UCLH BRC cardiovascular theme has transformed understanding of inherited cardiovascular disorders that affect 600,000 people in the UK, improving outcomes in affected families. Research is embedded in the UK’s largest inherited cardiac disease services, which evaluate over 8000 patients each year, creating databases of detailed genetic sequences of patients’ and relatives’ DNA, linked to clinical data to help interpret test results and support family screening. This has enabled new genetic discoveries1 and identified mutations placing patients at high risk of sudden death.
Now, three in five patients with inherited heart muscle disease receive a genetic diagnosis, enabling clinicians to more precisely target expensive, but lifesaving defibrillator treatment. At the same time, 53% of healthy relatives are discharged from lifelong screening.
With international collaborators, the UCLH team developed risk calculators for adults and children with hypertrophic cardiomyopathy and laminopathies. These are incorporated in European guidelines on defibrillator treatment, helping to prevent thousands of sudden cardiac deaths.
The UCLH team has also identified and maintained databases of mutations causing Familial Hypercholesterolaemia (FH), a condition leading to premature heart attacks prevented by early treatment with cholesterol-lowering statin drugs.
It was the first to show that FH is twice as common as previously thought, affecting 1 in 250 people, that only 7% of those affected have been identified and treated, and that patients with many weak genetic variants may masquerade as FH patients2.
Establishment by UCLH in 2012 of the UK Paediatric FH Register has demonstrated the safety and normal growth rate of children with FH treated with statins.
UCLH genetic discoveries are included in the National Genetic Testing portfolio, and UCLH research findings have informed the Chief Medical Officer (CMO) 2016 report on Genomic Medicine3, are incorporated in 2017 NICE guidance (CG71) on ligibility for FH cascade testing in families and had a direct influence on the 2019 NHS Long Term plan which has an ambition to identify 25% of undetected FH patients within the next 5 years.
Locally, the findings have supported the 24 lipid clinics within the greater London region and led to implementation of an FH screening tool through the North Thames Genomic Alliance and local GP services, with sequencing results now being added to health records.
1. Lopes LR., European Heart Journal, 2021; 2. Talmud, P., Lancet, 2013; 3. Humphries S., CMO Report 2016, Genomics
