International Scientific Forum on Alcohol Research
Critique 004: 24 May 2010
Subject: Alcohol, lifestyle
Article: Hansel B, Thomas F, Pannier B, Bean K, Kontush A, Chapman MJ, Guize L, Bruckert E. Relationship between alcohol intake, health and social status and cardiovascular risk factors in the urban Paris-Ile-De-France Cohort: is the cardioprotective action of alcohol a myth?
European J Clin Nutrition, advance online publication, doi:10:1038/ejcn.2010.61.
Observational studies document the inverse relationship between cardiovascular disease (CVD) and moderate alcohol intake. However, the causal role for alcohol in cardioprotection remains uncertain as such protection may be caused by confounders and misclassification. The aim of our study was to evaluate potential confounders, which may contribute to putative cadioprotection by alcohol.
We evaluated clinical and biological characteristics, including cardiovascular (CV) risk factors and health status, of 149,773 subjects undergoing examination at our Center for CVD Prevention (The Urban Paris-Ile-de-France Cohort). The subjects were divided into four groups according to alcohol consumption: never, low (≤10g/day), moderate (10-30g/day), and high >30 g/day; former drinkers were analyzed as a separate group.
Results showed that after adjustment for age, moderate male drinkers were more likely to display clinical and biological characteristics associated with lower CV risk, including low body mass index, heart rate, pulse pressure, fasting triglycerides, fasting glucose, stress and depression scores together with superior subjective health status, respiratory function, social status and physical activity. Moderate female drinkers equally displayed low waist circumference, blood pressure and fasting triglycerides and low-density lipoprotein-cholesterol. Alcohol intake was strongly associated with plasma high-density lipoprotein-cholesterol in both sexes. Multivariate analysis confirmed that moderate and low drinkers displayed better health status than did never drinkers. Importantly, few factors were causally related to alcohol intake.
The authors conclude that moderate alcohol drinkers display a more favorable clinical and biological profile, consistent with lower CV risk as compared with nondrinkers and heavy drinkers. Therefore, moderate alcohol consumption may represent a marker of higher social level, superior health status and lower CV risk.
This paper states that its goal was to evaluate how moderate alcohol consumption contributes to lower risk of cardiovascular disease when associated with other healthy lifestyle factors. The authors found most of the expected relations between alcohol consumption and indices of health (e.g., moderate drinkers had higher HDL-cholesterol, lower anxiety and depression, lower rates of obesity, etc., but higher rates of smoking and hypertension). However, there were some unusual findings among never drinkers (such as very low values for cholesterol, poorer self-reported health status, very low rates of smoking, higher anxiety levels, etc.); this suggests that this group may have been quite different in many ways from the groups that consumed alcohol.
There were also some questions regarding the analysis, in that p-values of <0.0001 are given for every variable in each table (not unexpected for the huge dataset, and essentially meaningless in this paper). It is unusual that “p for trend” values were reported for men in Table 1, whereas in the text the authors report a “U” or “J” shaped curve for many variables. Mainly, the results of associations with alcohol are the same as have been shown in most previous research: moderate drinkers have other healthy lifestyles and biological values indicating lower cardiovascular risk.
The unusual nature of this paper emerges in the discussion, where the authors are very selective in choosing previous research to support their conclusion than alcohol is not causally associated with essentially every risk factor they measured. Even for the positive association between alcohol and HDL-cholesterol, the authors ignore the results from most prospective epidemiologic studies and a huge amount of animal research that have indicated that HDL-cholesterol increases linearly with alcohol intake and is associated with lower atherosclerosis and coronary disease. They reach a conclusion that “. . . the influence of alcohol on HDL cannot simply be interpreted as a cardioprotective effect.”
Similarly, carefully selecting a few papers upon which to base their conclusions, the authors state that “Thus, there is no clear evidence of a favorable or an unfavorable effect of alcohol intake on weight and body fat distribution.” As for socioeconomic associations, they make the statement that “The majority of well-conducted studies which have assessed CVD as a function of alcohol intake do not take into account adjustment for social status.” This is not correct.
This cross-sectional analysis superficially can be interpreted to support the “healthy drinker hypothesis” – a variant of the “sick quitter hypothesis.” However, as a cross-sectional study, these data clearly cannot be the proper basis for assertion of causality. The authors seem quite ready to minimize the likelihood of causal benefit in what they concede were well-performed prospective observational studies. At the same time they readily imply causality in their own cross-sectional report.
We realize that confounding is a never-ending possibility in observational studies. The level of confounding, however, is difficult to measure. Even the direction of the confounding is not always clear-cut. An example is the connection between Good Health Evaluation, moderate alcohol consumption and future total mortality. The conclusion of Hansel et al is that moderate alcohol drinkers display a more favorable clinical and biological profile compared with non-drinkers and heavy drinkers. However, the percentage of current smokers was only 8.5% among never drinkers but 31.9% among moderate drinking men. The reduced risk of diabetes among moderate drinkers [OR 0.716, CI 0.622-0.825)] is considered by many to be one of the possible explanations for the lower cardiovascular risk of moderate drinkers; however, that important finding is not discussed by the authors of this report. No outcomes are described for subjects in this paper.
In addition to theoretical questions regarding the authors’ implications of their findings, there are indeed data in direct opposition to their conclusions. Mukamal et al1 found that among men with very healthy lifestyles, the addition of moderate drinking was associated with considerably lower risk of myocardial infarction. Several papers2,3,4 have demonstrated that the lower risk of diabetes among moderate drinkers is independent of other lifestyle factors. And the recent paper by Joosten et al5 shows how, even among very healthy subjects (non-smokers, on a healthy diet, physically active, and not obese), alcohol consumption was associated with a large decrease in the risk of diabetes. Joosten et al conclude that “moderate alcohol consumption could be regarded as a complement, rather than an alternative, to other low-risk lifestyle habits.” While these and other such epidemiologic papers may give some general information on the relation of alcohol to health, advice to individuals should always be adjusted according to their own family history, behaviors, other medical conditions, medications, etc.
References from Forum Critique
1. Mukamal KJ, Chiuve SE, Rimm EB. Alcohol consumption and risk for coronary heart disease in men with healthy lifestyles. Arch Intern Med 2006;166:2145-2150.
2. Stampfer MJ, Colditz GA, Willett WC, Manson JE, Arky RA, Hennekens CH, Speizer FE. A prospective study of moderate alcohol drinking and risk of diabetes in women. Am J Epidemiol 1988;128:549-558.
3. Beulens JWJ, Stolk RP, Van der Schouw YT, Grobbee DE, Hendriks HFJ, Bots ML. Alcohol consumption and risk of type 2 diabetes among older women. Diabetes Care 2005;28:2933–2938.
4. Hodge AM, English DR, O’Dea K, Giles GG. Alcohol intake, consumption pattern and beverage type, and the risk of Type 2 diabetes. Diabetic Medicine 2006;23:690–697.
5. Joosten MM, Grobbee DE, van der A DL, Verschuren WWM, Hendriks HFJ, Beulens JWJ. Combined effect of alcohol consumption and lifestyle behaviors on risk of type 2 diabetes. Am J Clin Nutrition, published on-line 21 April 2010. doi:10.3945/ajcn.2010.29170.
An analysis based on a very large number of subjects in France demonstrates, as have most other studies, that moderate consumers of alcohol have many associated healthy lifestyle habits: lower levels of body mass index, blood glucose, heart rate, stress and depression scores; higher subjective health status, HDL-cholesterol values, levels of physical activity and social status. The authors suggest that alcohol is not related causally to any of these factors, and that the other lifestyle factors, not alcohol consumption, are the reason that moderate drinkers have less cardiovascular disease. They chose a very narrow group of citations from the literature to support this contention.
The authors ignore a large number of well-conducted prospective epidemiologic studies showing that moderate drinkers are at lower risk over time of developing certain risk factors. Further, the authors of this paper ignore an immense basic science literature that suggests that alcohol is an important factor in the development of biological risk factors, atherosclerosis, and cardiovascular disease. Further, they do not describe a number of studies that have shown specifically that moderate drinking is associated with less cardiovascular disease and diabetes among subjects who are otherwise very healthy (non-smokers, not obese, physically active, and on a healthy diet).
There is no doubt that confounding by associated lifestyle factors can play a role in the lower risk of chronic diseases among moderate drinkers, who tend to also have other healthy behaviors. However, there is now a large body of scientific evidence that indicates that alcohol is an important factor in the lower rates of such diseases; current scientific data do not support the conclusions of the authors of this paper.
Contributions to this critique by the International Scientific Forum on Alcohol Research were made by
Roger Corder, PhD, MRPharmS, William Harvey Research Institute, Queen Mary University of London, UK
R. Curtis Ellison, MD, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA
Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA
Arthur Klatsky, MD, Dept. of Cardiology, Kaiser Permanente Medical Center, Oakland, CA, USA
Dominique Lanzmann-Petithory,MD, PhD, Nutrition/Cardiology, Praticien Hospitalier Hôpital Emile Roux, Paris, France
Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark
Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy