Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control -: Results from the pioneer study

被引:248
作者
Pfützner, A
Marx, N
Lübben, G
Langenfeld, M
Walcher, D
Konrad, T
Forst, T
机构
[1] Inst Clin Res & Dev, IKFE, D-55116 Mainz, Germany
[2] Univ Hosp, Ulm, Germany
[3] Univ Appl Sci, Rheinbach, Germany
[4] Takeda Pharma GmbH, Aachen, Germany
[5] Inst Metab Res, ISF, Frankfurt, Germany
关键词
D O I
10.1016/j.jacc.2005.03.041
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVES This study was performed to assess whether the anti-inflammatory and antiatherogenic effects of pioglitazone suggested by animal experiments are reproducible in man and independent from improvements in metabolic control. BACKGROUND Type 2 diabetes is associated with increased cardiovascular risk. METHODS A total of 192 patients were enrolled into a six-month, prospective, open-label, controlled clinical study. They were randomized to receive either pioglitazone (45 mg) or glimepiride (1 to 6 mg, with the intent to optimize therapy). Biochemical and clinical markers to assess therapeutic effects included HbA1c, fasting glucose, insulin, adiponectin, lipids, high-sensitivity C-reactive protein (hsCRP), intracellular adhesion molecule, vascular cell adhesion molecule, vascular endothelial growth factor, fibrinogen, von Willebrand factor, matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein (MCP)-1, soluble CD40 ligand, and carotid intima-media thickness (IMT). RESULTS The study was completed by 173 patients (66 female, 107 male; age [+/- SD]: 63 +/- 8 years; disease duration: 7.2 +/- 7.2 years; HbAlc: 7.5 +/- 0.9 %; pioglitazone arm: 89 patients). A comparable reduction in HbAlc was seen in both groups (p < 0.001). In the pioglitazone group, reductions were observed for glucose (p < 0.001 vs. glimepiride group at end point), insulin (p < 0.001), low-density lipoprotein/high-density lipoprotein ratio (p < 0.001), hsCRP (p < 0.05), MMP-9 (p < 0.05), MCP-1 (p < 0.05), and carotid IMT (p < 0.001), and an increase was seen in high-density lipoprotein (p < 0.001) and adiponectin (p < 0.001). Spearman ranks analysis revealed only one correlation between the reduction in cardiovascular risk parameters and the improvement in the metabolic parameters (MMP-9 and fasting blood glucose, p < 0.05) CONCLUSIONS This prospective study gives evidence of an anti-inflammatory and antiatherogenic effect of pioglitazone versus glimepiride. This effect is independent from blood glucose control and may be attributed to peroxisome proliferator-activated receptor gamma activation. (c) 2005 by the American College of Cardiology Foundation.
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页码:1925 / 1931
页数:7
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