{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T09:18:08Z","timestamp":1788427088728,"version":"build-2803163510"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"16","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001674","name":"Fondation Leducq","doi-asserted-by":"crossref","award":["13CVD03"],"award-info":[{"award-number":["13CVD03"]}],"id":[{"id":"10.13039\/501100001674","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"crossref","award":["16-RHUS-0007"],"award-info":[{"award-number":["16-RHUS-0007"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>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).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>This was a multinational prospective cohort study, which included patients with heterozygous FH aged 18\u201365 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\u2005mmoL\/L, P &amp;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\u20133.05), P = 0.0001.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Carriers of a null mutation have an independent \u223c2-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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwac188","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T07:18:55Z","timestamp":1662016735000},"page":"2125-2131","source":"Crossref","is-referenced-by-count":15,"title":["Effect of the LDL receptor mutation type on incident major adverse cardiovascular events in familial hypercholesterolaemia"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7555-1275","authenticated-orcid":false,"given":"Martine","family":"Paquette","sequence":"first","affiliation":[{"name":"Lipids, Nutrition, and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute , 110 avenue des Pins Ouest, Montreal, QC H2W 1R7 , 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Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Cariou","sequence":"additional","affiliation":[{"name":"Nantes Universit\u00e9, CHU Nantes, CNRS, Inserm, l\u2019institut du thorax , 8 Quai Moncousu, F-44000 Nantes , France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2861-5325","authenticated-orcid":false,"given":"Robert A","family":"Hegele","sequence":"additional","affiliation":[{"name":"Department of Medicine, Schulich School of Medicine and Dentistry, Western University , 1151 Richmond St, London, ON N6A 5C1 , Canada"},{"name":"Robarts Research Institute, Western University , 100 Perth Dr, London, ON N6A 5K8 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2248-9663","authenticated-orcid":false,"given":"Jacques","family":"Genest","sequence":"additional","affiliation":[{"name":"Research Institute of the McGill University Health Centre , 1001 Decarie Blvd, Montreal, QC H4A 3J1 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8447-2897","authenticated-orcid":false,"given":"Mark","family":"Trinder","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, University of British Columbia, Centre for Heart and Lung Innovation, University of British Columbia , 1081 Burrard St Room 166, Vancouver, BC V6Z 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam R","family":"Brunham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, University of British Columbia, Centre for Heart and Lung Innovation, University of British Columbia , 1081 Burrard St Room 166, Vancouver, BC V6Z 1Y6 , Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"B\u00e9liard","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Metabolic 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