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

• Published in: Cardiovascular drugs and therapy 2015-04, Vol.29 (2), p.129-135
• Main Authors: Eisen, A., Leshem-Lev, D., Yavin, H., Orvin, K., Mager, A., Rechavia, E., Bental, T., Dadush, O., Battler, A., Kornowski, R., Lev, E. I.
• Format: Article
• Language: English
• Subjects: Atorvastatin Calcium - administration & dosage; Atorvastatin Calcium - pharmacology; Atorvastatin Calcium - therapeutic use; Cardiology; Cell Count; Dose-Response Relationship, Drug; Endothelial Progenitor Cells - drug effects; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Male; Medicine; Medicine & Public Health; Middle Aged; Myocardial Infarction - prevention & control; Original Article; Percutaneous Coronary Intervention - adverse effects; Stem Cells - drug effects
• ISSN: 0920-3206; 1573-7241
• DOI: 10.1007/s10557-015-6575-8

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