@article{3107482,
    title = "Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies",
    author = "Wood, A.M. and Kaptoge, S. and Butterworth, A.S. and Willeit, P. and Warnakula, S. and Bolton, T. and Paige, E. and Paul, D.S. and Sweeting, M. and Burgess, S. and Bell, S. and Astle, W. and Stevens, D. and Koulman, A. and Selmer, R.M. and Verschuren, W.M.M. and Sato, S. and Njølstad, I. and Woodward, M. and Salomaa, V. and Nordestgaard, B.G. and Yeap, B.B. and Fletcher, A. and Melander, O. and Kuller, L.H. and Balkau, B. and Marmot, M. and Koenig, W. and Casiglia, E. and Cooper, C. and Arndt, V. and Franco, O.H. and Wennberg, P. and Gallacher, J. and de la Cámara, A.G. and Völzke, H. and Dahm, C.C. and Dale, C.E. and Bergmann, M.M. and Crespo, C.J. and van der Schouw, Y.T. and Kaaks, R. and Simons, L.A. and Lagiou, P. and Schoufour, J.D. and Boer, J.M.A. and Key, T.J. and Rodriguez, B. and Moreno-Iribas, C. and Davidson, K.W. and Taylor, J.O. and Sacerdote, C. and Wallace, R.B. and Quiros, J.R. and Tumino, R. and Blazer, D.G., II and Linneberg, A. and Daimon, M. and Panico, S. and Howard, B. and Skeie, G. and Strandberg, T. and Weiderpass, E. and Psaty, B.M. and Kromhout, D. and Salamanca-Fernandez, E. and Kiechl, S. and Krumholz, H.M. and Grioni, S. and Palli, D. and Huerta, J.M. and Price, J. and Sundström, J. and Arriola, L. and Arima, H. and Travis, R.C. and Panagiotakos, D.B. and Karakatsani, A. and Trichopoulou, A. and Kühn, T. and Grobbee, D.E. and Barrett-Connor, E. and van Schoor, N. and Boeing, H. and Overvad, K. and Kauhanen, J. and Wareham, N. and Langenberg, C. and Forouhi, N. and Wennberg, M. and Després, J.-P. and Cushman, M. and Cooper, J.A. and Rodriguez, C.J. and Sakurai, M. and Shaw, J.E. and Knuiman, M. and Voortman, T. and Meisinger, C. and Tjønneland, A. and Brenner, H. and Palmieri, L. and Dallongeville, J. and Brunner, E.J. and Assmann, G. and Trevisan, M. and Gillum, R.F. and Ford, I.F. and Sattar, N. and Lazo, M. and Thompson, S.G. and Ferrari, P. and Leon, D.A. and Davey Smith, G. and Peto, R. and Jackson, R. and Banks, E. and Di Angelantonio, E. and Danesh, J. and Veikko, S. and Gómez de la Cámara, A. and Rimm, E.B. and Dallongeville, J.-P. and Gillumn, R.F. and Thompson, S. and Emerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group",
    journal = "The Lancet Neurology",
    year = "2018",
    volume = "391",
    number = "10129",
    pages = "1513-1523",
    publisher = "The Lancet Publishing Group",
    doi = "10.1016/S0140-6736(18)30134-X",
    keywords = "adult;  age;  alcohol consumption;  all cause mortality;  aortic aneurysm;  Article;  cardiovascular disease;  cardiovascular mortality;  cerebrovascular accident;  cohort analysis;  controlled study;  coronary artery disease;  diabetes mellitus;  drinking behavior;  female;  follow up;  heart failure;  heart infarction;  high income country;  high risk patient;  human;  hypertension;  life expectancy;  major clinical study;  male;  medical history;  mortality risk;  priority journal;  prospective study;  reference value;  risk assessment;  risk factor;  sex;  smoking;  cardiovascular disease;  middle aged;  mortality, Alcohol Drinking;  Cardiovascular Diseases;  Female;  Humans;  Male;  Middle Aged;  Prospective Studies",
    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. © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license."
}