Circulating progenitor cells and racial differences a possible contribution to health disparity

Rationale: Blacks compared with whites have a greater risk of adverse cardiovascular outcomes. Impaired regenerative capacity, measured as lower levels of circulating progenitor cells (CPCs), is a novel determinant of adverse outcomes; however, little is known about racial differences in CPCs. Objective: To investigate the number of CPCs, PC-mobilizing factors, PC mobilization during acute myocardial infarction and the predictive value of CPC counts in blacks compared with whites. Methods and Results: CPCs were enumerated by?ow cytometry as CD45med+ blood mononuclear cells expressing CD34+, CD133+, VEGF2R+, and CXCR4+ epitopes in 1747 subjects, mean age 58.4±13, 55% male, and 26% self-reported black. Patients presenting with acute myocardial infarction (n=91) were analyzed separately. Models were adjusted for relevant clinical variables. SDF-1a (stromal cell-derived factor-1a), VEGF (vascular endothelial growth factor), and MMP-9 (matrix metallopeptidase-9) levels were measured (n=561), and 623 patients were followed for median of 2.2 years for survival analysis. Blacks were younger, more often female, with a higher burden of cardiovascular risk, and lower CPC counts. Blacks had fewer CD34+ cells (-17.6%; [95% confdence interval (CI),-23.5% to-11.3%]; P<0.001), CD34+/CD133+ cells (-15.5%; [95% CI,-22.4% to-8.1%]; P<0.001), CD34+/CXCR4+ cells (-17.3%; [95% CI,-23.9% to-10.2%]; P<0.001), and CD34+/VEGF2R+ cells (-27.9%; [95% CI,-46.9% to-2.0%]; P=0.04) compared with whites. The association between lower CPC counts and black race was not affected by risk factors or cardiovascular disease. Results were validated in a separate cohort of 411 patients. Blacks with acute myocardial infarction had signifcantly fewer CPCs compared with whites (P=0.02). Blacks had signifcantly lower plasma MMP-9 levels (P<0.001) which attenuated the association between low CD34+ and black race by 19% (95% CI, 13%-33%). However, VEGF and SDF-1a levels were not signifcantly different between the races. Lower CD34+ counts were similarly predictive of mortality in blacks (hazard ratio, 2.83; [95% CI, 1.12-7.20]; P=0.03) and whites (hazard ratio, 1.79; [95% CI, 1.09-2.94]; P=0.02) without signifcant interaction. Conclusions: Black subjects have lower levels of CPCs compared with whites which is partially dependent on lower circulating MMP-9 levels. Impaired regenerative capacity is predictive of adverse outcomes in blacks and may partly account for their increased risk of cardiovascular events.