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 has been linked to impaired endothelial function in atherosclerosis and may play a role in the pathogenesis of cardiovascular events. This study was designed to determine whether endothelial dysfunction and vascular oxidative stress have prognostic impact on cardiovascular event rates in patients with coronary artery disease.


RESULTS
Endothelium-dependent and -independent vasodilation was determined in 281 patients with documented coronary artery disease by measuring forearm blood flow responses to acetylcholine and sodium nitroprusside using venous occlusion plethysmography. The effect of the coadministration of vitamin C (24 mg/min) was assessed in a subgroup of 179 patients. Cardiovascular events, including death from cardiovascular causes, myocardial infarction, ischemic stroke, coronary angioplasty, and coronary or peripheral bypass operation, were studied during a mean follow-up period of 4.5 years. 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 regression analysis for conventional risk factors demonstrated that blunted acetylcholine-induced vasodilation (P=0.001), the effect of vitamin C (P=0.001), and 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 contribute not only to endothelial dysfunction but also to coronary artery disease activity.
Heitzer
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Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Innere Medizin, Abteilung Kardiologie, Hamburg, Germany. heitzer@uke.uni-hamburg.de
Schlinzig
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Krohn
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Meinertz
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Münzel
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D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000150:complications / Q000175:diagnosis / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D005542:Forearm / Q000098:blood supply; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D010991:Plethysmography; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000187:drug effects; D018570:Risk Assessment; D015996:Survival Rate; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000975:Antioxidants; D014665:Vasodilator Agents; D001205:Ascorbic Acid