Julius Ulrich
Lipidology and Lipoprotein Apheresis Center, Department of Internal Medicine III, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Fetscherstr. 74, 01307 Dresden, Germany.
Atheroscler Suppl. 2017 Nov;30:1-8. doi: 10.1016/j.atherosclerosissup.2017.05.034. Epub 2017 Jun 1.
This review tells the story of atherosclerosis research in the beginning of the 20th century. It presents the significance of cardiovascular diseases and addresses major questions currently being discussed among lipidologists and the current thinking with respect to low LDL-cholesterol levels and HDL. It provides an overview of the period during which lipid-modifying drugs were introduced and their relevance with respect to cardiovascular outcome data and lists possible reasons why some patients develop new cardiovascular events while being treated with statins. Especially impressive is the history of the appearance of the PCSK9 inhibitors on the market - only 12 years after PCSK9 was detected; a study completed in 2017 provides evidence about the cardiovascular effects of these new drugs. Other new drugs are also mentioned: mipomersen, lomitapide, and Alipogen Tiparvovec. Some promising drugs are still in the pipeline which inhibit the synthesis of apolipoprotein CIII, apolipoprotein(a), and the PCSK9 protein. During the 1970s, specific lipoprotein apheresis began to be used in high-risk patients with homozygous familial hypercholesterolemia, severe hypercholesterolemia and elevated Lipoprotein(a) levels and this review provides evidence of the effectiveness of the extracorporeal therapy with respect to the reduction of cardiovascular events. Particularly in patients with high Lipoprotein(a) levels, apheresis has been proven capable of reducing cardiovascular events by more than 80%. The current situation with regard to lipoprotein apheresis centers and patients in Germany is described herein, and, in conclusion, an estimation of the future of the therapeutic options in lipidology is given.
这篇综述讲述了20世纪初动脉粥样硬化的研究历程。它阐述了心血管疾病的重要性,探讨了脂质学家目前正在讨论的主要问题,以及关于低低密度脂蛋白胆固醇水平和高密度脂蛋白的当前观点。它概述了引入调脂药物的时期及其与心血管结局数据的相关性,并列出了一些患者在接受他汀类药物治疗时发生新的心血管事件的可能原因。尤其令人印象深刻的是前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂上市的历程——在检测到PCSK9仅12年后;2017年完成的一项研究提供了这些新药心血管效应的证据。文中还提到了其他新药:米泊美生、洛美他派和阿利泼金替帕罗韦克。一些有前景的药物仍在研发中,它们可抑制载脂蛋白CIII、载脂蛋白(a)和PCSK9蛋白的合成。20世纪70年代,特异性脂蛋白分离术开始用于纯合子家族性高胆固醇血症、严重高胆固醇血症和脂蛋白(a)水平升高的高危患者,本综述提供了体外治疗在减少心血管事件方面有效性的证据。特别是在脂蛋白(a)水平高的患者中,已证实分离术能够将心血管事件减少80%以上。本文描述了德国脂蛋白分离术中心和患者的现状,最后对脂质学治疗选择的未来进行了评估。