[HTML][HTML] Circulating progenitor cells and racial differences: a possible contribution to health disparity

AS Tahhan, M Hammadah, H Mohamed-Kelli… - Circulation …, 2018 - ncbi.nlm.nih.gov
AS Tahhan, M Hammadah, H Mohamed-Kelli, JH Kim, PB Sandesara, A Alkhoder, B Kaseer
Circulation research, 2018ncbi.nlm.nih.gov
Objectives 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 …
Objectives
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.
Conclusion
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.
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