Lipid Luminations: The Controversy Over Universal Cholesterol Screening for Children

In 2011, the NLA and the National Heart Lung and Blood Institute (NHLBI) sponsored expert panel on Integrated Cardiovascular Risk Reduction for Children and Adolescents each recommended universal lipid screening of United States children at age 9-11 years.^1,2 Prior reports recommended cholesterol measurement over age 2 years in the presence of a positive family history of heart disease or elevated cholesterol or the presence of a co-morbid condition known to increase cardiovascular risk. This latter recommendation was retained by the NHLBI Integrated Risk Reduction panel. The two guidelines, by design, are essentially identical with regard to formal recommendations; however, the purpose of each is somewhat different. The NLA recommendations are directed towards identifying all children with familial hypercholesterolemia (FH). The Integrated Risk Reduction guideline takes a different approach to cardiovascular risk reduction in youth, integrating risk factor management developmentally across childhood and across all the risk factors to provide comprehensive primordial and primary prevention strategies that consider the whole child rather than managing individual risk factors independently. Each set of recommendations has generated controversy.

In the NLA consensus-based statement, and for the first time in the United States, FH is considered as a distinct disease entity, separate from epidemiologically based lipid assessment. Thus, increased risk associated with lifelong exposure to severe and genetically elevated cholesterol levels is, finally, given appropriate consideration. The controversy related to the NLA recommendations is international, where many Western countries and some others have embraced cascade screening of identified index cases of FH, often with confirmation by genetic testing, as opposed to universal population screening as recommended in the NLA guideline. For example, in the Netherlands where FH genetic identification is most advanced, probably about 80% of FH carriers have been identified. In the United Kingdom, identification of those with FH between the ages of 40-70 years and subsequent cascade screening with genetic testing and lipid treatment is highly cost effective.³

In fact, if one looks deeply at current cost analyses for FH care, one learns that treating an identified patient with FH is highly cost effective (particularly with generic medications) and gene testing does not substantially worsen these projections (particularly as testing becomes much cheaper in the future). Adverse cost in FH management is largely incurred in case identification. The NLA panel recommended universal screening for FH because of the historic failure of physicians in this country to successfully implement cascade screening, the recognition that family history is an inadequate criterion for youth screening, and the high discrimination in childhood between true cases and unaffected individuals. Genetic testing was not recommended because risk is determined more by LDL cholesterol level than genotype. In contrast, in the rest of the world, universal lipid screening is prohibitively expensive, and index cases are identified at older ages when genetic testing often helps risk stratification. In my view, this discussion is not so much a controversy as a very healthy scientific and public health argument that in the short term will lead to increased recognition and awareness of FH in the medical and general community and, in the long term, to cost effective treatment strategies appropriate to the varied health care systems and resources around the world.

The controversy over the evidencebased NHLBI sponsored Integrated Cardiovascular Risk Reduction Guideline exists mostly within the United States. Concerns are raised about the true benefit in cardiovascular disease risk reduction from early identification, the unknown harms of pharmacologic treatment, and cost. These arguments are not that different from those raised 20 years ago when the first selective screening recommendations were made and are legitimate concerns.⁴ However, to be frank, I have a hard time accepting these arguments as sufficient. In contrast to the international debate on the best way to recognize and treat FH, this argument has the potential to destroy efforts to prevent heart disease in this country.

The current NHLBI-sponsored 2011 Integrated Guidelines are unique compared to prior expert recommendations. Most important, they are evidence-based and were developed according to the highest recommended process as defined by the Institute of Medicine.⁵ The critiques described above were considered in the weighting of evidence (these critiques are actually included in the text of the guideline) and the panel’s conclusion was that the evidence for universal screening far outweighed the evidence against. In the minds of the panel, the knowledge that atherosclerosis begins in youth and is directly related to risk factors, that genetic disorders of lipid metabolism provide overwhelming and consistent evidence for the benefit of lifelong LDL cholesterol levels below 100 mg/dL, that clinical trials have been conducted that show medium term safety and efficacy of statins with improvement in subclincal atherosclerosis outcomes, and that selective screening strategies fail to identify a significant percentage of those with severe elevations of cholesterol outweighed gaps in evidence related to long term safety and cost.

Perhaps the most radical (and underappreciated) change in the 2011 Integrated Guidelines compared to prior efforts is the fact that they are designed to evaluate all cardiovascular risk factors in every child both developmentally and across all risk factors, as opposed to creating "risk silos" engendered by prior guidelines for individual risk factors. The rationale for this approach comes from recognition of the importance of preventing risk development in the first place (primordial prevention), of the natural history of atherosclerosis and the importance of multiple risk factors to rapid atherosclerosis progression, of the need to tailor recommendations to the age of the child and the needs of the entire family, and of the importance of obesity to the development of multiple cardiovascular risk factors. Additionally, there is a small subset of children who need cardiovascular risk management: those with FH, diabetes, chronic kidney disease, and other high risk conditions. The focus on whether or not to measure cholesterol in children undercuts and deflects from the two more important goals of the 2011 guideline: to improve cardiovascular health across all risk factors before target organ injury is advanced and to make sure that small subgroup of children at highest risk is identified.

To summarize, it is probably worth considering if universal screening at age 9-11 years is that different from current recommendations. In ATP III, universal screening is recommended at age 20 years, when very few people regularly go to the doctor. Prior youth recommendations would test 60-65% of United States children, largely because of the high prevalence of obesity and positive family history. What these new recommendations do is increase awareness of the importance of healthy lifestyle habits for all, move the cholesterol test up about 10 years for about 35-40% of the population to an age when genetic dyslipidemias can be recognized and at an optimal time for intervention, and allow for dietary intervention at an age when preventive health care is the norm. Is that so bad?.

Editors’ Note: Dr. Gidding was a member of the NLA and NHLBI expert panels that drafted the lipid screening guidelines.