Circulating endothelial progenitor cells as predictors of long-term cardiovascular mortality after myocardial infarction: which definition should we use?

Abstract

\n \n \n Endothelial progenitor cells (EPCs) are bone marrow-derived cells that play a crucial role in vascular repair after an acute myocardial infarction (AMI). Recent studies suggest that circulating EPCs levels may be useful as a surrogate biomarker for cardiovascular (CV) events. Nevertheless, the lack of a consensual definition and phenotypic characterization of EPCs hampers its use in clinical practice. CD34+KDR+, CD45dimCD34+KDR+ and CD34+CD133+KDR+ are among the most used antigenic phenotypes to define circulating EPCs but the best phenotype to predict CV outcomes remains to be determined.\n \n \n \n To determine the EPCs surface phenotype that best predicts long-term CV death after an AMI, and to evaluate its optimal cut-off point.\n \n \n \n One-hundred AMI patients were prospectively enrolled in the study. Circulating EPCs were quantified through high-performance flow cytometer within the first 24 hours of admission using different surface markers combinations allowing to simultaneously compare three EPCs definitions: 1) CD34+KDR+, 2) CD45dimCD34+KDR+, 3) CD34+CD133+KDR+. Mean follow-up time was 8.0±2.2 years.\n \n \n \n The mean age of our population was 59.7±11.0, the majority of patients were male (90%), 65% had ST-elevation myocardial infarction (STEMI) and 35% non-ST segment elevation myocardial infarction (NSTEMI). Diabetes mellitus was present in 38% and hypertension in 67% of the studied sample. During the long-term follow-up, 34 patients had re-admissions due to cardiovascular causes, 11 of them for AMI. Thirty-one patients had major adverse cardiovascular events (MACE) and 19 died.\n Using ROC curves, the CD34+KDR+ phenotype showed the biggest area under the curve regarding prediction of CV mortality (0.722; p=0.010; confidence interval 95% (CI95%): 0.554 to 0.890). Patients with lower levels of EPCs according to this definition (≤0.022%) are 7 times more likely to die from CV causes at any time (hazard ratio = 7.55; p=0.008; CI95% 1.69 to 33.83).\n \n \n \n The CD34+KDR+ phenotype appears to be the best definition of circulating EPCs for predicting long-term CV mortality after AMI. Further studies with larger samples are needed to clarify the optimal cut-off point for determining patients at risk and its role in everyday Cardiology.\n \n \n \n Type of funding sources: Foundation. Main funding source(s): Bolsa de Estudo João Porto da Sociedade Portuguesa de Cardiologia CD34+KDR+ as a predictor of CV death\n