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CLINICAL RESEARCH: CORONARY DISEASE RISK

Persistent Impairment of Endothelial Vasomotor Function Has a Negative Impact on Outcome in Patients With Coronary Artery Disease

Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine, Yamanashi, Japan

Manuscript received April 10, 2008; revised manuscript received August 6, 2008, accepted August 30, 2008.

^_* Reprint requests and correspondence: Dr. Kiyotaka Kugiyama, Department of Internal Medicine II, University of Yamanashi, Faculty of Medicine, 1110 Shimokato, Chuo 409-3898, Japan (Email: kugiyama{at}yamanashi.ac.jp).

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 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.

Key Words: endothelium • prognosis • coronary artery disease • risk factor

Abbreviations and Acronyms   CAD = coronary artery disease   CVD = cardiovascular disease   EDNO = endothelium-derived nitric oxide   FMD = flow-mediated dilation   Hb = hemoglobin   LDL-C = low-density lipoprotein cholesterol   ROC = receiver-operator characteristic

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