Persistent impairment of endothelial vasomotor function has a negative impact on outcome in patients with coronary artery disease.

OBJECTIVES: We assessed the hypothesis that changes in endothelial vasomotor function in response to optimized therapy for atherosclerotic coronary artery disease predict future cardiovascular events.

BACKGROUND: Although endothelial vasomotor dysfunction is a predictor of cardiovascular events, it remains unclear whether reversibility of endothelial dysfunction in response to risk factor reduction provides prognostic information.

METHODS: This study included 251 patients with newly diagnosed coronary artery disease and an impaired flow-mediated dilation (FMD) of the brachial artery (FMD <5.5%). Measurement of FMD was repeated after 6 months for individualized and optimized therapy to reduce risk factors according to American College of Cardiology/American Heart Association guidelines. Patients were followed up for 36 months or until 1 of the following events occurred: cardiac death, nonfatal myocardial infarction, recurrent and refractory angina pectoris requiring coronary revascularization, or ischemic stroke.

RESULTS: FMD was persistently impaired (<5.5%) in 104 (41%) patients after 6 months of optimized therapy, whereas it improved (FMD > or =5.5%) in the remaining 147 (59%) patients. During 36 months of follow-up, events occurred in 27 (26%) patients with persistently impaired FMD and in 15 (10%) patients with improved FMD (p < 0.01 by chi-square test). Multivariate Cox hazards analysis showed that persistent impairment of FMD was an independent predictor of events (hazard ratio: 2.9, 95% confidence interval: 1.5 to 6.2, p < 0.01). Baseline FMD before the optimized therapy to reduce risk factor had no significant prognostic information.

CONCLUSIONS: Persistent impairment of endothelial vasomotor function despite optimized therapy to reduce risk factors has an adverse impact on outcome in coronary artery disease patients.