Source: Bellows BK, Zhang Y, Ruiz-Negrón N, et al. Familial hypercholesterolemia screening in childhood and early adulthood: a cost-effectiveness study. JAMA. 2026 Jan 13;335 (2): 140-153. doi: 10. 1001/jama. 2025. 20648. Investigators from multiple institutions developed a simulation model to evaluate the cost-effectiveness of universal low-density lipoprotein cholesterol (LDL-C) screening at 10 or 18 years of age, with genetic testing for heterozygous familial hypercholesterolemia (FH) for those with elevated screening LDL-C levels. Their analysis was based on the CVD policy model, a validated discrete event simulation of cardiovascular disease (CVD) risk factor management and CVD outcomes, based on data from participants in the National Health and Nutrition Examination Survey (NHANES). Using a hypothetical cohort of 4. 2 million 10-year-olds in the US, CVD outcomes with multiple screening strategies were modeled and compared to estimated outcomes for current usual care (age-and sex-specific screening strategies with no universal FH screening). Screening strategies assessed included universal lipid testing at 10 or 18 years of age, with FH genetic tests, for those with LDL-C levels ≥130 mg/dL, ≥160 mg/dL, or ≥190 mg/dL in various scenarios. Lifestyle therapy was included for all of those in the cohort with LDL-C levels ≥130 mg/dL, and lipid lowering therapy (LLT) was presumed for those with an LDL-C level ≥190 mg/dL and/or a positive FH screen. Using data from national surveys and prior studies, the effect of LLT in reducing CVD events was estimated and the costs of the screening program, including genetic testing evaluated. The rate of adverse events from LLT and proportion of individuals screened were modeled in the different screening plans. Based on the analysis, the cost per quality-adjusted life-years (QALYs) with each screening strategy was compared to usual care. A screening strategy was considered to be cost-effective if the cost per QALY gained was 100, 000, thus, not cost effective. The most cost-effective strategy was universal screening at 18 years, with FH testing for those with an LDL-C level ≥190 mg/dL, which yielded a cost per QALY gained of 289, 700 compared to usual care. The authors conclude that, based on their simulation model, universal lipid testing at 10 or 18 years of age, with genetic testing for FH for those with high levels, was not a cost-effective strategy to reduce CVD. Dr Doolittle has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device. Hyperlipidemia is an important, reversible driver of CVD in adulthood. 1 Early intervention has shown promise to reduce long-term morbidity. 1 Although the USPSTF found insu? cient evidence for universal screening, several professional societies recommend lipid screening at between ages 9–11 and 17–21. 2 However, until now, no study has explored the cost effectiveness of this intervention. Randomized controlled trials are impractical given the long timeline before discerning a statistical difference and di? culties with randomization and follow-up. 3 The current researchers designed a robust model based on real-world parameters to calculate the cost-effectiveness of universal screening. Their results were disappointing: Lipid screening with testing for FH was not cost-effective. There are some assumptions that could be questioned, although based on current standards, they are not optimized practice. 4, 5 It is possible that children deemed high-risk may have greater adherence to lifestyle modification and LLT. If our present screening model is not cost-effective, perhaps there are other focused screening modalities which may be. For example, screening for lipoprotein A, another genetically determined lipoprotein, with familial reverse cascade screening has shown promise. 6 Given the impact of CVD, a cost-effective screening program could reduce patient morbidity. Based on a simulation model, universal lipid screening at 10 and 18 years of age is not cost-effective. Promotion of policies that support reduction of dietary salt and increased physical activity may prove to be the most cost-effective approaches to universally prevent adult CVD. 7
A Sun, study studied this question.