Perspectives on Identifying and Treating Familial Hypercholesterolemia in Childhood.
Perspectives on Identifying and Treating Familial Hypercholesterolemia in Childhood.
复制标题
儿童时期家族性高胆固醇血症的识别和治疗的观点。
DOI：
10.1093/clinchem/hvab157
复制
发表时间：
2021
影响因子：
9.3
通讯作者：
Vernacchio,Louis
中科院分区：
文献类型：
--
作者：
Moderators;deFerranti,SarahD;Kazi,DhruvS;Experts:;Bibbins-Domingo,Kirsten;Daniels,Stephen;Howaniec,Barbara;Khera,AmitV;Newman,ThomasB;Vernacchio,Louis
家族性高胆固醇血症（FH）是一种常见的遗传性疾病，具有灾难性的长期后果。FH影响每200-500人中的一人，其中肝细胞对低密度脂蛋白胆固醇（LDL-C）的摄取不足导致血清LDL-C浓度非常高（例如，190 mg/dL）和过早动脉粥样硬化性心血管疾病（ASCVD）的风险增加。检测和治疗青年FH可能会预防未来的ASCVD，包括急性心肌梗死，缺血性心脏骤停和缺血性卒中。FH目前是美国疾病控制和预防中心确定的3种1级疾病之一，作为普通人群基因组筛查的高度优先事项。目前的建议是筛查所有类型的血脂紊乱，包括FH，如果有家族史或医疗条件，提高ASCVD风险（选择性筛查），从20岁开始，每个人在9至11岁之间进行一次血脂紊乱测试（普遍筛查），并在17至21岁之间再次进行一次。到目前为止，美国的重点一直是筛查血脂紊乱;没有建议专门筛查儿童FH。尽管FH的公共卫生重要性，以及儿科血脂检测的指南建议，FH筛查在儿科实践中并未广泛进行，基因检测尚未整合到筛查中，广泛的儿科FH筛查方法尚未在美国进行正式评估。儿童FH筛查率低的部分原因是他汀类药物和生活方式干预的长期疗效不确定，以及对长期他汀类药物暴露的已知和未知不良反应的担忧。由于这些原因，一些国家的指南提倡推迟FH筛查，直到20岁或更晚。其他FH筛查策略包括在儿童表型筛查中增加FH突变的基因检测，在FH家庭成员的儿童中进行反向级联筛查，将FH筛查整合到早期常规儿科健康访视和疫苗接种或铅筛查中。为了讨论这些方法和其他方法的意义，6位受邀专家回答了与儿童FH筛查相关的问题。作为与专家小组的虚拟圆桌会议，从各个利益攸关方收集了关于儿童FH筛查主题的观点。
Familial hypercholesterolemia (FH) is a common genetic disorder with catastrophic long-term consequences. FH affects one in every 200–500 people, in whom insufficient low-density lipoprotein cholesterol (LDL-C) uptake by hepatocytes results in very high concentrations of serum LDL-C (eg, 190mg/dL) and an increased risk of premature atherosclerotic cardiovascular disease (ASCVD). Detecting and treating FH in youth may prevent future ASCVD, including acute myocardial infarction, ischemic cardiac arrest, and ischemic stroke. FH is currently 1 of only 3 Tier 1 conditions identified by the US Centers for Disease Control and Prevention as high priority for genomic screening in the general population. Current recommendations are to screen for lipid disorders of all types—including FH—starting at age 2years if there is a family history or a medical condition that raises ASCVD risk (selective screening), and to test everyone for lipid disorders (universal screening) once between ages 9 and 11 years, and again once between 17 and 21 years. The emphasis in the USA to date has been to screen for lipid disorders in general; there are no recommendations to screen children specifically for FH. Despite the public health importance of FH, and guideline recommendations for pediatric lipid testing, FH screening is not widely performed in pediatric practice, genetic testing has not yet been integrated into screening, and broad pediatric FH screening approaches have not been formally evaluated in the USA. Low rates of screening for FH in childhood are due in part to uncertainty about the long-term efficacy of statins and lifestyle interventions, and concern about known and unknown adverse effects with long-term statin exposure. For these reasons, some national guidelines advocate delayingFH screening until age 20years or later. Alternative FH screening strategies include adding genetic testing for FH mutations to phenotypic screening in children, reverse cascade screening in the children of family members with FH, integrating FH screening into early routine pediatric wellness visits with vaccinations or lead screening. To discuss the implications of these and other approaches, 6 invited experts responded to the questions related to pediatric screening for FH. Perspectives were gathered on the topic of screening for FH in childhood from various stakeholders as a virtual roundtable with the panel of experts.