Critique 196: Adverse health effects of binge drinking on cardiovascular disease — 2 February 2017

Piano MR, Mazzuco A, Kang M, Phillips SA.   Cardiovascular Consequences of Binge Drinking: An Integrative Review with Implications for Advocacy, Policy, and Research. Alcoholism: Clinical and Experimental Research 2017; Pre-publication.  doi: 10.1111/acer.13329

Authors’ Abstract

Worldwide, binge drinking is a major public health problem. The popularized health risks associated with binge drinking include physical injury and motor vehicle crashes; less attention has been given to the negative effects on the cardiovascular (CV) system.

The primary aims of this review were to provide a summary of the adverse effects of binge drinking on the risk and development of CV disease and to review potential pathophysiologic mechanisms.

Using specific inclusion criteria, an integrative review was conducted that included data from human experimental, prospective cross-sectional, and cohort epidemiological studies that examined the association between binge drinking and CV conditions such as hypertension, myocardial infarction, stroke, and arrhythmias. Studies were identified that examined the relationship between binge drinking and CV outcomes.

Collectively, findings support that binge drinking is associated with a higher risk of pre-hypertension, hypertension, myocardial infarction, and stroke in middle-aged and older adults. Binge drinking may also have adverse CV effects in young adults (aged 18-30). Mechanisms remain incompletely understood; however, available evidence suggests that binge drinking may induce oxidative stress and vascular injury and be pro-atherogenic. Public health messages regarding binge drinking need to include the effects of binge drinking on the cardiovascular system.

Forum Comments

The majority of epidemiologic studies that contained data on the pattern of drinking have concluded that while truly moderate drinking has favorable effects on most types of cardiovascular disease (CVD), heavy episodic (binge) drinking tends to have adverse effects. The present paper provides a review of data relating binge drinking to a number of aspects of CVD: hypertension, myocardial infarction (MI), stroke, and cardiac arrhythmias.  The studies reviewed were quite consistent in showing that people who report binge drinking (variously defined) tend to have higher blood pressure as well as greater risk of MI, stroke, and cardiac arrhythmias.

After describing the data from epidemiologic studies, the authors attempt to determine what are the physiologic factors that explain why binge drinking has adverse effects on the risk of CVD. They report that “Data from these studies revealed that binge drinking was associated with vascular oxidative stress, changes in endothelial and smooth cell function, and vascular reactivity.  Binge drinking may also adversely affect lipid profiles and hemostatic/coagulation mechanisms, as well as increase the vulnerability of the myocardium to the development of arrhythmias by altering myocardial electrophysiological properties.”  They conclude this section by stating “Collectively, these data from animal models suggest that repeated and one-time binge drinking induces oxidative stress in both large (aortic) and resistance (mesenteric) vessels.”

The authors also summarized experimental data suggesting that, both acutely and over time, binge drinking impairs endothelial function, flow-mediated vasodilation and nitroglycerin-induced dilation. Binge drinking may also directly alter the vasoreactivity of smooth muscle cells, and may alter the response of the vasculature to vasoactive substances.

Finally, the authors describe how binge drinking may affect lipid profiles and hemostatic/coagulation factors, which can influence risk for MI or stroke, as well as induce cardiac arrhythmias that may relate to MI and sudden cardiac death. Both acute effects (as in “holiday heart syndrome”) and longer-term chronic effects from repeated binge drinking may occur.

The authors end their paper by stating that, in addition to other well-described adverse effects of binge drinking, the effects on CVD are less-well known. And they believe that better education of the public may help prevent binge drinking, although no evidence is presented for this.  While they do not develop any new hypotheses on mechanisms, they outline potential pathways by which binge drinking adversely affects CVD.

Specific comments from Forum members on this paper: Essentially all Forum members agree that the intent of the authors is commendable, as more information should be available to other scientists and to the public on the effects of binge drinking on CVD.  Forum member Finkel considered this to be a straightforward presentation and useful in increasing awareness that, in addition to how much one drinks, how one drinks is very important.  Now, we’ll need similar expositions of the roles of what one drinks (the type of beverage) and of the importance of eating while drinking.”

Reviewer Estruch noted: “Nowadays, cognitive decline and even Alzheimer disease are considered to have ‘common links’ with cardiovascular disease. In the review, I miss the effects of binge drinking on abnormalities of cognitive function, a very common medical disorder in chronic binge drinkers.”  Forum member De Gaetano added: “This review extends information gained from a meta-analysis by Bagnardi et al.  It is well written and the effects of binge drinking on CV outcomes clearly presented. The mechanisms underlying CV side effects are complex and not completely understood, but are well discussed.  It is a useful basic document for further investigation.  Most interesting are possibly the data on young people: it remains to be clarified why binge drinking induces cardiovascular harm in young individuals who usually have a very low CV risk.  In most epidemiologic studies, young people fail to show protection against CVD events from moderate drinking, mainly because of lack of clinical outcomes.”

Despite the enthusiasm for the paper by most Forum members, reviewer Puddey provided an extensive comment on a large number of research reports not covered by the authors that add considerable further information on the topic. Puddey states: “In this paper, Piano et al have reviewed a question that has important public health implications – the relevance of pattern of drinking (specifically binge drinking) in any assessment of the relationship between alcohol and either cardiovascular risk factors or cardiovascular endpoints. Although a very useful summary, the review in parts has not been sufficiently careful or comprehensive.

“For example, they state that only three studies have been identified that have studied the acute effect of drinking on blood pressure and state that the participants in those studies consumed 4-5 standard drinks over 2-5 hours. However, in the first of these studies (1) participants consumed 0.75g ethanol/kg within 15 minutes, in the second (2) 60 g of ethanol was drunk over 60 minutes, and in the third (3) 12 drinks (2.2g/kg) were consumed over 6 hours.  Further, there have been many other studies within this dose range on the administration of alcohol and its effects on blood pressure (4-9). This list of additional studies is by no means comprehensive and a fairer overall conclusion from all these reports combined would be that there is an acute depressor effect of alcohol within this dose range followed by an increase in blood pressure towards the second half of any 24-h period after drinking.

“The authors have also misrepresented the results of the 1999–2004 National Health and Nutrition Examination Survey [10], saying prevalence ratios for pre-hypertension with binge drinking occurred in both men and women who reported more than 1 episode of binge drinking per week. However, in that study the alcohol-blood pressure associations were different by gender: both higher drinking quantity and frequency of binge drinking were only associated with higher blood pressure in men, not in women.  Moreover, in that study it was noted that risk and frequency of binge drinking increase with frequency of drinking [11].  Because background alcohol intake was not taken into account in the analysis the question as to whether binge drinking independently influences BP was not sufficiently addressed.

“The present paper by Piano et al excludes intervention studies which have examined the relationship between pattern of consumption and level of blood pressure, studies which may indeed provide a higher level of evidence for any independent effect of binge drinking. In this regard, my colleagues and I conducted a carefully controlled intervention [12] where fourteen participants were categorized as predominantly weekend drinkers, while the remaining 41 participants drank regularly on a daily basis.  The two groups were drinking similar amounts of alcohol at baseline (~350g/week) with the first group concentrating the bulk of their intake from Friday to Sunday.  After 4 weeks of familiarization, all participants were randomly allocated to drinking low-alcohol beer (0.9% alc/vol) or to maintain their usual drinking pattern with provision of full-strength beer (5% alc/vol) for 4 weeks.  They then switched back to their usual drinking habits or low-alcohol beer, respectively, for a further 4 weeks while again maintaining their usual drinking pattern.  Baseline ambulatory systolic blood pressure in weekend but not in daily drinkers was 2.4 mmHg higher on Monday than it was on Thursday. This Monday-Thursday difference was lost during intervention.  When subjects switched from the high-alcohol to the low-alcohol period the falls in ambulatory systolic blood pressure in weekend (3.1 mmHg) and daily drinkers (2.2 mmHg) were similar.  Most of the fall was evident during week 1 of the low-alcohol period for weekend drinkers but not until week 4 for daily drinkers.  These results were interpreted as demonstrating that the blood pressure raising effect of alcohol is similar in magnitude in weekend and daily drinkers but with a more rapid onset and offset in weekend drinkers compared to daily drinkers.

“The PRIME study has been discussed in this paper in relation to the implications of binge drinking for ischemic heart disease [13] but the outcomes for BP in that study have not been referenced. In the PRIME study, which compared the population of Belfast with those of 3 French cities [14], the Northern Irish subjects consumed two thirds of their alcohol intake on the weekend and had higher BP on Monday, falling towards Thursday, while the French subjects consumed their alcohol in a more homogenous pattern and had constant BP throughout the week.  The same phenomenon was also highlighted by a British study of the alcohol–BP relationship [15].  That study found higher daily BP in heavy weekend drinkers than in moderate daily drinkers, even though total weekly alcohol intake was similar between the two groups.  Diagnosis of hypertension was more prevalent on Mondays than on Fridays in moderate and heavy weekend drinkers while in heavy daily drinkers, the prevalence of hypertension was substantially higher on both Monday and Tuesday.

“Finally, a previous meta-analysis of cohort and case-control studies that assessed the dose-response relationship between alcohol and CAD, and whether this was modified by pattern of alcohol intake, has not been discussed [16]. In that study, compared with those who abstained from alcohol, regular heavy drinkers exhibited a reduced pooled relative risk for CAD of 0.75 (95% CI 0.64 to 0.89) while for heavy irregular or binge drinkers the RR was increased to 1.10 (95% CI 1.03 to 1.17).  A further relevant report from the Kangwha Cohort Study from Korea that focussed on CV outcomes for hypertensive binge drinkers [17] has also not been included in the review.  In that analysis, after adjusting for total alcohol consumption, in binge drinkers with hypertension who reported 6 drinks per occasion there was a 4.41 increase in the hazard ratio for cardiovascular mortality, while in heavy binge drinkers (12 drinks per occasion) with hypertension there was a 12.7 fold increase.”

Potential mechanisms of alcohol’s effects: Forum reviewer Ursini noted: “I fully agree with the comments from epidemiologists.  For me, as a basic scientist interested to mechanisms, the results are quite obvious.  Ethanol (as the large part of nutrients and xenobiotics) has an hormetic effect: toxic at high dose and protective at low dose.  This is apparently due to a bimodal effect on nucleofilic tone, in turn controlling inflammation and eventually cell death.  Binge drinking is no more than a way to change the concentration (dose in a given time) of the ethanol (and of everything else that is present in the drink).  Paracelsus would agree.”  Reviewer Mattivi added: “I totally agree with the comments of Ursini.”  Reviewer Van Velden noted: “The authors emphasize oxidative stress as a major mechanism for CVD.  However, our own research has indicated that red wine does not cause oxidative stress compared to brandy; it seems that the authors used pure ethanol and did not include wine in the type of beverage in their analysis.”

Forum member Skovenborg added: “I agree with the comments of others and applaud the extended evidence base suggested by Puddey. I also agree with Finkel’s comments on the importance on how we drink, including information on what you drink (beverage type), e.g., the difference between drinking 5-6 shots of whiskey or cocktails during a few hours in a fasting condition compared to drinking 5-6 glasses of wine during a dinner with the serving of the courses setting the drinking pace.  In a Danish population of moderate drinkers, occasional binge drinking was not associated with risk of IHD and all-cause mortality (18).  To follow up on Ursini’s statement, ‘Binge drinking is no more than a way to change the concentration (dose in a given time) of the ethanol,’ I would add that the BAC levels resulting from the two different drinking scenarios could be quite different.”

Forum member Stockley stated that, overall, “This is a sound critique of a paper which highlights yet again the importance of pattern as well as amount of alcohol consumed when evaluating physiological effects. Strongly supported by other diet and lifestyle studies, this information needs to be imparted in alcohol drinking guidelines and captured in simple public health messages.”

Reviewer Ellison concluded that a “comprehensive review” of drinking patterns of alcohol in relation to the risk of CVD should include all of the available scientific data on the topic to be most useful. Taking into consideration the additional research results described in this critique by Forum member Puddey and others provides a much better overview of the effects of binge drinking on CVD.

References from Forum critique

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2. Rosito GA, Fuchs FD, Duncan BB. Dose-dependent biphasic effect of ethanol on 24-h blood pressure in normotensive subjects. Am J Hypertens 1999; 12:236-240.
3. Seppa K, Sillanaukee P. Binge drinking and ambulatory blood pressure. Hypertension 1999; 33:79-82.
4. Kupari M. Acute cardiovascular effects of ethanol. A controlled non- invasive study. British Heart Journal 1983; 49:174-182.
5. Ireland MA, Vandongen R, Davidson L, Beilin LJ, Rouse IL. Acute effects of moderate alcohol consumption on blood pressure and plasma catecholamines. Clin Sci 1984; 66:643-648.
6. Puddey IB, Vandongen R, Beilin LJ, Rouse IL. Alcohol stimulation of renin release in man: its relation to the hemodynamic, electrolyte, and sympatho-adrenal responses to drinking. J Clin Endocrinol Metab 1985; 61:37-42.
7. Abe H, Kawano Y, Kojima S, Ashida T, Kuramochi M, Matsuoka H, et al. Biphasic effects of repeated alcohol intake on 24-hour blood pressure in hypertensive patients. Circulation 1994; 89:2626-2633.
8. Kawano Y, Abe H, Kojima S, Ashida T, Yoshida K, Imanishi M, et al. Acute depressor effect of alcohol in patients with essential hypertension. Hypertension 1992; 20:219-226.
9. Aguilera MT, De la Sierra A, Coca A, Estruch R, Fernández-Solá J, Urbano-Márquez A. Effect of alcohol abstinence on blood pressure: assessment by 24-hour ambulatory blood pressure monitoring. Hypertension 1999; 33:653-657.
10. Fan AZ, Li Y, Elam-Evans LD, Balluz L. Drinking pattern and blood pressure among non-hypertensive current drinkers: findings from 1999-2004 National Health and Nutrition Examination Survey. Clinical epidemiology 2013; 5:21-27.
11. Paradis C, Demers A, Picard E, Graham K. The importance of drinking frequency in evaluating individuals’ drinking patterns: implications for the development of national drinking guidelines. Addiction 2009; 104:1179-1184.
12. Rakic V, Puddey IB, Burke V, Dimmitt SB, Beilin LJ. Influence of pattern of alcohol intake on blood pressure in regular drinkers – a controlled trial. J Hypertens 1998; 16:165-174.
13. Ruidavets JB, Ducimetiere P, Evans A, Montaye M, Haas B, Bingham A, et al. Patterns of alcohol consumption and ischaemic heart disease in culturally divergent countries: the Prospective Epidemiological Study of Myocardial Infarction (PRIME). Br Med J 2010; 341:c6077.
14. Marques-Vidal P, Arveiler D, Evans A, Amouyel P, Ferrieres J, Ducimetiere P. Different alcohol drinking and blood pressure relationships in France and Northern Ireland: The PRIME Study. Hypertension 2001; 38:1361-1366.
15. Wannamethee G, Shaper AG. Alcohol intake and variations in blood pressure by day of examination. J Hum Hypertens 1991; 5:59-67.
16. Bagnardi V, Zatonski W, Scotti L, La VC, Corrao G. Does drinking pattern modify the effect of alcohol on the risk of coronary heart disease? Evidence from a meta-analysis. J Epidemiol Community Health 2008; 62:615-619.
17. Sull JW, Yi SW, Nam CM, Choi K, Ohrr H. Binge drinking and hypertension on cardiovascular disease mortality in Korean men and women: a Kangwha cohort study. Stroke 2010; 41:2157-2162.
18. Skov-Ettrup LS, Eliasen M, Ekholm O, Grønbæk M, Tolstrup JS. Binge drinking, drinking frequency, and risk of ischaemic heart disease: A population-based cohort study. Scand J Public Health 2011;39:880-887.

Forum Summary

This review paper on the effects of binge drinking on the risk of cardiovascular disease (CVD) provides considerable information on a topic of importance to public health. It clearly indicates that subjects who binge drink, however defined, tend to be at increased risk for hypertension, myocardial infarction, stroke, and cardiac arrhythmias.  These adverse health outcomes are in addition to the well-known effects of binge drinking on drunkenness and many adverse health effects, both acute and chronic, as well as risk from violence and accidents to the drinker and to others.

While the members of the Forum applaud the efforts of the authors to present data on this relation, this paper failed to include many important previous research reports on the topic. Forum member Ian Puddey and others have prepared an extensive summary of many of the key research papers not addressed by the authors of this paper; their remarks are included in the full Forum critique. It describes how many factors, such as not only the amount but the rate at which alcohol is consumed, the type of beverage, whether or not food is being consumed, the prior drinking habits of the subjects, and many other factors can influence the effects of alcoholic beverages on health.

The Forum members conclude that a “comprehensive review” of binge drinking and other drinking patterns of alcohol in relation to the risk of CVD should include all of the available scientific data on the topic to be most useful. Taking into consideration the additional research results described in this critique provides a much better overview of the effects of binge drinking on CVD.  The bottom line is that episodic heavy drinking, or binge drinking, has adverse influences on many health outcomes, including the risk of CVD.

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

Elizabeth Barrett-Connor, MD, Distinguished Professor, Division of Epidemiology, Department of Family Medicine and Public Health and Department of Medicine, University of California, San Diego, La Jolla, CA USA

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

R. Curtis Ellison, MD, Professor of Medicine & Public Health, Boston University School of Medicine, Boston, MA, USA

Ramon Estruch, MD, PhD, Hospital Clinic, IDIBAPS, Associate Professor of Medicine, University of Barcelona, Spain

Harvey Finkel, MD, Hematology/Oncology, Boston University Medical Center, Boston, MA, USA

Fulvio Mattivi, MSc, Head of the Department of Food Quality and Nutrition, Research and Innovation Centre, Fondazione Edmund Mach, in San Michele all’Adige, Italy

Ian Puddey, MD, Dean, Emeritus, Faculty of Medicine, Dentistry & Health Sciences, University of Western Australia, Nedlands, Australia

Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark

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

Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway

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

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