Although brachial artery flow-mediated dilation (FMD) predicts recurrent cardiovascular events, its predictive value for incident cardiovascular disease (CVD) events in adults free of CVD is not well established. We assessed the predictive value of FMD for incident CVD events in the Multi Ethnic Study of Atherosclerosis (MESA).
Methods and Results
Brachial artery FMD was measured in a nested case- cohort sample of 3026 out of 6814 subjects (mean ± SD age 61.2 ± 9.9 years), in MESA, a population-based cohort study of adults free of clinical CV disease at baseline recruited at six clinic sites in the USA. The sample comprised 50.2% females, 34.3% Caucasian, 19.7% Chinese, 20.8% African Americans and 25.1% Hispanics. Probability-weighted Cox proportional hazard analysis was used to examine the association between FMD and five years of adjudicated incident CVD events, including incident myocardial infarction, definite angina, coronary revascularization (coronary artery bypass grafting, percutaneous transluminal coronary angioplasty or other revascularization), stroke, resuscitated cardiac arrest and CVD death.
Mean (SD) FMD of the cohort was 4.4 (2.8) %. In probability-weighted Cox models, FMD/unit SD was significantly associated with incident cardiovascular events in both the univariate(adjusted for age and gender) [hazard ratio; 0.79(95% CI, 0.65–0.97), p=0.01], after adjusting for the Framingham Risk Score (FRS) [hazard ratio; 0.80(95%CI, 0.62–0.97), p=0.025] and also in multivariable models [hazard ratio; 0.84(95%CI, 0.71–0.99), p=0.04] after adjusting for age, gender, diabetes mellitus, cigarette smoking status, systolic blood pressure, HDL, LDL, triglycerides, heart rate, statin use and blood pressure medication use. The c statistic (AUC) of FMD, FRS, FRS + FMD) were 0.65, 0.74 and 0.74 respectively. Compared with the FRS alone, the addition of FMD to the FRS net correctly re-classifies 52% of subjects with no incident CVD event, but net incorrectly reclassifies 23% of subjects with an incident CVD event; an overall net correct re-classification of 29% (p < 0.001).
Brachial FMD is a predictor of incident cardiovascular events in population based adults. Even though the addition of FMD to the FRS did not improve discrimination of subjects at risk of CVD events in ROC analysis, it did improve the classification of subjects as low, intermediate and high CVD risk compared to the FRS.