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Lancet. 2018 Apr 14;391(10129):1513-1523. doi: 10.1016/S0140-6736(18)30134-X.

Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.

Wood AM1, Kaptoge S2, Butterworth AS2, Willeit P3, Warnakula S2, Bolton T2, Paige E4, Paul DS2, Sweeting M2, Burgess S5, Bell S2, Astle W2, Stevens D2, Koulman A6, Selmer RM7, Verschuren WMM8, Sato S9, Njølstad I10, Woodward M11, Salomaa V12, Nordestgaard BG13, Yeap BB14, Fletcher A15, Melander O16, Kuller LH17, Balkau B18, Marmot M19, Koenig W20, Casiglia E21, Cooper C22, Arndt V23, Franco OH24, Wennberg P25, Gallacher J26, de la Cámara AG27, Völzke H28, Dahm CC29, Dale CE30, Bergmann MM31, Crespo CJ32, van der Schouw YT33, Kaaks R23, Simons LA34, Lagiou P35, Schoufour JD24, Boer JMA36, Key TJ37, Rodriguez B38, Moreno-Iribas C39, Davidson KW40, Taylor JO41, Sacerdote C42, Wallace RB43, Quiros JR44, Tumino R45, Blazer DG 2nd46, Linneberg A47, Daimon M48, Panico S49, Howard B50, Skeie G51, Strandberg T52, Weiderpass E53, Nietert PJ54, Psaty BM55, Kromhout D56, Salamanca-Fernandez E57, Kiechl S58, Krumholz HM59, Grioni S60, Palli D61, Huerta JM62, Price J63, Sundström J64, Arriola L65, Arima H66, Travis RC37, Panagiotakos DB67, Karakatsani A68, Trichopoulou A68, Kühn T23, Grobbee DE33, Barrett-Connor E69, van Schoor N70, Boeing H31, Overvad K71, Kauhanen J72, Wareham N73, Langenberg C73, Forouhi N73, Wennberg M25, Després JP74, Cushman M75, Cooper JA19, Rodriguez CJ76, Sakurai M77, Shaw JE78, Knuiman M79, Voortman T24, Meisinger C80, Tjønneland A81, Brenner H82, Palmieri L83, Dallongeville J84, Brunner EJ19, Assmann G85, Trevisan M86, Gillum RF87, Ford I88, Sattar N88, Lazo M89, Thompson SG2, Ferrari P90, Leon DA15, Smith GD91, Peto R37, Jackson R92, Banks E4, Di Angelantonio E2, Danesh J93; Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group.

Author information

1
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Electronic address: amw79@medschl.cam.ac.uk.
2
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
3
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; Medical University Innsbruck, Innsbruck, Austria.
4
National Centre for Epidemiology and Population Health, Australian National University, Canberra, Australia.
5
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK; MRC Biostatistics Unit, Cambridge Institute of Public Health, University of Cambridge, Cambridge, UK.
6
NIHR BRC Nutritional Biomarker Laboratory, University of Cambridge, Cambridge, UK.
7
Norwegian Institute of Public Health, Oslo, Norway.
8
National Institute for Public Health and the Environment, Bilthoven, Netherlands; Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
9
Chiba Prefectural Institute of Public Health, Chiba, Japan.
10
Department of Community Medicine, University of Tromsø, Tromsø, Norway.
11
Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, UK; The George Institute for Global Health, University of Sydney, Sydney, NSW, Australia; Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
12
THL-National Institute for Health and Welfare, Helsinki, Finland.
13
Copenhagen University Hospital, Copenhagen, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
14
School of Medicine, University of Western Australia, Perth, WA, Australia; Fiona Stanley Hospital, Perth, WA, Australia; Harry Perkins Institute of Medical Research, Perth, WA, Australia.
15
London School of Hygiene & Tropical Medicine, London, UK.
16
Department of Clinical Sciences, Malmö, Lund University, Malmö, Sweden.
17
Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
18
CESP INSERM UMRS 1018, Villejuif Cedex, France.
19
Department of Epidemiology and Public Health, University College London, London, UK.
20
92 Deutsches Herzzentrum München, Technische Universität München, Munich, Germany, DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany; University of Ulm Medical Center, Ulm, Germany.
21
Department of Medicine, University of Padua, Padua, Italy.
22
MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK.
23
German Cancer Research Center (DKFZ), Heidelberg, Germany.
24
Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands.
25
Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
26
Department of Primary Care and Public Health, Cardiff University, Cardiff, UK.
27
12 de Octubre Research Institute, CIBERESP, Madrid, Spain.
28
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
29
Department of Public Health, Aarhus University, Aarhus, Denmark.
30
Farr Institute of Health Informatics Research, UCL Institute of Health Informatics, University College London, London, UK.
31
German Institute of Human Nutrition, Potsdam-Rehbrüke, Germany.
32
School of Community Health, Portland State University, Portland, OR, USA.
33
Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, Netherlands.
34
St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
35
Hellenic Health Foundation, Athens, Greece; National and Kapodistrian University of Athens, Athens, Greece; Harvard TH Chan School of Public Health, Boston, MA, USA.
36
National Institute for Public Health and the Environment, Bilthoven, Netherlands.
37
Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, UK.
38
Office of Public Health Studies, University of Hawaii, Honolulu, HI, USA.
39
Instituto de Salud Pública de Navarra, IdiSNA - Navarra Institute for Health Research, Pamplona, Spain; Red de Investigación en Servicios de Salud en Enfermedades Crónicas (REDISSEC), Pamplona, Spain.
40
Columbia University Irving Medical Center, New York, NY, USA.
41
East Boston Neighborhood Health Center, Boston, MA, USA.
42
Città della Salute e della Scienza di Torino Hospital, Turin, Italy.
43
College of Public Health, The University of Iowa, Iowa City, IA, USA.
44
Consejería de Sanidad del Principado de Asturias, Oviedo, Asturias, Spain.
45
Civic - M. Arezzo Hospital, ASP Ragusa, Italy.
46
Duke Divinity School, Duke University, Durham, NC, USA.
47
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
48
Global Center of Excellence Program Study Group, Yamagata University Faculty of Medicine, Yamagata, Japan.
49
Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy.
50
Department of Biology, Tuskegee University, AL, USA.
51
Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway.
52
University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Center for Life Course Health Research, University of Oulu, Oulu, Finland.
53
Department of Community Medicine, UiT The Arctic University of Norway, Tromsø, Norway; Cancer Registry of Norway, Institute of Population-Based Cancer Research, Oslo, Norway; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Genetic Epidemiology Group, Folkhälsan Research Center, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
54
Medical University of South Carolina, Charleston, SC, USA.
55
Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, WA, USA; Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
56
Department of Agrotechnology and Food Sciences, University of Wageningen, Wageningen, Netherlands; Faculty of Medical Sciences, University of Groningen, Groningen, Netherlands.
57
Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria ibs.GRANADA, Hospitales Universitarios de Granada/Universidad de Granada, Granada, Spain; CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
58
Medical University Innsbruck, Innsbruck, Austria.
59
School of Medicine, Yale University, New Haven, CT, USA.
60
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
61
Cancer Research and Prevention Institute (ISPO), Florence, Italy.
62
CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
63
Usher Institute, University of Edinburgh, Edinburgh, UK.
64
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
65
CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Instituto BIO-Donostia, Basque Government, San Sebastian, Spain.
66
The University of Sydney and Royal Prince Alfred Hospital, Sydney, NSW, Australia; Department of Preventive Medicine and Public Health, Kyushu University, Fukuoka, Japan.
67
School of Health Science and Education, Harokopio University, Athens, Greece.
68
Hellenic Health Foundation, Athens, Greece; National and Kapodistrian University of Athens, Athens, Greece.
69
Department of Family Medicine and Public Health, University of California, San Diego, CA, USA.
70
EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, Netherlands.
71
Department of Public Health, Aarhus University, Aarhus, Denmark; Aalborg University Hospital, Aalborg, Denmark.
72
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
73
Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK.
74
Department of Kinesiology, Laval University, Quebec City, QC, Canada.
75
Department of Medicine, University of Vermont, Burlington, VT, USA.
76
Wake Forest University School of Medicine, Winston-Salem, NC, USA; Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
77
Department of Social and Environmental Medicine, Kanazawa Medical University, Ishikawa, Japan.
78
Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
79
Busselton Population Medical Research Institute, Busselton, WA, Australia; School of Population and Global Health, The University of Western Australia, Perth, WA, Australia.
80
Helmholtz Zentrum München German Research Center for Environmental Health, Germany.
81
Danish Cancer Society Research Center, Copenhagen, Denmark.
82
German Cancer Research Center (DKFZ), Heidelberg, Germany; Division of Clinical Epidemiology and Aging Research, University of Heidelberg, Heidelberg, Germany.
83
Istituto Superiore di Sanità, Rome, Italy.
84
Institut Pasteur de Lille, Lille, France.
85
Assmann-Stiftung für Prävention, Münster, Germany.
86
The City College of New York, New York, NY, USA.
87
Howard University Hospital, Washington DC, USA.
88
Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
89
School of Medicine, Johns Hopkins University, Baltimore, MD, USA.
90
International Agency for Research on Cancer, Lyon, France.
91
MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
92
School of Population Health, The University of Auckland, Auckland, New Zealand.
93
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. Electronic address: jd292@medschl.cam.ac.uk.

Erratum in

Abstract

BACKGROUND:

Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.

METHODS:

We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies.

FINDINGS:

In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.

INTERPRETATION:

In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.

FUNDING:

UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

PMID:
29676281
PMCID:
PMC5899998
DOI:
10.1016/S0140-6736(18)30134-X
[Indexed for MEDLINE]
Free PMC Article

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