Objectives-Thiazolidinediones, such as rosiglitazone, have been shown to retard atherosclerosis disease progression in diabetic subjects. These agents may have anti-atherosclerotic effects through direct inhibition of inflammatory processes in the vessel wall, and so their benefit may extend to patients with atherosclerotic disease, even in the absence of diabetes. In this study, we assessed the effect of rosiglitazone on common carotid intima-media thickness (IMT) progression in nondiabetic coronary artery disease (CAD) patients. Methods and Results-Consecutive subjects (nϭ92) with clinically stable, angiographically documented CAD and without diabetes mellitus were randomized in a double-blind manner to receive placebo or rosiglitazone for 48 weeks. They received single-dose placebo and rosiglitazone 4 mg daily for the initial 8 weeks, and the doses were doubled for the remainder of the study. Common carotid IMT together with fasting glucose, insulin, and lipid profile were measured at baseline and repeated after 24 and 48 weeks. Rosiglitazone-treated patients showed reduced IMT progression compared with the placebo group, Ϫ0.012 mm/48 weeks versus 0.031 mm/48 weeks (Pϭ0.03). Rosiglitazone treatment significantly reduced insulin resistance, estimated by homeostasis model of insulin resistance index, compared with placebo (Pϭ0.01). Key Words: PPAR-␥ Ⅲ agonists Ⅲ thiazolidinediones Ⅲ carotid intima-media thickness Ⅲ coronary artery disease. Conclusions-RosiglitazoneT he thiazolidinedione rosiglitazone, a peroxisome proliferator-activated receptor-␥ (PPAR-␥) agonist, is an insulin-sensitizing agent and is used in the treatment of type 2 diabetes mellitus. Data suggest that these agents may also retard atherosclerotic disease progression. Thiazolidinediones have been shown to reduce atherosclerotic lesion area in mouse models of atherosclerosis that exhibit hyperlipidemia and insulin-resistance. 1-3 Thiazolidinediones have also been reported to reduce common carotid arterial intima-media thickness (IMT) progression, a surrogate index of atherosclerotic disease progression, in type 2 diabetic subjects. 4,5 These results taken together suggest that insulin sensitization and glucose-lowering are important mechanisms underlying the antiatherogenic effects of these agents. [1][2][3][4][5] See page 798However, recent evidence suggests that PPAR-␥ agonists may also inhibit atherosclerotic disease progression by exerting anti-inflammatory effects within the artery wall. 6,7 Therefore, the potential antiatherogenic effects of PPAR-␥ agonists may not be confined to type 2 diabetic patients. 8 The PPAR-␥ agonist troglitazone has been shown to reduce atherosclerotic lesion formation and macrophage accumulation in plaques in nondiabetic low-density lipoprotein (LDL) receptor-deficient mice. 9 We recently found that rosiglitazone reduces circulating markers of inflammation, such as C-reactive protein, in nondiabetic patients with coronary artery disease (CAD). 10 In the present study, we measured the effect of treatment on com...

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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