Improvement of Cardiovascular Prognostic Value of Endothelial Function Tests by Repeated Measurements

Abstract

Background: The clinical significance of monitoring endothelial function in predicting cardiovascular events has not yet been fully explored.

Methods and Results: Patients with diabetes or hypertension were enrolled in this study. Three flow-mediated dilation (FMD) and 2 EndoPAT reactive hyperemia index (RHI) were measured periodically in 3 years at 1.5-year intervals. Patients were followed up for 10 years after the examination period. In the FMD study, 136 patients were classified as those with consistently good endothelial function, as defined by FMD >7% on 3 occasions (n=33), and those without (n=103). In multivariate Cox analysis, patients who maintained high FMD had less thromboembolic major cardiovascular events or angina pectoris (n=23; hazard ratio [HR] 0.216; 95% confidence interval [CI] 0.047–0.985; P=0.048). In the EndoPAT study, 120 patients were classified as those with consistently abnormal endothelial function, as defined by RHI <1.67 on 2 occasions (n=34), and those without (n=86). There were 9 (7%) all-cause deaths and 10 (8%) hospitalizations for heart failure. Patients with consistent RHI <1.67 had a higher mortality (HR 10.794; 95% CI 1.520–76.629; P=0.017) and incidence of heart failure (HR 5.356; 95% CI 1.301–22.052; P=0.020) after adjusting for age, sex, renal function, diabetes, and body mass index.

Conclusions: Repeated measurements improved the predictive performance and revealed differences between FMD and EndoPAT RHI, which were better at predicting coronary events and heart failure, respectively.