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Effect of the LDL receptor mutation type on incident major adverse cardiovascular events in familial hypercholesterolaemia

Paquette, Martine, Carrié, Alain, Bernard, Sophie, Cariou, Bertrand, Hegele, Robert A, Genest, Jacques, Trinder, Mark, Brunham, Liam R, Béliard, Sophie, Baass, Alexis·2022·European Journal of Preventive Cardiology
DOI 10.1093/eurjpc/zwac188
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Abstract

Aims: Patients with familial hypercholesterolaemia (FH) are at increased risk of cardiovascular disease (CVD) due to extremely high circulating LDL cholesterol (LDL-C) concentrations. Our objective was to study the effect of the type of LDL receptor (LDLR) mutation on the incidence of major adverse cardiovascular events (MACEs). Methods and results: This was a multinational prospective cohort study, which included patients with heterozygous FH aged 18–65 years, without a prior history of CVD, and carrying a pathogenic or likely pathogenic variant in the LDLR gene. A total of 2131 patients (20 535person-years of follow-up) were included in the study, including 1234 subjects carrying a defective mutation in the LDLR and 897 subjects carrying a null mutation. During the follow-up, a first MACE occurred in 79 cases (6%) in the defective group and in 111 cases (12%) in the null group. The mean baseline LDL-C concentration was 17% higher in the null group than in the defective group (7.90 vs. 6.73 mmoL/L, P < 0.0001). In a Cox regression model corrected for traditional cardiovascular risk factors, the presence of a null mutation was associated with a hazard ratio of 2.09 (1.44–3.05), P = 0.0001. Conclusion: Carriers of a null mutation have an independent ∼2-fold increased risk of incident MACE compared with patients carrying a defective mutation. This study highlights the importance of genetic screening in FH in order to improve patient care.

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Metadata

Authors
Paquette, M., Carrié, A., Bernard, S., Cariou, B., Hegele, R. A., Genest, J., Trinder, M., Brunham, L. R., Béliard, S., & Baass, A.
Venue
European Journal of Preventive Cardiology
Publisher
Oxford University Press (OUP)
Published
2022-09-01
Volume
29
Issue
16
Pages
2125-2131
ISSN
  • 2047-4873
  • 2047-4881
DOI
10.1093/eurjpc/zwac188
Cited by
15
References
0
Language
en
Licence
academic.oup.com/pages/standard-publication-reuse-rights (vor)
Funders
  • Fondation Leducq (13CVD03)
  • Agence Nationale de la Recherche (16-RHUS-0007)

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