The impact of high-dose statin therapy on transendothelial neutrophil migration and serum cholesterol levels in healthy male volunteers

Eur J Clin Pharmacol. 2011 Nov;67(11):1103-8. doi: 10.1007/s00228-011-1062-z. Epub 2011 Jun 8.

Abstract

Rationale: Cardiac surgery presents a risk to all major organs due to activation of the systemic inflammatory response. Patients referred for cardiac surgery are typically older, usually have comorbid conditions, and are thus at higher risk of postoperative multiorgan dysfunction. Patients demonstrating evidence of organ dysfunction require intensive postoperative management. Any means to predict and reduce the inflammatory response mounted postcardiac surgery could translate into a clinical benefit for the patient and reduce the length of stay in intensive care.

Objective: Statins are commonly used to prevent primary and secondary cardiovascular disease through their cholesterol-lowering effects. However, they have been shown to have anti-inflammatory properties, which may help reduce postoperative mortality and morbidity for patients undergoing cardiac surgery. The purpose of this study was to analyze the in vivo effects of high-dose atorvastatin (statin) on ex vivo neutrophil migration in healthy volunteers.

Methods: Thirteen healthy male volunteers consented and were placed on high-dose (40 mg) statin therapy for 2 weeks. At week 0 and week 2, full blood count, liver function, serum cholesterol and creatine kinase were assessed, as was neutrophil migration.

Results: Neutrophil migration of healthy volunteers was significantly reduced after 2 weeks of high-dose statin therapy (p = 0.002), as was serum cholesterol (p <0.001). There was no change in liver function during statin treatment.

Conclusion: Statins have an established role as cholesterol-lowering agents, and this study demonstrates that they also potentially have an anti-inflammatory effect in healthy male volunteers.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacology*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / immunology
  • Cardiovascular Diseases / surgery
  • Cholesterol / blood*
  • Dose-Response Relationship, Drug
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / immunology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Leukocyte Count
  • Male
  • Middle Aged
  • Neutrophils / cytology
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Postoperative Complications / blood
  • Postoperative Complications / immunology
  • Postoperative Complications / prevention & control
  • Transendothelial and Transepithelial Migration / drug effects*
  • Transendothelial and Transepithelial Migration / immunology

Substances

  • Anti-Inflammatory Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol