Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair.
BACKGROUND
The maintenance of endothelial integrity plays a critical role in preventing atherosclerotic disease progression. Endothelial progenitor cells (EPCs) were experimentally shown to incorporate into sites of neovascularization and home to sites of endothelial denudation. Circulating EPCs may thus provide an endogenous repair mechanism to counteract ongoing risk factor-induced endothelial injury and to replace dysfunctional endothelium.


RESULTS
In 120 individuals (43 control subjects, 44 patients with stable coronary artery disease, and 33 patients with acute coronary syndromes), circulating EPCs were defined by the surface markers CD34+KDR+ and analyzed by flow cytometry. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, PTCA, CABG, or ischemic stroke) served as outcome variables over a median follow-up period of 10 months. Patients suffering from cardiovascular events had significantly lower numbers of EPCs (P<0.05). Reduced numbers of EPCs were associated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis (P=0.0009). By multivariate analysis, reduced EPC levels were a significant, independent predictor of poor prognosis, even after adjustment for traditional cardiovascular risk factors and disease activity (hazard ratio, 3.9; P<0.05).


CONCLUSIONS
Reduced levels of circulating EPCs independently predict atherosclerotic disease progression, thus supporting an important role for endogenous vascular repair to modulate the clinical course of coronary artery disease.
Schmidt-Lucke
Caroline
C
Molecular Cardiology, Department of Medicine III, J.W. Goethe University, Frankfurt, Germany.
Rössig
Lothar
L
Fichtlscherer
Stephan
S
Vasa
Mariuca
M
Britten
Martina
M
Kämper
Ulrike
U
Dimmeler
Stefanie
S
Zeiher
Andreas M
AM
D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000097:blood; D018952:Antigens, CD34 / Q000032:analysis; D050197:Atherosclerosis / Q000209:etiology; D001772:Blood Cell Count; D001808:Blood Vessels / Q000502:physiology*; D002318:Cardiovascular Diseases / Q000175:diagnosis*; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood; D018450:Disease Progression; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D018952:Antigens, CD34; D040301:Vascular Endothelial Growth Factor Receptor-2