Regular aerobic physical exercise of moderate intensity is undeniably associated with improved health and increased longevity, with some studies suggesting that more is better. Endurance athletes exceed the usual recommendations for exercise by 15-fold to 20-fold. The need to sustain a large cardiac output for prolonged periods is associated with a 10–20% increase in left and right ventricular size and a substantial increase in left ventricular mass. A large proportion of endurance athletes have raised levels of cardiac biomarkers (troponins and B-type natriuretic peptide) and cardiac dysfunction for 24–48 h after events, but what is the relevance of these findings? In the longer term, some endurance athletes have an increased prevalence of coronary artery disease, myocardial fibrosis and arrhythmias. The inherent association between these ‘maladaptations’ and sudden cardiac death in the general population raises the question of whether endurance exercise could be detrimental for some individuals. However, despite speculation that these abnormalities confer an increased risk of future adverse events, elite endurance athletes have an increased life expectancy compared with the general population.
Regular, moderate, aerobic physical exercise reduces cardiovascular and all-cause morbidity and mortality.
Endurance exercise imposes huge demands on the cardiovascular system and, therefore, endurance athletes develop profound adaptations to exercise.
Sinus bradycardia, large QRS voltages, modest increases in left and right ventricular cavity size and high peak oxygen consumption are well-recognized features of an endurance athlete’s heart.
Some lifelong endurance athletes have an increased prevalence of high coronary artery calcium scores, myocardial fibrosis, right ventricular dysfunction, atrial fibrillation and sinus node disease compared with healthy non-athletes, with unknown consequences.
Long-term outcome data and information from studies identifying the concurrent factors that predispose healthy endurance athletes to developing these abnormalities are needed.
Humans are physiologically and anatomically evolved for endurance exercise, which might explain why pursuing a lifestyle of regular aerobic physical exercise protects against atherosclerotic cardiovascular disease and certain malignancies, slows the ageing process, minimizes disability in later life and increases the lifespan by 3–7 years1,2,3. Various mechanisms underlie the cardiovascular benefits of aerobic exercise on morbidity and mortality (Fig. 1). However, despite the overwhelming beneficial effects of aerobic exercise, a small number of studies have suggested a diminishing cardiovascular benefit among individuals participating in regular endurance exercise4. In parallel, some studies have reported high coronary artery calcium (CAC) scores, myocardial fibrosis and atrial arrhythmias in endurance athletes5,6.
In this Review, we provide an update on the effects of regular endurance exercise on the heart. Specifically, we explore the relationship between the dose of endurance exercise and mortality, physiological cardiac adaptations in endurance athletes, and the possibility that excessive endurance exercise might damage both diseased and otherwise normal hearts.
Benefits of endurance exercise
Overwhelming evidence indicates that regular exercise is associated with a reduction in all-cause and cardiovascular morbidity and mortality7,8. A meta-analysis investigating the relationship between physical activity (measured through either self-reporting or objective assessment) and mortality among 883,372 individuals demonstrated that the physically active groups had a 35% reduction in the risk of cardiovascular death and a 33% reduction in the risk of all-cause death over 20 years9. A further meta-analysis assessing the association between accelerometer-determined physical activity and all-cause mortality showed that, regardless of intensity, a greater exercise volume resulted in reduced mortality10. The greatest risk reduction occurred between 375 min of light-intensity physical activity and 24 min of moderate-to-vigorous-intensity physical activity per day. Another study showed that even low-intensity, leisure-time physical activity conferred a significant reduction in all-cause mortality compared with a sedentary lifestyle11.
Although cardiorespiratory fitness has a substantial genetic component12, exercise can improve cardiorespiratory fitness by 20–40%13,14. Both subjective and objective markers of cardiorespiratory fitness have been shown to have a positive correlation with cardiovascular and all-cause mortality15. In a study of 44,452 male health professionals who were followed up for 475,755 person-years, the ability to exercise intensively was independently associated with a reduced risk of myocardial infarction and fatal cardiovascular events16. Moderate (4–6 metabolic equivalents (METs)) and high-intensity (6–12 METs) physical activity conferred a significant risk reduction compared with low-intensity (<4 METs) physical activity16. Furthermore, data from several studies have demonstrated that each MET increase in fitness is associated with a 13–20% reduction in cardiovascular and all-cause mortality17,18,19,20.
A greater cardiorespiratory fitness has also been shown to reduce the risk of hospitalization for heart failure in later life, with each MET increase in fitness reducing this risk by 20%21,22,23. Similarly, among patients with an established diagnosis of heart failure, exercise training improves maximal oxygen consumption (VO2 max) and reduces hospitalization for heart failure and mortality by 28% and 35%, respectively24,25.
Exercise also slows vascular ageing. A study of >130 individuals reported that training for and completing a first marathon at a slow pace resulted in beneficial effects on central blood pressure and arterial stiffness, translating to a 4-year reduction in vascular age26. Older and slower marathon runners benefited the most26.
The WHO recommendations on exercise advocate a minimum of 150 min of moderate-intensity or 75 min of vigorous-intensity aerobic physical activity per week to reduce cardiovascular morbidity and mortality27. A number of studies have attempted to define a threshold ‘dose’ at which these benefits are maximized and have suggested that the ideal dose of exercise for maximal benefit is three to five times the current minimum recommendation11,28,29.
Exercise dose and mortality
Contrary to some of the data presented above, other reports suggest a gradual decline in the reduction in mortality with increasing volume and intensity of exercise. The Copenhagen City Heart Study30 suggested a reverse J-shaped dose–response relationship between lifetime exercise exposure and cardiovascular mortality by studying healthy joggers (n = 1,098) and non-joggers (n = 3,950). Joggers were grouped into light, moderate and strenuous categories of exercise; the joggers in the strenuous category performed four to six times the current recommendations for exercise. The greatest reduction in mortality was observed in light joggers (HR 0.22, 95% CI 0.10–0.47), followed by moderate joggers (HR 0.66, 95% CI 0.32–1.38). Strenuous joggers (HR 1.97, 95% CI 0.48–8.14) had an increased risk of death; however, the study was criticized for the small number of individuals included, the low number of deaths and the large confidence intervals for the hazard ratios in the strenuous-jogger category.
The Aerobics Center Longitudinal Study31 of 55,137 individuals with a mean age of 44 years revealed that just 5–10 min of running per day at <6 mph was sufficient to reduce all-cause mortality by 38%. However, maximal benefit was gained by those running 6–12 miles per week divided over three sessions at a pace of 6–7 mph (ref.31). Running more than six times per week at a pace of >8 mph and accumulating >20 miles per week conferred no incremental reduction in mortality compared with running one to three times per week at 6–7 mph and accumulating 6–12 miles per week. Further analysis of runners in the highest tertiles of exercise (31–49 MET hours per week) suggested a decline in the trend for a reduction in cardiovascular and all-cause mortality when compared with non-runners, although no upper limit at which exercise became detrimental was demonstrated32.
These data are suggestive of a curvilinear relationship between dose of endurance exercise and reduction in mortality, with a gradual plateau among individuals who exercise most intensively. However, much larger studies with high numbers of deaths are required to substantiate this concept.
Sudden death in endurance athletes
Despite the general benefit in terms of reduction in mortality, exercise can increase the risk of sudden cardiac death (SCD) in individuals harbouring underlying cardiac disease. The overall incidence of SCD during endurance exercise is estimated at 1 in 50,000 participants33,34,35. In young athletes (aged ≤35 years), most exercise-related SCD is attributable to inherited cardiomyopathies and channelopathies or congenital coronary anomalies36,37,38. Until recently, hypertrophic cardiomyopathy was considered the most common cause of death among young athletes36,37,39, although one small registry reported that arrhythmogenic right ventricular cardiomyopathy (ARVC) was the predominant cause38. However, a paradigm shift resulted from two large studies that demonstrated that sudden arrhythmic death syndrome, defined as SCD in the absence of structural heart disease, was the leading cause of death in young athletes40,41.
SCD during endurance exercise predominantly affects middle-aged men (aged 35–65 years), who constitute >40% of participants in mass endurance events42,43. Coronary atherosclerosis accounts for approximately 80% of these deaths35,42,44. Exercise acutely increases the risk of plaque rupture and resultant myocardial infarction by up to tenfold45,46,47. The risk of acute myocardial infarction and SCD during exercise is inversely related to the amount of habitual exercise performed, and previously sedentary individuals have a 50-fold greater risk of myocardial infarction and a sevenfold greater risk of SCD during exercise than individuals who exercise habitually45,47,48.
Physiological cardiovascular adaptation
Endurance athletes often exercise 15–20 times the level of the currently recommended 75 min of vigorous-to-intensive exercise per week27. The cardiovascular system of these athletes mounts a fivefold to sevenfold increase in cardiac output to sustain sufficient oxygen delivery to exercising muscles, which is achieved through an array of physiological structural and functional cardiac adaptations, collectively known as the ‘athlete’s heart’. The presence and degree of these adaptations varies depending on age, sex and ethnicity, as well as duration, volume, intensity and pattern of exposure to and type of exercise49,50. The huge cardiovascular demands of endurance exercise explain why these athletes develop the most profound cardiac adaptations, particularly left ventricular (LV) and right ventricular (RV) cavity enlargement.
The electrocardiographic changes in endurance athletes are largely secondary to increased vagal tone and a relative increase in cardiac size. These changes include sinus bradycardia, first-degree atrioventricular block and Mobitz type I atrioventricular block, increased QRS voltages, incomplete right bundle branch block and the early repolarization pattern49. Figure 2 shows an example of the electrocardiographic features that are commonly found in the hearts of endurance athletes.
Athletes have a 15–20% increase in LV wall thickness, a 10% increase in LV cavity size and a 24% increase in RV cavity size50. Male endurance athletes with a large body surface area develop the most profound increases in cardiac size51. Up to 50% of male athletes have LV and RV cavity dimensions that exceed the upper limits of normal for the general population52. In an Italian study of >1,000 Olympians, the LV end-diastolic dimension measured up to 70 mm in some male athletes52, whereas the normal upper limit is considered to be 59 mm in the general population. The same group reported that 1.7% of athletes (mostly endurance athletes) had an LV wall thickness above the normal range (≥12 mm), some as much as 16 mm (ref.52).
The right ventricle in athletes undergoes quantitative changes that are similar to those of the left ventricle, with balanced cavity enlargement and preserved systolic function53,54. More than 50% of athletes have RV outflow tract and basal RV diameters exceeding the upper limits of normal for the general population54. In some endurance athletes, the right ventricle is slightly larger than the left ventricle54.
Understanding cardiac adaptation in athletes aged >35 years — also known as ‘masters’ athletes — is complicated by the interaction between physiological adaptations to exercise and the cardiac effects of ageing. Few studies have examined cardiovascular adaptation in masters endurance athletes. Our experience suggests that masters endurance athletes generally have a greater increase in LV wall thickness and left atrial (LA) cavity size, and a smaller increase in LV cavity size compared with younger athletes55. One study reported LA diameters and areas exceeding 80% of the normal range in masters athletes56.
The inability to exercise as intensively with increasing age and the age-related decline in cardiomyocyte number57 are likely to explain the reduced magnitude of LV cavity dilatation in masters athletes compared with younger athletes, whereas increased LV afterload owing to reduced elasticity of the aorta explains the greater LV wall thickness and LA cavity size. Similarly, age-related increases in vascular and myocardial stiffness result in reduced diastolic filling58,59, ability to augment stroke volume and, therefore, capacity to increase VO2 max60. However, exercise seems to slow the age-related reductions in vascular and LV compliance. A study of 102 masters athletes revealed that exercise preserved LV compliance and distensibility and improved ventricular–arterial coupling — a reflection of LV diastolic stiffness and aortic stiffness combined — in a dose–response fashion, with four to five sessions per week being the optimal dose for preventing age-related decline. Low-dose, casual exercise was insufficient to prevent age-related loss of compliance61,62. The chronic anti-inflammatory effects of exercise are postulated to slow the development of arterial changes through preservation of vascular compliance and improvement of endothelial function63,64.
Studies of detraining in lifelong athletes show some regression of cardiac dimensions, LV hypertrophy and LA dilatation, although some indicate a persistently increased LV mass, LV cavity size and LA diameter. In one study of endurance athletes after 1–13 years of detraining (mean age 35 years; range 15–49 years), 50% had persistent LV enlargement, although probably secondary to increased body weight and ongoing exercise practices65.
Potential harm of endurance exercise
Animal studies in rats subjected to an endurance training programme have shown raised levels of biomarkers of fibrosis, increased cavity size, fibrosis of the atria and right ventricle, and inducible ventricular arrhythmias after the exercise period compared with sedentary rats66,67. Despite the absence of histological evidence of fibrosis in rats sacrificed 8 weeks after exercise cessation66, these data have led some to speculate that the transient rise in biomarkers of cardiac damage and ventricular dysfunction represent subclinical myocardial inflammation that might result in adverse cardiac remodelling and increased risk of cardiac arrhythmias in athletes. Several reports exist of small groups of seemingly healthy endurance athletes who have an increased prevalence of RV dysfunction, myocardial fibrosis, coronary atherosclerosis and atrial fibrillation (AF) (Fig. 3).
Intensive endurance exercise is associated with a transient increase in circulating levels of biomarkers of cardiac damage, such as serum troponins and B-type natriuretic peptide (BNP), in as many as 50% of endurance runners68. The pattern of a rapid rise and fall in the serum level of troponin is not consistent with the usual pattern observed in the context of a myocardial infarction. Instead, the mechanical and oxidative stress and the electrolyte shifts associated with acute endurance exercise might affect membrane permeability, with subsequent leakage of unbound troponin69. The large number of athletes with this phenomenon and the lack of correlation with abnormalities on functional imaging in most studies have led to the concept that an exercise-related rise in serum levels of troponin is a benign phenomenon. Limited numbers of studies have been conducted on the future outcomes in these athletes; however, one study of 725 participants in a 30–55 km long-distance walk has challenged this notion. A troponin level >99th percentile was recorded in 9% of participants, 27% of whom had an adverse cardiovascular event during the 43-month follow-up70. The numbers in this preliminary study are too small to draw any clinically meaningful conclusions, but the results suggest that exercise-induced rises in serum levels of troponin could unmask subclinical cardiac disease and provide prognostic information on future adverse events.
Acute cardiac changes
Several small studies have examined the acute changes in cardiac structure and function associated with endurance exercise71,72,73. One meta-analysis of 23 studies including a total of 372 athletes reported a 2% reduction in LV ejection fraction immediately after endurance exercise in athletes participating in ultra-endurance events and ‘untrained’ runners performing moderate-duration exercise74. A threshold of 6 h of sustained exercise, after which endurance athletes develop transient LV impairment, has been suggested. A dose–response effect seems to exist whereby participants in longer events and those with faster times have greater LV impairment75,76.
Some studies have reported that the right ventricle is more dilated and impaired than the left ventricle in the period immediately after exercise77,78,79,80. Echocardiography performed in 14 runners immediately after a 163-km mountain race showed increased RV dimensions and reduced RV fractional area change, but LV function was unchanged79. In another study, echocardiography performed on 40 athletes participating in an ultra-triathlon showed that RV function was impaired for up to 1 week after the event, whereas LV systolic function was preserved80. Levels of BNP, troponin I and RV dysfunction were correlated. In a study of 60 non-elite marathon runners, those with raised levels of biomarkers (including troponin and N-terminal pro-BNP) after the race had more diastolic dysfunction, higher pulmonary artery pressures and greater RV dysfunction81. However, most studies in this context have not shown a relationship between levels of cardiac biomarkers and cardiac dysfunction82,83.
The association between raised levels of biomarkers and cardiac inflammation is also uncertain. A cardiovascular MRI study performed after an endurance event in 14 athletes with persistently raised serum troponin concentrations (up to 3 days) revealed impaired biventricular filling but no evidence of myocardial oedema or late gadolinium enhancement that would suggest myocardial inflammation or damage84. A further small study of 17 endurance athletes with troponin levels above the cut-off level for myocardial infarction also found no evidence of myocardial inflammation using cardiovascular MRI85. By contrast, myocardial oedema and decreased LV function and perfusion were reported in 20 runners immediately after a marathon86. These changes were more pronounced in less-fit runners. Overall, the association between cardiac troponin levels, acute changes in cardiac structure and long-term damage remains speculative, with further research needed.
Exercise-induced RV cardiomyopathy
The right ventricle is subjected to the same volume of venous return as the left ventricle during exercise; however, the reduction in the pulmonary vascular resistance is considerably smaller than the reduction in systemic vascular resistance, resulting in an exponential rise in pulmonary artery pressure. Indeed, a >30-fold increase in RV wall stress occurs with exercise87, which might explain why some studies have shown transient dilatation and systolic impairment of the right ventricle.
Some endurance athletes, predominantly cyclists, have presented to expert electrophysiology centres with palpitations, syncope or aborted SCD, and subsequent investigations have shown RV impairment and associated ventricular arrhythmias, resembling ARVC. Complex RV arrhythmias were reported in 46 athletes (median age 45 years), almost 25% of whom had RV abnormalities during invasive ventriculography, nearly 50% had regional wall motion abnormalities on cardiovascular MRI, and almost 90% fulfilled criteria for ARVC88. Subsequently, 82% of 27 endurance athletes with RV arrhythmias were shown to have angiographic RV abnormalities, including reduced ejection fraction and fractional shortening, with 27% meeting task force criteria for ARVC89.
La Gerche and colleagues tested for pathogenic variants in genes encoding desmosomal proteins in 47 athletes with complex arrhythmias originating from the right ventricle and either a possible (36%) or definitive (51%) ARVC phenotype, according to task force diagnostic criteria90. Only 12% of athletes had pathogenic variants associated with ARVC compared with 40% of affected individuals from the general population. Sawant and colleagues studied 82 individuals with ARVC, 39 of whom had pathogenic variants in genes encoding desmosomal proteins, and 43 had no pathogenic variants. Individuals without an identified pathogenic variant were more likely to be endurance athletes, had performed more intensive exercise and were less likely to have a family history of the condition (9% versus 40%; P < 0.001) compared with athletes who had an identified pathogenic variant91. These studies suggest that endurance exercise might either directly result in ARVC in some athletes or unmask the condition in athletes with an otherwise quiescent genetic predilection. In a cardiovascular MRI study in 33 healthy, male lifelong masters endurance athletes (median age 47 ± 8 years) and 33 controls, no evidence of regional wall motion abnormalities or scarring in the right ventricle was observed in the athletes; however, the small number of athletes means that this study was not powered to identify exercise-induced ARVC92.
Studies of mice with mutations in genes encoding desmosomal proteins and exposed to endurance training showed either an acceleration of pre-existing RV abnormalities93 or the development of new changes94, all resembling the human ARVC phenotype, whereas sedentary mice underwent no changes. Studies of human carriers of mutations in desmosomal genes have also shown earlier phenotypic manifestation of disease and an increased risk of ventricular arrhythmias among individuals participating in vigorous and/or competitive sport95,96. Therefore, individuals with pathogenic variants (even in the absence of an overt phenotype) and those with phenotypically overt ARVC should be advised to cease competitive sport and pursue only light exercise97. Of note, adhering to the current recommendations for exercise does not seem to increase the risk of accelerating the phenotype severity of the ARVC phenotype91, and the risk is particularly low among individuals exercising within current recommendations at an intensity of <6 METs98.
A small proportion of studies have identified that seemingly healthy, male masters endurance athletes engaging in marathon running or triathlons have a prevalence of myocardial fibrosis of 11–17%99,100,101,102. The pattern of myocardial fibrosis in masters athletes is diverse, ranging from RV insertion point fibrosis (which is considered to be a benign consequence of chronic exercise) to more pathological appearances, including a subendocardial ischaemic pattern, subepicardial pattern and extensive mid-wall and diffuse fibrosis (Fig. 4). In one study, 14% of 106 male masters endurance athletes had myocardial fibrosis, with one-third having a pattern consistent with previous myocardial infarction, whereas the remainder had non-ischaemic mid-wall or subepicardial scarring55. Of the athletes with a scar that was compatible with myocardial infarction, only half had a coronary stenosis in the relevant coronary artery. These results suggest that masters athletes might sustain subclinical myocardial infarction from demand ischaemia, microemboli, plaque rupture or coronary spasm. The relevance of the other patterns of myocardial fibrosis is uncertain, although subepicardial fibrosis has been observed in individuals with previous myocarditis103.
Limited data suggest that a dose–response association might exist between endurance exercise and myocardial fibrosis. An increased prevalence of late gadolinium enhancement, consistent with a non-ischaemic pattern of myocardial fibrosis, was reported among 83 asymptomatic, middle-aged, competitive triathletes. Race distances, specifically longer cumulative swim and cycle distances, and a higher peak systolic blood pressure on exercise testing were predictive of the presence of myocardial fibrosis101. In another study of 12 lifelong masters endurance athletes (aged >50 years), 20 controls matched for age and 17 younger athletes (mean age 31 ± 5 years), 50% of the masters athletes had evidence of myocardial fibrosis (four had a non-specific pattern of fibrosis, one had fibrosis compatible with myocarditis and another had fibrosis compatible with myocardial infarction), compared with none of the controls or young athletes99. Myocardial fibrosis seemed to be related to the number of years of training and the number of endurance events completed.
Myocardial fibrosis is associated with ventricular arrhythmias and increased mortality in the general population104. Small studies have shown that athletes with complex ventricular arrhythmias and even aborted SCD have a higher prevalence of LV scarring compared with athletes without arrhythmias105,106. Longitudinal studies are required to understand the precise clinical relevance of myocardial fibrosis in masters athletes.
Coronary artery calcification and plaques
The CAC score is a strong predictor of future adverse coronary events and a powerful adjunct to conventional atherosclerotic risk factors in risk stratification in the non-athletic population107,108,109. Although exercise reduces the burden of atherosclerotic risk factors, male masters endurance athletes have a higher prevalence of high CAC scores (>100 Agatston units) on coronary CT angiography compared with controls55,110,111. In one study, a CAC score of >100 Agatston units was reported in almost one-third of masters athletes who had run five or more marathons111. Marathon runners had a median CAC score threefold higher than that of Framingham-matched controls111. In another study of 318 middle-aged, male endurance athletes with a predominantly low ESC risk score, >50% had CAC and 16% had a CAC score ≥100 Agatston units112. We compared 152 masters endurance athletes (aged 54.4 ± 8.5 years) with a low Framingham risk score who had exercised for a mean of 31 ± 12.6 years versus 92 controls of a similar age and with a similar Framingham risk score55. Almost 20% of male athletes had a CAC score ≥100 Agatston units, and 11% had a CAC score >300 Agatston units, compared with none of the male controls. Male athletes had twice the number of coronary plaques compared with male controls (44% versus 22%). In athletes, a greater proportion of atherosclerotic plaques were stable (that is, calcified) and therefore less prone to rupture than those in controls (72% versus 31%; P < 0.001)55.
In a study that evaluated the relationship between exercise dose, CAC score and plaque characteristics in 284 men engaged in competitive or recreational leisure sports, participants were categorized as exercising for <1,000, 1,000–2,000 or >2,000 MET-min per week113. Athletes with the highest dose of exercise had significantly higher CAC scores and more atherosclerotic plaques, but also the highest prevalence of calcified plaques113.
Lifelong, chronic endurance exercise might, in itself, increase atherosclerotic plaque formation through mechanisms including mechanical stress from the hyperdynamic ventricular systole causing flexing of the epicardial coronary arteries, exaggerated blood pressure rises during exercise and the acute pro-inflammatory state provoked by intense exercise114,115. In parallel, exercise might produce different endothelial repair mechanisms from those in individuals with conventional atherosclerotic risk factors as well as a statin-like anti-inflammatory effect that accelerates calcification within plaques116,117,118,119. Furthermore, CAC in athletes might be caused by calcification within the media of the coronary arteries that is secondary to oxidative stress or apoptosis of the smooth muscle cells, rather than within the intima, as is observed in conventional atherosclerotic plaques. Current coronary CT angiography sequences cannot be used to differentiate between intimal and endothelial calcification120. If exercise does indeed increase intimal calcium, with a disproportionate volume of dense calcium relative to the overall atheroma burden, the traditional interpretation of the CAC score and its prognostic relevance might not apply to athletes.
The longitudinal outcomes for athletes with coronary artery disease are unknown; however, medium-term studies indicate a favourable prognosis. In one study, cardiorespiratory fitness, CAC score and cardiovascular events were evaluated over an 8.4-year follow-up period in a cohort of 8,425 men121. Higher cardiorespiratory fitness attenuated the risk of cardiovascular events when adjusted for CAC score. For each MET increase in cardiorespiratory fitness (across all CAC scores and adjusted for risk factors), the cardiovascular event rate was reduced by 14%121. Although highly active men who performed >3,000 MET-min of exercise per week were more likely to have CAC, no associated increase in all-cause mortality was found compared with those who performed <1,500 MET-min of exercise per week122. These data suggest that higher levels of cardiorespiratory fitness alter the prognostic relevance of a raised CAC score.
Exercise at low-to-moderate doses protects against AF123,124,125 and might confer a lower risk of developing AF in later life through modification of risk factors126. However, chronic endurance exercise training increases the risk of developing AF by up to fivefold, with men aged <60 years being at greatest risk124,127. A large meta-analysis of 22 studies including a total of 656,750 individuals reported that moderate physical exercise protects both women and men against AF125. Intense exercise increases the risk of AF in men, but is protective against AF in women125.
The rate of regular sports participation was 63% among patients attending an AF clinic compared with 15% among the general population128. In a study of 134 Swiss former elite cyclists and age-matched golfers, the prevalence of AF was higher among the former cyclists (4% versus 0%)129. A cut-off duration of 1,500 lifetime-hours has been proposed as the threshold at which sporting participation increases the risk of AF124, with a positive correlation between AF risk and exercise dose and intensity130,131.
Data exploring the underlying mechanisms of AF in athletes are limited. The effect of increased vagal tone in inducing AF is thought to be the greatest contributor, and rat models suggest that this effect is secondary to increased baroreflex responsiveness and myocyte sensitivity to cholinergic stimulation132. The interaction between high vagal tone and age, male sex, height and exercise dose as well as LA remodelling from chronic repetitive atrial stretch and atrial fibrosis produce a sufficient substrate for AF in some athletes133,134,135,136.
A study of 208,654 cross-country skiers provides the first insights into risk of cardiovascular events in athletes with AF137. Female skiers had a 37% lower risk of AF than non-skiers, independent of performance and number of races completed. By contrast, the incidence of AF was slightly higher in male skiers than in non-skiers, and the number of races completed and faster finishing times were determinants of an increased incidence of AF. Overall, skiers had a 30% lower incidence of stroke than non-skiers. Skiers with AF had a greater incidence of stroke than skiers and non-skiers without AF (7.6% versus 0.6% versus 1.2%) but a lower incidence of stroke than non-skiers with AF (9.7%)137. These data suggest that athletes who develop AF are at increased risk of stroke and should be treated according to conventional anticoagulation guidelines. Substantial gaps in the research into AF in athletes remain, including long-term data on the recurrence rate of AF in athletes who continue to exercise after ablation therapy.
Approximately 10% of young athletes and up to 30% of masters athletes have >10 isolated ventricular premature beats on 24-h electrocardiogram monitoring138,139. Small studies suggest that the prevalence of ventricular premature beats is not greater than in non-athletes138,140,141. In a study in which young, competitive athletes aged 16–35 years as well as healthy, lifelong endurance athletes aged >30 years were compared with age-matched controls, no significant difference was found in the number of ventricular premature beats on 12-lead 24-h electrocardiogram monitoring between athletes and controls, and neither age nor exercise had a significant effect on the prevalence of ventricular arrhythmias138.
Most ventricular premature beats in athletes originate from the RV outflow tract or the LV fascicles, which are common sites for benign ectopy. Ventricular premature beats conducting with a wide right bundle branch block pattern and superior axis that are exacerbated by exercise should be investigated further because emerging reports indicate that these characteristics are associated with the presence of an LV scar139. Swiss former elite cyclists performing <4 h of extreme exercise per week had a significantly greater prevalence of non-sustained ventricular tachycardia compared with age-matched golfers (15% versus 3%); however, the precise origin of the ventricular tachycardia was uncertain from the single-lead Holter monitors129.
Sinus node dysfunction
Sinus bradycardia and sinus pauses are common in endurance athletes. Suppression of the sinoatrial node owing to high vagal tone is a widely accepted explanation for this finding, although modern studies in animals suggest that a reduction in the If (funny) current channels could be responsible for bradycardia through intrinsic sinus node changes142. Evidence suggests that these changes persist despite detraining129 and autonomic blockade143. These observations have led to speculation that lifelong endurance exercise might promote adverse remodelling of the conduction system through fibrotic changes that manifest in athletes with age. In one study, 40% of 20 athletes had evidence of sinus node disease on 24-h monitoring141. In another study, former cyclists had a higher prevalence of sinus node disease (16% versus 2%) and greater need for pacemaker implantation for bradyarrhythmia (3% versus 0%) than relatively sedentary golfers129. A study of 52,755 participants in the Vasaloppet 90-km cross-country skiing event reported that athletes who had participated in more races and had faster finishing times had a higher risk of pathological bradyarrhythmia, including sinus node disease or third-degree atrioventricular block130, supporting a potential dose–response effect.
Longevity in endurance athletes
Various studies of competitive athletes, including world-class elite endurance athletes, report increased longevity compared with sedentary controls and resistance-trained athletes144. In a study of 2,613 Finnish elite athletes, those participating in endurance sports lived an average of 5.7 years longer than controls145. Data from 15,000 Olympic medallists, regardless of sporting discipline or country, showed that these athletes lived an average of 2.8 years longer than controls146 and, in a follow-up study (mean 37.4 years; range 23.5–49.8 years), French athletes participating in at least one Tour de France event had a 41% lower mortality than the general population147. In a study of >70,000 participants in the non-elite Vasaloppet long-distance cross-country ski race, cardiovascular and all-cause mortality was >50% lower than the predicted standardized mortality ratios for the general population148. Therefore, despite speculation surrounding maladaptive changes, lifelong endurance athletes have improved survival compared with the general population.
The adaptations to endurance exercise in the hearts of female athletes are qualitatively similar but quantitatively less than those in the hearts of male athletes149,150. The occurrence of SCD in women during exercise is exceptionally rare36,39,42. Only a few studies of cardiac biomarkers have included large numbers of female athletes, and very few studies of CAC prevalence, myocardial fibrosis and RV dysfunction have been performed in female athletes. However, on the basis of the available data, female endurance athletes do not seem to have the increased prevalence of CAC or fibrosis that is observed in male athletes55,100. In one study, 46 female masters endurance athletes were compared with 38 female non-athletes of similar age and Framingham risk. No significant differences in CAC score or plaque morphology were observed between the two groups, and none of the female athletes had clinically significant narrowing of the coronary arteries55. In contrast to male athletes, female athletes seem to be protected from developing AF125. The mechanisms by which female athletes are largely protected against the abnormalities that occur in male athletes are uncertain. Comparisons between low-risk premenopausal women and age-matched men have suggested the protective effects of oestrogen or the deleterious effects of testosterone151, but further studies are needed.
Regular, moderate, aerobic physical exercise is imperative for maintaining optimal health. Endurance athletes exercise at the extreme end of the dose spectrum and consequently manifest some of the most profound cardiac adaptations to exercise. Emerging evidence suggests that some lifelong endurance athletes have a higher prevalence of high CAC scores (>100 Agatston units), myocardial fibrosis, RV dysfunction, AF and sinus node disease compared with healthy non-athletes. The mechanisms by which endurance athletes develop these anomalies are poorly understood, and their clinical relevance is unknown. Currently available longitudinal data, which are limited, have not revealed an association between these findings and cardiovascular mortality. The future of research into the hearts of endurance athletes requires broad, longitudinal outcome studies to determine the prognostic importance of CAC and myocardial fibrosis. Further work is needed to understand why only some athletes show potential adverse remodelling, with particular emphasis on the role of haemodynamic responses to exercise, diet, exposure to pollution, inflammation and genetic background. Overall, endurance athletes benefit from improved health and greater longevity, with SCD remaining rare. Until further data to the contrary are available, discouragement of lifelong endurance exercise is not justified.
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The authors declare no competing interests.
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Parry-Williams, G., Sharma, S. The effects of endurance exercise on the heart: panacea or poison?. Nat Rev Cardiol 17, 402–412 (2020). https://doi.org/10.1038/s41569-020-0354-3
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