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


METHODS
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).


RESULTS
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.


CONCLUSIONS
This study demonstrates that increased plasma levels of EMPs is a robust independent predictor of severe CV outcome in end-stage renal failure patients.
INSERM, U970, Paris Cardiovascular Research Center–PARCC, Paris, France.
Nicolas
N
Amabile
Alain P
AP
Guérin
Alain
A
Tedgui
Chantal M
CM
Boulanger
Gérard M
GM
London
D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000401:mortality*; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D007676:Kidney Failure, Chronic / Q000150:complications / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012044:Regression Analysis; D006435:Renal Dialysis; D012307:Risk Factors; D015996:Survival Rate