Vuorio Alpo, Tikkanen Matti J, Kovanen Petri T
Health Center Mehiläinen, Vantaa, Finland ; Finnish Institute of Occupational Health, Lappeenranta, Finland.
Heart and Lung Center, Helsinki University Central Hospital, Folkhälsan Research Center, Biomedicum, Helsinki, Finland.
Vasc Health Risk Manag. 2014 May 6;10:263-70. doi: 10.2147/VHRM.S36641. eCollection 2014.
Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density lipoprotein (LDL)-receptor gene (LDLR). Patients with homozygous FH (hoFH) have inherited a mutated LDLR gene from both parents, and therefore all their LDL-receptors are incapable of functioning normally. In hoFH, serum LDL levels often exceed 13 mmol/L and tendon and cutaneous xanthomata appear early (under 10 years of age). If untreated, this extremely severe form of hypercholesterolemia may cause death in childhood or in early adulthood. Based on recent data, it can be estimated that the prevalence of hoFH is about 1:500,000 or even 1:400,000. Until now, the treatment of hoFH has been based on high-dose statin treatment combined with LDL apheresis. Since the LDL cholesterol-lowering effect of statins is weak in this disease, and apheresis is a cumbersome treatment and not available at all centers, alternative novel pharmaceutical therapies are needed. Lomitapide is a newly introduced drug, capable of effectively decreasing serum LDL cholesterol concentration in hoFH. It inhibits the microsomal triglyceride transfer protein (MTTP). By inhibiting in hepatocytes the transfer of triglycerides into very low density lipoprotein particles, the drug blocks their assembly and secretion into the circulating blood. Since the very low density lipoprotein particles are precursors of LDL particles in the circulation, the reduced secretion of the former results in lower plasma concentration of the latter. The greatest concern in lomitapide treatment has been the increase in liver fat, which can be, however, counteracted by strictly adhering to a low-fat diet. Lomitapide is a welcome addition to the meager selection of drugs currently available for the treatment of refractory hypercholesterolemia in hoFH patients.
家族性高胆固醇血症（FH）是一种常染色体显性疾病，由低密度脂蛋白（LDL）受体基因（LDLR）突变引起。纯合子FH（hoFH）患者从父母双方遗传了突变的LDLR基因，因此他们所有的LDL受体都无法正常发挥功能。在hoFH中，血清LDL水平通常超过13 mmol/L，肌腱和皮肤黄色瘤出现较早（10岁以下）。如果不进行治疗，这种极其严重的高胆固醇血症形式可能导致儿童期或成年早期死亡。根据最近的数据，估计hoFH的患病率约为1:500,000，甚至1:400,000。到目前为止，hoFH的治疗一直基于高剂量他汀类药物治疗联合LDL单采。由于他汀类药物在这种疾病中降低LDL胆固醇的作用较弱，且单采是一种繁琐的治疗方法，并非所有中心都能提供，因此需要替代性的新型药物疗法。洛美他派是一种新引入的药物，能够有效降低hoFH患者的血清LDL胆固醇浓度。它抑制微粒体甘油三酯转移蛋白（MTTP）。通过抑制肝细胞中甘油三酯向极低密度脂蛋白颗粒的转移，该药物阻止其组装并分泌到循环血液中。由于极低密度脂蛋白颗粒是循环中LDL颗粒的前体，前者分泌减少导致后者血浆浓度降低。洛美他派治疗中最令人担忧的是肝脏脂肪增加，不过，严格坚持低脂饮食可以抵消这一影响。洛美他派是目前可用于治疗hoFH患者难治性高胆固醇血症的少量药物中的一个受欢迎的补充。
