Circulating Stem/Progenitor Cells as Prognostic Biomarkers in Macro- and Microvascular Disease: A Narrative Review of Prospective Observational Studies

Background: Circulating progenitor cells (CPCs) and endothelial progenitor cells (EPCs) are immature cells involved in vascular repair and related to many aspects of macro and microvascular disease. Objective: We aimed to review studies reporting the prognostic role of CPCs/EPCs measurement on development of cardiovascular disease and microangiopathy. Methods and Results: We reviewed the English language literature for prospective observational studies reporting the future development of cardiovascular disease or microangiopathy in patients having a baseline determination of CPCs/EPCs. We retrieved 34 studied reporting on cardiovascular outcomes and 2 studies reporting on microvascular outcomes. Overall, a reduced baseline level of CPCs/EPCs was associated with a significant increased risk of cardiovascular events, all-cause death, and onset/progression of microangiopathy. The most predictive phenotypes were CD34+ and CD34+CD133+. The main limitation was related to the high heterogeneity among studies in terms of patient characteristics and cell phenotypes. Conclusion: The present review shows that a reduced level of circulating progenitor cells is a risk factor for the development of future cardiovascular events and death. In addition, low CPCs/EPCs levels predict the onset or worsening of microalbuminuria and retinopathy in diabetic patients.