Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study

Abstract

Endothelial dysfunction in cardiovascular (CV) diseases is closely associated with increases in plasma level of shed membrane microparticles (MPs) of endothelial origin. As arterial damage is a major contributor to CV mortality, we examined whether or not increases in endothelial microparticles (EMPs) circulating levels could predict outcome in patients with end-stage renal disease (ESRD). This prospective pilot study conducted in a community hospital (median follow-up: 50.5 months), included 81 stable haemodialysed ESRD patients (59 ± 14 years; 63% male). Platelet-free plasma obtained 72 h after last dialysis was analysed by flow cytometry, and MPs cellular origin identified as endothelial (CD31+CD41-MPs; EMPs), platelets (CD31+CD41+MPs) or erythrocyte (CD235a+MPs). The main outcome measures were global and CV mortality (fatal myocardial infarction, stroke, acute pulmonary oedema and sudden cardiac death). Non-survivors (n = 24) were older (P < 0.001) and characterized by higher levels of EMPs (P < 0.01) and high-sensitivity C-reactive protein (P < 0.05) and lower diastolic blood pressure (P < 0.001). Kaplan-Meier analysis demonstrated significantly higher probability of all-cause (P < 0.001) and CV mortality (P < 0.0001) between the lower and upper EMPs tertiles. Multivariate Cox regression analysis demonstrated that baseline EMP levels independently predicted all-cause [hazard ratio (HR) = 21.7, 95% confidence interval (CI): 4.23-111.18 per log EMPs/μL; P = 0.0002] and CV mortality (HR = 20.0, 95% CI: 3.86-103.5) per log EMPs/μL; P < 0.0004) after adjustment for confounding factors. EMPs baseline level was a stronger predictor of poor outcome than classical risk factors. This study demonstrates that increased plasma levels of EMPs is a robust independent predictor of severe CV outcome in end-stage renal failure patients.