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 (CVD), as they promote angiogenesis and vascular repair.
Objective: We herein aimed to meta-analyse 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 4,155 patients, mostly with a high baseline cardiovascular risk. 60% 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 vasculo-regenerative properties represents a risk factor for adverse cardiovascular outcomes and death.
- Received January 16, 2016.
- Revision received April 7, 2016.
- Accepted April 12, 2016.