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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) (J Am Coll Cardiol 2009;54:601–8) © 2009 by the American
College of Cardiology Foundation
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