Endurance Athletes/Exercise & Longevity in Tour de France Cyclcists & Risk of arrhythmias in 52 755 long-distance cross-country skiers & Relation of Vigorous Exercise to Risk of Atrial Fibrillation (3 studies)
Download the PDF
Tour de France cyclists live longer than ordinary French men
Sept 3 2013 the heart.org Michael O'Roirden
Amsterdam, the Netherlands (updated) - Elite French cyclists participating in the Tour de France over the past 60 years have a significantly lower rate of mortality than French men in the general population, according to the results of a new study .
In evaluating the overall mortality rates of French cyclists who rode in the prestigious event between 1947 and 2012, investigators found the cyclists had a 41% lower mortality rate than men in France and that this lower mortality rate was consistent over time, including periods of reported heavy performance-enhancing-drug use. The lower rate was significant for deaths resulting from cancer and cardiovascular causes, and while it wasn't statistically significant for other causes of death, the mortality trends all favored the cyclists.
Dr Xavier Jouven
Presenting the results here today at the European Society of Cardiology (ESC) 2013 Congress, senior investigator Dr Xavier Jouven (Paris Descartes University, France) said that among the cyclists who rode in the Tour de France from 1947 to 1951, a period accounting for more than 60% of the deaths in the analysis, the elite athletes lived six years longer than men in the general population.
Jouven said the results, which are published concurrently in the European Heart Journal to coincide with the ESC hot-line session, back up his belief that the general population can benefit from exercise that goes beyond a mild walk in the park.
"There have been many concerns about elite athletes, but also concerns for the general population, including Sunday joggers," Jouven told heartwire. "Usually, we observe a slight increase in creatinine levels, a slight increase in troponin, or a slight increase in potassium. Studies have been suggesting it might be dangerous to exercise, to do marathons, and in one way it's true, but for a very small group of selected patients. In my mind, the overall message of harm, that doing sport is dangerous and that it's better to not do sport, is wrong."
While physicians must address the needs of their patients, including those with coronary artery disease and those who might be at risk for sudden cardiac death, the overall message for the general population is that the lifelong benefits of exercise, including high-intensity endurance sports, outweigh any potential risks when it comes to all-cause mortality, said Jouven.
"We need to balance our message and maybe start encouraging people to participate in sports, maybe even at a higher level than we are advising them," he told heartwire.
Results consistent across the different race eras
Of the 786 French cyclists who rode in the tour since 1947, 208 have died. Of these, 59 cyclists died from cancer, mainly neoplasms of the digestive tract, lung, and prostate, a number that is 44% lower than what would be expected if the cyclists had the same mortality rate as the general male population. Similarly, deaths from cardiovascular causes were reported in 53 cyclists, a 33% lower rate than what would be expected based on estimates in the general male population.
Overall, the cyclists had a higher risk of death related to external causes, although this trend did not reach statistical significance when compared with French men in the general population.
Standardized mortality ratio by causes of death
Mortality Standardized mortality ratio (95% CI)
Death from all causes 0.59 (0.51-0.68)
Death from neoplasms 0.56 (0.42-0.72)
Death from cardiovascular diseases 0.67 (0.50-0.88)
Speaking with the media, Jouven said they tracked only French cyclists because they were able to ascertain the cause of death from the French healthcare system
The researchers said they were surprised by the findings, with Jouven saying he had expected to see a downside to such elite training and racing. However, that does not appear to be the case. He cautioned that the Tour de France riders represent a highly selected population. In addition, it can't be stated definitively that the physical fitness arising from their years on tour is the reason for their lower mortality rates.
Speaking during the hot-line session, Dr Sanjay Sharma (St George's University, London, UK), who was not affiliated with the analysis, said that exercising 40 METs per week, broken up over five or six days, reduces the risk of cardiovascular disease by 40% to 50%. Endurance athletes like those in the Tour de France exercise at intensities 10- to 20-fold greater than this, however.
Regarding the potential deleterious effects, Sharma said studies have shown marathon runners with high circulating markers of cardiac damage, animal studies have suggested increased fibrosis and inflammation in the myocardium, and recent cardiac MR studies have shown increased fibrosis in veteran athletes.
It is the comparator arm, however, that Sharma took exception to in the French analysis. He said it is a comparison between "possibly the fittest human beings in the world, people that are physically, genetically, physiologically, and psychologically superior" and ordinary men. Among the general population, there is a much higher burden of comorbidities, risk factors for cardiovascular disease, and adverse lifestyles.
Sharma said the study shows that "if you are capable of doing the Tour de France, you might live six to seven years longer than the average individual in the community."
Dr John Mandrola (Baptist Health Louisville, KY), an electrophysiologist who writes a column for theheart.org and who is a competitive master's-level cyclist, said he was not surprised the tour riders live longer because they're genetically gifted athletes who compete and race in their peak years. However, they typically stop training once their career is finished. This contrasts with the master's-level athletes electrophysiologists treat, those who have exercised at high levels their whole life and who continue to train.
"The potential harm of exercise, like arrhythmias and fibrosis, seem to correlate with the cumulative effects over years," he told heartwire. "So, I guess the take-home message is that the effect of transient inflammation is different from long-term inflammation."
So, the drugs won't kill you then?
Speaking with heartwire, Dr Alfred Bove (Temple University, Philadelphia, PA), a past president of the American College of Cardiology who competes in triathlons and endurance running events, addressed the performance-enhancing-drug aspect of the tour, saying that whatever these athletes might have taken over the years to gain that critical edge, it didn't shorten their life.
"Now, there are some dangerous doping drugs, adrenalinelike doping drugs," said Bove. "There are some potent heart stimulants. but most of the cyclists, to my understanding, dope with [erythropoietin] EPO to build their red blood cell mass. If you build your red blood cell volume at the right time you can perform better, but from this standpoint, whatever they're doing, it's not doing any long-term harm."
Overall, Bove said the details of the study are difficult to interpret, so caution should be exercised about making conclusions. He said, however, that in the present era of sensitive testing, which includes biomarker assessments, ECGs, MRIs, and CT scans, first emerged in patients with heart disease.
"We do these tests in a sick hospital population, but when we take this information and try to apply it to a normal athletic population, it doesn't cross over properly," said Bove. As a result, ECGs and other sensitive tests are being read as abnormal when in fact the results might simply highlight the differences with an athlete's heart. "We don't have the details, but a lot of the Tour de France guys would have these abnormalities, and it's not causing a shortening of their life. It's an important piece of information."
Inflamed endurance athletes should take no comfort in Tour de France cycling study
Sep 3, 2013 10:54 EDT, theheart.org
Few sporting events inflame its competitors more than the Tour de France. Grand tour cyclists, like Christopher Froome, Bradley Wiggins, Lance Armstrong, and hundreds of others have endured the equivalent of a marathon a day for three weeks. And it's not just the stress of the race; intense training encompasses the life of a grand tour competitor for years.
There is much to learn from these genetically gifted humans. Two questions come quickly to mind:
1. Does the intense inflammation incurred from professional cycling compromise longevity, like it so obviously does for US football athletes?
2. Are there lessons to be learned about the long-term effects of extreme exercise?
A study released today at the European Society of Cardiology (ESC) 2013 Congress sought to answer these questions. French researchers studied 786 former tour participants. They gathered vital statistics from riders who competed between 1947 and 2012, including causes of death from 1968 on. Death rates of cyclists were compared with an age-matched male French population from a similar time period.
The results were not surprising. Researchers observed a 41% lower death rate in the tour cyclists. Lower mortality rates were preserved in both leading causes of death (cancer and vascular disease) and over time. On average, tour cyclists lived six extra years compared with the general population.
The authors were cautious in making conclusions. "Our results do not allow us to assess in detail the balance between positive effect of high-level sports activity and selection of healthy elite athletes vs any potential deleterious effects of excessive physical exercise or alleged doping."
This is a fun one, isn't it?
The answer to the first question is easy: Competing in the tour did not lead to a shorter life. In fact, it was the opposite.
There are two reasons this isn't surprising:
First, transient inflammation, even as intense as the tour, isn't dangerous in the long-term. Recall that stressing the body and inducing inflammation is a normal mammalian process. We are supposed to be able to endure periods of strain. How else would we have survived as a species? Exposure to stressful periods leads to adaptation-ie, a training effect.
The key word is transient. In most cases, professional athletes stop inflaming themselves. Contrast this with the masters-level aged athlete who keeps slogging on for three or more decades.
Look around at your local races. How many Kenyan masters runners are running for tee shirts? Wait, have you ever seen a Kenyan masters runner? How many former tour riders are racing for $100 criterium payouts? Professional athletes have been there, done that. They stop the madness. Though some former tour riders have been known to smoke and drink and carouse, it's likely that most fall back to the normal patterns of a healthy life. (The trial did not study posttour behaviors. This would have been useful information.)
The second reason these findings aren't surprising goes by the fancy medical term selection bias. Namely, tour cyclists are special. You don't get to be in the tour without having been gifted with health and strength. Yes, pro cyclists train like crazy and are mentally strong as well, but these folks are not representative of the general population. What's more, it's not a stretch to believe that professional athletes digest high training burdens more efficiently than you and me.
The second question is tougher. Does the good prognosis of tour riders tell us much about the upper limit of exercise dosage?
In Europe, the U-shaped dose-benefit curve of exercise is a hot topic. The debate session on whether endurance sports exert arrhythmogenic effects overflowed with European cardiologists. Discussants Dr Sanjay Sharma (UK) and Dr Louis Mont (Spain) agreed on a basic message: Regular exercise and the fitness that comes with it confer clear and measurable health benefits. Normal exercise, even intermittently intense exercise, is good. Really good. The benefits, however, do not accrue upward indefinitely. There is a plateau where more stops being better.
Both experts also agreed that the scientific evidence strongly supports the notion that "excess" exercise can create disease. Endurance athletes, for example, harbor a fivefold higher risk of AF(see below). Animal and human studies reveal that repeated bouts of inflammation-inducing exercise may lead to cardiac scarring and increased susceptibility to arrhythmia. Most distressing is that too much marathoning increases the risk of coronary calcification-a change consistent with aging. Now there's a paradox.
Perhaps the reason this study received so much attention is that all involved in the exercise debate seek answers. This cycling study tempts us to say something like: "Look . . . nothing is badder than the tour, and these guys are not dying sooner. So it's okay."
Don't fall for this. Even if you consider the ill effects of doping, tour riders don't provide a reliable model for the growing masses of enthralled endurance athletes. Transient inflammation, incurred by a very special segment of humans, during the prime of their lives, makes not a good model for the masses.
My take is still the same: Exercise is the best therapeutic intervention a doctor has to offer. It's safe, it's effective, and, yes, it's beautiful. But like everything else in life, too much of a good thing can lead to trouble. What we don't know is how much is too much.
Dosing exercise seems similar to dosing medicine: one patient's high dose is another's toxic dose.
Relation of Vigorous Exercise to Risk of Atrial Fibrillation - pdf attached
American Journal of Cardiology
1 June 2009
Limited data suggest that athletes may have a higher risk of developing atrial fibrillation (AF); however, there has been no large prospective assessment of the relation between vigorous exercise and AF. Logistic regression analyses stratified by time were used to assess the association between frequency of vigorous exercise and risk of developing AF in 16,921 apparently healthy men in the Physicians' Health Study. During 12 years of follow-up, 1,661 men reported developing AF. With increasing frequency of vigorous exercise (0, 1, 1 to 2, 3 to 4, 5 to 7 days/week), multivariate relative risks for the full cohort were 1.0 (referent), 0.90, 1.09, 1.04, and 1.20 (p = 0.04). This risk was not significantly increased when exercise habits were updated or in models excluding variables that may be in the biological pathway through which exercise influences AF risk. In subgroup analyses, this increased risk was observed only in men <50 years of age (1.0, 0.94, 1.20, 1.05, 1.74, p <0.01) and joggers (1.0, 0.91, 1.03, 1.30, 1.53, p <0.01), where risks remained increased in all analyses. In conclusion, frequency of vigorous exercise was associated with an increased risk of developing AF in young men and joggers. This risk decreased as the population aged and was offset by known beneficial effects of vigorous exercise on other AF risk factors.
Although vigorous exercise has numerous health benefits, case reports and limited data suggest that elite athletic men engaging in endurance exercise that increases parasympathetic tone, particularly jogging, may be at higher risk for the development of atrial fibrillation (AF).1, 2, 3 There are limited data on the role of vigorous exercise in the development of AF in men participating in exercise at a less competitive level, where the known beneficial effects of exercise may counterbalance this potential risk. We hypothesized that young men in whom parasympathetic tone is most pronounced may be at highest risk of developing AF. To further define the risks and benefits of exercise on AF risk, we prospectively examined the relation between amount and type of vigorous exercise and subsequent development of AF in men in the Physicians' Health Study.
The methods of the Physicians' Health Study have been described in detail elsewhere.4 The study complies with the Declaration of Helsinki, was approved by the institutional review board of Brigham and Women's Hospital (Boston, Massachusetts), and participants gave informed consent. Briefly, 22,071 men who were physicians, 40 to 84 years old in 1982, with no history of myocardial infarction, stroke, transient ischemic attacks, or cancer were randomized to aspirin and/or ß-carotene using a double-blind, placebo-controlled, 2 x 2 factorial design. Information on health status, risk factors for cardiovascular disease and AF, and dietary and lifestyle factors was collected by questionnaires. Participants who did not complete the 3-year follow-up questionnaire regarding exercise habits (n = 678) and those who reported a diagnosis of myocardial infarction, angina, percutaneous coronary artery intervention, coronary artery bypass surgery, transient ischemic attack, cerebrovascular disease, claudication, peripheral vascular surgery, congestive heart failure, or cancer before the 3-year questionnaire (n = 1,572) were excluded from the analyses.
Physicians were asked at 15, 17, 18, and 19 years after enrollment if they had ever been diagnosed with AF and the date of diagnosis. In addition, participants were asked annually to report any new medical conditions. Participants were excluded from the analyses if they did not return ≥1 questionnaire regarding AF diagnosis (n = 2,352) and had not reported AF on 1 of the annual questionnaires. Because AF onset often precedes diagnosis by months and AF often leads to fatigue and exercise intolerance that might effect exercise habits, participants who reported developing AF before or within 3 years after the 3-year exercise questionnaire were excluded (n = 548).5 After these exclusions, 16,921 participants were available for this study.
Three and 9 years after enrollment, information on exercise habits was collected. The questionnaires asked, "Do you engage in a regular program of exercise vigorous enough to work up a sweat?-Yes/No." Use of "exercise vigorous enough to break a sweat" has been validated to correlate with maximal oxygen uptake capacity and maximum exercise capacity on treadmill testing.6, 7 Subjects who responded "yes" were asked questions characterizing their exercise pattern. Exercise frequency was reported with response options of "<1 day/week, 1 to 2 days, 3 to 4 days, 5 to 7 days." Duration of each exercise episode was asked with responses of "≤10 minutes, 11 to 24 minutes, 25 to 40 minutes, 41+ minutes." The 3-year questionnaire asked, "What types of vigorous exercise do you engage in? Racquet sports, swimming, jogging/running, cycling (including indoor), other." This was followed with, "If you jog/run, how long is your usual distance? One mile or less, 1.1 to 2 miles, 2.1 to 3 miles, 3.1 to 4 miles, >4 miles."
AF cases were assessed by self-report. Although physicians have been documented to reliably self-report other cardiovascular end points such as angina and coronary revascularization, we performed a validation study on 400 randomly selected participants who reported AF on the 15-year questionnaire to determine the reliability of a self-reported diagnosis.8 These men were sent supplementary questionnaires with detailed questions regarding their diagnosis and treatment of AF and a request for permission to review AF documentation.
Of these men, 352 (88%) provided information regarding the previous self-report of AF. Nine of the 48 nonrespondents were deceased. Of these respondents, 39% had paroxysmal, 32% had persistent, and 29% had permanent AF. Medical records were available for 225 men, confirming the self-reported diagnosis of AF in 99% (n = 223). Another 101 men reported that medical record documentation existed but was currently unavailable. In only 26 of respondents (7%) was the diagnosis of AF not further supported. In addition to the 2 cases disconfirmed by medical record review, 12 subjects reported that they had never had a history of AF (misclassification on 15-year survey) and 14 reported that no medical records or electrocardiographic data ever existed to corroborate the diagnosis of AF (self-diagnosis). Although a participant's report of AF was found to be reliable, date of AF diagnosis was not reliably reported. The mean difference between patient-reported diagnosis dates and medical record diagnosis dates was 4.5 ± 7.8 years.
Means or proportions of baseline risk factors and treatment group assignment were computed for the 5 categories of vigorous exercise reported on the 3-year questionnaire. Significance of associations was tested using Mantel-Haenszel chi-square test for trend for categorical and linear regression for continuous variables. In primary analyses, we examined whether frequency of participation in a regular program of vigorous exercise, as reported on the 3-year questionnaire, was associated with development of AF. Secondary analyses examined the relation between duration and type of vigorous exercise and AF development. To examine associations specific to each type of vigorous exercise, participants who reported engaging in >1 exercise type were excluded from the analyses, and participants who did not exercise regularly and did not engage in any exercise types served as the reference group.
Because exercise habits change over time and because the effects of exercise on development of AF may change as the population ages, our prespecified analysis plan included a secondary analysis using updated exercise data from 9 years for cases of AF that developed 3 years after the 9-year exercise questionnaire (1,059 of 1,661 AF cases). Because date of AF onset was often assessed retrospectively and our validation study suggested that a participant's reported date of diagnosis might be unreliable, it was prespecified to use logistic regression stratified by time based on dates of AF questionnaires, rather than Cox regression, to obtain adjusted estimates of AF risk.
Three separate models were developed. Model 1 controlled for age and treatment assignment (aspirin or placebo, ß-carotene or placebo), and models 2 and 3 simultaneously controlled for additional AF risk factors. These 2 multivariable models were constructed to control for confounding while considering the effects of exercise on biological processes within the potential causal pathway for AF development. For example, participants with higher body mass index (BMI) may be less likely to exercise, and because BMI has been previously shown to independently predict the development of AF, it is a possible confounder.
However, exercise decreases BMI; thus BMI is possibly part of the means through which exercise may affect AF development. The first multivariable model (model 2) considers all AF risk factors influenced by exercise, such as BMI, as lying completely within the causal pathway. Model 2 therefore excludes these variables. In contrast, to adjust for possible confounding by a variable such as BMI, the variable must be included in the model. Model 3 treats risk factors as being solely confounders.
Because of the long follow-up, these variables were updated at various time points. To test for a trend between exercise frequency or duration and development of AF, frequency and duration were redefined continuously by assigning each participant the midpoint value of the appropriate response category. To test for plausible effect modification by age, cross-product terms between age and exercise frequency at 3 years were added to all 3 models. Analyses were also repeated after stratification by age at the time when exercise habits were reported.
At 3 years, 63% of participants reported engaging in a regular program of vigorous exercise and 13% reported exercising 5 to 7 times/week (Table 1). In regular exercisers, mean total amount of time spent exercising per week was 108 ± 78 minutes (Figure 1). Frequency of vigorous exercise was inversely associated with age, BMI, smoking, diabetes, and hypertension and directly associated with alcohol, fish, multivitamin, and vitamin C and E intakes.
Frequency of vigorous exercise at 3 years was not associated with subsequent development of AF in age-adjusted models or in model 2, which excluded covariates that were medical conditions and/or risk factors that could be influenced by exercise. After controlling for all potential confounding variables and medical conditions associated with AF (model 3), increasing frequency of vigorous exercise at 3 years was associated with a small increased risk of developing AF (for variables in each model, see Table 2). Men who exercised 5 to 7 times/week had the greatest risk of developing AF compared with those who did not exercise (p = 0.025). These analyses were repeated using exercise habits updated at 9 years. In the maximally adjusted model, the most frequent exercisers still had a marginal, but not significantly increased, risk of developing AF (relative risk [RR] 1.16, 95% confidence interval [CI] 0.99 to 1.36, p = 0.076); however, the trend over categories was no longer statistically significant. Duration of exercise was not related to development of AF in any of the 3- or 9-year updated models (data not shown).
Because previous associations between exercise and AF had been reported primarily in young men and the relation observed in the present study decreased over the course of the study, we hypothesized that the effects of vigorous exercise on the incidence of AF may decrease as the population ages. To test this hypothesis, it was prespecified to stratify men by their age (<50, 50 to 65, >65 years) at the time of the 3-year exercise questionnaire. In men <50 years old, increasing frequency of exercise was associated with an increased risk of developing AF across all 3 models (Table 3). The increase in risk appeared limited to those who exercised 5 to 7 times/week. In contrast, there was no association in men >50 years of age, and the test for an interaction between exercising 5 to 7 times/week and age >50 or <50 years was significant in the full multivariate model (p = 0.02). When age-stratified analyses were repeated using updated exercise habits at 9 years, exercise frequency across the 5 categories was not significantly associated with AF in any age group; however, risk of AF remained significantly increased in men <50 years old at the time of the 9-year questionnaire who exercised ≥5 times/week (RR 2.08, 95% CI 1.16 to 3.71, p = 0.014). The test for interaction between age >50 and <50 years and this category of exercise was not statistically significant in the updated model (p = 0.12).
Participants who exercised regularly were then subdivided based on type of vigorous exercise reported at 3 years (Figure 2). In the maximally adjusted model, men who regularly and exclusively jogged (9.6% of cohort) were at increased risk of developing AF (p <0.01), whereas no significant increase in risk was found with regular cycling, swimming, or racquet sports. Increased frequency of jogging was associated with an increased risk of developing AF in all 3 previously defined models (Figure 3). Men who jogged exclusively 5 to 7 times/week had a significantly increased risk of developing AF (RR 1.53, 95% CI 1.12 to 2.09, p <0.01) compared with men who did not exercise vigorously after controlling for multiple cardiovascular risk factors. There was also a direct, statistically significant relation between miles jogged per episode and development of AF across all 3 models. In the maximally adjusted model, men who jogged >4 miles were at the highest risk (RR 1.38, 95% CI 1.06 to 1.79, p = 0.016). When primary analyses were repeated in the subgroup of participants who did not jog regularly (n = 12,721), no association between frequency of vigorous exercise and development of AF was found in the age-adjusted or multivariate models (data not shown).
In this large prospective cohort study of apparently healthy men, a complex association between exercise and 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 increased risk was primarily in those who exercised 5 to 7 times/week. These men had a 20% increased risk of developing AF compared with those who did not exercise. The relation between vigorous exercise and AF was no longer significant when exercise habits were updated at 9 years or in models excluding possible biological intermediaries. The increase in risk decreased with increasing age. In men ≥50 years of age, no significant association was found; in men <50 years of age who exercised 5 to 7 times/week, the association was statistically significant in all analyses.
Secondary analyses found that frequency of jogging was most strongly associated with development of AF. Men who jogged ≥5 days/week had a 53% increased risk of developing AF compared with men who did not exercise, after controlling for multiple risk factors. When joggers were excluded, the relation 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 previous epidemiologic data regarding the relation 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 in men with lone AF compared with 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 with 0.9% in 495 healthy controls.3 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 exercisers in all studies was <60 years, 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 patients with lone AF, greater participation in cumulative moderate and heavy physical activity was significantly associated with development of AF even after controlling for left atrial size.11Part of this unexplained risk may be due to an increase in parasympathetic activity in habitual exercisers. Jogging in particular results in greater enhancement of the parasympathetic nervous system compared with other exercise types.18, 19 Heightened parasympathetic tone has been associated with AF onset in patients with structurally normal hearts; and in animal and human studies, parasympathetic stimulation frequently induces and maintains AF, whereas vagal denervation prevents AF.20, 21, 22
Aging results in decreased parasympathetic activity.23 Therefore, habitual exercise in older subjects may lead to a less significant increase of parasympathetic activity. Also, lone AF comprises a smaller proportion of AF cases in older patients in whom 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 because 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, decreasing the power to detect an association between exercise and AF.
In addition to the profibrillatory 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 decreases risk of cardiovascular disease. Removal of the potentially inappropriate control of these intermediaries (model 2) eliminated or significantly attenuated the association between exercise and AF compared with maximally adjusted analyses (model 3). This suggests that any profibrillatory effect of exercise is counterbalanced by additional antifibrillatory effects in most of but not the entire population.
Some limitations warrant discussion. First, our measurement of physical activity, although correlated with maximal oxygen uptake capacity, is limited compared with more objective measurements of physical fitness. Although we assessed exercise habits at 2 time points, physicians' habits may have further changed over time. If such misclassification of exercise habits were random, this may have decreased 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 underdetection may exist in these analyses, although it is less likely in a cohort of physicians. Because AF was self-reported, men who exercise may be more likely to notice they are in AF and seek medical attention. Perhaps participants who exercised frequently developed undiagnosed AF resulting in decreased exercise tolerance that could have influenced exercise habits leading to an underestimation of the association between exercise and AF. The limited number of men <50 years of age 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, namely healthy men physicians free of known cardiovascular disease at baseline. It is unclear if this same relation between exercise and AF extends to women or less healthy populations. Any participant who died before 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 prespecified, concern for multiple comparisons is warranted. However, the consistency and strength of the association of exercise with development of AF in men <50 of age and joggers and previous epidemiologic and physiologic studies supporting these findings support the validity of these results. As with any observational study, our study cannot prove causality and the present observed associations 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.
Endurance exercise and arrhythmia: It's time to believe
June 14 2013
The idea that long-term endurance exercise increases the risk of arrhythmia should no longer be considered counterintuitive. The list of published studies confirming this association is long, and this week, it got a little longer.
In a study published in the European Heart Journal, (see article below) researchers from Sweden report a cohort study of more than 52 000 cross-country skiers followed for decades. These were no ordinary weekend athletes; the analyzed group included finishers of the Vasaloppet, a grueling 90-km (55-mile) cross-country ski race. Reliable sources tell me that cross-country skiing over that distance is the Nordic equivalent of an Ironman or double marathon. Yikes.
The hypothesis of the study held that both the number of races completed (exercise dosage) and finishing time (exercise intensity) associate with arrhythmia. (I would have bet my new mountain bike on that one.)
The average age of athletes at study entry was 38, while the average age of first arrhythmia was 57. Of the 52 000 athletes studied, there were 919 inpatient visits for any arrhythmia during a mean follow-up of 9.7 years.
The most common diagnosis was atrial fibrillation (n=681), followed by bradyarrhythmia (n=119), including 34 athletes with complete AV block. Typical supraventricular tachycardia (SVT) occurred in 105 athletes, and premature ventricular contractions (PVCs)/ventricular tachycardia (VT) in 90. Only patients with symptoms were counted.
Athletes who completed the highest number of races had the highest risk of arrhythmia. Arrhythmia risk increased on a continuum by races completed, up to 30% higher for five-time finishers. Exercise intensity mattered too: Those who had the fastest finishing times had the higher risk of arrhythmia.
Three features of this report stand out
The study group included mostly high-level endurance athletes. The aerobic capacity required to finish such an event selects a narrow group. For instance, nearly 80% of Vasaloppet finishers participate in intense training all year round. These are not moderate exercisers dabbling in weekend 5Ks or spin classes.
The second finding was the strong correlation with dosage of exercise. The more races completed, the higher the risk of arrhythmia. The increase in risk was linear, with a 10% increase per race completed. And do not be fooled by the seemingly low overall incidence of arrhythmia (1.97%). That's more than double the rate one would expect in an age-matched group.
The third, and perhaps most striking, finding was the association with finishing time. The fastest finishers had the highest risk of arrhythmia. The "strollers," or those who finished in more than double the fastest finishing time, had the lowest risk of arrhythmia.
Summary and parting shots
It's pretty simple: extreme endurance exercise, done over the long term and with great intensity, increases the risk of arrhythmia. There's no refuting this strong association. These observations are both plausible and consistent with prior studies.
There should be no surprise when an endurance athlete shows up with atrial fibrillation or some other arrhythmia. We are not surprised when masters-aged athletes suffer from other inflammation-induced maladies, like overuse injuries, heart attacks, infections, and even divorce; why are we surprised they get AF?
But context is important. Previous studies have shown Vasaloppet finishers enjoy lower overall mortality. They smoke less, carry less body fat, and report better eating habits. This bolsters the idea that the lifestyle of endurance racing confers good overall health to most participants. Exercise is good. That observation remains unchanged and unchallenged. In the US, we would do better with an epidemic of over- rather than underexercise.
It's also important to emphasize that association is not causation. We don't know whether excessive exercise alone caused the arrhythmia episodes. There are too many possible confounding variables to make a causation link.
And . . . just because intense and long-term endurance exercise increases the risk of arrhythmia does not mean athletes should avoid a sport they love. These studies don't tell us to recommend against endurance exercise. They simply inform both doctor and athlete of possible consequences. There are always trade-offs.
As physicians and teachers, knowledge of the association between chronic inflammation and disease might help us give better advice to our athletic patients. My guess, and it is just a guess, I am no coach, is that the same things that help an athlete avoid AF might also make them faster. Do you think getting adequate rest and recovery improves VO2 max? Do you think being content with something less extreme than an Ironman or cross-country ski marathon might be antiarrhythmic? What's wrong with a fast 10K?
On a personal note, I admit to being drawn to these findings. It's normal to like science that validates one's beliefs: in this case, the dose-response relationship of exercise with arrhythmia only strengthens my theory that excess inflammation is the connector.
Risk of arrhythmias in 52 755 long-distance cross-country skiers: a cohort study
Eur Heart J (June 2013)
Aims We aimed to investigate the association of number of completed races and finishing time with risk of arrhythmias among participants of Vasaloppet, a 90 km cross-country skiing event.
Methods and results All the participants without cardiovascular disease who completed Vasaloppet during 1989-98 were followed through national registries until December 2005. Primary outcome was hospitalization for any arrhythmia and secondary outcomes were atrial fibrillation/flutter (AF), bradyarrhythmias, other supraventricular tachycardias (SVT), and ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA). Among 52 755 participants, 919 experienced arrhythmia during follow-up. Adjusting for age, education, and occupational status, those who completed the highest number of races during the period had higher risk of any arrhythmias [hazard ratio (HR)1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed race], AF (HR 1.29; 95% CI 1.04-1.61), and bradyarrhythmias (HR 2.10; 95% CI 1.28-3.47). Those who had the fastest relative finishing time also had higher risk of any arrhythmias (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time), AF (1.20; 95% CI 0.93-1.55), and bradyarrhythmias (HR 1.85; 95% CI 0.97-3.54). SVT or VT/VF/CA was not associated with finishing time or number of completed races.
Conclusions Among male participants of a 90 km cross-country skiing event, a faster finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by a higher incidence of AF and bradyarrhythmias. No association with SVT or VT/VF/CA was found.
Physical inactivity is a major risk factor for cardiovascular disease, and regular leisure-time exercise reduces cardiovascular risk significantly.1-4 On the other hand, strenuous physical exercise may induce life-threatening ventricular arrhythmias in patients with pre-existing heart disease; autopsies of 1435 athletes who suffered sudden cardiac death during training have revealed cardiac abnormalities in 97% of the cases.5-8
Endurance training can lead to a number of physiological structural cardiac changes, including left atrial dilation and left ventricular dilation and hypertrophy.9,10 Further, sinus bradycardia, first-degree atrioventricular block, and second-degree atrioventricular block type I (Wenckebach) are considered normal responses to training.11 These structural changes are at least partly reversible, but an increased incidence of sinus node dysfunction is seen in retired elite cyclists.12,13 Although some of these structural changes and bradyarrhythmias may be physiological, associations with adverse clinical outcomes are unknown. Several small case-control studies and one cohort study have demonstrated that athletes committed to endurance exercise have increased risk of atrial fibrillation and flutter compared with the normal population,14-20 but adequately powered cohort studies are lacking.
We hypothesized that a long-term increased workload as a consequence of prolonged endurance training would lead to structural changes in the heart and autonomic disturbances, which could increase arrhythmogenicity. We investigated the association of number of completed races and finishing time in the race, with the risk of hospitalization for arrhythmias in a cohort of 47 477 male and 5278 female participants in a long-distance cross-country ski race, ranging from recreational skiers to elite athletes.
Setting and participants
All Swedish participants in the 90 kilometre skiing event Vasaloppet (www.vasaloppet.se) who completed the race during the period 1989-98 were included. Vasaloppet takes place on the first Sunday in March every year and is a cross-country skiing event from Salen to Mora in Dalarna, Sweden.
Approximately 15 000 participants ranging from recreational to elite skiers complete the 90 kilometres of cross-country skiing every year. The 90 km Vasaloppet has two competitions: (i) the main race on the first Sunday of March where participants start in a large group; (ii) for those who prefer avoiding the stress of the group start, there are two additional race days ('oppet spar') where participants can start any time within an hour. The track completed is the same. This study includes both participants starting in the main race and in the 'oppet spar' race. During the inclusion period, one race was cancelled (1990, because of thawing).
The participants in Vasaloppet generally have higher leisure time physical activity, lower incidence of physical and mental illness, tobacco consumption, fat intake, and higher fibre consumption than average Swedes.21 Further, participants in the race have lower mortality in all major diagnostic groups (cancers and diseases of the circulation system), injuries and poisoning.21
The Vasaloppet office provided information on all Swedish participants who completed any of the races 1989-98 (49 117 men and 5443 women), including year of the race, finishing time, and the unique 10 digit national registration number to The National Board of Health and Welfare, Sweden. The National Board of Health and Welfare linked the data to: (i) the Swedish National In-Patient Register to obtain a list of diagnoses, (ii) censuses 1960, 1970, 1980, and 1990 to receive information on occupation and educational level, and (iii) the Swedish Population Register to obtain information of emigration. Anonymous data were then delivered to the authors. Participants hospitalized with cardiovascular disease (ICD-10 I.00-99 or similar diagnosis in ICD-7/8/9) before the baseline date were excluded (n = 1803). The final study sample comprised 47 477 men and 5278 women without any cardiovascular disease. The study protocol was approved by the Regional Ethical Review Board, Karolinska Institutet, Stockholm, Sweden.
Because improvements in VO2max are directly related to the intensity, duration, and frequency of training,22 we used the number of finished races and finishing time as a measure of the participants' duration and intensity of exposure to physical exercise. We investigated finishing time as a categorical variable, divided into four groups of percentages of the winning time that year [100-160%, 161-200%, 201-240%, and >240% (reference group)]. Only the best relative finishing time for each individual during the 10 year period was considered. Further, we investigated number of races as a categorical variable [1 race (reference group); 2 races; 3-4 races; and ≥5 races]. Number of races and finishing time before 1989 or after 1998 were not considered in the exposure assessment.
The cohort was linked to censuses 1960, 1970, 1980, and 1990 to receive information on occupation and educational level. The latest, most updated information for each person was used in this study. Occupation was grouped into four categories (blue-collar, lower-middle white-collar, high white-collar, and entrepreneur). Highest education level obtained was categorized as low (elementary school only), medium (secondary school), and high (university) levels. There were missing values for education in 3072 participants and for occupational status in 6331 participants.
Follow-up and outcome parameter
Participants were followed from the last participation in the race during the period from 1989-98 (the baseline date) to the date of first diagnosis of the outcome of interest, death, date of emigration, or the end of the follow-up (31st December 2005). Because the national registries were used for follow-up, loss to follow up was negligible.
The primary outcome was for any arrhythmia (all of the diagnoses below, plus ICD-10: I47.9). As secondary endpoint, we used (i) Bradyarrhythmias (ICD-10: I44.1, I44.2, I45.2, I45.3, I45.9, I49.5), (ii) Atrial fibrillation or flutter (AF) (ICD-10: I48.9), (iii) Other supraventricular tachycardias (SVT) (ICD-10: 45.6, I47.1), and (iv) ventricular tachycardia/ventricular fibrillation/cardiac arrest (VT/VF/CA) (ICD-10: I47.0, I47.2, I46.0, I46.1, I46.9, I49.0, R96.0). Corresponding codes for ICD-9 were used; see Supplementary material online, Table S1 for complete list of codes. Both main diagnosis and secondary diagnoses were taken under consideration. Note that use of ICD codes does not allow differentiation between Mobitz-types of A/V-block grade II.
Missing values for the variables 'occupational status' and 'education' were imputed from all other variables using multiple imputations by a chained equation approach (number of imputation cycles 25).23 For each endpoint, person-years of risk were calculated and Nelson-Aalen plots were produced to test the hazard proportionality assumption. No deviation was observed. To investigate associations of the exposures 'number of races' and 'finishing time group' with risk of arrhythmia outcomes, a Cox proportional hazards regression model was used. We modelled the risk of the primary endpoint (all arrhythmias) and the secondary endpoints (bradyarrhythmias, AF, other SVT, VT/VF/CA) in separate models. Using directed acyclic graphs, a model adjusting for age, occupational status, and education was deemed sufficient to estimate the total effect (evaluating all causal paths) of training level on arrhythmias, also in the absence of important covariates such as blood pressure, diabetes, hyperthyroidism, use of doping, smoking, and alcohol intake (Supplementary material online, Figure S1).24 Hence, two sets of models were investigated: (i) age-adjusted and (ii) adjusted for age, occupational status, and education. Further, to test for a trend by increasing exposure, a model treating 'numbers of races' and 'finishing time group' as continuous variables were performed. Multiplicative interaction terms between contrasting levels of the variables 'number of races' and 'finishing time group', and each of those two variables with contrasting age and sex groups, were investigated in the primary endpoint models using likelihood-ratio tests, but did not indicate important interactions. Stata 12 (StataCorp LP, USA) was used for all calculations, and two-tailed 95% confidence intervals (CI) were considered.
Baseline characteristics of the participants are shown in Table 1. For the primary outcome any arrhythmia, the median follow-up time was 9.7 years (minimum 0.01 years; maximum 16.8 years). Mean age at inclusion was 38.5 (SD 12.2) years, and mean age of first diagnosis was 56.8 (SD 13.5) years. Tables with separate results for men and women are shown in Supplementary material online, Table S2.
During a total of 513 496 person-years at risk, 919 cases of arrhythmia were reported (17.9; 95% CI 16.8-19.1/10 000 person-years at risk). Cumulative incidence of arrhythmias by number of completed races and finishing time is shown in Figure 1. Adjusting for age, education, and occupational status, we observed higher incidence of arrhythmias with increasing number of races (HR 1.30; 95% CI 1.08-1.58; for ≥5 vs. 1 completed races) and by faster finishing time (HR 1.30; 95% CI 1.04-1.62; for 100-160% vs. >240% of winning time) (Figure 2). Treating exposure as a continuous variable resulted in a HR of 1.06; 95% CI 0.99-1.13 by each step of 'finishing time group' and a HR of 1.10; 95% CI 1.03-1.16 by each step of 'number of races' group. A model only adjusting for age was also tested showing similar results (data not shown). Noteworthy, because of the natural loss of performance with increasing age, the number of elderly athletes in the fastest finishing time groups was limited.
During follow-up, 119 participants were diagnosed with a bradyarrhythmia (2.3; 95% CI 1.9-2.8/10 000 person-years at risk), mainly grade II and III atrioventricular blocks and sick sinus syndromes (Table 2). When adjusting for age, education, and occupational status, higher risk of bradyarrhythmias was observed with increasing number of races (HR 2.10; 95% CI 1.28-3.47; for ≥5 vs. 1 completed races) and with faster finishing times (HR 1.85; 95% CI 0.97-3.54; for 100-160% vs. 240% of winning time) (Tables 3 and 4). Treating exposure as a continuous variable resulted in a HR of 1.29; 95% CI 1.10-1.52 by each step of 'number of races' group and a HR of 1.16; 95% CI 0.95-1.40 by each step of 'finishing time group'. As a sensitivity analysis, we excluded potentially non-pathological bradyarrhythmias (atrioventricular blocks II and bi- and tri-fascicular blocks) from the outcome, with comparable results (Supplementary material online, Table S2).
Atrial fibrillation and flutter
The most frequent arrhythmia was atrial fibrillation, which occurred in 681 skiers (13.2; 95% CI 12.3-14.3/10 000 person-years at risk). In a model adjusted for age, educational, and occupational status, we observed higher incidence of atrial fibrillation with higher number of races (HR 1.29; 95% CI 1.04-1.61 for ≥5 vs. 1 completed races) and a tendency to higher incidence of atrial fibrillation with faster finishing times (HR 1.20; CI 0.93-1.55; for 100-160% vs. 240% of winning time) (Tables 3 and 4). Treating exposure as a continuous variable resulted in a HR of 1.09; 95% CI 1.02-1.17 by each step of 'number of races' group and a HR of 1.04; 95% CI 0.96-1.13 by each step of 'finishing time group'.
The secondary endpoints of other SVT (n = 105) and VT/VF/CA (n = 90) were analysed in the same way. No associations of number of completed races or finishing time group with risk of SVT or VT/VF/CA were found (Tables 3 and 4).
This study confirms findings from earlier studies of higher incidence of arrhythmias with higher training level in athletes.14-20 We observed a higher rate of AF and bradyarrhythmias among skiers with higher number of completed races and with faster relative finishing times, over a 10 year follow-up period. We did not observe associations between the number of completed races or finishing time group and the risk of other SVT or the more dangerous VT/VF/CA. This study extends current knowledge by providing cohort study data on persons in the higher end of the distribution of physical activity.
Abnormal ECG patterns are very common among elite athletes. Distinctly or mildly abnormal ECGs have been observed in as much as 50-60% of athletes committed to endurance sports.11 Sinus bradycardia, grade I atrioventricular block, and grade II Mobitz type I block should be considered as normal findings11,12,25-27 but even the incidence of AV-block grade III is reported more frequently among athletes than that in the general population.26 Further, one earlier study reports higher rate of subclinical sinus node dysfunction among retired elite cyclists.13 The present study observed an approximately two-fold higher risk of hospitalization for bradyarrhythmias in athletes who completed five or more races compared with those who only completed one race. Of note, in order to capture clinically relevant bradyarrhythmias (i.e. potentially requiring a pacemaker), sinus bradycardia and grade I atrioventricular block were not included in this outcome. The use of ICD codes did not give opportunity to differ between atrioventricular blocks II Mobitz type I and II. For this reason, it is possible that some normal variants are included as pathological findings. However, grade II atrioventricular block only represents 23% of the bradyarrhythmia cases, and the results were consistent after excluding potentially non-pathological bradyarrhythmias (atrioventricular blocks II and bi- and tri-fascicular blocks) from the outcome. Interestingly, there may exist a link between bradycardia and increased risk of atrial fibrillation since atrial size, long PQ time, and bradycardia seem to be risk factors for atrial fibrillation among endurance trained athletes.19
Earlier case-control studies report higher incidence of atrial fibrillation in endurance sports-trained athletes and present odds ratios between 1.9 and 8.8 compared with non-athletes.15-18 The effects of physical training in the present study may seem modest compared with earlier findings, but there are several methodological differences between the present study and the earlier studies, and the risks of bias in case-control studies are higher than in cohort studies. It is important to stress that this study only compares the risk of arrhythmias in an active population, and there may be a threshold training amount, below the level of most Vasaloppet participants. The Physicians Health study among 1572 healthy physicians showed increased risk of atrial fibrillation by increasing days per week of exercise vigorous enough to break a sweat.14 Although neither that study nor the present study had direct measurements of fitness level, the present study likely investigates individuals at a higher fitness level and hence extends the dose-response curve. It is possible that associations of physical training level with atrial fibrillation would have been even greater had the cohort included also less physically active people.
Incidence rates of atrial fibrillation have been sparsely reported for young people. The Rotterdam and Framingham studies report incidence rates of atrial fibrillation among men aged 55-64 representing the general population at 22 and 31 per 10 000 person-years at risk, respectively.28,29 In the present cohort, we find an incidence rate of atrial fibrillation and flutter of 49 (95% CI 43-51) per 10 000 person-years at risk among men aged 55-64. Although there are several methodological differences between the studies, this could indicate a higher rate in the skiers of this study than in the general population.
Other arrhythmias and death
It is well established that young athletes with pre-existing heart disease are at higher risk of sudden cardiac death.5 The heart disease is often unknown to the athlete, and this may also pertain to Vasaloppet participants. We did not observe higher incidence of sudden cardiac death with higher number of completed races or finishing time, but again it must be stressed that this study does not compare with the normal population. We have previously shown that participants in Vasaloppet have lower mortality than the general population and that mortality decreases with increasing number of races.21 Similar associations were observed in a Dutch long-distance skating event.30 We hence believe that it is generally safe to prepare for and participate in the race.
The Swedish National Board of Health and Welfare recommends, in accordance with the recommendations of the European Society of Cardiology,31 that all athletes competing at elite level have a physical evaluation including personal and family medical history, physical examination, and resting ECG. Only if these investigations reveal abnormal findings, further examinations (like echocardiography or stress testing) are performed. Which athletes are regarded as elite is defined by the specific sports associations (for skiers, the Swedish Ski Association). The elite group in Vasaloppet consists of a few hundred skiers of different nationality (this study only includes Swedish participants). We hence believe that the potential bias of screening is low, and for all practical purposes, this cohort should be regarded as non-screened.
Earlier cross-sectional studies report similar prevalence of SVT among athletes and the normal population, and this study supports independence of training level and SVT, at least in the setting of recreational skiers to elite athletes.26 This is not surprising since these arrhythmias (e.g. AV nodal reentrant tachycardia and Wolff-Parkinson-White) often rely on congenital or developmental changes in the heart's conduction system.
Strength and limitations
Strengths of the present study include the very large sample size of more than 52 000 athletes without known pre-existing heart disease, the cohort design, and the use of official registries for determination of socioeconomic measures and identification of the outcomes, which also minimizes loss-to-follow-up.
Some limitations of the study are worth noting. The incidence of atrial fibrillation increases dramatically with age, and because this cohort is quite young, possibly important associations at older age remain unknown. The exposure may be imprecisely measured, as the exposure is not limited to the participation in the race but may also include training before the race. Furthermore, many participants are likely committed to other sports activities during the summer. Indeed, in an earlier study of this population, 79.1% participants, compared with 29.5% in the normal population, reported strenuous exercise over the last year.21 Hence, our exposure measure may reflect all-year activity, which on the other hand may be viewed as a strength. Since we do not have any information on participation in races before the index date, it is possible that some of the participants have completed other races before the index date and only one afterwards. Likewise, follow-up was longer than the inclusion time, and participants could continue to race. Thus, it is likely that we may underestimate this exposure. This misclassification is not suspected to affect exposure groups differentially and should hence not bias the associations, but may affect the interpretation of the absolute numbers of races. It is possible that some participants did not complete the race because they developed arrhythmia during the race, and such participants are not included in the cohort. We do not have any information on non-fatal arrhythmias during the race, but we know that only one participant died in the track during the inclusion period.8
It is possible that some of the athletes have suffered from ischaemia-induced arrhythmias or arrhythmias of other specific aetiology, but we excluded persons with previous cardiovascular disease, and the incidence of subsequent cardiovascular disease is low in this population of physically active persons.21 Residual protopathic bias by pre-existing cardiovascular disease is possible (which would tend to bias results towards the null) but is unlikely a major explanation, as Vasaloppet is a strenuous race.
The study design limits the possibility of adjusting for several potentially important confounders, including smoking, alcohol use, blood pressures, and diabetes, but these were not identified as crucial covariates in order to minimize bias using the directed acyclic graphs approach, although residual confounding by these and other unmeasured factors is possible. This study is also limited by the lack of comparison of the sport active persons with inactive persons. The use of data from the Swedish National In-patient Register likely identifies outcomes with some random misclassification, which would tend to bias us towards the null and also precludes separation of atrial flutter and fibrillation or grade II atrioventricular blocks type I or II. On the other hand, this study uses diagnoses that can be read from standard ECG also by non-experienced doctors. Furthermore, it is possible that physically active persons have a lower threshold for seeking hospital service for arrhythmia symptoms than less physically active persons. We believe this potential confounding to be limited because the present cohort consists of persons with a training level needed for 90 km strenuous cross-country skiing; hence, most of the participants will likely experience symptoms and seek hospital services for arrhythmias regardless of race result or number of completed races. The generalizability to other ethnic groups is unknown. We did not find any interactions between sexes, but the limited number of women did not allow us to draw any firm conclusions regarding any sex-specific effect of exercise and risk of arrhythmias in women. This study cannot assess causality, but other studies suggest that longstanding endurance training could lead to vagal predominance32 and increased risk of extrasystoles and increases left atrial size33 and the amount of myocardial fibrosis,34,35 which may act as arrhythmia triggers and substrates.
In this study of 52 755 participants of a 90 km cross-country skiing event, a fast finishing time and a high number of completed races were associated with higher risk of arrhythmias. This was mainly driven by associations with risk of atrial fibrillation and bradyarrhythmias. No associations of number of completed races or finishing time with other SVT or dangerous arrhythmias such as VT/VF/CA were observed, which parallels previous observations in this cohort of lower standardized mortality with higher number of completed races.21