Department of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute.
Department of Child Health and Welfare (Pediatrics), Faculty of Medicine, University of the Ryukyu.
J Atheroscler Thromb. 2018 Jun 1;25(6):539-553. doi: 10.5551/jat.CR002. Epub 2018 Feb 6.
This paper describes consensus statement by Joint Working Group by Japan Pediatric Society and Japan Atherosclerosis Society for Making Guidance of Pediatric Familial Hypercholesterolemia (FH) in order to improve prognosis of FH.FH is a common genetic disease caused by mutations in genes related to low density lipoprotein (LDL) receptor pathway. Because patients with FH have high LDL cholesterol (LDL-C) levels from the birth, atherosclerosis begins and develops during childhood which determines the prognosis. Therefore, in order to reduce their lifetime risk for cardiovascular disease, patients with FH need to be diagnosed as early as possible and appropriate treatment should be started.Diagnosis of pediatric heterozygous FH patients is made by LDL-C ≥140 mg/dL, and family history of FH or premature CAD. When the diagnosis is made, they need to improve their lifestyle including diet and exercise which sometimes are not enough to reduce LDL-C levels. For pediatric FH aged ≥10 years, pharmacotherapy needs to be considered if the LDL-C level is persistently above 180 mg/dL. Statins are the first line drugs starting from the lowest dose and are increased if necessary. The target LDL-C level should ideally be ＜140 mg/dL. Assessment of atherosclerosis is mainly performed by noninvasive methods such as ultrasound.For homozygous FH patients, the diagnosis is made by existence of skin xanthomas or tendon xanthomas from infancy, and untreated LDL-C levels are approximately twice those of heterozygous FH parents. The responsiveness to pharmacotherapy should be ascertained promptly and if the effect of treatment is not enough, LDL apheresis needs to be immediately initiated.
本文件描述了日本儿科学会和日本动脉硬化学会联合工作组为制定儿科家族性高胆固醇血症（FH）指导意见而达成的共识，旨在改善 FH 的预后。FH 是一种常见的遗传性疾病，由与低密度脂蛋白（LDL）受体途径相关的基因突变引起。由于 FH 患者从出生起就具有高 LDL 胆固醇（LDL-C）水平，因此动脉粥样硬化在儿童期开始并发展，这决定了预后。因此，为了降低其终生心血管疾病风险，FH 患者需要尽早诊断，并尽早开始适当的治疗。杂合子 FH 患者的诊断标准为 LDL-C≥140mg/dL，且具有 FH 家族史或早发 CAD。确诊后，需要改善生活方式，包括饮食和运动，但有时这不足以降低 LDL-C 水平。对于年龄≥10 岁的儿科 FH 患者，如果 LDL-C 水平持续高于 180mg/dL，则需要考虑药物治疗。他汀类药物是起始剂量最低的一线药物，如果需要可以增加剂量。理想的 LDL-C 目标水平应＜140mg/dL。动脉粥样硬化的评估主要通过非侵入性方法进行，如超声。对于纯合子 FH 患者，从婴儿期开始存在皮肤黄色瘤或肌腱黄色瘤即可确诊，且未经治疗的 LDL-C 水平约为杂合子 FH 父母的两倍。应迅速确定药物治疗的反应性，如果治疗效果不足，应立即开始 LDL 吸附治疗。
