CLINICAL RESEARCH: VASCULAR EFFECTS OF ROFECOXIB AND ROSIGLITAZONE
The effects of rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, on markers of endothelial cell activation, C-reactive protein, and fibrinogen levels in non-diabetic coronary artery disease patients
Jagdip S. Sidhu, MRCP*,
Dahlia Cowan, BSc* and
Juan-Carlos Kaski, MD, DSc, FACC*,*
* Coronary Artery Disease Research Unit, Cardiological Sciences, St. George's Hospital Medical School, London, United Kingdom.
Manuscript received September 11, 2002;
revised manuscript received February 22, 2003,
accepted April 4, 2003.
* Reprint requests and correspondence: Prof. Juan-Carlos Kaski, Head of the Coronary Artery Disease Research Unit, St. George's Hospital Medical School, Cranmer Terrace, London SW17 ORE, United Kingdom.
jkaski{at}sghms.ac.uk
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.
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Abbreviations and Acronyms
| | CAD | = coronary artery disease | | CAM | = cell adhesion molecule | | CRP | = C-reactive protein | | HDL | = high-density lipoprotein | | HOMA-R | = homeostasis model of insulin resistance index | | LDL | = low-density lipoprotein | | NF-kappa-B | = nuclear factor-kappa-B | | PPAR-gamma | = peroxisome proliferator-activated receptor-gamma | | vWF | = von Willebrand factor |
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