Cardiology

Familial hypercholesterolaemia (FH)

Familial hypercholesterolaemia (FH) affects approximately 1 in 250 Australians, yet up to 90% of individuals remain undiagnosed, representing a significant missed opportunity for early cardiovascular risk reduction.

FH is an autosomal dominant inherited disorder characterised by markedly elevated low-density lipoprotein cholesterol (LDL-C) from an early age. It is frequently under-recognised and may be misclassified as polygenic or lifestyle-related hypercholesterolaemia, despite requiring distinct and more intensive management.

Untreated FH is associated with a significantly increased risk of premature atherosclerotic cardiovascular disease:

• Men with untreated FH have an approximately 50% risk of a coronary event by age 50.
• Women with untreated FH have an approximately 30% risk by age 60.

Early identification and treatment can substantially reduce morbidity and mortality.

Our Panel

This assay analyses a 9-gene panel associated with FH and related lipid disorders.

The majority of pathogenic variants are identified in:

• LDLR
• APOB
• PCSK9

Genetic testing for FH may be performed in two key scenarios:

• Diagnostic testing (index patient)
  Performed in individuals with suspected FH to identify a causative genetic variant

• Cascade testing (family members)
  Targeted single-gene testing for relatives once a familial variant is identified, enabling rapid and cost-effective identification of at-risk individuals

Where a familial variant is identified, Genomic Diagnostics offers targeted single-gene testing for at-risk relatives, supporting streamlined cascade testing. This testing may be eligible for Medicare rebate where clinical criteria are met, and can be requested by a GP or specialist with appropriate clinical information, supporting cost-effective family screening.

Why screen patients for Familial Hypercholesterolaemia?

Genetic testing supports the diagnosis and management of FH and has several important clinical applications:

• Diagnostic confirmation
  Differentiates monogenic FH from multifactorial hypercholesterolaemia

Testing should be considered in patients with:

• Early intervention
  Enables timely initiation and intensification of lipid-lowering therapy to reduce cardiovascular risk

• LDL-C ≥6.5 mmol/L (in the absence of secondary causes)
• LDL-C 5.0–6.5 mmol/L with features suggestive of FH
• DLCN score ≥6 (probable/definite FH)
• A known familial pathogenic variant

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• Cascade testing
  Facilitates identification of at-risk relatives, allowing early monitoring and preventive care

FH is inherited in an autosomal dominant manner. First-degree relatives have a 50% probability of carrying the variant, supporting targeted cascade testing.

• Clinical decision support
  Complements established tools (e.g. DLCN criteria) to guide long-term management

_{Birkenhead K et al. Familial hypercholesterolaemia in Australia. Medicine Today, 2023.}

_{Reamy BV. Familial Hypercholesterolemia: Screening, Diagnosis, and Treatment. AAFP, 2024.}