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FROM THE AMERICAN ACADEMY OF PEDIATRICS: Stephen R. Daniels, Frank R. Greer and the Committee on Nutrition Lipid Screening and Cardiovascular Health in Childhood Pediatrics 2008; 122: 198-208 [Abstract] [Full text] [PDF]

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eLetters published:

Comparison with the adult guidelines

E-P. Barrette   (8 July 2008)

Evidence based guidelines?

Martin Lalinec-Michaud   (22 July 2008)

STATINS IN CHILDREN: MORE SHADE THAN LIGHT.

Zemira Cannioto, Federico Marchetti   (23 July 2008)

Omissions from new lipid screening guidelines

Costan G. Magnussen   (24 December 2008)

Comparison with the adult guidelines 8 July 2008
E-P. Barrette, Associate Professor of Medicine Washington University School of Medicine Send letter to journal: Re: Comparison with the adult guidelines epbarrette{at}im.wustl.edu E-P. Barrette	The new pediatric guidelines have proposed considering pharmacologic treatment for children with an LDL that is persistently > 160 mg/dl despite diet therapy and who are also obese. This will potentially create a dilemma for teenagers as they transition to adulthood and see an internist. Consider an obese 16 year old who does not smoke, has no hypertension, has an HDL which is above 40 mg/dl, and has adult parents who are in their 40's. The parents are both on statins for lipid control but neither has had a cardiovascular event. The child has a fasting glucose that is not in the diabetic range. Based on the new pediatric guidelines if this child has a LDL that was persistently 175 mg/dl, his/her physician would probably recommend a statin. However, if this child is seen in an internal medicine clinic two years later, based on the most recent update for the National Cholesterol Education Program (note 1), pharmacologic treatment should only be considered for an LDL greater than 190 mg/dl based on this individual's risk profile. If this prototypical adolescent is started on a statin, an internist will be faced with the decision whether to continue this medication or reassess lipids and possibly decide the adult guidelines are more applicable at age 18. Since the adult guidelines only count hypertension, cigarette smoking, family history of premature coronary heart disease, or low HDL cholesterol (less than 40 mg/dl), and age (men older than 44, women older than 54) as cardiovascular risk factors, it is the new inclusion of obesity which is distinct from the adult guidelines and thus creates this dilemma. One should consider that the 10 year risk of coronary death or myocardial infarction for a 20 year old man with no smoking, no treatment for hypertension and a systolic blood pressure of 135 mm Hg, and a total cholesterol of 300 mg/dl and a HDL of 40 mg/dl is only 1% (note 2). Many obese teenagers with an LDL between 160 and 190 who will be started on a statin will have a total cholesterol much lower than 300 and will also have a very low risk of a cardiac event over the next 15 years. I look forward to further recommendations from the American College of Physicians and the National Cholesterol Education Program on what may be the best age to consider starting pharmacotherapy for elevated cholesterol. note 1 Grundy SM, Cleeman JI, Merz CNB, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ, Implication of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation 2004;110:227-239. note2 Risk assessment tool for estimating 10 year risk of developing hard CHD (myocardial infarction and coronary death) accessed July 7, 2008 http://hp2010.nhlbihin.net/atpiii/calculator.asp?usertype=prof Conflict of Interest: None declared
Evidence based guidelines? 22 July 2008
Martin Lalinec-Michaud, General Practitioner Laval University, Quebec, Canada Send letter to journal: Re: Evidence based guidelines? martin.lalinec-michaud{at}mfa.ulaval.ca Martin Lalinec-Michaud	I was interested in reading this clinical report of the AAP on lipid screening. I do believe like the authors that cardiovasular health of children should be taken into account and that the obesity epidemic is very concerning. I have not seen the level of evidence that can be attributed to the guideline proposed. Will we be contributing to an increased wellbeing and health of children by screening high risk individuals and treating those affected? I have not seen the data that supports this, in the article. I think that following the recommendations to screen and treat individuals according to the criterion cited here will lead to increased physician visits, lab tests and treatment based on expert opinion mainly. So increased healthcare spending for what results? Maybe the criterion could be stricter until data shows a clear benefit without too much of the side effects/danger that we are bound to see in developing humans and with the very long term duration of treatment. I believe that money would be better spent at the root of the obesity epidemic (lifestyle, activity, diet), not lower down when collateral damages are done or ongoing, especially when it has not been supported by data. I am concerned that, contrary to many authors of article in peer reviewed journals and to myself writing this commentary, there is no disclosure of competing interests by the authors. I look forward for continuing interest in this area and further development of guidelines and strategies to help physician, parents and children dealing with higher cardiovascular risks. Conflict of Interest: None declared
STATINS IN CHILDREN: MORE SHADE THAN LIGHT. 23 July 2008
Zemira Cannioto, Paediatrician Department of Pediatrics, IRCCS Burlo Garofolo, Trieste, Italy, Federico Marchetti Send letter to journal: Re: STATINS IN CHILDREN: MORE SHADE THAN LIGHT. zemira79{at}hotmail.com Zemira Cannioto, et al.	Dear Editor, We read with interest the new guidelines on cholesterol screening and treatment in childhood recently issued by the American Academy of Pediatrics (1). Compared to the previous statement (2), the most important innovation regards the fact that statins are now recommended to younger patients too (8 years and older instead of 10 years and older) within the same risk categories. However, we believe that given the paucity of long term efficacy and poor safety data available to date, there are still too many concerns regarding the using of statins in children. In this term, it’s important to underline that almost all clinical trials developed in children have considered patients affected by Familial Hypercolesterolemia. In this particular condition the strong correlation with adult-onset cardiovascular disease (CVD) appeared so well demonstrated to justify a prompt pharmacological intervention (3). The same condition might be assumed individually in children with severe non familial hypercolesterolemia in presence of multiple cardiovascular risk factors. However, crucial concerns about statins treatment persist for overweight/ mildly obese children with non familial hypercolesterolemia. We believe that in this kind of patients (certainly the more one) efficacy data on primary end point (such as mortality and morbility for CVD) and long term safety data are required before recommending such an extended pharmacological approach. That especially considering the lenght of treatment (potentially for life) and therefore the possibility of adverse effects related to the exposure to a major cumulative dose in children than in adults and also problems dealing with compliance to treatment. Clinical trials in children and adolescents “have shown statins to be safe” but only in a short-term with a mean time of treatment of 27 weeks (range 6-96 weeks) (4). So far, according to the efficacy, clinical trials demonstrated the power of statins in lowering cholesterol and in some cases in improving vascular structure and function. However, we believe that the lack of strong evidence in terms of primary prevention of adult-onset CVD forces a prudential prescription of statins especially considering that the use of statins in primary prevention of cardiovascular events appears to be controversial in adults too (5). We hope, otherwise, that future data from RCT on hypercholesterolemic children/adolescents treated for long time could reinforce the statement of a prompt statin treatment in childhood according to a strong evidence of efficacy and safety profile. References: 1.Stephen R. Daniels, Frank R. Greer and the Committee on Nutrition Lipid Screening and Cardiovascular Health in Childhood Pediatrics 2008; 122: 198-208 2.American Academy of Pediatrics, Committee on Nutrition. Cholesterol in childhood. Pediatrics. 1998;101(1 pt 1):141–147 3.Rodenburg J, Vissers MN, Wiegman A, et al. Statin treatment in children with Familial Hypercolesterolemia: the younger, the better. Circulation 2007; 116: 664-68 4.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;195(2):339-47 5.Moride Y, Hegele RA, Langer A, McPherson R, Miller DB, Rinfret S. Clinical and public health assessment of benefits and risks of statins in primary prevention of coronary events: resolved and unresolved issues. Can J Cardiol. 2008;24(4):293-300. Conflict of Interest: None declared
Omissions from new lipid screening guidelines 24 December 2008
Costan G. Magnussen, Academic Menzies Research Institute Send letter to journal: Re: Omissions from new lipid screening guidelines cmagnuss{at}utas.edu.au Costan G. Magnussen	To the Editor.— The update of lipid screening guidelines for pediatrics reported by Daniels, Greer, and the American Academy of Pediatrics Committee on Nutrition1 has some important omissions. The first regards the consideration of lipid and lipoprotein cut-points to denote normal, borderline-, and high-risk concentrations. The authors correctly state that the previous ‘fixed’ cut-points issued by the National Cholesterol Education Program (NCEP)2 may be limited as they do not account for age- and sex-specific differences in lipid and lipoprotein concentrations. However, in their discussion, they do not mention the work by Jolliffe and Janssen3 who proposed age- and sex-specific cut-points from growth curve data that were linked to the established NCEP Adult Treatment Panel dyslipidemia thresholds,4 and the work by myself and colleagues that has attempted to determine if these cut-points predict adult risk any better than the original NCEP cut-points.5, 6 Instead, the authors propose yet another set of cut-points for classification based on percentiles from the Lipid Research Clinics Prevalence Study.7 This may add to the confusion around which cut-points should ultimately be adopted. The proposed new cut -points have a number of limitations that were not properly considered. For example, the lipid and lipoprotein distributions were derived from white children7 and as such, should be applied to biracial populations with caution. Data from the Bogalusa Heart Study have not only shown differences in the distribution of lipid and lipoprotein levels by race, but that dynamic changes in blood lipid and lipoprotein levels that occur at the onset of puberty are differentially influenced by race.8, 9 In addition, although the authors recommend lipid screening to commence from the age of two years, the proposed cut-points begin from age five. How then should the blood lipid and lipoprotein concentrations of children aged from two to four years be classified? Second the authors have not considered non-HDL cholesterol in the revised guidelines. Because the measurement of non-HDL cholesterol averts certain limitations of LDL cholesterol measurement (including the requirement of samples to be from fasting individuals) it is increasingly being used in clinical research involving adult populations,10, 11 and has also been specified as a secondary target for therapy among patients with the metabolic syndrome or diabetes mellitus in the NCEP Adult Treatment Panel recommendations.4 The failure to mention non-HDL cholesterol in the revised guidelines for pediatric populations is puzzling considering that available data have shown child non-HDL cholesterol to be a better predictor of adult dyslipidemia and non-lipid CVD risk factors in adulthood such as hyperinsulinemia, and hyperglycemia than LDL cholesterol;12 non-HDL to be strongly predictive of metabolic-related risk factors such as triglycerides, HDL cholesterol, adiposity, and HBA1c in childhood;13, 14 youth with Type 1 and Type 2 diabetes commonly have elevated non-HDL cholesterol;15, 16 and the prevalence of high non-HDL cholesterol levels in youth with Type 1 diabetes increases with poor glycaemic control and duration of diabetes.14 These findings suggest that childhood non-HDL cholesterol levels have a place in the prediction of, and thus screening for, dyslipidemia and nonlipid CVD risk factors, particularly metabolic-related abnormalities. REFERENCES 1. Daniels SR, Greer FR. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008;122(1):198-208. 2. National Cholesterol Education Program (NCEP): highlights of the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics. 1992;89(3):495-501. 3. Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation. 2006;114(10):1056-1062. 4. 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) final report. Circulation. 2002;106(25):3143-3421. 5. Magnussen CG, Raitakari OT, Thomson R, et al. Utility of currently recommended pediatric dyslipidemia classifications in predicting dyslipidemia in adulthood: evidence from the Childhood Determinants of Adult Health (CDAH) study, Cardiovascular Risk in Young Finns Study, and Bogalusa Heart Study. Circulation. 2008;117(1):32-42. 6. Magnussen CG, Venn A, Thomson R, et al. The association of pediatric LDL-cholesterol and HDL-cholesterol dyslipidemia classifications and change in dyslipidemia status with carotid intima-media thickness in adulthood: Evidence from the Cardiovascular Risk in Young Finns Study, the Bogalusa Heart Study, and the Childhood Determinants of Adult Health (CDAH) Study. J Am Coll Cardiol. In Press. 7. Tamir I, Heiss G, Glueck CJ, et al. Lipid and lipoprotein distributions in white children ages 6-19 yr. The Lipid Research Clinics Program Prevalence Study. J Chronic Dis. 1981;34(1):27-39. 8. Berenson GS, McMahan CA, Voors AW, et al. Cardiovascular Risk factors in Children: The Early Natural History of Atherosclerosis and Essential Hypertension New York, NY: Oxford University Press; 1980. 9. Berenson GS, Srinivasan SR, Cresanta JL, et al. Dynamic changes of serum lipoproteins in children during adolescence and sexual maturation. Am J Epidemiol. 1981;113(2):157-170. 10. Frost PH, Davis BR, Burlando AJ, et al. Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP). Circulation. 1996;94(10):2381- 2388. 11. Frost PH, Havel RJ. Rationale for use of non-high-density lipoprotein cholesterol rather than low-density lipoprotein cholesterol as a tool for lipoprotein cholesterol screening and assessment of risk and therapy. Am J Cardiol. 1998;81(4A):26B-31B. 12. Srinivasan SR, Frontini MG, Xu J, et al. Utility of childhood non -high-density lipoprotein cholesterol levels in predicting adult dyslipidemia and other cardiovascular risks: the Bogalusa Heart Study. Pediatrics. 2006;118(1):201-206. 13. Srinivasan SR, Myers L, Berenson GS. Distribution and correlates of non-high-density lipoprotein cholesterol in children: the Bogalusa Heart Study. Pediatrics. 2002;110(3):e29. 14. Edge JA, James T, Shine B. Longitudinal screening of serum lipids in children and adolescents with Type 1 diabetes in a UK clinic population. Diabet Med. 2008;25(8):942-948. 15. Kershnar AK, Daniels SR, Imperatore G, et al. Lipid abnormalities are prevalent in youth with type 1 and type 2 diabetes: the SEARCH for Diabetes in Youth Study. J Pediatr. 2006;149(3):314-319. 16. Schwab KO, Doerfer J, Hecker W, et al. Spectrum and prevalence of atherogenic risk factors in 27,358 children, adolescents, and young adults with type 1 diabetes: cross-sectional data from the German diabetes documentation and quality management system (DPV). Diabetes Care. 2006;29(2):218-225. Conflict of Interest: None declared