Effects of clopidogrel therapy on oxidative stress, inflammation, vascular function, and progenitor cells in stable coronary artery disease.

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.

Usefulness of serum high-density lipoprotein cholesterol level as an independent predictor of one-year mortality after percutaneous coronary interventions.

Low levels of high-density lipoprotein (HDL) cholesterol are a marker of coronary artery disease progression and are associated with cardiovascular events. However, whether low HDL cholesterol is a useful prognostic indicator after percutaneous coronary intervention (PCI) is not known. In a sample of 4,088 patients who underwent PCI we evaluated 1-year mortality and repeat revascularization as a function of baseline HDL levels classified into approximate quartiles of very low (<35 mg/dl), low (35 to 40 mg/dl), medium (41 to 47 mg/dl) and high (48 to 120 mg/dl) HDL cholesterol. Decreasing levels of HDL cholesterol were associated with younger age, male gender, smoking, diabetes mellitus, and a history of bypass surgery (p <0.0001 for all). One-year mortality and coronary revascularization were significantly higher in the very low HDL cholesterol group compared with the other groups (very low HDL cholesterol 6.5% and 25.4%, respectively; low HDL cholesterol 3.1% and 20.8%; medium HDL cholesterol 4.3% and 22.7%; high HDL cholesterol 3.1% and 20.6%, p = 0.0001 and p = 0.007). One-year mortality was significantly higher in men with an HDL cholesterol level <33 mg/dL and in women with an HDL cholesterol level <38 mg/dL. In multivariable analysis, very low HDL was associated with nearly twofold the risk of death after adjusting for other independent predictors of outcome. In conclusion, in patients with coronary artery disease undergoing PCI, a baseline HDL cholesterol level <35 mg/dl is an important prognostic indicator. Baseline HDL cholesterol levels <33 mg/dl for men and <38 mg/dl were associated with higher one-year mortality after PCI.