NEW STRATEGIES FOR THE EARLY DIAGNOSIS, RISK STRATIFICATION AND CO-MANAGEMENT OF FAMILIAL HYPERCHOLESTEROLEMIA

Familial hypercholesterolemia (FH) is the most common inherited metabolic disorder in the world with about 2.5 million Europeans affected. An accurate diagnosis through genetic testing confirms the disorder in only about 50% of the cases.

Different effective treatments to reduce cardiovascular disease exist; however these high-risk individuals are not being clinically identified.

FH-EARLY will enable new strategies for earlier diagnosis and co-management of familial hypercholesterolemia facilitated by well-defined data flows, identifying new mechanisms through multiomics, explainable AI modelling and co-creation with families with FH and caregivers.

Its specific objectives are:1.Use co-creation methods to involve FH patients, families and care teams during the project.2.Enhance 4 federated multi-modal datasets collated from established cohorts, and realworld datasets.3.Conduct large-scale functional characterization of FH-related gene variants, to illuminate affected protein function and the variability of the FH phenotype4.Develop and test an integrative precision health profiling methodology using explainable AI for FH risk prediction.5.Test and validate a new chip array for early diagnosis6.Establish clinical and health economic benefits for the signature biomarker in a multicenter interventional study for FH screening.7.Integrate the early signature biomarker into clinical practice to improve treatment selection and risk assessment of FH and severe hypercholesterolemia patients FH-EARLY will deliver a chip array for earlier, cheaper diagnosis, a signature biomarker assay for unique risk stratification and a XAI driven integrative precision health profiling tool.

These will help reduce the burden of atherosclerotic cardiovascular disease, while shifting towards a holistic co-management approach including healthier living in families with FH. This will have a significant impact on cardiovascular health for families with FH and the wider population