Predictive value of brachial flow-mediated dilation for incident cardiovascular events in a population-based study: the multi-ethnic study of atherosclerosis

Abstract

Background: 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 of 6814 subjects (mean+/-SD age, 61.2+/-9.9 years) in MESA, a population-based cohort study of adults free of clinical CVD at baseline recruited at 6 clinic sites in the United States. The sample included 50.2% female, 34.3% white, 19.7% Chinese, 20.8% black, and 25.1% Hispanic subjects. Probability-weighted Cox proportional hazards analysis was used to examine the association between FMD and 5 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 the univariate model (adjusted for age and sex) (hazard ratio, 0.79; 95% confidence interval, 0.65 to 0.97; P=0.01), after adjustment for the Framingham Risk Score (FRS) (hazard ratio, 0.80; 95% confidence interval, 0.62 to 0.97; P=0.025), and in the multivariable model (hazard ratio, 0.84; 95% confidence interval, 0.71 to 0.99; P=0.04) after adjustment for age, sex, diabetes mellitus, cigarette smoking status, systolic blood pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, heart rate, statin use, and blood pressure medication use. The c statistic (area under the curve) values of FMD, FRS, and 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 reclassifies 52% of subjects with no incident CVD event but net incorrectly reclassifies 23% of subjects with an incident CVD event, an overall net correct reclassification of 29% (P<0.001).

Conclusions: 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 receiver operating characteristic analysis, it improved the classification of subjects as low, intermediate, and high CVD risk compared with the FRS.

Figure 1

Weighted curves showing cumulative event-free survival stratified by FMD > or =/ < the sex-specific median value for the cohort (follow-up truncated at 1700 days due to small numbers of subjects at risk for follow-up > 1700 days).*indicates number at risk. FMD: Brachial flow mediated dilation CVD: Cardiovascular disease

Figure 2

Probability-weighted Cox Proportional Hazard Ratios for nested models of FMD vs CVD events with and without cardiovascular risk factors and the Framingham Risk Score (FRS). * of change in FMD/ unit SD. ** adjusted for age, gender, diabetes mellitus, cigarette smoking, systolic blood pressure, blood pressure medication use,HDL, LDL cholesterol, triglycerides, heart rate and Statin use FMD: Brachial flow-mediated dilation FRS: Framingham Risk Score

Figure 3

Univariate* and multivariable**(full model) probability- weighted Cox proportional hazard ratios of change in FMD/unit SD vs CVD events stratified by ethnicity. Full model was adjusted for age, gender, diabetes mellitus, cigarette smoking, systolic blood pressure, blood pressure medication use,HDL, LDL cholesterol, triglycerides, heart rate and Statin use. CVD: cardiovascular disease FMD: flow mediated dilation

Figure 4

Receiver Operator Curves for the Framingham risk score (AUC=0.74), brachial FMD (AUC=0.65) and Framingham risk score + FMD (AUC=0.74) to predict incident CVD events. FMD: Flow mediated dilation AUC: area under the curve

Figure 5

Hazard Ratio (95%CI)for cardiovascular event for brachial diameter/ unit SD (height adjusted) in univariate and four multivariable models. * FRS represents the Framingham risk score **Full model was adjusted for age, gender, diabetes mellitus, cigarette smoking, systolic blood pressure, blood pressure medication use, HDL, LDL cholesterol, triglycerides, heart rate and Statin use BD: brachial artery diameter (height adjusted)