Endothelial dysfunction, oxidative stress, and risk of cardiovascular events in patients with coronary artery disease

Background-Endothelial function is impaired in coronary artery disease and may contribute to its clinical manifestations. Increased oxidative stress h as been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was de signed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients wit h coronary artery disease. Methods and Results-Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by meas uring forearm blood flow responses to acetylcholine and sodium nitroprussid e using venous occlusion plethysmography. The effect of the coadministratio n of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Card iovascular events, including death from cardiovascular causes, myocardial i nfarction, ischemic stroke, coronary angioplasty, and coronary or periphera l bypass operation, were studied during a mean follow-up period of 4.5 year s. Patients experiencing cardiovascular events (n=91) had lower vasodilator responses to acetylcholine (P <0.001) and sodium nitroprusside (P <0.05), but greater benefit from vitamin C (P <0.01). The Cox proportional regressi on analysis for conventional risk factors demonstrated that blunted acetylc holine-induced vasodilation (P=0.001), the effect of vitamin C (P=0.001), a nd age (P=0.016) remained independent predictors of cardiovascular events. Conclusions-Endothelial dysfunction and increased vascular oxidative stress predict the risk of cardiovascular events in patients with coronary artery disease. These data support the concept that oxidative stress may contribu te not only to endothelial dysfunction but also to coronary artery disease activity.