Circulating CD34+ Progenitor Cells are Predictive of All-Cause and Cardiovascular Mortality and are Influenced by Physical Activity

Background
Circulating progenitor cells (CPCs) play an important role in vascular repair and may influence cardiovascular (CV) health and longevity. Exercise is known to modulate these cells via mobilization from the bone marrow. The primary aims of this study were to evaluate the association of CPCs with mortality and explore the association between physical activity (PA) and CPCs.

Design
We studied 1,751 individuals from the Framingham Offspring cohort (66 ± 9 years [40-92 years], 54% female). CPCs (CD34⁺, CD34⁺CD133⁺, CD34⁺CD133⁺KDR⁺) were measured in participants using flow cytometry. Multivariable cox regression analyses were performed to investigate relationship of CPCs with future CV event, CV mortality and all-cause mortality. Multivariate regression analyses were performed to determine the relationship between self-reported PA and CPC counts.

Results
Following adjustment for standard risk factors, there was an inverse association between CD34⁺ CPCs and all-cause mortality (hazard ratio (HR) per unit increase in CD34⁺, 0.79; 95% CI 0.64 – 0.98, P=0.036). CD34⁺CD133⁺ CPCs were inversely associated with CV mortality (HR 0.63, 95% CI 0.44 – 0.91, P=0.013). Associations of CD34⁺ and CD34⁺CD133⁺ with mortality were strongest in participants with pre-existing CVD. PA was associated with CD34⁺ CPCs only in CVD participants. This relationship was maintained after adjustment for confounding variables.

Conclusions
Higher number of CD34⁺ and CD34⁺ CD133⁺ CPCs were inversely associated with all-cause and CV mortality. These associations were strongest in participants already diagnosed with CVD. PA is independently associated with CD34⁺ CPCs in individuals with CVD only, suggestive of greater benefit for this population group.