Background:Familial hypercholesterolemia (FH) is the most common cardiovascular genetic disorder and, if left untreated, is associated with increased risk of premature atherosclerotic cardiovascular disease, the leading cause of preventable death in the United States. Although FH is common, fatal, and treatable, it is underdiagnosed and undertreated due to a lack of systematic methods to identify individuals with FH and limited uptake of cascade testing.Methods and Results:This mixed-method, multi-stage study will optimize, test, and implement innovative approaches for both FH identification and cascade testing in 3 aims. To improve identification of individuals with FH, in Aim 1, we will compare and refine automated phenotype-based and genomic approaches to identify individuals likely to have FH. To improve cascade testing uptake for at-risk individuals, in Aim 2, we will use a patient-centered design thinking process to optimize and develop novel, active family communication methods. Using a prospective, observational pragmatic trial, we will assess uptake and effectiveness of each family communication method on cascade testing. Guided by an implementation science framework, in Aim 3, we will develop a comprehensive guide to identify individuals with FH. Using the Conceptual Model for Implementation Research, we will evaluate implementation outcomes including feasibility, acceptability, and perceived sustainability as well as health outcomes related to the optimized methods and tools developed in Aims 1 and 2.Conclusions:Data generated from this study will address barriers and gaps in care related to underdiagnosis of FH by developing and optimizing tools to improve FH identification and cascade testing.

中文翻译：

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开发和优化解决家族性高胆固醇血症诊断不足的创新工具

背景：家族性高胆固醇血症 (FH) 是最常见的心血管遗传疾病，如果不及时治疗，会增加早发动脉粥样硬化性心血管疾病的风险，这是美国可预防死亡的主要原因。尽管 FH 是常见的、致命的和可治疗的，但由于缺乏识别 FH 个体的系统方法和级联检测的应用有限，因此诊断和治疗不足。 方法和结果：这项混合方法、多阶段研究将优化，测试，并在 3 个目标中实施用于 FH 识别和级联测试的创新方法。为了改进对 FH 个体的识别，在目标 1 中，我们将比较和改进基于自动表型和基因组的方法来识别可能患有 FH 的个体。为了提高高危人群的级联测试接受度，在目标 2 中，我们将使用以患者为中心的设计思维过程来优化和开发新颖、积极的家庭沟通方法。使用前瞻性、观察性的实用试验，我们将评估每种家庭沟通方法在级联测试中的采用率和有效性。在实施科学框架的指导下，在目标 3 中，我们将制定综合指南来识别 FH 患者。使用实施研究的概念模型，我们将评估实施结果，包括可行性、可接受性和感知可持续性以及与目标 1 和 2 中开发的优化方法和工具相关的健康结果。 结论：