In this review of 84 studies of alcohol consumption and cardiovascular disease, alcohol consumption at 2.5–14.9 g/day (about ≤1 drink a day) was consistently associated with a 14–25% reduction in the risk of all outcomes assessed compared with abstaining from alcohol. Such a reduction in risk is potentially of clinical importance, but consumption of larger amounts of alcohol was associated with higher risks for stroke incidence and mortality.
To our knowledge, this systematic review and meta-analysis is the most comprehensive to date. Although roughly similar estimates of lower risk were observed in previous meta-analyses of both coronary heart disease and stroke,1 2 3 4 5 6 7 8
our review extends the findings by assessing a broader array of relevant cardiovascular outcomes and adding several new important studies. Our review clarifies several discrepancies among prior reports. Corrao et al reported a J shaped relation between alcohol intake and coronary heart disease,2
whereas the review by Maclure described this relation as L shaped because he did not observe an increase in coronary heart disease risk associated with higher alcohol consumption.6
Our updated meta-analysis supports the latter association for coronary heart disease, with a 25–35% risk reduction for light to moderate drinking106
that also is present with heavier drinking.
Our analysis of multiple cardiovascular outcomes also shows the complexities inherent in the study of alcohol consumption. Modest alcohol intake was associated with lower stroke incidence and mortality, but the risk increased substantially with heavier drinking (that is, a J shaped relation). Furthermore, the association of alcohol consumption is complex and differs by stroke subtype, with a slightly lower risk of ischaemic stroke but higher risk of haemorrhagic stroke. These differential associations probably reflect the known antithrombotic effects of alcohol.107
Alcohol consumption, particularly at high doses, also seems to have an adverse association with blood pressure that may account, in part, for the higher risk of haemorrhagic stroke associated with heavier drinking.108
Additionally, our analysis does not consider other known detrimental effects of high alcohol consumption.3
Therefore, our findings lend further support for limits on alcohol consumption.106 109
Our review also highlights other important aspects of the relation between alcohol consumption and cardiovascular disease. Firstly, the lower risk of coronary heart disease associated with alcohol consumption was at least as strong for women as for men. Limited evidence suggests that the risk of stroke related to alcohol is lower for women than men, but this may only reflect lower alcohol intake among women. Secondly, inclusion of former drinkers did not seem to bias the association of alcohol consumption with cardiovascular disease. Thirdly, when studies were summarised chronologically, we found that the overall association between drinking and cardiovascular disease and coronary heart disease became apparent at least a decade ago, and ongoing studies have done little to revise the estimated associations.
An argument for causation
From the extensive body of literature summarised here, the association between alcohol consumption and decreased cardiovascular risk is not in question, as additional research has not changed this conclusion. Rather, the lingering question is whether this association is causal. Clearly, observational studies cannot establish causation. However, when the present results are coupled with those from our companion review paper summarising interventional mechanistic studies focusing on biomarkers associated with cardiovascular disease,110
the argument for causation becomes more compelling. Indeed, the mechanistic biomarker review shows biological plausibility for a causal association by showing favourable changes in pathophysiologically relevant molecules.
Therefore, we can now examine the argument for causation based on Hill’s criteria.111
Beyond the biological plausibility argument discussed above, there is an appropriate temporal relation with alcohol use preventing cardiovascular disease. Secondly, we have observed a greater protective association with increasing dose, except that it seems to be offset somewhat by negative associations with the risk of haemorrhagic stroke. Thirdly, the protective association of alcohol has been consistently observed in diverse patient populations and in both women and men. Fourthly, the association is specific: moderate drinking (up to 1 drink or 12.5 g alcohol per day for women and 2 drinks or 25 g alcohol per day for men106
) is associated with lower rates of cardiovascular disease but is not uniformly protective for other conditions, such as cancer.112
Lastly, the reduction in risk is notable even when controlling for known confounders (such as smoking, diet, and exercise). Any potential unmeasured confounder would need to be very strong to explain away the apparently protective association.
Limitations of study
The results of our meta-analysis should be interpreted in context of the limitations of available data. Firstly, the quality of individual studies varied, with some studies having limited follow-up and limited adjustment for potential confounding. With respect to study follow-up, it is possible that misclassification of alcohol consumption may increase with study length because of changes in drinking habits over time. It is also possible that potential biological effects of alcohol vary with time of exposure. However, arguing against both these possibilities, the analysis stratified by length of follow-up did not show different associations between alcohol intake and outcome for shorter follow-up times versus longer times.
Secondly, only a limited subset of studies provided specific risk estimates for different beverages. Although there is great interest in differences between beer, wine, and spirits, alcoholic drinks generally have similar effects on high density lipoprotein cholesterol,113
and it is likely that any particular benefit of wine is prone to confounding by diet and socioeconomic status.114 115
None the less, this remains an interesting topic for further investigation.
Thirdly, we found only limited information on the relation between alcohol intake and mortality from subtypes of stroke, so this topic continues to be important for large observational cohort studies. Finally, we observed significant heterogeneity across studies for several of our pooled analyses. This may be due in great part to large study sample sizes, which can confer greater statistical power to heterogeneity tests, whereas the clinical relevance of this heterogeneity may be quite modest.10
Visual inspection of our various forest plots and the relative consistency of pooled relative risks across clinical and methodological variables suggest that there is considerable consistency in the relative risk findings across studies and across strata.
Given the consistency observed in our findings and compelling mechanistic data pointing to causation in our companion review, additional observational studies will have limited value except to elucidate more precisely the association of alcohol and stroke.116
Rather, debate should centre now on how to integrate this evidence into clinical practice and public health messages. In the realm of clinical practice, the evidence could form a foundation for proposing counselling for selected patients to incorporate moderate amounts of alcohol into their diets to improve their coronary heart disease risk. However, such a clinical strategy requires formal evaluation in pragmatic clinical trials that assess the questions of optimal patient selection, compliance, risks, and benefits. The focus of such trials would shift from assessing the association between alcohol and disease outcomes to evaluating the receptivity of both physicians and patients to the recommended consumption of alcohol for therapeutic purposes and the extent to which it can be successfully and safely implemented. In support of implementation trials, our two papers show that alcohol consumption in moderation has reproducible and plausible effects on markers of coronary heart disease risk.
With respect to public health messages, there may now be an impetus to better communicate to the public that alcohol, in moderation, may have overall health benefits that outweigh the risks in selected subsets of patients. Again, any such strategy would need to be accompanied by rigorous study and oversight of impacts. One approach would be to undertake public health messaging pilot studies on well defined target populations (such as a workplace or in a small jurisdiction) to permit detailed evaluation of effects on measures such as knowledge, attitudes, self reported drinking behaviours, and perhaps, secondarily, health outcomes.
The debate on how to integrate this evidence into clinical practice and public health messages will require integration of all possible effects of alcohol—from injury and violence to glucose metabolism and inflammation—and recognition that these effects may be distributed unequally across the population. For example, injury risk probably disproportionately affects younger individuals, whereas cardiovascular disease mainly affects older adults. Robust studies that examine multiple outcomes simultaneously are needed to identify those subsets of the population in which reduced cardiovascular risk might dominate against those for whom the risks of social and medical problems (including several cancers and injury112 117
) are too great. Despite the latter concerns, results of our secondary analysis of overall mortality (fig 5) support the notion that moderate alcohol consumption is associated with net benefit, at least in populations similar to those studied in the extant literature.
Our two systematic review papers summarise a surprisingly extensive body of literature on the relation between alcohol and cardiovascular disease. Our findings point to the need to define implications for clinical and public health practice. These reviews and the perspectives above provide a foundation for that dialogue.
What is already known on this topic:
- Systematic reviews have addressed the association of alcohol consumption with various cardiovascular outcomes
- However, these reviews are somewhat out of date, and none has comprehensively studied a broad spectrum of relevant cardiovascular end points
What this study adds
- This meta-analysis provides a summary of current knowledge regarding alcohol associations with six meaningful clinical end points—cardiovascular disease mortality, coronary heart disease incidence and mortality, stroke incidence and mortality, and all cause mortality
- The results confirm the beneficial effects of moderate alcohol consumption and the need to elucidate the underlying pathophysiological mechanisms