Enhancing the detection of familial hypercholesterolaemia in general practice: A model for supporting genetic cascade testing in the community

Familial hypercholesterolaemia (FH) is a common, co-dominant cause of premature coronary artery disease that remains under-recognised worldwide. Genetic testing, the most accurate diagnostic method, is particularly valuable in the cascade testing of close blood relatives, but there is little experience in general practice. We developed a tertiary-primary shared care model to identify genetic FH among first-degree relatives (FDRs) of FH index cases. Service and clinical outcomes were assessed. From a total of 153 FDRs of 90 adult FH index cases, 105 (corresponding to 64 index cases) undertook genetic testing by their general practitioner (GP). Median age of the FDRs was 14.8 years (range 3–79 years), 54% being male, 80% Caucasian, 61% children/adolescents, and 80% progeny. The number of new FDRs with a pathogenic variant per index case was 0.89 (95% CI, 0.69–1.10), with an uptake and yield of testing of 95% and 50%, respectively. Relatives with a pathogenic variant had significantly higher LDL-cholesterol than those without (5.9 ± 1.8 vs. 2.7 ± 0.9 mmol/L, p < 0.001). Among 31 relatives initiated on treatment after a genetic diagnosis, a 46% reduction in LDL-cholesterol was achieved with 45% attaining guideline-directed goals. Genetic cascade testing of FDRs of index cases with FH is feasible and effective in a shared-care model in which GPs are supported by a tertiary centre. These preliminary findings inform the development of centralised and sustained models of care, with implications for the detection of FH in communities.