Simons L A, Sullivan D, Simons J, Celermajer D S
University of New South Wales Lipid Research Department, St. Vincent's Hospital, Darlinghurst, Australia.
Atherosclerosis. 1998 Mar;137(1):197-203. doi: 10.1016/s0021-9150(97)00252-9.
Endothelial dysfunction is an important early event in atherogenesis. Changes in arterial endothelial physiology were studied in patients with severe primary hypercholesterolaemia participating in an ongoing clinical trial evaluating atorvastatin and simvastatin. Endothelial function was assessed non-invasively using brachial ultrasound and the primary outcome measure was flow-mediated endothelium-dependent dilatation (FMD) in response to reactive hyperaemia. Patients were studied upon entry while still using simvastatin 40 mg daily and again after a 10-week washout (baseline). Over the next 30 weeks, 20 patients received atorvastatin titrated up to 80 mg daily and 12 patients received simvastatin titrated up to 40 mg daily (plus cholestyramine 4 g daily in 10/12), followed by a final ultrasound study. During simvastatin washout, total and low density lipoprotein (LDL) cholesterol rose by a median 23-29% and 30-34%, respectively. During atorvastatin therapy, total and LDL cholesterol fell by a median of 41 and 46%, respectively, triglycerides fell by 45%, and high density lipoprotein (HDL) cholesterol rose by 10%. During simvastatin plus cholestyramine therapy, the respective median changes were - 32, - 39, - 44 and + 11%. Patients at baseline showed evidence of impaired FMD and this improved significantly on either treatment, from a median + 2.2 to + 5.5% on atorvastatin and from + 1.8 to + 4.5% on simvastatin plus cholestyramine (P < 0.01 for both treatments). Typical response in healthy subjects would be from + 8 to + 9%. FMD at baseline was correlated with HDL cholesterol (r=0.49, P < 0.01). Change in FMD was inversely correlated with baseline FMD (r=-0.54, P < 0.001). Endothelial dysfunction in primary hypercholesterolaemia was improved by treatment with atorvastatin or simvastatin plus cholestyramine and this effect may result in the prevention of future coronary events.
内皮功能障碍是动脉粥样硬化发生过程中的一个重要早期事件。在一项正在进行的评估阿托伐他汀和辛伐他汀的临床试验中，对患有严重原发性高胆固醇血症的患者的动脉内皮生理变化进行了研究。使用肱动脉超声对内皮功能进行无创评估，主要结局指标是对反应性充血的血流介导的内皮依赖性舒张（FMD）。患者在入组时仍每日服用40mg辛伐他汀，在10周洗脱期后（基线期）再次进行研究。在接下来的30周内，20名患者接受阿托伐他汀滴定至每日80mg，12名患者接受辛伐他汀滴定至每日40mg（12名中有10名加用每日4g考来烯胺），随后进行最后一次超声研究。在辛伐他汀洗脱期，总胆固醇和低密度脂蛋白（LDL）胆固醇分别中位数升高23 - 29%和30 - 34%。在阿托伐他汀治疗期间，总胆固醇和LDL胆固醇分别中位数下降41%和46%，甘油三酯下降45%，高密度脂蛋白（HDL）胆固醇升高10%。在辛伐他汀加考来烯胺治疗期间，相应的中位数变化分别为 - 32%、 - 39%、 - 44%和 + 11%。基线期患者显示出FMD受损的证据，两种治疗均可使其显著改善，阿托伐他汀治疗时从中位数 + 2.2%改善至 + 5.5%，辛伐他汀加考来烯胺治疗时从 + 1.8%改善至 + 4.5%（两种治疗P均 < 0.01）。健康受试者的典型反应应为 + 8%至 + 9%。基线期FMD与HDL胆固醇相关（r = 0.49，P < 0.01）。FMD的变化与基线期FMD呈负相关（r = - 0.54，P < 0.001）。原发性高胆固醇血症中的内皮功能障碍通过阿托伐他汀或辛伐他汀加考来烯胺治疗得到改善，这种作用可能有助于预防未来的冠状动脉事件。
