J. S. Sidhu, D. Cowan, J. Kaski
Nov 19, 2003
Citations
5
Influential Citations
202
Citations
Quality indicators
Journal
Journal of the American College of Cardiology
Abstract
OBJECTIVES We sought to assess the effect of rosiglitazone on markers of endothelial cell activation and acute-phase reactants in non-diabetic patients with coronary artery disease (CAD). BACKGROUND Inflammation plays a key role in all stages of atherosclerosis and in the genesis of acute coronary syndromes. Rosiglitazone, a peroxisome proliferator-activated receptor gamma agonist, is used in the treatment of type 2 diabetes mellitus, and previous data suggest that it may have anti-inflammatory effects on atherosclerosis. METHODS Patients with stable, angiographically documented CAD without diabetes mellitus were investigated. Patients were randomized in a double-blind manner to receive treatment with placebo or rosiglitazone (4 mg/day for 8 weeks followed by 8 mg/day for 4 weeks) for 12 weeks. Eighty-four patients completed the study. Fasting glucose, insulin, lipid profile, markers of endothelial activation, and inflammatory markers were measured at baseline and after 12 weeks. RESULTS Rosiglitazone treatment resulted in a significant reduction in E-selectin (p = 0.03), von Willebrand factor (p = 0.007), C-reactive protein (p < 0.001), fibrinogen (p = 0.003) and the homeostasis model of insulin resistance index (p = 0.02), compared with placebo. Significant elevations in low-density lipoprotein and triglyceride levels were observed in the rosiglitazone group (p < 0.01). Within the rosiglitazone-treated group, reductions in C-reactive protein and von Willebrand factor were significantly correlated with a reduction in insulin resistance. CONCLUSIONS Rosiglitazone significantly reduces markers of endothelial cell activation and levels of acute-phase reactants in CAD patients without diabetes. Potential underlying mechanisms include insulin sensitization and direct modification of transcription within the vessel wall.