AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
A 10-Year Evaluation of a Lean National Cascade Screening Program for Familial Hypercholesterolemia
By Weijs B, Boor D, Corpeleijn W et al.
Background and Aims: Familial hypercholesterolemia (FH) is a prevalent genetic disorder (~1 in 300) causing lifelong elevated LDL-cholesterol and premature cardiovascular disease, yet it remains widely underdiagnosed. After the well-funded Dutch national FH screening program ended in 2013, screening continued under the LEEFH foundation with ~80% less funding (є350k vs є1.5M annually) and a reduced scale comprising 3 versus 14 FTE. We evaluated the first 10 years of this lean model to assess its effectiveness as a framework for global FH screening. Methods: In this repeated cross-sectional study, we analysed retrospective data from the Dutch FH cascade screening program (LEEFH, 2014-2024). Outcomes included the number of tested individuals, diagnostic yield, identified relatives per index patient, the genetic spectrum of variants, and referral patterns over time. Geographic coverage was assessed by mapping testing data to 90 regions and comparing detected cases with FH prevalence estimated at 1:300. Results: Between 2014 and 2024, 31,487 individuals underwent genetic testing, with annual testing rising from 1,416 to 4,356. Of 22,681 potential index patients, 3,029 (13.4%) carried a pathogenic variant. Referrals by general practitioners more than doubled (12.1% to 26.9%), whereas yield among indexes declined from >13% to 10.0%, coinciding with progressively broader testing of lower-probability individuals. Out of 8,447 relatives tested, 4,312 (51.0%) were FH-positive, consistent with autosomal dominant inheritance. Pathogenic variants occurred in LDLR (n=5,725; 78.0%), APOB (n=1,394; 19.0%), PCSK9 (n=208; 2.8%), and LDLRAP1 (n=7; 0.1%). Notably, cascade screening efficiency more than doubled in 10 years, rising from 0.69 to 1.78 FH-positive relatives identified per index. Among FH-positive relatives, 45.2% were <18 years and 13.3% <8 years, and the proportion diagnosed before age 18 grew from 41.4% to 48.1%. Geographic reach broadened as the hospital network expanded from 4 to 39 centers; municipalities reaching ≥50% diagnostic coverage increased from 31 (34.4%) to 59 (65.5%) of 90 regions, while those below 25% fell from 11 to 1. Cumulatively, identified FH patients rose from 28,274 in 2014 to 35,612 in 2024, approximately 60% of the estimated national FH population. Conclusion: Despite an 80% funding cut and only a three-FTE team, the LEEFH program sustained national FH detection, improved cascade efficiency, broadened geographic coverage, and increasingly identified children with FH. These results offer a practical, low-resource model for FH screening efforts worldwide.