Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: the SIROCO study.

Abstract

AIM:

Individually, statins and thiazolidinediones (TZDs) show positive effects on atherosclerosis progression in cellular and animal models as well as patients with diabetes; however, their combined effects have not been studied. This study examines the effects of simvastatin combined with rosiglitazone on vascular inflammation, oxidant stress, ambulatory blood pressure (BP) and other atherosclerotic factors in patients with the metabolic syndrome.

METHODS:

This is a randomized, double blind, placebo-controlled study in 53 subjects with the metabolic syndrome. Participants were randomized to simvastatin 40 mg/day plus placebo vs. simvastatin 40 mg/day plus rosiglitazone 4 mg/day for 6 months. The primary endpoint was the between-group difference in high-sensitivity C-reactive protein (hs-CRP) and secondary variables including urinary isoprostanes, serum malondialdehyde (MDA), ambulatory BP, adiponectin, and lipid and glycaemic profiles.

RESULTS:

At study end, the group randomized to the simvastatin/rosiglitazone combination had a greater reduction in hs-CRP of 1.33 mg/dl, (p = 0.029) and showed a trend for a greater reduction in urinary isoprostane (-39%), (p = 0.056) compared to simvastatin/placebo group. Changes in MDA levels did not differed between groups (p = 0.81). 24-h systolic blood pressure (SBP) also showed a 4.5 mmHg reduction at 6 months (p = 0.06). Adiponectin levels increased by 3.91 µg/ml in the combination group over placebo, (p = 0.03) and blood glucose decreased in combination group vs. placebo.

CONCLUSION:

Our data show that patients with the metabolic syndrome given a statin/TZD combination manifest greater reductions in markers of vascular inflammation and oxidant stress, 24-h ambulatory BP and increases in adiponectin as well as improved glycaemic indices.

• Authors: I Lazich, P Sarafidis, E de Guzman, A Patel, R Oliva, G Bakris
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 14 Issue 2 Pg. 181-6 (Feb 2012) ISSN: 1463-1326 [Electronic] England
• PMID: 21955403 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 Blackwell Publishing Ltd.

Chemical References

• Adiponectin
• Blood Glucose
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Isoprostanes
• Lipids
• Thiazolidinediones
• Rosiglitazone
• Malondialdehyde
• C-Reactive Protein
• Simvastatin

Topics

• Adiponectin (blood)
• Adult
• Aged
• Blood Glucose (drug effects)
• Blood Pressure (drug effects)
• Blood Pressure Monitoring, Ambulatory
• C-Reactive Protein (drug effects)
• Coronary Artery Disease (physiopathology, prevention & control)
• Double-Blind Method
• Drug Therapy, Combination
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypolipidemic Agents (therapeutic use)
• Inflammation (blood, drug therapy)
• Isoprostanes (urine)
• Lipids (blood)
• Male
• Malondialdehyde (blood)
• Metabolic Syndrome (drug therapy, physiopathology)
• Middle Aged
• Oxidative Stress (drug effects)
• Rosiglitazone
• Simvastatin (therapeutic use)
• Thiazolidinediones (therapeutic use)