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).
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.
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)].
Brachial artery median FMD independently predicts long-term adverse cardiovascular
events in healthy subjects in addition to traditional risk factor assessment.