In this large cohort of older people with cardiovascular disease or diabetes with end-organ damage followed for 56 months, we found that moderate alcohol intake, as defined using median cut-off values based on guidelines used in various countries,10
was associated with an increased risk of atrial fibrillation. This finding remained after we adjusted for many of the potential confounders shown to be associated with incident atrial fibrillation. The magnitude of risk was strongly and significantly related to alcohol intake in a dose–response fashion irrespective of other risk factors and lifestyle. Binge drinking, even by those in the moderate-intake group, was significantly associated with an increased incidence of atrial fibrillation, with the magnitude of risk comparable to habitual heavy drinking. Subgroup analyses in our study showed a similar pattern of results across all major subgroups.
Because moderate alcohol consumption has been found to be associated with a reduced risk of cardiovascular-related outcomes, including death,13
the reduced risk of death that we observed among participants who consumed moderate levels of alcohol may allow them to survive long enough to manifest the atrial fibrillation, whereas patients at equal risk of atrial fibrillation who drink little or no alcohol may die before the atrial fibrillation reveals itself. However, when this competing risk was examined by further regression analyses, the HRs did not change materially, which suggests that the harmful effect of alcohol on atrial fibrillation persisted despite the potential for competing risks from death.
Our findings are consistent with those from most of the studies included in a meta-analysis that showed a linear relation (rather than a J-shaped or threshold curve) between alcohol consumption and risk of atrial fibrillation.14
We extend these findings by providing evidence of a graded relation between alcohol intake and atrial fibrillation among high-risk patients with existing cardiovascular disease or diabetes. The incidence rates of atrial fibrillation that we observed at each level of alcohol intake in this high-risk population were several times higher than the rates reported in the general population or among patients with diabetes.15,16
The absolute increase in risk of 2.8 events per 1000 person-years associated with moderate alcohol consumption () was much higher than the absolute increases in risk reported in the general population.15,16
The effect of moderate alcohol consumption on incident atrial fibrillation is less clear. Our finding of an increased risk of incident atrial fibrillation associated with moderate alcohol consumption among high-risk patients is in contrast to that of several studies that found no increased risk associated with moderate alcohol consumption among people free of cardiovascular disease.15,17–20
In patients with existing cardiovascular disease, moderate alcohol consumption may incur an equal, or possibly stronger, effect on the risk of atrial fibrillation.
Because drinking moderate quantities of alcohol was common in our study (36.6% of the participants), our findings suggest that the effect of increased alcohol consumption, even in moderate amounts, on the risk of atrial fibrillation among patients with existing cardiovascular disease may be considerable. Using Levin’s formula for calculating attributable risk,21
we estimated that, for every 100 events of atrial fibrillation occurring in the population of moderate drinkers, an estimated 4.9 events (95% CI 1.4–8.7) would be prevented if every person quit drinking. This estimate is comparable to population attributable risk estimates for several other established cardiovascular risk factors.22,23
We also examined the effect of binge drinking on the risk of atrial fibrillation in our cohort. The limited data on the association between binge drinking and atrial fibrillation among people with healthy hearts7
suggested that heavy binge drinking, as may occur on weekends or during holidays (“holiday heart syndrome”) may increase the risk in general, but it was unknown whether this would be the case among patients at high risk of cardiovascular events, who do not tend to indulge in heavy binge drinking. Our study showed that the occasional habit of binge drinking placed moderate drinkers at increased risk. Of note, the association between moderate alcohol consumption and atrial fibrillation risk was robust after we excluded binge drinkers from the analysis, and the dose–response relation between alcohol intake and risk of atrial fibrillation was maintained.
The underlying mechanisms linking alcohol intake to atrial fibrillation are likely multifactorial. Several experimental studies suggest associated harmful effects on maintenance of normal heart rhythm,14
including a hyperadrenergic state and impairment of vagal tone. Acute alcohol intake in healthy men has been shown to decrease heart rate variability because of diminished vagal modulation.24
Increased alcohol intake shortens the effective refractory period of the right atrium, which promotes propagation of a critically timed premature atrial complex.25
Conduction block occurs in some instances,26
which sets up a disturbed milieu conducive to triggering atrial fibrillation. In patients with stable coronary artery disease, a moderate amount of alcohol ingestion (1.25 g/kg per day) has elicited a significant decrease in vagal modulation of the heart initially, followed by a shift to sympathetic predominance and increased vasomotor activity.27
Moreover, alcohol intake leading to cardiomyopathy, increased thickening and scarring of cardiac connective tissue, altered oxidative stress, induced electrolyte imbalance and negative inotropic effect through calcium-channel inhibition in ventricular cells may also play roles in the pathogenic process.
Strengths and limitations
We examined the association between alcohol consumption and risk of atrial fibrillation in a cohort of high-risk older patients with existing cardiovascular disease or diabetes, in contrast to other studies that involved otherwise healthy individuals in the general population. Other strengths of our study are its prospective design, the large sample, the large number of events, worldwide participants, the availability of detailed covariates that could be used to adjust for a broad range of potential confounders, high completeness of systematically collected data and confirmed outcomes.
Our study had limitations. First, alcohol intake was self-reported at baseline but was not assessed during follow-up. Any changes in alcohol consumption over time would not have been captured. Second, the proportion of participants who were heavy drinkers was small, because those who were recruited and who remained in the trials were unlikely to include the heaviest drinkers. Third, recorded levels of alcohol ingestion may have been influenced by observer and respondent interpretation; however, the definition we used is commonly used in epidemiologic studies. Fourth, because ECGs were not required at each follow-up visit, episodes of asymptomatic paroxysmal atrial fibrillation may have been missed; therefore, the incidence of atrial fibrillation may be underestimated. Fifth, patients with atrial fibrillation at baseline were excluded from our analysis. Such patients may have had atrial fibrillation as a result of alcohol consumption; therefore, the association between alcohol consumption and atrial fibrillation may be underestimated. Finally, information on thyroid function was not available.
Moderate to high alcohol intake was associated with an increased incidence of atrial fibrillation among patients aged 55 or older with existing cardiovascular disease or diabetes. Among moderate drinkers, the effect of binge drinking on the risk of atrial fibrillation was similar to that of habitual heavy drinking. Recommendations about the protective effects of moderate alcohol intake in patients at high risk of cardiovascular disease may need to be tempered with these findings.