No effect of high-dose atorvastatin on leukotriene B₄ formation from neutrophils in patients treated with coronary bypass surgery: a randomized placebo-controlled double-blinded trial with a crossover design.
Inflammation plays a pivotal role in the pathophysiology of cardiovascular disease, (CVD) and leukotrienes may play a role in atherogenesis. Statins reduce mortality from CVD by reducing LDL cholesterol and potentially by other (pleiotropic) mechanisms. The aim of this study was to investigate if atorvastatin exerts an anti-inflammatory effect by reducing leukotriene B₄ (LTB₄) formation from stimulated neutrophils in patients treated with coronary artery bypass grafting. The study was a randomized, placebo-controlled, double-blinded crossover study. Patients (n=80) were allocated to 80 mg atorvastatin or placebo for 6 weeks before crossing over to the opposite treatment for another 6 weeks. There was no significant correlation between baseline LDL cholesterol levels on formation of LTB₄, and atorvastatin had no effect on LTB₄ formation. Hence, this study does not support any effect of atorvastatin on LTB₄ formation as part of the explanation for its beneficial effect on CVD.
Department of Cardiology, Center for Cardiovascular Research, Aalborg Hospital, Aarhus University Hospital, Søndre Skovvej 15, Aalborg 9000, Denmark.
C
C
Lysgaard
M S
MS
Nielsen
J H
JH
Christensen
S
S
Lundbye-Christensen
S
S
Riahi
E B
EB
Schmidt
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D000069059:Atorvastatin; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D008078:Cholesterol, LDL / Q000097:blood; D003131:Combined Modality Therapy; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000209:etiology / Q000517:prevention & control; D007975:Leukotriene B4 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018375:Neutrophil Activation / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D011758:Pyrroles / Q000008:administration & dosage* / Q000627:therapeutic use
D000894:Anti-Inflammatory Agents, Non-Steroidal; D061207:Calcium Ionophores; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D007975:Leukotriene B4; D000001:Calcimycin; D000069059:Atorvastatin