Endothelial Dysfunction and the Risk of Hypertension: The Multi-Ethnic Study of Atherosclerosis

Hypertension is associated with impaired endothelial function in cross-sectional studies. However, few longitudinal data exist on whether endothelial dysfunction precedes the development of hypertension. We examined the cross-sectional and longitudinal relationships between endothelial-dependent brachial artery flow-mediated dilation (FMD) and hypertension prevalence and incidence in 3500 participants from the Multi-Ethnic Study of Atherosclerosis, an ethnically diverse, community-based cohort study. At baseline, the prevalence ratios (95% CI) of hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.26 (1.12 to 1.40), 1.35 (1.21 to 1.52), and 1.68 (1.50 to 1.87; linear trend P<0.001). This association remained (P=0.017) after adjustment for demographics (age, sex, and ethnicity), Multi-Ethnic Study of Atherosclerosis site, and other risk factors. Of the 1869 participants without hypertension at baseline, 584 (31.3%) developed hypertension over a median follow-up of 4.8 years. The unadjusted relative risks (95% CI) of incident hypertension from the highest to the lowest quartile of FMD were 1.00 (referent), 1.38 (1.14 to 1.67), 1.44 (1.19 to 1.74), and 1.64 (1.36 to 1.97; linear trend P<0.001). However, after adjustment for demographics and Multi-Ethnic Study of Atherosclerosis site, the relationship between FMD and incident hypertension was attenuated and not statistically significant: 1.00 (referent), 1.26 (1.04 to 1.52), 1.19 (0.98 to 1.44), and 1.18 (0.97 to 1.44). The longitudinal results also did not appreciably change after adjustment for additional risk factors and baseline blood pressure levels. In this sample, reduced FMD was not an independent predictor of hypertension incidence, suggesting that impaired endothelial function does not play a major role in the development of hypertension.