Circulating Progenitor Cells and Racial Differences: A Possible Contribution to Health Disparity

• Type of Material: Article
• Authors: Ayman Samman Tahhan, Emory University; Muhammad Hammadah, Emory University; Heval Mohamed-Kelli, Emory University; Jeong Hwan Kim, Emory University; Pratik B. Sandesara, Emory University; Ayman Alkhoder, Emory University; Belal Kaseer, Emory University; Mohamad Mazen Gafeer, Emory University; Matthew Topel, Emory University; Salim S. Hayek, Emory University; Wesley T. O'Neal, Emory University; Malik Obideen, Emory University; Yi-An Ko, Emory University; Chang Liu, Emory University; Iraj Hesaroieh, Emory University; Ernestine Mahar, Emory University; Edmund K Waller, Emory University; Viola Vaccarino, Emory University; Arshed Quyyumi, Emory University
• Language: English
• Date: 2018-08-03
• Publisher: American Heart Association
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 American Heart Association, Inc.
• Final Published Version (URL): http://dx.doi.org/10.1161/CIRCRESAHA.118.313282
• Title of Journal or Parent Work: Circulation Research
• ISSN: 0009-7330
• Volume: 123
• Issue: 4
• Start Page: 467
• End Page: 476
• Grant/Funding Information: AST is supported by the Abraham J. & Phyllis Katz Foundation (Atlanta, GA) and NIH/NIA grant AG051633.; AAQ is supported by 1R61HL138657-01, 1P30DK111024-01, AHA: 0000031288, 5P01HL101398-02, 1P20HL113451-01, 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, 1U10HL110302-01, 2P01HL086773-06A1 and the Emory Predictive Health Institute.
• Keywords: MYOCARDIAL-INFARCTION; REGENERATIVE CAPACITY; CORONARY-ARTERY-DISEASE; Science & Technology; Peripheral Vascular Disease; Life Sciences & Biomedicine; RECRUITMENT; Cardiovascular System & Cardiology; BLOOD; NEOVASCULARIZATION; outcomes; ENDOTHELIAL-CELLS; HEMATOPOIETIC STEM; BONE-MARROW; CD34+; disparity; MMP-9; Hematology; progenitor cells; black; Cardiac & Cardiovascular Systems; MOBILIZATION
• Research Categories: Health Sciences, Medicine and Surgery; Biology, Biostatistics

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.