Download Marathon run: cardiovascular adaptation and

REVIEW
European Heart Journal (2014) 35, 3091–3096
doi:10.1093/eurheartj/eht502
Clinical update
Marathon run: cardiovascular adaptation
and cardiovascular risk
Hans-Georg Predel*
Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Am Sportpark Mu¨ngersdorf 6, Cologne 50933, Germany
Received 21 November 2012; revised 24 October 2013; accepted 20 November 2013; online publish-ahead-of-print 9 January 2014
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Marathon run † Endurance exercise † Middle-aged athletes † Cardiovascular adaptation
Introduction
Inspired by the ancient run from Marathon to Athens 490 BC, the idea
to revive this long-distance run was born in the context of the first
modern Olympic Games in 1896 taking place in Athens, Greece.
While this first marathon run of modern times had a distance of
40 km today’s official distance of 42.195 km was established with
the marathon run of the Olympic Games in London 19081
(Table 1). In recent decades, participation in a ‘marathon run’ has
become increasingly attractive for millions of non-professional endurance athletes worldwide each year. Regarding the cohort of athletes participating in city-marathon events, there are only a small
number of high-performance professional athletes aged between
18 and 35 years. These athletes are generally healthy, continuously
medically supervised, and supported by experienced trainers. In contrast, the number of non-elite recreational marathon runners, including individuals of all age groups, is continuously rising. Indeed, the
athletic and demographical characteristics of marathon runners are
rapidly changing. According to a demographical analysis of these
amateur athletes, the majority are middle-aged male amateur
runners competing at amazing performance levels.2 For example,
the winning time of the marathon run of the Olympic Games in
1936 was matched by the running time of the best M55 amateur
runner of the 2012 Berlin marathon.3 These aspects are of special importance since several studies revealed that middle-aged amateur
runners frequently exhibit a cardiovascular risk profile, which is
typical for their age group.2,4,5
Meanwhile, it is well known and widely accepted that regular and
moderate physical activity (PA) has beneficial effects on nearly all biological structures and functions of the human body, including the cardiopulmonary system (Table 2). With respect to the ideal dose of
endurance PA, the Harvard Alumni Study demonstrated an optimal
cardiovascular health effect by an additional energy consumption of
2000– 3000 kcal/week or 300–400 kcal/day.6,7 Even moderate
* Corresponding author. Tel: +49 221 49825270, Fax: +49 221 4912906, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2013. For permissions please email: [email protected]
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The first marathon run as an athletic event took place in the context of the Olympic Games in 1896 in Athens, Greece. Today, participation in a
‘marathon run’ has become a global phenomenon attracting young professional athletes as well as millions of mainly middle-aged amateur athletes
worldwide each year. One of the main motives for these amateur marathon runners is the expectation that endurance exercise (EE) delivers
profound beneficial health effects. However, with respect to the cardiovascular system, a controversial debate has emerged whether the marathon run itself is healthy or potentially harmful to the cardiovascular system, especially in middle-aged non-elite male amateur runners. In this
cohort, exercise-induced increases in cardiac biomarkers—troponin and brain natriuretic peptide—and acute functional cardiac alterations
have been observed and interpreted as potential cardiac damage. Furthermore, in the cohort of 40- to 65-year-old males engaged in intensive
EE, a significant risk for the development of atrial fibrillation has been identified. Fortunately, recent studies demonstrated a normalization of
the cardiac biomarkers and the functional alterations within a short time frame. Therefore, these alterations may be perceived as physiological
myocardial reactions to the strenuous exercise and the term ‘cardiac fatigue’ has been coined. This interpretation is supported by a recent analysis
of 10.9 million marathon runners demonstrating that there was no significantly increased overall risk of cardiac arrest during long-distance running
races. In conclusion, intensive and long-lasting EE, e.g. running a full-distance Marathon, results in high cardiovascular strain whose clinical relevance especially for middle-aged and older athletes is unclear and remains a matter of controversy. Furthermore, there is a need for evidence-based recommendations with respect to medical screening and training strategies especially in male amateur runners over the age of
35 years engaged in regular and intensive EE.
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Table 1
H.-G. Predel
History of the ‘Marathon’ run
490 BC
First ‘Marathon’ (Marathon—Athens 40 km) Pheidippides:
3 –4 h
1896
First modern Olympics Marathon Athens, Greece [40.0 km
(24.85 miles)] Spyridon Louis: 2:58:50 h
1908
Olympic Games London Great Britain: new distance:
42.195 km (26.22 miles) Johnny Hayes: 2:55:18 h
1921
International Amateur Athletic Federation (IAAF) setting
42.195 km (26.22 miles) as the standard distance
2013
Current World record for women: Paula Radcliffe: 2:15:25 h
(London 2003)
2013
Current World record for men: Patrick Makau: 2:03:38 h
(Berlin 2011)
Table 2
training
Cardiovascular benefits of regular endurance
Endothelial function
Coronary flow reserve
Tolerance of myocardial ischaemia
Figure 1 Potential association between dose of endurance
sports and cardiovascular events (modified from La Gerche et al.38).
emerged whether preparation for and participation in a marathon
run is beneficial or harmful to the human health.
Thus, the following review will critically analyse the available information on the acute and chronic effects of marathon running on the
cardiovascular system focussing on middle-aged amateur marathon
runners.
Ventricular fibrillation thresholds
Arterial blood pressure
Arterial stiffness
amounts of regular PA (15 min per day) are associated with significant preventive effects towards a variety of diseases, e.g. diabetes,
cancer, and cardiovascular events,8 but also prolonging life expectancy.9,10 However, concerning beneficial health effects, it is difficult
to define the optimal individual amount of endurance exercise (EE)
as well as the upper ‘dose-limit’ on the basis of currently available
studies. Nevertheless, regarding certain cardiovascular diseases,
such as atrial fibrillation (AF), there are indications about potential
‘overdoses’ of EE. 11 In this context, in a case –control study, Elosua
et al.12 identified a threshold of more than 1500 lifetime hours of exercising. Furthermore, Mo¨hlenkamp et al.5 observed a relatively high
coronary artery calcification (CAC) burden in presumably healthy
male athletes (.55 years old) who had performed at least five marathon runs during the previous 3 years. Taking these considerations
into account, regular EE at moderate doses and intensities is recommended for the prevention of cardiovascular diseases by international guidelines (Figure 1).13 – 16
Acute and chronic adaptations
of the cardiovascular system
to marathon running
Regarding these aspects and based on a series of studies in
middle-aged amateur marathon runners, a controversial debate has
Myocardial adaptations
to endurance exercise
Intensive and long-lasting EE is characterized by a significant increase
in skeletal muscle oxygen demand met by a marked elevation of pulmonary oxygen uptake and transport of the oxygen-enriched blood
to the working skeletal muscles. Under physiological conditions, the
acute cardiopulmonary adaptation to EE encompasses increases in
pulmonary ventilation, heart rate, stroke volume, and cardiac
output accompanied by a moderate increase in systolic blood pressure, peripheral vasoconstriction, and vasodilatation.17 On the
aerobic exercise level, these acute cardiac adaptation processes can
be maintained over several hours by the endurance-trained heart.
In high-performance endurance athletes, these adaptations may
lead to the development of the so-called athlete’s heart, which is
morphologically characterized by harmonically increased left ventricular (LV) and right ventricular (RV) volumes, increased LV wall
thickness, and myocardial mass and functionally by a five- to sixfold increased cardiac output and reduced resting heart rate.17 – 19
It must be stressed, however, that the development of an athlete’s
heart requires intensive endurance training.20 Whether the development of the athlete’s heart in middle-aged and older amateur endurance athletes follows the same patterns than in young endurance
athletes is not entirely clear and needs further investigations.17
Potential functional and structural
myocardial abnormalities in
marathon runners
The adaptation processes leading to the athlete’s heart must be
strongly differentiated from pathological structural myocardial adaptations occurring in the context of hypertensive heart disease or
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Myocardial capillary density
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Cardiovascular adaptation and cardiovascular risk
after the Hawaii Ironman Triathlon. Neilan et al.31 described diastolic
myocardial dysfunction in predominantly middle-aged male marathon runners directly after finishing the Boston Marathon. In contrast
to these acute reactions, the chronic effects are characterized by a
significantly improved diastolic function in endurance trained athletes
(see below).
Furthermore, Neilan et al.31 observed increased troponin levels
related to training volumes and interpreted these findings as myocardial injury. This interpretation sparked an intensive debate about
the potential negative heath consequences of marathon running
especially for the cohort of inadequately trained middle-age male
runners. Recent advances in echocardiographic and magnetic resonance tomography (MRT) imaging, tissue Doppler imaging, and strain
rate imaging, including tools for the quantitative assessment of segmental ventricular function, have enabled investigators to collect
more detailed information concerning the functional and structural
status of the marathon runners heart. With respect to LV systolic
function, the findings are quite controversial. A recent meta-analyses
based on 294 individuals performing EE (60–1440 min) revealed a
small but significant transient reduction of LV systolic function with
signs of LV strain and twist.19,32 – 34
The evaluation of diastolic functional parameters related to EE provided more consistent findings. In general, EE leads to an increased
early diastolic LV filling, suggesting that diastolic function is superior
in highly trained endurance athletes when compared with untrained
controls. The findings of suppressed diastolic function directly after
the marathon run especially in untrained non-elite amateur runners
was opposed by further echocardiographic studies demonstrating a
complete normalization of these functional alterations generally
within 24 h after the marathon run.35,36 Therefore, such a transient
exercise-induced reduction in ventricular systolic and/or diastolic function is often interpreted as physiological ‘cardiac fatigue’.30,37
Focus on the right heart
Figure 2 Myocardial adaptation to intensive endurance exercise
in middle-aged athletes—physiological vs. Pathological.
The introduction of innovative imaging techniques allowing to investigate the right ventricle revealed signs of potential structural and
functional abnormalities affecting the right ventricle occurring in
young professional as well as in middle-aged amateur athletes
engaged in intensive EE. In most studies, these abnormalities returned
to normal within a short time frame. Especially, long-term intensive
EE may cause dilation of the right atrium and ventricle also showing
signs of potential myocardial scarring and/or myocardial fibrosis in
prone individuals.38 – 41 However, the available data are inconsistent
and at present many issues related to the effects of endurance training
on the right heart remain unclear. The long-term clinical significance
of these alterations requires further investigations.
In summary, based on our current knowledge, the alterations of
systolic and diastolic myocardial function associated with marathon
running may be interpreted as a phenomenon within the physiological range at least in the majority of endurance athletes. A small subgroup of prone runners may develop functional and/or structural
abnormalities with clinical significance. Further studies, using
modern imaging techniques such as MRT are necessary to further
clarify the effect of marathon running on myocardial structure and
function and to identify athletes at risk for maladaptation.
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hypertrophic cardiomyopathy.21 Nevertheless, ever since its first description by Henschen in 1899,22 the athlete’s heart has provoked
controversial discussions with respect to its health-related consequences. Although professional young athletes may also experience
serious cardiovascular maladaptations and/or complications,23 – 25
the available data do not suggest that these adverse cardiovascular
events are generally related to the functional and structural adaptations associated with the development of an athlete’s heart. In accordance with this view, long-term studies in professional endurance
athletes26,27 do not point towards an increased cardiovascular
event rate in this cohort. A recently published study on Tour de
France participants even revealed a significantly lower cardiovascular
event rate and a prolonged life expectancy when compared with agematched ‘ordinary’ French men.28
The situation may be different in middle-aged amateur marathon
runners frequently performing on a level that was previously
reserved to professional and young athletes. In this cohort, high training volumes and intensities as well as exercising during the marathon
run are requiring cardiac outputs of 20– 25 L/min over periods of
several hours. It is evident that this workload imposes a high
degree of stress to all myocardial structures including the coronary
vessels and the electrical conduction system which may potentially
lead to functional and structural maladaptations and/or myocardial
injury and fibrosis at least in a subgroup of prone middle-aged individuals (Figure 2).5,29
With the development of advanced and mobile Doppler echocardiography, it became possible to perform detailed non-invasive
functional and structural measurements of the heart of highly
endurance-trained athletes under resting and exercising conditions.
Many working groups have utilized 2D and Doppler techniques
before and after marathon runs in order to evaluate the morphological and functional myocardial status. Already in 1987, Douglas
et al.30 described abnormalities in LV systolic and diastolic function
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Marathon and myocardial injury
Numerous studies have reported clinically significant increases in
serological markers potentially indicating myocardial damage
during and/or directly after a marathon run.31,42 – 46 Recent findings,
however, demonstrated that the elevated cardiac biomarkers
regressed to normal values within a period of 24 –48 h and, therefore, may be the result of transient and reversible alterations of the
cardiac myocytes without negative clinical consequences.35,47,48
This interpretation is supported by a recent study of Hanssen
et al.49 who combined measurements of cardiac biomarkers with
cardiac magnetic resonance, including late gadolinium enhancement,
demonstrating an absence of detectable myocardial necrosis despite
a transient increase in cardiac biomarkers.
Nevertheless, taking into account the complexity of myocardial
troponin and brain natriuretic peptide release, further experimental
studies are warranted to elucidate the biochemical mechanisms and
the clinical dignity of the increases in these cardiac biomarkers.
Marathon and the vascular system
platelet hyperreactivity, and increased activity of several coagulation
factors. In contrast, regularly endurance trained subjects reveal a significant increase in the fibrinolysis activity. These potentially adaptive
changes might offer protection against the risks of thrombotic
events.58,59 The precise clinical relevance of these findings is unclear,
however.
In summary, functional and structural responses of the arterial vasculature and the blood clotting system to acute and chronic intensive
EE are very complex and await further investigation.
Coronary arteries and marathon
running
In recent years, evidence has accumulated that regular PA is protective
with respect to coronary artery disease (CAD). A large number of
studies have shown that regular PA over longer time periods is associated with a marked reduction in CAD and all-cause mortality.
These protective effects were especially observed in subjects exercising in mild and moderate exercise intensities when compared with sedentary individuals. These beneficial effects are mainly mediated
through improvements of risk factors for CAD, positive effects on
endothelial function, autonomic balance, and the blood coagulation
system.16,60,61 In contrast to these beneficial findings, Mo¨hlenkamp
et al.5 found CAC scores in 108 middle-aged male marathon runners
who have completed five marathon runs during previous 3 years
exceeding the CAC scores of controls matched for age and Framingham risk score. The authors offered several potential explanations
for these somewhat unexpected findings: a rise in vascular oxidative
stress due to exercise-induced high blood flow,62 inflammatory cytokines induced by intensive EE such as marathon running.63
Potential proarrhythmic effects
of marathon running
There is a general consensus that elite endurance athletes commonly
present several electrophysiological alterations frequently in combination with atrial and ventricular ectopy (VE), which have been
perceived as functional adaptations not predisposing to serious
arrhythmogenic events or sudden cardiac death (SCD).64 – 66
However, at least in a subgroup of middle-aged male endurance athletes, a significant, five-fold, increase in the prevalence of AF has been
observed.67 – 69 Although clear evidence about the underlying causes
and the pathophysiological mechanisms is lacking, the following hypothesis among others are being discussed: alterations in the autonomic system, fluid shifts, and electrolyte abnormalities potential
chronic systemic inflammation, fibrosis of myocardial structures,
and even the potential intake of illicit drugs (Figure 3). Clinically, AF
associated with EE occurs usually paroxysmal and frequently at
night in the beginning, often progressing to persistent AF. Despite
the high prevalence, AF in athletes is perceived as abnormal and clinical relevant and requires intensive diagnostic procedures by cardiovascular and sports-medical experts including a thorough sport
anamnesis.11,70 The natural course and long-term prognosis of lone
AF has not been intensively documented in endurance athletes. In a
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There is sufficient evidence that long-term EE induces beneficial functional and structural adaptations of the vascular system, including positive effects on arterial vascular stiffness.50,51 In a recent meta-analysis
relating to high-performance endurance athletes, Green et al.52
came to the conclusion that endurance athletes possess enlarged arteries with a decrease in arterial wall thickness. With respect to peripheral resistance arteries, middle-aged endurance trained athletes exhibited
improved acetylcholine-mediated vasodilatation suggesting—according
to the authors—that athletic training may retard the effects of ageing
on the vasculature. On the other hand, there is limited evidence
for improved arterial responsiveness to exercise-induced stimulation
in athletes. In conclusion, the majority of the available data suggests
that there is an improved function of peripheral resistance vessels
in high-performance athletes.52
The effects of acute and chronic EE on blood pressure and heart
rate are well documented, demonstrating a significant decrease in
peripheral blood pressure, peripheral arterial resistance, and heart
rate, which is especially pronounced in hypertensive patients.53
However, no sufficient data are available on the effects of EE on
central blood pressure.54,55 In contrast, in strength-trained athletes,
an increase in arterial stiffness was observed.55,56
In a recent study in 49 regularly trained middle-aged marathon
runners, a slight increase of blood pressure and pulse wave velocity
was observed when compared with age-matched controls. Directly
after the marathon run, a significant fall in wave reflections in the presence of an unchanged pulse wave velocity was detected. The authors
hypothesized that long lasting extremely vigorous and competitive
exercise like marathon running may result in an inverted U-shaped relation with arterial stiffness.57 Again, further studies are warranted to
clarify this issue.
A further interesting field of research is the status of the blood clotting system during and after prolonged EE. Acute and intensive exercise
results in a transient hypercoagulability state, especially pronounced in
untrained individuals mostly due to increased thrombin generation,
H.-G. Predel
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Cardiovascular adaptation and cardiovascular risk
Figure 3 Potential mechanisms for atrial fibrillation induced by high-intensity-endurance sports.
Complex ventricular ectopy and
sudden cardiac death associated
with endurance exercise
Complex VE, including ventricular tachycardia, is also well documented in endurance-trained athletes; they typically originate from a
mildly dysfunctional RV and/or the interventricular septum.42,45,74,75
The severity and clinical significance of the VEs are very variable and
subject of controversial discussions. Serious VEs leading to cardiac
arrest mainly result from underlying heart disease, such as cardiomyopathies or coronary abnormalities as well as inflammatory and fibrosing
processes.37,74 – 76
Fortunately, SCD among marathon runners is very rare.42,44,77 In
this context, Kim et al.45 investigated the incidence and outcome of
cardiac arrests during marathon and half-marathon races in the
USA and Canada during the period from 2000 to 2010. In the 10.9
million runners examined, 59 cases of cardiac arrests occurred in association with a marathon run. Men were significantly more likely to
experience cardiac arrest and SCD than women. These findings are
consistent with other reports.78,79 The event rates were significantly
correlated with the age of the runners and significantly more frequent
in ‘full’ marathon runs (42.195 km) than in ‘half’ marathon runs.45
Indeed, the final mile (1.6 km), representing ,5% of the whole marathon distance, accounts for almost 50% of the SCDs.42,45,80
Risk stratification in endurance
athletes
There is general acceptance for the need of regular medical screenings of endurance athletes. The European Society of Cardiology (ESC)
has published recommendations for an athlete’s screening.76
However, there is a controversy about the detailed diagnostic procedures in order to effectively detect potential pathologic conditions
predisposing to exercise-related cardiovascular events. This refers
especially to the value of the electrocardiography (ECG) as a diagnostic tool. For instance, in high-performance athlete’s screening, the
European guidelines differ from the US recommendations. While
the European guidelines suggest a routine ECG, the US recommendations are principally limited to physical examination and anamnesis.76,81 Currently, the controversy regarding the role of a
routine ECG screening remains unsettled. Considering the serious
consequences of exercise-induced cardiovascular events on one
side and the large number of athletes to be screened on the other
side, it is strongly necessary to evaluate the diagnostic sensitivity of
all components of the proposed screening procedures, including
the ECG, and to develop effective diagnostic strategies that are
highly sensitive in detecting athletes at increased risk for such
events. In addition, the clinical value of further diagnostic tools,
such as cardiac biomarkers, echocardiography, and/or advanced
imaging techniques remains to be clarified.
Referring to the cohort of middle-aged and older endurance athletes, the appraisal concerning the role of the ECG is different.
There is general consensus that in this cohort, an exercise ECG especially in the presence of CV risk factors is recommendable.82 The
European Association of Cardiovascular Prevention and Rehabilitation
has recently published a comprehensive position stand for the cardiovascular evaluation of middle-aged/ senior individuals engaged in leisuretime sport activities.60 The authors state that these recommendations
‘rely on existing scientific evidence, and in the absence of such, on
expert consensus’. For the screening of this very large cohort, selfassessment of the habitual PA level and of the cardiovascular risk
profile based on systematic coronary risk evaluation (SCORE) are
recommended.83 In individuals at increased risk and those who
intend to exercise at moderate and high intensity, the medical
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prospective study with 9-year follow-up in 30 male endurance athletes with paroxysmal AF, Hoogsteen et al.71 observed that paroxysmal AF remained stable in 50% and the progression to permanent AF
occurred only in 17% of the athletes.
Treatment of AF in endurance-trained athletes as well as estimating the prognosis is difficult because large-scale prospective, randomized clinical trials and guidelines focussing directly on the
endurance-trained athletes are lacking. Nevertheless, the current
guidelines for the management of AF may be helpful and also apply
to middle-aged and older endurance athletes. The therapeutic
options include restriction of dose and intensity of EE, direct-current
cardioversion, and ablation strategies. The value and indication of
pharmacotherapy is controversial especially with respect to
thromboembolic prophylaxis.72,73
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screening should include anamnesis including family history, physical
examination, and a 12-lead resting ECG. Because the sensitivity of the
resting ECG with respect to CAD is rather low, in middle-aged/older
individuals, an additional exercise test with ECG is recommended in
order to detect potential CAD by ST-segment depression and also to
evaluate the functional capacity.
Despite the absence of strong evidence for these recommendations, we strongly suggest applying these recommendations in
middle aged and older endurance athletes, especially in those with
increased global risk score.
H.-G. Predel
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Conclusion
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Acknowledgement
The author would like to thank Mrs Nora Zoth, PhD for her excellent
assistance in the preparation of the manuscript.
Conflict of interest: none declared.
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