High-dose atorvastatin reloading before percutaneous coronary intervention increased circulating endothelial progenitor cells and reduced inflammatory cytokine expression during the perioperative period

J Cardiovasc Pharmacol Ther. 2014 May;19(3):290-5. doi: 10.1177/1074248413513500. Epub 2013 Dec 16.

Abstract

Objective: We investigated atorvastatin reloading effects on endothelial progenitor cell (EPC) count and inflammatory cytokine expression after percutaneous coronary intervention (PCI) in patients with stable angina pectoris who had previously received long-term statin treatments.

Methods: Patients with stable angina pectoris were treated with 80 mg atorvastatin 12 hours and 40 mg atorvastatin 2 hours before coronary angioplasty (n = 15) or preoperatively with 40 mg/d atorvastatin for 7 days (n = 15) or did not receive atorvastatin (n = 15). CD45-/133+/34+, CD45-/CD34+/kinase insert domain receptor (KDR)+, and CD45-/CD144+/KDR+ EPCs in the peripheral blood were determined by flow cytometry 1 hour before as well as 1 hour, 6 hours, and 24 hours after PCI. Soluble intercellular adhesion molecule 1 (sICAM-1), hypersensitive C-reactive protein (hCRP), and troponin-I (TnI) serum concentrations were analyzed immediately prior to and 24 hours after PCI.

Results: In the 40mg Atorvastatin and control groups, none of the analyzed EPC blood concentrations changed significantly from 1h before operation to 1h and 6 h postoperative values. In contrast, the number of circulating early differentiation stage EPCs CD45-/133+/34+ and CD45-/CD34+/ KDR+ raised significantly from 1 h preoperative values (57.3±9.3; 57.3 ± 10.7) to 1 h postoperative ((74.4 ± 11.4; 78.8 ± 16.2), (p < 0.05)) and 6 h postoperative ((93 ± 16.9; 99.7 ± 11.9), (p < 0.05)) concentrations after coronary angioplasty in the 80mg Atorvastatin medication patients. In the control group, the sICAM-1 (174.55 ± 38.91 vs 204.11 ± 58.24) and hCRP (1.89 ± 1.93 vs 9.0 ± 11.1) serum concentrations at 24 hours after PCI were significantly elevated (P < .05) compared to preoperative values, whereas the increases in the 2 groups treated with atorvastatin were not significant. In addition, the rise in serum TnI concentration level from pre- to postoperative in the 80-mg (0.02 ± 0.02 vs 0.09 ± 0.08) and the 40-mg (0.01 ± 0.03 vs 1.2 ± 2.59) reloading groups was less than that of the controls (0.01 ± 0.02 vs 1.75 ± 3.09) (p < 0.05).

Conclusion: Our results suggested that high-dose atorvastatin application before PCI triggered early EPC circulation. Furthermore, postoperative inflammatory cytokine sICAM-1 as well as hCRP serum levels were reduced, while postinterventional myocardial injury marker TnI elevations were inversely correlated with statin reloadings.

Keywords: arthrosclerosis; endothelial progenitor cells; percutaneous coronary intervention.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Angina Pectoris / surgery
  • Antigens, CD / metabolism
  • Atorvastatin
  • C-Reactive Protein / metabolism
  • Cytokines / drug effects*
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Endothelial Progenitor Cells / drug effects*
  • Endothelial Progenitor Cells / metabolism
  • Female
  • Heptanoic Acids / administration & dosage*
  • Heptanoic Acids / pharmacology*
  • Humans
  • Inflammation Mediators / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / prevention & control
  • Percutaneous Coronary Intervention / methods*
  • Perioperative Period*
  • Pyrroles / administration & dosage*
  • Pyrroles / pharmacology*
  • Troponin I / metabolism

Substances

  • Antigens, CD
  • Cytokines
  • Heptanoic Acids
  • Inflammation Mediators
  • Pyrroles
  • Troponin I
  • Intercellular Adhesion Molecule-1
  • C-Reactive Protein
  • Atorvastatin