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

J Am Coll Cardiol. 2003 Nov 19;42(10):1757-63. doi: 10.1016/j.jacc.2003.04.001.

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents / therapeutic use
  • Biomarkers / blood
  • C-Reactive Protein / drug effects*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / immunology*
  • Diabetes Mellitus
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / physiopathology
  • Female
  • Fibrinogen / drug effects*
  • Humans
  • Insulin Resistance / immunology
  • Male
  • Middle Aged
  • Receptors, Cytoplasmic and Nuclear / agonists*
  • Rosiglitazone
  • Thiazolidinediones / pharmacology*
  • Thiazolidinediones / therapeutic use
  • Transcription Factors / agonists*
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • Biomarkers
  • Receptors, Cytoplasmic and Nuclear
  • Thiazolidinediones
  • Transcription Factors
  • Vasodilator Agents
  • Rosiglitazone
  • Fibrinogen
  • C-Reactive Protein