Abstract 4871: Circulating Endothelial Microparticles: A Novel Biomarker for Prediction of Subsequent Death and Cardiovascular Events in End-stage Renal Disease

Abstract

Background: Endothelial dysfunction is closely associated with increased circulating levels of endothelial microparticles (EMPs) in patients with end-stage renal disease (ESRD). As arterial damage is a major contributor to cardiovascular mortality, we examined whether or not circulating levels of EMPs could predict outcome in ESRD. Methods: This prospective study included 81 stable hemodialyzed patients with ESRD (age 59±14 yr; 63% male; follow-up 57 months). Baseline plasma microparticles (MPs) levels, cell origin and reproducibility were analyzed by flow cytometry. The primary end-point was the occurrence of any death. Secondary end-points included cardiovascular death and occurrence of major adverse cardiovascular events (MACE). Results: Non-survivors (n=19) were older (70.6±9.2, vs. 55.1±13.2 y, p<0.001) and were characterized by lower diastolic blood pressure (70.8±10.5 vs. 80±12.4 mmHg, p<0.01), higher levels of hsCRP (6.9±4.4 vs. 5.0±4.3 mg/L, p<0.05) and endothelial CD31+CD41- EMPs (1822±1516 vs. 934±207 ev/ μ l, p<0.001), whereas other MPs subtypes were not different. Mutivariate Cox analysis demonstrated that baseline EMPs levels independently predicted all-cause death (HR=4.0 [1.2–13.0] per log unit, p=0.02), cardiovascular mortality (HR=8.81 [2.4 –31.8], p<0.001) and MACE (HR=3.28 [1.2 – 8.9], p<0.01) after adjustment for age, traditional cardiovascular risk factors, medications and biological parameters. ROC curve analysis showed that baseline EMPs levels correctly predicted all-causes and cardiovascular mortality (AUC: 0.80±0.008 and 0.83±0.008 respectively, p<0.001 for all). EMP baseline level > 710 event/ μ L correctly identified subsequent death with a sensitivity of 92% and a specificity of 63%. Kaplan-Meier analysis revealed that survival of patients with EMPs levels above median was worse than other patients (p<0.01, log rank analysis), whereas platelet MPs levels did not affect outcome. Conclusions: Increased circulating levels of endothelial microparticles is a robust independent predictor of all-causes and mainly cardiovascular mortality in patients with ESRD and could help identify asymptomatic patients at higher risk of developing cardiovascular diseases and adjust therapy.