Familial hypercholesterolaemia (FH) is the most common inherited lipid disorder, affecting about one in 300 people worldwide (1). If untreated, elevated low-density lipoprotein cholesterol (LDL‑C) levels from birth confer an increased risk of premature atherosclerotic cardiovascular disease. Early detection and treatment are therefore crucial to reduce the burden of preventable cardiovascular complications. Unfortunately, as demonstrated by the European Atherosclerosis Society (EAS) Familial Hypercholesterolaemia Studies Collaboration (FHSC) global registry in over 42,000 adults, late diagnosis (in the 40s) is usual (2).
Universal cholesterol screening in early life has been advocated as an effective strategy, first in 1998 by the World Health Organization as a public health priority in FH care (3), and more recently, by the World Heart Federation and the European Commission Public Health Best Practice Portal (5-7), the latter which recommended paediatric FH screening as one of the best practices in non-communicable disease prevention (6). In reality, however, this vital opportunity to impact the long-term health of children with FH is missed, as demonstrated by latest data from the FHSC, published recently in The Lancet (7).
This report from the FHSC included data from 11,848 children with heterozygous FH, about half of whom were girls, representing the largest pool of real-world data for this group. Over two-thirds of these children were identified via cascade screening after a parent or relative had a cardiovascular event or cardiovascular disease was suspected, and this was consistent across high- and non-high-income regions of the world (7). These data reinforce that children are not the primary focus of FH detection.
The FHSC registry data also highlighted the limitations of relying on clinical criteria used in adult FH screening. For example, physical signs such as xanthomas were present in only a minority of children, less than 2% of those in high-income countries and less than 15% in non-high-income countries, and evidence of cardiovascular risk factors (other than elevated cholesterol) or cardiovascular disease was rare (7). Moreover, reliance on the LDL-C cutoffs used in adult screening would miss detection of FH in up to 75% of children, when compared with the gold standard of genetic testing (7). Given issues with accessibility to and the cost of genetic testing in less affluent regions, there is clearly an urgent need to develop cholesterol screening criteria that are specific for children.
These new data from the FHSC should prompt an urgent rethink on priorities for FH detection in current practice. First, accumulating evidence from the FHSC reaffirms that finding children with FH should be the primary priority, given the long-term benefits associated with avoiding preventable premature cardiovascular disease (4). Second, the urgency of the challenge has been highlighted. Already it is estimated that there are 6.4 million children and adolescents living with FH (largely undetected)(8), and with 450,000 new cases born each year, this number will more than double by 2040 (9). Focusing on finding FH in young children will also reap rewards for finding FH earlier in their parents and relatives through reverse cascade testing, an approach with proven cost-effectiveness (10,11). Thus, aligning with the 2022 Prague Declaration, now is the time to act so that FH paediatric screening is integrated into routine childhood screening (12). Successful intervention will require the involvement of all stakeholders in FH care, to ensure that these individuals are identified and treated early, ensuring they can live long and healthy lives.
References
1. Hu P, Dharmayat KI, Stevens CAT, Sharabiani MTA, Jones RS, Watts GF, 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.
2. 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). Lancet 2021;398:1713-25.
3. WHO Human Genetics Programme. Familial hypercholesterolaemia (FH): report of a second WHO consultation, Geneva, 4 September 1998. Geneva: World Health Organization; 1999. [cited 2022 Sep 13]. Available from: https://apps.who.int/iris/handle/10665/66346
4. 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.
5. World Heart Federation. Improving prevention and control of raised cholesterol: a call to action. World Heart federation White Paper. Geneva: World Heart Federation; 2021.
6. European Commission Public Health Best Practice Portal. Selection of best practices in non-communicable disease prevention: Paediatric screening of FH (Familial Hypercholesterolaemia) patients. 2021. [cited 2022 Sep 13]. Available from: https://webgate.ec.europa.eu/dyna/bp-portal/practice.cfm?id=390
7. 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
8. United Nations: World Population Prospects 2022. https://www.un.org/en/desa/world-population-reach-8-billion-15-november-2022
9. Global Change Data Lab & United Nations. 2022. https://ourworldindata.org/grapher/number-of-births-per-year
10. McKay AJ, Hogan H, Humphries SE, et al. Universal screening at age 1–2 years as an adjunct to cascade testing for familial hypercholesterolaemia in the UK: a cost-utility analysis. Atherosclerosis 2018;275:434-43.
11. Wald DS, Bestwick JP, Morris JK, et al. Child–parent familial hypercholesterolemia screening in primary care. N Engl J Med 2016;375:1628-37.
12. 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.