Ariansen I, Degerud E, Gjesdal K, Tell GS, Næss O. Examining the lower range of the association between alcohol intake and risk of incident hospitalization with atrial fibrillation. IJC Heart & Vasculature 2020;31:100679.
Background: Evidence is sparse on the association between alcohol intakes in the lower range and risk of atrial fibrillation (AF). We aimed to investigate self-reported low and moderate alcohol intakes and subsequent risk of incident AF among current drinkers.
Methods: Norwegian population-based health examination surveys assessing self-reported daily alcohol intake (mean grams per day) were linked to health and population registers. Hazard ratios (HR) (95% confidence interval) for time to incident (first) hospitalization with AF by alcohol intake level were assessed by Cox regression, with adjustment for educational level and cardiovascular risk factors except blood pressure.
Results: The study population included 234,392 participants (49% men). Incident hospitalization with AF was identified in 5043 (2.2%) persons during a mean follow-up of 9 years. Compared to a very low alcohol intake of <1 unit weekly, a moderate consumption in the range of 1 to <2 units daily increased the risk of incident AF by 18% (HR 1.18 [1.06–1.32]). The average risk of incident AF increased by 9% per daily alcohol unit of 12 g (HR 1.09 [1.03, 1.14]). In sex-stratified analyses significant associations were found in men only.
Conclusions: We found that less than two alcohol units/day significantly increased the risk of incident AF, however, in men only. Reduction of even a moderate alcohol intake may thus reduce the risk of AF at the population level.
Background: Forum member Stockley provided an overview of her interpretation of previous research on the association between alcohol and AF. “From a quick review of previously published literature, the relationship between atrial fibrillation and alcohol has generally appeared to be a causal, linear and dose-response relationship, which may reflect alcohol-induced electrophysiological changes in atrial cells (Steinbigler et al; Marcus et al; Samokhvalov et al; Kodama et al).” Other reviewers noted, however, that many previous studies have suggested that the risk of AF is not increased with light or moderate drinking (Bazal et al; Di Castelnuovo et al), and a recent meta-analysis did not show an increase in risk of AF for consumers averaging 1 drink/day (Gallagher et al). The present large study was designed to judge whether or not there is a threshold level of drinking that is associated with an increased risk of AF.
Comments on the present paper: Reviewer Ellison pointed out that this study was based on a large number of population-based subjects in Norway (more than 200,000), with 9-year follow up. Most potentially confounding variables (e.g., education, smoking, marital status, physical activity, diabetes, history of cardiovascular disease) were considered in their analysis. He noted: “The investigators used two rather unwieldy approaches for assessing alcohol intake: (1) the number of drinks in the past two weeks, from which they calculated the average daily amount of alcohol per year (without considering seasonality of drinking, type of beverage, with or without food, etc.); (2) the reported number of total drinks within the last year (‘how often did you drink?’ ‘how many drinks on each occasion?’), but with no information provided on the type of beverage and only limited information on the pattern of drinking, both factors that have been shown to markedly affect health effects of alcohol consumption.”
Ellison added: “In their Discussion, the authors admit that their results are weakened because their assessments may have been gross under-estimates of alcohol intake: based on the levels of HDL found in the categories of 2 to < 12 grams of alcohol/day and 12 to <14 grams/day, they estimate that their calculated alcohol intake may have been underestimates of the actual consumption by 50%. They state that “One self-reported drink/day may in fact represent two drinks/day, as suggested by the HDL-cholesterol level.” Yet, this is not mentioned in their Abstract, in which they conclude without any reservations: ‘We found that less than two alcohol units/day significantly increased the risk of incident AF, however, in men only.’ In my opinion, they should have ‘hedged their bet’ in their conclusions by mentioning that their own evidence indicates that the up to 1 drink/day category may well have included many subjects who consumed more.”
Reviewer Skovenborg agreed that their analyses should be viewed with skepticism as to the “moderate” drinkers in their study. He stated: “The authors estimated an underreporting of over 50% resulting in a self-reported one drink/day may in fact representing two drinks/day. The magnitude of underreporting in Norway has been studied in the Norwegian island of Spitzbergen, Svalbard, that offers a unique setting for validation studies of self-reported alcohol consumption: no counterfeit production or illegal import exist making complete registration of all sources of alcohol possible. In this population, Høyer et al found that the self-reported volume of alcohol consumption accounted for approximately 40% of the amount estimated from sales volume. This serious caveat should have been emphasized in the abstract.”
A number of Forum members noted that the assessments of alcohol were done only at baseline, and potential changes during follow up were not assessed. The investigators indicated that they had no information on previous drinking, so they excluded from their analysis all non-drinkers, assuming that many were “ex-heavy drinkers.” Thus, they used those reporting < 2 grams of alcohol per day as their reference group. (In many population-based studies, a large proportion of “light drinkers” report an average of < 2 grams/day, so many such drinkers may have been included in this reference category.)
Skovenborg noted further: “Norway is a country with a strong temperance tradition, and according to WHO lifetime abstainers have been estimated as 4.5% of men and 14.2% of women. It should have been possible to establish a reference group of lifetime abstainers. Also, as it is often the case in ‘dry’ countries, binge-drinking is rather prevalent; the WHO report found a prevalence of heavy episodic drinking of 15+ year-old men to be 55.2%, and of women to be 21.9%, and it was especially high among male adults; this may have contributed to the increased risk of AF among men. In countries with a ‘Mediterranean alcohol-drinking pattern’ (generally red wine consumption with meals), a moderate alcohol consumption (<30 g alcohol/day men, <15 g/day women) has not been associated with increased risk of AF in several studies (e.g., Di Catelnuovo et al; Bazal et al).
“Almost all studies included in meta-analyses are from the United States or Northern European countries, where wine is not the alcoholic beverage of preference and the tendency toward episodic heavy drinking, or drinking outside meals, is higher than in the Mediterranean populations. A recent example (Csengeri et al) comprised five community-based cohorts with only one Italian cohort (Moli-sani) and four cohorts from Northern Europe. The analysis found a cut-off for statistically significantly increased risk for AF observed with regular alcohol consumption of 2 g/day. The proposed mechanism for alcohol’s effects on arrhythmogenesis outlined in that paper is very hard to reconcile with a presumed low chance of elevated blood alcohol concentration, as complete hepatic First Pass Metabolism would have reduced the BAC to near zero. Such untrustworthy results make you suspect residual confounding in addition to drinking pattern issues in that paper as well as in the current one. Further, it makes it difficult to estimate the applicability of their results to many other populations.” A 2017 review and meta-analysis by Gallagher et al did not find that consuming alcohol up to one drink per day was associated with an increased risk of AF; those authors concluded: “Low alcohol intake, of up to 1 standard drink (SD) per day, was not associated with AF development (HR 0.95, 95% CI 0.85–1.06, p = 0.37).”
Reviewer Svilaas wrote: “I agree with the comments of other Forum members that the Methods and Discussion sections of this paper are disappointing, and surprising in this very large study.” Reviewer Finkel also noted: “This Norwegian study base is appropriately large, but I am disappointed in the looseness of the epidemiological rigor of the study.” Reviewer Van Velden noted: “The problem as I see it is the fact that all confounders were not taken into consideration, and that self-reporting of alcohol consumption will always be very subjective!” He added: “Holistic wellness is more than not just drinking in moderation; physical, emotional and spiritual wellness must also be taken into consideration.”
Overall, 2.2% of subjects were found to have a hospital diagnosis of AF; given that non-hospitalized subjects were not included, it is probable that many cases of AF were not identified. The authors truncated all cases reporting 24 or more grams of alcohol/day into one category; however, in a figure in the paper, they plot estimates for up to 100 g/day, based on a spline analysis adjusted only for age and sex. From the columns shown in the same figure, indicating the frequency of intake by participants, there are almost none above about 25 g/day.
Forum member Goldfinger noted: “In considering the potential mechanisms that are presented of a lowered fibrillation threshold in association with low doses of alcohol, the lack of association in women is interesting. Might this reflect the difference in strategy of consumption in men versus women, incidence of binge drinking, type of alcohol consumed, or other such causes.”
Forum member de Gaetano, in conjunction with his colleague Di Castelnuovo, wrote: “As discussed above by Skovenborg, in a recent paper from the MORGAM collaboration (107,845 individuals from 5 community-based European cohorts, mainly from the north, but including one cohort from Italy), we found that one unit of alcohol (12 g/d) was associated with 16% (11% to 22%) higher risk of developing AF (Csangeri et al). The risk was also apparent at low doses of alcohol and was fairly similar for women and men. Besides the differential role of sex, our findings are in agreement with that of Ariansen et al. In contrast, we found a J-shaped relationship with incident heart failure (HF), P < 0.0001; the lowest HRs for HF were observed at levels up to 20 g/day, or 1.6 drinks/day. This differential association of alcohol intake with AF and HF had also been observed in the Moli-sani population (Di Castelnuovo et al). In that publication, we did not show any significant increased risk of AF in relation to alcohol consumption.”
Reviewer Lanzmann-Petithory noted: “Heavy drinking is a well-known factor for AF, but I agree with all the critics of the group that this paper does not allow us to really answer the question of the relationship between moderate intake of alcohol and AF onset; this is due mainly to difficulties in determining a possible threshold effect of alcohol because of underreporting (more pronounced in the men), absence of an adequate drinking pattern analysis, no information on type of alcohol or consumption of a Mediterranean pattern of eating, variations of consumption with time, etc. The difference between sexes is interesting. In regard to recurrences of AF, that are very common, it may be useful to mention an Australian randomized study that demonstrated that drinkers with persistent or recurring AF who stopped drinking had fewer occurrences of AF than those who continued to drink (Voskoboinik et al).
Adverse health effects of AF: The most significant adverse health effect directly associated with AF is ischemic stroke. Since an early report from the Nurses’ Health Study in 1988 (Stampfer et al), most prospective epidemiologic studies have shown that light-to-moderate alcohol intake decreases the risk of ischemic stroke (as well as total mortality). It is noted that a recent paper from Korea reports that for subjects who already have AF, alcohol intake is associated with higher, rather than lower, risk of ischemic stroke (Lee et al). [In the latter study, however, there are problems relating to the intake of alcohol (which in Korea, consists mainly of beer or of soju, a traditional beverage with a relatively high alcohol content) to beverages consumed in western countries, and the failure of those authors to consider the influence of pattern of drinking. In addition, the analyses were adjusted for a number of potential confounders that are known to relate to alcohol consumption (including dyslipidemia, hypertension, and cardiovascular disease); also these investigators included as abstainers both former drinkers and never drinkers. Further, in their main analyses in that paper, all alcohol consumers were grouped as “current drinkers,” regardless of the amount consumed.]
Overall, scientific data continue to show that light-to-moderate alcohol intake, especially when the pattern of drinking is considered, is associated with a lower risk of ischemic stroke and death. For the effects of alcohol intake on the risk of AF, the situation remains unclear. Unfortunately, the present study cannot answer the question as to whether there is, or is not, a clear threshold effect for alcohol intake on the risk of AF.
References from Forum critique:
Bazal P, Gea A, Martínez-Gonzáles MA, Salas-Salvadó J, Asensio EM, Muňoz-Bravo C, et al. Mediterranean alcohol-drinking pattern, low to moderate alcohol intake and risk of atrial fibrillation in the PREDIMED study. Nutr Metab Cardiovasc Dis 2019;7:676-683. doi: 10.1016/j.numecd.2019.03.007.
Csengeri D, Sprünker N-A, Di Castelnuovo A, Niiranen T, Vishram-Nielsen JK, Constanzo S, et al. Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes. European Heart J 2021;42:1170-1177.
Di Castelnuovo A, Costanzo S, Bonaccio M, Rago L, De Curtis A, Perisichillo M, et al. Moderate alcohol consumption is associated with lower risk of heart failure but not atrial fibrillation. J Am Coll Cardiol HF 2017;5:837-844.
Gallagher C, Hendriks JML, Elliott AD, Wong CK, Rangnekar G, Middeldorp ME, et al. Alcohol and incident atrial fibrillation – A systematic review and meta-analysis. Int J Cardiol 2017;246:46-52. DOI:https://doi.org/10.1016/j.ijcard.2017.05.133.
Høyer G, Nilssen O, Brenn T, Schirmer H. The Svalbard study 1988-89: a unique setting for validation of self-reported alcohol consumption. Addiction 1995;90:539-544.
Kodama S, Saito K, Tanaka S, Horikawa C, Saito A, Heianza Y, Anasako Y, Nishigaki Y, Yachi Y, Iida KT, Ohashi Y, Yamada N, Sone H. Alcohol consumption and risk of atrial fibrillation: a meta-analysis. J Am Coll Cardiol 2011;57:427-436.
Lee S-R, Choi E-K, Jung J-H, Han K-D, Oh S, Lip GYH. Lower risk of stroke after alcohol abstinence in patients with incident atrial fibrillation: a nationwide population–based study. Eur Heart J 2021;pre-publication. Doi: 10.1093/eurheartj/ehab315.
Marcus GM, Smith LM, Whiteman D, Tseng ZH, Badhwar N, Lee BK, Lee RJ, Scheinman MM, Olgin JE. Alcohol intake is significantly associated with atrial flutter in patients under 60 years of age and a shorter right atrial effective refractory period. Pacing Clin Electrophysiol 2008;31:266-272.
Samokhvalov AV, Irving HM, Rehm J. Alcohol consumption as a risk factor for atrial fibrillation: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil 2010;17:706-712.
Stampfer MJ, Colditz GA, Willett WC, Speizer FE, Hennekens CH. A prospective study of moderate alcohol consumption and the risk of coronary disease and stroke in women. NEJM 1988;319:267-283.
Steinbigler P, Haberl R, König B, Steinbeck G. P-wave signal averaging identifies patients prone to alcohol-induced paroxysmal atrial fibrillation. Am J Cardiol 2003;91:491-494.
Voskoboinik A, Kalman JM, De Silva A, et al. Alcohol Abstinence in Drinkers with Atrial Fibrillation. N Engl J Med 2020;382:20-28. doi: 10.1056/NEJMoa1817591.
While many epidemiologic studies have demonstrated an increase in the risk of AF for consumers of alcoholic beverages, there remains a question as to whether or not there is a threshold amount that would increase the risk. The present study concludes that “less than two alcohol units/day significantly increased the risk of incident AF, however, in men only. Reduction of even a moderate alcohol intake may thus reduce the risk of AF at the population level.”
While this may be the case, Forum members had a number of concerns about using the results of the present study to determine whether or not there is a threshold amount of alcohol necessary to increase the risk of AF. The methods used to judge alcohol consumption did not report the type of beverage or have a good estimate of the pattern of drinking, both of which factors are known to modify the health effects of alcohol. Further, the authors stated that there was evidence of considerable under-reporting of alcohol in their cohort, as the level of HDL noted in their “light” drinkers was above the level expected. This suggested to them that subjects in their lowest category of alcohol may actually have consumed more than they reported (probably about twice the reported amount of alcohol). This makes it difficult to determine if truly “light” drinking is associated with an increased risk of AF.
Overall, scientific data continue to show that light-to-moderate alcohol intake, especially when the pattern of drinking is found to be regular moderate consumption with food and without binge drinking, is associated with a lower risk of ischemic stroke and death. For the effects of alcohol intake on the risk of AF, the situation remains unclear. Unfortunately, the present study cannot answer the question as to whether there is, or is not, a clear threshold effect of alcohol intake on the risk of developing AF.
* * * * * * *
Comments included in 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 (prepared in conjunction with his colleague, Augusto Di Castelnuovo)
R. Curtis Ellison, MD, Professor of Medicine, Section of Preventive Medicine & Epidemiology, Boston University School of Medicine, Boston, MA, USA
Harvey Finkel, MD, Hematology/Oncology, Retired (Formerly, Clinical Professor of Medicine, Boston University Medical Center, Boston, MA, USA)
Tedd Goldfinger, DO, FACC, Desert Cardiology of Tucson Heart Center, University of Arizona School of Medicine, Tucson, AZ, USA
Erik Skovenborg, MD, specialized in family medicine, member of the Scandinavian Medical Alcohol Board, Aarhus, Denmark
Creina Stockley, PhD, MSc Clinical Pharmacology, MBA; Principal, Stockley Health and Regulatory Solutions; Adjunct Senior Lecturer, The University of Adelaide, Adelaide, Australia
Dominique Lanzmann-Petithory, MD, PhD, Nutrition Geriatrics, Hôpital Emile Roux, APHP Paris, Limeil-Brévannes, France
Arne Svilaas, MD, PhD, general practice and lipidology, Oslo University Hospital, Oslo, Norway
David Van Velden, MD, Dept. of Pathology, Stellenbosch University, Stellenbosch, South Africa