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Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells After Percutaneous Coronary Intervention (HIPOCRATES Study)

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Abstract

Background

Pretreatment with high-dose statins given before percutaneous coronary intervention (PCI) has been shown to have beneficial effects, in particular by reducing peri-procedural myocardial infarction. The mechanism of these lipid-independent beneficial statin effects is unclear. Circulating endothelial progenitor cells (EPCs) have an important role in the process of vascular repair, by promoting re-endothelization following injury. We hypothesized that statins can limit the extent of endothelial injury induced by PCI and promote re-endothelization by a positive effect on EPCs. We, therefore, aimed to examine the effect of high-dose statins given prior to PCI on EPCs profile.

Methods

Included were patients, either statin naïve or treated chronically with low-dose statins, with stable or unstable angina who underwent PCI. Patients were randomized to receive either high-dose atorvastatin (80 mg the day before PCI and 40 mg 2–4 h before PCI) or low- dose statin. EPCs profile was examined before PCI and 24 h after it. Circulating EPCs levels were assessed by flow cytometry as the proportion of peripheral mononuclear cells co-expressing VEGFR-2+ CD133+ and VEGFR-2+ CD34+. The capacity of the cells to form colony forming units (CFUs) was quantified after 7 days of culture.

Results

Twenty three patients (mean age 61.4 ± 7.4 years, 87.0 % men) were included in the study, of which 12 received high-dose atorvastatin prior to PCI. The mean number of EPC-CFUs before PCI was higher in patients treated with high-dose atorvastatin vs. low-dose statins (165.8 ± 58.8 vs. 111.7 ± 38.2 CFUs/plate, respectively, p < 0.001). However, 24 h after the PCI, the number of EPC-CFUs was similar (188.0 ± 85.3 vs. 192.9 ± 66.5 CFUs/plate in patients treated with high-dose atorvastatin vs. low- dose statins, respectively, p = 0.15). There were no statistical significant differences in FACS analyses between the 2 groups.

Conclusions

The current study showed higher EPC- CFUs levels in patients treated with high-dose atorvastatin before PCI and a lower increment in EPC-CFUs after PCI. These findings could account for the beneficial effects of statins given prior to PCI, yet further investigation is required.

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Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Cardiology Department, Rabin Medical Center, 39 Jabotinsky St., 49100, Petah Tikva, Israel

    A. Eisen, H. Yavin, K. Orvin, A. Mager, E. Rechavia, T. Bental, A. Battler, R. Kornowski & E. I. Lev

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    A. Eisen, H. Yavin, K. Orvin, A. Mager, E. Rechavia, T. Bental, A. Battler, R. Kornowski & E. I. Lev

  3. The Felsenstein Medical Research Institute, Rabin Medical Center, Petah Tikva, Israel

    D. Leshem-Lev & O. Dadush

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  1. A. Eisen
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  2. D. Leshem-Lev
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  3. H. Yavin
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  4. K. Orvin
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  5. A. Mager
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  6. E. Rechavia
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  7. T. Bental
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  9. A. Battler
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  11. E. I. Lev
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Correspondence to A. Eisen.

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Eisen, A., Leshem-Lev, D., Yavin, H. et al. Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells After Percutaneous Coronary Intervention (HIPOCRATES Study). Cardiovasc Drugs Ther 29, 129–135 (2015). https://doi.org/10.1007/s10557-015-6575-8

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  • DOI: https://doi.org/10.1007/s10557-015-6575-8

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