Duell P Barton, Jialal Ishwarlal
1 Knight Cardiovascular Institute, Oregon Health Sciences University , Portland, Oregon.
2 California Northstate University College of Medicine , Elk Grove, California.
Metab Syndr Relat Disord. 2016 Dec;14(10):463-467. doi: 10.1089/met.2016.29011.due. Epub 2016 Oct 31.
Familial hypercholesterolemia (FH) is a common genetic disorder that can manifest clinically as both the severe homozygous (HoFH) form that often presents in childhood and the commoner heterozygous (HeFH) form that is typically identified in adults. The majority of genetic causes are due to defects in low-density lipoprotein (LDL) receptor synthesis and action. Until recently, it was exceedingly difficult to achieve the goal of a 50% reduction in LDL-cholesterol or LDL-C < 70-100 in these patients. Established therapies include statins, niacin, bile-acid sequestrants, and ezetimibe in various combinations. The recent advent of monoclonal antibodies to PCSK9 (evolocumab and alirocumab) has revolutionized the management of FH and results in a substantial reduction in LDL-C and also reductions in Lp(a). In addition, the previous ushering in of antisense therapy against apoB (mipomersen) and inhibition of microsomal transfer protein (lomitapide) for use in HoFH greatly enhanced our ability to manage refractory hypercholesterolemia in these patients. Hence, the therapeutic landscape for this common disorder has changed dramatically for these patients, with a strong promise for a reduction in cardiovascular events.
家族性高胆固醇血症（FH）是一种常见的遗传性疾病，临床上可表现为严重的纯合子（HoFH）形式，常于儿童期出现，以及较常见的杂合子（HeFH）形式，通常在成人中被识别。大多数遗传病因是由于低密度脂蛋白（LDL）受体合成和功能缺陷。直到最近，在这些患者中实现将低密度脂蛋白胆固醇降低50%或使低密度脂蛋白胆固醇（LDL-C）<70-100的目标仍极其困难。既定的治疗方法包括他汀类药物、烟酸、胆汁酸螯合剂和依折麦布的各种组合。最近针对前蛋白转化酶枯草溶菌素9（PCSK9）的单克隆抗体（依洛尤单抗和阿利西尤单抗）的出现彻底改变了FH的治疗方式，导致LDL-C大幅降低，同时脂蛋白（a）[Lp(a)]也降低。此外，先前引入的针对载脂蛋白B（apoB）的反义疗法（米泊美生）和用于HoFH的微粒体转移蛋白抑制剂（洛美他派）极大地增强了我们管理这些患者难治性高胆固醇血症的能力。因此，对于这些患者，这种常见疾病的治疗前景发生了巨大变化，有望减少心血管事件。
