This is a plain English summary of an original research article. The views expressed are those of the author(s) and reviewer(s) at the time of publication.
Familial hypercholesterolaemia is an inherited condition that causes high cholesterol levels from birth. After someone is diagnosed, clinicians, family, or both, contact close relatives to come forward for testing and treatment.
This study, part of a major NIHR project on familial hypercholesterolaemia, concluded that:
- clinician contact results in more people being tested
- overall, clinician contact is the most acceptable approach
- family or combined contact may be better for some families.
More information on familial hypercholesterolaemia is available from Heart UK.
The issue: most people with familial hypercholesterolaemia are not diagnosed
In the UK, 320,000 people are estimated to have familial hypercholesterolaemia, but most (80%) are not diagnosed. This means that opportunities to prevent early heart disease and death are being missed. Another study in the same NIHR project found that people with the condition are 9 times more likely to develop cardiovascular disease than others in the general population.
This study went on to explore the most effective way of identifying people who carry the affected gene. When one person is diagnosed, their closest relatives (sibling or parent, for example) have a 50% chance of also carrying the gene. But on average, for every one person diagnosed with the condition, only one relative is identified.
To find affected relatives, family members are contacted either by a clinician, the person diagnosed, or both. Researchers used several methods to assess which approach is most effective and offers the best value for money.
What’s new?
In this study:
- a literature review (of 4 studies, including 2449 participants in all) suggested that combined clinician and family contact led to slightly more people being tested (40%) than clinician-only (33%) or family-only (34%) contact
- analysis of a database (including people from England and Wales) then found that people were more than twice as likely to be tested (111% increase) if contacted by a clinician rather than a relative
- computer modelling found that the most cost-effective approach was for clinicians to contact all relatives simultaneously (rather than contacting close relatives first, and less-close relatives in a second stage).
The researchers interviewed 40 people with familial hypercholesterolaemia, their family, and clinicians. Interviewees preferred the clinician approach; it ensured that contact had taken place, information was communicated appropriately, and follow-up of people who did not respond was simpler.
However, participants said that the most acceptable approach could depend on the family; the person diagnosed may be best-placed to determine which approach would be most effective for their family. A nurse-led contact service, with more time for conversations and better continuity of care, was strongly supported by clinicians and patients.
Why is this important?
The most effective approach for identifying people with familial hypercholesterolaemia, and the one that offers best value for money, is likely to be contact by clinicians. The findings suggest that clinicians contact first degree relatives (sibling or parent, for example) and second degree relatives (grandparent or nephew, for example) at the same time (not in stages). Combined approaches may be more suitable for some families.
The strength of the findings is reduced by assumptions in the cost-effectiveness analysis (including estimates of the likely burden of high cholesterol levels over someone’s lifetime). Also, the studies included in the literature review did not directly compare testing approaches. The database study, which found that contact by clinicians was most effective, could not rule out other potential factors, such as distance to hospital.
What’s next?
The findings suggest that clinicians contact relatives, and ask the person diagnosed which approach would work best for their family. A nurse-led service could be effective. The researchers say that a randomised controlled trial could compare the different approaches for making contact with relatives.
Genetic testing is expensive, time consuming, and requires specialist resources. The economic analysis suggested that, if the cost of genetic testing is a limiting factor, in some circumstances relatives could be diagnosed on their cholesterol levels alone.
This major NIHR project also found that few (26%) people with familial hypercholesterolaemia receive cholesterol-lowering medications within 2 years of diagnosis. When treated, few (less than 30%) reached their target cholesterol level. Along with better diagnosis, the researchers call for a greater emphasis on treatment for people with this condition.
You may be interested to read
This is a summary of: Qureshi N, and others. Alternative cascade-testing protocols for identifying and managing patients with familial hypercholesterolaemia: systematic reviews, qualitative study and cost-effectiveness analysis. Health Technology Assessment 2023; 27: 1 – 174.
A summary of the study by Heart UK.
Information on familial hypercholesterolaemia from the British Heart Foundation.
Information on taking part in NIHR research on high cholesterol.
Funding: This study was funded by the NIHR Health Technology Assessment programme.
Conflicts of Interest: Several authors received fees and funding from pharmaceutical companies. See paper for full details.
Disclaimer: Summaries on NIHR Evidence are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that the views expressed are those of the author(s) and reviewer(s) at the time of publication. They do not necessarily reflect the views of the NHS, the NIHR or the Department of Health and Social Care.
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