Endothelial Function Assessed by Automatic Measurement of Enclosed Zone Flow-Mediated Vasodilation Using an Oscillometric Method Is an Independent Predictor of Cardiovascular Events

Abstract

Background: A new device for automatic measurement of flow-mediated vasodilation (FMD) using an oscillometric method has been developed to solve technical problems of conventional FMD measurement. This device measures enclosed zone FMD (ezFMD). The purpose of this study was to evaluate the prognostic value of endothelial function assessed by ezFMD for future cardiovascular events.

Methods and results: We measured ezFMD in 272 participants who underwent health-screening examinations. First, we investigated cross-sectional associations between ezFMD and cardiovascular risk factors, and then we assessed the associations between ezFMD and first major cardiovascular events (death from cardiovascular causes, stroke, and coronary revascularization). Univariate regression analysis revealed that ezFMD was significantly correlated with age, triglycerides, glucose, smoking pack-years, estimated glomerular filtration rate, high-sensitivity C-reactive protein, and Framingham risk score. During a median follow-up period of 36.1 months (interquartile range 18.8-40.1 months), 12 participants died (6 from cardiovascular causes), 3 had stroke, 8 had coronary revascularization, and 10 were hospitalized for heart failure. There was no episode of acute coronary syndrome during the study period. Participants were divided into tertiles (low, intermediate, and high) based on ezFMD. Kaplan-Meier curves for first major cardiovascular events among the 3 groups were significantly different (P=0.004). After adjustment for cardiovascular risk factors, the low group was significantly associated with an increased risk of first major cardiovascular events compared with the high group (hazard ratio 6.47; 95% CI 1.09-125.55; P=0.038).

Conclusions: These findings suggest that endothelial function assessed by ezFMD may be useful as a surrogate marker of future cardiovascular events.

Clinical trial registration: URL: https://upload.umin.ac.jp. Unique identifier: UMIN000004902.

Keywords: atherosclerosis; biomarker; cardiovascular events; endothelial function.

Figure 1

Bar graphs show enclosed zone flow‐mediated vasodilation (ezFMD) in the no‐risk, at‐risk, and cardiovascular disease (CVD) groups.

Figure 2

Receiver operating characteristic curves of enclosed zone flow‐mediated vasodilation for predicting first major cardiovascular events. AUC indicates area under the curve.

Figure 3

Kaplan–Meier curves of cumulative event‐free survival of first major cardiovascular events (death from cardiovascular causes, stroke, and coronary revascularization) according to enclosed zone flow‐mediated vasodilation (ezFMD). High group indicates ezFMD >32.3%, intermediate group indicates ezFMD 19.5% to 32.3%, and low group indicates ezFMD <19.5%.

Figure 4

Kaplan–Meier curves of cumulative event‐free survival of death from cardiovascular causes (A), stroke (B), coronary revascularization (C), hospitalization for heart failure (D), and death from any cause (E), according to the enclosed zone flow‐mediated vasodilation (ezFMD). High group indicates ezFMD >32.3%, intermediate group indicates ezFMD 19.5% to 32.3%, and low group indicates ezFMD <19.5%.

Figure 5

Scatter plots show the relationships between enclosed zone flow‐mediated vasodilation (ezFMD) and flow‐mediated vasodilation (FMD) (A) and reactive hyperemia ratio (B).