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Cholesterol abnormalities in children and adolescents: time for an update of the 1992 National Cholesterol Education Program guidelines
Progress in Pediatric Cardiology 17 (2003) 109–111
Cholesterol abnormalities in children and adolescents: time for an update of the 1992 National Cholesterol Education Program guidelines Stephen R. Daniels* Division of Cardiology, Department of Pediatrics, University of Cincinnati, College of Medicine and the Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 44195, USA Accepted 1 May 2003
Abstract Cholesterol abnormalities are important as risk factors for the development of cardiovascular disease. Increased knowledge gained in the last decade supports the need for an update of the 1992 pediatric guidelines from the National Cholesterol Education Program. The manuscripts in this issue document much of this progress. 䊚 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Adolescents; Cholesterol abnormalities; National Cholesterol Education Program
Coronary heart disease is a major cause of morbidity and mortality in adults in the United States. Several lines of evidence indicate that cholesterol abnormalities, specifically abnormalities in LDL-Cholesterol and HDLCholesterol are major risk factors for the development of cardiovascular disease outcomes w1x. In 2001, the National Cholesterol Education Program (NCEP) published the third set (ATP III) of recommendations for the management of high blood cholesterol in the United States. This provides a blueprint for internists, family practitioners and cardiologists to identify and treat adults with cholesterol abnormalities. There is strong evidence that atherosclerosis, and therefore the outcome associated with it, has its onset in childhood. Several lines of evidence including epidemiologic, pathologic and genetic now support that concept. In recognition of this evidence, in 1992 the National Cholesterol Education Program published pediatric guidelines for the identification and treatment of children and adolescents with abnormal cholesterol w3x. These guidelines were a landmark in that for the first time pediatricians had a consensus report that outlined both a population and an individual approach to cholesterol management. There were some controversies at the time of publication of the guidelines. For example, the NCEP recommended targeted screening for cholesterol *Tel.: q1-513-636-8265; fax: q1-513-636-0162. E-mail address: [email protected] (S.R. Daniels).
abnormalities based on a positive family history, when others supported a population-based approach to screening and still others recommend no screening in the pediatric age range at all. The NCEP guidelines recommended pharmacologic management after age 10 for patients with marked elevation of cholesterol, while others believed that such management was not warranted in this age group. Since the publication of the guidelines in 1992, some of these debates have continued w4x. Nevertheless, most pediatric practitioners have used the 1992 NCEP pediatric guidelines in their practice. Since 1992, there has been substantial research on pediatric cholesterol abnormalities both from a basic science and a clinical perspective. The manuscripts published in this issue of Progress in Pediatric Cardiology document much of this progress. Berenson and Srinivasan review the evidence for the role of cholesterol abnormalities in the early natural history of atherosclerosis w5x. In particular, they present pathologic evidence from the Bogalusa Heart Study documenting that cholesterol abnormalities are particularly important in conjunction with other risk factors in the development of atherosclerotic lesions in the aorta and coronary arteries. This is important, as we better understand the impact of the metabolic syndrome, which is a consequence of obesity. In his article on secondary causes of cholesterol, Daniels highlights the increasing prevalence of obesity and the metabolic syndrome as a cause of cholesterol
1058-9813/03/$ - see front matter 䊚 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S1058-9813(03)00047-X
110
S.R. Daniels / Progress in Pediatric Cardiology 17 (2003) 109–111
abnormalities in the pediatric population w6x. Sprecher and Stevens amplify this in their discussion of triglyceride and HDL-Cholesterol abnormalities which are hallmarks of the metabolic syndrome w7x. This issue is a prominent aspect of the new NCEP guidelines for adults w2x, but was barely mentioned in the 1992 pediatric guidelines w3x. This is because the national epidemic of obesity and its role in the development of the metabolic syndrome and type 2 diabetes mellitus in adolescents have only been recognized in the last decade. Clauss and Kwiterovich present an overview of the genetic disorders which lead to the phenotypic expression of cholesterol abnormalities faced in the clinical setting w8x. With increasing knowledge of the human genome, more is being learned about genetic disorders of lipoprotein transport. This knowledge may in turn lead to new therapeutic approaches for cholesterol abnormalities. While gene therapy remains a future consideration, improved understanding of the physiology of lipid and lipoprotein metabolism may lead to new pharmacologic treatments. Childhood and adolescence is a time of rapid growth and development. Because cholesterol is intimately involved in both through its role in cellular membranes and as a building block for hormones, it should come as no surprise that lipids and lipoproteins can change dramatically during the pediatric age range. Morrison describes what is known about the changes in lipids and lipoproteins during pubertal development w9x. These alterations have important implications in the screening for patients with lipid abnormalities. Labarthe et al. add further information on this subject from Project Heartbeat! and NHANES III w10x. The 1992 NCEP pediatric guidelines recommend a single set of standards to identify those from age 2 to 18 in the borderline and elevated range for total and LDL-Cholesterol. It is clear that this approach leads to substantial misclassification of individuals depending on the age, sex and stage of pubertal development of the individual. It appears advisable to consider a classification strategy along the lines recommended for blood pressure by the National High Blood Pressure Education Program w11x. Couch et al. present evidence for the dietary management of cholesterol abnormalities in children w12x. New information is now available regarding the safety and efficacy of dietary treatment. For example, the Dietary Intervention Study in Children (DISC) has demonstrated the safety and efficacy of a diet low in saturated fat and cholesterol in school age children w13x. An important question has been at what age to begin dietary intervention. The 1992 NCEP pediatric guidelines recommend that limitation of dietary fat not begin until after age 2 years w3x. However, data from the STRIP study in Finland support the safety and efficacy for cholesterol lowering of a lower fat diet in children under the age
of 2 years w14x. This will be an important consideration as new pediatric guidelines for diet are considered. However, concern has also been raised that lowering the fat content of the diet in the population has led to increased carbohydrate intake which may be in part responsible for the emerging epidemic of obesity in children and adolescents w15x. The optimum diet for children and adolescents remains elusive and diet recommendations may have to be more individualized than in the past. McCrindle presents new information on the pharmacologic management of lipid abnormalities in pediatric patients w16x. He also discusses some alternative and complementary medicine approaches to treating hypercholesterolemia, which have become popular with parents. The 1992 NCEP pediatric guidelines focus almost exclusively on bile acid sequestering agents as drug treatment for cholesterol abnormalities w3x. At that time, these medications were not routinely available as a tablet formulation. This has changed their tolerability for some pediatric patients. In addition, data are now available on the use of HMG CoA Reductase Inhibitors in pediatric patients. These medications have revolutionized the treatment of hyperlipidemia in adults and are now doing so for pediatric patients as well. In a recent multicenter randomized controlled clinical trial, de Jongh et al. demonstrated that simvastatin significantly reduced LDL-Cholesterol, total cholesterol, triglyceride, VLDL Cholesterol and Apolipoprotein B levels in male and female children aged 10–17 years with heterozygous familial hypercholesterolemia w17x. There was no evidence of an adverse impact on growth or pubertal development over a 48-week period. These data provide support for the use of statin medications in appropriate pediatric patients. The time has come for a second NCEP pediatric panel. The new evidence presented in this issue of Progress in Pediatric Cardiology documents that the present guidelines need reconsideration and revision as we move into the 21st century. As pediatricians and pediatric cardiologists do a better job of identifying, and treating children and adolescents with cholesterol abnormalities, it is likely that progress in the prevention of adult coronary heart disease will be made. References w1x Wilson PW, Castelli WP, Kannel WB. Coronary risk prediction in adults (The Framingham Study). Am J Cardiol 1987;59:91G–94G. w2x Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001). Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285, 2508–2509.
S.R. Daniels / Progress in Pediatric Cardiology 17 (2003) 109–111 w3x National cholesterol education program: report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992, 89, 525–584. w4x Newman TB, Garber AM. Cholesterol screening in children and adolescents. Pediatrics 2000;105(3 Pt 1):637 –638. w5x Berenson, G.S., Srinivasan, S. (2003). Cholesterol as a risk factor for early atherosclerosis: the bogalusa heart study. Progress in Pediatric Cardiology. w6x Daniels, S.R. (2003). Lipid metabolism and secondary forms of dyslipoproteinemia in children. Progress in Pediatric Cardiology. w7x Sprecher, D.L., Stevens, M. (2003). Triglycerides and HDLCholesterol in pediatric patients. Progress in Pediatric Cardiology. w8x Clauss, S.B., Kwiterovich, P.O. (2003). Genetic disorders of lipoprotein transport. Progress in Pediatric Cardiology. w9x Morrison, J.A. (2003). A longitudinal evaluation of lipids and lipoproteins in cohorts of adolescent girls and boys. Progress in Pediatric Cardiology. w10x Labarthe, D.R., Dai, S., Fulton, J.E. (2003). Cholesterol screening in children: insights from project heartbeat! and NHANES III. Progress in Pediatric Cardiology. w11x Falkner, B., Daniels, S.R., Horan, M.J., Loggie, J.M.H., Prineas, R.J., Rosner, B., et al. (1996). Update on the task force report (1987) on high blood pressure in children and adoles-
w12x
w13x
w14x
w15x w16x w17x
111
cents: a working group report from the national high blood pressure education program. Pediatrics 98, 649–958. Couch, S.C., Daniels, S.R., Deckelbaum, R.J. (2003). Current concepts of diet therapy for children with hypercholesterolemia. Progress in Pediatric Cardiology. Obarzanek E, Kimm SY, Barton BA, et al. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: seven-year results of the dietary intervention study in children. Pediatrics 2001;107:256 –264. Rask-Nissila L, Jokinen E, Ronnemaa T, Viikari J, Tammi A, Niinikoski H, et al. Prospective, randomized, infancy-onset trial of the effects of a low-saturated-fat, low-cholesterol diet on serum lipids and lipoproteins before school age: The Special Turku Coronary Risk Factor Intervention Project (STRIP). Circulation 2000;102(13):1477 –1483. Daniels SR. Abnormal weight gain and weight management: are carbohydrates the enemy? J Pediatr 2003;142:225 –227. McCrindle, B.W. (2003) Drug therapy of hyperlipidemia. Progress in Pediatric Cardiology. de Jongh S, Ose L, Szamosi T, Gagne C, Lambert M, Scott R, 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 –2237.
Cholesterol abnormalities in children and adolescents: time for an update of the 1992 National Cholesterol Education Program guidelines Stephen R. Daniels* Division of Cardiology, Department of Pediatrics, University of Cincinnati, College of Medicine and the Children’s Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 44195, USA Accepted 1 May 2003
Abstract Cholesterol abnormalities are important as risk factors for the development of cardiovascular disease. Increased knowledge gained in the last decade supports the need for an update of the 1992 pediatric guidelines from the National Cholesterol Education Program. The manuscripts in this issue document much of this progress. 䊚 2003 Elsevier Ireland Ltd. All rights reserved. Keywords: Adolescents; Cholesterol abnormalities; National Cholesterol Education Program
Coronary heart disease is a major cause of morbidity and mortality in adults in the United States. Several lines of evidence indicate that cholesterol abnormalities, specifically abnormalities in LDL-Cholesterol and HDLCholesterol are major risk factors for the development of cardiovascular disease outcomes w1x. In 2001, the National Cholesterol Education Program (NCEP) published the third set (ATP III) of recommendations for the management of high blood cholesterol in the United States. This provides a blueprint for internists, family practitioners and cardiologists to identify and treat adults with cholesterol abnormalities. There is strong evidence that atherosclerosis, and therefore the outcome associated with it, has its onset in childhood. Several lines of evidence including epidemiologic, pathologic and genetic now support that concept. In recognition of this evidence, in 1992 the National Cholesterol Education Program published pediatric guidelines for the identification and treatment of children and adolescents with abnormal cholesterol w3x. These guidelines were a landmark in that for the first time pediatricians had a consensus report that outlined both a population and an individual approach to cholesterol management. There were some controversies at the time of publication of the guidelines. For example, the NCEP recommended targeted screening for cholesterol *Tel.: q1-513-636-8265; fax: q1-513-636-0162. E-mail address: [email protected] (S.R. Daniels).
abnormalities based on a positive family history, when others supported a population-based approach to screening and still others recommend no screening in the pediatric age range at all. The NCEP guidelines recommended pharmacologic management after age 10 for patients with marked elevation of cholesterol, while others believed that such management was not warranted in this age group. Since the publication of the guidelines in 1992, some of these debates have continued w4x. Nevertheless, most pediatric practitioners have used the 1992 NCEP pediatric guidelines in their practice. Since 1992, there has been substantial research on pediatric cholesterol abnormalities both from a basic science and a clinical perspective. The manuscripts published in this issue of Progress in Pediatric Cardiology document much of this progress. Berenson and Srinivasan review the evidence for the role of cholesterol abnormalities in the early natural history of atherosclerosis w5x. In particular, they present pathologic evidence from the Bogalusa Heart Study documenting that cholesterol abnormalities are particularly important in conjunction with other risk factors in the development of atherosclerotic lesions in the aorta and coronary arteries. This is important, as we better understand the impact of the metabolic syndrome, which is a consequence of obesity. In his article on secondary causes of cholesterol, Daniels highlights the increasing prevalence of obesity and the metabolic syndrome as a cause of cholesterol
1058-9813/03/$ - see front matter 䊚 2003 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/S1058-9813(03)00047-X
110
S.R. Daniels / Progress in Pediatric Cardiology 17 (2003) 109–111
abnormalities in the pediatric population w6x. Sprecher and Stevens amplify this in their discussion of triglyceride and HDL-Cholesterol abnormalities which are hallmarks of the metabolic syndrome w7x. This issue is a prominent aspect of the new NCEP guidelines for adults w2x, but was barely mentioned in the 1992 pediatric guidelines w3x. This is because the national epidemic of obesity and its role in the development of the metabolic syndrome and type 2 diabetes mellitus in adolescents have only been recognized in the last decade. Clauss and Kwiterovich present an overview of the genetic disorders which lead to the phenotypic expression of cholesterol abnormalities faced in the clinical setting w8x. With increasing knowledge of the human genome, more is being learned about genetic disorders of lipoprotein transport. This knowledge may in turn lead to new therapeutic approaches for cholesterol abnormalities. While gene therapy remains a future consideration, improved understanding of the physiology of lipid and lipoprotein metabolism may lead to new pharmacologic treatments. Childhood and adolescence is a time of rapid growth and development. Because cholesterol is intimately involved in both through its role in cellular membranes and as a building block for hormones, it should come as no surprise that lipids and lipoproteins can change dramatically during the pediatric age range. Morrison describes what is known about the changes in lipids and lipoproteins during pubertal development w9x. These alterations have important implications in the screening for patients with lipid abnormalities. Labarthe et al. add further information on this subject from Project Heartbeat! and NHANES III w10x. The 1992 NCEP pediatric guidelines recommend a single set of standards to identify those from age 2 to 18 in the borderline and elevated range for total and LDL-Cholesterol. It is clear that this approach leads to substantial misclassification of individuals depending on the age, sex and stage of pubertal development of the individual. It appears advisable to consider a classification strategy along the lines recommended for blood pressure by the National High Blood Pressure Education Program w11x. Couch et al. present evidence for the dietary management of cholesterol abnormalities in children w12x. New information is now available regarding the safety and efficacy of dietary treatment. For example, the Dietary Intervention Study in Children (DISC) has demonstrated the safety and efficacy of a diet low in saturated fat and cholesterol in school age children w13x. An important question has been at what age to begin dietary intervention. The 1992 NCEP pediatric guidelines recommend that limitation of dietary fat not begin until after age 2 years w3x. However, data from the STRIP study in Finland support the safety and efficacy for cholesterol lowering of a lower fat diet in children under the age
of 2 years w14x. This will be an important consideration as new pediatric guidelines for diet are considered. However, concern has also been raised that lowering the fat content of the diet in the population has led to increased carbohydrate intake which may be in part responsible for the emerging epidemic of obesity in children and adolescents w15x. The optimum diet for children and adolescents remains elusive and diet recommendations may have to be more individualized than in the past. McCrindle presents new information on the pharmacologic management of lipid abnormalities in pediatric patients w16x. He also discusses some alternative and complementary medicine approaches to treating hypercholesterolemia, which have become popular with parents. The 1992 NCEP pediatric guidelines focus almost exclusively on bile acid sequestering agents as drug treatment for cholesterol abnormalities w3x. At that time, these medications were not routinely available as a tablet formulation. This has changed their tolerability for some pediatric patients. In addition, data are now available on the use of HMG CoA Reductase Inhibitors in pediatric patients. These medications have revolutionized the treatment of hyperlipidemia in adults and are now doing so for pediatric patients as well. In a recent multicenter randomized controlled clinical trial, de Jongh et al. demonstrated that simvastatin significantly reduced LDL-Cholesterol, total cholesterol, triglyceride, VLDL Cholesterol and Apolipoprotein B levels in male and female children aged 10–17 years with heterozygous familial hypercholesterolemia w17x. There was no evidence of an adverse impact on growth or pubertal development over a 48-week period. These data provide support for the use of statin medications in appropriate pediatric patients. The time has come for a second NCEP pediatric panel. The new evidence presented in this issue of Progress in Pediatric Cardiology documents that the present guidelines need reconsideration and revision as we move into the 21st century. As pediatricians and pediatric cardiologists do a better job of identifying, and treating children and adolescents with cholesterol abnormalities, it is likely that progress in the prevention of adult coronary heart disease will be made. References w1x Wilson PW, Castelli WP, Kannel WB. Coronary risk prediction in adults (The Framingham Study). Am J Cardiol 1987;59:91G–94G. w2x Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001). Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 285, 2508–2509.
S.R. Daniels / Progress in Pediatric Cardiology 17 (2003) 109–111 w3x National cholesterol education program: report of the expert panel on blood cholesterol levels in children and adolescents. Pediatrics 1992, 89, 525–584. w4x Newman TB, Garber AM. Cholesterol screening in children and adolescents. Pediatrics 2000;105(3 Pt 1):637 –638. w5x Berenson, G.S., Srinivasan, S. (2003). Cholesterol as a risk factor for early atherosclerosis: the bogalusa heart study. Progress in Pediatric Cardiology. w6x Daniels, S.R. (2003). Lipid metabolism and secondary forms of dyslipoproteinemia in children. Progress in Pediatric Cardiology. w7x Sprecher, D.L., Stevens, M. (2003). Triglycerides and HDLCholesterol in pediatric patients. Progress in Pediatric Cardiology. w8x Clauss, S.B., Kwiterovich, P.O. (2003). Genetic disorders of lipoprotein transport. Progress in Pediatric Cardiology. w9x Morrison, J.A. (2003). A longitudinal evaluation of lipids and lipoproteins in cohorts of adolescent girls and boys. Progress in Pediatric Cardiology. w10x Labarthe, D.R., Dai, S., Fulton, J.E. (2003). Cholesterol screening in children: insights from project heartbeat! and NHANES III. Progress in Pediatric Cardiology. w11x Falkner, B., Daniels, S.R., Horan, M.J., Loggie, J.M.H., Prineas, R.J., Rosner, B., et al. (1996). Update on the task force report (1987) on high blood pressure in children and adoles-
w12x
w13x
w14x
w15x w16x w17x
111
cents: a working group report from the national high blood pressure education program. Pediatrics 98, 649–958. Couch, S.C., Daniels, S.R., Deckelbaum, R.J. (2003). Current concepts of diet therapy for children with hypercholesterolemia. Progress in Pediatric Cardiology. Obarzanek E, Kimm SY, Barton BA, et al. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: seven-year results of the dietary intervention study in children. Pediatrics 2001;107:256 –264. Rask-Nissila L, Jokinen E, Ronnemaa T, Viikari J, Tammi A, Niinikoski H, et al. Prospective, randomized, infancy-onset trial of the effects of a low-saturated-fat, low-cholesterol diet on serum lipids and lipoproteins before school age: The Special Turku Coronary Risk Factor Intervention Project (STRIP). Circulation 2000;102(13):1477 –1483. Daniels SR. Abnormal weight gain and weight management: are carbohydrates the enemy? J Pediatr 2003;142:225 –227. McCrindle, B.W. (2003) Drug therapy of hyperlipidemia. Progress in Pediatric Cardiology. de Jongh S, Ose L, Szamosi T, Gagne C, Lambert M, Scott R, 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 –2237.