Background: Endothelial dysfunction is considered an important prognostic factor in atherosclerosis. The aim of this study was to detect the long-term association of peripheral vascular endothelial function and clinical outcome in healthy subjects without apparent coronary artery disease (CAD).
Methods: We prospectively assessed brachial flow-mediated dilation (FMD) in 435 consecutive healthy subjects: 281 (65%) men, mean age 54+/-12 years and body mass index 28+/-4 kg/m(2). After overnight fasting and discontinuation of all medications for > or =12 h, FMD and endothelium-independent nitroglycerin-mediated vasodilation were assessed using high resolution linear array ultrasound.
Results: Subjects were divided into 2 groups: below (n=221) and above (n=214) the median FMD of 10.7%, and were comparable regarding CAD risk factors, lipoproteins, fasting glucose, C-reactive protein, and concomitant medications, with a mean clinical follow-up of 32+/-2 months. Composite cardiovascular endpoints (all-cause mortality, non-fatal myocardial infarction, heart failure or angina pectoris hospitalization, stroke, coronary artery bypass grafting and percutaneous coronary interventions) were significantly more common in subjects with below median FMD of 10.7%, than above (11.8% vs 4.7%, p=0.007, respectively). Univariate analysis demonstrated that median FMD significantly predicted cardiovascular events [odds ratio (OR) of 2.78 and 95% CI 1.35 to 5.71 (p=0.003)]. After multivariate analysis including conventional CAD risk factors, median FMD was the best independent predictor of long-term cardiovascular adverse events [OR of 2.70 and 95% CI 1.16 to 6.32 (p=0.011)].
Conclusions: Brachial artery median FMD independently predicts long-term adverse cardiovascular events in healthy subjects in addition to traditional risk factor assessment.