Hypercholesterolemia in children and adolescents: focus on the familial variant

Familial hypercholesterolemia is characterized by a significant increase in serum low-density lipoprotein cholesterol concentration, which even in the absence of other risk factors leads to the development of atherosclerotic vascular lesions beginning in childhood. With significant prevalence in the population, familial hypercholesterolemia is rarely diagnosed in time due to the Long absence of clinical manifestations. Today the urgent task is to develop and implement programs of primary detection of familial hypercholesterolemia in children and adolescents. Early detection of patients with familial hypercholesterolemia and timely initiation of adequate lipid-lowering therapy will curb the rate of atherosclerosis progression, which will significantly reduce disability and mortality from cardiovascular diseases in older age groups. There are four types of screening: cascade, targeted, opportunistic and universal. Cascade screening is currently considered the most effective and cost-effective way to identify new patients with familial hypercholesterolemia among relatives of an index patient, the patient with the established diagnosis. Targeted screening is based on searching for individuals with familial hypercholesterolemia among groups of patients with the early development of atherosclerotic vascular lesions, for example, in cardiology or neurology hospitals. Opportunistic screening is a non-systematic, sporadic determination of cholesterol levels in patients seeking medical care for any reason. It is most applicable in primary care health care settings. Universal screening is a mass screening of certain age groups and is a highly effective way of early diagnosis, especially in combination with reverse cascade screening of parents, siblings, and other relatives of the index patient. Implementation of programs of early childhood detection of familial hypercholesterolemia, setting up systems of adequate routing of patients, timely prescription of effective lipid-lowering therapy will contribute to health preservation and prolongation of working age, development, and preservation of labor potential of the country.

1. Ivanova O.N., Vasiliev P.A., Zakharova E.Yu. Molecular Bases of Primary Monogenic Dyslipidemia. Meditsinskaya genetika = Medical Genetics. 2020;19(12):4-17. (In Russ.) Available at: https://www.medgen-journal.ru/jour/article/view/1811.

2. Ramaswami U., Humphries S.E., Priestley-Barnham L., Green P., Wald D.S., Capps N. et al. Current Management of Children and Young People with Heterozygous Familial Hypercholesterolaemia - HEART UK Statement of Care. Atherosclerosis. 2019;290:1-8. https://doi.org/10.1016/j.atherosclerosis.2019.09.005.

3. Kastelein JJ.P., Reeskamp L.F., Hovingh G.K. Familial Hypercholesterolemia: The Most Common Monogenic Disorder in Humans. J Am Coll Cardiol. 2020;75(20):2567-2569. https://doi.org/10.1016/j.jacc.2020.03.058.

4. Beheshti S.O., Madsen C.M., Varbo A., Nordestgaard B.G. Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects. J Am Coll Cardiol. 2020;75(20):2553-2566. https://doi.org/10.1016/j.jacc.2020.03.057.

5. Hu P., Dharmayat K.I., Stevens C.A.T., Sharabiani M..TA., Jones R.S., Watts G.F. 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(22):1742-1759. https://doi.org/10.1161/CIRCULATIONAHA.119.044795.

6. Wald D.S., Bestwick J.P., Morris J.K., Whyte K., Jenkins L., Wald NJ. Child-Parent Familial Hypercholesterolemia Screening in Primary Care. N Engl J Med. 2016;375(17):1628-1637. https://doi.org/10.1056/NEJMoa1602777.

7. Meshkov A.N., Ershova A.I., Shalnova S.A., Alieva A.S., Bazhan S.S., Barbarash O.L. et al. Cross-Sectional Study to Estimate the Prevalence of Familial Hypercholesterolemia in Selected Regions of the Russian Federation: Relevance, Design of the Study and Initial Characteristics of the Participants. Ratsional’naya farmakoterapiya к kardiologii = Rational Pharmacotherapy in Cardiology. 2020;16(1):24-32. (In Russ.) https://doi.org/10.20996/1819-6446-2020-02-17.

8. Ezhov M.V., Barbarash O.L., Voevoda M.I., Gurevich V.S., Vezikova N.N., Sadykova D.I. et al. Organization of Lipid Centers Operation in the Russian Federation - New Opportunities. Rossiyskiy kardiologicheskiy zhurnal = Russian Journal of Cardiology. 2021;26(6):4489. (In Russ.) https://doi.org/10.15829/1560-4071-2021-4489.

9. Vallejo-Vaz A.J., De Marco M., Stevens C.A.T., Akram A., Freiberger T., Hovingh G.K. et al. Overview of the Current Status of Familial Hypercholesterolaemia Care in over 60 Countries - The EAS Familial Hypercholesterolaemia Studies Collaboration (FHSC). Atherosclerosis. 2018;277:234-255. https://doi.org/10.1016/j.atherosclerosis.2018.08.051.

10. Wang N., Fulcher J., Abeysuriya N., Park L., Kumar S., Di Tanna G.L. et al. Intensive LDL Cholesterol-Lowering Treatment beyond Current Recommendations for the Prevention of Major Vascular Events: A Systematic Review and Meta-Analysis of Randomised Trials Including 327 037 Participants. Lancet Diabetes Endocrinol. 2020;8(1):36-49. https://doi.org/10.1016/S2213-8587(19)30388-2.

11. Lazaro P., Perez de Isla L., Watts G.F., Alonso R., Norman R., Muniz O. et al. Cost-Effectiveness of a Cascade Screening Program for the Early Detection of Familial Hypercholesterolemia. J Clin Lipidol. 2017;11(1):260-271. https://doi.org/10.1016/j.jacl.2017.01.002.

12. Louter L., Defesche J., Roeters van Lennep J. Cascade Screening for Familial Hypercholesterolemia: Practical Consequences. Atheroscler Suppl. 2017;30:77-85. https://doi.org/10.1016/j.atherosclerosissup.2017.05.019.

13. Rubio-Marin P, Michan-Dona A., Maraver-Delgado J., Arroyo-Olivares R., Barrado Varea R., Perez de Isla L., Mata P Cascade Screening Program for Familial Hypercholesterolemia. Endocrinol Diabetes Nutr (Engl Ed). 2018;65(5):280-286. https://doi.org/10.1016/j.endinu.2017.12.009.

14. Kramer A.I., Trinder M., Brunham L.R. Estimating the Prevalence of Familial Hypercholesterolemia in Acute Coronary Syndrome: A Systematic Review and Meta-Analysis. Can J Cardiol. 2019;35(10):1322-1331. https://doi.org/10.1016/j.cjca.2019.06.017.

15. Jellinger P.S. American Association of Clinical Endocrinologists/American College of Endocrinology Management of Dyslipidemia and Prevention of Cardiovascular Disease Clinical Practice Guidelines. Diabetes Spectr. 2018;31(3):234-245. https://doi.org/10.2337/ds18-0009.

16. Galimova L.F., Sadykova D.I., Slastnikova E.S., Usova N.E. Diagnosis of Familial Hypercholesterolemia in Children: Cascade Screening from Theory to Practice. Kardiovaskulyarnaya terapiya i profilaktika = Cardiovascular Therapy and Prevention. 2020;19(3):2348. (In Russ.) https://doi.org/10.15829/1728-8800-2020-2348.

17. Bell DA., Hooper AJ., Bender R., McMahon J., Edwards G., van Bockxmeer F.M. et al. Opportunistic Screening for Familial Hypercholesterolaemia via a Com munity Laboratory. Ann Clin Biochem. 2012;49(Pt 6):534-537. https://doi.org/10.1258/acb.2012.012002.

18. Mirzaee S.M., Choy K.C., Doery J.D., Nasis A.N., Cameron J.C. The Place of a Tertiary Laboratory in an Opportunistic Screening for Familial Hypercholesterolemia. Eur Heart J. 2017;38(Suppl 1):1331-1332. https://doi.org/10.1093/eurheartj/ehx493.P6245.

19. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents: Summary Report. Pediatrics. 2011;128(Suppl 5):S213-S256. https://doi.org/10.1542/peds.2009-2107C.

20. Kusters D.M., de Beaufort C., Widhalm K., Guardamagna O., Bratina N., Ose L., Wiegman A. Paediatric Screening for Hypercholesterolaemia in Europe. Arch Dis Child. 2012;97(3):272-276. https://doi.org/10.1136/archdis-child-2011-300081.

21. Klancar G., Groselj U., Kovac J., Bratanic N., Bratina N., Trebusak Podkrajsek K., Battelino T. Universal Screening for Familial Hypercholesterolemia in Childr en. J Am Coll Cardiol. 2015;66(11):1250-1257. https://doi.org/10.1016/j.jacc.2015.07.017.