NLA Statement on New Cholesterol Guidelines for Children

When the American Academy of Pediatrics (AAP) issued a recommendation on July 7, 2008, in the form of a paper on the treatment of children with high cholesterol,¹ it generated a strong response from the community of medical professionals and patients. The National Lipid Association (NLA) believes that the AAP has acted in the interests of patient care by raising the issue of lipid abnormalities in children, and suggests that the AAP guidelines be understood in the proper context.

"Healthy lifestyles with good diet and exercise at an early age are the best level of prevention from future issues of related disease. We enthusiastically want children to participate in healthy choices and that parents, medical practices, schools, and the community should partner whenever possible to offer good interventions and choices," says Dr Thomas Bersot, president of the NLA and Professor of Medicine at the University of California in San Francisco.

The Bogalusa Heart Study and the Pathobiological Determinants of Atherosclerosis in Youth demonstrated that early atherosclerotic lesions of fatty streaks and fibrous plaques in children, adolescents and young adults, who died from accidental deaths, are significantly related to higher antecedent levels of total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), lower levels of high density lipoprotein cholesterol (HDL-C), and to other cardiovascular disease (CVD) risk factors, such as obesity, higher blood pressure levels and cigarette smoking. The effects of these risk factors in youth on coronary lesion severity are multiplicative rather than additive.

Risk factors track from childhood into adulthood. For example, higher levels of LDL-C and non-HDL-C (TC minus HDL-C) in youth predicted both adult dyslipidemia and carotid intima medial thickness (IMT) from adolescence through young adulthood in The Cardiovascular Risk in Young Finns Study (SCRIP) and the Bogalusa Heart Study. Risk factors at baseline in the Coronary Artery Risk Development in Young Adults (CARDIA) and the Muscatine Study were significant longitudinal predictors of coronary artery calcium 15 years later.

Thus, atherosclerosis often begins in childhood and adolescence, contrary to popular belief that this is a health concern only for middle-aged and elderly persons. In some affected children, such as those with the inherited disorder, familial hypercholesterolemia (FH), or in those whose parent suffered coronary artery disease (CAD) before 50 years of age, atherosclerosis progresses more rapidly, leading to heart attacks and death from CAD in their 30s, 40s and 50s.

For the majority of children, diet and lifestyle therapy are sufficient to achieve and maintain good health through adolescence and into adulthood. Early intervention for those who are overweight or obese in childhood is of key importance and the NLA concurs with AAP that a lifelong approach to cardiovascular disease (CVD) prevention is instrumental to our efforts to reduce death and morbidity from dyslipidemia. Indeed, the most recent issue of the Journal of Clinical Lipidology² is entirely focused on pediatric lipidology and presents an in-depth exploration of the subject. The issue contains a series of articles presenting a review of the many aspects of pediatric hyperlipidemia from etiology, clinical evaluation, personal treatment, and potential for institutional changes.

Discussion of Therapeutics: Much of the controversy surrounding the AAP guidelines appears to stem from a misinterpretation regarding the use of statins and other lipid-lowering drugs. These are options for managing specific genetic hypercholesterolemias such as FH, and severe hypertriglyceridemias. There is no randomized clinical trial data of statin treatment begun in childhood with regard to adult CAD event outcomes and it is unlikely that such data will be forthcoming for decades, if ever. The use of a statin for two years in FH children aged 8 to 15 years from the Netherlands decreased thickening of carotid IMT, compared to those on placebo. As judged by a meta-analysis of a half-dozen placebo-controlled statin trials, the benefits of such an approach are likely to outweigh the risks when treating children with FH or others who have LDL-C values that exceed 190mg/dL (> 160mg/dL if there is a family history of premature CAD, or ≥ 2 additional risk factors or in the presence of diabetes mellitus). These threshold values for initiating drug treatment are well above 95th percentile values of LDL-C among children in the United States.

Four statins have been approved by the FDA for use in FH adolescents. Available studies of about two years' duration have not demonstrated adverse effects on growth or development. In most cases drug treatment can begin in adolescence although there may be particular children at very high risk who may warrant consideration for even earlier treatment. However, the more common dyslipidemias correlated with insulin resistance and obesity should not be routinely managed with drugs, as diet and exercise remain the best treatment choices.

We recognize that the increasing prevalence of obesity and type 2 diabetes mellitus in childhood are bringing lipid abnormalities to the fore in this population. These disorders, especially when accompanied by other risk factors or genetic defects such as FH may warrant medical therapy in childhood. We applaud the current deliberations of the National Heart Lung and Blood Institute's Integrated Pediatric Cardiovascular Risk Reduction Panel and eagerly await their recommendations and guidelines for pediatric populations. Long-term studies are needed and the NLA encourages physicians and allied professionals who manage healthcare in children to work together to meet the need for additional education and research in this area.

References:
1. Daniels R, Greer F, and the Committee on Nutrition. Lipid Screening and Cardiovascular Health in Childhood Pediatrics. 2008; 122 (1):198-208
2. Brown WV, Ed. The Journal of Clinical Lipidology. 2008; 2(3):117-201

The NLA contributors to this paper have provided full disclosures, and their thoughts on this matter have not been influenced by bias or commercial interest. The viewpoints expressed here represent the clinical experience and opinion of our experts and the scientific evidence, which serves as the basis of clinical lipidology. All members of the organization and others reviewing this document are urged to thoroughly review the study and place this, in addition to other learned comment, in the context of meeting the interests of patient care. The NLA further discloses that the association has received educational grants from multiple manufacturers to support accredited medical educational activities. There was no funding or any interaction with any manufacturer in regard to this statement.

Disclosures:
T. Bersot
Consultant: Merck & Co., Merck-Schering Plough, and Abbott Laboratories. Speaker honoraria from: Merck & Co., Merck-Schering Plough, and Abbott Laboratories.

P. Kwiterovich
Research grant support from: Pfizer, Abbott Laboratories, AstraZeneca. Speaker honoraria from: Merck, Schering/Plough, Reliant, GlaxoSmithKline, Astrazeneca, and Pfizer.

V. Brown
Consultant for: Abbott Laboratories, Atherogenics, Merck, Schering/Plough, Amgen, Pfizer, AstraZeneca, Solvay and Liposcience. Research grant support from: Abbott Laboratories. Speaker honoraria from: Abbott Laboratories, AstraZeneca, Solvay and Sanofi-Aventis.

P. Jones
Consultant for: Abbott Laboratories, and AstraZeneca. Speaker honoraria from: Abbott Laboratories, AstraZeneca, Merck, and Pfizer.