title: Effect of High Dose Statin Pretreatment on Endothelial Progenitor Cells After Percutaneous Coronary Intervention (HIPOCRATES Study).
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.
authors.affiliation: Cardiology Department, Rabin Medical Center, 39 Jabotinsky St., 49100, Petah Tikva, Israel, a_alon1@netvision.net.il.
authors.forename: A
authors.initials: A
authors.lastname: Eisen
authors.forename: D
authors.initials: D
authors.lastname: Leshem-Lev
authors.forename: H
authors.initials: H
authors.lastname: Yavin
authors.forename: K
authors.initials: K
authors.lastname: Orvin
authors.forename: A
authors.initials: A
authors.lastname: Mager
authors.forename: E
authors.initials: E
authors.lastname: Rechavia
authors.forename: T
authors.initials: T
authors.lastname: Bental
authors.forename: O
authors.initials: O
authors.lastname: Dadush
authors.forename: A
authors.initials: A
authors.lastname: Battler
authors.forename: R
authors.initials: R
authors.lastname: Kornowski
authors.forename: E I
authors.initials: EI
authors.lastname: Lev
mesh_terms: D000069059:Atorvastatin / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D066026:Endothelial Progenitor Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D013234:Stem Cells / Q000187:drug effects
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000069059:Atorvastatin