Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease.
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.
Shechter
Michael
M
Heart Institute, Chaim Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Israel. shechtes@netvision.net.il
Issachar
Assaf
A
Marai
Ibrahim
I
Koren-Morag
Nira
N
Freinark
Dov
D
Shahar
Yael
Y
Shechter
Alon
A
Feinberg
Micha S
MS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001916:Brachial Artery / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D003935:Diagnostic Techniques, Cardiovascular; D004452:Echocardiography; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin; D011237:Predictive Value of Tests; D011379:Prognosis; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D012307:Risk Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents; D055815:Young Adult
D014665:Vasodilator Agents; D005996:Nitroglycerin