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Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk

Institute for Clinical Research and Development, Mainz, Germany.

Birgit Wilhelm

Institute for Clinical Research and Development, Mainz, Germany.

Andreas Pfützner

Institute for Clinical Research and Development, Mainz, Germany.

Winfried Fuchs

Takeda Pharma GmbH, Aachen, Germany.

Ute Lehmann

Takeda Pharma GmbH, Aachen, Germany.

Frank Schaper

GWT-TUD, Dresden, Germany.

Matthias Weber

Johannes Gutenberg University, Department of Endocrinology, Mainz, Germany.

Jürgen Müller

Acromion, Frechen, Germany.

Thomas Konrad

Institute for Metabolic Research, Frankfurt, Germany.

Markolf Hanefeld

GWT-TUD, Dresden, Germany.

We investigated the effect of atorvastatin monotherapy and combined treatment with atorvastatin and pioglitazone on intima-media thickness, vascular function and the cardiovascular risk profile. In all, 148 patients (76 male, 72 female; aged 61.4±6.5 years; body mass index [BMI] 29.2±4.1 kg/m²; mean±SD) with increased cardiovascular (CV) risk factors were randomised. Intima-media thickness (IMT), the augmentation index (Aix@75), the microvascular response to acetylcholine (LDF), lipid status, and plasma levels of intact proinsulin, adiponectin, interleukin-6 (IL-6), monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), sCD40L, P-selectin, tissue plasminogen activator (t-PA) and blood lipids were monitored over six months.

Atorvastatin treatment, alone and in combination with pioglitazone, revealed a significant regression in IMT (0.923±0.013 to 0.874±0.012 mm and 0.921±0.015 to 0.882±0.015 mm; mean ± SEM; p<0.05 respectively) and Aix@75 (27.3±1.2 to 25.9±1.4; and 25.6±1.4 to 24.8±1.7%; p<0.05). The endothelial response to acetylcholine as measured by laser Doppler fluximetry (LDF) improved during combined treatment (373±57 to 576±153 AU; p<0.05). Addition of pioglitazone to atorvastatin resulted in significant further effects on high-sensitivity C-reactive protein (hsCRP), t-PA, P-selectin, adiponectin, triglycerides and high-density lipoprotein (HDL) cholesterol (p<0.05 respectively).

Atorvastatin significantly improved IMT and vascular elasticity. Co-administration of pioglitazone provided additional effects on endothelial function, lipid profile and laboratory markers of inflammation.

Key Words: atherosclerosis • inflammation • intima-media thickness • PPAR • statins.

Diabetes and Vascular Disease Research, Vol. 5, No. 4, 298-303 (2008)
DOI: 10.3132/dvdr.2008.043


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