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

Year: 2017

Type: article

Abstract: AIMS: To appraise the clinical and genetic evidence that low-density lipoproteins (LDLs) cause atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: 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. CONCLUSION: Consistent evidence from numerous and multiple different types of clinical and genetic studies unequivocally establishes that LDL causes ASCVD.

Source: European Heart Journal

DOI: 10.1093/eurheartj/ehx144

Institutions: Wayne State University, Columbia University, Trinity College Dublin, Imperial College London, University of Glasgow, Inserm, Assistance Publique – Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Fondation pour l’innovation en Cadiométabolisme et Nutrition, Western University, Robarts Research Institute, University of the Witwatersrand, German Centre for Cardiovascular Research, Deutsches Herzzentrum München, Technical University of Munich, The University of Western Australia, Royal Perth Hospital, Sahlgrenska University Hospital, University of Gothenburg, Oregon Health & Science University, The University of Texas Southwestern Medical Center, Universitat Rovira i Virgili, South Australian Health and Medical Research Institute, The University of Adelaide, University of Copenhagen, Frederiksberg Hospital, Herlev Hospital, Copenhagen University Hospital, Gentofte Hospital, University Medical Center Groningen, University of Groningen, University of Helsinki, Helsinki University Hospital, Hacettepe University, Charité - Universitätsmedizin Berlin, Universitätsklinikum des Saarlandes, European Atherosclerosis Society, Université Pierre-et-Marie-Curie, University of Milan, MultiMedica

Language: English

Topic: Lipoproteins and Cardiovascular Health

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $5,922

OpenAlex ID: W2609543937