Reduced numbers of circulating endothelial progenitor cells in patients with coronary artery disease associated with long-term statin treatment

Atherosclerosis. 2007 Jun;192(2):413-20. doi: 10.1016/j.atherosclerosis.2006.05.031. Epub 2006 Jul 11.


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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD34 / analysis
  • Cell Count
  • Coronary Artery Disease / drug therapy*
  • Endothelial Cells / cytology*
  • Female
  • Flow Cytometry
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Vascular Endothelial Growth Factor Receptor-2 / blood


  • Antigens, CD34
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Vascular Endothelial Growth Factor Receptor-2