Author + information
- Giovanni de Gaetano, MD, PhD∗ ( and )
- Simona Costanzo, MS, PhD
- Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy
- ↵∗Address for correspondence:
Dr. Giovanni de Gaetano, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Via dell’Elettronica, 86077 Pozzilli (Isernia), Italy.
The accepted interpretation of the J-shaped curve relating alcohol intake to cardiovascular events or mortality is that the lowest point on the curve (light-to-moderate drinking) represents optimum exposure to alcohol, and the increased risk in nondrinkers or heavy drinkers reflects the consequence of suboptimal exposure. This means that unlike tobacco, for which there is no safe level of consumption (Figure 1), the nadir of J-shaped curves for alcohol (Figure 2) is proposed as a healthy range for the general population (1,2).
Numerous studies have used J-shaped curves to describe the relationship between alcohol use and total mortality. In a meta-analysis of 34 prospective studies in men and women, including more than 1 million subjects and more than 94,500 deaths (2), a clear J-shaped relationship between alcohol intake and mortality was observed. After an initial reduction in mortality, as alcohol intake increased, the curve reached a nadir and then showed an increase in mortality at higher doses (Figure 2). The lowest mortality risk (−19%) was observed at 6 g/day of alcohol or approximately one-half of a drink per day, but lower mortality compared with no alcohol consumption was observed with up to 4 drinks/day in men and 2 drinks/day in women. Higher doses of alcohol were associated with increased mortality (2). The basic J-shaped curve persisted after adjustment for many relevant confounding variables.
However, prominence is often given to the hypothesis that the well documented J-curve relationship of lower risk of mortality with light-to-moderate alcohol intake might be due to a misclassification of drinking patterns. The higher risk among abstainers might have been due to the inclusion of high-risk subjects who had become abstainers (3).
In 2010, an analysis of 9 nationally representative samples of U.S. adults showed that light-to-moderate alcohol consumption was inversely associated with cardiovascular mortality (4).
Compared with lifetime abstainers, a significant protection of 31% and 38% among light and moderate drinkers was found, respectively. The magnitude of lower risk was similar in subgroups of sex, age, or baseline health status. There was no simple relation of drinking pattern with risk, but risk was consistently higher among those who consumed >3 compared with 2 drinks/day (4).
In this issue of the Journal, Xi et al. (5) analyzed the amount of alcohol intake and risk of all-cause, cardiovascular, and cancer deaths in 333,247 American adults from 13 waves of U.S. National Health Interview data. After a median follow-up of 8.2 years, 34,754 participants died from all causes (including 8,947 cardiovascular disease [CVD] deaths and 8,427 cancer deaths). Compared with lifetime abstainers, light-to-moderate alcohol consumers were at significantly reduced risk of all-cause (light: −21%; moderate: −22%) and CVD mortality (light: −26%; moderate: −29%), respectively. In contrast, significantly increased risks of all-cause (11%) and cancer mortality (27%) were found in adults with heavy alcohol consumption compared with those who never consumed. The data by Xi et al. (5) appear to be largely confirmatory (2,4,6), but the authors have pointed out relevant drawbacks from some of the previous studies, such as “abstainer bias” or inappropriate adjustment for confounders or different patterns of alcohol drinking.
The conclusion by Xi et al. (5) that their study “re-emphasized the existence of a J-shaped curve in the alcohol–mortality association” may look like a religious claim. However, it was not a theological statement, but a robust scientific conclusion. Their work helps clarify the debate over the existence of a J-shaped curve, an issue frequently discussed as a problem of beliefs rather than scientific data.
The number of people involved in their study was impressive, the methodology sound (inclusion of only lifetime abstainers in the reference group), and the statistical approach correct and supported by important ancillary analyses. The results supported the conclusion that the J-shaped relationship between alcohol consumption and mortality risk cannot be dismissed and should guide the formulation of public policies on alcohol consumption.
Alcohol’s multiple effects on health not only depend on quantities but also on patterns of alcohol use (whether intake is concentrated—such as during weekends—or regularly dispersed during meals) (7). Binge drinking was also associated with a significant increased risk of all-cause (13%) and cancer mortality (22%) (5). Consistent with some previous observations, they also failed to show heavy or binge drinking to be associated with CVD-specific mortality. In a very recent study, heavy drinkers were more likely to initially present with death from causes other than CVD (8); this might be due to competing risks in heavy or binge drinkers, or it might mean that they are less likely to initially present with any CVD because they die from other causes before developing CVD. Another explanation might be that even ingesting large amounts of polyphenols from heavy alcohol consumption might have some protective effect on the cardiovascular system (9).
Numerous mechanisms have been proposed to explain the benefit that light-to-moderate alcohol intake has on the heart, including an increase in high-density lipoprotein cholesterol and fibrinolysis; reductions in plasma viscosity, fibrinogen concentration, and platelet aggregation; improvement in endothelial function; reduction in inflammatory responses; and promotion of antioxidant effects. Controversy exists about whether alcohol has a direct cardioprotective effect on the ischemic myocardium (2,10). Conversely, alcoholic cardiomyopathy, a rare consequence of severe alcohol use disorders, is thought to be a direct consequence of alcoholic cytotoxicity (10).
Another important result presented by Xi et al. (5): light alcohol consumption appeared to be protective against cancer mortality. Although there is general agreement that heavy alcohol is associated with increased cancer risk (10,11), some public organizations insist on considering alcohol harmful even when consumed in light amounts (“zero tolerance”) (12). In line with Xi et al. (5), a recent meta-analysis of 60 cohort studies concluded that light drinking was not associated with the incidence of most cancers except for a mild increase of female breast and male colorectal cancer, although it was not associated with increased breast cancer mortality (13). The important issue of possible cancer risk from light-to-moderate alcohol intake remains clouded by uncertainty about whether the findings are confounded by under-reporting and other traits (14). Thus, younger people should be informed to not expect any substantial benefit from moderate drinking. For most older persons, the overall benefits of light drinking, especially the reduced CVD risk, clearly outweigh possible cancer risk. For young women with no coronary disease risk factors, the breast cancer data suggest limiting alcohol intake to very modest amounts, but post-menopausal women (at relatively high risk of CVD) should consider the overall health advantage if choosing to drink a moderate amount of alcohol daily. A similar approach should be taken by patients with CVD (15).
Last, but not least, the results by Xi et al. (5) supported previous studies that had shown a significant reduction in total mortality with light-to-moderate drinking versus abstention or heavy drinking (2). The importance of determining the effect on total mortality is clear if one considers that a layman would be less interested in the effects of alcohol on this or that disease or clinical outcome, but more on life expectancy.
Epidemiological research is generally given a lower place in the hierarchy of causal inference than truly experimental research. Thus, despite the consistent evidence from observational studies regarding the beneficial effects of moderate alcohol consumption on fatal and nonfatal CVD and total mortality, as discussed here, a controlled, randomized, long-term trial is highly desirable and appears to be feasible (16). In the meantime, the following provisional conclusions can be proposed:
• Regular moderate alcohol consumption protects against fatal and nonfatal CVD and all-cause mortality, both in healthy adults and in CVD patients.
• The dose-effect relationship is characterized by a J-shaped curve.
• For light-to-moderate levels of alcohol consumption, the risks of some cancers (breast, colorectal, oral) are relatively small and should be considered in the context of each individual global risk.
• Lifelong alcohol abstainers should not start drinking for health reasons only, but should be encouraged to adopt healthy lifestyles (regular physical activity, no smoking, weight control, and dietary habits such as the Mediterranean diet).
• Excessive or irregular (binge) alcohol use is detrimental to human organs and function and is a major public health and social problem.
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Dr. Costanzo is a visiting scientist at the Department of Nutrition, Harvard TH Chan School of Public Health, Boston, Massachusetts, as the recipient of a Fondazione Umberto Veronesi Travel Grant. Dr. de Gaetano is a member of the International Scientific Forum on Alcohol Research, an independent organization of scientists that prepares critiques of emerging research reports on alcohol and health. The members of the Forum donate their time and effort in the review of papers, and receive no financial support. The Forum itself receives no support from any organization or company in the alcoholic beverage industry. He is also a consultant to the Web Newsletter of Assobirra, the Italian Association of the Beer and Malt Industries; and is a corresponding member of the nonprofit Accademia Italiana della Vite e del Vino. Dr. Costanzo has reported that she has no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
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