8 February, 2016: 

Alcohol consumption has been associated with both benefits and harms, but most studies investigated men rather than women, or analyzed data from mixed cohorts composed of males and females, with necessary adjustments for age and sex. Also, most studies focused on one alcohol-related outcome or on a single group of related diseases rather than seeing the entire spectrum of human health. Despite a wealth of information on the outcomes of drinking alcohol, there is still inconsistency on some bottom-line guiding messages related to consumption patterns (quantity, frequency, and stratified combinations), and types of alcohol consumed. Ethnicity, socio-economical features, age and gender may be factors that influence disease protection or risk.

A recent study addressed the outcomes of drinking alcohol in a large cohort which included people from 12 countries in five continents with different socio-economical characteristics [1]. The PURE study included 114,970 adults, of whom 12,904 (11%) were from high-income countries, 24,408 (21%) were from upper-middle-income countries, 48,845 (43%) were from lower-middle-income countries, and 28,813 (25%) were from low-income countries. Mean age was 50 (41–58) years; median follow-up was 4.3 years (IQR 3.0–6.0). In the high- and upper-middle income countries, around 50% of the cohorts were women, but there were only 4% of women in the low-income countries. Overall, 74,685 (65%) participants were never drinkers, 4255 (4%) were former drinkers, and 36,030 (31%) were current drinkers. Of current drinkers, 26,025 (72%) had low intake, 6114 (17%) had moderate intake, and 2931 (8%) had high intake. Associations with mortality (n = 2723), cardiovascular disease (n = 2742), myocardial infarction (n = 979), stroke (n = 817), alcohol-related cancer (n = 764), injury (n = 824), admission to hospital (n = 8786), and for a composite of these outcomes (n = 11 963) were calculated. Data was adjusted for age and sex. Current drinking was associated with reduced myocardial infarction risk (HR 0.76; 95% CI 0.63–0.93), but with increased alcohol-related cancers (HR 1.51; 95% CI 1.22–1.89) and injury (HR 1.29; 95% CI 1.04–1.61). High intake was associated with increased mortality (HR 1.31; 95% CI 1.04–1.66). Compared with never drinkers, significantly reduced hazards for the composite outcome for current drinkers in high-income countries and upper-middle-income countries (HR 0.84; 95% CI 0.77–0.92), but not in lower-middle-income countries and low-income countries, for which there were no reductions in this outcome (HR 1.07; 95% CI 0.95–1.2).

Comment

Perhaps the best-known clinical bright side of alcohol consumption is cardiovascular protection, whereas the dark side is, of course, cirrhosis of the liver. The question was always how much one should drink to achieve benefits yet to avoid harms, and numerous publications have addressed this issue. The usual recommendation for healthy lifestyle encourages women to drink alcohol 'in moderation' in order to reduce the risk of cardiovascular disease. The American Heart Association guideline for the prevention of cardiovascular disease in women mentions in its Appendix that the desired quantity should be ≤ 1 serving/day, namely up to 4 oz wine, 12 oz beer, 1.5 oz of 80-proof spirits, or 1 oz of 100-proof spirits [2].

Twenty years ago, the 12-year follow-up data from the Nurses' Health Study showed that the relative risks of death in drinkers as compared with non-drinkers were 0.83 (0.74–0.93) for women who consumed 1.5–4.9 g of alcohol per day (one to three drinks per week), 0.88 (0.80–0.98) for those who consumed 5.0–29.9 g per day, and 1.19 (1.02–1.38) for those who consumed 30 g or more per day, after adjustment for other predictors of mortality [3]. Light-to-moderate drinking (1.5–29.9 g per day) was associated with a 27–43% lower risk of death from cardiovascular disease. The benefit associated with light-to-moderate drinking was most apparent among women with risk factors for coronary heart disease and those 50 years of age or older. A more recent publication on the same cohort addressed the younger women enrolled (27–44 years old at baseline) followed for 20 years [4]. The idea was to examine whether primordial prevention, defined as prevention of the development of clinical risk factors through maintenance or adoption of a healthy lifestyle, will sustain women in a low cardiovascular risk profile and reduce their future incidence of coronary heart disease. While optimal keeping of all lifestyle factors led to 92% lower risk compared to those women who did not follow any of the healthy lifestyle recommendations, the contribution of 'light drinking' (up to 14.9 g/day of alcohol intake) was in the order of 40% reduction in risk. The Women's Health Initiative Observational Study demonstrated similar results [5]. The cohort included 93,676 postmenopausal women 50–79 years of age at enrollment, followed for a median period of 10 years. Moderate alcohol use (consumption of greater than none but less than 1 drink per day) was associated with reduced incidence of cardiovascular disease [HR 0.83; 95% CI 0.72–0.95) as compared to all other non-smoking participants. This benefit was not seen in women who had more than 1 drink/day (HR 0.94; 95% CI 0.75–1.18). Another large study, the Women's Health Study, highlighted a linear association between alcohol consumption and cardiovascular disease risk [6]. Women above age 45 years (mean 55 ± 7 years, n = 26,399, mean follow-up of 12.2 years) were evaluated for different levels of alcohol intake. There were 1039 cardiovascular events and 785 deaths (153 cardiovascular deaths) during that period. Alcohol intake of 5–14.9 g/day was associated with 26%, 35%, and 51% lower risk of cardiovascular disease, total death, and cardiovascular death, respectively. Contrarily, lower (0.1–4.9 g/day), or higher (15–29.9 g/day, > 30 g/day) intakes gave non-significant benefits as confidence intervals included 1.

In conclusion, although the exact definitions of light or moderate alcohol intake vary in different studies, it seems well validated that small amounts of alcohol have potential protective cardiac effects. However, in regard to stroke, some studies show favorable consequences, while other studies are less promising in this respect. Women consuming < 2 drinks/day in the Nurses' Health Study (to note that it included a primarily white cohort) had a 12–18% lower risk of ischemic stroke compared with non-drinkers [7]. In contrast, new data from the Atherosclerosis Risk in Communities study showed that self-reported light-to-moderate alcohol consumption at midlife was not associated with reduced stroke risk compared with abstention over 20 years of follow-up [8]. Furthermore, heavier consumption increased the risk for both ischemic and hemorrhagic stroke, as did moderate intake for intracerebral bleeding. The downside of alcohol consumption should be balanced with the benefits. In the Nurses' Health Study, heavier drinking was associated with an increased risk of death from several causes, particularly breast cancer (up to 67%) and cirrhosis (255%) [3]. The link between breast cancer and alcohol deserves more attention because of the continuously increasing incidence of both drinking and breast cancer in recent decades.

Amos Pines
Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel

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 Sep 17. Epub ahead of print
http://www.ncbi.nlm.nih.gov/pubmed/26386538 
2. Mosca L, Benjamin EJ, Berra K, et al. Effectiveness-based guidelines for the prevention of cardiovascular disease in women--2011 update: a guideline from the American Heart Association. J Am Coll Cardiol 2011;57:1404-23
http://www.ncbi.nlm.nih.gov/pubmed/21388771 
3. Fuchs CS, Stampfer MJ, Colditz GA, et al. Alcohol consumption and mortality among women. N Engl J Med1995;332:1245-50
http://www.ncbi.nlm.nih.gov/pubmed/7708067 
4. Chomistek AK, Chiuve SE, Eliassen AH, et al. Healthy lifestyle in the primordial prevention of cardiovascular disease among young women. J Am Coll Cardiol 2015;65:43-51
http://www.ncbi.nlm.nih.gov/pubmed/25572509 
5. Paynter NP, LaMonte MJ, Manson JE, et al. Comparison of lifestyle-based and traditional cardiovascular disease prediction in a multiethnic cohort of nonsmoking women. Circulation 2014;130:1466-73
http://www.ncbi.nlm.nih.gov/pubmed/25156990 
6. Djoussé L, Lee IM, Buring JE, Gaziano JM. Alcohol consumption and risk of cardiovascular disease and death in women: potential mediating mechanisms. Circulation 2009;120:237-44
http://www.ncbi.nlm.nih.gov/pubmed/19597054 
7. Jimenez M, Chiuve SE, Glynn RJ, et al. Alcohol consumption and risk of stroke in women. Stroke 2012;43:939–45
http://www.ncbi.nlm.nih.gov/pubmed/22403048 
8. Jones SB, Loehr L, Avery CL, et al. Midlife alcohol consumption and the risk of stroke in the Atherosclerosis Risk in Communities Study. Stroke 2015;46:3124-30
http://www.ncbi.nlm.nih.gov/pubmed/26405203