Effect of atorvastatin on peripheral endothelial function and systemic inflammatory markers in patients with stable coronary artery disease.
BACKGROUND
Endothelial dysfunction, detectable by an impaired flow-mediated vasodilation (FMD) of the brachial artery, has been shown to be associated with increased levels of circulating proinflammatory markers. Therapeutic interventions such as lipid-lowering with statins increase FMD and decrease inflammatory markers, like soluble (s) E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1) or high-sensitivity Creactive protein (hsCRP). The effect of atorvastatin therapy on both FMD and inflammatory markers in patients with stable coronary artery disease (CAD) has not been investigated.


METHODS
Thirty hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. FMD was assessed using highresolution ultrasound (13 MHz, Acuson Sequoia, C256). High-sensitivity CRP was measured with Latex agglutination assay, sE-selectin and sICAM-1 were determined with ELISA.


RESULTS
Baseline characteristics were not different between groups. FMD improved in patients on atorvastatin (6.7+/-3.8% to 8.5+/-4.4%; p<0.01), but remained unchanged in placebo-treated patients (8.2+/-3.3% to 8.9+/-5.1%; p=NS). Atorvastatin treatment was associated with decreases of sICAM-1 (from 274.2+/-92.2 to 197.9+/-70.0 ng/ml; p<0.01) and hsCRP (from 0.57+/-0.45 to 0.18+/-0.15 mg/dl; p<0.01), whereas placebo treatment had no effect on these markers. sE-selectin levels were not influenced by either treatment. No correlations were found between changes in FMD, lipids and inflammatory markers.


CONCLUSIONS
Treatment with atorvastatin leads to an improvement in endothelial function and a reduction in inflammatory markers in patients with stable CAD. The lack of correlation between changes in FMD and inflammatory markers may support the concept of pleiotropic effects of statins in humans.
Alber
Hannes Franz
HF
Division of Cardiology, Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Frick
Matthias
M
Süssenbacher
Alois
A
Dörler
Jakob
J
Dichtl
Wolfgang
W
Stocker
Eva-Maria
EM
Pachinger
Otmar
O
Weidinger
Franz
F
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D002097:C-Reactive Protein / Q000378:metabolism; D003327:Coronary Disease / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000924:Anticholesteremic Agents; D019040:E-Selectin; D006538:Heptanoic Acids; D018836:Inflammation Mediators; D011758:Pyrroles; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein; D000069059:Atorvastatin