Обзорная статья

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

Brian A. FerenceDivision of Translational Research and Clinical Epidemiology, Division of Cardiovascular Medicine, Wayne State University School of Medicine, Detroit, MI 48202, USAHenry N. GinsbergIrving Institute for Clinical and Translational Research, Columbia University, New York, NY, USAIan GrahamTrinity College Dublin, IrelandKausik K. RayDepartment of Primary Care and Public Health, Imperial Centre for Cardiovascular Disease Prevention, Imperial College, London, UKChris J. PackardCollege of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow, UKÉric BruckertINSERM UMRS1166, Department of Endocrinology-Metabolism, ICAN - Institute of CardioMetabolism and Nutrition, AP-HP, Hôpital de la Pitié, Paris, FranceRobert A. HegeleDepartment of Medicine, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, CanadaRonald M. KraussFrederick J. RaalFaculty of Health Sciences, University of Witwatersrand, Johannesburg, South AfricaHeribert SchunkertDeutsches Herzzentrum München, Technische Universität München, Munich 80636, GermanyGerald F. WattsLipid Disorders Clinic, Centre for Cardiovascular Medicine, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, AustraliaJan BorénDepartment of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, SwedenSergio FazioDepartment of Medicine, Center for Preventive Cardiology of the Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USAJay D. HortonDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USAL. MasanaResearch Unit of Lipids and Atherosclerosis, University Rovira i Virgili, C. Sant Llorenç 21, Reus 43201, SpainStephen J. NichollsSouth Australian Health and Medical Research Institute, University of Adelaide, Adelaide, AustraliaBørge G. NordestgaardDepartment of Clinical Biochemistry and The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, DenmarkBart van de SluisDepartment of Pediatrics, Molecular Genetics Section, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan 1, Groningen AV 9713, The NetherlandsMarja‐Riitta TaskinenHelsinki University Central Hospital and Research Programs’ Unit, Diabetes and Obesity, Heart and Lung Centre, University of Helsinki, Helsinki, FinlandLâle TokgözoğluHacettepe University, Ankara, TurkeyUlf LandmesserDepartment of Cardiology, Charité-Universitätsmedizin Berlin (CBF), Hindenburgdamm 30, Berlin 12203, GermanyUlrich LaufsKlinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Homburg, Saar, GermanyOlov WiklundDepartment of Cardiology, Sahlgrenska University Hospital, Gothenburg, SwedenJane K. StockEuropean Atherosclerosis Society, Gothenburg, SwedenM. John ChapmanINSERM, Dyslipidemia and Atherosclerosis Research, and University of Pierre and Marie Curie, Pitié-Sâlpetrière University Hospital, Paris, FranceAlberico L. CatapanoDepartment of Pharmacological and Biomolecular Sciences, University of Milan and IRCCS Multimedica, Milan, Italy

2017en

ABI

Аннотация

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.

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Идентификаторы

DOI: 10.1093/eurheartj/ehx144

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Цитирований: 4Использованных источников: 0

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