Atherosclerotic cardiovascular disease (ASCVD) is traditionally recognized as a disease of midadulthood. However, atherogenesis begins in childhood. Subclinical atherosclerosis can be detected as early as 8-10 years of age.^1,2 Prolonged exposure to dyslipidemia is a major determinant of lifetime ASCVD risk,¹ but lipid screening in pediatric populations remains inconsistently implemented, with only 10-20% of children undergoing testing.^1,3

The practice-changing 2026 multisociety Guideline on the Management of Dyslipidemia recommends a shift toward life-course cardiovascular (CV) prevention and early intervention. This guideline issues a Class 1 recommendation for universal lipid screening in children 9-11 years of age to identify familial hypercholesterolemia (FH). This approach strategically precedes the physiologic decline in low-density lipoprotein cholesterol (LDL-C) levels by 10-20% during puberty, underestimating true lipid burden.¹ This screening recommendation aligns with guidance from the American Academy of Pediatrics (AAP).³ Notably, this recommendation is an escalation from the 2018 multisociety Guideline on the Management of Blood Cholesterol, which supported a Class 2b recommendation for screening in children without risk factors.

Moreover, a Class 2a recommendation supports cascade screening beginning as early as 2 years of age to identify FH in those with first- or second-degree relatives with premature ASCVD or severe hypercholesterolemia. The 2026 multisociety guideline on dyslipidemia supports ASCVD-prevention strategies in childhood. This analysis highlights the role of early detection through exploration of FH, obesity-related dyslipidemia in children, and the implementation gaps limiting pediatric lipid screening (Figure 1).

Figure 1: Atherosclerotic Disease Beginning in Childhood: The Case for Early Screening

ASCVD = atherosclerotic cardiovascular disease; CIMT = carotid intima-media thickness; HeFH = heterozygous familial hypercholesterolemia; HoFH = homozygous familial hypercholesterolemia; LDL-C = low-density lipoprotein cholesterol.

Familial Hypercholesterolemia

Early detection of FH is a primary goal of the 2026 multisociety guideline on dyslipidemia. Heterozygous familial hypercholesterolemia (HeFH) affects approximately 1:250-300 individuals and confers a two- to fourfold increased risk of premature ASCVD. HeFH is estimated to be present in 20% of adults presenting with premature myocardial infarction. Nevertheless, nearly 90% of affected individuals remain undiagnosed. The pathophysiology of FH is driven by early and lifelong elevation of LDL-C levels, resulting in cumulative atherogenic exposure.¹ Identification enables timely initiation of lipid-lowering therapy (LLT), which significantly reduces LDL-C levels and ASCVD risk; however, pediatric outcome data remain limited.¹

In a simulation study of 15,900 US 10-year-olds with HeFH, early LLT projected a reduction in CV event rates to that of the general pediatric population, highlighting the impact of early screening and subsequent initiation of therapy to reduce cumulative LDL-C exposure.⁴ Cascade screening further amplifies the yield of early detection strategies. In a large simulated cohort of 4.2 million US 10-year-olds, childhood or early adulthood FH screening effectively reduced cardiovascular disease (CVD) events but was not cost-effective, largely due to discounting of long-term benefits under traditional modeling assumptions.^5,6 However, when treatment was initiated on the basis of elevated LDL-C levels alone without sequential genetic testing, screening became cost-effective, underscoring the benefit of early screening and intervention for the general population.^5,6 These simulation findings are clinically and economically compelling, although modeled data warrant validation in real-world populations.

Homozygous familial hypercholesterolemia (HoFH) represents a severe phenotype characterized by markedly elevated LDL-C levels from birth and a high risk of early and recurrent CV events, with median first major adverse events occurring at 37 years of age in high-income countries and reports of ASCVD as early as 2 years of age.¹ Results from the CASCADE FH (Cascade Screening for Awareness and Detection Familial Hypercholesterolemia) Registry demonstrate that HoFH remains underdiagnosed and undertreated, with a substantial proportion of individuals identified retrospectively in a large database as having a HoFH-consistent phenotype rather than being recognized in routine clinical care.⁷ Among these individuals, 40% were not receiving LLT, suggesting missed opportunities for earlier detection and therefore suboptimal treatment.⁷

HoFH is of particular interest due to its emblematic resistance to LLT, requiring early referral to lipid specialists and initiation of multiple agents including maximally tolerated statin therapy, ezetimibe, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies, bempedoic acid, evinacumab, LDL apheresis, and possibly lomitapide.^1,7 In the CASCADE FH Registry, most adults and children did not meet their LDL-C goals despite multiple lipid-lowering agents.⁷ Thus, early detection is critical to optimize treatment.

Childhood Obesity

Beyond monogenic dyslipidemias, secondary dyslipidemia related to obesity represents a growing driver of ASCVD.¹ Approximately 20% of adolescents have remarkable lipid levels, and 5% have LDL-C levels >130 mg/dL.¹ These data parallel the rising prevalence of pediatric obesity, now affecting an estimated 36.5 million US children.^1,2 Youth with obesity have threefold higher rates of dyslipidemia than children with normal weight, underlining the metabolic burden of obesity driving secondary lipid disorders.² Emerging data from biomarker studies further suggest that pediatric obesity is associated with proteomic alterations, reflecting early cardiometabolic remodeling.⁸ Children with obesity are also more likely to undergo lipid screening, reflecting a reliance on weight-based risk stratification.³ However, lipid abnormalities are also observed in youth with normal weight.^3,9 This discordance supports the rationale for universal lipid screening independent of weight-based risk alone.^1-3

There are no randomized controlled trial data demonstrating the effect of pharmacologic intervention for dyslipidemia of obesity in children. The DO IT! (Dyslipidemia of Obesity Intervention in Teens) trial using pitavastatin in this population for lipid outcomes was terminated early, although the main results were pending at the time of this writing.² Lifestyle modification is the cornerstone for management of secondary dyslipidemia in children.² Early identification of remarkable lipid profiles in children may reinforce heart-healthy behavioral modifications with the potential to attenuate their lifetime risk.¹

Implementation Gap

Implementation of childhood lipid screening remains suboptimal. Barriers include limited clinician familiarity with FH, clinic time constraints, uncertainty of treatment for secondary lipidemia, ambiguity in US Preventive Services Task Force recommendations, and parental hesitancy.^9,10 Given that ASCVD is a result of cumulative exposure to atherogenic lipoproteins, the 2026 multisociety guideline on dyslipidemia's recommendation for universal lipid screening at 9-11 years of age offers a scalable opportunity to identify children at risk, initiate timely intervention, and alter CVD trajectory. However, its impact will depend on coordinated implementation across clinicians, patients and their families, and health systems to ensure earlier identification and treatment of dyslipidemia in routine practice.

References

1. Blumenthal RS, Morris PB, Gaudino M, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of dyslipidemia: a report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. Published online March 13, 2026. doi:10.1016/j.jacc.2025.11.016
2. de Ferranti SD, Teng JE, Arslanian SA, et al. A multicenter trial to test pitavastatin calcium in youth with combined dyslipidemia of obesity: design, implementation, challenges, and responses. Am Heart J. 2026;294:107327. doi:10.1016/j.ahj.2025.107327
3. Thompson-Paul AM, Kraus EM, Porter RM, et al. Pediatric lipid screening prevalence using nationwide electronic medical records. JAMA Netw Open. 2024;7(7):e2421724. Published 2024 Jul 1. doi:10.1001/jamanetworkopen.2024.21724
4. Huang YL, de Ferranti SD, Hartz J, et al. Impact of early, delayed, or interrupted treatment in children with familial hypercholesterolemia. J Am Coll Cardiol. 2026;87(7):793-796. doi:10.1016/j.jacc.2025.09.1613
5. Bellows BK, Zhang Y, Ruiz-Negrón N, et al. Familial hypercholesterolemia screening in childhood and early adulthood: a cost-effectiveness study. JAMA. 2026;335(2):140-153. doi:10.1001/jama.2025.20648
6. Bellows BK, de Ferranti SD, Moran AE. Cost-effectiveness of familial hypercholesterolemia screening in childhood and early adulthood-reply. JAMA. 2026;335(15):1366. doi:10.1001/jama.2026.0675
7. Cuchel M, Lee PC, Hudgins LC, et al. Contemporary homozygous familial hypercholesterolemia in the United States: insights from the CASCADE FH Registry. J Am Heart Assoc. 2023;12(9):e029175. doi:10.1161/JAHA.122.029175
8. Lin Z, Rifas-Shiman SL, de Ferranti SD, Perng W, Hivert MF, Aris IM. Cardiovascular health across childhood and adolescence and proteomic biomarkers in late adolescence. Eur J Prev Cardiol. Published online April 3, 2026. doi:10.1093/eurjpc/zwag176
9. Leopold S, Zachariah JP. Pediatric lipid disorders. Pediatr Ann. 2021;50(3):e105-e112. doi:10.3928/19382359-20210218-01
10. Schubert TJ, Gidding SS, Jones LK. Overcoming the real and imagined barriers to cholesterol screening in pediatrics. J Clin Lipidol. 2024;18(3):e297-e307. doi:10.1016/j.jacl.2024.02.008