Heritability of flow-mediated dilation: A twin study

Background: Endothelial dysfunction assessed by brachial artery flow-mediated dilation (FMD) is a marker for early atherosclerotic vascular disease and future cardiovascular events. Objective: To estimate the heritability of brachial artery FMD using a twin design. Methods: We estimated the heritability of FMD using 94 middle-aged male twin pairs. FMD was measured by ultrasound, and traditional coronary heart disease risk factors were measured. Genetic modeling techniques were used to determine the relative contributions of genes and environment to the variation in FMD. Results: The mean age of the twin participants was 54.9 ± 2.8years. The mean FMD was 0.047 ± 0.030. The intraclass correlation coefficient was higher in MZ twins [0.38, 95%; confidence interval (CI) 0.32-0.43] than in DZ twins (0.19, 95% CI 0.11-0.26), suggesting a role of genetic influence in FMD variation. Structural equation modeling showed that both genetic and unique environmental factors contributed significantly to the variation in FMD. The crude FMD heritability was 0.37 (95% CI 0.15-0.54). After adjustment for traditional cardiovascular risk factors, including age, total cholesterol, blood pressure, and body mass index, the heritability of FMD was 39% (95% CI 0.18-0.56). The remaining variation in FMD could be explained by individual-specific environment. Conclusion: This is the first study using twins to estimate the relative contributions of genetics and environment to the variation in FMD in a US population. Our results demonstrate a moderate genetic effect on brachial artery FMD, independent of traditional coronary risk factors. Our data also highlight the importance of unique environment on the variability in FMD.