Abstract 6202: Elevated Plasma Levels of Endothelial Microparticles Add Prognostic Value to Coronary Risk Factors in Patients at High Risk for Coronary Heart Disease
Endothelium-derived-microparticles (EMP) are small membrane-shed vesicles generated from endothelial cell surfaces in response to endothelial activation/injury, suggesting they can be a useful plasma marker of endothelial dysfunction. We investigated whether plasma CD144-EMP levels can be used to predict future cardiovascular events in patients at high risk for coronary heart disease (CHD). We measured plasma CD144-EMP levels by flow cytometry in 450 consecutive patients with variable CHD risk. We followed 352 stable patients at high risk for CHD for 50 months until the occurrence of cardiovascular events (cardiovascular death, myocardial infarction, unstable angina, ischemic stroke, coronary revascularization to new lesions, and lower limb amputation). Plasma CD144-EMP levels elevated significantly with increased cardiovascular risk and clinical manifestation: patients with low risk for CHD (risk factor ≤1, n=48, median [range], 0.271 [0.138 to 0.351]), multiple risk factors (risk factors ≥2, n=142, 0.491 [0.338 to 0.660]), stable coronary artery disease (n=214, 0.586 [0.434 to 0.790]), and acute coronary syndromes (n=46, 0.983 [0.718 to 1.208]×106/ml) (p<0.001). During a mean follow-up of 30 months, 44 patients developed cardiovascular events. Kaplan-Meier analysis demonstrated a significantly higher probability of cardiovascular events in the high-EMP group (above median; log-rank test p<0.001). Multivariate Cox proportional hazards analysis adjusting for age, gender, and significant factors in univariate analysis identified high-EMP level as the only significant predictors of cardiovascular events (hazard ratio 2.23 [95% CI, 1.05 to 4.71], p=0.04). The addition of EMP score (based on hazard ratio of cardiovascular events in multivariate analysis) to scores of conventional risk factors improved risk prediction, as measured by the C statistic (C statistics: 0.76 for conventional risk factors, 0.80 for conventional risk factors with EMP). Plasma levels of CD144-EMP in patients at high risk for CHD can independently predict future cardiovascular events, indicating CD144-EMP is a potentially useful maker of endothelial dysfunction leading to cardiovascular complications.