Hostname: page-component-7c8c6479df-5xszh Total loading time: 0 Render date: 2024-03-28T12:16:50.530Z Has data issue: false hasContentIssue false

Treatment of familial hypercholesterolaemia in children and adolescents in the last three decades

Published online by Cambridge University Press:  10 May 2013

Avishay Elis
Affiliation:
Department of Medicine, Rabin Medical Center, Beilinson Campus, Petah-Tikva and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Rong Zhou
Affiliation:
Medpace Inc., Cincinnati, Ohio, United States of America
Evan A. Stein
Affiliation:
Metabolic & Atherosclerosis Research Center and Cholesterol Treatment Center, Cincinnati, Ohio, United States of America

Abstract

Background: This study evaluated the effectiveness of long-term intensive lipid-lowering therapy in children and adolescents with familial hypercholesterolaemia. Methods: The charts of 89 children and adolescents with heterozygous familial hypercholesterolaemia among ∼1000 patients treated from 1974 to 2008 were reviewed. Familial hypercholesterolaemia was defined as low-density lipoprotein cholesterol level >90th percentile in individuals with a history of familial hypercholesterolaemia. Results: Of the 89 patients, 51% were male; the mean age at diagnosis was 8 ± 4 years, and the mean follow-up was 13 ± 8 years. Baseline and most recent low-density lipoprotein cholesterol levels (mg/dl) under treatment were 250 ± 50 and 142 ± 49, respectively, reduced 43% from baseline (p < 0.0001). At the most recent visit, 39 patients received statin monotherapy, mainly atorvastatin or rosuvastatin, and 50 (56%) patients received combination therapy, mainly vytorin or rosuvastain/ezetimibe, 15 patients were >30 years of age, and none developed symptomatic cardiovascular disease or needed revascularisation. Conclusions: Long-term statin-based therapy can reduce low-density lipoprotein cholesterol levels in most children and adolescents with heterozygous familial hypercholesterolaemia and decrease cardiovascular risk significantly.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Goldstein, JL, Brown, MS. Familial hypercholesterolemia. In: Scriver CR (ed.). The Metabolic Basis of Inherited Disease. McGraw Hill, New York, 1995: 12151245.Google Scholar
2. Austin, MA, Hutter, CM, Zimmern, RL, Humphries, SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol 2004; 160: 421429.Google Scholar
3. Slack, J. Risks of ischemic heart-disease in familial hyperlipoproteinaemic states. Lancet 1969; 2: 13801382.Google Scholar
4. Stone, NJ, Levy, RI, Fredrickson, DS, Verter, J. Coronary artery disease in 116 kindred with familial type II hyperproteinemia. Circulation 1974; 49: 476488.Google Scholar
5. Ribiero, P, Shapiro, LM, Gonzales, A, Thompson, GR, Oakley, CM. Cross sectional echocardiographic assessment of the aortic root and coronary ostial stenosis in familial hypercholesterolemia. Br Heart J 1983; 50: 432437.CrossRefGoogle Scholar
6. Yamamoto, A, Kamiya, T, Yamamura, T, Yokoyama, S, Horiguchi, Y. Clinical features of familial hypercholesterolemia. Arteriosclerosis 1989; 9 (Suppl): I66I74.Google Scholar
7. Brown, BG, Lin, JT, Kelsey, S, et al. Progression of coronary atherosclerosis in patients with probable familial hypercholesterolemia. Quantitative arteriographic assessment of patients in NHLBI type II study. Arteriosclerosis 1989; 9 (Suppl): I81I90.Google Scholar
8. Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Register Group. BMJ 1991; 303: 893896.Google Scholar
9. Marks, D, Thorogood, M, Neil, HAW, Humphries, SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis 2003; 68: 114.Google Scholar
10. McCrindle, BW, Urbina, EM, Dennison, BA, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing. Circulation 2007; 15: 19481967.CrossRefGoogle Scholar
11. Iughetti, L, Predieri, B, Balli, F, Calandra, S. Rational approach to the treatment for heterozygous familial hypercholesterolemia in childhood and adolescence: a review. J Endocrinol Invest 2007; 30: 700719.Google Scholar
12. Stein, EA. Statins in children. Why and when. Nutr Metab Cardiovasc Dis 2001; 5: 2429.Google Scholar
13. Justo, RN. Management of familial hypercholesterolaemia in children and adolescents. J Paediatr Child Health 2012; 48: E53E58.Google Scholar
14. Descamps, OS, Tenoutasse, S, Stephenne, X, 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: 272280.Google Scholar
15. Goldberg, AC, Hopkins, PN, Toth, PP, 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: 133140.CrossRefGoogle Scholar
16. Braamskamp, MJ, Wijburg, FA, Wiegman, A. Drug therapy of hypercholesterolaemia in children and adolescents. Drugs 2012; 72: 759772.Google Scholar
17. Tonstad, S, Knudtzon, J, Sivertsen, M, Refsum, H, Ose, L. Efficacy and safety of cholestyramine therapy in peripubertal and prepubertal children with familial hypercholesterolemia. J Pediatr 1996; 129: 4249.Google Scholar
18. Glueck, CJ, Tsang, RC, Fallat, RW, Mellies, M. Therapy of familial hypercholesterolemia in childhood: diet and cholestyramine resin for 24 to 36 months. Pediatrics 1997; 59: 433441.Google Scholar
19. Lambert, M, Lupien, PJ, Gagné, C, et al. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group. Pediatrics 1996; 97: 619628.Google Scholar
20. Stein, EA, Illingworth, DR, Kwiterovich, PO Jr, et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia. JAMA 1999; 281: 137144.Google Scholar
21. Clauss, SB, Holmes, KW, Hopkins, P, et al. Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. Pediatrics 2005; 116: 682683.CrossRefGoogle ScholarPubMed
22. Hedman, M, Matikainen, T, Fohr, A, et al. Efficacy and safety of pravastatin in children and adolescents with heterozygous familial hypercholesterolemia: a prospective clinical follow-up study. J Clin Endocrinol Metab 2005; 90: 19421952.Google Scholar
23. Knipscheer, HC, Boelen, CC, Kastelein, JJ, et al. Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. Pediatr Res 1996; 39: 867871.Google Scholar
24. Van der Graaf, A, Nierman, MC, Firth, JC, et al. Efficacy and safety of fluvastatin in children and adolescents with heterozygous familial hypercholesterolemia. Acta Paediatr 2006; 95: 14611466.Google Scholar
25. Dirisamer, A, Hachemian, N, Bucek, RA, et al. The effect of low-dose simvastatin in children with familial hypercholesterolemia: a 1-year observation. Eur J Pediatr 2003; 162: 421425.Google Scholar
26. Athyros, VG, Papageorgiou, AA, Kontopoulos, AG. Long-term treatment with atorvastatin in adolescent males with heterozygous familial hypercholesterolemia. Atherosclerosis 2002; 63: 205206.Google Scholar
27. Gandelman, K, Glue, P, Laskey, R, et al. An eight-week trial investigating the efficacy and tolerability of atorvastatin for children and adolescents with heterozygous familial hypercholesterolemia. Pediatr Cardiol 2011; 32: 433441.Google Scholar
28. Avis, HJ, Hutten, BA, Gagne, C, et al. Efficacy and safety of rosuvastatin therapy for children with familial hypercholesterolemia. J Am Coll Cardiol 2010; 55: 11211126.Google Scholar
29. McCrindle, BW. Familial hypercholesterolemia in children and adolescents. Curr Opin Lipidol 2012; 23: 525531.CrossRefGoogle ScholarPubMed
30. Hainline, A Jr, Karon, JM, Winn, CL, Gill, JB. Accuracy and comparability of long-term measurements of cholesterol. Clin Chem 1986; 32: 611615.Google Scholar
31. Arambepola, C, Farmer, AJ, Perera, R, Neil, HA. Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis. Atherosclerosis 2007; 95: 339347.Google Scholar
32. Avis, HJ, Vissers, MN, Stein, EA, et al. A systemic review and meta-analysis of statin therapy in children with familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 2007; 27: 18031810.Google Scholar
33. Rodenburg, J, Vissers, MN, Trip, MD, et al. The spectrum of statin therapy in hyperlipidemic children. Semin Vasc Med 2004; 4: 313320.Google Scholar
34. Wiegman, A, Hutten, BA, de Groot, E, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: a randomized controlled trial. JAMA 2004; 292: 331337.Google Scholar
35. Rodenburg, J, Vissers, MN, Wiegman, A, et al. Statin treatment in children with familial hypercholesterolemia: the younger, the better. Circulation 2007; 116: 664668.Google Scholar
36. Kastelein, JJ, Akdim, F, Stroes, ES, et al. Simvastatin with or without ezetimibe in familial hypercholesterolemia. N Eng J Med 2008; 358: 14311443.CrossRefGoogle ScholarPubMed
37. Stein, EA. After ENHANCE: is more LDL cholesterol lowering even better? Clin Chem 2008; 54: 940942.Google Scholar
38. de Jongh, S, Lilien, MR, op't Roodt, J, et al. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol 2002; 40: 21172121.Google Scholar
39. Ferreira, WP, Bertolami, MC, Santos, SN, et al. One-month therapy with simvastatin restores endothelial function in hypercholesterolemic children and adolescents. Pediatr Cardiol 2007; 28: 813.Google Scholar
40. Greene, O, Durrington, P. Clinical management of children and young adults with heterozygous familial hypercholesterolemia in the UK. J R Soc Med 2004; 97: 226229.Google Scholar
41. Carreau, V, Girardet, JP, Bruckert, E. Long-term follow-up of statin treatment in a cohort of children with familial hypercholesterolemia: efficacy and tolerability. Paediatr Drugs 2011; 13: 267275.Google Scholar
42. Hamilton-Craig, I, Kostner, K, Colquhoun, D, Woodhouses, S. Combination therapy of statin and ezetimibe for the treatment of familial hypercholesterolemia. Vasc Health Risk Manag 2010; 6: 10231037.CrossRefGoogle ScholarPubMed
43. Clauss, S, Wai, KM, Kavey, RE, Kuehl, K. Ezetimibe treatment of pediatric patients with hypercholesterolemia. J Pediatr 2009; 154: 869872.Google Scholar
44. Yeste, D, Chacon, P, Clemente, M, et al. Ezetimibe as monotherapy in the treatment of hypercholesterolemia in children and adolescents. J Pediatr Endocrinol Metab 2009; 22: 487492.Google Scholar
45. van der Graaf, A, Cuffie-Jackson, C, Vissers, MN, et al. Efficacy and safety of coadministration of ezetimibe and simvastatin in adolescents with heterozygous familial hypercholesterolemia. J Am Coll Cardiol 2008; 52: 14211429.Google Scholar