Introduction: Familial hypercholesterolemia (FH) is a common autosomal dominant genetic disorder conferring a high risk of premature atherosclerotic cardiovascular disease (ASCVD), without early diagnosis and treatment. Underdiagnosis remains a major public health problem; cascade testing (systematically identifying blood relatives) can mitigate this burden. The Identification Methods, Patient Activation, and Cascade Testing for FH (IMPACT-FH, 5R01HL148246-04) study evaluated family communication strategies for FH cascade testing and significantly increased uptake in a population genomic screening setting. The current IMPACT-FH Renewal (2R01HL148246-05) will next adapt these strategies to individuals diagnosed with FH outside of population genomic screening, evaluate the cost and performance of detection strategies within health systems, and define elements which help sustain FH screening programs. Methods: A pragmatic trial guided by the Conceptual Model of Implementation Research will be conducted to evaluate generalized family communication strategies to facilitate FH cascade testing in primary care (Aim 1). We will apply economic evaluation modeling methods to compare implementation costs, efficiency, and performance of FH implementation strategies, and develop a generic modeling tool for other healthcare systems to support local decision-making (Aim 2). We will use a convergent mixed-methods approach guided by the Integrated Sustainability Framework to understand factors influential in sustaining FH screening programs at an international level (Aim 3). Conclusion: By addressing novel communication strategies, economic impact, and sustainability of FH cascade testing, this study seeks to develop generalizable approaches to improving identification of FH to reduce the high burden of FH-associated ASCVD.
Morgan et al. (Fri,) studied this question.