Critique 120: Binge drinking impairs endothelial function in young people — 20 August 2013

Goslawski M, Piano MR, Bian J-T, Church EC, Szczurek M, Phillips SA.  Binge drinking impairs vascular function in young adults. J Am Coll Cardiol 2013;62:201–207.

Authors’ Abstract

Objectives  The aim of this study was to assess whether young binge drinkers (BD) have impaired macrovascular and microvascular function and cardiovascular disease risk factors compared with age-matched alcohol abstainers (A).

Background  Binge drinking rates are highest on college campuses and among those age 18 to 25 years; however, macrovascular and microvascular endothelial function in young adults with histories of repeated binge drinking (≥5 standard drinks in 2 h in men, ≥4 standard drinks in 2 h in women) has not been investigated.

Methods  Cardiovascular profiles, brachial artery endothelial-dependent flow-mediated dilation (FMD), and flow-independent nitroglycerin (NTG)–mediated dilation and vasoreactivity of resistance arteries (isolated from gluteal fat biopsies) were evaluated in A and BD.

Results Men and women (18 to 25 years of age; A, n = 17; BD, n = 19) were enrolled.  In the BD group, past-month mean number of binge episodes was 6 ± 1, and the mean duration of binge drinking behavior was 4 ± 0.6 years. FMD and NTG-mediated dilation were significantly lower in the BD group (FMD: 8.4 ± 0.7%, p = 0.022; NTG-mediated dilation: 19.6 ± 2%, p = 0.009) than in the A group (FMD: 11 ±  0.7%; NTG-mediated dilation: 28.6 ± 2%).   Acetylcholine-induced and sodium nitroprusside–induced dilation in resistance arteries was not significantly different between the A and BD groups.  However, endothelin-1–induced constriction was significantly enhanced in the BD group compared with the A group (p = 0.032). No differences between groups were found in blood pressure, lipoproteins, and C-reactive protein.

Conclusions  Alterations in the macrocirculation and microcirculation may represent early clinical manifestations of cardiovascular risk in otherwise healthy young BD. This study has important clinical implications for screening young adults for a repeated history of binge drinking.

Forum Comments

The function of the vascular endothelium is a key process in the development of atherosclerosis and coronary heart disease.  Most studies of the effects of alcohol consumption on endothelial function have been carried out among middle-aged or older adults, and generally show that moderate drinking improves function, whereas binge drinking decreases function.  Whether or not alcohol consumption among young people has any lasting biological effects on cardiovascular risk is unclear: risk factors tend to track from childhood into adulthood, but specific long-lasting effects related only to drinking in young people are not known.  Hence, data are currently not available to answer the question as to when during life people might consider beginning the moderate consumption of alcohol for the potential lowering of cardiovascular risk later in life.  The present study does not answer that question, as it only compares abstaining young people with binge drinkers, and does not compare abstainers with moderate drinkers (perhaps since few young people are regular moderate drinkers). 

In this study, binge drinkers were defined as males reporting that they consumed ≥ 5 typical drinks in 2 hours or females reporting consuming ≥ 4 typical drinks in 2 hours; the average number of binge-drinking episodes among these subjects was 6 ± 1 episodes in the past month.  The paper concludes that binge drinking among 18 – 25 year olds has clear adverse effects on endothelial function.

Specific comments by Forum members:  This is not a large study, and the low numbers tend to limit the usefulness of p-values to determine effect (or lack of effect).  The investigators estimated macrovascular dysfunction through studying brachial artery endothelium-dependent and endothelium-independent dilation, which is the standard approach for its assessment.  They used vascular function assessed in vitro in arteries obtained from subjects through gluteal fat pad biopsies as an estimate of microvascular effect.  

The authors conclude that their study showed adverse effects on both microvascular and macrovascular function to be associated with frequent binge drinking in young people.  It is hoped that the investigators in this study, or others, will provide data on the effects on vascular  function of regular, moderate alcohol consumption among young people, and to determine how long such effects persist, with or without continued alcohol intake.

Forum member Finkel stated that he had long thought it “unwise to focus attention only on the vasculature of middle-aged and older individuals when we know that atherosclerosis starts in the young; beginning with pathological studies of very young soldiers during the Korean War, we’ve had ample evidence of this.  If atherosclerosis begins so early, and gets to be clinically evident only years later, it should be important to prevent its development and progression starting early.   I therefore welcome this paper, which also serves to focus attention on two other vital issues: the evils of binge drinking and the central role of the blood vessels.”

Forum member Goldfinger also had comments: “Firstly, the methodology used by these investigators was ambitious and should be lauded, as it reflects a comprehensive assessment of vascular responsiveness in both groups.  Both groups demonstrated a (+) FMD, the non-bingers more so than the bingers. Thus both had a normal response.  In subjects with atherogenic risk factors or frank atherosclerotic disease, we usually see no vasodilation and in fact, inappropriate vasoconstriction in response to endothelial stimulation (FMD).  I am not aware that a less robust, albeit normal response, is in fact a notable difference.  The same is true for NTG response (endothelial independent).  The subtle suggestion that binge drinkers may have stiffer arteries is an opinion based on these data . . . but may, in fact, be true.  Both groups had a normal response, and I believe that is all that can be said here.

“The difference regarding endothelin production is novel.  This may be an important observation that can explain the paradox of why heavy alcohol drinkers may have accelerated atherosclerosis.  In general NO production is favorable even with higher levels of alcohol (specifically  – actually exclusively — with wine consumption).  ETOH itself has been shown repeatedly by my group and others not to alter FMD significantly.  It may be that not the lesser vasodilation potential, but the enhanced vasoconstriction potential hurts binge drinkers.  Of course, what needs to be considered is that college students are less likely wine drinkers and typically rather consumers of beer and inexpensive spirits.”

An invited comment from Professor  Roger Corder stated that he “was not convinced that the groups were adequately matched.  The isolated vessel studies have only been conducted on a proportion of the two groups, so these results may not be entirely representative.  There is no analysis of the effect of sex or ethnicity confounders on the isolated vessel responses.”  Reviewer de Gaetano was also concerned about inadequate adjustment of potential confounders.  He points out that “the authors acknowledge that their study was cross-sectional: it would be interesting to know if the described effects of binge drinking are permanent or reversibile, and in the latter case after how long they are reversed following the last bingeing episode.  Otherwise, the implications of these data for atherosclerosis development in older age would be rather weak.”  He added: “It would also be interesting to see whetheer wine or gin binge drinking would have the same effects on vascular function.” 

Reviewer Djoussé stated:  This is an interesting paper in support of adverse effects of binge drinking on vascular function in young people, but the study design precludes a firm conclusion.  For example, residual confounding by other characteristics associated with binge drinking in young adults could have led to an overestimation of the effect of binge drinking on flow mediated dilation (FMD).   Matching on age alone does not appear to be sufficient to address this concern.  Poor response of FMD on nitroglycerine in binge drinkers compared to abstainers could be partially explained by imbalanced distribution of risk factors for endothelial dysfunction between the two groups.”

Reviewer Skovenborg stressed that “the long time consequences of temporarily impaired FMD in young adults are unknown.  Further, the study is cross-sectional and confounding may be present; for example, no information on food intake before or together with alcohol intake is given.”  He added that while most studies show adverse vascular effects of binge drinking, other studies (e.g., Skov-Ettrup et al, 2011) have not demonstrated an effect of binge drinking on the risk of ischemic heart disease.

Reference from Forum critique:  Skov-Ettrup LS, Eliasen M, Ekholm O, Grønbaek M, Tolstrup JS. Binge drinking, drinking frequency, and risk of ischaemic heart disease: A population-based cohort study. Scandinavian Journal of Public Health 2011;39:880–887.

Forum Summary

The function of the vascular endothelium is a key process in the development of atherosclerosis and coronary heart disease, and extensive studies among middle-aged and elderly adults generally show beneficial effects of moderate drinking on vascular function.  Whether or not alcohol consumption among young people has any lasting biological effects on cardiovascular risk is unclear: risk factors tend to track from childhood into adulthood, but specific long-lasting effects related only to drinking in young people are not known.  Hence, data are currently not available to answer the question as to when during life people might consider beginning the moderate consumption of alcohol for the potential lowering of cardiovascular risk later in life.

The present study does not answer that question, as it only compares abstaining young people with binge drinkers, with the latter being defined as subjects reporting that they consumed ≥ 5 drinks in 2 hours for males, and ≥ 4 drinks in 2 hours for females.  (The average number of binge-drinking episodes for these subjects was 6 ± 1 within the past month.)   It does not compare abstainers with moderate drinkers.  However, the paper does show that binge drinking among 18 – 25 year olds has adverse effects on endothelial function.

Forum reviewers were pleased to see this study, but point out that it is a cross-sectional analysis, and only compares binge drinkers with non-drinking young people.  Further, inadequate data are presented to know the degree to which the results of the study may suffer from residual confounding from other factors.

The authors conclude that their study showed adverse effects on both microvascular and macrovascular function to be associated with frequent binge drinking in young people.  It is hoped that these investigators, or others, will in the future provide data on the effects on vascular  function of regular, moderate alcohol consumption among young people.  It would also be interesting to learn if effects are different for high-polyphenol wine than for other beverages.  Further, it will be important to determine how long beneficial or adverse effects on vascular function may persist, with or without continued alcohol intake.   

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Comments on this paper were provided by the following members of the International Scientific Forum on Alcohol Research:

Luc Djoussé, MD, DSc, Dept. of Medicine, Division of Aging, Brigham & Women’s Hospital and Harvard Medical School, Boston, MA, USA 

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

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

Pierre-Louis Teissedre, PhD, Faculty of Oenology – ISVV, University Victor Segalen Bordeaux 2, Bordeaux, France

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

Imke Janssen, PhD, Department of Preventive Medicine, Rush University Medical Centre, Chicago, IL, USA

Dag S. Thelle, MD, PhD, Senior Professor of Cardiovascular Epidemiology and Prevention, University of Gothenburg, Sweden; Senior Professor of Quantitative Medicine at the University of Oslo, Norway

Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, Dept. of Cardiology, University of Arizona School of Medicine, Tucson, Arizona, USA

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

Also, this critique includes an invited commentary from Roger Corder, PhD, MRPharmS, William Harvey Research Institute, Queen Mary University of London, UK