OBJECTIVES: We investigated whether a multiple biomarkers strategy that includes plasma levels of endothelium-derived microparticles (EMP), reflecting
endothelial dysfunction, can improve prediction of future
cardiovascular events in patients at high risk for
coronary heart disease (CHD). BACKGROUND: Detailed risk stratification using multiple biomarkers can provide clinical benefits in high-risk patients.
Endothelial dysfunction has been described as a predictor of
cardiovascular complications. METHODS: We measured 3 biomarkers in 488 consecutive patients with various CHD risks: B-type natriuretic
peptide (BNP), high-sensitivity
C-reactive protein (hsCRP), and EMP. We followed 387 stable patients at high risk for CHD and examined future
cardiovascular events. RESULTS: During a
mean follow-up of 36 months, 55 patients developed
cardiovascular events.
Multivariate Cox proportional hazards analysis adjusted for established
risk factors identified age, BNP, hsCRP, and EMP as significant and independent predictors of future
cardiovascular events (age:
hazard ratio [HR]: 1.042, 95%
confidence interval [CI]: 1.007 to 1.080, p = 0.02; BNP: HR: 1.242, 95% CI: 1.004 to 1.536, p = 0.046; hsCRP: HR: 1.468, 95% CI: 1.150 to 1.875, p = 0.002; EMP: HR: 1.345, 95% CI: 1.094 to 1.652, p = 0.005). The C
statistics for
cardiovascular events increased when each biomarker or combinations of biomarkers were added to the Framingham risk model (C
statistics: Framingham risk model alone 0.636, Framingham risk + BNP 0.695, Framingham risk + hsCRP 0.696, Framingham risk + EMP 0.682, and Framingham risk + BNP + hsCRP + EMP 0.763). CONCLUSIONS: The assessment of
endothelial dysfunction by plasma levels of EMP can independently predict future
cardiovascular events in patients at high risk for CHD. A multiple biomarkers strategy that includes
endothelial dysfunction assessed by EMP can identify patients vulnerable to
cardiovascular disease. (University Hospital Medical Information Network number: UMIN000000876).
