Objective Familial hypercholesterolaemia (FH) is a common inherited disorder that remains mostly undetected in the general population. Through FH case-finding and direct access to genetic testing in primary care, this intervention study described the genetic and lipid profile of patients found at increased risk of FH and the outcomes in those with positive genetic test results. Methods In 14 Central England general practices, a novel case-finding tool (Familial Hypercholetserolaemia Case Ascertainment Tool, FAMCAT1) was applied to the electronic health records of 86 219 patients with cholesterol readings (44.5% of total practices’ population), identifying 3375 at increased risk of FH. Of these, a cohort of 336 consenting to completing Family History Questionnaire and detailed review of their clinical data, were offered FH genetic testing in primary care. Results Genetic testing was completed by 283 patients, newly identifying 16 with genetically confirmed FH and 10 with variants of unknown significance. All 26 (9%) were recommended for referral and 19 attended specialist assessment. In a further 153 (54%) patients, the test suggested polygenic hypercholesterolaemia who were managed in primary care. Total cholesterol and low-density lipoprotein-cholesterol levels were higher in those patients with FH-causing variants than those with other genetic test results (p=0.010 and p=0.002). Conclusion Electronic case-finding and genetic testing in primary care could improve identification of FH; and the better targeting of patients for specialist assessment. A significant proportion of patients identified at risk of FH are likely to have polygenic hypercholesterolaemia. There needs to be a clearer management plan for these individuals in primary care. Trial registration number [NCT03934320][1]. No data are available. We do not have consent from participants to share their data for the purposes of future research. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03934320&atom=%2Fheartjnl%2F107%2F24%2F1956.atom

中文翻译：

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初级保健中家族性高胆固醇血症的病例发现和基因检测

目的 家族性高胆固醇血症 (FH) 是一种常见的遗传性疾病，在普通人群中大多未被发现。通过 FH 病例发现和在初级保健中直接进行基因检测，这项干预研究描述了发现 FH 风险增加的患者的遗传和血脂谱以及基因检测结果呈阳性的患者的结果。方法 在英格兰中部的 14 个全科诊所中，一种新的病例发现工具（家族性高胆固醇血症病例确定工具，FAMCAT1）被应用于 86 219 名有胆固醇读数的患者（占诊所总人口的 44.5%）的电子健康记录，确定了 3375 名患者FH 的风险增加。其中，一组 336 人同意完成家族史问卷调查并详细审查他们的临床数据，在初级保健中提供 FH 基因检测。结果 283 例患者完成基因检测，新发现 16 例经基因证实的 FH 和 10 例意义不明的变异。所有 26 人 (9%) 都被推荐转诊，19 人参加了专家评估。在另外 153 名 (54%) 患者中，该测试表明在初级保健中接受治疗的多基因高胆固醇血症。具有引起 FH 变异的患者的总胆固醇和低密度脂蛋白胆固醇水平高于具有其他基因检测结果的患者（p=0.010 和 p=0.002）。结论 初级保健中的电子病例发现和基因检测可提高 FH 的识别率；以及更好地针对患者进行专家评估。确定有 FH 风险的患者中有很大一部分可能患有多基因高胆固醇血症。在初级保健中需要为这些人制定更清晰的管理计划。试用注册号[NCT03934320][1]。没有可用数据。我们没有征得参与者的同意，可以出于未来研究的目的共享他们的数据。[1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03934320&atom=%2Fheartjnl%2F107%2F24%2F1956.atom