Turpin G, Bruckert E
Service d'Endocrinologie-Métabolisme, Groupe Hospitalier Pitié-Salpêtrière, Paris.
Ann Med Interne (Paris). 1999 Dec;150(8):605-14.
Familial hypercholesterolemia is characterized by a high plasma LDL-cholesterol level. The low-density particles are the end-product of the triglyceride-rich particles, i.e. VLDL, synthetized by the liver. These triglyceride-rich particles are subsequently transformed into intermediate density lipoprotein by the lipoprotein lipase and LDL after further triglyceride hydrolysis by the hepatic lipase. The LDL particles are taken up in all cells by the mean of the LDL receptor. A large body of evidence (including experimental, clinical, epidemiological data as well as the results of large trial with lipid lowering drugs) has accumulated to establish that these particles are one of the major causative factor of atherosclerosis and its complications. Two different mechanisms may be at work in the familial hypercholesterolemia: a mutation in the LDL receptor or a single mutation in the apolipoprotein B100. Specific therapeutic intervention should be undertaken to decrease the risk to develop cardiovascular disease, mainly coronary heart disease. The therapeutic intervention includes both a diet low in saturated fatty acids and cholesterol and statins which are now the first line therapy. Fibrates are proposed to those who do not tolerate statins and LDL-apheresis is associated to statin in the rare homozygous familial hypercholesterolemia.
家族性高胆固醇血症的特征是血浆低密度脂蛋白胆固醇水平升高。低密度颗粒是肝脏合成的富含甘油三酯颗粒（即极低密度脂蛋白）的终产物。这些富含甘油三酯的颗粒随后被脂蛋白脂肪酶转化为中间密度脂蛋白，并在肝脏脂肪酶进一步水解甘油三酯后转化为低密度脂蛋白。低密度脂蛋白颗粒通过低密度脂蛋白受体被所有细胞摄取。大量证据（包括实验、临床、流行病学数据以及降脂药物大型试验的结果）已经积累起来，以证实这些颗粒是动脉粥样硬化及其并发症的主要致病因素之一。家族性高胆固醇血症可能有两种不同的机制在起作用：低密度脂蛋白受体突变或载脂蛋白B100的单个突变。应采取特定的治疗干预措施以降低发生心血管疾病（主要是冠心病）的风险。治疗干预包括饱和脂肪酸和胆固醇含量低的饮食以及他汀类药物，他汀类药物现在是一线治疗药物。对于不耐受他汀类药物的患者，建议使用贝特类药物，在罕见的纯合子家族性高胆固醇血症中，低密度脂蛋白分离术与他汀类药物联合使用。
