Rosiglitazone Reduces Plasma Levels of Inflammatory and Hemostatic Biomarkers and Improves Global Endothelial Function in Habitual Heavy Smokers Without Diabetes Mellitus or Metabolic Syndrome

Background/Purpose: Thiazolidinediones have anti-atherothrombotic effects in diabetic patients. However, the effects of rosiglitazone on inflammatory and hemostatic markers, as well as global endothelial function in non-diabetic smokers are unknown. Methods: Twenty-seven healthy male heavy smokers without metabolic syndrome were enrolled in this double-blind, controlled study. Fourteen subjects received 4 mg/day rosiglitazone for 8 weeks (group R) and 13 subjects received placebo (group C). Changes in the reflection index (ΔRI) of β-agonist-induced endothelium-dependent vasodilatation by photoplethysmography and plasma biomarkers were measured before and after treatment. Results: Matrix metalloproteinase-9, fibrinogen, and high-sensitivity C-reactive protein were reduced significantly in group R after treatment as compared with the baseline [84.1 (45.6 139.0) vs. 123.9 (58.4 141.8) ng/mL, p = 0.03; 2914 (2400-3553) vs. 3220 (2542-3940) mg/L, p = 0.04; and 3.4 (2.2 5.1) vs. 5.5 (4.1 6.8) mg/L, p = 0.009, respectively]. ΔRI was improved markedly in group R as compared with the baseline [13.5 (4.2 65.1) vs. 2.5 (-10.6 to 9.3)%; p = 0.024]. These biomarkers and ΔRI did not differ significantly in the group C. There were no significant changes in fasting plasma glucose, insulin, homeostasis model assessment index, and lipid profile in both groups R and group C. Conclusion: Rosiglitazone significantly reduces plasma levels of inflammatory and hemostatic biomarkers, and restores global endothelial dysfunction, independently from insulin sensitization, in healthy smokers.