Anti-Inflammatory Effects of Pioglitazone and/or Simvastatin in High Cardiovascular Risk Patients With Elevated High Sensitivity C-Reactive Protein

Autor: Ulf Stier, Georg Lübben, Markolf Hanefeld, Werner Baurecht, E. Karagiannis, Nikolaus Marx, Thomas Forst, Andreas Pfützner
Rok vydání: 2007
Předmět:
Zdroj: Journal of the American College of Cardiology. 49:290-297
ISSN: 0735-1097
Popis: Objectives The purpose of this study was to test the safety and efficacy of pioglitazone and simvastatin in combination versus each drug individually in non-diabetic subjects with cardiovascular disease (CVD) and elevated high-sensitivity C-reactive protein (hs-CRP) levels. Background Low-grade inflammation is a pathogenic factor for atherosclerosis. High-sensitivity CRP, matrix metalloproteinase (MMP)-9, and plasminogen activator inhibitor (PAI)-1 are markers of inflammation. Statins and peroxisome proliferator-activated receptor (PPAR)-γ agonists lower inflammatory markers and reduce CVD in type 2 diabetes. Methods In a 12-week, prospective, double-blind trial, 125 subjects were randomized to simvastatin or pioglitazone plus placebo or a simvastatin/pioglitazone combination. We tested changes in hs-CRP by analysis of covariance. A subgroup analysis was performed in patients with and without the metabolic syndrome (MetS). The correlation between changes in hs-CRP and homeostasis model assessment (HOMA; a measure of insulin resistance) was calculated with the Spearman’s rank test. Results At baseline, there were no significant between-group differences. At 12 weeks, pioglitazone and simvastatin monotherapies significantly reduced hs-CRP (3.64 ± 2.42 mg/l to 2.48 ± 1.77 mg/l and 3.26 ± 2.02 mg/l to 2.81 ± 2.11 mg/l) and the combination regimen had an additive effect (from 3.49 ± 1.97 mg/l to 2.06 ± 1.42 mg/l, p Conclusions Pioglitazone, probably by reducing insulin resistance, has additive anti-inflammatory effects to simvastatin in non-diabetic subjects with CVD and high hs-CRP.
Databáze: OpenAIRE