Genomic Medicine Institute, Geisinger, Danville, Pennsylvania.
Department of Medicine, Division of Cardiovascular Medicine, and Cardiovascular Institute, Stanford University, Stanford California; The Familial Hypercholesterolemia Foundation, Pasadena, California.
J Am Coll Cardiol. 2018 Aug 7;72(6):662-680. doi: 10.1016/j.jacc.2018.05.044.
Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.
尽管家族性高胆固醇血症（FH）的意识正在提高，但这种常见的、潜在致命的、可治疗的疾病仍然诊断不足。尽管 FH 是一种遗传性疾病，但很少进行基因检测。家族性高胆固醇血症基金会召集了一个国际专家小组，评估 FH 基因检测的效用。其基本原理包括以下几点：1）有助于明确诊断；2）致病性变异表明心血管风险更高，这表明可能需要更积极地降低血脂；3）提高治疗的开始和依从性；4）对高危亲属进行级联检测。专家共识小组建议 FH 基因检测成为确诊或可能患有 FH 的患者及其高危亲属的标准护理。检测应包括编码低密度脂蛋白受体（LDLR）、载脂蛋白 B（APOB）和前蛋白转化酶枯草溶菌素/柯萨奇蛋白酶 9（PCSK9）的基因；还可能需要根据患者表型分析其他基因。预期结果包括更多的诊断、更有效的级联检测、更早开始治疗以及更准确的风险分层。
