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

Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group

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461 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1513-1523
Number of pages11
JournalThe Lancet
Volume391
Issue number10129
DOIs
Publication statusPublished - 14 Apr 2018
Externally publishedYes

Bibliographical note

Funding Information:
ASB reports grants from European Commission Framework 7 (HEALTH-F2-2012-279233), the European Research Council (268834), the British Heart Foundation (SP/09/002 and RG/08/014 and RG13/13/30194), the UK Medical Research Council (G0800270 and MR/L003120/1), from National Institute for Health Research (through the NIHR Cambridge Biomedical Research Centre), during the conduct of the study; and grants from Merck, Biogen, Bioverativ, Novartis, and Pfizer, outside the submitted work. BMP reports that he serves on the DSMB of a clinical trial funded by Zoll LifeCor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. MD reports grants from Japan Society for the Promotion of Science, during the conduct of the study. EDA reports grants from European Commission Framework 7, the European Research Council, the British Heart Foundation, the UK Medical Research Council, and the National Institute for Health Research, during the conduct of the study; and grants from NHS Blood and Transplant, outside the submitted work. EB reports grants from the National Health and Medical Research Council of Australia, during the conduct of the study. HMK reports a research agreement (through Yale) from Johnson & Johnson (Janssen) and Medtronic to develop methods of clinical trial data sharing; personal fees from UnitedHealth, IBM Watson, Element Science, and Aetna; a personal health information platform from Hugo; grants from the FDA and Medtronic; and contracts from Centers for Medicare & Medicaid Services to develop and maintain measures that are publicly reported, outside the submitted work. JD reports grants from the UK Medical Research Council, the British Heart Foundation, the UK National Institute of Health Research, and the European Commision, during the conduct of the study; personal fees and non-financial support from Merck Sharp and Dohme UK Atherosclerosis, personal fees and non-financial support from Novartis Cardiovascular and Metabolic Advisory Board, grants from the British Heart Foundation, European Research Council, Merck, the National Institute of Health Research, NHS Blood and Transplant, Novartis, Pfizer, the UK Medical Research Council, the Wellcome Trust, and AstraZeneca, and personal fees and non-financial support from Pfizer Population Research Advisory Panel, outside the submitted work. ML reports grants from National Institutes of Health, during the conduct of the study; grants from National Kidney Foundation, outside the submitted work; and Funding from the National Institutes of Health, Grant 5U10AA025286, to Johns Hopkins University. MS reports grants from the UK Medical Research Council, the British Heart Foundation, the National Institute for Health Research, European Commission Framework 7, and the European Research Council, during the conduct of the study. NvS reports grants from the Netherlands Ministry of Health Welfare and Sports, Directorate of Long-Term Care, during the conduct of the study. OHF reports grants from Nestle and Metagenics, outside the submitted work. PJN reports grants from the NIH, during the conduct of the study. SGT reports grants from the UK Medical Research Council and the British Heart Foundation, during the conduct of the study. SKi reports grants from FFG COMET program: “Research Center of Excellence in Vascular Ageing—Tyrol, VASCage” (K-Project No. 843536) funded by the BMVIT, BMWFW, Wirtschaftsagentur Wien and Standortagentur Tirol, outside the submitted work. SKa reports grants from the UK Medical Research Council and the British Heart Foundation, during the conduct of the study. WK reports personal fees from AstraZeneca, Novartis, Pfizer, The Medicines Company, GSK, DalCor, Sanofi, Berlin-Chemie, Kowa, and Amgen; grants and non-financial support from Roche Diagnostics, Beckmann, Singulex, and Abbott, outside the submitted work. The other authors declare no competing interests.

Funding Information:
The study's coordinating centre (Emerging Risk Factors Collaboration and EPIC-CVD Coordinating Centres, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, UK) has been underpinned by grants from the UK Medical Research Council (G0800270 and MR/L003120/1), British Heart Foundation (SP/09/002, RG/08/014 and RG13/13/30194), National Institute for Health Research (through the National Institute for Health Research Cambridge Biomedical Research Centre), European Commission Framework 7 (through the EPIC-CVD award; HEALTH-F2-2012-279233), and the European Research Council (through an Advanced Investigator Award to JD; 268834). JD holds a BHF Professorship and NIHR Senior Investigator Award. A study website Funding for the EPIC-InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). A study website includes a list that investigators have provided of funding agencies that have supported individual EPIC centres. A study website includes a list that investigators have provided of funding agencies that have supported individual cohorts of the ERFC contributing to the present consortium. This research has been conducted using the UK Biobank resource (application 21886). We thank Nicola Kerrison and Stephen Sharp (both from the University of Cambridge MRC Epidemiology Unit, Cambridge, UK) for the former's data management in the EPIC-InterAct subcohort and the latter's statistical input into development of the EPIC-CVD's analytical guidelines.

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

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