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Published on: September 15, 2018
Cascade screening for familial hypercholesterolaemia: implications of a pilot study for national screening programmes
D Marks1, M Thorogood, S M Neil
1London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
Insights
Cascade screening for familial hypercholesterolaemia by a specialist clinic identified new cases but did not significantly increase overall prevalence. Direct contact by clinic staff is recommended to improve response rates among relatives.
Area of Science:
- Cardiology
- Genetics
- Public Health
Background:
- Familial hypercholesterolaemia (FH) is an inherited condition causing high cholesterol levels.
- Early diagnosis and treatment of FH are crucial to prevent cardiovascular disease.
- Cascade screening is a method to identify affected relatives of diagnosed individuals.
Purpose of the Study:
- To assess the yield of heterozygous familial hypercholesterolaemia cases identified through cascade screening.
- To determine the impact of this screening on the diagnosed prevalence of FH within a defined population.
- To evaluate the effectiveness of specialist hospital-led cascade screening.
Main Methods:
- A specialist lipid clinic in Oxfordshire, UK, conducted cascade screening.
- First-degree relatives of 227 index FH cases were invited for genetic testing.
- Data were collected on relative response rates and diagnostic yield.
Main Results:
- Cascade screening identified new FH cases in 12% of adult relatives and 23% of children tested.
- The prevalence of diagnosed FH increased by 14.4%, reaching 33.5% of predicted cases.
- Low response rates were observed when relatives were asked to self-initiate testing.
Conclusions:
- Specialist clinic-led cascade screening did not substantially increase diagnosed FH prevalence.
- Direct outreach by clinic staff is essential to enhance relative participation.
- Standardized diagnostic criteria and DNA testing may improve FH diagnosis accuracy.
Objectives:
To determine what proportion of cases of heterozygous familial hypercholesterolaemia would be identified by cascade screening conducted by a specialist hospital clinic, and by how much this would increase the prevalence of diagnosed cases.
Setting:
Hospital clinic serving a population of 605,900 in Oxfordshire, UK.
Methods:
A specialist nurse obtained details of living first-degree relatives from 227 adult patients with heterozygous familial hypercholesterolaemia currently or previously attending Oxford lipid clinic after excluding 79 adults without relatives living in Oxfordshire and 48 children. Index cases were asked to invite relatives resident in Oxfordshire for testing.
Results:
A total of 227 index cases had 1075 first-degree relatives, including 442 adults and 117 children aged < 18 years resident in Oxfordshire. We excluded 171 previously screened adults and 46 for other reasons. Among 225 eligible adult relatives, 28 responders (12%) planned to consult their general practitioner and 52 (23%) attended the clinic for testing. Parents of 113 children (97%) wanted them tested. The positive diagnostic rate was 29% (15/52) in adults and 32% (36/113) in children. Screening increased prevalence by 14.4%, from 0.58/1000 (95% confidence intervals [CI] 0.52-0.65) to 0.67/1000 (95% CI 0.60-0.73), representing 33.5% of predicted cases.
Conclusions:
Cascade screening conducted by a specialist hospital clinic within its population catchment area did not substantially increase the prevalence of diagnosed familial hypercholesterolaemia. To maximize response rates, clinic staff need to approach relatives directly. Validated age, sex and country-specific diagnostic criteria should be defined, possibly with access to DNA-based tests, to help resolve diagnostic uncertainty.
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