Circulation. 2005;111:2981-2987
Published online before print May 31, 2005, doi: 10.1161/CIRCULATIONAHA.104.504340
Published online before print May 31, 2005, doi: 10.1161/CIRCULATIONAHA.104.504340
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(Circulation. 2005;111:2981-2987.)
© 2005 American Heart Association, Inc.
Vascular Medicine |
Reduced Number of Circulating Endothelial Progenitor Cells Predicts Future Cardiovascular Events
Proof of Concept for the Clinical Importance of Endogenous Vascular Repair
From Molecular Cardiology, Department of Medicine III, J.W. Goethe University, Frankfurt, Germany.
Correspondence to Stefanie Dimmeler, PhD, or Andreas M. Zeiher, MD, Department of Internal Medicine III, Division of Cardiology, J.W. Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. E-mail dimmeler{at}em.uni-frankfurt.de or zeiher@em.uni-frankfurt.de
Received September 7, 2004; revision received December 20, 2004; accepted December 21, 2004.
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.
Methods and 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.
Key Words: atherosclerosis • coronary disease • stem cells, endothelial • endothelium • prognosis
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