Alcohol consumption affects different CVD events in different ways
Risk thresholds for alcohol consumption: combined analysis of individual-participant data for 599 912 current drinkers in 83 prospective studies
Literature - Wood AM, Kaptoge S, Butterworth AS et al., - The Lancet 2018: 391 (10129):1513–1523Introduction and methods
Substantial variation is seen worldwide in guideline recommendations on alcohol consumption. This may be the consequence of ambiguity about alcohol intake thresholds in relation to the lowest risk of mortality, and uncertainty about specific consequences, for instance effects on CV disease. Recently, the concept that moderate alcohol consumption is associated with lower CV disease risk has been challenged [1,2], but the dose-response relationship remains unclear.
This study analyzed individual participant data from 83 long-term prospective studies, conducted in 19 high-income countries. Its aim was to characterize risk thresholds for all-cause mortality, and for CVD subtypes in current drinkers of alcohol. The data were obtained from three large-scale data sources, which each provided quantitative information on alcohol intake (Emerging Risk Factors Collaboration [ERFC, n=356.819, current drinkers at baseline: 247.504], European Prospective Investigation into Cancer and Nutrition EPIC-CVD (n=30.703, current drinkers: 26.036), and UK Biobank (n=358.833, current drinkers: 326372). Overall, 19% (186.875) of participants reported to be a non-drinker at baseline, leaving 599.912 current drinkers. To harmonize data between the different studies, alcohol consumption was quantified by conversion of 1 unit = 8 g to a (UK) standard scale of grams per week.
Participants had no history of CVD at baseline, and were followed for at least 1 year. Mean age was 57 years (SD: 9). Current drinkers were categorized into eight groups according to the amount of alcohol consumed per week: >0–≤25, >25–≤50, >50–≤75, >75–≤100, >100–≤150, >150–≤250, >250–≤350, and >350 g per week. Consumption data were collected by means of self-administered or interview-led questionnaires, or by food frequency questionnaires or dietary recall survey.
Main results
- About 50% of participants reported drinking over 100 g alcohol per week, and 8.4% consumed more than 350 g per week. Baseline alcohol consumption varied across studies, and was generally lower in studies with more recent recruitment (baseline year ranged from 1964-2010).
- 40310 deaths (11762 vascular and 15150 neoplastic deaths) were seen during 5.4 million person-years (median: 7.5 years of follow-up), as well as 39018 incident CV disease outcomes.
- For all-cause mortality, a positive curvilinear association was seen with alcohol consumption. All categories up to 100 mg/week showed a HR (adjusted for age, smoking, and history of diabetes) of about 1 (0-25 g/week is reference category). HR of >100–≤150 g/week is greater than 1, but not the 95%CI, and with >150–≤250 g/week and the categories above, both HR and 95%CI are greater than 1. Associations were similar for men and women.
- For the aggregated CV disease outcomes (MI, CHD and stroke), a J-shaped curve was seen, with a reduced risk in the >25–≤50 up to >150–≤250 g/week categories, as compared to the lowest consumption category, only the highest consumption category showed a clearly increased risk.
- When the CVD outcomes were separated, different patterns were seen. Positive associations (adjusted for age, sex, smoking and diabetes) were seen for stroke (HR per 100 g/week higher consumption: 1.14, 95%CI: 1/10-1.17), coronary disease excluding MI (HR: 1.06, 95%CI: 1.00-1.11, although not a clear linear association), and heart failure (HR: 1.09, 95%CI: 1.03-1.15). MI, on the contrary, showed a negative association (HR: 0.94, 95%CI: 0.91-0.97).
- Associations for stroke were similar for fatal and non-fatal outcomes. For non-MI coronary disease, the associations were stronger for fatal than for non-fatal outcomes. For MI association, the association of non-fatal MI was clearer (HR: 0.93, 95%CI: 0.90-0.97) than the one of fatal MI, which was HR: 0.99, with a 95%CI that included 1 (0.93-1.05).
Conclusion
These data suggest that for all-cause mortality, current drinkers reporting consumption up to 100 g/week alcohol confers the same risk as the lowest category with 0-25 g/week. The risk of most CV outcomes was increased with every extra 100 g/week alcohol, except for non-fatal MI, which showed a lower risk with increasing alcohol intake.
Life expectancy calculations suggest that in comparison with those who report drinking 0-100 g/week, those who report 100-200 g/week have a lower life expectancy at age 40 years of approximately 6 months, and those who report 200-350 g/week of about 1-2 years, and with >350 g/week of about 4-5 years. Current guidelines recommend upper limits higher than those suggested to be safe by these data.
Editorial comment
According to Connor and Hall [3], this study 'substantially improves on previous meta-analyses to define low-risk drinking thresholds'. (...) 'Non-drinkers were excluded to minimise the possibilities of reverse causality (eg, if ex-drinkers had abstained because of poor health) or unmeasured effect modification (ie, if lifetime abstainers fundamentally differ from drinkers).'
In addition to giving a summary of the results presented above, they note that 'With some exceptions, the findings persisted after adjustment for known cardiovascular disease risk factors. The notable exceptions were adjustment for HDL cholesterol weakened the inverse association between alcohol use and myocardial infarction while strengthening the association between alcohol consumption and increased risks for coronary heart disease and heart failure. Meanwhile, adjustment for systolic blood pressure strengthened the inverse association between alcohol use and myocardial infarction but weakened the positive associations with all other cardiovascular outcomes.' (...)
'Wood and colleagues estimate that, at the population level, reductions in alcohol consumption could increase life expectancy by up to 2 years in a 40-year-old drinker. However, these gains only become evident at alcohol consumption below 100 g per week, and are not offset by the reductions in rates of myocardial infarction. The 100 g per week threshold is substantially lower than current guidelines in many high-income countries (eg, 196 g/week in the USA).' Although, according to these authors, the drinking levels that stem from this study will likely be considered to be implausible and impractical by some, they think these data should provoke informed public and professional debate.
References
1. Smyth A, Teo KK, Rangarajan S, et al. Alcohol consumption and cardiovascular disease, cancer, injury, admission to hospital, and mortality: a prospective cohort study. Lancet 2015; 386: 1945–54.
2. Bell S, Daskalopoulou M, Rapsomaniki E, et al. Association between clinically recorded alcohol consumption and initial presentation of 12 cardiovascular diseases: population based cohort study using linked health records. BMJ 2017; 356: j909.
3. Connor J, Hall W. Thresholds for safer alcohol use might need lowering. Lancet 2018; 391:1460–1461
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