Effects of conventional and aggressive statin treatment on markers of endothelial function and inflammation.
BACKGROUND
Atherosclerosis is considered to be a chronic inflammatory disorder. Several large-scale clinical studies demonstrate that markers of inflammation, such as high-sensitivity C-reactive protein (hsCRP), fibrinogen, and soluble CD40 ligand, are potent and independent predictors of vascular risk.


OBJECTIVE
The study was undertaken to investigate the effect of increasing the statin dose from conventional to aggressive treatment on lipids levels, inflammation, and endothelial function in patients with coronary artery disease (CAD).


METHODS
We randomized 97 patients to either 20 mg simvastatin or 80 mg atorvastatin. Plasma levels of lipids, hsCRP, fibrinogen, soluble adhesion molecules, and nitric oxide-total were analyzed at baseline and after 6 months of treatment.


RESULTS
Lipid values were significantly reduced in both treatment groups, but with significantly greater reduction in the aggressively treated group. Furthermore, aggressive statin treatment significantly decreased hsCRP and fibrinogen, while only small reductions were seen in the conventionally treated group, resulting in significant differences between the two treatment groups (p < 0.001). Nitric oxide-total increased significantly in both treatment groups, although the increase was more pronounced in the aggressively treated group (22.6 vs. 15.6%).


CONCLUSIONS
Aggressive statin treatment significantly improved lipid status and reduced markers of inflammation and improved endothelial function compared with conventional treatment in patients with CAD. No interaction was observed, and high-dose treatment did not offer additional benefit compared with standard-dose treatment with respect to soluble adhesion molecules.
Hognestad
Aina
A
Department of Cardiology, Rikshospitalet, Oslo, Norway. aina.hognestad@klinmed.uio.no
Aukrust
Pål
P
Wergeland
Ragnhild
R
Stokke
Oddvar
O
Gullestad
Lars
L
Semb
Anne Grete
AG
Holm
Torbjørn
T
Andreassen
Arne K
AK
Kjekshus
John K
JK
D001161:Arteriosclerosis / Q000188:drug therapy*; D000069059:Atorvastatin; D002097:C-Reactive Protein / Q000187:drug effects*; D002908:Chronic Disease; D003324:Coronary Artery Disease / Q000188:drug therapy; D019040:E-Selectin / Q000097:blood / Q000187:drug effects; D005260:Female; D005340:Fibrinogen / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D019040:E-Selectin; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D009569:Nitric Oxide; D005340:Fibrinogen; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin