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Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction
Mohamed Abo-Aly1,2, Elica Shokri1, Lakshman Chelvarajan1
1Gill Heart and Vascular Institute, University of Kentucky, Lexington, KY 40536, USA.
Insights
High levels of nonclassical CD14+CD16++ monocytes predict adverse outcomes in ST-elevation myocardial infarction (STEMI) patients. These monocytes, especially subsets expressing CCR2, CD42, and CD11b, are key predictors of clinical events post-STEMI.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Biomarker Discovery
Background:
- Monocyte subsets (classical, intermediate, nonclassical) have distinct roles in cardiovascular health and disease.
- The prognostic value of specific monocyte subsets in coronary artery disease, particularly ST-elevation myocardial infarction (STEMI), requires further elucidation.
Purpose of the Study:
- To assess the predictive efficacy of different monocyte subsets for adverse clinical outcomes in STEMI patients undergoing primary percutaneous coronary intervention (PCI).
Main Methods:
- Recruited 100 STEMI patients undergoing primary PCI.
- Collected blood samples at baseline and at 3, 6, 12, and 24 hours post-presentation.
- Defined and subdivided monocytes based on CD14, CD16, CCR2, CD11b, and CD42 expression.
- Analyzed a composite endpoint of death, heart failure hospitalization, stent thrombosis, restenosis, and recurrent myocardial infarction using Cox proportional hazards models.
Main Results:
- Elevated levels of nonclassical CD14+CD16++ monocytes were associated with a significantly increased risk of adverse clinical outcomes.
- Specific subsets, including CD14+/CD16++/CCR2+, CD14+/CD16++/CD42b+, and CD14+/CD16++/CD11b+, showed significant predictive value (aHRs ranging from 3.37 to 5.17).
- Classical (CD14++CD16-) and intermediate (CD14++CD16+) monocyte subsets did not significantly predict the composite endpoint.
Conclusions:
- The nonclassical monocyte subset (CD14+CD16++) and its specific expressing subsets (CCR2, CD42, CD11b) are potent predictors of clinical outcomes in STEMI patients.
- These monocyte subsets may serve as valuable biomarkers for risk stratification in STEMI.
- Larger studies are warranted to validate these findings across diverse coronary artery disease phenotypes.
Abstract:
Circulating monocytes have different subsets, including classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++), which play different roles in cardiovascular physiology and disease progression. The predictive value of each subset for adverse clinical outcomes in patients with coronary artery disease is not fully understood. We sought to evaluate the prognostic efficacy of each monocyte subset in patients with ST-elevation myocardial infarction (STEMI). We recruited 100 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Blood samples were collected at the time of presentation to the hospital (within 6 h from onset of symptoms, baseline (BL)) and then at 3, 6, 12, and 24 h after presentation. Monocytes were defined as CD45+/HLA-DR+ and then subdivided based on the expression of CD14, CD16, CCR2, CD11b, and CD42. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, stent thrombosis, in-stent restenosis, and recurrent myocardial infarction. Univariate and multivariate Cox proportional hazards models, including baseline comorbidities, were performed. The mean age of our cohort was 58.9 years and 25% of our patients were females. Patients with high levels (above the median) of CD14+CD16++ monocytes showed an increased risk for the primary endpoint in comparison to patients with low levels; adjusted hazard ratio (aHR) for CD14+/CD16++ cells was 4.3 (95% confidence interval (95% CI) 1.2-14.8, p = 0.02), for CD14+/CD16++/CCR2+ cells was 3.82 (95% CI 1.06-13.7, p = 0.04), for CD14+/CD16++/CD42b+ cells was 3.37 (95% CI 1.07-10.6, p = 0.03), for CD14+/CD16++/CD11b+ was 5.17 (95% CI 1.4-18.0, p = 0.009), and for CD14+ HLA-DR+ was 7.5 (95% CI 2.0-28.5, p = 0.002). CD14++CD16-, CD14++CD16+, and their CD11b+, CCR2+, and CD42b+ aggregates were not significantly predictive for our composite endpoint. Our study shows that CD14+ CD16++ monocytes and their subsets expressing CCR2, CD42, and CD11b could be important predictors of clinical outcomes in patients with STEMI. Further studies with a larger sample size and different coronary artery disease phenotypes are needed to verify the findings.
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