Elsevier

International Journal of Cardiology

Volume 318, 1 November 2020, Pages 123-125
International Journal of Cardiology

Short communication
Endothelial progenitor cells predict long-term outcome in patients with coronary artery disease: Ten-year follow-up of the PROCREATION extended study

https://doi.org/10.1016/j.ijcard.2020.06.002Get rights and content

Highlights

  • Endothelial progenitor cells relate to prognosis in coronary artery disease.

  • Subpopulations of EPCs can improve also long-term risk factor characterization.

  • EPCs might be helpful for more precisely predicting individual risk.

Abstract

Background

Levels of circulating endothelial progenitor cells (EPCs) are associated with the short-term prognosis of patients with coronary artery disease (CAD). No previous study, however, has ascertained if EPCs are related also to long-term outcome. We performed a pre-specified analysis of the PROCREATION (PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention) study in order to assess if EPCs predict the 10-year prognosis.

Methods and results

Consecutive stable patients with CAD who were included in the PROCREATION study were evaluated. Patients underwent an extended 10-year follow-up to assess major adverse cardiac or cerebrovascular events (MACCE), i.e. death, stroke, myocardial infarction, and revascularization. During follow-up, MACCE occurred in 79 of 149 patients (53%). Most clinical and angiographic baseline variables were similar in patients with or without MACCE, apart from age, diabetes, chronic kidney disease, ejection fraction, and extent of CAD. Comparison of EPCs, conversely, showed that patients with MACCE had greater levels of CD34+/KDR+/CD45- cells (p=0.0002) and CD133+/KDR+/CD45- cells (p=0.0001). Multivariate analysis showed that factors independently associated with 10-year MACCEs were age (p=0.001), ejection fraction (p=0.018), and CD34+/KDR+/CD45- cells (p=0.024).

Conclusion

Subpopulations of EPCs can improve long-term risk factor characterization in patients with CAD. (ClinicalTrials.gov: NCT01575431)

Introduction

Endothelial progenitor cells (EPCs) are bone marrow-derived cells that play a key role in maintaining homeostasis of the endothelium [1]. In the last decade, several studies have been carried out to assess the predictive role of circulating EPCs in patients with coronary artery disease (CAD) [2,3]. Overall, these previous investigations have correlated subpopulations of EPCs with the short-term outcome of patients with CAD, but have not ascertained if EPCs are related also to long-term events. To address this issue, we performed a pre-specified subanalysis of the PROCREATION (PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention) study, a prospective investigation in a large population of patients with CAD [5]. In the main study, we found that EPCs were associated with the occurrence of restenosis or progression of coronary atherosclerosis [5]. We subsequently showed that subtypes of EPCs improved the characterization of 10-year prognosis [6]. In the present study, we performed a pre-specified analysis of the PROCREATION study in order to assess if levels of EPCs relate to the 10-year prognosis.

Section snippets

Patient population

Consecutive patients with stable angina and angiographically assessed CAD who underwent percutaneous coronary intervention were considered for this substudy. The detailed study protocol was described in the main publication [5]. The study protocol complies with the Declaration of Helsinki, and was approved by our Institutional Review Board. Written informed consent was obtained from all participating patients. The PROCREATION study is registered at ClinicalTrials.gov (Identifier: NCT01575431).

Blood samples and flow cytometry

Follow-up

Of the 155 patients included in the original study, follow-up information up to 10 years were obtained in 149 cases (96%). MACCEs occurred in 79 patients (53%). As regards the predefined composite endpoints, all-cause death occurred in 20 patients, stroke in 3 patients, myocardial infarction in 9 patients, and repeat revascularization in 47 patients, i.e. 40 percutaneous coronary intervention and 8 coronary artery by-pass grafting.

Baseline clinical, angiographic, and procedural characteristics

Patients with or without MACCE during follow-up did not show any

Discussion

Our findings demonstrate that the long-term outcome of stable angina patients with angiographically assessed CAD is associated with the baseline finding of increased levels of circulating EPCs, as we found higher levels of circulating CD34+/KDR+/CD45- cells and CD133+/KDR+/CD45- cells at referral in those patients who experienced an adverse event over the 10-year follow-up time frame.

Multiple studies have assessed the prognostic significance of EPCs in patients with CAD so far. These

Declaration of Competing Interest

The authors report no conflict of interest.

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