Filippatos Theodosios D, Kei Anastazia, Rizos Christos V, Elisaf Moses S
1 Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece.
J Cardiovasc Pharmacol Ther. 2018 Jan;23(1):3-12. doi: 10.1177/1074248417724868. Epub 2017 Aug 22.
Low-density lipoprotein cholesterol (LDL-C) is a major cardiovascular risk factor, but other lipid variables such as triglycerides (TRGs), high-density lipoprotein cholesterol (HDL-C) and lipoprotein a [Lp(a)] also affect cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors significantly lower LDL-C concentration but also modestly improve the concentrations of TRGs and HDL-C and more robustly decrease Lp(a) levels. The review presents the associated mechanisms of the beneficial effects of PCSK9 inhibitors on the other than LDL-C lipid variables, including the effects on lipid/apolipoprotein secretion and clearance and the heteroexchange between lipoproteins, as well as the possible effects on other variables involved in lipid metabolism such as sortilin. Proprotein convertase subtilisin/kexin type 9 inhibitors improve the overall lipid profile, and these beneficial effects may play a role in the reduction of cardiovascular risk.
低密度脂蛋白胆固醇(LDL-C)是主要的心血管危险因素,但其他脂质变量,如甘油三酯(TRGs)、高密度脂蛋白胆固醇(HDL-C)和脂蛋白a [Lp(a)] 也会影响心血管风险。前蛋白转化酶枯草溶菌素/kexin 9型(PCSK9)抑制剂可显著降低LDL-C浓度,但也能适度改善TRGs和HDL-C的浓度,并更有效地降低Lp(a)水平。本文综述了PCSK9抑制剂对LDL-C以外脂质变量产生有益作用的相关机制,包括对脂质/载脂蛋白分泌和清除的影响、脂蛋白之间的异质交换,以及对sortilin等其他参与脂质代谢的变量可能产生的影响。前蛋白转化酶枯草溶菌素/kexin 9型抑制剂可改善整体脂质谱,这些有益作用可能在降低心血管风险中发挥作用。