Conflicting Recommendations for Lipid Screening and Management in Children: The Need for Consensus

In July 2008, the American Academy of Pediatrics (AAP) updated their recommendations on lipid screening and cardiovascular health in childhood.¹ The new recommendations created a media stir because of the endorsement of the use of statins in certain at-risk children as young as 8 years. However, the greatest difficulty that the new recommendations may pose to pediatricians "in the trenches" likely has less to do with this specific endorsement than with the mounting general confusion in this area of practice- an inevitable result of a growing list of differing recommendations by various organizations for lipid screening in children and the subsequent management of abnormalities. Other published statements on this subject include those by the American Heart Association (AHA) in 2006,² the National Cholesterol Education Program (NCEP) in 1991,^3-6 and the American Diabetes Association (ADA) in 2008.⁷

Here we attempt to shed some light on the nature of the confusion that has arisen. We also attempt to distill some clarity from the multiple discrepancies and differences among these sets of guidelines.

SCREENING RECOMMENDATIONS: AAP PROVIDES MORE SPECIFICS

The recent AAP guidelines agree with the previously published NCEP guidelines with regard to risk factors that warrant testing. However, the AAP guidelines go one step further by recommending specific ages for testing and more aggressive repeat testing in at-risk patients.

Both the AAP and NCEP recommend screening with a fasting lipid profile for children with a family history of dyslipidemia or premature (age 55 years or younger for men and 65 years or younger for women) cardiovascular disease (CVD); those with an unknown family history; and those with other risk factors, including lifestyle (smoking, physical inactivity), metabolic disorders (diabetes, low high-density lipoprotein cholesterol level), and hypertension.

In addition, the AAP guidelines recommend screening after age 2 years and no later than 10 years. If values are within normal limits for the child's age, repeat testing is recommended 3 to 5 years later.

DIFFERENCES REGARDING TREATMENT

The most notable differences between recommendations for the treatment of dyslipidemia in children concern:

• The low-density lipoprotein (LDL) cholesterol levels at which pharmacological intervention should be considered.

• Treatment targets.

AAP recommendations. For patients 8 years or older, the AAP recommends pharmacological intervention in those with an LDL cholesterol level of 190 mg/dL or above, in those with an LDL cholesterol level of 160 mg/dL or above who also have a family history of early heart disease or 2 or more additional risk factors (as enumerated above), and in those with diabetes mellitus whose LDL cholesterol level is 130 mg/dL or greater. The goal of therapy as set forth in the AAP recommendations is to decrease the LDL cholesterol level to less than 160 mg/dL initially, but clinicians are urged to consider targets as low as 130 mg/dL or even 110 mg/dL in patients who have diabetes, metabolic syndrome, obesity, or a strong family history of CVD.

NCEP recommendations. The 1991 NCEP guidelines are similar to the AAP guidelines, but in certain respects their treatment recommendations are less aggressive. For example, the NCEP guidelines do not consider diabetes to be a risk factor that warrants a lower LDL cholesterol target, and they recommend starting pharmacological intervention at a later age (10 years). The difference in the recommended age for initiation of pharmacotherapy between the NCEP and AAP guidelines is likely the result of FDA approval of pravastatin for children 8 years and older-which occurred after publication of the NCEP guidelines.

The NCEP guidelines recommend dietary and lifestyle changes as the initial intervention in all patients with dyslipidemia. If after a 6- to 12-month period the LDL cholesterol level does not fall below 160 mg/dL, consideration of pharmacological intervention is recommended for children 10 years or older who meet 1 of the following sets of criteria:

• An LDL cholesterol level between 160 and 189 mg/dL and a family history of premature CVD.

• An LDL cholesterol level between 160 and 189 mg/dL and 2 of the CVD risk factors mentioned above (in the section on screening recommendations).

• An LDL cholesterol level of 190 mg/dL or above, regardless of other risk factors.

AHA recommendations. The 2006 AHA recommendations employ a different approach than either the AAP or the NCEP guidelines. The former assign patients to an early CVD risk tier based primarily on diseases or conditions that are or were present (Table). Any patient with 2 additional risk factors (abnormal fasting lipid profile, smoking history, family history of early CVD, hypertension, elevated body mass index, impaired fasting glucose, or sedentary lifestyle) is moved up 1 tier. The AHA also advocates more aggressive targets. The LDL cholesterol goal for patients in tier III is 160 mg/dL; for those in tier II, 130 mg/dL; and for those in tier I, 100 mg/dL. In patients older than 10 years, pharmacological therapy with a statin is recommended to achieve these goals. Because type 1 diabetes is included in tier I, a statin is therefore recommended in any child older than 10 years who has type 1 diabetes and an LDL cholesterol level higher than 100 mg/dL and in whom a 6-month trial of lifestyle and dietary changes has failed.

Table

ADA recommendations. The ADA recommends that all children older than 10 years who have diabetes be screened after glycemic control is achieved. Both the AHA and ADA guidelines recommend that patients with an LDL cholesterol level higher than 100 mg/dL make appropriate lifestyle changes in both diet and exercise. However, the ADA does not recommend starting statin therapy unless a patient's LDL cholesterol level is higher than 160 mg/dL (or higher than 130 mg/dL if 1 or more additional CVD risk factors are present).

SO NOW WHAT DO WE DO?

This brief analysis of the differing recommendations by the various organizations underscores the need for achieving consensus. The guidelines for providers who care for younger patients with type 1 diabetes are particularly confusing: 3 different thresholds for initiation of pharmacotherapy have been recommended, and 4 different target LDL cholesterol levels have been proposed.

Moreover, the strength of the evidence for existing recommendations is uneven. A significant increase in atherosclerosis in adolescents and young adults with diabetes compared with nondiabetic persons has indeed been demonstrated^8,9-and in adults, the presence of diabetes is regarded as equivalent to a history of coronary artery disease (hence the more aggressive LDL cholesterol targets). It remains to be determined, however, whether pharmacological intervention in children as young as 8 or 10 years will lead to a significant decrease in coronary disease or at least to a reversal of arterial dysfunction (indicative of accelerated atherosclerosis).

Until a good evidence-based consensus is available, we must decide which recommendations are the most appropriate for our patients. The AAP guidelines (which are the most recent of those discussed here) set forth clear recommendations for screening and treatment, take into account recent changes in the FDA-approved ages for statin therapy, and are not overly aggresive (ie, they do not suggest LDL cholesterol goals of less than 100 mg/dL for patients who have type 1 diabetes without clear clinical evidence, as the AHA guidelines do). With the obvious allowance that in certain situations-which only good clinical judgment can determine- one of the other sets of guidelines might be more appropriate, we recommend using those recently issued by the AAP

References:

• Daniels SR, Greer FR; Committee on Nutrition. Lipid screening and cardiovascular health in childhood. Pediatrics. 2008;122:198-208.

• Kavey RW, Allada V, Daniels SR, et al. Cardiovascular risk reduction in high-risk pediatric patients: a scientific statement from the American Heart Association Expert Panel on Population and Prevention Science; the Councils on Cardiovascular Disease in the Young, Epidemiology and Prevention, Nutrition, Physical Activity and Metabolism, High Blood Pressure Research, Cardiovascular Nursing, and the Kidney in Heart Disease; and the Interdisciplinary Working Group on Quality of Care and Outcomes Research: endorsed by the American Academy of Pediatrics. Circulation. 2006;114:2710-2738.

• National Institutes of Health, US Department of Health and Human Services. National Cholesterol Education Program. Highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Bethesda, MD: National Institutes of Health; September 1991;1-11. NIH publication 91-2731.

• National Institutes of Health, US Department of Health and Human Services. National Cholesterol Education Program. Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Bethesda, MD: National Institutes of Health; 1991. NIH publication 91-2732.

• National Cholesterol Education Program. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA. 1993;269:3015-3023.

• National Cholesterol Education Program. 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. 2001;285:2486-2497.

• American Diabetes Association. Standards of Medical Care in Diabetes-2008. Diabetes Care. 2008;31 (suppl 1):S12-S54.

• Krantz JS, Mack WJ, Hodis HN, et al. Early onset of subclinical atherosclerosis in young persons with type 1 diabetes. J Pediatr. 2004;145:452-457.

• Haller MJ, Samyn M, Nichols WW, et al. Radial artery tonometry demonstrates arterial stiffness in children with type 1 diabetes. Diabetes Care. 2004;27: 2911-2917.