Effect of erythropoietin on level of circulating endothelial progenitor cells and outcome in patients after acute ischemic stroke.
BACKGROUND
Erythropoietin (EPO) enhances the circulating level of endothelial progenitor cells (EPCs), which has been reported to be associated with prognostic outcome in ischemic stroke (IS) patients. The aim of this study was to evaluate the time course of circulating EPC level and the impact of EPO therapy on EPC level and clinical outcome in patients after acute IS.


METHODS
In total, 167 patients were prospectively randomized to receive either EPO therapy (group 1) (5,000 IU each time, subcutaneously) at 48 h and 72 h after acute IS, or serve as placebo (group 2). The circulating level of EPCs (double-stained markers: CD31/CD34 (E1), CD62E/CD34 (E2) and KDR/CD34 (E3)) was determined using flow cytometry at 48 h and on days 7 and 21 after IS. EPC level was also evaluated once in 60 healthy volunteers.


RESULTS
Circulating EPC (E1 to E3) level at 48 h after IS was remarkably higher in patients than in control subjects (P < 0.02). At 48 h and on Day 7 after IS, EPC (E1 to E3) level did not differ between groups 1 and 2 (all P > 0.1). However, by Day 21, EPC (E1 to E3) level was significantly higher in group 1 than in group 2 (all P < 0.03). Additionally, 90-day recurrent stroke rate was notably lower in group 1 compared with group 2 (P = 0.022). Multivariate analysis demonstrated that EPO therapy (95% confidence interval (CI), 0.153 to 0.730; P = 0.006) and EPC (E3) (95% CI, 0.341 to 0.997; P = 0.049) levels were significantly and independently predictive of a reduced 90-day major adverse neurological event (MANE) (defined as recurrent stroke, National Institutes of Health Stroke scale ≥8, or death).


CONCLUSIONS
EPO therapy significantly improved circulating EPC level and 90-day MANE.


BACKGROUND
ISRCTN: ISRCTN96340690.
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital - Kaohsiung Medical Center, Chang Gung University College of Medicine, 123 Ta-Pei Road, Niaosong District, Kaohsiung City 833, Taiwan. han.gung@msa.hinet.net
Hon-Kan
HK
Yip
Tzu-Hsien
TH
Tsai
Hung-Sheng
HS
Lin
Shu-Fang
SF
Chen
Cheuk-Kwan
CK
Sun
Steve
S
Leu
Chun-Man
CM
Yuen
Teng-Yeow
TY
Tan
Min-Yu
MY
Lan
Chia-Wei
CW
Liou
Cheng-Hsien
CH
Lu
Wen-Neng
WN
Chang
D000368:Aged; D015415:Biomarkers / Q000097:blood; D042783:Endothelial Cells / Q000378:metabolism*; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006397:Hematinics / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D013234:Stem Cells / Q000378:metabolism*; D020521:Stroke / Q000097:blood / Q000188:drug therapy*; D013997:Time Factors; D016896:Treatment Outcome
D015415:Biomarkers; D006397:Hematinics; D004921:Erythropoietin
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