Repository logo
 
Publication

Proposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS)

2025-06-20Journal article Open access
Simple item page
datacite.subject.fosCiências Médicas
dc.contributor.authorKafol, Jan
dc.contributor.authorMiranda, Beatriz
dc.contributor.authorSikonja, Rok
dc.contributor.authorSikonja, Jaka
dc.contributor.authorWiegman, Albert
dc.contributor.authorMedeiros, Ana Margarida
dc.contributor.authorAlves, Ana Catarina
dc.contributor.authorFreiberger, Tomas
dc.contributor.authorHutten, Barbara A.
dc.contributor.authorMlinaric, Matej
dc.contributor.authorBattelino, Tadej
dc.contributor.authorHumphries, Steve E.
dc.contributor.authorBourbon, Mafalda
dc.contributor.authorGroselj, Urh
dc.date.accessioned2025-12-04T16:00:38Z
dc.date.available2025-12-04T16:00:38Z
dc.date.issued2025-06-20
dc.descriptionFH-PeDS Collaborators: Barbara Cugalj Kern, Jernej Kovač, Ana Drole Torkar, Maja Filipič, Mia Becker, Žiga Iztok Remec, Barbka Repič Lampret, Maruša Debeljak, Katarina Trebušak Podkrajšek, Zlatko Fras, Borut Jug, Fouzia Sadiq, António Guerra, Ana Gaspar, Henedina Antunes, Sílvia Sequeira, Susana Correia, Paula Garcia, Luísa Diogo Matos, Goreti Lobarinhas, Paula Martins, Guida Gama, Mónica Tavares, Eduard Ostarijas, Zala Jelinčič, Dimitar Trifunoski, Luka Pesjak
dc.description.abstractBackground 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.eng
dc.description.abstractLay Summary: - Familial hypercholesterolemia (FH) is a common inherited condition that causes high cholesterol from childhood and increases heart disease risk, but it is often missed early in life; - We developed two new tools—FH-PeDS and ML-FH-PeDS—that identify children with FH more accurately than current diagnostic scores; - These tools can help clinicians decide which children need genetic testing, especially in countries where such testing is limited.eng
dc.description.sponsorshipThis work was supported by the Slovenian Research and Innovation Agency (grants: P3-0343 and J3-2536). The Portuguese FH Study has been funded by Science and Technology Foundation and Portuguese Cardiology Society. B.M. acknowledges funding support from ‘la Caixa’ Foundation and Fundação para a Ciência e Tecnologia under the grant agreement LCF/PR/HP23/52330032. S.E.H. was supported by a grant from the British Heart Foundation (BHF grant PG 08/008) and received additional support from the National Institute for Health Research University College LondonHospitals Biomedical Research Centre. T.F. was supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (programme EXCELES, ID Project No. LX22NPO5104)—Funded by the European Union—Next Generation EU.
dc.identifier.citationEur J Prev Cardiol. 2025 Jun 20:zwaf352. doi: 10.1093/eurjpc/zwaf352. Online ahead of print.
dc.identifier.doi10.1093/eurjpc/zwaf352
dc.identifier.eissn2047-4881
dc.identifier.issn2047-4873
dc.identifier.pmid40578816
dc.identifier.urihttp://hdl.handle.net/10400.18/10639
dc.language.isoeng
dc.peerreviewedyes
dc.publisherOxford University Press
dc.relationLCF/ PR/HP23/523300
dc.relationLX22NPO5104
dc.relation.hasversionhttps://academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwaf352/8169832
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/
dc.subjectCardiovascular Disease
dc.subjectChildren
dc.subjectDetection
dc.subjectDiagnostic Criteria
dc.subjectFamilial Hypercholesterolemia
dc.subjectMachine Learning Model
dc.subjectDoenças Cardio e Cérebro-vasculares
dc.titleProposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS)eng
dc.typejournal article
dcterms.referenceshttps://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/eurjpc/PAP/10.1093_eurjpc_zwaf352/2/zwaf352_supplementary_data.docx?Expires=1767885732&Signature=Qi3u3H~OomSDPEn9k-KAc1wp0xDIDLZVlous5gmbMNcSbeKv-d1vCMzztZYO66yJtAgRR4JEl0Y-Yslt1RcMApzvDT2ftIDL3sGeYvwplfjAtP~pc4Zy98tNU-nEtnit5L2HOKkTE68ft3Nc5Ht0~Bh1FXS7eGRDzm0rkUb~LPB7z41h9I4SDKtUQttHBEuGOZI2A~NHPR-BIZFXoCNqoQk18RjQw7n~zKHKsHLIsjoNAx9v8ogYmtHOeikkJq2a6wcdEJOMwGwYPEuhw4HJ8PEiRjVf3pSnqMbc2lrqIxYxcaM1e8K~T7dKmX5Kqe096OLiCi4qgr7zzZ-WOR6riQ__&Key-Pair-Id=APKAIE5G5CRDK6RD3PGA
dspace.entity.typePublication
oaire.citation.startPagezwaf352
oaire.citation.titleEuropean Journal of Preventive Cardiology
oaire.versionhttp://purl.org/coar/version/c_970fb48d4fbd8a85

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
2025. Proposal of a Familial Hypercholesterolemia Pediatric Diagnostic Score (FH-PeDS).pdf
Size:
927.18 KB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
license.txt
Size:
4.03 KB
Format:
Item-specific license agreed upon to submission
Description:
Download

Collections

DPSPDNT - Artigos em revistas internacionais
INSA - Artigos em revistas internacionais