Association Between Change in Circulating Progenitor Cells During Exercise Stress and Risk of Adverse Cardiovascular Events in Patients With Coronary Artery Disease

1.  A decrease in circulating progenitor cells during exercise stress-testing in patients with stable coronary artery disease is associated with worse outcomes than the presence of myocardial ischemia.

Evidence Rating Level: 2 (Good)

Risk stratification for stable coronary artery disease (CAD) typically involves the measurement of stress-induced myocardial ischemia, often using single-photon emission computed tomography (SPECT) myocardial perfusion imaging. However, given the cost and radiation exposure associated with this technique, efforts are being focused towards the identification of surrogate biomarkers. Recent evidence suggests that levels of circulating progenitor cells (CPCs) and resident stem cells may be decreased in patients with myocardial ischemia, however, the impact on adverse cardiovascular events is unknown. In this prospective cohort study, 454 patients with stable CAD were studied to investigate the association between the change in CPC counts during stress testing and the risk of adverse cardiovascular events, specifically, cardiovascular death and myocardial infarction (MI). CPCs were enumerated with flow cytometry as CD34⁺ mononuclear cells, with additional evaluation of subsets co-expressing the chemokine receptor 4 (CXCR4⁺), at rest and 45 minutes after stress testing. Stress-induced myocardial ischemia was measured with SPECT myocardial perfusion imaging at rest and 30 to 60 minutes after stress testing. At baseline, 76% of patients were men, and 31.3% had stress-induced ischemia by SPECT. Researchers found that those with stress-induced ischemia had a decrease in circulating CD34⁺/CXCR4⁺ cells (median decrease 20.2%, IQR -45.3 to 5.5, p<0.001), whereas those without stress-induced ischemia experienced a cell count increase (median increase 3.2%, IQR -20.6 to 35.1, p<0.001). After adjusting for demographic variables and comorbidities, every unit increase in the ischemic defect was found to be associated with a 13% decrease in CD34⁺ cell counts after exercise stress. During a median follow-up of 3 years, 5.2% of patients experienced adverse events (12 cardiovascular deaths, 12 MIs). Stress-induced ischemia was significantly associated with adverse events after adjustment for covariates (HR 2.79, 95% CI 1.55 to 5.03). Furthermore, each 50% decrease in the CD34⁺/CXCR4⁺ count after stress testing, was found to be significantly associated with adverse outcomes, even after adjusting for presence of ischemia (HR 1.84, 95% CI 1.34 to 3; HR 2.59, 95% CI 1.15 to 5.32, respectively). In summary, this study suggests that a decreased CPC count during and after exercise is an even stronger predictor of adverse outcomes in patients with stable CAD than stress-induced myocardial ischemia. Thus, further research on the prognostic implications of increasing CPC mobilization are warranted.

Click to read the study in JAMA Cardiology

Image: PD

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