Abstract 4082: Effects of Peroxisome Proliferator-Activated Receptor (PPAR) Ligands on Vascular Function in Patients with the Metabolic Syndrome
Background: Insulin resistance plays an important role in the pathogenesis of atherosclerosis in patients with the metabolic syndrome. We assessed the effects of PPAR ligands, pioglitazone (PPAR-γ ligand) and fenofibrate (PPAR-γ ligand), on vascular function (endothelial function, aortic stiffness, and augmentation index), insulin resistance, inflammation, and oxidative stress in patients with the metabolic syndrome.
Methods: Thirty six patients with the metabolic syndrome were randomized to receive PPAR ligands, pioglitazone and fenofibrate (PPAR group: n=18) or not to receive PPAR ligands (Control group: n=18). Flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of brachial artery were measured by using ultrasound system. We also measured aortic pulse wave velocity (PWV) to evaluate aortic stiffness and augmentation index (AI) by using oscilometric technique (form PWV/ABI®, COLIN). Insulin resistance was evaluated by HOMA-IR. We also measured high sensitivity C-reactive peptide (hsCRP), and thiobarbituric acid reactive substance (TBARS) as indexes of inflammation and oxidative stress. These measurements were performed at baseline, 3 and 6 months after the treatment.
Results: At baseline, there was no difference in all parameters between the both groups. After 6 months, FMD was significantly increased, and PWV and AI were significantly decreased in the PPAR group. HOMA-IR and hsCRP were significantly decreased in the PPAR group. TBARS was also significantly decreased in the PPAR group (PPAR group: 3.82±0.64 to 1.91±0.22 nmol/mL, p<0.01; control group: 3.82±0.89 to 3.68±0.78 nmol/mL). NID did not change during this study.
Conclusion: Combination therapy with PPAR ligands, pioglitazone and fenofibrate, improves vascular function due to the improvement of insulin resistance, inflammation and oxidative stress in patients with the metabolic syndrome.