High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study

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• dc.contributor.author Prats Uribe, Albert
• dc.contributor.author Sayols Baixeras, Sergi, 1988-
• dc.contributor.author Fernández Sanlés, Alba, 1988-
• dc.contributor.author Subirana Cachinero, Isaac
• dc.contributor.author Carreras-Torres, Robert
• dc.contributor.author Vilahur, Gemma
• dc.contributor.author Civeira, Fernando
• dc.contributor.author Marrugat de la Iglesia, Jaume
• dc.contributor.author Fitó Colomer, Montserrat
• dc.contributor.author Hernáez, Álvaro
• dc.contributor.author Elosua Llanos, Roberto
• dc.date.accessioned 2022-03-01T08:30:17Z
• dc.date.available 2022-03-01T08:30:17Z
• dc.date.issued 2020
• dc.description.abstract Background: To assess whether genetically determined quantitative and qualitative HDL characteristics were independently associated with coronary artery disease (CAD). Methods: We designed a two-sample multivariate Mendelian randomization study with available genome-wide association summary data. We identified genetic variants associated with HDL cholesterol and apolipoprotein A-I levels, HDL size, particle levels, and lipid content to define our genetic instrumental variables in one sample (Kettunen et al. study, n = 24,925) and analyzed their association with CAD risk in a different study (CARDIoGRAMplusC4D, n = 184,305). We validated these results by defining our genetic variables in another database (METSIM, n = 8372) and studied their relationship with CAD in the CARDIoGRAMplusC4D dataset. To estimate the effect size of the associations of interest adjusted for other lipoprotein traits and minimize potential pleiotropy, we used the Multi-trait-based Conditional & Joint analysis. Results: Genetically determined HDL cholesterol and apolipoprotein A-I levels were not associated with CAD. HDL mean diameter (β = 0.27 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (β = 0.29 [95%CI = 0.17; 0.40]), and triglyceride content in very large HDLs (β = 0.14 [95%CI = 0.040; 0.25]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (β = -0.076 [95%CI = -0.10; -0.052]) was inversely related to this risk. These results were validated in the METSIM-CARDIoGRAMplusC4D data. Conclusions: Some qualitative HDL characteristics (related to size, particle distribution, and cholesterol and triglyceride content) are related to CAD risk while HDL cholesterol levels are not.
• dc.description.sponsorship This work was supported by the Instituto de Salud Carlos III– European Regional Development Fund [grant numbers CD17/00122, IFI14/00007, PI18/00017], the Medical Research Council [grant numbers MR/K501256/1, MR/N013468/1], the Spanish Ministry of Economy and Competitiveness [grant numbers BES-2014-069718, SAF2015-71653- R], the European Union's Horizon 2020 Research and Innovation Program [grant number 796216], and the Government of Catalonia through the Agency for Management of University and Research Grants [2017 SGR 222]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. CIBER Enfermedades Cardiovasculares (CIBERCV), Epidemiología y Salud Pública (CIBERESP), and Fisiopatología de la Obesidad y Nutrición (CIBEROBN) are initiatives of the Instituto de Salud Carlos III, Madrid, Spain, and financed by the European Regional Development Fund.
• dc.format.mimetype application/pdf
• dc.identifier.citation Prats-Uribe A, Sayols-Baixeras S, Fernández-Sanlés A, Subirana I, Carreras-Torres R, Vilahur G, et. Al. High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study. Metabolism. 2020 Nov; 112: 154351. DOI: 10.1016/j.metabol.2020.154351
• dc.identifier.doi http://dx.doi.org/10.1016/j.metabol.2020.154351
• dc.identifier.issn 0026-0495
• dc.identifier.uri http://hdl.handle.net/10230/52598
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/796216
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BES2014-069718
• dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-71653-R
• dc.rights © Elsevier http://dx.doi.org/10.1016/j.metabol.2020.154351
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword Coronary artery disease
• dc.subject.keyword HDL quality
• dc.subject.keyword High-density lipoprotein
• dc.subject.keyword Mendelian randomization
• dc.title High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion