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

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.