Coakley John C
Retired Head of Biochemistry Department, The Children's Hospital at Westmead, Westmead, NSW 2145, Australia.
Clin Biochem Rev. 2018 Aug;39(3):65-76.
Atherosclerosis often begins in childhood or adolescence. Post-mortem studies in children have shown the presence of coronary atheroma, and there are hereditary conditions associated with hyperlipidaemia in childhood which lead to premature cardiovascular disease. Detection of hyperlipidaemia early in life can be crucial in the prevention of premature death from atherosclerosis. The circulating lipoproteins are in a constant state of flux, with passage of apolipoproteins and lipids between the various particles. Genetic variants of apolipoproteins can cause both hypercholesterolaemia and hypertriglyceridaemia. Elevated concentrations of lipoprotein(a) predispose to coronary artery disease. Another important molecule in lipid metabolism, proprotein convertase subtilisin/kexin type 9 (PCSK9), plays a crucial role in the removal of low-density lipoprotein (LDL) receptors. Reference intervals for the various lipid subfractions are now available for children, and there are guidelines regarding when to take action regarding paediatric hyperlipidaemia. The most important genetic condition in children which may lead to premature death from coronary heart disease is familial hypercholesterolaemia (FH). FH is best diagnosed and treated early in life. Most cases are due to defects in the LDL receptor. Pharmacotherapy for FH usually involves the statin group of drugs, although newer medications are now available, especially for the treatment of homozygous FH. Statin therapy has been demonstrated to be successful in preventing cardiac events in FH. Secondary dyslipidaemia in childhood can be associated with numerous diseases including diabetes, lifestyle disorders such as obesity, and drugs. Treatment of the underlying condition usually resolves the hyperlipidaemia.
动脉粥样硬化通常始于儿童期或青少年期。对儿童的尸检研究已显示存在冠状动脉粥样瘤,并且存在与儿童高脂血症相关的遗传性疾病,这些疾病会导致过早发生心血管疾病。在生命早期检测高脂血症对于预防因动脉粥样硬化导致的过早死亡可能至关重要。循环脂蛋白处于不断变化的状态,载脂蛋白和脂质在各种颗粒之间传递。载脂蛋白的基因变异可导致高胆固醇血症和高甘油三酯血症。脂蛋白(a)浓度升高易患冠状动脉疾病。脂质代谢中的另一个重要分子,前蛋白转化酶枯草杆菌蛋白酶/kexin 9型(PCSK9),在低密度脂蛋白(LDL)受体的清除中起关键作用。现在已有儿童各种脂质亚组分的参考区间,并且有关于何时对儿童高脂血症采取行动的指南。儿童中可能导致因冠心病过早死亡的最重要的遗传疾病是家族性高胆固醇血症(FH)。FH最好在生命早期进行诊断和治疗。大多数病例是由于LDL受体缺陷所致。FH的药物治疗通常涉及他汀类药物,尽管现在有了更新的药物,特别是用于治疗纯合子FH。他汀类药物治疗已被证明在预防FH的心脏事件方面是成功的。儿童继发性血脂异常可能与多种疾病有关,包括糖尿病、肥胖等生活方式紊乱以及药物。治疗潜在疾病通常可使高脂血症得到缓解。