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

Area of Science:

• Cardiovascular Genetics
• Public Health
• Primary Care Medicine

Background:

• Familial hypercholesterolaemia (FH) is a prevalent genetic disorder causing premature coronary artery disease, often underdiagnosed globally.
• Accurate diagnosis via genetic testing is crucial for identifying affected first-degree relatives (FDRs) through cascade testing.
• General practice has limited experience with genetic testing for FH, necessitating new care models.

Purpose of the Study:

• To develop and assess a tertiary-primary shared care model for identifying genetic FH in FDRs of index cases.
• To evaluate the feasibility, uptake, and clinical outcomes of genetic cascade testing within this model.

Main Methods:

• A shared care model was implemented, involving general practitioners (GPs) supported by a tertiary center for genetic FH identification.
• Genetic testing was offered to 153 FDRs of 90 FH index cases, with data collected on uptake, yield, and clinical outcomes.
• LDL-cholesterol levels were compared between relatives with and without pathogenic variants, and treatment outcomes were assessed.

Main Results:

• Genetic testing uptake was 95% among eligible FDRs, with a yield of 50% for pathogenic variants.
• Relatives with pathogenic variants had significantly higher LDL-cholesterol levels (5.9 ± 1.8 mmol/L) compared to those without (2.7 ± 0.9 mmol/L).
• Initiated treatment in 31 relatives led to a 46% LDL-cholesterol reduction, with 45% achieving guideline goals.

Conclusions:

• A tertiary-primary shared care model facilitates effective genetic cascade testing for FH in FDRs.
• This model demonstrates feasibility and positive clinical outcomes, supporting the detection of FH in community settings.
• Findings support the development of centralized, sustained care models for FH management.