Global FHSC registry makes the case for universal cholesterol screening of children for familial hypercholesterolaemia

December 13, 2023 – Gothenburg, Sweden

Finding children with familial hypercholesterolaemia (FH), the most common inherited lipid disorder, relies on family cascade screening, usually after a parent or relative has a heart attack, as physical signs of FH in children are uncommon, meaning that detection is delayed in most. These were the key findings from the European Atherosclerosis Society Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry, including nearly 12,000 children with FH from 48 countries, which was published in The Lancet today.1 As early detection and treatment of FH are essential to prevent heart attacks associated with high cholesterol in later life, these data make the case for a paradigm shift to universal screening in children to avoid delays in detection.

According to Professor Kausik K. Ray (Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care & Public Health, Imperial College London, UK), who leads the FHSC registry: ‘Twenty-five years ago, the World Health Organization (WHO) recognised FH as a public health priority, recommending early identification and treatment to prevent cardiovascular complications in later life.2 These recommendations have been echoed recently by patient advocacy groups, the European Commission, and scientific societies as part of the Prague Declaration3 to move towards universal screening for FH.4,5 Early childhood is the ideal opportunity to detect FH and improve long term outcome. However, as shown by these latest data from the FHSC, the current realities of FH care show that children are not the primary focus of detection strategies. For a condition in which early intervention prevents heart attacks in later life, we should be shifting to universal cholesterol screening in early life, to identify and treat children with FH across the world so that they can live long and healthy lives.’ 

FH affects about one in 300 people,6 meaning that worldwide in 2023, there are more than 6 million children and adolescents with FH. With nearly half a million born with FH annually,7 low current identification rates (<10%) will translate to a further 7.3 million affected children by 2040, unless urgent action is taken.

The FHSC registry was established in 2015 with the mission of empowering the global clinical community to seek change in how FH is detected and managed. First data from over 42,000 adults with FH published in 2021 showed that only about 2% are diagnosed as children,8 meaning that delayed diagnosis may account for one in 10 heart attacks under the age of 50 years.9

This latest report from the FHSC is the largest global analysis of children and adolescents with FH, providing a snapshot of current practices for finding FH in this population. The registry includes 11,848 children with FH, about half of whom were girls, with a median age of 9.6 years at entry.1 The median low-density lipoprotein (LDL) cholesterol level for untreated children was 5.0 mmol/L (about 195 mg/dL), higher in those under 9 years and in girls.

Over two-thirds of children with FH are found with family cascade screening after a parent or relative has a heart attack or other cardiovascular event, or suspected cardiovascular disease, rather than identified directly. Importantly, clinical criteria used for detecting FH in adults have limited relevance for detecting FH in children. For example, irrespective of world region, physical signs of FH such as xanthomas or bumps in the skin containing cholesterol, are uncommon, seen in less than 2% of children with FH in high-income countries and less than 15% of those in less affluent regions. Therefore, relying on clinical criteria is likely to miss most children with FH, especially among those with a milder phenotype. 

In adults, LDL cholesterol cut-offs are integral to the diagnosis of clinical FH, especially in lower-income regions with limited access to genetic testing, the gold standard for diagnosis. Even when these LDL cholesterol cut-offs are adapted for children, their use would miss between a quarter and over one-half of children with FH, when compared with genetic testing. Instead, the FHSC registry showed that novel age-specific LDL cholesterol distributions may have potential as a screening tool to improve early diagnosis, as these were able to differentiate children with and without FH from the first year of life.1

‘These latest findings from the FHSC show that we urgently need to implement universal cholesterol screening from an early age into public health policy and clinical care. The clock is ticking; already there are more than 6 million children with FH globally, with the vast majority undetected. We need to act now to reduce the widening gap between new cases and detection, and identify and treat children with FH early to avoid costly preventable heart disease in later life,’ said Professor Ray.

Chief Executive of FH Europe Foundation, Magdalena Daccord added: ‘These results from the FHSC on the detection and diagnosis of FH in children are alarming. However, there is now an important shift to promoting cardiovascular disease prevention and cardiovascular health. With the Prague Declaration, evidence from this global registry, and the cost effectiveness of screening on the one hand, and multidisciplinary collaborations that influence national and regional health policies together with increased awareness, education, and patient-citizen engagement on the other, we have a new opportunity to bend the curve. The right to health is a fundamental human right and with early FH detection through universal cholesterol screening we can deliver on the right for cardiovascular health for those children in the future and cardiovascular disease prevention for their parents today.’

Contact:

EAS Office, Dr Carmel Hayes

+46768 61 00 51
E-mail: office@eas-society.org

References

  1. EAS Familial Hypercholesterolaemia Studies Collaboration. Global Perspective of Familial Hypercholesterolaemia in Children and Adolescents: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). The Lancet 2023; doi: https://doi.org/10.1016/S0140-6736(23)01842-1
  2. Familial Hypercholesterolemia [FH]: Report of a WHO Consultation. World Health Organization, Human Genetics Programme, Division of Noncommunicable Diseases. WHO/HGN/FH/CONS/98.7. Geneva, 1998.
  3. Bedlington N, Abifadel M, Beger B, et al. The time is now: Achieving FH paediatric screening across Europe–The Prague Declaration. GMS Health Innov Technol 2022; 16:Doc04. doi: 10.3205/hta00013.
  4. Wilemon KA, Patel J, Aguilar-Salinas C, et al. Reducing the clinical and public health burden of familial hypercholesterolemia: a global call to action. JAMA Cardiol 2020;5:217-29.
  5. Gidding SS, Wiegman A, Groselj U, et al. Paediatric familial hypercholesterolaemia screening In Europe-Public Policy background and recommendations. Eur J Prevent Cardiol 2022;29:2301-11.
  6. Hu P, Dharmayat KI, Stevens CAT, et al. Prevalence of familial hypercholesterolemia among the general population and patients with atherosclerotic cardiovascular disease: A systematic review and meta-analysis. Circulation 2020;141:1742-59.
  7. Our World in Data, Global Change Data Laboratory & United Nations. 2022. https://ourworldindata.org/grapher/number-of-births-per-year.
  8. Vallejo-Vaz AJ, Stevens CA, Lyons AR, et al. Global perspective of familial hypercholesterolaemia: a cross-sectional study from the EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). The Lancet 2021;398:1713-25.
  9. Familial Hypercholesterolemia. https://rarediseases.org/rare-diseases/familial-hypercholesterolemia/. Updated 25 May 2023.

Notes for editors

About the FHSC

The European Atherosclerosis Society (EAS) FHSC was launched in 2015 with the mission to empower the medical and global community to seek change in how FH is detected and managed, aiming to promote early diagnosis and more effective treatment of this condition.

EAS FHSC is a global initiative led by Prof Kausik K. Ray, an International Executive Committee comprising Prof Alberico L. Catapano (Italy), Dr Tomas Freiberger (Czech Republic), Prof John Kastelein, Prof G. Kees Hovingh (Netherlands), Prof Pedro Mata (Spain), Dr Handrean Soran (UK), Prof Gerald Watts (Australia), Prof Frederick Raal (South Africa), and Prof Raul Santos (Brazil), and an International Steering Committee comprising over 80 national lead investigators from 66 countries. The Coordinating Centre is based at Imperial Centre for Cardiovascular Disease Prevention, Imperial College London, UK.

The key objectives of the EAS FHSC include:

  • Generating robust information to accurately and reliably investigate the burden of both homozygous and heterozygous FH, how FH is detected and managed, and the clinical consequences of current practices on delivery of care and outcomes.
  • Disseminating the information gained from the registry to an international audience including physicians, other healthcare professionals, policymakers and patient organizations.
  • Consolidating a network of investigators interested in FH, through which collaborative research and networking on FH can be conducted on a large-scale.

For further information: https://www.eas-society.org/page/fhsc

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