Levels of Circulating Progenitor Cells, Cardiovascular Outcomes and Death: A Meta-Analysis of Prospective Observational Studies

Abstract

Rationale: Circulating progenitor cells (CPCs), including endothelial progenitor cells (EPCs) are biologically related to many aspects of cardiovascular disease, as they promote angiogenesis and vascular repair.

Objective: We herein aimed to meta-analyze studies reporting the prognostic role of the CPC/EPC measure on cardiovascular outcomes and death.

Methods and results: We screened the English-language literature for longitudinal studies reporting the association between baseline CPC/EPC levels, future cardiovascular events, and death. We retrieved 28 studies, 21 of which contained poolable data and entered the meta-analysis, for a total of 4155 patients, mostly with a high baseline cardiovascular risk. Sixty percent of the studies met at least 11 of 16 items of quality assessment. Overall, reduced CPC/EPC levels were associated with a ≈2-fold increased risk of future cardiovascular events and cardiovascular death. The most predictive phenotype was CD34(+)CD133(+): low versus high levels predicted cardiovascular events, restenosis after endovascular intervention, cardiovascular death, and all-cause mortality. Heterogeneity among studies and according to the CPC/EPC phenotype was generally high. Excluding studies for which the risk estimate had to be extrapolated or limiting the analyses to higher quality studies still indicated a significant risk for future cardiovascular events and death in patients with low versus high progenitor cell counts.

Conclusions: This meta-analysis shows that a reduction in the levels of circulating cells putatively provided with vasculoregenerative properties represents a risk factor for adverse cardiovascular outcomes and death.

Keywords: endothelial progenitor cells; epidemiology; prevention & control; regeneration; stem cells.