Clinical Research
Biomarkers
Significance of a Multiple Biomarkers Strategy Including Endothelial Dysfunction to Improve Risk Stratification for Cardiovascular Events in Patients at High Risk for Coronary Heart Disease

https://doi.org/10.1016/j.jacc.2009.05.022Get rights and content
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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)

Key Words

biomarkers
endothelium
microparticles
follow-up studies
coronary heart disease

Abbreviations and Acronyms

ACS
acute coronary syndromes
BNP
B-type natriuretic peptide
CAD
coronary artery disease
CHD
coronary heart disease
CI
confidence interval
DM
diabetes mellitus
eGFR
estimated glomerular filtration rate
EMP
endothelium-derived microparticle(s)
HDL
high-density lipoprotein
HR
hazard ratio
hsCRP
high-sensitivity C-reactive protein
LDL
low-density lipoprotein

Cited by (0)

This study was supported, in part, by grants-in-aid for Scientific Research (#C19590869 to Dr. Sugiyama) from the Ministry of Education, Science, and Culture, Japan; Advanced Education Program for Integrated Clinical, Basic and Social Medicine, Graduate School of Medical Sciences, Kumamoto University in Kumamoto, Japan (Support Program for Improvement of Graduate School Education, MEXT, Japan); and Kimura Memorial Heart Foundation Bayer Grant for Clinical Vascular Function 2008, Kurume, Japan.