Endothelial Dysfunction and the Risk of Heart Failure in a Community-Based Study: the Multi-Ethnic Study of Atherosclerosis

Aims: We aimed to investigate the association between endothelial dysfunction, assessed by brachial flow-mediated dilation (FMD), and the incidence of heart failure (HF) in the community-based Multi-Ethnic Study of Atherosclerosis.

Methods and results: Brachial artery FMD was measured in a nested case-cohort sample including 3496 of 6814 Multi-Ethnic Study of Atherosclerosis participants without prevalent cardiovascular disease (mean age 61 years, 50% women). Multivariable probability-weighted Cox proportional hazards analysis was used to examine the association between FMD and incident HF. We also investigated the association between FMD and HF with reduced vs. preserved ejection fraction [HFrEF (left ventricular ejection fraction <45%) vs. HFpEF (left ventricular ejection fraction ≥45%)]. During follow-up (median 12 years), 149 participants developed incident HF (incidence rate 3.7 events per 1000 person years). There were 56 HFrEF and 69 HFpEF events (incidence rates 1.4 and 1.7 events per 1000 person years, respectively). In multivariable models adjusted for established HF risk factors (age, sex, race/ethnicity, body mass index, systolic blood pressure, antihypertensive treatment, heart rate, diabetes mellitus, history of myocardial infarction, current smoker, and former smoker status), individuals in the highest quartile of FMD (reflecting better endothelial function) had a lower HF risk compared with individuals in the lowest quartile [hazard ratio 0.53, 95% confidence interval (CI) 0.31-0.95]. Lower risk according to higher FMD was particularly evident for HFrEF, but not for HFpEF (hazard ratio per standard deviation increase 0.79, 95% CI 0.64-0.97 vs. 0.99, 95% CI 0.78-1.26, respectively). Results remained similar after adjustment for baseline natriuretic peptide levels. The addition of FMD to established HF risk factors generally rendered no or only modest improvement in C-statistics [C-statistics for model with established HF risk factors: 0.774, and with the addition of FMD: 0.776 (delta C 0.002, 95% confidence interval -0.002 to 0.006)].

Conclusions: Endothelial dysfunction was independently associated with HF in this community cohort, suggesting a pathophysiological contribution of endothelial function to the development of HF, in particular HFrEF. However, the value of FMD measurements for HF risk prediction seems limited.