USPSTF: Insufficient Evidence for Recommendation on Screening for Lipid Disorders in Asymptomatic Children

Li Li, MD, PhD, MPH
Credit: University of Virginia Health

In a move that is sure to come as a disappointment to many in the cardiology community, the United States Preventive Services Task Force (USPSTF) has concluded there is insufficient current evidence to assess the benefits and harms of screening for lipid disorders in asymptomatic children and adolescents.

The organization’s first update on the subject since 2016, the latest recommendation from the USPSTF reaffirms the organization’s 2016, with the group concluding the current evidence was insufficient to balance the benefits and harms of screen for this patient population.¹

“The foundation of Task Force recommendations is a careful assessment of the evidence on both benefits and harms. In this case, we don’t have enough evidence to tell us whether or not screening all children and adolescents for high cholesterol is beneficial,” said Li Li, MD, PhD, MPH, USPSTF member and chair of the University of Virginia Department of Family Medicine.² “We are calling for more research to address this important issue, specifically on whether screening for high cholesterol in childhood helps to prevent premature heart attacks, strokes, and death in adulthood.”

Among the medical community, there has been a growing recognition of the role of LDL-C and cholesterol as a driver of cardiovascular risk that spans decades. As a result of this growing recognition of the need to address dyslipidemia, many have begun to adopt the practice of examining cumulative LDL exposure as a measurement of cardiovascular risk, which compounds the need for greater emphasis on the early detection and diagnosis of dyslipidemia.³ According to the US Centers for Disease Control and Prevention, recent evidence indicates about 7% of those in the US aged 6 to 19 years have high total cholesterol.⁴

Accompanying the publishing of the latest recommendation from the USPSTF was the evidence report used as the basis for the recommendation. A systematic review and meta-analysis of data from the MEDLIONE and Cochrane Central Register of Controlled Trials databases, investigators identified 43 published for inclusion in their review of evidence. For inclusion, studies needed to be conducted as an English-language randomized clinical trial (RCT) of lipid screening efforts, large US-based cohort studies reporting diagnostic yield or screen positivity, or an RCT of lipid-lowering interventions.⁵

The 43 studies identified for inclusion contained data related to 491,516 individuals. Investigators failed to identify any RCTs directly assessing screening effectiveness and harms. Included in the 43 studies were 3 US-based studies, encompassing 395,465 individuals, reporting prevalence of phenotypically defined familial hypercholesterolemia, with prevalence in these studies ranging from 0.2% to 0.4%, which correlates to rates of approximately 1-in-250 and 1-in-500, respectively. A group of 5 studies, encompassing 142,257 individuals, reported the prevalence of multifactorial dyslipidemia, with prevalence of LDL-C of 200 mg/dL or greater ranging from 7.1% to 9.4% and the presence of any lipid abnormality of 19.2%.⁵

Investigators called attention to a group of 10 RCTs conducted in children and adolescents with familial hypercholesterolemia, with a total combined study population of 1230. Within these RCTS, the observed use of statins was associated with an 81- to 82-mg/dL greater mean reduction in levels of total cholesterol and LDL-C compared with placebo to 2 years. In nonstatin-drug trials, results pointed to a statistically significant reduction of lipid levels in familial hypercholesterolemia populations, but investigators pointed out few studies were available for any single drug. Investigators noted observational studies purported statin treatment for familial hypercholesterolemia in childhood or adolescence was associated with reduced long-term cardiovascular disease risk.⁵

A pair of trials identified examined multifactorial dyslipidemia behavioral counseling trials. In these trials, which included 934 individuals, results suggested participation in such counseling was associated with a reduction in total cholesterol levels of 3 to 6 mg/dL, but investigators underlined these findings did not persist at the longest follow-up.⁵

Published simultaneously with the latest recommendations and supporting evidence document was an editorial penned by Sara de Ferranti, MD, MPH, of the Department of Pediatrics at Harvard Medical School, Andrew Moran, MD, MPH, of the Division of General Medicine at Columbia University Irving Medical Center, and Dhruv Kazi, MD, MSc, of the Richard A. and Susan F. Smith Center for Outcomes Research in the Division of Cardiology at Beth Israel Deaconess Medical Center and Harvard Medical School. In the editorial, the trio note the USPSTF determination may be discouraging to some, but the growing body of evidence and emphasis on need for universal screening suggest the possibility of systematic screening protocol may be on the eventual horizon.⁶

“The current I statement from the USPSTF pushes the possibility of a systematic national childhood lipid screening program into the future. However, we believe that the evidence supporting specific screening for and treatment of [familial hypercholesterolemia] in childhood is growing, and a universal screening approach to reduce the burden of premature atherosclerotic cardiovascular disease among persons with [familial hypercholesterolemia] will likely be adopted in the future,” wrote the authors.⁶ “In the meantime, clinicians can rely on existing guidelines and decide together with pediatric patients and their families if and when to screen for lipid disorders in childhood.”

References:

1. US Preventive Services Task Force. Screening for Lipid Disorders in Children and Adolescents: US Preventive Services Task Force Recommendation Statement. JAMA. 2023;330(3):253–260. doi:10.1001/jama.2023.11330
2. U.S. Preventive Services Task Force (USPSTF). U.S. Preventive Services Task Force Issues Final Recommendation Statement on Screening Children for Lipid Disorders. USPSTF Newsroom. July 18, 2023. Accessed July 18, 2023. https://uspreventiveservicestaskforce.org/uspstf/sites/default/files/file/supporting_documents/lipid-disorders-screening-children-adolescents-final-rec-bulletin.pdf.
3. Campbell P. Rethinking statins: Time for primordial prevention? HCPLive. September 27, 2022. Accessed July 17, 2023. https://www.hcplive.com/view/rethinking-statins-time-for-primordial-prevention.
4. US Centers for Disease Control and Prevention. High cholesterol facts. Centers for Disease Control and Prevention. May 15, 2023. Accessed July 17, 2023. https://www.cdc.gov/cholesterol/facts.htm.
5. Guirguis-Blake JM, Evans CV, Coppola EL, Redmond N, Perdue LA. Screening for Lipid Disorders in Children and Adolescents: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force. JAMA. 2023;330(3):261–274. doi:10.1001/jama.2023.8867
6. de Ferranti SD, Moran AE, Kazi DS. Still “on the Fence” About Universal Childhood Lipid Screening: The USPSTF Reaffirms an I Statement. JAMA. 2023;330(3):225–227. doi:10.1001/jama.2023.11258