Raal F J, Pilcher G, Rubinsztein D C, Lingenhel A, Utermann G
Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Atherosclerosis. 1997 Feb 28;129(1):97-102. doi: 10.1016/s0021-9150(96)06007-8.
We studied an extended family of similar genetic and environmental background to determine whether there is a difference in response to statin therapy in those subjects with heterozygous familial hypercholesterolaemia (FH Afrikaner-1 (FH1) or FH Afrikaner-2 (FH2)) compared to those with familial defective apo B-100 (FDB), or both FH plus FDB. Fasting lipid profiles and Lp(a) levels were done on 18 members of the family and then repeated following 6 weeks of therapy with simvastatin 20 mg daily. Statin therapy reduced LDL-cholesterol (LDL-C) by 31% in those with FH (n = 7); 29.8% in FDB (n = 5) and 25.4% in those with both FDB and FH (n = 5). There was no response to statin therapy in the single subject with both FH1, FH2, as well as FDB. Lp(a) levels did not change significantly either within or between any of the groups following statin therapy (FH from 6.5 (1.2-72.3) to 5.3 (1.2-52.3), FDB from 6.1 (4.70-71) to 8.2 (5.7 79) and FDB plus FH from 4.5 (2.6-17.4) to 3.1 (1.9-24) mg/dl). Statins are equally effective in lowering LDL-C in related subjects with heterozygous FH, FDB or both FDB plus FH. The ability of statins to lower LDL-C in FDB is probably due to increased hepatic uptake of lipoprotein precursors of LDL that can bind via apo E receptors. Lp(a) concentration is not reduced by drugs that stimulate LDL receptor activity implying that LDL receptors do not contribute greatly to normal clearance of Lp(a) in hypercholesterolaemic subjects with defects in receptor-mediated endocytosis of LDL.
我们研究了一个具有相似遗传和环境背景的大家庭，以确定杂合子家族性高胆固醇血症（FH南非白人-1（FH1）或FH南非白人-2（FH2））患者与家族性载脂蛋白B-100缺陷（FDB）患者或同时患有FH和FDB的患者相比，对他汀类药物治疗的反应是否存在差异。对该家族的18名成员进行了空腹血脂谱和Lp(a)水平检测，然后在每天服用20 mg辛伐他汀治疗6周后重复检测。他汀类药物治疗使FH患者（n = 7）的低密度脂蛋白胆固醇（LDL-C）降低了31%；FDB患者（n = 5）降低了29.8%，同时患有FDB和FH的患者（n = 5）降低了25.4%。在同时患有FH1、FH2以及FDB的单一受试者中，他汀类药物治疗无反应。他汀类药物治疗后，任何组内或组间的Lp(a)水平均无显著变化（FH从6.5（1.2 - 72.3）降至5.3（1.2 - 52.3），FDB从6.1（4.70 - 71）升至8.2（5.7 - 79），FDB加FH从4.5（2.6 - 17.4）降至3.1（1.9 - 24）mg/dl）。他汀类药物在降低杂合子FH、FDB或同时患有FDB和FH的相关受试者的LDL-C方面同样有效。他汀类药物降低FDB患者LDL-C的能力可能是由于肝脏对可通过载脂蛋白E受体结合的LDL脂蛋白前体的摄取增加。刺激LDL受体活性的药物不会降低Lp(a)浓度，这意味着在低密度脂蛋白受体介导的内吞作用存在缺陷的高胆固醇血症患者中，LDL受体对Lp(a)的正常清除作用不大。
