Применение статинов при семейной гиперхолестеринемии у детей

Семейная гиперхолестеринемия — самое распространенное генетическое заболевание в мире. Характеризуется повышением в организме уровня общего холестерина и липопротеинов низкой плотности с детства. Оптимальными признаны диагностика и начало терапии заболевания в детском возрасте до появления осложнений, таких как аортальный стеноз, атеросклеротические изменения стенок артерий. Для лечения в качестве препаратов первой линии рекомендованы статины. Однако ввиду немногочисленного опыта мнения среди клиницистов относительно возраста начала липидснижающей терапии различаются. В настоящем обзоре предпринята попытка критически изучить имеющиеся данные мировой литературы, касающиеся применения статинов у детей с семейной гиперхолестеринемией, их эффективности и безопасности.

1. . Mathers C.D., Iburg B.K., Fat M.D., Shibuya K., Inoue M., Stein C. et al. Global Burden of Disease in 2002: data sources, methods and results. Global Programme on Evidence for Health Policy Discussion Paper No. 54 World Health Organization December 2003. https://www.who.int/healthinfo/pa-per54.pdf.

2. Weiss L.A., Pan L., Abney M., Ober C. The sex-specific genetic architecture of quantitative traits in humans. Nature Genetics 2006; 38(2): 218-222. DOI: 10.1038/ng1726

3. Arnett D.K., Blumenthal R.S., Albert M.A., Buroker A.B., Gold-berger Z.D., Hahn E.J. et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 140(11): e596—e646. DOI: 10.1161/CIR.0000000000000678

4. Ежов М.В., Близнюк С.А., Тмоян Н.А. Рожкова Т.А., Ду-пляков Д.В., Сальченко В.А. и др. Регистр пациентов с семейной гиперхолестеринемией и пациентов оченьвысокого сердечно-сосудистого риска с недостаточной эффективностью проводимой гиполипидемической терапии (РЕНЕССАНС). Российский кардиологический журнал 2019; 5: 7—13. DOI: 10.15829/1560-4071-2019-5-7-13

5. Классификация и эффекты статинов. [Электронный ресурс]. https://noatero.ru/ru/klassifikaciya-i-effekty-statinov

6. Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., Bruckerd E. et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies: a consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017; 38: 2459-2472. DOI:10.1093/eurheartj/ehx144

7. Grundy S.M., Arai H, Barter P., Bersot T.P., Betteridge D.J., Carmena R. et al. An International Atherosclerosis Society Position Paper: global recommendations for the management of dyslipidemia — full report. J Clin Lipidol 2014; 8: 29-60. DOI: 10.1016/j.jacl.2013.12.005

8. Luirink I.K., Wiegman A., Kusters D.M., Hof M.H., Groothoff J.W., de Groot E. et al. 20-Year Follow-up of Statins in Children with Familial Hypercholesterolemia. New Engl J Med 2019; 381(16): 1547—1556. DOI: 10.1056/nejmoa1816454

9. Wiegman A., Gidding S.S., Watts G.F., Chapman M.J., Ginsberg H.N., Cuchel M. et al. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015; 36(36): 2425—2437. DOI: 10.1093/eurheartj/ehv157

10. Clauss S.B., Holmes K.W., Hopkins P., Stein E., Cho M., Tate A.C. et al. Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. Pediatrics 2005; 116: 682—688. DOI: 10.1542/peds.2004-2090

11. Wiegman A., Hutten B.A., de Groot E., Rodenburg J., Bac-cer H., Buller H. R. et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. JAMA 2014; 292: 331—337. DOI: 10.1001/jama.292.3.331

12. Mamann N., Lemale J., Karsenty A., Dubern B., Girardet J.-P., Tounian P. Intermediate-Term Efficacy and Tolerance of Statins in Children. J Pediatr 2019; 210: 161—165. DOI: 10.1016/j.jpeds.2019.03.032

13. McCrindle B.W., Ose L., Marais A.D. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr 2013; 142: 74—80. DOI: 10.1016/j.accreview.2003.09.056

14. Vuorio A., Kuoppala J., Kovanen P.T., Humphries S.E., Tons-tad S., Wiegman A. et al. Statins for children with familial hypercholesterolemia. Cochrane Database of Syst Rev 2019; 11: CD006401. DOI: 10.1002/14651858.cd006401.pub5

15. Avis H.J., Hutten B.A., Gagne C., Langslet G., McCrindle B.W., Wiegman A. et al. Efficacy and Safety of Rosuvastatin Therapy for Children With Familial Hypercholesterolemia. J Am Coll Cardiol 2010; 55(11): 1121—1126. DOI: 10.1016/j.jacc.2009.10.042

16. Raitakari O.T., Juonala M., Kahonen M., Taittonen L., Lai-tinen T., Maki-Torkko N. et al. Cardiovascular risk factors in children and carotid intima-media thickness in adulthood: the Cardiovascular Risk in Young Finns Study. JAMA 2003; 290: 2277—2283. DOI: 10.1001/jama.290.17.2277

17. Kusters D.M., Wiegman A., Kastelein J.J.P., Hutten B.A. Carotid Intima-Media Thickness in Children With Familial Hypercholesterolemia. Circulation Res 2013; 114(2): 307— 310. DOI: 10.1161/circresaha.114.301430

18. Braamskamp M.J., Hutten B.A., Wiegman A. Early initiation of statin treatment in children with familial hypercholes-terolaemia. Curr Opin Lipidol 2015; 26(3): 236—239. DOI: 10.1097/mol.0000000000000177

19. De Jongh S., Lilien M.R., op’t Roodt J., Stroes E.S., Bak-ker H.D., Kastelein J.J. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol 2002; 40(12): 2117—2121. DOI: 10.1016/s0735-1097(02)02593-7

20. Harada-Shiba M., Ohta T., Ohtake A., Ogura M., Dobashi K., Nohara A. et al. Guidance for Pediatric Familial Hypercholesterolemia 2017. J Atheroscler Thromb 2018; 25(6): 539—553. DOI: 10.5551/jat.14621

21. Watts G., Gidding S., Wierzbicki A., Toth P. P., Alonso R., Brown W.V. et al. Integrated guidance on the care of familial hypercholesterolaemia from the International FH Foundation. Inter J Cardiol 2014; 171: 309—325. DOI: 1016/j.ijcard.2013.11.025

22. Goldberg A.C., Hopkins P.N., Toth P.P., Ballantyne C.M., Rader D.J., Robinson J.G. et al. Familial hypercholesterolemia: screening, diagnosis and management of pediatric and adult patients: clinical guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol 2011; 5(3 Suppl): S1—8. DOI: 10.1016/j.jacl.2011.03.001

23. Descamps O.S., Tenoutasse S., Stephenne X., Gies I., Beau-loye V., Lebrethon M.C. et al. Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization. Atherosclerosis 2011; 218(2): 272—280. DOI: 10.1016/j.atherosclerosis.2011.06.016

24. Kennedy M.J., Jellerson K.D., Snow M.Z., Zacchetti M.L. Challenges in the pharmacologic management of obesity and secondary dyslipidemia in childrenand adolescents. Pediatr Drugs 2013; 15: 335—342. DOI: 10.1007/s40272-013-0028-2

25. De Ferranti S., Ludwig D.S. Storm over statins—the controversy surrounding pharmacologic treatment of children. N Engl J Med 2008; 359(13): 1309—1312. DOI: 10.1056/NEJMp0805953

26. Wagner J.B. Children Are Not Small Adults: Specific Findings in Statin Exposure and Response in a Growing Population. Clin Pharmacol Therap 2019; 106(2): 278—280. DOI: 10.1002/cpt.1431

27. Thompson P.D. Statin-Associated Myopathy. JAMA 2003; 289: 1681. DOI: 10.1001/jama.289.13.1681

28. Avis H.J., Vissers M.N., Stein E.A. A systematic review and meta-analysis of statin therapy in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2007; 27: 1803—1810. DOI: 10.1161/ATVBAHA.107.145151

29. Mach F., Baigent C., Catapano A.L., Koskinas K.C., Casu-la M., Badimon L. ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J 2020; 41(1): 111—188. DOI: 10.1093/eu-rheartj/ehz455

30. Desai N.K., Mendelson M.M., Baker A., Ryan H.H., Griggs S., Boghani M. et al. Hepatotoxicity of Statins as Determined by Serum Alanine Aminotransferase in a Pediatric Cohort With Dyslipidemia. JPGN 2019; 68; 2: 175—181. DOI: 10.1097/MPG.0000000000002174

31. Vuorio A., Kuoppala J., Kovanen P.T., Humphries S. E., Tonstad S., Wiegman A. et al. Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev 2019; 2019(11): CD006401. DOI: 10.1002/14651858.CD006401.pub5

32. Wiegman A., Gidding S.S., Watts G.F., Chapman M.J., Ginsberg H.N., Cuchel M. Familial hypercholesterolaemia in children and adolescents: gaining decades of life by optimizing detection and treatment. Eur Heart J 2015; 36(36): 2425— 2437. DOI: 10.1093/eurheartj/ehv157

33. Shafiq N., Bhasin B., Pattanaik S., Pandhi P, Venkate-shan S.P., Singh M. et al. A meta-analysis to evaluate the efficacy of statins in children with familial hypercholesterolemia. Int J Clin Pharmacol Therap 2007; 45: 548—555. DOI: 10.5414/CPP45548

34. Carreau V., Girardet J.P., Bruckert E. Long-term follow-up of statin treatment in a cohort of children with familial hypercholesterolemia. Efficacy and tolerability. Pediatr Drugs.2011; 13: 267-275. DOI: 10.2165/11591650-000000000-00000

35. Besseling J., Kastelein J.J., Defesche J.C., Hutten B.A., Ho-vingh G.K. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA 2015; 313(10): 358-361. DOI: 10.1001/jama.2015.1206

36. Kusters D.M., Wiegman A., Kastelein J.J.P., Hutten B.A. Carotid Intima-Media Thickness in Children With Familial Hypercholesterolemia. Circulation Res 2013, 114(2): 307-310. DOI: 10.1161/circresaha.114.301430

37. Joyce N., Zachariah J.P., Eaton C.B., Trivedi A.N., Welle-nius G.A. Statin Use and the Risk of Type 2 Diabetes Mellitus in Children and Adolescents. Acad Pediatr 2017; 17(5): 515— 522. DOI: 10.1016/j.acap.2017.02.006

38. Grundy S.M., Stone N.J., Bailey A.L., Beam C., Birtc-her K.K., Blumenthal R.S. et al. 2018 AHA/ACC/AACVPR/ AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation 2019; 139(25): e1082-e1143. DOI: 10.1161/CIR.0000000000000625

39. Ramaswami U., Futema M., Bogsrud M.P., Holven K.B., Roeters van Lennep J., Wiegman A. et al. Comparison of the characteristics at diagnosis and treatment of children with heterozygous familial hypercholesterolaemia (FH) from eight European countries. Atherosclerosis 2020; 292: 178-187. DOI: 10.1016/j.atherosclerosis.2019.11.012

40. Клинические рекомендации. Семейная гиперхолестеринемия. 2018 г. https://noatero.ru/sites/default/files/proekt_klinicheskie_rekomendacii_sghs_mz_rf_18.01.pdf.