TY - JOUR
T1 - Genetic testing increases the likelihood of a diagnosis of familial hypercholesterolaemia among people referred to lipid clinics
T2 - Danish national study
AU - Hedegaard, Berit Storgaard
AU - Bork, Christian Sørensen
AU - Kanstrup, Helle Lynge
AU - Thomsen, Kristian Korsgaard
AU - Heitmann, Merete
AU - Bang, Lia Evi
AU - Henriksen, Finn Lund
AU - Andersen, Lars Juel
AU - Gohr, Thomas
AU - Mouridsen, Mette Rauhe
AU - Soja, Anne Merete Boas
AU - Elpert, Frank Peter
AU - Jakobsen, Tomas Joen
AU - Sjøl, Anette
AU - Joensen, Albert Marni
AU - Nordestgaard, Børge Grønne
AU - Klausen, Ib Christian
AU - Schmidt, Erik Berg
N1 - Funding Information:
This project was supported by NOVARTIS A/S.
Publisher Copyright:
© 2023 The Authors
PY - 2023/5
Y1 - 2023/5
N2 - Background and aims: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. Methods: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. Results: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. Conclusions: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.
AB - Background and aims: It is unclear to what extent genetic testing improves the ability to diagnose familial hypercholesterolaemia (FH). We investigated the percentage with FH among individuals referred to Danish lipid clinics, and evaluated the impact of genetic testing for a diagnosis of FH. Methods: From September 2020 through November 2021, all patients referred for possible FH to one of the 15 Danish lipid clinics were invited for study participation and >97% (n = 1488) accepted. The Dutch Lipid Clinical Network criteria were used to diagnose clinical FH. The decision of genetic testing for FH was based on local practice. Results: A total of 1243 individuals were referred, of whom 25.9% were diagnosed with genetic and/or clinical FH. In individuals genetically tested (n = 705), 21.7% had probable or definite clinical FH before testing, a percentage that increased to 36.9% after genetic testing. In individuals with unlikely and possible FH before genetic testing, 24.4% and 19.0%, respectively, had a causative pathogenic variant. Conclusions: In a Danish nationwide study, genetic testing increased a diagnosis of FH from 22% to 37% in patients referred with hypercholesterolaemia suspected of having FH. Importantly, approximately 20% with unlikely or possible FH, who without genetic testing would not have been considered having FH (and family screening would not have been undertaken), had a pathogenic FH variant. We therefore recommend a more widespread use of genetic testing for evaluation of a possible FH diagnosis and potential cascade screening.
KW - Cardiovascular disease
KW - Familial hypercholesterolaemia
KW - Genetic testing
KW - LDL cholesterol
KW - Lipid clinics
KW - Referral criteria
U2 - 10.1016/j.atherosclerosis.2023.04.003
DO - 10.1016/j.atherosclerosis.2023.04.003
M3 - Journal article
C2 - 37080006
AN - SCOPUS:85152707351
VL - 373
SP - 10
EP - 16
JO - Journal of atherosclerosis research
JF - Journal of atherosclerosis research
SN - 1567-5688
ER -