High-density lipoprotein characteristics and coronary artery disease: a Mendelian randomization study
Por:
Prats-Uribe A., Sayols-Baixeras S., Fernández-Sanlés A., Subirana I., Carreras-Torres R., Vilahur G., Civeira F., Marrugat J., Fitó M., Hernáez Á., Elosua R.
Publicada:
1 ene 2020
Resumen:
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 (ß = 0.27 [95%CI = 0.19; 0.35]), cholesterol levels in very large HDLs (ß = 0.29 [95%CI = 0.17; 0.40]), and triglyceride content in very large HDLs (ß = 0.14 [95%CI = 0.040; 0.25]) were directly associated with CAD risk, whereas the cholesterol content in medium-sized HDLs (ß = -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. © 2020 The Authors
Filiaciones:
Prats-Uribe A.:
Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Preventive Medicine and Public Health Unit, Parc de Salut Mar-Universitat Pompeu Fabra-ISGLOBAL, Barcelona, Spain
Centre for Statistics in Medicine, Botnar Research Centre, NDORMS, University of Oxford, Oxford, United Kingdom
Sayols-Baixeras S.:
Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Campus del Mar, Universitat Pompeu Fabra, Barcelona, Spain
Consorcio CIBER, M.P. Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Molecular Epidemiology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
Fernández-Sanlés A.:
Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Campus del Mar, Universitat Pompeu Fabra, Barcelona, Spain
MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, United Kingdom
Subirana I.:
Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Consorcio CIBER, M.P. Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain
Carreras-Torres R.:
Colorectal Cancer Group, ONCOBELL Program, Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Spain
Vilahur G.:
Consorcio CIBER, M.P. Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Cardiovascular Program-ICCC, Research Institute-Hospital de la Santa Creu i Sant Pau, IIB-Sant Pau, Barcelona, Spain
Civeira F.:
Consorcio CIBER, M.P. Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Lipid Unit, Hospital Universitario Miguel Servet, IIS Aragon, Zaragoza, Spain
Marrugat J.:
Consorcio CIBER, M.P. Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Girona Heart Registre Research Group (REGICOR), IMIM, Barcelona, Spain
Fitó M.:
Cardiovascular Risk and Nutrition Research Group, IMIM, Barcelona, Spain
Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
Hernáez Á.:
Cardiovascular Risk and Nutrition Research Group, IMIM, Barcelona, Spain
Consorcio CIBER, M.P. Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
Cardiovascular Risk, Nutrition, and Aging Research Unit, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Barcelona, Spain
Blanquerna School of Life Sciences, Universitat Ramon Llull, Barcelona, Spain
Elosua R.:
Cardiovascular Epidemiology and Genetics Research Group, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain
Consorcio CIBER, M.P. Enfermedades Cardiovasculares (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
Medicine Department, Faculty of Medicine, University of Vic-Central University of Catalonia (UVic-UCC), Vic, Spain
Green Submitted, Green Published, Green Accepted, All Open Access, Bronze, Green
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