Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes

• Type of Material: Article
• Authors: Ayman Samman Tahhan, Emory University; Muhammad Hammadah, Emory University; Mohamad Raad, Emory University; Zakaria Almuwaqqat, Emory University; Ayman Alkhoder, Emory University; Pratik B Sandesara, Emory University; Heval Mohamed-Kelli, Emory University; Salim S Hayek, Emory University; Jeong Hwan Kim, Emory University; Wesley T O'Neal, Emory University; Matthew L Topel, Emory University; Aubrey J Grant, Emory University; Nabil Sabbak, Emory University; Robert E Heinl, Emory University; Mohamad Mazen Gafeer, Emory University; Malik Obideen, Emory University; Belal Kaseer, Emory University; Nasser Abdelhadi, Emory University; Yi-An Ko, Emory University; Chang Liu, Emory University; Iraj Hesaroieh, Emory University; Ernestine A Mahar, Emory University; Viola Vaccarino, Emory University; Edmund K Waller, Emory University; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2018-05-25
• 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.118.312821
• Title of Journal or Parent Work: Circulation Research
• ISSN: 0009-7330
• Volume: 122
• Issue: 11
• Start Page: 1565
• End Page: 1575
• Grant/Funding Information: AST is supported by the Abraham J. & Phyllis Katz Foundation (Atlanta, GA) and NIH/NIA grant AG051633.; AAQ is supported by 5P01HL101398-02, 1P20HL113451-01, 1R56HL126558-01, 1RF1AG051633-01, R01 NS064162-01, R01 HL89650-01, HL095479-01, 1U10HL110302-01, 1DP3DK094346-01, 2P01HL086773-06A1.; We also acknowledge Caladrius, sponsors of PreSERVE-AMI study that enabled bone marrow sampling from patients enrolled in the trial.
• Keywords: LEFT-VENTRICULAR FUNCTION; REGENERATIVE CAPACITY; MOBILIZATION; Hematology; prognosis; Science & Technology; BONE-MARROW; non-ST elevated myocardial infarction; ACUTE MYOCARDIAL-INFARCTION; MONONUCLEAR-CELLS; acute coronary syndrome; ISCHEMIC-HEART; myocardial infarction; coronary artery disease; Cardiac & Cardiovascular Systems; Cardiovascular System & Cardiology; ARTERY-DISEASE; Peripheral Vascular Disease; ENDOTHELIAL-CELLS; Life Sciences & Biomedicine; STEM-CELLS
• Research Categories: Biology, Biostatistics; Biology, Cell; Health Sciences, Oncology

Abstract

Rationale: Circulating progenitor cells (CPCs) mobilize in response to ischemic injury, but their predictive value remains unknown in acute coronary syndrome (ACS). Objective: We aimed to investigate the number of CPCs in ACS compared with those with stable coronary artery disease (CAD), relationship between bone marrow PCs and CPCs, and whether CPC counts predict mortality in patients with ACS. Methods and Results: In 2028 patients, 346 had unstable angina, 183 had an acute myocardial infarction (AMI), and the remaining 1499 patients had stable CAD. Patients with ACS were followed for the primary end point of all-cause death. CPCs were enumerated by flow cytometry as mononuclear cells expressing a combination of CD34+, CD133+, vascular endothelial growth factor receptor 2+, or chemokine (C-X-C motif) receptor 4+. CPC counts were higher in subjects with AMI compared those with stable CAD even after adjustment for age, sex, race, body mass index, renal function, hypertension, diabetes mellitus, hyperlipidemia, and smoking; CD34+, CD34+/CD133+, CD34+/CXCR4+, and CD34+/VEGFR2+ CPC counts were 19%, 25%, 28%, and 142% higher in those with AMI, respectively, compared with stable CAD. There were strong correlations between the concentrations of CPCs and the PC counts in bone marrow aspirates in 20 patients with AMI. During a 2 (interquartile range, 1.31-2.86)-year follow-up period of 529 patients with ACS, 12.4% died. In Cox regression models adjusted for age, sex, body mass index, heart failure history, estimated glomerular filtration rate, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% confidence interval, 1.18-5.13) increase in all-cause mortality, P=0.01. CD34+/CD133+ and CD34+/CXCR4+, but not CD34+/VEGFR2+ PC counts, had similar associations with mortality. Results were validated in a separate cohort of 238 patients with ACS. Conclusions: CPC levels are significantly higher in patients after an AMI compared with those with stable CAD and reflect bone marrow PC content. Among patients with ACS, a lower number of hematopoietic-enriched CPCs are associated with a higher mortality.