{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T08:20:11Z","timestamp":1793262011356,"version":"4.5.0"},"reference-count":85,"publisher":"American Medical Association (AMA)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2026,1,13]]},"abstract":"\n Importance<\/jats:title>\n Heterozygous familial hypercholesterolemia (FH), a genetic condition, results in lifelong increased low-density lipoprotein cholesterol (LDL-C) and increases lifetime cardiovascular disease (CVD) risk. Most individuals with FH remain undiagnosed, so early FH identification and treatment could lower CVD burden.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the projected cost-effectiveness of population sequential FH screening (lipid testing followed by genetic testing after a high LDL-C measurement) at 10 or 18 years of age.<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n The CVD Policy Model, a validated discrete event simulation of CVD risk factor management and CVD outcomes in National Health and Nutrition Examination Survey participants, was used to simulate lifetime health and economic outcomes from a health care sector perspective for a hypothetical cohort of 4.2 million US 10-year-olds. Individual characteristics and health care processes informed CVD events (coronary heart disease or stroke) and survival probabilities. Model inputs included national data sources, clinical trials, pooled longitudinal cohort studies, and published literature.<\/jats:p>\n <\/jats:sec>\n \n Interventions<\/jats:title>\n Usual care assumed only opportunistic lipid testing and LDL-C and CVD risk-guided treatment. When added to usual care, sequential FH screening strategies examined combinations of childhood (age 10 years) or early adulthood (age 18 years) screening with 3 LDL-C thresholds (\u2265130 mg\/dL, \u2265160 mg\/dL, or \u2265190 mg\/dL) to select patients for genetic testing.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n Primary outcomes were direct health care costs (2021 US dollars), quality-adjusted life-years (QALYs), and an incremental cost-effectiveness ratio (ICER). Future costs and QALYs were discounted 3% annually. Strategies with an ICER of less than $100\u202f000 per QALY gained were considered cost-effective.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n For the simulated cohort, usual care would lead to 3\u202f118\u202f000 (95% uncertainty interval, 3\u202f061\u202f000-3\u202f192\u202f000) total lifetime CVD events, with 16\u202f182 (95% uncertainty interval, 15\u202f683-16\u202f827) among those with FH. Childhood FH screening could avert between 1385 and 1820 CVD events (&amp;lt;0.1% reduction in overall population), and early adulthood FH screening could avert between 1154 and 1448 CVD events (&amp;lt;0.1% reduction). While effective, no FH screening strategies were cost-effective relative to usual care; screening at age 18 years using an LDL-C threshold of 190 mg\/dL or greater had the lowest ICER, at $289\u202f700 per QALY gained. Sequential FH screening could become cost-effective vs usual care if lifetime lipid monitoring plus lifestyle therapy increased after a high screening LDL-C result, including for patients with non-FH dyslipidemias.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n Sequential FH screening in childhood or early adulthood could be effective but not cost-effective vs usual care. However, sequential FH screening could become cost-effective under highly optimistic assumptions about increased lifestyle therapy and increased lifetime lipid monitoring for patients with non-FH dyslipidemias.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jama.2025.20648","type":"journal-article","created":{"date-parts":[[2025,11,9]],"date-time":"2025-11-09T22:30:23Z","timestamp":1762727423000},"page":"140","source":"Crossref","is-referenced-by-count":11,"title":["Familial Hypercholesterolemia Screening in Childhood and Early Adulthood"],"prefix":"10.1001","volume":"335","author":[{"given":"Brandon K.","family":"Bellows","sequence":"first","affiliation":[{"name":"Division of General Medicine, Columbia University Irving Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of General Medicine, Columbia University Irving Medical Center, New York, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Ruiz-Negr\u00f3n","sequence":"additional","affiliation":[{"name":"NDB Consulting Services LLC, St Cloud, Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhruv S.","family":"Kazi","sequence":"additional","affiliation":[{"name":"Richard A. and Susan F. 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