Progenitor Cells and Clinical Outcomes in Patients with Acute Coronary Syndromes

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 to 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+, VEGFR2+, or CXCR4+. 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, 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 to 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 (IQR 1.31-2.86)-year follow-up period of 529 ACS patients, 12.4% died. In Cox regression models adjusted for age, gender, body mass index, heart failure history, estimated GFR, and AMI, subjects with low CD34+ cell counts had a 2.46-fold (95% CI 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 to 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.