Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies - PubMed (original) (raw)

. 2018 Apr 14;391(10129):1513-1523.

doi: 10.1016/S0140-6736(18)30134-X.

Stephen Kaptoge 2, Adam S Butterworth 2, Peter Willeit 3, Samantha Warnakula 2, Thomas Bolton 2, Ellie Paige 4, Dirk S Paul 2, Michael Sweeting 2, Stephen Burgess 5, Steven Bell 2, William Astle 2, David Stevens 2, Albert Koulman 6, Randi M Selmer 7, W M Monique Verschuren 8, Shinichi Sato 9, Inger Njølstad 10, Mark Woodward 11, Veikko Salomaa 12, Børge G Nordestgaard 13, Bu B Yeap 14, Astrid Fletcher 15, Olle Melander 16, Lewis H Kuller 17, Beverley Balkau 18, Michael Marmot 19, Wolfgang Koenig 20, Edoardo Casiglia 21, Cyrus Cooper 22, Volker Arndt 23, Oscar H Franco 24, Patrik Wennberg 25, John Gallacher 26, Agustín Gómez de la Cámara 27, Henry Völzke 28, Christina C Dahm 29, Caroline E Dale 30, Manuela M Bergmann 31, Carlos J Crespo 32, Yvonne T van der Schouw 33, Rudolf Kaaks 23, Leon A Simons 34, Pagona Lagiou 35, Josje D Schoufour 24, Jolanda M A Boer 36, Timothy J Key 37, Beatriz Rodriguez 38, Conchi Moreno-Iribas 39, Karina W Davidson 40, James O Taylor 41, Carlotta Sacerdote 42, Robert B Wallace 43, J Ramon Quiros 44, Rosario Tumino 45, Dan G Blazer 2nd 46, Allan Linneberg 47, Makoto Daimon 48, Salvatore Panico 49, Barbara Howard 50, Guri Skeie 51, Timo Strandberg 52, Elisabete Weiderpass 53, Paul J Nietert 54, Bruce M Psaty 55, Daan Kromhout 56, Elena Salamanca-Fernandez 57, Stefan Kiechl 58, Harlan M Krumholz 59, Sara Grioni 60, Domenico Palli 61, José M Huerta 62, Jackie Price 63, Johan Sundström 64, Larraitz Arriola 65, Hisatomi Arima 66, Ruth C Travis 37, Demosthenes B Panagiotakos 67, Anna Karakatsani 68, Antonia Trichopoulou 68, Tilman Kühn 23, Diederick E Grobbee 33, Elizabeth Barrett-Connor 69, Natasja van Schoor 70, Heiner Boeing 31, Kim Overvad 71, Jussi Kauhanen 72, Nick Wareham 73, Claudia Langenberg 73, Nita Forouhi 73, Maria Wennberg 25, Jean-Pierre Després 74, Mary Cushman 75, Jackie A Cooper 19, Carlos J Rodriguez 76, Masaru Sakurai 77, Jonathan E Shaw 78, Matthew Knuiman 79, Trudy Voortman 24, Christa Meisinger 80, Anne Tjønneland 81, Hermann Brenner 82, Luigi Palmieri 83, Jean Dallongeville 84, Eric J Brunner 19, Gerd Assmann 85, Maurizio Trevisan 86, Richard F Gillum 87, Ian Ford 88, Naveed Sattar 88, Mariana Lazo 89, Simon G Thompson 2, Pietro Ferrari 90, David A Leon 15, George Davey Smith 91, Richard Peto 37, Rod Jackson 92, Emily Banks 4, Emanuele Di Angelantonio 2, John Danesh 93; Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group

Collaborators, Affiliations

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

Angela M Wood et al. Lancet. 2018.

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.

Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Associations of usual alcohol consumption with all-cause mortality and the aggregate of cardiovascular disease in current drinkers Cardiovascular disease was defined as an aggregate of myocardial infarction, coronary heart disease, and stroke. Hazard ratios are adjusted for age, smoking, and history of diabetes, and stratified by sex and EPIC centre. The reference category is the lowest baseline alcohol consumption category (between 0 and 25 g/week). HRs are plotted against the mean usual alcohol consumption in each category. Sizes of the boxes are proportional to the inverse of the variance of the log-transformed hazard ratios. Vertical lines represent 95% CIs.

Figure 2

Figure 2

Associations of usual alcohol consumption with cardiovascular subtypes in alcohol drinkers Hazard ratios are adjusted for age, smoking, and history of diabetes, and stratified by sex and EPIC centre. The reference category is the lowest baseline alcohol consumption category (between 0 and 25g/week). Hazard ratios are plotted against the mean usual alcohol consumption in each category. Studies with fewer than five events of any outcome were excluded from the analysis of that outcome. Sizes of the boxes are proportional to the inverse of the variance of the log-transformed hazard ratios. Vertical lines represent 95% CIs. Deaths from other cardiovascular disease include the following outcomes: cardiac dysrhythmia, hypertensive disease, sudden death, and aortic aneurysm.

Figure 3

Figure 3

Hazard ratios for subtypes of cardiovascular outcomes in current drinkers, per 100 g per week higher usual alcohol consumption Hazard ratios are adjusted for age, smoking, and history of diabetes, and stratified by sex and centre. Studies with fewer than five events of any outcome were excluded from the analysis of that outcome.

Figure 4

Figure 4

Estimated future years of life lost by extent of reported baseline alcohol consumption compared with those who reported consuming >0–≤100 g per week The estimates of cumulative survival from 40 years of age onwards in the alcohol-drinking groups were calculated by applying hazard ratios (specific to age at risk) for all-cause mortality associated with categorised baseline alcohol consumption to US death rates at the age of 40 years or older. Mean usual levels of alcohol consumption within each baseline alcohol consumption category were 56, 123, 208 and 367 g per week, respectively, for the groups >0–≤100 g per week, >100–≤200 g per week, >200–≤350 g per week, and >350 g per week.

Comment in

References

    1. Department of Health Alcohol Guidelines Review: Report from the guidelines development group to the UK Chief Medical Officers. 2016. https://www.gov.uk/government/uploads/system/uploads/attachment_data/fil... (accessed Feb 5, 2018).
    1. Kalinowski A, Humphreys K. Governmental standard drink definitions and low-risk alcohol consumption guidelines in 37 countries. Addiction. 2016;111:1293–1298. -PubMed
    1. Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. N Engl J Med. 1988;319:267–273. -PubMed
    1. Boffetta P, Garfinkel L. Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study. Epidemiology. 1990;1:342–348. -PubMed
    1. Thun MJ, Peto R, Lopez AD. Alcohol consumption and mortality among middle-aged and elderly U.S. adults. N Engl J Med. 1997;337:1705–1714. -PubMed

Publication types

MeSH terms

Grants and funding

LinkOut - more resources