title: Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment.
abstract: While statin treatment may transiently mobilize endothelial progenitor cells (EPCs), the dose-dependent effects of a continuous statin therapy on EPCs in patients with chronic coronary artery disease (CAD) have not been analyzed. In 209 patients with angiographically documented CAD, 144 of which received 10-40 mg/day of statins for >8 weeks, the EPC number was determined by flow cytometry directly (CD34(+)/KDR(+), n=58) and after in vitro-culture (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled Ac-LDL (DiI-Ac-LDL(+))/lectin(+), n=209). EPC function was assessed by the formation of colony forming units (CFUs). Univariate analysis revealed that the dose of continuous statin therapy inversely correlated with the EPC number. Treatment with 40 mg/day significantly reduced EPC counts. Multivariate analysis unveiled the statin dose and extent of CAD as independent predictors of reduced EPC numbers. Conversely, obesity predicted increased counts, while CFU development was not detectable in all patients and augmented in females and smokers but not in statin-treated patients. Compared with matched controls, statin-treated patients showed significantly reduced absolute and relative EPC counts. In a prospective analysis, initiation of statin therapy significantly diminished the number of circulating and isolated EPCs after 3 but not after 1 month(s). Thus, the statin dose during chronic and continuous treatment independently predicts reduced numbers of circulating as well as isolated EPCs in patients with CAD.
authors.affiliation: Institute for Molecular Cardiovascular Research, RWTH Aachen University, University Hospital Aachen, Aachen, Germany.
authors.forename: Mihail
authors.initials: M
authors.lastname: Hristov
authors.forename: Christian
authors.initials: C
authors.lastname: Fach
authors.forename: Carolin
authors.initials: C
authors.lastname: Becker
authors.forename: Nicole
authors.initials: N
authors.lastname: Heussen
authors.forename: Elisa A
authors.initials: EA
authors.lastname: Liehn
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Blindt
authors.forename: Peter
authors.initials: P
authors.lastname: Hanrath
authors.forename: Christian
authors.initials: C
authors.lastname: Weber
mesh_terms: D018952:Antigens, CD34 / Q000032:analysis; D002452:Cell Count; D003324:Coronary Artery Disease / Q000188:drug therapy*; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood
chemical_list: D018952:Antigens, CD34; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D040301:Vascular Endothelial Growth Factor Receptor-2