title: The impact of high-dose statin therapy on transendothelial neutrophil migration and serum cholesterol levels in healthy male volunteers.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: National Center for Cardiothoracic Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. aiskinsella@yahoo.com
authors.forename: Aisling
authors.initials: A
authors.lastname: Kinsella
authors.forename: Adnan
authors.initials: A
authors.lastname: Raza
authors.forename: Susan
authors.initials: S
authors.lastname: Kennedy
authors.forename: Yue
authors.initials: Y
authors.lastname: Fan
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Wood
authors.forename: R W
authors.initials: RW
authors.lastname: Watson
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000097:blood / Q000276:immunology / Q000601:surgery; D002784:Cholesterol / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011183:Postoperative Complications / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D057705:Transendothelial and Transepithelial Migration / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol