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Lancet. 2019 Dec 14;394(10215):2173-2183. doi: 10.1016/S0140-6736(19)32519-X. Epub 2019 Dec 3.

Application of non-HDL cholesterol for population-based cardiovascular risk stratification: results from the Multinational Cardiovascular Risk Consortium.

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University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany.
National Institute for Health and Welfare, Helsinki, Finland.
Centre for Public Health, Queens University of Belfast, Belfast, UK.
Catalan Department of Health, Barcelona, Spain.
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Department of Cardiovascular, Endocrine-metabolic Diseases, and Ageing, National Institutes of Health-ISS, Rome, Italy.
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy.
Cardiovascular Epidemiology Unit, Institute of Cardiovascular Research, University of Dundee, Dundee, UK.
Department of Epidemiology and Public health, University Hospital of Strasbourg, Strasbourg, France.
Department of Epidemiology and Prevention, IRCCS Neuromed, Pozzilli, Italy; Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Research Center in Epidemiology and Preventive Medicine, Department of Medicine and Surgery, University of Insubria, Varese, Italy.
Clinica Medica, Department of Medicine and Surgery, University of Milano Bicocca, Milan, Italy.
Department of Clinical Medicine, University of Tromsø-The Arctic University of Tromsø, Tromsø, Norway; Department of Neurology and Neurophysiology, University Hospital of North Norway, Tromsø, Norway.
Department of Public Health and Clinical Medicine, and Heart Center, Cardiology, Umeå University, Umeå, Sweden.
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Risk Factors and Molecular Determinants of Aging Diseases, University of Lille, Lille, France; Inserm, Lille, France; Centre Hospitalier Universitaire de Lille, Lille, France; Institut Pasteur de Lille, Lille, France.
Toulouse University School of Medicine, Toulouse, France.
Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Research Institute of Internal and Preventive Medicine, Branch of Federal Research Center, Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, Novosibirsk, Russia.
Department of Epidemiology, Cardiovascular Disease Prevention and Health Promotion, National Institute of Cardiology, Warsaw, Poland.
Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany.
Department of Cardiology, Charité Berlin-University Medicine, Campus Benjamin Franklin, Berlin, Germany; German Centre for Cardiovascular Research, Partner Site Berlin, Berlin, Germany.
Baker Heart and Diabetes Institute, Melbourne, VIC, Australia.
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
University of New South Wales, Sydney, NSW, Australia; St Vincent's Hospital, Sydney, NSW, Australia.
Department of Epidemiology, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, Netherlands.
Boston University and the National Heart, Lung, and Blood Institute's Framingham Study, Framingham, MA, USA.
Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Department of Primary Care and Population Health, University College London, London, UK.
Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism, Uppsala University, Uppsala, Sweden.
Departments of Medicine and Epidemiology, Columbia University, New York, NY, USA.
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Cardiology, Division of Medicine, Akershus University Hospital, Lørenskog, Norway; Center for Heart Failure Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Department of Cardiology, Charité Berlin-University Medicine, Campus Benjamin Franklin, Berlin, Germany; German Centre for Cardiovascular Research, Partner Site Berlin, Berlin, Germany; Berlin Institute of Health, Berlin, Germany.
University Heart & Vascular Center Hamburg, Department of Cardiology, Hamburg, Germany; German Center for Cardiovascular Research, Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany. Electronic address:

Erratum in



The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.


In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol.


Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7-59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0-20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol <2·6 mmol/L to 33·7% for ≥5·7 mmol/L in women and from 12·8% to 43·6% in men; p<0·0001). Multivariable adjusted Cox models with non-HDL cholesterol lower than 2·6 mmol/L as reference showed an increase in the association between non-HDL cholesterol concentration and cardiovascular disease for both sexes (from hazard ratio 1·1, 95% CI 1·0-1·3 for non-HDL cholesterol 2·6 to <3·7 mmol/L to 1·9, 1·6-2·2 for ≥5·7 mmol/L in women and from 1·1, 1·0-1·3 to 2·3, 2·0-2·5 in men). The derived tool allowed the estimation of cardiovascular disease event probabilities specific for non-HDL cholesterol with high comparability between the derivation and validation cohorts as reflected by smooth calibration curves analyses and a root mean square error lower than 1% for the estimated probabilities of cardiovascular disease. A 50% reduction of non-HDL cholesterol concentrations was associated with reduced risk of a cardiovascular disease event by the age of 75 years, and this risk reduction was greater the earlier cholesterol concentrations were reduced.


Non-HDL cholesterol concentrations in blood are strongly associated with long-term risk of atherosclerotic cardiovascular disease. We provide a simple tool for individual long-term risk assessment and the potential benefit of early lipid-lowering intervention. These data could be useful for physician-patient communication about primary prevention strategies.


EU Framework Programme, UK Medical Research Council, and German Centre for Cardiovascular Research.

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