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Effectiveness of genetic cascade screening for familial hypercholesterolaemia using a centrally co-ordinated clinical
Damon A Bell1, Jing Pang2, Sally Burrows2
1Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, Australia; School of Medicine and Pharmacology, University of Western Australia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Royal Perth Hospital, Perth, Australia.
Insights
Genetic cascade screening effectively identifies familial hypercholesterolaemia (FH) in Australia. This strategy detects new FH cases, many with other cardiovascular risks, and leads to significant LDL-cholesterol reduction.
Area of Science:
- Cardiovascular Genetics
- Public Health Screening
- Lipid Metabolism
Background:
- Familial hypercholesterolaemia (FH) is an inherited disorder impacting LDL catabolism, leading to high LDL-cholesterol and early coronary artery disease (CAD).
- Genetic cascade screening of relatives is recommended but clinical implementation data is limited.
Purpose of the Study:
- To evaluate the effectiveness and acceptability of a centralized genetic cascade screening program for FH in Western Australia.
- To determine the yield of new FH diagnoses and assess the impact on LDL-cholesterol levels.
Main Methods:
- 100 index cases with genetically confirmed FH and their relatives underwent genetic and lipid testing.
- Effectiveness measured by new FH cases per index case and LDL-cholesterol reduction post-treatment.
- Participant satisfaction with screening and care was assessed.
Main Results:
- 51.4% of 366 relatives tested had a pathogenic FH mutation, averaging 2 new cases per index case.
- Newly diagnosed relatives were younger and less likely to have FH stigmata or premature CAD compared to index cases.
- Significant LDL-cholesterol reduction achieved (-24.3% overall), with untreated new cases reaching 42.5% reduction; over 90% satisfaction.
Conclusions:
- Centralized genetic cascade screening is effective and acceptable for FH detection in Australia.
- A substantial number of newly diagnosed FH cases present with other cardiovascular risk factors and may already be on statins without a prior FH diagnosis.
Background:
Familial hypercholesterolaemia (FH) is a co-dominantly inherited disorder of low-density lipoprotein (LDL) catabolism, causing elevated LDL-cholesterol and premature coronary artery disease (CAD). Several guidelines recommend genetic cascade screening relatives of probands (index cases) with genetically proven FH, but experience in a clinical service setting is limited.
Methods:
Relatives from 100 index cases with genetically confirmed FH underwent genetic and lipid testing via a centralised screening program in Western Australia. The program's effectiveness was evaluated as the number of newly diagnosed relatives with FH per index case and the proportional reduction in LDL-cholesterol after treatment.
Results:
Of 366 relatives tested for FH, 188 (51.4%) were found to have a pathogenic mutation. On average, 2 cases were detected per index case. Affected relatives were younger and less likely to have physical stigmata of FH and premature CAD than index cases (p < 0.001). Of the new cases, 12.8% had hypertension, 2.7% had diabetes and 16.0% were smokers; 48.4% were already on statin therapy and these were older (p < 0.001) and had more vascular risk factors and CAD (p < 0.01) than those not on therapy. Significant reductions in LDL-cholesterol (-24.3%, p < 0.001) were achieved overall, with previously untreated new cases of FH attaining a maximal average reduction of 42.5% in LDL-cholesterol after drug therapy. Over 90% of subjects were satisfied with screening and care.
Conclusion:
Genetic cascade screening co-ordinated by a centralised service is an effective and acceptable strategy for detecting FH in an Australian setting. A significant proportion of new cases exhibit other CAD risk factors and are already on statins, but have not received a prior diagnosis of FH.
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