Departments of Medicine and Biochemistry, and Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Nat Rev Cardiol. 2019 Jan;16(1):9-20. doi: 10.1038/s41569-018-0052-6.
Familial hypercholesterolaemia is the most commonly encountered genetic condition that predisposes individuals to premature cardiovascular disease. Nevertheless, most patients are undiagnosed, and treatment is often suboptimal even when the diagnosis seems certain. Advances in molecular technologies are reshaping our understanding of this condition, including revision upwards of the population prevalence. Furthermore, the underlying pathophysiological complexity has been exposed by the range of causative genetic loci, breadth of types and classes of rare disease-causing variants, and polygenic basis of the phenotype in many patients. Genetic testing is not always helpful or definitive. Familial hypercholesterolaemia can be envisioned as a group of related disorders, of which the classic 'textbook' phenotype is a subset. Features such as clinical stigmata, family history of dyslipidaemia or cardiovascular disease, and presence of a rare pathogenic variant all increase diagnostic certainty. However, even in the absence of these elements, the essential feature remains an elevated level of plasma LDL cholesterol, which alone should prompt a dialogue between the care provider and the patient on lifestyle modification and lipid-lowering therapy as the foundation of a long-term strategy to prevent or delay the onset of cardiovascular disease.
家族性高胆固醇血症是最常见的遗传疾病，使个体易患心血管疾病。然而，大多数患者未被诊断，即使诊断似乎明确，治疗也往往不理想。分子技术的进步正在改变我们对这种疾病的理解，包括对人群患病率的修正。此外，致病基因座的范围、罕见致病变异的类型和种类的广度以及许多患者表型的多基因基础，揭示了潜在的病理生理学复杂性。基因检测并不总是有帮助或确定的。家族性高胆固醇血症可以被视为一组相关的疾病，其中经典的“教科书”表型是一个子集。临床体征、血脂异常或心血管疾病家族史以及罕见致病性变异的存在等特征都增加了诊断的确定性。然而，即使没有这些因素，其基本特征仍然是血浆 LDL 胆固醇水平升高，这本身就应该促使医疗保健提供者与患者就生活方式改变和降脂治疗进行对话，作为预防或延迟心血管疾病发生的长期策略的基础。
