Critique 150: A new meta-analysis on the relation of alcohol consumption to the risk of ischemic heart disease — 6 November 2014

Roerecke M, Rehm J.  Alcohol consumption, drinking patterns, and ischemic heart disease: a narrative review of meta-analyses and a systematic review and meta-analysis of the impact of heavy drinking occasions on risk for moderate drinkers. BMC Medicine 2014;12:182.

Authors’ Abstract

Background: Alcohol consumption is a major global risk factor for mortality and morbidity.  Much discussion has revolved around the diverse findings on the complex relationship between alcohol consumption and the leading cause of death and disability, ischemic heart disease (IHD).

Methods: We conducted a systematic search of the literature up to August 2014 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify meta-analyses and observational studies examining the relationship between alcohol drinking, drinking patterns, and IHD risk, in comparison to lifetime abstainers.  In a narrative review we have summarized the many meta-analyses published in the last 10 years, discussing the role of confounding and experimental evidence.  We also conducted meta-analyses examining episodic heavy drinking among on-average moderate drinkers.

Results: The narrative review showed that the use of current abstainers as the reference group leads to systematic bias.  With regard to average alcohol consumption in relation to lifetime abstainers, the relationship is clearly J-shaped, supported by short-term experimental evidence and similar associations within strata of potential confounders, except among smokers.  Women experience slightly stronger beneficial associations and also a quicker upturn to a detrimental effect at lower levels of average alcohol consumption compared to men.  There was no evidence that chronic or episodic heavy drinking confers a beneficial effect on IHD risk.  People with alcohol use disorder have an elevated risk of IHD (1.5- to 2-fold).  Results from our quantitative meta-analysis showed that drinkers with average intake of <30 g/day and no episodic heavy drinking had the lowest IHD risk (relative risk = 0.64, 95% confidence interval 0.53 to 0.71). Drinkers with episodic heavy drinking occasions had a risk similar to lifetime abstainers (relative risk = 1.12, 95% confidence interval 0.91 to 1.37).

Conclusions: Epidemiological evidence for a beneficial effect of low alcohol consumption without heavy drinking episodes is strong, corroborated by experimental evidence.  However, episodic and chronic heavy drinking do not provide any beneficial effect on IHD. Thus, average alcohol consumption is not sufficient to describe the risk relation between alcohol consumption and IHD.  Alcohol policy should try to reduce heavy drinking patterns.

Forum Comments

Epidemiologic studies for decades have demonstrated that regular, moderate drinkers tend to have considerably lower risk than non-drinkers of developing ischemic heart disease (IHD), another name for coronary heart disease.  Despite an immense amount of observational and experimental data, and limited clinical trial evidence, that support this association, a number of scientists continue to have difficulty in accepting that this relation might be causal.  Numerous papers have attempted to “explain” the inverse association between moderate drinking and heart disease by suggesting confounding by other lifestyle factors, errors in studies, the inclusion of ex-drinkers in the referent group, etc.

The present paper is from authors who have tended in most of their previous work to focus on the dangers of alcohol consumption.  Hence, it is surprising that in the present paper they present what Forum members consider to be a balanced appraisal of the relation of alcohol to IHD.   

Specific comments on this paper:  Forum reviewers considered this to be a well-done study. Most epidemiologists and Forum members have been stating for many years that simply taking the average amount of alcohol consumed per week to characterize a person’s alcohol intake is inadequate, and it is reassuring that the authors of this paper agree that the assessment of drinking pattern is also important.  As stated by reviewer Skovenborg, “What is new is the acknowledgement of these authors of a J-shaped relation between alcohol consumption and IHD, which is supported by high quality epidemiological evidence and short-term experimental data.” 

Skovenborg also stated that it was somewhat surprising that the following two statements by the authors were on the same page: “For drinkers having one to two drinks per drinking day without episodic heavy drinking, there is substantial and consistent evidence from epidemiological and short-term experimental studies for a beneficial association with IHD risk when compared to lifetime abstainers.  The alcohol-IHD relationship fulfills all criteria for a causal association proposed by Hill.”  However, the authors then state: “Alcohol consumption should be as low as possible; no amount of consumption is safe.” 

Reviewer Finkel commented on this as well: “The first sentence is from the scientific brains, the second sentence from the puritanical souls of the authors, showing great stress of internal conflict.”   Forum member de Gaetano and others agreed with this assessment, and reviewer Ursini added: “When soul conflicts with brain, the risk of killing science is not irrelevant, and eventually also a freedom is at risk.”  Reviewer Stockley considered this paper to reflect “a huge turn-around for these authors who recently have been extremely negative about the beneficial effects of alcohol on cardiovascular disease.”  She suggested that the disparate messages from these two sentences of the authors may indicate “an internal struggle of the authors in their conclusions.”

Reviewer Ellison thought it was interesting that the authors included a separate analysis of the relation of alcohol with IHD for Russia, but not for other countries.  It appears that they wanted to emphasize the dangers of alcohol, and separately reporting on Russia tends to do this.  It is well known that alcohol abuse remains rampart in Russia, and is a leading cause of death.

Forum member Lanzmann-Petithory had some interesting observations: “In Russia, alcoholism is a scourge (primarily with vodka); I tend to think as always that the J-shape in much of Europe is largely due to the consumption of wine, and not only to the drinking pattern.”  She adds: “The data showing the large difference in effect between consumption by moderate drinkers who are not episodic heavy drinkers and those who are episodic heavy drinkers is striking.  I wonder what would be the risk for a moderate regular drinker who only occasionally binge drinks? Maybe somewhere between the two?  Unfortunately, by using data based only on the average intake, the authors include in the same group regular moderate drinkers and binge drinkers; in other words, combining people who drink in what has been described as the typical French pattern (regularly, moderate consumption, usually of wine) with those who drink in the pattern frequently seen in Northern Europe: heavy episodic consumption.”  (As described in Lanzmann-Petithory, 2013.) 

She continues: “In the discussion about the confounding factors, age, smoking, physical activity, BMI etc., they did not mention at all the different alcoholic beverages that can modulate the relation between alcohol consumption and CHD risk.  You cannot find the words wine or beer or spirits in the paper; only pure alcohol is considered.  Moreover, the type of alcoholic beverage interacts probably with drinking pattern (less binge drinking among typical wine consumers).”

Reviewer Van Velden stated “This is a well-balanced view of the health implications of alcohol consumption.  It also mentions that the etiology of IHD is multi-factorial, and other lifestyle factors have to be taken into consideration before a causal relationship can be found.  Responsible drinkers usually have a healthy lifestyle, and we must make adjustments for confounding.  It is interesting to see that subjects reporting episodic heavy drinking occasions had a risk similar to that of lifetime abstainers.”

Reference from Forum critique:  Lanzmann-Petithory D.  Commentary on Kerr et al. The French Paradox versus binge drinking. Addiction 2013;108:1049-1050. doi:10.1111/add.12211.

Forum Summary

This meta-analysis is from authors who in the past have tended to argue that the demonstrated inverse association between moderate alcohol consumption and ischemic heart disease (IHD) shown in most studies is due to confounding by other lifestyle factors.  However, in this paper, they come to the conclusion (in their words): “Results from our quantitative meta-analysis showed that drinkers with average intake of < 30 g/day and no episodic heavy drinking had the lowest IHD risk (relative risk = 0.64, 95% confidence interval 0.53 to 0.71).  Drinkers with episodic heavy drinking occasions had a risk similar to lifetime abstainers (relative risk = 1.12, 95% confidence interval 0.91 to 1.37).” 

The conclusions of the authors thus not only support a “J-shaped” curve for alcohol consumption and IHD but provide additional support suggesting that the effect may be causal, i.e., related to the alcohol consumption and not to other associated lifestyle factors.  They state: “For drinkers having one to two drinks per drinking day without episodic heavy drinking, there is substantial and consistent evidence from epidemiological and short-term experimental studies for a beneficial association with IHD risk when compared to lifetime abstainers.  The alcohol-IHD relationship fulfills all criteria for a causal association proposed by Hill.”

It is clear from epidemiologic studies that moderate drinkers may exhibit moderation in other lifestyle factors (such as not smoking, eating a healthy diet, etc.).  Indeed, there is aggregation of healthy lifestyle factors that must be considered when judging how a single factor (such as moderate drinking) relates to disease outcomes.  This meta-analysis suggests that other lifestyle factors do not explain the lower risk of IHD found to occur among moderate drinkers.  In fact, increasingly, moderate drinking is found to be an independent (and rather important) lifestyle factor that lowers the risk of cardiovascular disease, regardless of other factors.  Such protection is not seen when drinking is more than moderate, defined in this paper as an average of 30 grams or more of alcohol per day, the equivalent of about 2 ½ to 3 typical drinks.

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Comments on this critique have been provided by the following members of the International Scientific Forum on Alcohol Research:

Giovanni de Gaetano, MD, PhD, Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo NEUROMED, Pozzilli, Italy

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

Dominique Lanzmann-Petithory,MD, PhD, Nutrition/Cardiology, Praticien Hospitalier Hôpital Emile Roux, Paris, France

Erik Skovenborg, MD, Scandinavian Medical Alcohol Board, Practitioner, Aarhus, Denmark

Creina Stockley, PhD, MBA, Clinical Pharmacology, Health and Regulatory Information Manager, Australian Wine Research Institute, Glen Osmond, South Australia, Australia

Fulvio Ursini, MD, Dept. of Biological Chemistry, University of Padova, Padova, Italy

David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa