APA
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Kafol, J., Miranda, B., Sikonja, R., Šikonja, J., Wiegman, A., Medeiros, A., … Grošelj, U. (2025). Proposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS). European Journal of Preventive Cardiology. https://doi.org/10.1093/eurjpc/zwaf352
Chicago/Turabian
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Kafol, Jan, Beatriz Miranda, Rok Sikonja, J. Šikonja, A. Wiegman, A. Medeiros, A. Alves, et al. “Proposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS).” European Journal of Preventive Cardiology (2025).
MLA
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Kafol, Jan, et al. “Proposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS).” European Journal of Preventive Cardiology, 2025, doi:10.1093/eurjpc/zwaf352.
BibTeX Click to copy
@article{jan2025a,
title = {Proposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS).},
year = {2025},
journal = {European Journal of Preventive Cardiology},
doi = {10.1093/eurjpc/zwaf352},
author = {Kafol, Jan and Miranda, Beatriz and Sikonja, Rok and Šikonja, J. and Wiegman, A. and Medeiros, A. and Alves, A. and Freiberger, Tomáš and Hutten, B. A. and Mlinarič, M. and Battelino, T. and Humphries, Steve E and Bourbon, M. and Grošelj, U.}
}
BACKGROUND AND AIMS Familial hypercholesterolemia (FH) significantly increases cardiovascular risk from childhood yet remains widely underdiagnosed. This cross-sectional study aimed to evaluate existing pediatric FH diagnostic criteria in real-world cohorts and to develop two novel diagnostic tools: a semi-quantitative scoring system (FH-PeDS) and a machine learning model (ML-FH-PeDS) to enhance early FH detection.
METHODS Five established FH diagnostic criteria were assesed (Dutch Lipid Clinics Network [DLCN], Simon Broome, EAS, Simplified Canadian, and Japanese Atherosclerosis Society) in Slovenian (N=1,360) and Portuguese (N=340) pediatric hypercholesterolemia cohorts, using FH-causing variants as the reference standard. FH-PeDS was developed from the Slovenian cohort, and ML-FH-PeDS was trained and tested using a 60%/40% split before external validation in the Portuguese cohort.
RESULTS Only 47.4% of genetically confirmed FH cases were identified by all established criteria, while 10.9% were missed entirely. FH-PeDS outperformed DLCN in the combined cohort (AUC 0.897 vs. 0.857; p<0.01). ML-FH-PeDS showed superior predictive power (AUC 0.932 in training, 0.904 in testing vs. 0.852 for DLCN; p<0.01) and performed best as a confirmatory test in the testing subgroup (39.7% sensitivity, 87.7% PPV at 98% specificity). In the Portuguese cohort, ML-FH-PeDS maintained strong predictive performance (AUC 0.867 vs. 0.815 for DLCN; p<0.01) despite population differences.
CONCLUSIONS Current FH diagnostic criteria perform suboptimally in children. FH-PeDS and ML-FH-PeDS provide tools to improve FH detection, particularly where genetic testing is limited. They also help guide genetic testing decisions for hypercholesterolemic children. By enabling earlier diagnosis and intervention, these tools may reduce long-term cardiovascular risk and improve outcomes.