title: Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease.
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.
authors: *Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, GA; †Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Atlanta, GA; and ‡Division of Cardiology, Department of Medicine, American University of Beirut, Beirut, Lebanon.
authors: Ronnie
authors: R
authors: Ramadan
authors: Saurabh S
authors: SS
authors: Dhawan
authors: Hamid
authors: H
authors: Syed
authors: F Khan
authors: FK
authors: Pohlel
authors: Jose N G
authors: JN
authors: Binongo
authors: Ziyad B
authors: ZB
authors: Ghazzal
authors: Arshed A
authors: AA
authors: Quyyumi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001808:Blood Vessels / Q000187:drug effects* / Q000503:physiopathology; D002196:Capillaries / Q000187:drug effects; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004548:Elasticity; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D011446:Prospective Studies; D013234:Stem Cells / Q000187:drug effects*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D059289:Vascular Stiffness / Q000187:drug effects
chemical_list: D015415:Biomarkers; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine