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

  • Aisling Kinsella
  • Adnan Raza
  • Susan Kennedy
  • Yue Fan
  • Alfred E. Wood
  • R. W. Watson
Clinical Trial

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.

Keywords

Systemic inflammatory response syndrome Neutrophil migration Statin therapy Cardiothoracic surgery Therapeutic intervention 

Abbreviations

ABTS

2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid

ARDS

Adult respiratory distress syndrome

CK

Creatine kinase

DMEM

Dulbecco’s modified Eagle’s medium

FBC

Full blood count

FCS

Fetal calf serum

fMLP

Formyl-methionyl-leucyl-phenylalanine

HDL

High-density lipoprotein

HPAEC

Human pulmonary artery endothelial cell

sICAM

Soluble intercellular adhesion molecule

LDH

Lactate dehydrogenase

LDL

Low-density lipoprotein

LFT

Liver function test

LPS

Lipopolysaccharide

MI

Myocardial infarction

MPO

Myeloperoxidase

NO

Nitric oxide

UK

United Kingdom

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Aisling Kinsella
    • 1
    • 2
    • 3
  • Adnan Raza
    • 1
  • Susan Kennedy
    • 2
  • Yue Fan
    • 2
  • Alfred E. Wood
    • 1
  • R. W. Watson
    • 2
  1. 1.National Center for Cardiothoracic SurgeryMater Misericordiae University HospitalDublinIreland
  2. 2.UCD School of Medicine & Medical Sciences, UCD Conway Institute of Biomolecular and Biomedical ResearchUniversity College DublinDublinIreland
  3. 3.Mater Misericordiae University HospitalIrish Heart and Lung Transplant ProgrammeDublinIreland

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