Farmacoriflessioni
Statine, iperlipidemia e obesità. Stato dell’arte
STATINS, HYPERLIPIDEMIA AND OBESITY. THE STATE OF THE ART
Zemira Cannioto
Clinica Pediatrica, IRCCS “Burlo Garofolo”, Scuola di Specializzazione in Pediatria, Università di Trieste
Maggio 2008 - pagg. 309 -318
Abstract
The prevalence of lipid abnormalities in children is increasing in relation to the concomitant epidemic of obesity and metabolic syndrome. The 3-hydroxy-3-metylglutaryl coenzyme A reductase inhibitor and statins have been shown to effectively reduce cardiovascular
mortality and morbidity in high risk adults. Their use in pediatric population is still debated.
We review the current medical strategy in screening and treating lipid abnormalities in children, especially looking at the knowledge base of the use of statins treatment in children and pediatric literature.
Parole chiave
Suggerite dall'AI
Classificazione MeSH
Bibliografia
Effects
of secular trends in obesity on coronary
risk factor in children: the Bogalusa Heart
Study. J Pediatr 1995;127:868-74.
2. Cook S, Weitzman M, Auinger P, et al. Prevalence of a metabolic syndrome phenotipe in adolescents. Findings from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003; 157:821-7.
3. Belay B, Belamarich PF, Tom-Revzon C. The use of statins in pediatrics: knowledge base, limitations, and future directions. Pediatrics 2007;119:370-80; http://www.pediatrics. org/cgi/content/full/119/2/370.
4. Relationship of atheroclerosis in young men to serum lipoprotein cholesterol concentrations and smoking: a preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA 1990;264:3018-24.
5. Berenson GS, Srinivasan SR, Bao W, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: the Bogalusa Heart Study. N Engl J Med 1998;338:1650-6.
6. Tuzcu EM, Kapadia SR, Tutar E, et al. High prevalence of coronary atherosclerosis in asyntomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation 2001;103:2705-10.
7. Hansson GK. Inflammation, atherosclerosis and coronary artery disease. N Engl J Med 2005;352:1685-95.
8. Davies MJ. The pathophysiology of acute coronary syndrome. Heart 2000;83:361-6.
9. Mohiaddin RH, Burman ED, Prasad SK, et al. Glasgov remodelling of the atherosclerotic aorta demonstrated by cardiovascular megnetic resonance: the CORDA Asymptomatic Sublect Plaque Assessment Research (CASPAR) Project. J Cardiovasc Magn Reson 2004;6:517-25.
10. Zimmer P, Alberti G, Kaufman E, et al. The metabolic syndrome in children and adolescents. Lancet 2007;369:2059-61.
11. American Academy of Pediatrics. National Cholesterol Education Program: report of the Expert Panel on Blood Cholesterol Level in Children and Adolescents. Pediatrics 1992;89: 525-84.
12. McCrindle BW, Elaine M, Urbina EM, 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; 115;1948-67.
13. Rifai N, Neufeld E, Ahldtrom P, et al. Failure of current guidelines for cholesterol screening in urban African-American adolescents. Pediatrics 1996;98:383-8.
14. Bachman RP, Schoen EJ, Stembridge A, et al. Compliance with childhood cholesterol screening among members of a prepaid healthplan. Am J Dis Child 1993;147:382-5.
15. Diller PM, Huster GA, Leach AD, et al. Definition and application of discretionary screening indicators according to the National Cholesterol Education Program for children and adolescents. J Pediatr 1995;126:345-52.
16. Dennison BA, Kikuchi DA, Srinivasan SR, et al. Serum total cholesterol screening for the detection of elevated low density lipoprotein in children and adolescents: the Bogalusa Heart Study. Pediatrics 1990;85:472-9.
17. Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation 2006;114:1056-62.
18. Gidding SS, Stone NJ, Bookstein LC, et al. Month-to-month variability of lipids, lipoproteins and apolipoproteins and the impact of acute infection in adolescents. J Pediatr 1998; 133:242-6.
19. Windorski SK, Kalb KA. Educating NPs to educate patients: cholesterolscreening in pediatric primary care. J Pediatr Health Care 2002;16:60-6.
20. Boyd GS, Koenigsberg J, Falknr B, et al. Effect of obesity and high blood pressure on plasma lipid levels in children and adolescents. Pediatrics 2005;116:442-6.
21. Ogden CL, Flegal KM, Carrol MD, et al. Prevalence and trends in overweight among US children and adolescents, 1999-2000. JAMA 2002;288:1728-32.
22. Freedman DS, Dietz WH, Srinivasan SR, et al. The relation of overweight to cardiovascular risk factor s among children and adolescents: the Bogalusa Heart Study. Pediatrics 1999;103:1175-82.
23. Vrecer M, Turk S, Drinovec J, et al. Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke: meta-analysis of randomized trials. Int J Clin Pharmacol Ther 2003;41:567-77.
24. Buck ML. HMG-CoA reductase inhibitor for the treatment of hypercolesterolemia in children and adolescents. Pediatr Pharmacol 2002;8(9); http://www.healthsystem. virginia. edu/internet/pediatrics/pharma-news/ v8n9. pdf.
25. Grundy SM, Cleeman JI, Merz CN, et al. Implication of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III. Circulation 2004;110: 227-39.
26. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-504.
27. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol level: results of AFCAPS/tex CAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279: 1615-22.
28. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercolesterolemia. West of Scotland Coronary Pevention Study Group. N Engl J Med 1995;333:1301-7.
29. Nissen SF, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein and coronary artery disease. N Engl J Med 2005;352:29-38.
30. Wiegman A, Rodenburg j, de Jongh s, et al. Family history and cardiovascular risk in familial hypercolesterolemia. Data in more than 1000 children. Circulation 2003;107: 1473-8.
31. Arambepola C, Farnet AJ, Perera R, et al. Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis. Atherosclerosis (2006), doi:10.1016/j. atherosclerosis. 2006.09.030 (in press).
32. 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: 331-7.
33. de Jongh S, Ose L, Szamosi T, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia. A randomized, double-blind, placebo-controlled trial with simvastatin. Circulation 2002;106:2231-7.
34. Stein EA, Illingworth DR, Kwiterovich PO, et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia. A randomized controlled trial. JAMA 1999;281:137-44.
35. de Jongh S, Lilien MR, Roodt J, Stroes ESG, Bakker HD, Kastelein JJP. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol 2002;40:2117-21.
36. McCrindleBW, Ose L, Marais AD. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr 2003; 142:74-80.
37. Clauss SB, Holmes KW, Hopkins P, et al. Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. Pediatrics 2005;116:682-8.
38. Knipscheer HC, Boelen CC, Kastelein JJ, et al. Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. Pediatr Res 1996;39:867-71.
39. Couture P, Brun LD, Szots F, et al. Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 1998;18:1007-12.
40. McCrindle BW, Helden E, Cullen-Dean G, Conner WT. A randomized crossover trial of combination pharmacologic therapy in children with familial hyperlipidemia. Pediatr Res 2002;51:715-21.
41. Stefanutti C, Lucani G, Vivenzio A, Di Giacomo S. Diet only and diet plus simvastatin in the treatment of heterozygous familial hypercholesterolemia in childhood. Drugs Exp Clin Res 1999;25:23-8.
42. Lambert M, Lupien PJ, Gagne C, et al. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group. Pediatrics 1996;97:619-28.
43. Athyros VG, Papageorgiou AA, Kontopoulos AG. Long-term treatment with atorvastatin in adolescent males with heterozygous familial hypercholesterolemia. Atherosclerosis 2002;163:205-6.
44. Ducobu J, Brasseur D, Chaudron JM, Deslypere JP, Muls E, Thomson M. Simvastatin use in children. Lancet 1992;339:1488.
45. 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; 90:1942-52.
46. Hedman M, Miettinen TA, Gylling H, Ketomaki A, Antikainen M. Serum noncholesterol sterols in children with heterozygous familial hypercholesterolemia undergoing pravastatin therapy. J Pediatr 2006;148:241-6.
47. Dirisamer A. The effect of low-dose simvastatin in children with familial hypercholesterolaemia: a 1-year observation. Eur J Pediatr 2003;162:421-5.
48. Sinzinger H, Schmid P, Pirich C, et al. Treatment of hypercholesterolaemia in children. Lancet 1992;340:548-9.
49. Stein EA. Treatment of familial hypercholesterolemia with drugs in children. Arteriosclerosis 1989(1 Suppl):145-51.
50. Hedman M, Neuvonen PJ, Neuvonen M, Holmberg C, Antikainen M. Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia. Clin Pharmacol Ther 2003;74:178-85.
51. Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002;346:539-40.
52. Edison RJ, Muenke M. Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins. Am J Med Genet 2004;131:287-98.
53. Rodenburg J, Vissers MN, Wiegman A, et al. Statin treatment in children with Familial Hypercolesterolemia: the younger, the better. Circulation 2007;116:664-8.
54. Baker JL, Olsen LW, Sorensen T. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med 2007;357:2329-37.
2. Cook S, Weitzman M, Auinger P, et al. Prevalence of a metabolic syndrome phenotipe in adolescents. Findings from the Third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003; 157:821-7.
3. Belay B, Belamarich PF, Tom-Revzon C. The use of statins in pediatrics: knowledge base, limitations, and future directions. Pediatrics 2007;119:370-80; http://www.pediatrics. org/cgi/content/full/119/2/370.
4. Relationship of atheroclerosis in young men to serum lipoprotein cholesterol concentrations and smoking: a preliminary report from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. JAMA 1990;264:3018-24.
5. Berenson GS, Srinivasan SR, Bao W, et al. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults: the Bogalusa Heart Study. N Engl J Med 1998;338:1650-6.
6. Tuzcu EM, Kapadia SR, Tutar E, et al. High prevalence of coronary atherosclerosis in asyntomatic teenagers and young adults: evidence from intravascular ultrasound. Circulation 2001;103:2705-10.
7. Hansson GK. Inflammation, atherosclerosis and coronary artery disease. N Engl J Med 2005;352:1685-95.
8. Davies MJ. The pathophysiology of acute coronary syndrome. Heart 2000;83:361-6.
9. Mohiaddin RH, Burman ED, Prasad SK, et al. Glasgov remodelling of the atherosclerotic aorta demonstrated by cardiovascular megnetic resonance: the CORDA Asymptomatic Sublect Plaque Assessment Research (CASPAR) Project. J Cardiovasc Magn Reson 2004;6:517-25.
10. Zimmer P, Alberti G, Kaufman E, et al. The metabolic syndrome in children and adolescents. Lancet 2007;369:2059-61.
11. American Academy of Pediatrics. National Cholesterol Education Program: report of the Expert Panel on Blood Cholesterol Level in Children and Adolescents. Pediatrics 1992;89: 525-84.
12. McCrindle BW, Elaine M, Urbina EM, 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; 115;1948-67.
13. Rifai N, Neufeld E, Ahldtrom P, et al. Failure of current guidelines for cholesterol screening in urban African-American adolescents. Pediatrics 1996;98:383-8.
14. Bachman RP, Schoen EJ, Stembridge A, et al. Compliance with childhood cholesterol screening among members of a prepaid healthplan. Am J Dis Child 1993;147:382-5.
15. Diller PM, Huster GA, Leach AD, et al. Definition and application of discretionary screening indicators according to the National Cholesterol Education Program for children and adolescents. J Pediatr 1995;126:345-52.
16. Dennison BA, Kikuchi DA, Srinivasan SR, et al. Serum total cholesterol screening for the detection of elevated low density lipoprotein in children and adolescents: the Bogalusa Heart Study. Pediatrics 1990;85:472-9.
17. Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation 2006;114:1056-62.
18. Gidding SS, Stone NJ, Bookstein LC, et al. Month-to-month variability of lipids, lipoproteins and apolipoproteins and the impact of acute infection in adolescents. J Pediatr 1998; 133:242-6.
19. Windorski SK, Kalb KA. Educating NPs to educate patients: cholesterolscreening in pediatric primary care. J Pediatr Health Care 2002;16:60-6.
20. Boyd GS, Koenigsberg J, Falknr B, et al. Effect of obesity and high blood pressure on plasma lipid levels in children and adolescents. Pediatrics 2005;116:442-6.
21. Ogden CL, Flegal KM, Carrol MD, et al. Prevalence and trends in overweight among US children and adolescents, 1999-2000. JAMA 2002;288:1728-32.
22. Freedman DS, Dietz WH, Srinivasan SR, et al. The relation of overweight to cardiovascular risk factor s among children and adolescents: the Bogalusa Heart Study. Pediatrics 1999;103:1175-82.
23. Vrecer M, Turk S, Drinovec J, et al. Use of statins in primary and secondary prevention of coronary heart disease and ischemic stroke: meta-analysis of randomized trials. Int J Clin Pharmacol Ther 2003;41:567-77.
24. Buck ML. HMG-CoA reductase inhibitor for the treatment of hypercolesterolemia in children and adolescents. Pediatr Pharmacol 2002;8(9); http://www.healthsystem. virginia. edu/internet/pediatrics/pharma-news/ v8n9. pdf.
25. Grundy SM, Cleeman JI, Merz CN, et al. Implication of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III. Circulation 2004;110: 227-39.
26. Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med 2004;350:1495-504.
27. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol level: results of AFCAPS/tex CAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA 1998;279: 1615-22.
28. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercolesterolemia. West of Scotland Coronary Pevention Study Group. N Engl J Med 1995;333:1301-7.
29. Nissen SF, Tuzcu EM, Schoenhagen P, et al. Statin therapy, LDL cholesterol, C-reactive protein and coronary artery disease. N Engl J Med 2005;352:29-38.
30. Wiegman A, Rodenburg j, de Jongh s, et al. Family history and cardiovascular risk in familial hypercolesterolemia. Data in more than 1000 children. Circulation 2003;107: 1473-8.
31. Arambepola C, Farnet AJ, Perera R, et al. Statin treatment for children and adolescents with heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis. Atherosclerosis (2006), doi:10.1016/j. atherosclerosis. 2006.09.030 (in press).
32. 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: 331-7.
33. de Jongh S, Ose L, Szamosi T, et al. Efficacy and safety of statin therapy in children with familial hypercholesterolemia. A randomized, double-blind, placebo-controlled trial with simvastatin. Circulation 2002;106:2231-7.
34. Stein EA, Illingworth DR, Kwiterovich PO, et al. Efficacy and safety of lovastatin in adolescent males with heterozygous familial hypercholesterolemia. A randomized controlled trial. JAMA 1999;281:137-44.
35. de Jongh S, Lilien MR, Roodt J, Stroes ESG, Bakker HD, Kastelein JJP. Early statin therapy restores endothelial function in children with familial hypercholesterolemia. J Am Coll Cardiol 2002;40:2117-21.
36. McCrindleBW, Ose L, Marais AD. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial. J Pediatr 2003; 142:74-80.
37. Clauss SB, Holmes KW, Hopkins P, et al. Efficacy and safety of lovastatin therapy in adolescent girls with heterozygous familial hypercholesterolemia. Pediatrics 2005;116:682-8.
38. Knipscheer HC, Boelen CC, Kastelein JJ, et al. Short-term efficacy and safety of pravastatin in 72 children with familial hypercholesterolemia. Pediatr Res 1996;39:867-71.
39. Couture P, Brun LD, Szots F, et al. Association of specific LDL receptor gene mutations with differential plasma lipoprotein response to simvastatin in young French Canadians with heterozygous familial hypercholesterolemia. Arterioscler Thromb Vasc Biol 1998;18:1007-12.
40. McCrindle BW, Helden E, Cullen-Dean G, Conner WT. A randomized crossover trial of combination pharmacologic therapy in children with familial hyperlipidemia. Pediatr Res 2002;51:715-21.
41. Stefanutti C, Lucani G, Vivenzio A, Di Giacomo S. Diet only and diet plus simvastatin in the treatment of heterozygous familial hypercholesterolemia in childhood. Drugs Exp Clin Res 1999;25:23-8.
42. Lambert M, Lupien PJ, Gagne C, et al. Treatment of familial hypercholesterolemia in children and adolescents: effect of lovastatin. Canadian Lovastatin in Children Study Group. Pediatrics 1996;97:619-28.
43. Athyros VG, Papageorgiou AA, Kontopoulos AG. Long-term treatment with atorvastatin in adolescent males with heterozygous familial hypercholesterolemia. Atherosclerosis 2002;163:205-6.
44. Ducobu J, Brasseur D, Chaudron JM, Deslypere JP, Muls E, Thomson M. Simvastatin use in children. Lancet 1992;339:1488.
45. 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; 90:1942-52.
46. Hedman M, Miettinen TA, Gylling H, Ketomaki A, Antikainen M. Serum noncholesterol sterols in children with heterozygous familial hypercholesterolemia undergoing pravastatin therapy. J Pediatr 2006;148:241-6.
47. Dirisamer A. The effect of low-dose simvastatin in children with familial hypercholesterolaemia: a 1-year observation. Eur J Pediatr 2003;162:421-5.
48. Sinzinger H, Schmid P, Pirich C, et al. Treatment of hypercholesterolaemia in children. Lancet 1992;340:548-9.
49. Stein EA. Treatment of familial hypercholesterolemia with drugs in children. Arteriosclerosis 1989(1 Suppl):145-51.
50. Hedman M, Neuvonen PJ, Neuvonen M, Holmberg C, Antikainen M. Pharmacokinetics and pharmacodynamics of pravastatin in children with familial hypercholesterolemia. Clin Pharmacol Ther 2003;74:178-85.
51. Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med 2002;346:539-40.
52. Edison RJ, Muenke M. Mechanistic and epidemiologic considerations in the evaluation of adverse birth outcomes following gestational exposure to statins. Am J Med Genet 2004;131:287-98.
53. Rodenburg J, Vissers MN, Wiegman A, et al. Statin treatment in children with Familial Hypercolesterolemia: the younger, the better. Circulation 2007;116:664-8.
54. Baker JL, Olsen LW, Sorensen T. Childhood body-mass index and the risk of coronary heart disease in adulthood. N Engl J Med 2007;357:2329-37.
Corrispondenza: zemira79@hotmail.com