In this large prospective cohort study of apparently healthy men, a complex association between exercise and the development of AF was observed. After adjustment for multiple potentially confounding lifestyle factors and health conditions, higher frequency of participation in a regular program of vigorous exercise at 3 years was associated with a modestly increased risk of developing AF. This elevated risk was primarily among those who exercised 5−7 times weekly. These men had a 20% increased risk of developing AF compared to those who did not exercise. The relationship between vigorous exercise and AF was no longer significant when exercise habits were updated at 9 years or in models excluding possible biologic intermediaries. The increase in risk diminished with increasing age. In men 50 years or older, no significant association was found; while in men younger than 50 years who exercised 5−7 times/week, the association was statistically significant in all analyses.
Secondary analyses found that frequency of jogging was most strongly associated with the development of AF. Men who jogged 5 or more days per week, had a 53% increased risk of developing AF compared to men who did not exercise, after controlling for multiple risk factors. When joggers were excluded, the relationship between frequency of vigorous exercise and AF was no longer present, suggesting that jogging may account for much of the association.
These results expand on prior epidemiologic data regarding the relationship between exercise and AF, which is limited to case series and small case control studies. Case series have suggested that the incidence of AF may be higher in athletes.1,2,9
A retrospective case-control study found a higher incidence of long-term sport activity among men with lone AF compared to controls.10,11,12,13
In a small prospective study, the 10-year cumulative incidence of lone AF in 300 top-ranked runners was 5.3% compared to 0.9% in 495 healthy controls.5
Although limited, these data are consistent with our findings that frequent endurance exercise, particularly jogging, may increase the risk of developing AF. In addition, the mean age of the exercisers in all studies was < 60, consistent with our finding that the association is strongest in younger populations.13
There are several mechanisms through which frequent exercise might influence risk of AF, including left atrial enlargement, left ventricular hypertrophy, left ventricular dilation, and the most commonly cited mechanism, an increase in parasympathetic tone.2,14,15
Left atrial size is significantly increased in competitive athletes, and left atrial size is a strong and independent risk factor for AF.16,17
However, left atrial size does not appear to explain the entire association between exercise and AF. In a case-control study including 107 lone AF patients, greater participation in cumulative moderate and heavy physical activity was significantly associated with the development of AF even after controlling for left atrial size.11
Part of this unexplained risk may be due to an increase in parasympathetic activity among habitual exercisers. Jogging in particular result in a greater enhancement of the parasympathetic nervous system compared to other exercise types.18,19
Heightened parasympathetic tone has been associated with AF onset in patients with structurally normal hearts, and in both animal and human studies, parasympathetic stimulation frequently induces and maintains AF, while vagal denervation prevents AF. 20,21,22
Aging results in reduced parasympathetic activity.23
Therefore, chronic exercise in older individuals may lead to a less significant enhancement of parasympathetic activity. Also, lone AF comprises a smaller proportion of AF cases among older individuals where underlying structural heart disease is more common. This may explain why no association between exercise and AF in older men was found. Alternatively, men susceptible to AF as a result of exercise may have developed AF at a younger age and therefore would be excluded from analyses of older populations. It is also possible that participants exercised less vigorously as they aged, diminishing the power to detect an association between exercise and AF.
In addition to the pro-fibrillatory effects, exercise has multiple beneficial effects on cardiovascular health that may lower AF risk. Exercise lowers blood pressure, improves lipid profile and glucose control, and reduces risk of cardiovascular disease. Removal of the potentially inappropriate control of these intermediaries (Model 2) either eliminated or significantly attenuated the association between exercise and AF when compared to maximally adjusted analyses (Model 3). This suggests that any pro-fibrillatory effect of exercise is counterbalanced by additional anti-fibrillatory effects in the majority of, but not the entire population.
A number of limitations warrant discussion. First, our measure of physical activity, although correlated with VO2 max, is limited compared to more objective measures of physical fitness. Although we assessed exercise habits at 2 time points, physician habits may have further changed over time. If such misclassification of exercise habits were random, this may have reduced our ability to detect associations between exercise habits and AF. AF can be occult and serial electrocardiograms were not available for the entire cohort, thus under-detection may exist in these analyses, although less likely in a cohort of physicians. As AF was self-reported, men who exercise may be more likely to notice they are in AF and seek medical attention. It is possible that participants who exercised frequently developed undiagnosed AF resulting in reduced exercise tolerance that could have influenced exercise habits leading to an underestimation of the association between exercise and AF. The limited number of men under age 50 at the time of the 9-year exercise questionnaire (n=949, 6.3%) may have limited our power to detect an association in the updated analysis.
With respect to generalizability, our findings are limited by the selective nature of the cohort, healthy male physicians free of known cardiovascular disease at baseline. It is unclear if this same relationship between exercise and AF extends to women or less healthy populations. Any participant who died prior to 1997 (n= 1,713) did not complete 1 of the AF questionnaires. As a result, participants with healthy lifestyle habits, such as exercise, may have been over-represented.
Although the primary, secondary, and subgroup analyses were pre-specified, concern for multiple comparisons is warranted. However the consistency and strength of the association of exercise with the development of AF among men age < 50 and joggers, and prior epidemiologic and physiologic studies supporting these findings, supports the validity of these results. Finally, as with any observational study, our study cannot prove causality and the associations observed here could be due, at least in part, to residual confounding. However, vigorous exercise was directly associated with several AF risk factors, and therefore, it is also possible that more complete control for risk factors would have strengthened the inverse associations observed.