Abstract 6165: Increased Circulating Cd62e+ Endothelial Microparticles Levels Predict Poor Outcome in Pulmonary Hypertension Patients

Abstract

Pulmonary hypertension (PH) is characterized by vascular remodeling and endothelial dysfunction. Levels of endothelial (EMPs) and leukocytes-derived (LMPs) microparticles, which are submicron membrane fragments shed from damaged or activated cells, have been shown to be significantly increased in PH patients compared to healthy controls. We hypothesized that the levels of circulating endothelial and leukocytes-MPs could predict outcome in these patients. Patients undergoing right heart catheterization for untreated pre-capillary PH, and without any conditions associated with increased circulating MPs levels, were eligible for the study. The following were measured at the time of enrollment: body mass index, mean pulmonary artery pressure (mPAP), C reactive protein (CRP)and BNP. CD62e+, CD144+, and CD31+/CD41− EMPs and CD45+ LMPs were measured using flow cytometry in platelet-free plasma from venous blood. After inclusion, patients were treated at the discretion of the physician and prospectively followed for 12 months. The primary endpoint assessed was the combined occurrence of death and readmission for right heart failure (RHF) or worsening of RHF symptoms. Seven of 21 patients (mean age=54.1±3.5y/62% female) experienced an adverse clinical event during this period. These patients had significantly higher baseline levels of CD62e+ EMPs (581±123 vs. 202±52 ev/μL, p=0.003), CD45+ LMPs (500±141 vs. 247±44 ev/μL, p=0.03) and CRP (9.9±2.2 vs. 3.8±0.7 IU/L, p=0.004) than patients without events, whereas no difference was observed for CD31+/CD41− and CD144+ EMPs, mPAP or baseline plasma BNP values. Moreover, CD62e+ levels correlated significantly with CD45+ LMPs (r=0.70, p=0.001). Multivariate analysis revealed that 4th quartile levels of CD62e+ EMPs was an independent predictor of adverse event after adjustment for CRP, CD45+ LMPs levels, body mass index and gender. These preliminary results show that high levels of circulating CD62e+ EMPs prior to treatment, but not other MPs subpopulations, are associated with clinical adverse events in PH subjects. These data suggest that this new biological parameter may be useful to predict outcome in patients with PH.