Those who think they have not time for bodily exercise will sooner or later have to find time for illness. – Edward StanleyReference Stanley 1
In the midst of a global obesity crisis,Reference Seidell and Halberstadt 2 exercise can be a cost-effective, therapeutic tool to improve a patient’s cardiovascular risk profile. Engaging in daily aerobic exercise confers benefits that include lowered blood pressure, improved blood lipid profile, weight loss, and increased insulin sensitivity.Reference Pescatello, Franklin and Fagard 3 – Reference Boule, Haddad, Kenny, Wells and Sigal 6 The risk of coronary heart disease is also diminished, with a reported 30–50% risk reduction.Reference Mora, Cook, Buring, Ridker and Lee 7 – Reference van Dam, Li, Spiegelman, Franco and Hu 10 The most recent American Heart Association recommendations indicate that children should participate in moderate- to vigorous-intensity aerobic activities for at least 60 minutes a day, whereas adults should have a minimum of 150 minutes of moderate-intensity aerobic exercise per week, to achieve these benefits.Reference Mozaffarian, Benjamin and Go 11 Historical and cultural fears about excessive exercise, as suggested by the exclusion of female runners from distance races in the Olympics,Reference Lovett 12 predate the emerging data that suggest regular physical activity may incur some cardiovascular risk. A U-shaped relationship between exercise intensity and cardiovascular outcomes has been proposed, with moderate-intensity exercise conferring the greatest benefits but vigorous exercise being associated with more harm in some individuals.Reference Merghani, Malhotra and Sharma 13 The increased demand on the cardiovascular system has been shown to have acute and chronic cardiac effects and be associated with electrophysiological abnormalities. These may be substrates for lethal arrhythmias resulting in sudden cardiac death. It is not known whether this risk with exercise is important for all or just a select few endurance athletes, all of whom regularly exceed the recommendations for physical activity. A greater proportion of the general population can now be categorised as endurance athletes, as the popularity of endurance sports such as cycling and running and multisport events has increased. When it comes to exercise, much more may not necessarily be better.
Acute cardiac effects
The association between exercise and myocardial strain not only forms the basis of the graded exercise test,Reference Brawner 14 but is the foundation for the field of research examining the cardiovascular health of athletes. In 1961, Beswick et alReference Beswick and Jordan 15 recorded resting electrocardiographic data from athletes in the British Empire and Commonwealth games and noted nuanced variations unique to the athletic population. These differences quickly became an area of interest. Shortly after Beswick’s findings, others found evidence for myocardial injury in both recreational athletesReference LaPorta, Linde, Bruce and Fitzsimons 16 and marathon runners.Reference Siegel, Silverman and Lopez 17 , Reference Schiff, MacSearraigh and Kallmeyer 18 Since then, multiple studies involving large cohorts of athletes have demonstrated increases in serum concentrations of biomarkers for cardiac damage immediately following exercise.Reference Middleton, George, Whyte, Gaze, Collinson and Shave 19 – Reference Shave, Whyte, George, Gaze and Collinson 22 It is currently not well understood whether this damage can serve as a substrate for cardiac dysfunction or arrhythmias. Rats exercised for 16 weeks, the equivalent of 10 human years, had pronounced left ventricular hypertrophy, diastolic dysfunction, and marked fibrosis in the right ventricle and atria.Reference Benito, Gay-Jordi and Serrano-Mollar 23 Of significance, ventricular arrhythmias were inducible in 42% of exercised rats compared with only 6% of sedentary rats. In a human study, more than half of non-elite participants in the Boston Marathon had elevated biomarkers for cardiac damage, and these increases were associated with altered ventricular function.Reference Neilan, Januzzi and Lee-Lewandrowski 21 The association was most pronounced in runners who had prepared the least for the marathon. This apparent link between cardiac damage and ventricular dysfunction, however, does not provide evidence for a causal relationship. It is unknown whether the increase in cardiac biomarkers is of any significance, or if it simply represents temporary adaptations to regular exercise.Reference O’Keefe, Patil, Lavie, Magalski, Vogel and McCullough 24 Recent evidence supports the notion that exercise-induced depression of ventricular function is transient rather than persistent. Runners completing the Manitoba Marathon had abnormal biochemical profiles immediately after race along with echocardiographic data that indicated right ventricular systolic and biventricular dysfunction.Reference Mousavi, Czarnecki and Kumar 25 A week later, contrast-enhanced MRI showed no indication of persistent dysfunction or fibrosis in any of the runners. In contrast, runners of the 89-km Comrades Marathon had no correlation between biochemical and echocardiographic evidence of cardiac damage.Reference George, Shave and Oxborough 26 Conflicting findings in this area of research highlight the need for further studies.
Chronic cardiac effects
Athlete’s heart
With the increased use of echocardiography, clinicians have become aware of a phenotype of hypertrophy associated with exercise. The characteristics of this exercise-induced hypertrophy overlap with that of hypertrophic cardiomyopathy, the leading cause of sudden cardiac death in athletes.Reference Sharma, Merghani and Mont 27 Guidelines for normal cardiac changes in response to exercise are lacking; however, information regarding symptoms and family history is important to guide further investigations and exercise restrictions.Reference Prior and La Gerche 28
Sustained increases in cardiac output and altered loading characteristics from regular athletic training drive the structural and functional adaptations in the heart, collectively termed as “athlete’s heart”.Reference Prior and La Gerche 28 This is most notable in athletes participating in dynamic sports.Reference Prior and La Gerche 28 Athlete’s heart is usually benign and reversible after periods of prolonged de-conditioning.Reference Prior and La Gerche 28 There are little data on the minimum training required to induce re-modelling; however, a meta-analysis found that engaging in leisure sports activity for more than 3 hours/week was sufficient to lower resting heart rate and increase VO2 max and left ventricular mass.Reference Fagard 29 Athlete’s heart is evidenced by dilation of both ventricles, thickening of the ventricular walls, and atrial dilation in proportion to the ventricular expansion.Reference Prior and La Gerche 28 This occurs in order to compensate for the additional volume load.Reference Prior and La Gerche 28 The extent of structural re-modelling lies on a continuum, with reported ranges in cardiac volumes and masses and variances in VO2 max across different types of athletics.Reference La Gerche, Burns, Taylor, Macisaac, Heidbuchel and Prior 30 , Reference Steding, Engblom and Buhre 31 Left ventricular ejection fraction is preserved in most athletes similar to that of the general population.Reference Prior and La Gerche 28 High-calibre athletes may have a reduced left ventricular ejection fraction at rest, and this is positively correlated with the degree of left ventricular hypertrophy.Reference Abergel, Chatellier and Hagege 32
Genetic susceptibility: arrhythmogenic right ventricular cardiomyopathy
Although the most common cause of sudden unexpected death in athletes in the United States of America is hypertrophic cardiomyopathy, exacerbation of that disease phenotype has not been linked to exercise.Reference Maron, Doerer, Haas, Tierney and Mueller 33 In contrast, arrhythmogenic right ventricular cardiomyopathy has been shown to progress with exercise.Reference Kirchhof, Fabritz and Zwiener 34 , Reference Ruwald, Marcus and Estes 35 This cardiomyopathy predisposes affected patients to sudden cardiac death and arrhythmias via abnormalities in the right ventricle.Reference Corrado and Zorzi 36 Recent evidence in animal models and in humans suggests that regular endurance exercise predicts a more severe phenotype, increasing the risk of sudden cardiac death. Mice heterozygous for plakoglobin (plakoglobin+/−), an established mutation in right ventricular cardiomyopathy, subjected to strenuous exercise were compared with inactive plakoglobin+/− mice.Reference Kirchhof, Fabritz and Zwiener 34 Exercised mice displayed worsened right ventricular function and a higher incidence of spontaneous arrhythmias compared with inactive mice. Similar results were found in competitive athletes diagnosed with right ventricular cardiomyopathy.Reference Ruwald, Marcus and Estes 35 Compared with recreational or inactive patients with right ventricular cardiomyopathy, competitive athletes presented with symptoms earlier and had a twofold increased risk for ventricular tachyarrhythmias or death if exercise was not restricted after diagnosis. Patients engaging in recreational sports only had the same risk as those who were sedentary for these adverse outcomes.Reference Ruwald, Marcus and Estes 35 The results suggest that right ventricular cardiomyopathy patients may be able to participate in recreational sports without conferring additional risks of ventricular tachyarrhythmias or death, but competitive athletes may benefit from activity restrictions. Although right ventricular cardiomyopathy is predominantly an autosomal-dominant disease, with a mutation rate of 27–52%, recent evidence suggests that an exercise-induced right ventricular cardiomyopathy-like syndrome may also exist.Reference La Gerche, Robberecht and Kuiperi 37 In a cohort of athletic patients, where 51% met the 2010 Task Force criteria for right ventricular cardiomyopathy and 36% had clinically suspected right ventricular cardiomyopathy, pathogenic mutations in desmosome genes were found in 12.8% of athletes.Reference La Gerche, Robberecht and Kuiperi 37 This frequency is significantly lower than the reported mutation rate for right ventricular cardiomyopathy.Reference La Gerche, Robberecht and Kuiperi 37 In addition, desmosomal mutations were not found in those athletes who exercised above the weekly average. It is likely that there are many factors, including genetic variants, which predispose athletes to the development of myocardial abnormalities in response to exercise.
Electrophysiological considerations
The structural adaptations to exercise are frequently coupled with electrical changes, visible on electrocardiogram. Most changes are benign, including sinus bradycardia, first-degree atrioventricular block, incomplete bundle branch block, early re-polarisation changes, and voltage criteria for left ventricular hypertrophy.Reference Prior and La Gerche 28 These are largely due to the ventricular expansion and heightened vagal tone associated with sustained training. Abnormal findings such as pathological Q waves, complete bundle branch blocks, or T wave inversions are important to identify as uncommon in athletes.Reference Prior and La Gerche 28 These can be key indicators of cardiac pathologies that often lack phenotypic structural changes, such as the inherited channelopathies: long and short QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.Reference Behere and Weindling 38 Further investigation in these cases is vital for diagnosis and preventing sudden cardiac death in these athletes.Reference Prior and La Gerche 28 , Reference Behere and Weindling 38
Atrial fibrillation
Atrial fibrillation is the most common tachyarrhythmia in athletes.Reference Link, Homoud, Wang and Estes 39 Although it is known that arrhythmias depend on triggers, substrates, and modulators,Reference Farre and Wellens 40 the aetiology and pathophysiology of atrial fibrillation are poorly understood. Atrial fibrillation decreases the contribution of atrial contraction to cardiac output causing reduced exercise tolerance. The most devastating complication of atrial fibrillation, however, is systemic thromboembolism. Atrial and ventricular ectopies are found to be increased as a consequence of intense physical activity.Reference Wilhelm, Roten, Tanner, Wilhelm, Schmid and Saner 41 , Reference Bjornstad, Storstein, Meen and Hals 42 Atrial ectopy has been shown to be the trigger in most episodes of paroxysmal atrial fibrillation.Reference Haissaguerre, Jais and Shah 43 Increased ectopy may be one of the mechanisms explaining the increased vulnerability of athletes to atrial fibrillation, provided that this ectopy acts upon a vulnerable substrate. Whether athletes have a structural substrate is still in debate. Atrial dilatation and fibrosis have been shown to increase susceptibility to atrial fibrillation in animal models.Reference Guasch, Benito and Qi 44
The vulnerability of athletes to atrial fibrillation has been explained by the elevated vagal tone, which may in turn increase the susceptibility to atrial fibrillation by changing the dispersion of the atrial refractory period.Reference Mont, Elosua and Brugada 45 Coumel originally described “vagal atrial fibrillation” in his work on the influence of autonomic tone on the occurrence of atrial fibrillation. The clinical pattern of atrial fibrillation is preceded by bradycardia during periods of vagal tone predominance – at rest, sleep, or post-prandial – and was observed in male athletes with structurally normal hearts.Reference Coumel 46 Experimental studies in animals have demonstrated that vagal stimulation increases the variability in atrial refractoriness.Reference Liu and Nattel 47 This in turn enhances the ability to sustain atrial fibrillation when it is induced by an atrial trigger.Reference Liu and Nattel 47
The relationship between physical activity and atrial fibrillation is complex and follows a U-shaped relationship.Reference Stirbys 48 In a series of 107 healthy individuals presenting with atrial fibrillation, “vagal atrial fibrillation” occurred in 70% of cases.Reference Mont, Tamborero and Elosua 49 Light-to-moderate exercise was associated with a lower relative risk of new-onset atrial fibrillation in the cardiovascular health study.Reference Mozaffarian, Furberg, Psaty and Siscovick 50 In contrast, long-term high levels of endurance exercise appear to increase the incidence of atrial fibrillation. In 16,921 apparently healthy men in the Physicians’ Health Study, the risk of atrial fibrillation increased with the number of days per week of vigorous physical activity.Reference Aizer, Gaziano, Cook, Manson, Buring and Albert 51 Other studies have shown an increase in atrial fibrillation among endurance athletes, with a fivefold increased relative risk in these athletes.Reference Sorokin, Araujo, Zweibel and Thompson 52 , Reference Abdulla and Nielsen 53 There is some evidence that the recurrence of paroxysmal atrial fibrillation may be reduced by limiting physical activity.Reference Furlanello, Bertoldi and Dallago 54
Sudden cardiac death
Sudden cardiac death is the most frequent medical cause of death in athletes. It is often due to an underlying cardiac condition, most commonly hypertrophic cardiomyopathy.Reference Maron, Doerer, Haas, Tierney and Mueller 33 These tragedies are devastating and unexpected, leaving families, communities, and healthcare professionals searching for answers. Sudden cardiac death in sports is highly visible, attracting media and public attention. Implementation of screening programmes aimed to prevent sudden cardiac death have been widely debated in recent years, but the overall rarity of this tragic event calls into question the efficacy of implementing such large-scale programmes. The reported incidence of sudden cardiac death is quite low: between 1 : 40,000 and 1 : 80,000 athletes each year;Reference Harmon, Drezner, Wilson and Sharma 55 nevertheless, numerous studies have reported that athletes who regularly train are at risk for sudden cardiac death.Reference Maron, Doerer, Haas, Tierney and Mueller 33 , Reference Toresdahl, Rao, Harmon and Drezner 56 – Reference Harmon, Asif and Maleszewski 58
In an analysis of sudden death in young competitive athletes in the United States of America over a 27-year period, over half (56%) of the deaths were judged to be definitely or probably sudden cardiac death; 80% of these occurred during exercise.Reference Maron, Doerer, Haas, Tierney and Mueller 33 A 2-year prospective study of sudden cardiac arrests in high school athletes revealed that 69% of the arrests occurred during physical actvity.Reference Toresdahl, Rao, Harmon and Drezner 56 Male gender appears to confer a greater risk of sudden cardiac arrest, as 89% of victims were male athletes in both studies. This may be attributed to gender differences in physical activity. Lenhart et alReference Lenhart, Hanlon, Kang, Daly, Brown and Patterson 59 found that male high-school students were more likely to participate in physical activities than their female peers, and a greater proportion of males than females were considered highly active, with 5–7 days of activity/week. There are discrepancies in the reported rates of sudden cardiac death during exercise. Pilmer et al studied sudden cardiac death in children and found that only 16% of sudden cardiac deaths occurred during exercise, a figure much lower than that previously reported.Reference Maron, Doerer, Haas, Tierney and Mueller 33 , Reference Pilmer, Kirsh, Hildebrandt, Krahn and Gow 57 Teenage athletes were over-represented in this group, indicating that adolescence may be a time of risk for sudden cardiac death during exercise.Reference Pilmer, Kirsh, Hildebrandt, Krahn and Gow 57 Male teenagers had a risk of sudden cardiac death 3.2 times that of women, corroborating the finding that the male gender is a risk factor. Among National Collegiate Athletic Association athletes, a little over half of sudden cardiac deaths occurred with exertion.Reference Harmon, Asif and Maleszewski 58 Black athletes were found to be at a substantially higher risk of sudden cardiac death, suggesting that racial factors may play a role in predisposing athletes to sudden cardiac death. Reporting bias, differing methodologies, and heterogeneous populations have contributed to the variations in reported incidence rates of sudden cardiac death in athletes.
Higher endurance states produce increased cardiac stress, because they require a higher percentage of the individual’s maximal heart rate over a longer time period and generate more catecholamine spillover into the circulation. High levels of catecholamines are known to be cardiotoxic. The mechanism of cardiotoxicity is multifactorial, including intracellular calcium overload, coronary spasm, focal myocardial cell damage, depletion of high-energy stores, and ventricular arrhythmias.Reference Dhalla, Temsah and Netticadan 60 It is assumed that most exercise-related sudden cardiac deaths are due to ventricular arrhythmias, but the pathological substrate for sudden cardiac death varies with the age of the victim.
The endurance athlete
Endurance athletes undergo systematic training, regularly surpassing standard exercise recommendations, and participate in long-distance and high-intensity athletic events.Reference Sharma, Merghani and Mont 27 They often compete regularly against others and place an emphasis on athletic excellence.Reference Maron, Araujo and Thompson 61 Although a typical healthy individual exercises roughly 6 hours each week at an intensity of 6–10 metabolic equivalents of task, endurance athletes train over 20 hours/week at an intensity of 15 metabolic equivalents of task.Reference Sharma, Merghani and Mont 27 The result of heightened public awareness surrounding the benefits of habitual exercise has been greater participation in long-distance running events; in 2010, ~2 million runners participated in half-marathon or marathon races in the United States of America compared with <1 million 10 years earlier.Reference Kim, Malhotra and Chiampas 62
Recently, a large multi-centre study investigated the incidence of sudden cardiac arrests during marathons and half-marathons in the United States of America.Reference Kim, Malhotra and Chiampas 62 The overall sudden cardiac arrest rate was low, with an incidence of 0.54/100,000 runners. Sudden cardiac arrests in marathon events were significantly more frequent than in half-marathons (1.01/100,000 versus 0.27/100,000, respectively). Comparison of the survivors of sudden cardiac arrest versus non-survivors shed light on key discrepancies: survivors were older at the time of arrest, had been running for a greater number of years, and were more likely to have a close relationship with a primary-care physician. The cause of sudden cardiac arrest in this group was most frequently attributed to myocardial ischaemia, whereas death in non-survivors was more commonly linked to hypertrophic cardiomyopathy or possible hypertrophic cardiomyopathy.
The emergence of a new group of athletes, the so-called “recreational endurance athletes”, has been brought about by the recent spike in participants of long-distance races. These non-competitive athletes are typically older than their competitive counterparts and engage in moderate-to-vigorous activities in an informal manner.Reference Corrado, Schmied and Basso 63 There appears to be little difference in the incidence rates of exercise-related sudden cardiac death between competitive and non-competitive athletes. A comparison of these two groups in a Danish population revealed a sudden cardiac death incidence of 0.43/100,000 in non-competitive athletes aged 12–35 years and 0.47/100,000 for the same age group of competitive athletes.Reference Risgaard, Winkel and Jabbari 64 In the older age group (36–49 years), competitive athletes had a significantly greater incidence of sudden cardiac death. Overall, sudden cardiac death was less frequent in both groups of athletes in comparison with the general population. In addition to the cardiovascular risks of endurance training, numerous non-cardiac morbidities have been documented, including rhabdomyolysis, heat injury, hyponatraemia, and dehydration.Reference Lee 65 – Reference Casa, Guskiewicz and Anderson 68
Longevity of endurance athletes
The impression that high-calibre training may confer additional health risks makes the long-term outcomes of these endurance athletes an area of great interest. Numerous studies have revealed that participating in grueling athletic events increases longevity.Reference Marijon, Tafflet and Antero-Jacquemin 69 – Reference Coate and Sun 72 A significant 41% lower mortality among participants in the Tour de France was reported over a 65-year period in comparison with the community average.Reference Marijon, Tafflet and Antero-Jacquemin 69 This corresponded to an average increase in lifespan of 6.3 years. Similarly, Olympic medalists have been found to live an average of 2.8 years longer than controls with the greatest survival advantage noticed in athletes from endurance events.Reference Clarke, Walter, Hayen, Mallon, Heijmans and Studdert 70 These survival benefits have also been noted in Major League Baseball players and tennis champions.Reference Saint Onge, Rogers and Krueger 71 , Reference Coate and Sun 72
The cost of competition
Over a million athletes in the United States of America have been estimated to use, or have used, androgen-anabolic steroids to enhance athletic performance.Reference Santos, Oliveira and Silva 73 Androgen-anabolic steroids were introduced to the sports community in the 1950s and originally used to recover muscles after stress and exhaustion.Reference Sharma, Merghani and Mont 27 , Reference Santos, Oliveira and Silva 73 As their presence in sport quickly increased, it was noted that high dosage and repeated use of androgen-anabolic steroids could have both cardiac and non-cardiac consequences.Reference Santos, Oliveira and Silva 73 Dyslipidaemia, hypertension, increased cardiac tissue collagen, diastolic dysfunction, and sudden cardiac death are some of the more severe cardio-toxic effects of androgen-anabolic steroids.Reference Sharma, Merghani and Mont 27 , Reference Santos, Oliveira and Silva 73
Conclusions
The proposal of a U-shaped relationship between exercise intensity and cardiovascular benefits has encouraged evaluation of the potential risks associated with exercise.Reference Merghani, Malhotra and Sharma 13 Electrical and structural re-modelling is a frequently benign side-effect of persistent athletic training, but may serve as a substrate for more severe outcomes such as arrhythmias or cardiac dysfunction. Sudden cardiac death is an important risk for endurance athletes, but the media attention this tragedy garners has exaggerated the true incidence rates. Multiple studies have found that sudden cardiac death during sports is still a rare occurrence.Reference Harmon, Drezner, Wilson and Sharma 55 Although the number of participants in ultra-endurance events has increased in recent years, this still represents a small proportion of the athletic population. There are little data on more typical recreational athletes. Overall, the cardiovascular benefits of exercise still outweigh the potential risks, and high performers appear to have improved longevity across a number of sports.
Acknowledgements
None.
Financial Support
This review article received no specific grant from any funding agency or from commercial or not-for-profit sectors.
Conflicts of Interest
None.
Ethical Standards
The authors assert that all referenced work contributing to this review complies with the ethical standards of biomedical or medicolegal investigation.
