Progenitor Cells and Clinical Outcomes in Patients With Acute Coronary Syndromes
Ayman Samman Tahhan1,2, Muhammad Hammadah1,2, Mohamad Raad1,2
1From the Emory Clinical Cardiovascular Research Institute Atlanta, GA (A.S.T., M.H., M.R., Z.A., A.A., P.B.S., H.M.-K., S.S.H., J.H.K., W.T.O., M.L.T., A.J.G., N.S., R.E.H., M.M.G., M.O., B.K., N.A., Y.-A.K., I.H., V.V., A.A.Q.).
Insights
Circulating progenitor cells (CPCs) are elevated after acute myocardial infarction (AMI) but lower CPC counts predict higher mortality in acute coronary syndrome (ACS) patients. This finding aids in risk stratification for cardiovascular disease.
Area of Science:
- Cardiovascular Medicine
- Regenerative Medicine
- Hematology
Background:
- Circulating progenitor cells (CPCs) are known to mobilize during ischemic injury.
- The predictive value of CPCs in acute coronary syndrome (ACS) has not been established.
- Understanding CPC dynamics is crucial for risk stratification in cardiovascular disease.
Purpose of the Study:
- To compare CPC counts in ACS patients versus stable coronary artery disease (CAD) patients.
- To investigate the relationship between bone marrow progenitor cells (PCs) and CPCs.
- To determine if CPC counts predict mortality in ACS patients.
Main Methods:
- Flow cytometry was used to enumerate CPCs (CD34+, CD133+, VEGFR2+, CXCR4+) in 2028 patients (ACS and stable CAD).
- CPC counts were correlated with bone marrow PC counts in a subset of patients.
- Mortality was assessed over a median follow-up of 2 years in 529 ACS patients.
Main Results:
- CPC counts were significantly higher in patients with acute myocardial infarction (AMI) compared to stable CAD, even after multivariate adjustment.
- Low counts of CD34+ CPCs were associated with a 2.46-fold increased risk of all-cause mortality in ACS patients.
- Results were validated in an independent cohort, confirming the prognostic value of CPCs.
Conclusions:
- Elevated CPC levels are observed post-AMI and reflect bone marrow progenitor cell content.
- Lower counts of hematopoietic-enriched CPCs are a significant predictor of mortality in patients with ACS.
- CPC enumeration offers a novel biomarker for risk stratification in 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 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.
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