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

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

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

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

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.