In:
European Journal of Preventive Cardiology, Oxford University Press (OUP), Vol. 29, No. 16 ( 2022-11-15), p. 2125-2131
Abstract:
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 & lt; 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.
Type of Medium:
Online Resource
ISSN:
2047-4873
,
2047-4881
DOI:
10.1093/eurjpc/zwac188
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2022
detail.hit.zdb_id:
2646239-4
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