Vascular effects of PPAR activation: Inflammation
Campia U et al. Circulation. 2006;113: Pioglitazone improves endothelial vasodilation and decreases inflammation Forearm blood flow (% from baseline) after 16 wks N = 80 with hypertension or hypercholesterolemia and no diabetes Pioglitazone 45 mg/d Placebo Bradykinin (ng/min) All subjects Insulin resistant Insulin sensitive CRP (mg/L) P = P = 0.38 P = P = P = 0.41 P = 0.02
PPAR agonists impact inflammatory markers and adiponectin N = 54 adults with metabolic syndrome and no diabetes Samaha FF et al. Arterioscler Thromb Vasc Biol. 2006;26: *P = 0.002; † P = 0.027; ‡ P < Change from baseline after 12 weeks (%) * † ‡ PlaceboRosiglitazone 8 mg/d IL-6CRP Adiponectin
Surrogate outcome results driving major TZD trials TZDs are associated with reductions in atherosclerotic progression and restenosis TZDs reduce inflammatory markers (CRP, TNF ) independent of glycemic control Reducing CV risk factors with TZDs may also reduce CV morbidity and mortality Dormandy JA et al. Lancet. 2005;366: