effect on endothelial function, arterial stiffness, inflammatory and oxidative stress markers, or progenitor cells. Conclusions: Our findings suggest a solitary antiplatelet effect of clopidogrel therapy in patients with stable coronary artery disease, with no effect on other subclinical markers of cardiovascular disease risk.