Original pre-clinical science
Increased CD62e+ Endothelial Microparticle Levels Predict Poor Outcome in Pulmonary Hypertension Patients

https://doi.org/10.1016/j.healun.2009.06.005Get rights and content

Background

Endothelial and leukocytes-derived microparticles (EMPs and LMPs, respectively) are increased in patients with pulmonary hypertension (PH). We hypothesized that the levels of circulating EMPs and LMPs could predict outcome in these patients.

Methods

Patients undergoing right heart catheterization for untreated pre-capillary PH were eligible for the study. Baseline hemodynamics and biologic and clinical parameters were measured at the time of enrollment. Measurements of CD62e+, CD144+ and CD31+/CD41− EMPs and CD45+ LMPs were performed using flow cytometry in venous platelet-free plasma samples. After inclusion, patients were treated at the discretion of the physician and prospectively followed for 12 months. The primary end-point was the combined occurrence of death and re-admission for right heart failure (RHF) or worsening of RHF symptoms.

Results

Seven of 21 patients (mean age 54.1 ± 3.5 years, 62% female) experienced the primary end-point during the study period. These patients had higher baseline levels of CD62e+ EMPs, LMPs and hsCRP (high sensitivity C-reactive protein) compared to patients without events (p < 0.05), whereas no difference was observed for other microparticles and functional and hemodynamics parameters. Receiver operating curve analysis showed that baseline CD62e+ EMPs levels of >353 events/μl predicted clinical complications. Kaplan–Meier analysis revealed that patients with baseline CD62e+ EMPs above this cut-off value had a significantly worse prognosis compared with those subjects who had levels below this cut-off (p = 0.02, log-rank statistics).

Conclusions

Elevated levels of circulating CD62e+ EMPs but not LMPs in PH patients prior to treatment are associated with adverse clinical events. Assessment of CD62e+ EMPs levels may represent a new tool for stratification of PH patients.

Section snippets

Inclusion Criteria

Patients who had already been scheduled for right heart catheterization as part of a planned work-up for PH were asked to participate in this study.8 Subjects ≥18 years old with pre-capillary pulmonary hypertension, without any PH-specific therapy (current treatment with endothelin-1 receptor antagonists, prostacyclin analogs or type 5 phosphodiesterase inhibitors), were eligible for inclusion. Exclusion criteria included: left ventricular (LV) ejection fraction <50%; pulmonary capillary wedge

Increased Levels of CD62e+ EMPs and LMPs in Patients Having Adverse Clinical Outcomes

Twenty-one patients were enrolled in this study. Their baseline characteristics are presented in Table 1. As reported previously, baseline CD31+/CD41− EMPs (2,480 ± 366 ev/μl), CD144+ EMPs (1,009 ± 175 ev/μl), CD62e+ EMPs (328 ± 66 ev/μl) and LMPs (319 ± 49 ev/μl) were higher in this group of PH patients than in 20 age- and gender-matched controls (781 ± 132 ev/μl, 199 ± 33 ev/μl, 75 ± 12 ev/μl and 139 ± 22 ev/μl, respectively; p < 0.05 for all) and chronic obstructive pulmonary disease (COPD)

Discussion

The main findings of the present study are: (1) levels of CD62e+ EMPs and LMPs are higher in patients with pre-capillary PH who experience adverse clinical events as compared with those who remain free of adverse events; and (2) a high level of circulating CD62e+ EMPs prior to initiation of a specific PH treatment is an independent predictor of poor clinical outcome.

PH is a multifactorial disease likely due to interactions between genetic susceptibility and various initiating stimuli such as

Disclosure Statement

Supported by an educational grant from the Wayne and Gladys Valley Foundation, the UCSF Cardiology Council and the Harold Castle Foundation (to Y.Y. and W.G.).

The authors have no conflicts of interest to disclose.

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Published by Elsevier Inc.