Circulating endothelial progenitor cells and cardiovascular outcomes

N Engl J Med. 2005 Sep 8;353(10):999-1007. doi: 10.1056/NEJMoa043814.


Background: Endothelial progenitor cells derived from bone marrow are believed to support the integrity of the vascular endothelium. The number and function of endothelial progenitor cells correlate inversely with cardiovascular risk factors, but the prognostic value associated with circulating endothelial progenitor cells has not been defined.

Methods: The number of endothelial progenitor cells positive for CD34 and kinase insert domain receptor (KDR) was determined with the use of flow cytometry in 519 patients with coronary artery disease as confirmed on angiography. After 12 months, we evaluated the association between baseline levels of endothelial progenitor cells and death from cardiovascular causes, the occurrence of a first major cardiovascular event (myocardial infarction, hospitalization, revascularization, or death from cardiovascular causes), revascularization, hospitalization, and death from all causes.

Results: A total of 43 participants died, 23 from cardiovascular causes. A first major cardiovascular event occurred in 214 patients. The cumulative event-free survival rate increased stepwise across three increasing baseline levels of endothelial progenitor cells in an analysis of death from cardiovascular causes, a first major cardiovascular event, revascularization, and hospitalization. After adjustment for age, sex, vascular risk factors, and other relevant variables, increased levels of endothelial progenitor cells were associated with a reduced risk of death from cardiovascular causes (hazard ratio, 0.31; 95 percent confidence interval, 0.16 to 0.63; P=0.001), a first major cardiovascular event (hazard ratio, 0.74; 95 percent confidence interval, 0.62 to 0.89; P=0.002), revascularization (hazard ratio, 0.77; 95 percent confidence interval, 0.62 to 0.95; P=0.02), and hospitalization (hazard ratio, 0.76; 95 percent confidence interval, 0.63 to 0.94; P=0.01). Endothelial progenitor-cell levels were not predictive of myocardial infarction or of death from all causes.

Conclusions: The level of circulating CD34+KDR+ endothelial progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and may help to identify patients at increased cardiovascular risk.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antigens, CD34
  • Biomarkers / blood
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / mortality
  • Cell Count
  • Colony-Forming Units Assay
  • Coronary Disease / blood*
  • Disease-Free Survival
  • Endothelial Cells* / immunology
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Mortality
  • Regression Analysis
  • Risk Factors
  • Stem Cells*
  • Vascular Endothelial Growth Factor Receptor-2


  • Antigens, CD34
  • Biomarkers
  • Vascular Endothelial Growth Factor Receptor-2