Familial hypercholesterolaemia: evolving knowledge for designing adaptive models of care

Optimal care for familial hypercholesterolaemia (FH) requires patient-centred management, multidisciplinary teamwork, involvement of primary care practitioners, patient networks, support groups and high-quality clinical registries, implemented through models of care adapted to FH. Models of care — evidence-based and context-specific frameworks that aim to deliver the highest quality of care for patients and their families — allow the application of precision and multidisciplinary medicine to FH care and can serve as paradigms for the prevention of premature atherosclerotic cardiovascular disease in all at-risk patients and families worldwide. The exponential growth in the number of publications on diverse aspects of FH has provided new knowledge for developing essential elements of existing models of care. These elements include clinical diagnostic criteria and genetic testing; risk restratification strategies; LDL-cholesterol treatment targets; management protocols for children; care of women in pregnancy; use of pharmacotherapies, including ezetimibe and PCSK9 inhibitors; use of lipoprotein apheresis for severe FH; and addressing barriers to care. However, substantial gaps remain that need to be addressed by a broad research agenda, implementation strategies and global collaboration and advocacy, aimed at improving the uptake, cost-effectiveness and routine implementation of evidence-based standards. In this Review, we summarize the dramatic increase in knowledge that informs adaptive models of care, with an emphasis on articles published since 2014. Familial hypercholesterolaemia is a genetic disorder that impairs the hepatic clearance of LDL, leading to premature atherosclerotic cardiovascular disease. In this Review, Watts and colleagues summarize the latest advances that can inform the development and implementation of new models of care for familial hypercholesterolaemia. Key points Effective identification of familial hypercholesterolaemia (FH) requires the coordination of several screening strategies, with an emphasis on early detection and a central role for primary care. Clinical diagnostic criteria for FH can be imprecise and need refining with affordable genetic testing; detection of a pathogenic mutation has prognostic utility and allows cascade testing and the initiation of treatment in childhood. Incident atherosclerotic cardiovascular disease is variable in FH and can be predicted by genetic and phenotypic factors, including LDL-cholestero