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Author Notes:

Address correspondence to: Dr. Arshed A. Quyyumi, Division of Cardiology, Emory Clinical Cardiovascular Research Institute, Emory University School of Medicine, 1462 Clifton Rd. NE, Suite 507, Atlanta, GA 30322, Tel: (404) 727-3655, Fax: (404) 712-8785, aquyyum@emory.edu

None of the authors have conflicts of interest to disclose.

Subjects:

Research Funding:

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.

AST is supported by the Abraham J. & Phyllis Katz Foundation (Atlanta, GA) and NIH/NIA grant AG051633.

We also acknowledge Caladrius, sponsors of PreSERVE-AMI study that enabled bone marrow sampling from patients enrolled in the trial.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cardiac & Cardiovascular Systems
  • Hematology
  • Peripheral Vascular Disease
  • Cardiovascular System & Cardiology
  • acute coronary syndrome
  • coronary artery disease
  • myocardial infarction
  • non-ST elevated myocardial infarction
  • prognosis
  • ACUTE MYOCARDIAL-INFARCTION
  • LEFT-VENTRICULAR FUNCTION
  • BONE-MARROW
  • STEM-CELLS
  • ENDOTHELIAL-CELLS
  • ARTERY-DISEASE
  • REGENERATIVE CAPACITY
  • MONONUCLEAR-CELLS
  • ISCHEMIC-HEART
  • MOBILIZATION

Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes

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Journal Title:

Circulation Research

Volume:

Volume 122, Number 11

Publisher:

, Pages 1565-1575

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2018 American Heart Association, Inc.

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