Author, as appears in the article.: Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., Bruckert E., Hegele R.A., Krauss R.M., Raal F.J., Schunkert H., Watt G.F., Borén J., Fazio S., Horton J.D., Masana L., Nicholls S.J., Nordestgaard B.G., Van De Sluis B., Taskinen M.R., Tokgözo?lu L., Landmesser U., Laufs U., Wiklund O., Stock J.K., Chapman M.J., Catapano A.L.
Department: Medicina i Cirurgia
URV's Author/s: Masana Marín, Luis
Keywords: Statin therapy Statin Risk Retention Recommendations Pcsk9 Mendelian randomization Low-density lipoprotein Ldl cholesterol General-population Familial hypercholesterolemia Ezetimibe Coronary-heart-disease Clinical trials Causality Cardiovascular disease Atherosclerosis Association recommendations pcsk9 mendelian randomization low-density lipoprotein ezetimibe clinical trials causality cardiovascular disease atherosclerosis
Abstract: To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD).We assessed whether the association between LDL and ASCVD fulfils the criteria for causality by evaluating the totality of evidence from genetic studies, prospective epidemiologic cohort studies, Mendelian randomization studies, and randomized trials of LDL-lowering therapies. In clinical studies, plasma LDL burden is usually estimated by determination of plasma LDL cholesterol level (LDL-C). Rare genetic mutations that cause reduced LDL receptor function lead to markedly higher LDL-C and a dose-dependent increase in the risk of ASCVD, whereas rare variants leading to lower LDL-C are associated with a correspondingly lower risk of ASCVD. Separate meta-analyses of over 200 prospective cohort studies, Mendelian randomization studies, and randomized trials including more than 2 million participants with over 20 million person-years of follow-up and over 150?000 cardiovascular events demonstrate a remarkably consistent dose-dependent log-linear association between the absolute magnitude of exposure of the vasculature to LDL-C and the risk of ASCVD; and this effect appears to increase with increasing duration of exposure to LDL-C. Both the naturally randomized genetic studies and the randomized intervention trials consistently demonstrate that any mechanism of lowering plasma LDL particle concentration should reduce the risk of ASCVD events proportional to the absolute reduction in LDL-C and the cumulative duration of exposure to lower LDL-C, provided that the achieved reduction in LDL-C is concordant with the reduction in LDL particle number and that there are no competing deleterious off-target effects.Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.© The Author 2017. Published on behalf of the European Society of Cardiology
Thematic Areas: Saúde coletiva Nutrição Medicina iii Medicina ii Medicina i Interdisciplinar General medicine Farmacia Educação física Direito Ciências biológicas ii Ciências biológicas i Cardiology and cardiovascular medicine Cardiac & cardiovascular systems
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 15229645
Author's mail: luis.masana@urv.cat
Author identifier: 0000-0002-0789-4954
Record's date: 2024-09-07
Papper version: info:eu-repo/semantics/publishedVersion
Link to the original source: https://academic.oup.com/eurheartj/article/38/32/2459/3745109
Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
Papper original source: European Heart Journal. 38 (32): 2459-2472
APA: Ference B.A., Ginsberg H.N., Graham I., Ray K.K., Packard C.J., Bruckert E., Hegele R.A., Krauss R.M., Raal F.J., Schunkert H., Watt G.F., Borén J., F (2017). Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel.. European Heart Journal, 38(32), 2459-2472. DOI: 10.1093/eurheartj/ehx144
Article's DOI: 10.1093/eurheartj/ehx144
Entity: Universitat Rovira i Virgili
Journal publication year: 2017
Publication Type: Journal Publications
Repositori URV