Forst Thomas, Wilhelm Birgit, Pfützner Andreas, Fuchs Winfried, Lehmann Ute, Schaper Frank, Weber Matthias, Müller Jürgen, Konrad Thomas, Hanefeld Markolf
Medical Director, Institute for Clinical Research and Development, Mainz, Germany.
Diab Vasc Dis Res. 2008 Nov;5(4):298-303. doi: 10.3132/dvdr.2008.043.
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.
我们研究了阿托伐他汀单药治疗以及阿托伐他汀与吡格列酮联合治疗对内膜中层厚度、血管功能和心血管风险状况的影响。总共148例心血管（CV）危险因素增加的患者（76例男性，72例女性；年龄61.4±6.5岁；体重指数[BMI]29.2±4.1kg/m²；均值±标准差）被随机分组。在6个月期间监测内膜中层厚度（IMT）、增强指数（Aix@75）、对乙酰胆碱的微血管反应（激光多普勒血流仪[LDF]）、血脂状况以及完整胰岛素原、脂联素、白细胞介素-6（IL-6）、单核细胞趋化蛋白-1（MCP-1）、基质金属蛋白酶-9（MMP-9）、可溶性CD40配体（sCD40L）、P-选择素、组织型纤溶酶原激活剂（t-PA）的血浆水平和血脂。阿托伐他汀单独治疗以及与吡格列酮联合治疗均显示IMT有显著消退（分别从0.923±0.013至0.874±0.012mm以及从0.921±0.015至0.882±0.015mm；均值±标准误；p<0.05）以及Aix@75有显著消退（从27.3±1.2至25.9±1.4；以及从从25.6±1.4至24.8±1.7%；p<0.05）。联合治疗期间，通过激光多普勒血流仪（LDF）测量的对乙酰胆碱的内皮反应有所改善（从373±57至576±153任意单位；p<0.05）。在阿托伐他汀基础上加用吡格列酮对高敏C反应蛋白（hsCRP）、t-PA、P-选择素、脂联素、甘油三酯和高密度脂蛋白（HDL）胆固醇产生显著的进一步影响（分别p<0.05）。阿托伐他汀显著改善了IMT和血管弹性。联合使用吡格列酮对内皮功能、血脂谱和炎症实验室指标有额外影响。
