07957nas a2201657   4500000000100000008004100001260001600042653001100058653001100069653000900080653001600089653002400105653002800129653002100157100001900178700001800197700002200215700002500237700002900262700002000291700001800311700001900329700001600348700001700364700001700381700001600398700002100414700002000435700001600455700001600471700001700487700001800504700001800522700001600540700002000556700002100576700001800597700002300615700001800638700001600656700001400672700002100686700002000707700001600727700001800743700001800761700001900779700001700798700001700815700001800832700002000850700001900870700002400889700001200913700002000925700001800945700001700963700002000980700001901000700002001019700002101039700001701060700001701077700001701094700002001111700001901131700002701150700001801177700001901195700001801214700002101232700001801253700002601271700001701297700001601314700001801330700002001348700001701368700001601385700002201401700002501423700002001448700001701468700002301485700001901508700001901527700001901546700001501565700002001580700001801600700002101618700001901639700001501658700002001673700001701693700001801710700003001728700001801758700002001776700001601796700001901812700001701831700001701848700002101865700001601886700002901902700002101931700002501952700001701977700002301994700001602017700002302033700001702056700001902073700002502092700001702117700001802134700002102152700001902173700001902192700002202211700002102233700001902254700002302273700001702296700001702313700002202330700001902352700001302371700001702384700001902401700001902420700001502439700002902454700008002483245015202563300001402715490000802729520354802737022001406285       2018                            d  c3161610857110aFemale10aHumans10aMale10aMiddle Aged10aProspective Studies10aCardiovascular Diseases10aAlcohol Drinking1 aArima Hisatomi1 aWoodward Mark1 aGrobbee Diederick1 aWeiderpass Elisabete1 aBarrett-Connor Elizabeth1 aBrenner Hermann1 aShaw Jonathan1 aKauhanen Jussi1 aDanesh John1 aSmith George1 aPeto Richard1 aPsaty Bruce1 aSundström Johan1 aKnuiman Matthew1 aBanks Emily1 aJackson Rod1 aWareham Nick1 aBoeing Heiner1 aSattar Naveed1 aWood Angela1 aKaptoge Stephen1 aButterworth Adam1 aWilleit Peter1 aWarnakula Samantha1 aBolton Thomas1 aPaige Ellie1 aPaul Dirk1 aSweeting Michael1 aBurgess Stephen1 aBell Steven1 aAstle William1 aStevens David1 aKoulman Albert1 aSelmer Randi1 aVerschuren W1 aSato Shinichi1 aNjølstad Inger1 aSalomaa Veikko1 aNordestgaard Børge1 aYeap Bu1 aFletcher Astrid1 aMelander Olle1 aKuller Lewis1 aBalkau Beverley1 aMarmot Michael1 aKoenig Wolfgang1 aCasiglia Edoardo1 aCooper Cyrus1 aArndt Volker1 aFranco Oscar1 aWennberg Patrik1 aGallacher John1 ade la Cámara Agustín1 aVölzke Henry1 aDahm Christina1 aDale Caroline1 aBergmann Manuela1 aCrespo Carlos1 avan der Schouw Yvonne1 aKaaks Rudolf1 aSimons Leon1 aLagiou Pagona1 aSchoufour Josje1 aBoer Jolanda1 aKey Timothy1 aRodriguez Beatriz1 aMoreno-Iribas Conchi1 aDavidson Karina1 aTaylor James1 aSacerdote Carlotta1 aWallace Robert1 aJ Quiros Ramon1 aTumino Rosario1 aBlazer Dan1 aLinneberg Allan1 aDaimon Makoto1 aPanico Salvatore1 aHoward Barbara1 aSkeie Guri1 aStrandberg Timo1 aNietert Paul1 aKromhout Daan1 aSalamanca-Fernandez Elena1 aKiechl Stefan1 aKrumholz Harlan1 aGrioni Sara1 aPalli Domenico1 aHuerta José1 aPrice Jackie1 aArriola Larraitz1 aTravis Ruth1 aPanagiotakos Demosthenes1 aKarakatsani Anna1 aTrichopoulou Antonia1 aKühn Tilman1 avan Schoor Natasja1 aOvervad Kim1 aLangenberg Claudia1 aForouhi Nita1 aWennberg Maria1 aDesprés Jean-Pierre1 aCushman Mary1 aCooper Jackie1 aRodriguez Carlos1 aSakurai Masaru1 aVoortman Trudy1 aMeisinger Christa1 aTjønneland Anne1 aPalmieri Luigi1 aDallongeville Jean1 aBrunner Eric1 aAssmann Gerd1 aTrevisan Maurizio1 aGillum Richard1 aFord Ian1 aLazo Mariana1 aThompson Simon1 aFerrari Pietro1 aLeon David1 aDi Angelantonio Emanuele1 aEmerging Risk Factors Collaboration/EPIC-CVD/UK Biobank Alcohol Study Group00aRisk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies.  a1513-15230 v3913 a<p>
<b>BACKGROUND: </b>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.
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<b>METHODS: </b>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.
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<b>FINDINGS: </b>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 &gt;0-≤100 g per week, those who reported drinking &gt;100-≤200 g per week, &gt;200-≤350 g per week, or &gt;350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.
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<b>INTERPRETATION: </b>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.
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<b>FUNDING: </b>UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.
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