Critique 146: Alcohol and the risk of abdominal aortic aneurysm — 4 September 2014

Stackelberg O, Björck M, Larsson SC, Orsini N, Wolk A.  Alcohol Consumption, Specific Alcoholic Beverages, and Abdominal Aortic Aneurysm.  Circulation 2014;130:646-652.

Authors’ Abstract

Background—Studies investigating the role of alcohol consumption in the development of abdominal aortic aneurysm (AAA) are scarce. We aimed to examine associations between total alcohol consumption and specific alcoholic beverages and the hazard of AAA.

Methods and Results—The study population was made up of 44 715 men from the Cohort of Swedish Men and 35 569 women from the Swedish Mammography Cohort who were 46 to 84 years of age at baseline in 1998. Cox proportional hazards models were used to estimate hazard ratios with 95% confidence intervals for the associations between alcohol consumption, assessed through a food frequency questionnaire, and AAA, identified by means of linkage to the Swedish Inpatient Register and the Swedish Vascular Registry (Swedvasc). Over the 14-year follow-up until December 2011 (1 019 954 person-years), AAAs occurred in 1020 men and 194 women. Compared with the consumption of 1 glass of alcohol per week (12 g of ethanol), the hazard ratio of AAA among men who consumed 10 glasses per week was 0.80 (95% confidence interval, 0.68–0.94). The corresponding hazard ratio among women who consumed 5 glasses per week was 0.57 (95% confidence interval, 0.40–0.82). Among participants free from cardiovascular disease, total alcohol consumption did not seem to be associated with hazard of the disease. The most commonly consumed alcoholic beverages, beer among men and wine among women, were inversely associated, whereas no association was observed for liquor.

Conclusions—Moderate alcohol consumption, specifically wine and beer, was associated with a lower hazard of abdominal aortic aneurysm. The associations between higher doses of alcohol and risk of the disease remain unknown.

Forum Comments

While there have been a huge number of studies on the effects of alcohol consumption on the risk of coronary heart disease and stroke, and a considerable number on the effects on the risk of heart failure, few studies have related alcohol intake to the development of abdominal aortic aneurysm (AAA).  Such studies have had inconsistent results. 

The present study is based on very large population-based cohorts, followed prospectively for the development of AAA.  In their cohorts, there were a total of more than 1,200 cases of AAA, of which about 20% had rupture of their aneurysms. 

The results of this study suggest that moderate drinking is associated with a lower risk of AAA, with the beneficial effect primarily among consumers of beer or wine.  There were too few heavy drinkers to ascertain if large amounts of alcohol may increase risk.

Specific comments from Forum members:  Forum member Skovenborg considered this to be “A fine study, well planned and well executed, with trustworthy results on risk reduction and reasonable suggestions of biological mechanisms.”  Reviewer Finkel agreed: “This seems to me a straight-forward study, without prejudice or methodological pitfalls.  With all the evidence supporting coronary and ischemic stroke risk reduction associated with moderate drinking, it certainly is consistent that the risk of AAA, another manifestation of atherosclerosis, would also be reduced.”

Reviewer de Gaetano had similar comments: “This is a well performed study. It supports findings that wine polyphenols are anti-inflammatory, anti-oxidant, anti-platelet compounds; there seem to be few differences in epidemiologic studies between wine and beer in cardiovascular protection.  To my knowledge no study has compared the cardiovascular protective effects of non-alcoholic components of wine and beer.  One must presume that a combined effect of alcohol and non-alcoholic substances is responsible for the comparable cardiovascular protection offered by wine or beer. Spirits do not share this combined effect.”

Forum member Goldfinger stated: “Mechanistically, the authors speak to the potential of reduced atherosclerotic burden and reduced vascular inflammation as possible mechanisms for the decreased incidence of AAA.  Yet, little is mentioned of hypertension, which is a well-known consequence of alcohol, if not the most important instigator of AAA.”

Goldfinger noted the report by Renaud et al on alcohol and hypertension “which showed the predictable increase in blood pressure from alcohol consumption but a reduced incidence of coronary heart disease even among hypertensives who were wine drinkers.”  The Renaud et al study reported that moderate wine drinkers had significantly lower risks of death from all causes than did abstainers.  Even for the highest quartile of blood pressure, moderate wine drinkers were protected from all-cause mortality; no significant reduction in all-cause mortality was seen in relation to systolic blood pressure in consumers of other beverages containing alcohol.   Goldfinger suggests that “this may be attributed to the robust salutary vascular benefits that red wine has on vascular biology.  This however might not be expected to protect against AAA though, as aneurysm of the abdominal aorta is strongly related to elevated blood pressure, and there is little argument that alcohol raises blood pressure.”

Goldfinger continued: “The authors report an unexpected low incidence of hypertension in their study population.  It looks like the mean age of the study group was about 60 years with an incidence of hypertension of about 25%.  The CDC in the US reports incidence of hypertension among ages 55 – 64 at 54% in men and 53.3% in women, with about one half of these persons have controlled hypertension.  Could this have affected their results?”

Reviewer Lanzmann-Petithory questioned the finding of similar effects of beer and wine, stating that beer actually has much lower levels of polyphenols than wine.  She believed that increasing polyphenol intake from fruit and vegetables may be a more appropriate comparison with wine if polyphenols play an important role in preventing AAA.  In addition, she pointed out that the consumption of wine increased markedly in Sweden during the follow-up period.  Many of the subjects reporting beer at baseline may well have been consuming more wine during follow up.

The relation of alcohol consumption to blood pressure:  In response to questions as to whether even moderate alcohol consumption raises blood pressure, Forum reviewer Powell contended that “The relationship between wine consumption and blood pressure is linear; it is steeper for systolic than for diastolic blood pressure.  However, the elevation in blood pressure for moderate drinkers is small and not clinically significant.  This is one of the few cardio-metabolic risk factors that does not follow the J-shaped distribution.”

Reviewer Ellison pointed out that “While blood pressure has long been recognized to increase with alcohol consumption, a number of large prospective studies have suggested that light drinking may not increase blood pressure, and may even relate to a small decrease.  The Kaiser-Permanente Study has shown that blood pressure increases linearly with alcohol only after about 2 drinks/day.  Klatsky et al reported in the New England Journal of Medicine that, ‘As compared to nondrinkers, blood pressures of men taking two or fewer drinks per day were similar.  Women who took two or fewer drinks per day had slightly lower pressures.’  Similarly, the Atherosclerosis Risk in Communities Study (Fuchs et al) found that for white men and women and African-American women, an increase in blood pressure was only seen for people reporting more than 210 g of alcohol per week (the equivalent of about 2 ½ to 3 typical drinks per day); only African-American males showed an increased risk of hypertension with lower intake.  Kannel et al reported similar results from the Framingham Heart Study: an increase in the risk of hypertension only among heavier drinkers.”

Forum member Estruch stated that he and his colleagues (Chiva-Blanch et al) evaluated blood pressure and nitric oxide levels in a clinical trial of gin, wine, and wine phenolics.  He stated: “After a one-month intervention with 30 g of ethanol as gin or red wine, as well as the same amount of polyphenols as dealcoholized red wine, we found the following:

1. Dealcoholized red wine significantly decreased blood pressure and increased plasma NO;
2. Red wine decreased blood pressure but the decrease did not achieve statistical significance;
3. Gin (alcohol) did not modify blood pressure.

Thus, according to our results, the final effects of moderate drinking on blood pressure depend on the polyphenolic content of the alcoholic beverages.” 

The differences in effect according to the type of beverage shown in the Chiava-Blanch et al report could help explain the findings in the present paper of a decrease in AAA only among consumers of beer or wine.  However, reviewer Skovenborg added, “The lack of effect of spirits might also be due to residual confounding or due to a limited number of spirits drinkers reporting more than small amounts of alcohol.”

References from Forum review

Chiva-Blanch G, Urpi-Sarda M, Ros E, Arranz S, Valderas-Martínez P, Casas R, Sacanella E, Llorach R, Lamuela-Raventos RM, Andres-Lacueva C, Estruch R.  Dealcoholized Red Wine Decreases Systolic and Diastolic Blood Pressure and Increases Plasma Nitric Oxide Short Communication.  Circ Res 2012;111:1065-1068.

Fuchs FD, Chambless LL, Whelton PK, Nieto FJ, Heiss G.  Alcohol Consumption and the Incidence of Hypertension The Atherosclerosis Risk in Communities Study.  Hypertension 2001;37:1242-1250.

Kannel WB, Sorlie P:  Hypertension in Framingham , in Paul O (ed): Epidemiology and Control of Hypertension . New York, Stratton Intercontinental Medical Book Corp, 1974, pp 553-592.

Klatsky AL, Friedman GD, Siegelaub AB, Gérard MJ.  Alcohol consumption and blood pressure Kaiser-Permanente Multiphasic Health Examination data.  N Engl J Med 1977;296:1194-1200.

Renaud SC, Guéguen R, Conard P, Lanzmann-Petithory D, Orgogozo JM, Henry O.  Moderate wine drinkers have lower hypertension-related mortality: a prospective cohort study in French men.  Am J Clin Nutr 2004;80:621-625.

Forum Summary

The large majority of prospective epidemiologic studies on the effects of alcohol consumption and the risk of coronary heart disease and stroke have shown a significant reduction in risk for moderate drinkers.  There have been few studies relating alcohol intake to the development of abdominal aortic aneurysm (AAA), and results have been inconsistent.  The present study is based on two very large population-based cohorts in Sweden that were followed prospectively for the clinical development of AAA (identified by radiography, surgical repair, or death resulting from rupture).  There were more than 1,200 cases identified during a 14-year follow-up period.  The results of this study suggest that moderate drinking is associated with a lower risk of AAA, with the beneficial effects primarily among consumers of beer or wine. 

Forum reviewers were unanimous in considering this to be a well-done analysis, with unbiased estimates of effect of alcohol on the risk of aneurysm.  The reduced risk of AAA among moderate drinkers was similar to that seen for common manifestations of atherosclerosis, especially coronary heart disease and ischemic stroke.  Reviewers were uncertain why only consumers of wine and beer showed a beneficial effect, but not consumers of spirits: this could be explained by the polyphenols present in wine, and to a less extent in beer, that have been shown to be anti-inflammatory, anti-oxidant, and anti-platelet aggregation (all mechanisms that may relate to the development of AAA).  However, residual confounding could also play a role. 

It was noted that the percentage of the population with hypertension, probably the most important risk factor for AAA, was much lower than is common in most industrialized countries, but the degree to which this affected the results cannot be known.  While alcohol is known to increase blood pressure, some large studies suggest that an increase occurs only with more than light-to-moderate drinking.  Further, there were few very heavy drinkers (the highest category of alcohol was an average consumption of ≥1 drink/day among women and ≥2 drinks/day among men), so this study could not assess whether or not large amounts of alcohol might increase risk of AAA.

There have been a very limited number of studies on alcohol intake and aortic aneurysm.  While this study suggests a slight decrease in occurrence of AAA with moderate wine and beer intake, it will be important for other large studies to evaluate this association.  Additional studies on polyphenol intake and occurrence of AAA will also be useful.  

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

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

Ramon Estruch, MD, PhD, Department of Medicine, University of Barcelona, Spain

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

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

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

Lynda Powell, MEd, PhD, Chair, Dept of Preventive Medicine, Rush University Medical School, Chicago, IL, USA

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

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

Gordon Troup, MSc, DSc, School of Physics, Monash University, Victoria, Australia