Circulating Progenitor Cells and Racial Differences: A Possible Contribution to Health Disparity
Rationale: Blacks compared to 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 (AMI) and the predictive value of CPC counts in Blacks compared with Whites.
Methods and Results: CPCs were enumerated by flow cytometry as CD45med+ blood mononuclear cells expressing CD34+,CD133+,VEGF2R+ and CXCR4+ epitopes in 1747 subjects, mean age 58.4±13, 55%male, 26%self-reported Black. Patients presenting with AMI (n=91) were analyzed separately. Models were adjusted for relevant clinical variables. Stromal cell-derived factor-1α(SDF-1α), vascular endothelial growth factor(VEGF), and matrix metallopeptidase-9(MMP-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%CI[-23.5%,-11.3%];P<0.001), CD34+/CD133+ cells (-15.5%;95%CI[-22.4%,-8.1%];P<0.001), CD34+/CXCR4+ cells (-17.3%;95%CI[-23.9%,-10.2%];P<0.001) and CD34+/VEGF2R+ cells (-27.9%;95%CI[-46.9%,-2.0%];P=0.04) compared to 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 AMI had significantly fewer CPCs compared to Whites (P=0.02). Blacks had significantly lower plasma MMP-9 levels (P<0.001) which attenuated the association between low CD34+ and Black race by 19% (95%CI13-33%). However, VEGF and SDF-1α levels were not significantly different between the races. Lower CD34+ counts were similarly predictive of mortality in Blacks (HR=2.83[95%CI 1.12-7.20];P=0.03) and Whites (HR=1.79[95%CI 1.09-2.94];P=0.02) without significant interaction.
Conclusions:Black subjects have lower levels of CPCs compared to 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.
- Received April 24, 2018.
- Revision received June 8, 2018.
- Accepted June 20, 2018.