title: High dose statin prophylaxis in cardiopulmonary bypass related surgery: clinical utility.
abstract: BACKGROUND
  Previous studies from our group demonstrated the anti-inflammatory properties of statins on cardiopulmonary bypass (CPB), through inhibition of neutrophil transendothelial migration. We sought to determine the utility of preoperative statin on patients undergoing cardiac surgery, to investigate any moderating effects on the systemic inflammatory response (SIRS) with CPB, and to evaluate any clinical impact on our patients.
  
  
  METHODS
  This is a prospective, randomised controlled trial with national regulatory body approval. Eligible patients were already on oral statin therapy. They were then randomly assigned to either investigation arm (n = 15, atorvastatin 80 mg for 2 weeks before surgery) or control arm (n = 15, no change to current statin therapy). Blood and urine samples were collected at 3 timepoints. Postoperative clinical measures were documented.
  
  
  RESULTS
  Patients in the investigation arm have significantly lower troponin level (p = 0.016), and lower level of urine neutrophil gelatinase-associated lipocalin (NGAL; p = 0.002); thus demonstrating a lesser degree of cardiac and renal injury in these patients. Higher level of Interleukin-8 (IL-8) at baseline (p = 0.036) and 4 h post cross-clamp removal (p = 0.035) in the investiation arm. A similar trend is also observed in Matrix Metalloproteinase-9 (MMP-9; p > 0.05). There were however no differences in clinical outcomes.
  
  
  CONCLUSIONS
  Maximizing the dose of statin in patients waiting for cardiac surgery has measurable biological effects. There is evidence of less cardiac and renal damage. The use of preoperative statins and in particular, high dose preoperative statin therapy, may prove a useful new tool for optimal preparation of patients for cardiac surgery.
  
  
  BACKGROUND
  EudraCT no. 2012-003396-20 . Registered 05 November 2012.
authors.affiliation: Cardiothoracic Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland. yrchee@icloud.com.|Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland. yrchee@icloud.com.
authors.forename: Yie Roei
authors.initials: YR
authors.lastname: Chee
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: R William G
authors.initials: RW
authors.lastname: Watson
authors.affiliation: Cardiothoracic Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
authors.affiliation: Cardiothoracic Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: Jehan Zeb
authors.initials: JZ
authors.lastname: Chughtai
authors.affiliation: Cardiothoracic Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: Lars
authors.initials: L
authors.lastname: Nölke
authors.affiliation: Cardiothoracic Surgery, Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland.
authors.forename: David G
authors.initials: DG
authors.lastname: Healy
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D006348:Cardiac Surgical Procedures / Q000379:methods*; D002315:Cardiopulmonary Bypass / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D016209:Interleukin-8 / Q000097:blood*; D000071068:Lipocalin-2 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D016209:Interleukin-8; D000071068:Lipocalin-2
keywords: Cardiopulmonary bypass; End-organ injury; Statin