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

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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 , Watts , G F , Boren , J , Fazio , S , Horton , J D , Masana , L , Nicholls , S J , Nordestgaard , B G , van de Sluis , B , Taskinen , M-R , Tokgözoglu , L , Landmesser , U , Laufs , U , Wiklund , O , Stock , J K , Chapman , M J & Catapano , A L 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 , vol. 38 , no. 32 , pp. 2459-2472 . https://doi.org/10.1093/eurheartj/ehx144

Title: 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
Author: Ference, Brian A.; Ginsberg, Henry N.; Graham, Ian; Ray, Kausik K.; Packard, Chris J.; Bruckert, Eric; Hegele, Robert A.; Krauss, Ronald M.; Raal, Frederick J.; Schunkert, Heribert; Watts, Gerald F.; Boren, Jan; Fazio, Sergio; Horton, Jay D.; Masana, Luis; Nicholls, Stephen J.; Nordestgaard, Borge G.; van de Sluis, Bart; Taskinen, Marja-Riitta; Tokgözoglu, Lale; Landmesser, Ulf; Laufs, Ulrich; Wiklund, Olov; Stock, Jane K.; Chapman, M. John; Catapano, Alberico L.
Contributor: University of Helsinki, Research Programs Unit
Date: 2017-08-21
Language: eng
Number of pages: 14
Belongs to series: European Heart Journal
ISSN: 0195-668X
URI: http://hdl.handle.net/10138/224265
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.
Subject: Atherosclerosis
Cardiovascular disease
Low-density lipoprotein
Mendelian randomization
Clinical trials
Statin
Ezetimibe
PCSK9
Causality
Recommendations
CORONARY-HEART-DISEASE
HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA
CHOLESTEROL-FED RABBITS
STATIN THERAPY
MENDELIAN RANDOMIZATION
LDL CHOLESTEROL
GENERAL-POPULATION
RISK
METAANALYSIS
TRIAL
3121 General medicine, internal medicine and other clinical medicine
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