Increased CD62e(+) endothelial microparticle levels predict poor outcome in pulmonary hypertension patients.
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/microl 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.
Department of Medicine, Division of Cardiology, University of California at San Francisco, San Francisco, California, USA.
Nicolas
N
Amabile
Christian
C
Heiss
Vivian
V
Chang
Franca S
FS
Angeli
Lauren
L
Damon
Eddie J
EJ
Rame
Dana
D
McGlothlin
William
W
Grossman
Teresa
T
De Marco
Yerem
Y
Yeghiazarians
D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D055252:Cell-Derived Microparticles / Q000276:immunology*; D015331:Cohort Studies; D019040:E-Selectin / Q000097:blood*; D004730:Endothelium, Vascular / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000453:epidemiology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000175:diagnosis* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
D015415:Biomarkers; D019040:E-Selectin; D002097:C-Reactive Protein