USPSTF: Not Enough Evidence to Recommend Routine Lipid Screening in Children and Adolescents


There are not enough data currently available to support widespread cholesterol testing in asymptomatic children and adolescents. 

That is the conclusion of the United States Preventive Services Task Force (USPSTF) charged with reviewing and evaluating the evidence on screening for heterozygous familial hypercholesterolemia (FH) and dyslipidemia caused by various environmental and behavioral factors, including obesity.

In a report published August 9, 2016, in the Journal of the American Medical Association, the USPSTF states that the “current evidence is insufficient to assess the balance of benefits and harms of screening for lipid disorders” in children and adolescents. Screening is awarded an I (insufficient) statement, meaning the evidence is lacking, of poor quality, or conflicting and the balance of benefit and harms cannot be determined.

The decision updates the 2007 USPSTF statement on screening for lipid disorders in children, adolescents, and young adults—which also said the evidence was insufficient to recommend screening—and is in line with recommendations for the American Academy of Family Physicians. The new USPSTF document is accompanied in JAMA by two reports, both led by Paula Lozano, MD (Group Health Research Institute, Seattle, WA), evaluating the evidence on the benefits and harms of screening adolescents and children for heterozygous FH and multifactorial dyslipidemia (which is defined as LDL cholesterol levels ≥ 130 mg/dL or total cholesterol ≥ 200 mg/dL).

The USPSTF, which is chaired by Kirsten Bibbins-Domingo, MD (University of California, San Francisco), states that most children with elevated lipid levels will not progress to a clinically important lipid disorder or develop premature cardiovascular disease. “Screening could result in the labeling of children with a ‘nondisease,’ parental or child anxiety, or unnecessary or harmful testing and treatment,” according to the USPSTF statement. “The adverse effects of long-term use of lipid-lowering pharmacotherapy and lifestyle modification (including diet and physical activity) have not been adequately studied.”

In contrast, a 2011 expert panel on cardiovascular health and risk reduction from the National Heart, Lung, and Blood Institute (NHLBI), as well as the American Academy of Pediatrics, recommend screening for elevated cholesterol levels in children aged 9 to 11 years old followed by another full lipid screening between 17 to 21 years old. According to the NHLBI, cholesterol screening is strongly recommended, although the recommendation is based solely on observational studies, genetic natural history studies, and other reports and not on randomized controlled trials.

Beyond efforts to addresses these questions in children and adolescents, another group of researchers concluded there is no direct evidence supporting widespread screening of dyslipidemia in young adults. In a separate review for USPSTF published in the Annals of Internal Medicine, Roger Chou, MD (Oregon Health and Science University, Portland), and colleagues evaluated the evidence for screening individuals aged 21 to 39 years old and also concluded the data supporting screening and treatment were unavailable. This review will be used to update the 2008 USPSTF statement focused on young adults, which recommended screening in men aged 20 to 35 years and women 20 to 45 years with coronary heart disease risk factors (B recommendation).

Weighing In on the USPSTF Statement

With the USPSTF “insufficient” statement regarding screening in children and adolescents, there is now no shortage of experts weighing in on the recommendation. Some support the decision, while others believe lipid screening does have a role in pediatric clinical practice.

In an editorial published in JAMA Internal Medicine, Thomas Newman, MD (University of California, San Francisco), Alan Schroeder, MD (Stanford University, CA), and Mark Pletcher, MD (University of California, San Francisco), agree with the advice of the USPSTF, stating there is currently no evidence showing the benefit of screening and treatment.

The editorialists say that given the absolute risk of cardiovascular events in childhood is close to zero, screening and treating these kids would only lead to increased costs and harms—including diabetes caused by statins—without quantifiable benefit. Although the USPSTF said the state of evidence is “insufficient,” the editorialists go so far to state that had the task force considered costs and value, a recommendation against screening would have been appropriate.  

“High-value solutions to reduce the cardiovascular disease burden in the United States are more likely to come from lifestyle-focused measures than from within the healthcare system,” write Newman et al. “Diet, smoking, and exercise are obvious targets.”

In a JAMA editorial, Elaine Urbina, MD (Cincinnati Children’s Hospital Medical Center, OH), and Sarah de Ferranti, MD (Boston Children’s Hospital, MA), have a different take. They argue that until there is enough high-quality evidence to provide support for universal screening of lipid disorders in children and adolescents, there remains a need for some system to identify high-risk patients, such as those with heterozygous FH. More than 525,000 infants born each year have FH, they estimate, and yet “few are identified early in life.”

Conceding there are potential harms to screening, such as anxiety in children and families labeled with a lipid disorder, the imperfect tracking of elevated lipid levels with future atherosclerotic cardiovascular disease, and costs of screening and follow-up testing, Urbina and de Ferranti state there is mounting evidence that adolescence is a “critical window in atherosclerosis development.” With FH, which is usually asymptomatic in childhood, the disease is associated with an early risk of cardiovascular disease.

“Considering that all newborns undergo screening for phenylketonuria, which has a prevalence of 1 in 10,000, it seems reasonable that clinicians should also perform screening to detect FH (and pediatric lipid disorders), a disease that is far more common and is known to cause early morbidity and mortality,” write the editorialists.

In 2010, the USPSTF recommended clinicians screen for obesity in children 6 years or older, and said physicians could refer these overweight or obese children to a comprehensive, intensive behavioral intervention (B recommendation). In 2013, the task force stated the evidence was insufficient to recommend widespread screening for high blood pressure in children and adolescents.

Why the Disparity With the NHLBI?

For JAMA, Stephen Daniels, MD (University of Colorado School of Medicine, Aurora), and Samuel Gidding, MD (A.I. DuPont Hospital for Children, Wilmington, DE), both writing members of the 2011 NHLBI expert panel that recommended universal lipid screening in children and adolescents, looked at the gap between the NHLBI and USPSTF decisions, noting the two groups have different priorities when evaluating the current evidence.

In an editorial published in JAMA Cardiology, Gidding points out the USPSTF was tasked with asking critical questions about the value and benefit of screening based on available evidence. The core question for the task force was whether measuring cholesterol in childhood prevents future atherosclerotic events and if the measurement has any unintended consequences. The insufficient grade awarded by the USPSTF doesn’t necessarily advocate against screening, but rather means that a conclusion cannot be made about its clinical value, writes Gidding.

In contrast, the NHLBI expert panel was tasked with making recommendations for pediatric medical care professionals concerned about preventing cardiovascular disease in adulthood, “recognizing that conventional risk factors exist in some children and that atherosclerosis initiates in childhood,” according to Gidding.

“Recommendations of the 2011 panel were driven by the consistency of the evidence relating severely elevated cholesterol levels to premature development of atherosclerosis as well as the impossibility and ethical limitations of conducting a 40-year randomized trial to prove that lowering LDL cholesterol in childhood prevents cardiovascular disease events,” writes Gidding.

For Daniels, whose editorial appears in JAMA Pediatrics, the insufficient evidence does leave physicians in a clinical quandary, particularly when trying to decide on a course regarding screening in practice. However, physicians also have the benefit of looking at recommendations from other organizations, including those who rely on expert opinion when gaps in evidence don’t provide firm answers, he added.

 


 

 

 

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Sources
  • US Preventive Services Task Force. Screening for lipid disorders in children and adolescents. JAMA. 2016;316:625-633.

  • Lozano P, Henrikson NB, Morrison CC, et al. Lipid screening in childhood and adolescence for detection of multifactorial dyslipidemia. JAMA. 2016;316;634-644.

  • Lozano P, Henrikson NB, Dunn J, et al. Lipid screening in childhood and adolescence for detection of familial hypercholesterolemia. JAMA .2016;316:645-655.

  • Chou R, Dana T, Blazina I, et al. Screening for dyslipidemia in younger adults: a systematic review to update the 2008 US Preventive Services Task Force recommendation. Ann Intern Med. 2016;Epub ahead of print.

  • Urbina EM, de Ferranti SD. Lipid screening in children and adolescents. JAMA. 2016;316;589-591.

  • Gidding SS. Why cholesterol testing in children and adolescents matters. JAMA Cardiol 2016;Epub ahead of print.

  • Newman TB, Schroeder AR, Pletcher MJ. Lipid screening in children. JAMA Intern Med. 2016;Epub ahead of print.

  • Daniels SR. On the US Preventive Services Task Force statement on screening for lipid disorders in children and adolescents. JAMA Pediatrics. 2016;Epub ahead of print.

Disclosures
  • Members of the USPSTF statement on screening for lipid disorders in children and adolescent report no conflicts of interest.
  • Research/analysis conducted to support the USPSTF statement was funded by the Agency for Healthcare Research and Quality (AHRQ).
  • Chou reports receiving grant support from the AHRQ.
  • Urbina reports receiving grant support from the National Institutes of Health (NIH) and American Heart Association, as well as travel support from AtCor Medical. de Ferranti reports receiving grant support from the NIH and the New England Congenital Cardiology Research Fund, as well as royalties from UpToDate.
  • Gidding reports serving as a member of the scientific advisory board and the publications committee of the FH Foundation; receiving research funding from the NHLBI and the National Institute of Diabetes and Digestive and Kidney Diseases as coinvestigator at the echocardiography reading centers of the CARDIA and TODAY studies; receiving honoraria from the International Atherosclerosis Society for lectures and manuscripts related to familial hypercholesterolemia; and serving as a member of the NHLBI expert panel and the American Academy of Pediatrics Bright Futures program that published the Integrated Guidelines for Cardiovascular Risk Reduction in Children and Adolescents in 2011.
  • Newman, Schroeder, and Pletcher report no conflicts of interest.
  • Daniels reports serving as a member of the data monitoring committee for Novo Nordisk and a member of an advisory committee for Sanofi.

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