Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies
Angela M Wood, Stephen Kaptoge(University of Cambridge), Adam S Butterworth(University of Cambridge), Peter Willeit, Samantha Warnakula(University of Cambridge), Thomas Bolton(University of Cambridge), Ellie Paige(Australian National University), Dirk S Paul(University of Cambridge), Michael Sweeting(University of Cambridge), Stephen Burgess, Steven Bell(University of Cambridge), William Astle(University of Cambridge), David Stevens(University of Cambridge), Albert Koulman(University of Cambridge), Randi M Selmer(Norwegian Institute of Public Health), W M Monique Verschuren, Shinichi Sato(Chiba Prefectural Institute of Public Health), Inger Njølstad(UiT The Arctic University of Norway), Mark Woodward, Veikko Salomaa(Finnish Institute for Health and Welfare), Børge G Nordestgaard, Bu B Yeap, Astrid Fletcher(London School of Hygiene & Tropical Medicine), Olle Melander(Lund University), Lewis H Kuller(University of Pittsburgh), Beverley Balkau(Inserm), Michael Marmot(University College London), Wolfgang Koenig, Edoardo Casiglia(University of Padua), Cyrus Cooper(MRC Lifecourse Epidemiology Unit), Volker Arndt(Heidelberg University), Oscar H Franco(Erasmus MC), Patrik Wennberg(Umeå University), John Gallacher(Cardiff University), Agustín Gómez de la Cámara(Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública), Henry Völzke(Universitätsmedizin Greifswald), Christina C Dahm(Aarhus University), Caroline E Dale(Farr Institute), Manuela M Bergmann, Carlos J Crespo(Portland State University), Yvonne T van der Schouw(University Medical Center Utrecht), Rudolf Kaaks(German Cancer Research Center), Leon A Simons(UNSW Sydney), Pagona Lagiou, Josje D Schoufour(Erasmus MC), Jolanda M A Boer(National Institute for Public Health and the Environment), Timothy J Key(University of Oxford), Beatriz Rodriguez(University of Hawaii System), Conchi Moreno-Iribas, Karina W Davidson(Columbia University Irving Medical Center), James O Taylor(Neighborhood Health), Carlotta Sacerdote(Azienda Ospedaliera Citta' della Salute e della Scienza di Torino), Robert B Wallace(University of Iowa), J Ramon Quiros(Gobierno del Principado de Asturias), Rosario Tumino(Azienda Usl 8 Arezzo), Dan G Blazer(Duke University), Allan Linneberg(University of Copenhagen), Makoto Daimon(Yamagata University), Salvatore Panico(Federico II University Hospital), Barbara Howard(Tuskegee University), Guri Skeie(UiT The Arctic University of Norway), Timo Strandberg, Elisabete Weiderpass, Paul J Nietert(Medical University of South Carolina), Bruce M Psaty, Daan Kromhout, Elena Salamanca-Fernandez, Stefan Kiechl(Innsbruck Medical University), Harlan M Krumholz(Yale University), Sara Grioni(Fondazione IRCCS Istituto Nazionale dei Tumori), Domenico Palli(Piedmont Reference Center for Epidemiology and Cancer Prevention), José M Huerta, Jackie Price(University of Edinburgh), Johan Sundström(Uppsala University), Larraitz Arriola, Hisatomi Arima, Ruth C Travis(University of Oxford), Demosthenes B Panagiotakos(Harokopio University of Athens), Anna Karakatsani, Antonia Trichopoulou, Tilman Kühn(German Cancer Research Center), Diederick E Grobbee(University Medical Center Utrecht), Elizabeth Barrett-Connor(University of California, San Diego), Natasja van Schoor(EMGO Institute for Health and Care Research), Heiner Boeing, Kim Overvad, Jussi Kauhanen(University of Eastern Finland), Nick Wareham(University of Cambridge), Claudia Langenberg(Medical Research Council), Nita Forouhi(Medical Research Council), Maria Wennberg(Umeå University), Jean-Pierre Després(Université Laval), Mary Cushman(University of Vermont), Jackie A Cooper(University College London), Carlos J Rodriguez, Masaru Sakurai(Kanazawa Medical University), Jonathan E Shaw(Baker Heart and Diabetes Institute), Matthew Knuiman, Trudy Voortman(Erasmus MC), Christa Meisinger(Helmholtz Zentrum München), Anne Tjønneland(Danish Cancer Society), Hermann Brenner, Luigi Palmieri(Istituto Superiore di Sanità), Jean Dallongeville(Institut Pasteur de Lille), Eric J Brunner(University College London), Gerd Assmann(Homann-Stiftung), Maurizio Trevisan(City College of New York), Richard F Gillum(Howard University Hospital), Ian Ford(University of Glasgow), Naveed Sattar(University of Glasgow), Mariana Lazo(Johns Hopkins Medicine), Simon G Thompson(University of Cambridge), Pietro Ferrari(Centre International de Recherche sur le Cancer), David A Leon(London School of Hygiene & Tropical Medicine), George Davey Smith(University of Bristol), Richard Peto(University of Oxford), Rod Jackson(University of Auckland), Emily Banks(Australian National University), Emanuele Di Angelantonio(University of Cambridge), John Danesh, Angela M Wood, Stephen Kaptoge(University of Cambridge), Adam Butterworth(University of Cambridge), Peter Willeit, Samantha Warnakula(University of Cambridge), Thomas Bolton(University of Cambridge), Ellie Paige(Australian National University), Dirk S Paul(University of Cambridge), Michael Sweeting(University of Cambridge), Stephen Burgess, Steven Bell(University of Cambridge), William Astle(University of Cambridge), David Stevens(University of Cambridge), Albert Koulman(University of Cambridge), Randi M Selmer(Norwegian Institute of Public Health), Monique Verschuren, Shinichi Sato(Chiba Prefectural Institute of Public Health), Inger Njølstad(UiT The Arctic University of Norway), Mark Woodward, Salomaa Veikko, Børge G Nordestgaard, Bu B Yeap, Astrid Flecther, Olle Melander(Lund University), Lewis H Kuller(University of Pittsburgh), Beverley Balkau(Inserm), Michael Marmot(University College London), Wolfgang Koenig, Edoardo Casiglia(University of Padua), Cyrus Cooper(University of Southampton), Volker Arndt(German Cancer Research Center), Oscar H Franco(Erasmus MC), Patrik Wennberg(Umeå University), John Gallacher(Cardiff University), Agustín Gómez de la Cámara(Research Institute Hospital 12 de Octubre), Henry Völzke(Universitätsmedizin Greifswald), Christina C Dahm(Aarhus University), Caroline E Dale(University College London), Manuela Bergmann, Carlos Crespo(Portland State University), Yvonne T van der Schouw(University Medical Center Utrecht), Rudolf Kaaks(Heidelberg University), Leon A Simons(St Vincent's Clinic), Pagona Lagiou, Josje D Schoufour(Erasmus MC), Jolanda M.A Boer(National Institute for Public Health and the Environment), Timothy J Key(University of Oxford), Beatriz Rodriguez(University of Hawaii System), Conchi Moreno-Iribas, Karina W Davidson(Columbia University Irving Medical Center), James O Taylor(Neighborhood Health), Carlotta Sacerdote(Azienda Ospedaliera Citta' della Salute e della Scienza di Torino), Robert B Wallace(University of Iowa), J. Ramon Quiros(Gobierno del Principado de Asturias), Eric B Rimm, Rosario Tumino(Azienda Usl 8 Arezzo), Dan G Blazer III(Duke University), Allan Linneberg(University of Copenhagen), Makoto Daimon(Yamagata University), Salvatore Panico(Federico II University Hospital), Barbara Howard(Tuskegee University), Guri Skeie(UiT The Arctic University of Norway), Veikko Salomaa(Finnish Institute for Health and Welfare), Timo Strandberg, Elisabete Weiderpass, Paul J Nietert(Medical University of South Carolina), Bruce M Psaty, Daan Kromhout, Elena Salamanca-Fernandez, Stefan Kiechl(Innsbruck Medical University), Harlan M Krumholz(Yale University), Sara Grioni(Fondazione IRCCS Istituto Nazionale dei Tumori), Domenico Palli(Piedmont Reference Center for Epidemiology and Cancer Prevention), José M Huerta, Jackie Price(University of Edinburgh), Johan Sundström(Uppsala University), Larraitz Arriola, Hisatomi Arima, Ruth C Travis(University of Oxford), Demosthenes B Panagiotakos(Harokopio University of Athens), Anna Karakatsani, Antonia Trichopoulou, Tilman Kühn(Heidelberg University), Diederick E Grobbee(University Medical Center Utrecht), Elizabeth Barrett-Connor(University of California, San Diego), Natasja van Schoor(EMGO Institute for Health and Care Research), Heiner Boeing, Kim Overvad, Jussi Kauhanen(University of Eastern Finland), Nick Wareham(Medical Research Council), Claudia Langenberg(Medical Research Council), Nita Forouhi(University of Cambridge), Maria Wennberg(Umeå University), Jean-Pierre Després(Université Laval), Mary Cushman(University of Vermont), Jackie A Cooper(University College London), Carlos J Rodriguez, Masaru Sakurai(Kanazawa Medical University), Jonathan E Shaw(Baker Heart and Diabetes Institute), Matthew Knuiman, Trudy Voortman(Erasmus MC), Christa Meisinger(Helmholtz Zentrum München), Anne Tjønneland(Danish Cancer Society), Hermann Brenner, Luigi Palmieri(Istituto Superiore di Sanità), Jean-Pierre Dallongeville(Institut Pasteur de Lille), Eric J Brunner(University College London), Gerd Assmann(Homann-Stiftung), Maurizio Trevisan(City College of New York), Richard F Gillumn, Ian Ford Ford(University of Glasgow), Naveed Sattar(University of Glasgow), Mariana Lazo(Johns Hopkins University), Simon Thompson(University of Cambridge), Pietro Ferrari(Centre International de Recherche sur le Cancer), David A Leon(London School of Hygiene & Tropical Medicine), George Davey Smith(University of Bristol), Richard Peto(University of Oxford), Rod Jackson(University of Auckland), Emily Banks(Australian National University), Emanuele Di Angelantonio(University of Cambridge), John Danesh
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.