title: Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk.
abstract: 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 atorva-statin 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.
authors.affiliation: Medical Director, Institute for Clinical Research and Development, Mainz, Germany. thomasf@ikfe.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Birgit
authors.initials: B
authors.lastname: Wilhelm
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
authors.forename: Winfried
authors.initials: W
authors.lastname: Fuchs
authors.forename: Ute
authors.initials: U
authors.lastname: Lehmann
authors.forename: Frank
authors.initials: F
authors.lastname: Schaper
authors.forename: Matthias
authors.initials: M
authors.lastname: Weber
authors.forename: Jürgen
authors.initials: J
authors.lastname: Müller
authors.forename: Thomas
authors.initials: T
authors.lastname: Konrad
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging / Q000187:drug effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005858:Germany; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008875:Middle Aged; D000077205:Pioglitazone; D011446:Prospective Studies; D011758:Pyrroles / Q000627:therapeutic use*; D017534:Radial Artery / Q000187:drug effects / Q000503:physiopathology; D018570:Risk Assessment; D012867:Skin / Q000098:blood supply; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018836:Inflammation Mediators; D008055:Lipids; D011758:Pyrroles; D045162:Thiazolidinediones; D000069059:Atorvastatin; D000077205:Pioglitazone