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

Ayman Samman Tahhan, Muhammad Hammadah, Heval Mohamed Kelli, Jeong Hwan Kim, Pratik B. Sandesara, Ayman Alkhoder, Belal Kaseer, Mohamad Mazen Gafeer, Matthew Topel, Salim S. Hayek, Wesley T. O'Neal, Malik Obideen, Yi An Ko, Chang Liu, Iraj Hesaroieh, Ernestine Mahar, Viola Vaccarino, Edmund K. Waller, Arshed A. Quyyumi

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)467-476
Number of pages10
JournalCirculation research
Volume123
Issue number4
DOIs
StatePublished - 2018
Externally publishedYes

Keywords

  • Black
  • Cd34+
  • Disparity
  • Mmp-9
  • Outcomes
  • Progenitor cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint

Dive into the research topics of 'Circulating progenitor cells and racial differences a possible contribution to health disparity'. Together they form a unique fingerprint.

Cite this