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Wine, alcohol and cardiovascular risk: an epidemiological perspective presented by G. de Gaetano at Winehealth 2007
A number of questions still remain controversial in the topic of wine, alcohol and health. Epidemiological studies have explored the hypothesis that consuming alcohol in the form of wine might confer a significant protection against cardiovascular disease above that expected from its alcohol content. Wine might indeed show additional non-ethanol related beneficial effects due to specific properties of its polyphenolic constituents. In spite of a large number of experimental studies that confirm this hypothesis, epidemiological evidence of a greater effect of wine has not been definitely established. A meta-analysis from our group tested such a hypothesis.

The overall protective effect against cardiovascular disease was 32 % (95% CI: 23% to 41%; 13 studies, 209,418 subjects) in favour of moderate (1-2 drinks a day) wine drinkers versus abstainers and 22% (95% CI: 14% to 30%; 15 studies, 208,036 persons) in favour of moderate beer drinkers versus abstainers.

In addition, there was strong evidence from 10 studies (involving 176,042 persons) to support a J-shaped relationship between different amounts of wine intake and vascular risk (a statistically significant inverse association was found up to a daily intake of 150 ml of wine), whereas no significant relationship between different amounts of beer intake and vascular risk could be found.

Some authors investigated the hypothesis that any coronary protection from moderate alcohol drinking is unlikely to outweigh the known harms, mainly because of uncontrolled confounding by associated lifestyle factors; the hypothesis is that drinkers may have many healthier characteristics than nondrinkers, leading them to a lower ischemic heart disease risk. However, Mukamal et al., in a recent large USA population study, found that moderate drinking is only modestly associated with healthier lifestyle characteristics, the association being lower after adjustment for race and education.

We paid special attention to the possible effect of confounding in a metaanalysis including 34 prospective studies on alcohol and mortality. We pooled findings from more than one million subjects and about 95,000 deaths from any cause.

The expected J-shaped relationship between total mortality and increasing amounts of alcohol consumed, showed that low to moderate consumption of alcohol (<1 drink/day in women and < 2 drink/day in men) significantly reduces total mortality, while higher doses increase it. 29 studies showed adjusted relative risks at least for age; among them, 15 were adjusted for social status too, and 6 for social status and dietary markers. P for difference was highly significant (P<0.0001), showing that part of heterogeneity is indeed attributable to adjustment. However, while the protection decreased in adjusted studies (from 36% to 17%), it remained substantial and statistically significant. Moreover, we compared adjusted or not unadjusted data from the same studies. In this case the effect due to known confounders (age, smoking, social status, dietary factors) led to the reduction of the maximum protection from 19% to 16%; by analogy, even in the pessimistic hypothesis that residual confounding would have a similar strength as the known one in lowering the protection, one can assume that the « real » (maximum) protection against total mortality associated with low consumption of alcohol would be largely higher than 10%. Although the protection by alcohol or wine decreases when data are adjusted, thus confirming the importance of confounding in assessing drinking effects, it remains significant and in a range of undoubted public health value.

A meta-analysis of 54 studies on moderate alcohol and total mortality investigated the degree to which the inclusion of abstainers in control group influences the results. Most of the prospective studies analyzed ¨C the authors argue ¨C were plagued by the error of including in the control group people who had stopped drinking owing to illness. The analysis of the studies judged to be error-free did not show any significant cardiovascular protection, suggesting that the cardiovascular protection by moderate alcohol consumption may have been overestimated. However, in our meta-analysis on alcohol dosing and total mortality, we tested the same hypothesis by comparing studies that used as reference group the category of no alcohol intake and/or excluded former drinkers with studies which, in contrast, included in the reference group occasional or former drinkers or people reporting low alcohol intake: the protection was indeed lower in the first studies, but remained statistically significant.

In conclusion, a review of the most recent literature confirms that light-to-moderate alcohol consumption is protective for cardiovascular morbidity and total mortality. Whether wine possesses some additional beneficial properties in respect to other alcoholic beverages is suggested but not definitely established.

G. de Gaetano*, A. Di Castelnuovo, S. Costanzo, M. Benedetta Donati and L. Iacoviello Research Laboratories, John Paul II Centre for High Technology Research and Education in Biomedical Sciences, Catholic University, 86100 Campobasso, Italy

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