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© 2016 Journal of Clinical and Preventive Cardiology | Published by Wolters Kluwer - Medknow
The habitual level of physical activity of the human race has significantly and
abruptly declined in the last few generations due to technological developments.
The professional societies and government health agencies have published minimum
physical activity requirement guidelines to educate the masses about the importance
of exercise and to reduce cardiovascular (CV) and all‑cause mortality at the
population level. There is growing participation in marathon running by amateur,
middle‑aged cases with a belief that more intense exercise will give incremental
health benefits. Experts have cautioned the nonathlete amateurs about the “exercise
paradox” and probable deleterious effects of high‑intensity prolonged exercise on CV
and musculoskeletal system. The epidemiological studies suggest a “reverse J shaped”
relationship between running intensity and CV mortality. The highest benefits of
reduction in CV and all‑cause mortality are achieved at a lower intensity of running
while the benefits tend to get blunted at a higher intensity of running. The physicians
should have a balanced discussion with the amateur runners training for a marathon,
about risks and benefits of high‑intensity exercise, and should evaluate them to rule
out the occult coronary disease.
Key Words: Cardiovascular mortality, exercise paradox, marathon running, physical activity
Marathon running for amateurs: Benefits and risks
Nitin Burkule1, MD, DM, DNB, FACC, FASE
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DOI: 10.4103/2250-3528.192681
society. The digital revolution about two generations
ago made office work, entertainment, and daily life
chores available at fingertips causing an epidemic of
sedentary behavior.
A multitude of epidemiological studies showed health
and survival benefits of regular physical activity
through exercise and sports.[2‑4] Intuitively, the society
assumes that higher the level of intense physical activity
higher is the health benefit.[5] The highly accomplished
sportsperson in extreme sports are regarded as the
epitome of health. The participation of amateur runners
in highly advertised and sponsored marathon events has
increased 25‑fold in last two decades.[6] Many amateur
runners take up to running in their late thirties, train
vigorously in their leisure time and may be exposing
themselves to overuse musculoskeletal injuries, adverse
cardiac events and addicting effects of exercise‑induced
endorphin release.
Review Article
IntroductIon
Marathon running is a rapidly growing sports
hobby among middle aged, non athletic
population. There are diverse views about habitual
high intensity exercise circulated in both scientific
literature and lay press. The physician should analyze
the conflicting data with scientific rigor and take a
balanced view while advising our patients about high
intensity exercise.
PhysIcAl ActIvIty through the Ages
“Homo” sapiens species evolved about 2.4 million
years ago. For 84,000 generations, human beings
survived in wild as hunter‑gatherers. They required
to perform a variety of daily physical activity just for
survival.[1] The agricultural revolution approximately
350 generations ago ushered in the dawn of
civilization. The human beings as farmers or artisans
continued to be physically active to meet the demands
of earning their livelihood. However, with the advent
of Industrial Revolution, about seven generations ago
there was a great disruptive change in the lifestyle of
the humanity. The machines took over a lot of physical
labor from day‑to‑day life. This resulted in a significant
reduction of physical activity in a large section of the
From the 1Department
of Cardiology, Jupiter
Hospital, Thane,
Maharashtra, India
Received: September, 2016.
Accepted: September, 2016.
Address for correspondence:
Dr. Nitin Burkule, MD, DM, DNB, FACC, FASE,
Jupiter Hospital, Eastern Express Highway, Thane ‑ 400 606,
Maharashtra, India.
E‑mail: burkule.nitin@gmail.com
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How to cite this article: Burkule N. Marathon running for amateurs: Benefits
and risks. J Clin Prev Cardiol 2016;5:113-24.
AbstrAct
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Burkule: Marathon running for amateurs – Benefits and risks
114 Journal of Clinical and Preventive Cardiology ¦ Oct-Dec 2016 ¦ Volume 5 ¦ Issue 4
the greAt dIvIde
The modern society is sharply divided into a growing
number of intense exercise enthusiasts and a much
larger section of highly sedentary individuals.[5]
Marathon running participation has increased[5] from
25,000 runners in 1976 to approximately 2 million
in 2010. The current recommendation of physical
activity, for optimum reduction of cardiovascular (CV)
morbidity and mortality in the society, is 150 min/week
of moderate intensity exercise or 75 min/week of
vigorous intensity exercise.[7,8] The training duration in
the amateur marathon runners far exceeds these public
health recommendations.[9]
The lay press and the scientific literature have both
high‑pitched “alarmist” proclaiming deleterious effect
of intense physical training and “ardent” supporters
claiming incremental benefit. The percentage of
sudden cardiac deaths (SCDs) of the runners during a
marathon is very small and accounts for only 5%–6%
of all SCD in the general population.[10] Although rare,
marathon‑related SCD has got prominent headlines
causing a shock wave in the community.[10] To advise
our nonathlete patients diligently, the physician needs
to review the scientific evidence, mostly coming from
the epidemiological studies, thoroughly and then take a
balanced view.
A PhysIcIAn’s dIleMMA
The majority of sports‑related SCD (approximately
94%) occurs in individuals older than 35 years.[10] Since
increasing numbers of older people are participating in
city marathon events, the incidence of running‑related
SCD is expected to rise in near future.[10]
Individuals planning to participate in popular city
marathons often consult physicians for advice regarding
preparticipation preventive check‑up and to certify them
fit for endurance sport. Most of the new recruits of the
marathon are middle‑aged, amateur, and leisure time
runners with minimal or no background of regular sports
activity during school or college years. Some of them have
rapidly switched from sedentary life to daily jogging and
may be harboring occult coronary artery disease (CAD)
due to earlier poor lifestyle.[10] Asymptomatic patients
with stable CAD, remote acute coronary syndrome, or
previous coronary revascularization also aspire to take
part in the marathons.
The guidelines for preparticipation screening of athletes
for National and Olympic level competitive sports are
published which offer effective history questionnaires
and highly selective referral for a physical
examination.[11] Routine use of electrocardiogram
and echocardiography is contraindicated due to very
low‑pretest probability and high false positive results.
Recommendations and consensus documents are
published for screening nonathlete amateur runners
with the above‑mentioned clinical profile.[12,13]
Amateur runners who are training regularly may consult
the physician for new onset of symptoms such as chest
pain, easy fatigue, declining performance, dizziness, or
palpitation. The intensity of these symptoms is often
understated due to the effects of high level of endorphin
release during endurance sports. The physician should
carefully evaluate even minimal symptoms in these
middle‑aged runners. Even after diagnosing potentially
hazardous CV condition, the physician is faced with a
challenge to dissuade successfully, the running addicted
patient, from participating in the next marathon.
cArdIAc reModelIng wIth exercIse
High level of endurance sports activity like long‑distance
running cause morphological and functional adaptive
changes in the heart. The “athlete’s heart” syndrome
is a variable extent of morphological and electrical
remodeling in response to the sporting activities such
as endurance (long‑distance running), power (lifting
or throwing heavy objects), or a combination of power
and endurance (cycling and rowing).[14] Its accurate
differentiation from cardiomyopathies is critical.[14]
The upper limits of remodeling of the athlete’s heart
on echocardiography are defined in the literature[14,15]
[Table 1]. Normalizing the cardiac dimensions for body
surface area removes most of the differences between
male and female runners. The eccentric hypertrophy
of left ventricle (LV), increased LV and left atrial (LA)
volume, increased right ventricular (RV) volume, resting
bradycardia, and lower resting LV ejection fraction (EF)
are the typical findings in endurance athletes.[15] They
are considered as physiologic adaptations, and their
upper limits serve to distinguish athlete’s heart from
hypertrophic or dilated cardiomyopathies.[14]
In a cardiac magnetic resonance imaging (MRI) study[16]
of 33 competitive elite male endurance athletes (age
30–60 years) with a training history of 29 ± 8 years,
Table 1: Echocardiographic measurements in male
and female ultramarathon athletes
Dimensions Male athletes Female athletes
LVIDd/BSA 3.8±0.3 (3.2‑4.5) 3.9±0.2 (3.4‑4.5)
IVSd (cm) 1.1±0.2 (0.8‑1.4) 1.0±0.1 (0.6‑1.2)
PWTd (cm) 1.0±0.1 (0.7‑1.2) 0.8±0.1 (0.6‑1.0)
LV mass/BSA 71±13 (39‑105) 66±10 (51‑88)
LAD (cm) 3.7±0.4 (2.6‑4.7) 3.4±0.4 (2.5‑4.1)
LVEDV/BSA 51±10 (26‑90) 55±10 (33‑87)
LVESV/BSA 18±7 (8‑38) 19±6 (8‑33)
EF (%) 64±10 (49‑82) 67±9 (50‑82)
LVIDd=Left ventricle internal dimension in diastole,
BSA=Body surface area, IVSd=Interventricular septum
in diastole, PWTd=Posterior wall thickness in diastole,
LV=Left vascular, LAD=Left anterior descending,
LVEDV=Left ventricular end‑diastolic volume, LVESV=Left
ventricular end‑systolic volume, EF=Ejection fraction. Data
adapted from study by George KP et al.[15]
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indexed LV mass and RV mass and indexed LV
end‑diastolic volume and RV end‑diastolic volume
were significantly higher in athletes as compared with
controls [Table 2]. The RV EF did not differ between
athletes and controls.
In a study[17] of previously sedentary cases (age 25–35 years),
who embarked upon training for a marathon, cardiac
MRI for RV and LV volumes was performed at baseline
and after 3, 6, 9, and 12 months of training. LV and RV
mass increased progressively with training and reached
levels similar to those of elite endurance athletes. LV
initially showed concentric remodeling during the first
6–9 months of endurance training. Thereafter, LV showed
dilatation (eccentric remodeling) and restored the baseline
mass‑to‑volume ratio. The RV responded with eccentric
remodeling at all levels of training. This study gives
insight into the time frame required for training to make
the heart “marathon ready.”
A follow‑up echocardiographic study[18] of 114 Italian
Olympic athletes (78% male; mean age 22 ± 4 years)
undergoing intensive and uninterrupted training
over 4–17 years for 2–5 consecutive Olympic
Games (total 344 Olympic events) did not show adverse
effects of athlete’s adaptive cardiac remodeling. The
global LVEF remained unchanged, and new wall
motion abnormalities were absent. The LV volumes
and LV mass index remained unchanged, and LV
filling patterns remained within normal limits. The
LA dimension showed a mild increase in follow‑up.
Therefore, in young Olympic athletes, extreme and
uninterrupted endurance training, over a long period
did not show deterioration of LV systolic and diastolic
function or progression of LV hypertrophy.
Some experts caution about the overlap of
morphometric values of the athlete’s heart with the
clinical cardiomyopathies and also doubt the assumed
“physiological” nature of the cardiac remodeling in
endurance athletes.[14] In general, compensatory chamber
hypertrophy in cardiac diseases is counterproductive.
The myocardial hypertrophy with myocardial fibrosis
alters the chamber compliance leading to clinical heart
failure and arrhythmias.
benefIts of PhysIcAl ActIvIty
Regular exercise has a lot of pleiotropic health benefits
through positive modulation of plethora of physiological
processes [Table 3]. Exercise at minimum recommended
level positively affects all the modifiable coronary
risk factors,[19] improves CV function,[9] modulates
genomic expression,[1] and reduces the incidence of
malignancies. Exercise promotes psychological health
and improves sleep pattern.
Interestingly, when an individual switch from
sedentary habit to an active lifestyle, a large quantum
of CV benefits, and improved life expectancy is already
Table 3: Pleiotropic benefits of regular exercise
Positive effects of exercise
Modification of CAD risk factors[9,19]
Increase in
HDL cholesterol
Insulin sensitivity
Reduction in
LDL cholesterol
Triglycerides
Blood sugar
Blood pressure
Body mass index
Systemic inflammation
Cardiac effects[10,54,66,67]
Improved peak oxygen consumption
Improved diastolic function
Improved stroke volume
Reduce LV compliance
Increase vagal tone
Reduce acute risk of MI and SCD during exercise
Vascular effects[9]
Improve endothelial function
Increase nitric oxide bioavailability
Cause vascular remodeling
Reduce systemic vascular resistance
Improve coronary vasomotor response
Neuropsychological effects[1]
Promote feeling of wellbeing
Reduce depression and anxiety
Improve sleep architecture
Improve sexual drive and performance
Miscellaneous[1]
Modulates multiple genes expression
Improves immunity
Reduces incidence of malignancies
Reduces circulating adipokines and cytokines
HDL=High‑density lipoprotein, LDL=Low‑density
lipoprotein, MI=Myocardial infarction, SCD=Sudden
cardiac death, CAD=Coronary artery disease
Table 2: Cardiac magnetic resonance imaging
measurements in elite endurance master athletes
and control cases
Dimensions Master athletes Controls
LV mass (g/m2) 96±13 96±13
RV mass (g/m2) 36±7 36±7
LVEDV (mL/m2) 104±13 69±18
RVEDV (mL/m2) 110±22 66±16
RV EF (%) 52±8 54±6
LV=Left vascular, RV=Right vascular, LVEDV=Left
ventricular end‑diastolic volume, RVEDV=Right
ventricular end‑diastolic volume, EF=Ejection fraction.
Data adapted from study by Bohm P et al.[16]
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accrued at the much lower intensity of regular physical
activity.[2,20] Simply standing >2 h/day is associated with
a 10% reduction in all‑cause mortality compared with
standing <2 h/day. The lowest mortality was achieved
in individuals standing >8 h/day.[21] Even 15 min of
brisk walking per day (half of current public health
recommendation) reduced mortality from ischemic
heart disease by 25% and increased life expectancy
by 3‑year.[2] Running only 10 min/day at slow speed
<6 miles/h, weekly running <51 min, <6 miles,
1–2 times, or <506 metabolic equivalents (METS)‑min
are sufficient to substantially reduce risk of mortality,
compared with not running.[3,22] This amount of light
exercise is easily achievable, can cause 30% and 45%
reduction in all‑cause and CV mortality, respectively,
and add 3 years of gain in life expectancy.[3] Data
extracted from 26 cohort studies show that increment
of 1 MET h/week of energy expenditure, which
is equivalent to 2–3 min of moderate to vigorous
physical activity per day, results in a 0.8% reduction
of the average relative risk (RR) of mortality from
noncommunicable diseases.[23] The Japanese Public
Health recommendation of daily 10+ min of moderate
to vigorous activity, of any nature, aims at reducing RR
by 3.2% at the population level.[23]
Both brisk walking and running can achieve an
equivalent level of reduction in CV events except that
the time spent in walking should be 2–4 times that of
running.[24] Walking is much easier to perform daily, is
sustainable and safe with regards to musculoskeletal
injuries, and gives an opportunity for social networking.
Young individuals with busy lifestyle and time crunch
can achieve significant CV benefits by short bouts of
running even 10 min a day 3–4 times, less than an
hour per week.[22,24]
The relation of CV mortality reduction and quantum of
physical activity is not linear but curvilinear.[2,9] This
observation suggests that at a higher level of exercise
further gain in CV benefits is less or may plateau for
every additional METS of exercise performed.[3,4] It
is unclear whether there is a ceiling dose of exercise.
According to some experts, there is no significant
benefit beyond 9 METS of exercise in women and 10
METS of exercise in men per session[6,25] or 3–10 times
the recommended physical activity level[4] or beyond
120 min/week of exercise.[3] Even among the extremely
active Ache Hunters of Paraguay, who had much
superior cardiorespiratory fitness than people in
developed world, the average daily distance covered
for aging was approximately 6 miles.[1] A moderate
range of intensity, frequency, and duration of exercise
may be important for maximizing health and longevity
benefits.[6] The human race has been evolutionarily
adapted to a variety of physical activities performed
intermittently at moderate intensities for moderate
durations and not to just one type of endurance activity
like long distance running.[1]
the exercIse PArAdox
It seems that the first marathon run claimed a life! In
490 B.C. Pheidippides, the Greek professional courier,
ran from Marathon to Athens and declared the Greek’s
victory over Persians saying “Nike” and then collapsed
and died.[20] However, historians think that it is a myth
and in reality Pheidippides further continued to run to
Sparta to carry the message for military help.[26]
There is sufficient evidence to suggest that there is a
short‑term rise in myocardial infarction (MI) and SCD
during the hour‑long period of exercise and recovery
than during the rest 23 h when the individuals are
less active.[27,28] The risk of MI with each bout of
physical activity is approximately doubled even for a
fit individual who regularly performs vigorous exercise
5 times a week.[5] However, the RR of MI during intense
physical activity is 50 times higher in habitually
sedentary individuals who suddenly get engaged in
exercise bout than the individuals who are regularly
performing moderate to high level of exercise.[29] The
overall RR of SCD within 30 min of vigorous exercise is
seven‑fold higher in those who exercise less than once
per week as compared to those who exercise >5 times
per week.[30] Although exercise increases the acute
risk of SCD and MI, paradoxically “regular” exercise
of moderate to high intensity is highly protective
and reduces the exercise induced the risk of SCD by
7–10‑fold and of MI by 50‑fold.[10]
The risk of SCD during marathon events is as small
as 0.8–2/100,000 marathon runners and the risk of
all sports‑related SCD is as insignificant as 4–5/1
million population of the nation.[31,32] In a marathon,
runners >30 years of age, approximately 80% of
SCD are caused by atherosclerotic CAD.[11,31] In this
age group, a small fraction of SCDs are attributed to
cardiomyopathies, myocarditis, congenital coronary
anomalies, trauma, heat stroke, or channelopathies.[11]
For leisure time joggers, the annual incidence of SCD
is higher than marathon events (13 SCD per 100,000
joggers per year).[33] Their imaging and autopsy
studies reveal nonobstructive coronary plaques, with
a thin cap ruptured in the center of the plaque, with
large overlying thrombus.[10] This suggests a role of
hemodynamic shear force on the vessel wall and
adrenergic hypercoagulable state during intense and
prolonged exercise.
The epidemic of atrial fibrillation (AF) in the later
part of life is increasingly viewed as lifestyle disease.
There is a strong evidence to suggest that middle‑aged
individuals who are habitually physically active have
a lesser incidence of AF in the later part of life.[34,35]
Exercise effectively controls the risk factors for AF such
as hypertension, obesity, and obstructive sleep apnea
and prevent age‑related decline in LV compliance.
For every 1‑MET increase in cardiorespiratory fitness
level, there is an associated 7% decrease in the risk of
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A F. [36] Paradoxically, individuals engaged in an extreme
level of sports activity in the early part of life have
a higher incidence of AF in the later part of life. In
a study[34] of 44,410 Swedish men, intense exercise
of more than 5 h per week at the age of 30 years
increased the risk of developing AF later in life. In
contrast, moderate intensity of physical activity such
as walking or bicycling, in the middle age, decreased
the risk of AF.
The increased risk of AF is thought to be mediated
through adaptive cardiac remodeling such as
LA dilatation due to increased cardiac output,
increased atrial conduction time, LA fibrosis, and
resting bradycardia with intermittent exposure to
high‑catecholamine levels with training.[36]
chAllenges of InterPretIng ePIdeMIologIcAl
studIes of PhysIcAl ActIvIty
Population‑based epidemiological studies of physical
activity have given unambiguous scientific evidence
of a reduction in all‑cause mortality and CV mortality
with an active lifestyle.[19,25,37] One should be aware of
certain aspects and limitations of these studies. It is
highly challenging to measure exact exercise dose at
the individual level. There is no standard definition
of what constitutes an athlete, intense exercise,
or endurance exercise.[38] Change of lifestyle from
sedentary to active promotes incremental health and
feeling of well‑being in an individual. The healthier
individual in turn is likely to exercise more, thus
blurring or confounding the simple exercise dose and
health effect relationship.[24]
Most of the studies rely on cases’ self‑reporting of
exercise with regards to perceived intensity, time
duration per session, and frequency per week. From
this data, a parameter called “METS‑hour per week”
of energy expenditure is calculated which is a product
of predicted METS per unit time for the kind of
exercise × time duration per session × frequency per
week.[9] Moderate intensity activities are 3.0–5.9 METS,
whereas vigorous activities are >6.0 METS. However,
the definition of intense exercise used in the cardiology
literature is 10 METS which may be perceived as
a warm‑up for elite competitive athletes.[38] Even in
amateur runners, the perceived intensity of similar
jogging pace may be “strenuous’” for a deconditioned
middle‑aged man while it may be “light” for a young
active teen.[39]
There are also significant differences between amateur
runners and the elite athletes.[6] The athletes start their
strenuous exercise program in first or early second
decade of life before the significant atherosclerotic
process can start in the coronaries. It is highly
likely that they are genetically endowed for physical
excellence. They exercise under professional guidance
for exercise technique, cross training, and diet. They
maintain overall healthy lifestyle and take adequate
rest for the healing of overuse injuries.[6] Postcareer,
they systematically reduce the training intensity and
duration. In the developed world, athletes maintain
high standards of living and have access to medical
care which can also contribute to increased longevity.
For the same reason of high standards of living,
even Nobel Prize or Oscar Award winners have a
superior life expectancy as compared to the general
population.[6]
In contrast, amateur runners are lay people who
take up running in middle age when the occult
atherosclerotic process may have already set in.
Professional athletes usually perform >80% of their
training sessions at subjectively light intensities (50%–
70% of their maximal heart rate) compared with novice
runners who often train relatively and subjectively at
too high intensities.[40] In fact, numerous middle‑aged
and poorly prepared runners start strenuous
running programs immediately after CV disease
diagnosis.[40] Although many nonathletic people get
addicted to running, not all of them stop smoking
or make healthy dietary choices.[27] Many of them,
during training, drink excess of insulin spiking and
high‑carbohydrate energy drinks. Most of them enter
into grueling training schedule without compromising
their working hours but add their exercise schedule
to the demands of a job, marriage, and parenting.
There is no adequate rest period for healing overuse
injuries such as plantar fasciitis, Achilles tendonitis,
shin splints, and patellar chondromalacia.[6] Not all
of them have easy access to professional exercise
trainers and higher medical care. Hence, increased
longevity data of athletes cannot be extrapolated to
amateur runners just because they are engaged in the
same kind of physical activity.
There are also a difference in leisure time running
and marathon training for amateur runners. The
leisure time running is noncompetitive with adequate
time to relax. While marathon training as referred
to earlier is competitive, arbitrarily structured,
and compromises adequate rest in busy, working
individuals. Novice amateur runners may fail to
optimize their running performance and CV health
by blindly following modern training methods used
by elite athletes.[40]
The epidemiological studies of jogging divide the
observational cohort into different groups, namely
sedentary controls, predefined mild, moderate, high,
and extremely high levels of joggers. In general
population, a number of individuals in the groups at
high to extremely high level of habitual exercise are
distinctly underrepresented. Small events of all‑cause
mortality in these groups get proportionately magnified
with wide confidence intervals (CIs).
With these limitations in mind, let us explore the
evidence of health benefits and hazards with the
increasing dose of running.
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Is there A hArM wIth hIgh‑IntensIty exercIse?
The view
Few animal experiments (marathon rats) and some large
population‑based observational studies have indicated
deleterious effects on the heart with high‑intensity
prolonged exercise. “Cardiac fatigue” is a phrase coined
to describe transient functional and biochemical
changes in myocardium after extraordinary endurance
events[41] [Table 4]. The theoretical hazards involved
with intense exercise are as follows:
• Increased troponin and B‑type natriuretic
peptide (BNP) release[42] was noted during marathon
running suggesting myocardial injury, which
may compound over time to cause myocardial
fibrosis. In Boston Marathon Study[42] of sixty
nonelite participants, at the end of the race, 60%
had increased troponins above the 99th percentile
of normal and 40% had troponin levels above the
diagnostic threshold for MI. Compared with athletes
training 45 miles/week, athletes who trained
35 miles/week demonstrated higher troponins and
BNP
• In ultra‑endurance triathlon participants,
reduced LVEF, reduced LV fractional shortening,
and segmental wall motion abnormalities in a
nonvascular distribution have been documented on
echocardiography, immediately after the race.[43,44]
The biochemical and functional abnormalities of
LV and RV may last 3–17 h after endurance
events.[45] Increased myocardial fibrosis and
increased susceptibility to arrhythmia are seen in
experimental marathon rats[52]
• Transient RV dilatation and dysfunction and rise
in pulmonary artery pressure are documented in
marathon[14] and triathlon athletes.[45] A cardiac
MRI study[53] reported that marathon running
caused acute dilation of the right atrium and the
right ventricle, reduction in the RV EF, parallel
with elevations in cardiac troponin I and BNP.
Extraordinary endurance exercise may cause acute
fatigue of cardiac muscles, which seems to be more
prominent in the right than the LV.[54] However, this
recovers quickly even after a very long event. The
repetitive postexercise RV abnormalities may have
potential to cause permanent RV injury, fibrosis, and
risk of arrhythmias[55,56]
• Cardiac MRI has shown increased incidence
of late gadolinium enhancement (LGE) in both
coronary (subendocardial) and noncoronary (septal
insertion sites) distribution in endurance athletes.[9]
Almost half of older lifelong endurance athletes had
shown evidence of myocardial fibrosis, whereas
age‑matched controls or young athletes had no
fibrosis on LGE‑MRI.[46] The cause may be acute
myocardial injury, myocardial edema[54] leading to
permanent septal or RV fibrosis with putative future
arrhythmic risk
• In a study[47] of 108 healthy, middle‑aged (50 years)
marathon runners, cardiac computed
tomography (CT) showed a higher level of coronary
artery calcium score (CAC) compared to Framingham
risk score‑matched population but a similar level of
CAC compared to age‑ and sex‑matched sedentary
population. This population is representative of
typical amateur runners since they started training
within the preceding decade and their exercise
training volume was relatively modest. More than
half of these cases were previous smokers, and
their body mass indices were at the higher end of
normal range. Thirty‑six percent of these marathon
runners had CAC score 100 or more and 9% of
these required coronary revascularization during
2 years of follow‑up indicating no protective effect
of running for atherosclerosis in late life[54]
• LGE was observed in 12% of these athletes.
CAC percentile values and number of marathons
independently predicted the presence of LGE.
Runners with LGE had higher subclinical CAD
Table 4: Probable adverse effects of long‑term,
high‑intensity exercise
Myocardial fatigue and injury[42‑45]
Release of cardiac injury biomarkers troponin, BNP
Increased incidence of myocardial edema on cardiac
LGE‑MRI
Transient LV regional wall motion abnormality
Transient RV systolic dysfunction and dilatation
Cardiac morphological effects[9,16,46]
Progressive LA dilatation and fibrosis
Eccentric LV hypertrophy and RV dilatation
Increased incidence of myocardial fibrosis on cardiac
LGE‑MRI
Coronary vascular effects[27,30,47,48]
Increased coronary calcium score
Acceleration of established atherosclerosis
Rupture of vulnerable plaque
Acute MI and SCD
Arrhythmias[9,49‑51]
Increased incidence of atrial fibrillation in late adulthood
Increased risk of arrhythmia due to electrolyte imbalance
and heat stroke
Increased phenotypic expression of RV cardiomyopathy in
patients with desmosomal mutation
Musculoskeletal injuries[1,6]
Plantar fasciitis
Achilles tendonitis
Shin splints
Patellar chondromalacia
Spine osteopenia
LV=Left vascular, RV=Right vascular, MI=Myocardial
infarction, SCD=Sudden cardiac death, LGE=Late
gadolinium enhancement, MRI=Magnetic resonance
imaging, LA=Left atrial, BNP=B‑type natriuretic peptide
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burden and had higher increases in troponin I
during marathon, suggesting a causal relationship.
Higher CAC scores and LGE are shown to be
associated with higher coronary event rates on
long‑term follow‑up.[53,57] Some marathoners may
have higher levels of CAC due to an increase in
PTH levels during running[54]
• A study[48] comparing coronary angiograms
of marathon runners with that of sedentary,
age‑matched controls showed that male
veterans (who ran at least one marathon each year
for 25 consecutive years) had significantly increased
amounts of both hard and soft coronary plaques. It is
unlikely that the high‑dose vigorous exercise causes
atherosclerosis but it may potentiate the existing
atherosclerosis process by increasing repetitive
arterial shear stress and chronic pro‑inflammatory
state[27]
• Significantly higher incidence of late‑life AF is
seen in individuals participating in prolonged
high‑intensity exercise in the early part of life. In a
rat model,[52] chronic endurance exercise increased
AF susceptibility due to autonomic changes,
increased vagal tone, atrial dilation, and fibrosis. In a
Swedish study,[49] 52,755 participants in Vasaloppet,
a 90 km cross‑country skiing event, from the year
1989 to 1998 were followed up until the year
2005. AF and bradyarrhythmias were experienced
by 919 participants. A faster finishing time and a
high number of completed races were associated
with higher risk of AF. In a meta‑analysis[50] of
six case–control studies of 655 athletes and 895
controls, AF was documented in 23% of athletes
and 12.5% in controls. The odds ratio (OR) for AF
in the athlete group was 5.29 (95% CI 3.57–7.85).
In a study[58] of 115 cases of athletes with AF,
compared with 57 age‑matched controls, the OR
for new AF was 4.52 for cumulative heavy sports
activity (>2000 h) which was almost equivalent to
cases with sleep apnea (OR 5.04) and higher than
even sedentary individuals (OR 3.85)
• Majority of SCD occur in full marathons than in
half marathons and that too strikingly in the final
quartile of full marathons.[10] The cause may be
multifactorial such as sympathetic overactivation,
electrolyte imbalance, activation of hemostatic
system, shear stress on vulnerable coronary plaques,
or hemorrhage into the plaque.[10] The heat stroke
may be a major cause of SCD during endurance
running events[51]
• The risk of myocardial biomarker release, acute
MI, and SCD during marathon running or training
is higher in poorly trained marathon runners
as compared to highly trained athletes. The
musculoskeletal injuries with running are common
and can be severe enough to stop participation in
aerobic exercise. In an 8‑week training session
for 4 miles run, 25% of participants developed
significant musculoskeletal injuries requiring
cessation of training[59]
• Among individuals who carry a desmosome
mutation for RV cardiomyopathy, the endurance
training can cause deterioration of RV function
and accelerate the phenotype expression of RV
cardiomyopathy.[9,54]
The counter view
Except for higher incidence of AF, there is no clear
evidence of highly significantly increased the risk of
ventricular arrhythmias, heart failure, CV, or all‑cause
mortality in endurance athletes and active individuals
from epidemiological studies.[19] The risk for SCD from
running is negligible and is as low as 4/1 million.[60]
The elite athletes have fewer hospitalizations, require
less asthma, CV, and anti‑inflammatory medications,
and live longer than nonathletic people.[27] In
Vasaloppet, the 90 km cross‑country skiing event,
there was no increase in ventricular tachycardia,
ventricular fibrillation, or cardiac arrest.[49] The
cross‑country skiers had 52% reduction in all‑cause
mortality, with the highest life expectancy found
in older participants and athletes who participated
in multiple races.[61] More than 15,174 Olympic
medalists from nine different country groups
were followed up over decades after their first
medal.[54] The participants of the endurance sports
had higher survival (2.8 years) compared to age‑ and
sex‑matched controls from the general population
in those countries.[62] Finnish skiers and world‑class
endurance athletes demonstrated an increased life
expectancy of 2.8–6 years compared with reference
cohorts.[63‑65] Masters athletes, who had been training
for more than 25 years, competing successfully in
multiple marathons, triathlons had LV compliance,
vascular age, and vasodilatory function similar to
young adults.[54] Their ventricular–arterial coupling
was superior so that they could increase more than
two times their stroke volume for any given increase
in left ventricular filling pressure.
Commencing from 1986, a 22 years long, biennial
questionnaire‑based follow‑up study[19] of 44,551 men,
aged 40–75 years, showed that increasing amounts of
vigorous activity remains inversely associated with
CV and malignancy disease risk. This relationship
existed even among men in the highest categories of
intenseexercise.Running≥5haweek was associated
with the lowest CV risk. Vigorous intensity of exercise
at 10 METS h/week further reduced mortality by
4% points over the moderate intensity of exercise of
identical energy expenditure. A recent study[66] showed
that the committed exercisers, who have trained
regularly, 4–5 days a week for most of their adult
lives, have ventricles that are almost as compliant as
those of master athletes. In contrast, casual exercisers,
who trained not more than 2–3 times per week, had
no apparent benefit in terms of LV compliance.
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Recreational marathon training reduces CV risk
factors (obesity and lipid levels) and increases CV
efficiency (improved peak oxygen consumption and
diastolic function).[67]
Both views, for and against habitual strenuous exercise,
should be interpreted cautiously and should not be
used indiscriminately to dissuade strenuous physical
activity in trained, healthy athletes or to encourage
strenuous physical activity in ill‑trained amateur
runners.
the reverse J shAPe relAtIonshIP of runnIng
And MortAlIty
The epidemiological studies in general population
studying the relationship of the quantum of running
and mortality reduction consistently show a reverse J
shape pattern.[3,4]
In the Copenhagen City Heart Study,[20] 1098 healthy
joggers and 3950 healthy nonjoggers were prospectively
followed up since 2001. Joggers were categorized as
light (n = 576), moderate (n = 262), and strenuous
joggers (n = 40) depending on the combination
of self‑reported pace (slow, average, and fast),
quantity (<2.5 h/week, 2.5–4 h/week, and >4 h/week),
and frequency (<3 times/week, >3 times/week). For
example, a case with slow or average pace jogging for
<2.5 h/week and <3 times/week will be categorized as
“light jogger” whereas a case with fast pace jogging for
>2.5 h/week and >3 times/week will be categorized as
“strenuous jogger.” The lowest hazards ration (HR) for
mortality was found 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) and strenuous joggers (HR: 1.97;
95% CI: 0.48–8.14). Jogging up to 2.5 h/per week at a
slow or average pace and a frequency of <3 times per
week was associated with the lowest mortality. Those
who jogged >4 h/week, at a fast pace, and >3 times/
week appeared to lose many of the longevity benefits.
In other words, light and moderate joggers have
lower mortality than sedentary nonjoggers whereas
strenuous joggers have a mortality rate not statistically
different from that of sedentary nonjoggers (U‑shaped
association). The study was criticized for nonobjective
“self‑reporting” of pace[39] and low number of strenuous
joggers exaggerating the HR in this group (n = 40
with two deaths). Similar reverse J shape findings for
intensity and duration of exercise were not found in the
studies of walking and cycling by the same authors.[68,69]
Cooper Clinic in Dallas, Texas, followed up of 55,137
adults for 15‑year to examine associations of running
with all‑cause and CV mortality.[3,22] They used five
quintiles of running so there would be an equal number
of cases across different doses of running. CV mortality
appeared to be relatively higher in those with higher
doses of running compared with lower doses (reverse
J‑shaped association) and a slight nonsignificant trend
of less benefit, for all‑cause mortality, with higher doses
of running compared with lower doses of running.
However, there continued to be significantly lower
risks of mortality in the highest quintiles of running
time (>176 min/week) and frequency (>6 times/week)
compared to the nonrunners (no U‑shaped association).
Despite all the limitations of methodologies in
these studies, few distinct trends emerge, which are
hypothesis generating [Figure 1]. More is definitely
not better[22] but may not be harmful.[3,22] The benefit
of maximal reduction in mortality is achieved at light
to moderate intensity of regular jogging as compared
to habitual sedentary behavior. There is no further
reduction in mortality with a higher dose of jogging but
rather the benefits tend to get blunted or reduced at a
higher intensity or extreme level of running.
The reverse J shape relation of exercise and mortality
has also been shown in post‑MI patients and patients
with stable CAD. In a study[70] of 2377 MI survivors, 15%
average risk reduction in CV mortality was achieved for
every additional 1 MET h/day of exercise (equivalent
of running 1 km/day) only till 7.2 MET h/day. Regular
exercise above this level, in this post‑MI population,
did not benefit but rather increased CV events. Relative
to the CV risk reduction at 7.2 MET h/day exercise, the
CV risk of exercising above 7.2 MET h/day increased
3.2‑fold. In another study of 1038 cases[71] with stable
CAD, the frequency of strenuous leisure time physical
activity was assessed over 10 years of follow‑up. The
CV events, mortality, and all‑cause mortality were
highest in the sedentary group and then progressively
declined from infrequent (1–4 times a month) to
moderate activity (2–4 times a week) groups. However,
the CV events, CV mortality, and all‑cause mortality
again climbed progressively in the frequent (5–6 times
Figure 1: Conceptual graph of the approximate relationship of “intensity
of jogging” (time, distance, speed, frequency, and metabolic equivalents
min/week) and reduction in “cardiovascular mortality” derived from data of Lee
et al. [3] showing reverse J shape. There is significant reduction in cardiovascular
mortality at the lower quintiles of running intensity, while the benefits appear
to get blunted at higher quintiles of running intensity
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a week) to daily strenuous activity group. The all‑
cause mortality rate per 1000 persons‑year was 44.3 in
sedentary group, 14.1 in infrequent activity (1–4 times
a week) group, 7.6 in moderate activity (2–4 times a
week) group, 8.7 in frequent activity (5–6 times a week)
group, and 16.2 in daily strenuous activity group.
It is controversial and probably not true that
individuals lose all the benefits of exercise at habitual
high or extremely high intensity of exercise and the
mortality climbs back to that of sedentary level[22] (the
U‑shaped relation). Therefore, the strenuous level
of running is not better for sure but not necessarily
harmful.[27] A weekly cumulative dose of vigorous
exercise of not more than 5 h may be the safe upper
range for optimal CV health and life expectancy. It
may be beneficial to take 1 or 2 days a week off from
vigorous exercise and not to perform high‑intensity
exercise on a daily basis.[6]
screenIng of AMAteur runners
The preparticipation electrocardiography (ECG)
screening of young athletes is controversial considering
financial and logistics cost of ECG acquisition and
interpretation, high rate of false‑positive findings,
cost of follow‑up testing after abnormal ECG, and
the problems of future insurability of athletes with
abnormal ECG.[72] However, the risk of SCD in older
athletes is 5‑fold higher during training than during
the marathon event.[10] The physician has to diligently
screen for occult CAD in the sedentary individuals,
above the age of thirty, who wish to first‑time start
training for a marathon. There are three published
documents for preparticipation screening of the older
athlete for risk stratification.[12,13,73]
A comprehensive history as outlined in the
questionnaire[74] is very useful to detect patients
needing detail physical examination and ECG [Table 5].
A high‑risk case can be identified by clinical features[10]
For example, strong family history of premature CAD
or SCD, Framingham risk score >5%, high‑body
mass index, high‑LDL cholesterol, or diabetes with
microalbuminuria. When the patient has high‑CAD
risk profile and the gap between his/her daily
physical activity and planned training level is large,
the physician should perform a maximal stress
test.[10] The incremental value of the selective use of
echocardiography, cardiac MRI, or CT coronary calcium
score is not defined in this population.
counselIng of the AMAteur runners
Physicians should have a detail and balanced discussion
with the amateur runner training for the marathon.
Most of these individuals are performing physical
activity far more than the minimal recommendations
for the society.[27] It should be made clear that exercise
benefits far outweigh the risks at every level of
exercise. Although no optimal dose of exercise exists,
the maximal CV benefits are already achieved at a
moderate intensity of exercise. Although the routine
performance of high level of exercise bestows relative
protection from CV mortality, unfortunately no level of
exercise gives complete immunity from CV disease or
mortality.[27] The higher level of training does not mean
better CV benefits. Higher running dose is associated
Table 5: Preparticipation self‑assessment
questionnaire for amateur runners
Questions Response
History of
Heart attack
Heart surgery
Cardiac catheterization or
angiography
Coronary angioplasty
Heart rhythm disturbance
Pacemaker/implantable cardiac
defibrillator
Heart valve disease
Heart failure
Congenital heart disease
Musculoskeletal problems
Heart or blood pressure
medication
Pregnant
Heart transplantation
If any one point is tick
marked, please consult
physician before
starting training
Symptoms of
Chest discomfort with exertion
Breathlessness with exertion
Dizziness, fainting, and
blackouts with exertion
If any one point is tick
marked, please consult
physician before
starting training
CV risk factors
Male >45 years
Woman >55 years or
posthysterectomy or
postmenopausal
Smoker
Blood pressure >140/90
Blood pressure never measured
Total cholesterol >240 mg/dl
Cholesterol level never
measured
Heart attack <55 years
in father or brother or
age<65 years in mother or
sister
Diabetes mellitus
Physically inactive (<30 min
of physical activity<3 days/
week)
Overweight
If any two points are
tick marked please
consult physician
before starting training
CV=Cardiovascular. Questionnaire adapted from
recommendations by Balady GJ et al.[74]
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122 Journal of Clinical and Preventive Cardiology ¦ Oct-Dec 2016 ¦ Volume 5 ¦ Issue 4
with higher level of cardiorespiratory fitness, but this
does not translate into better survival (which already
peaks at low dose of exercise).[6] The exercise paradox
must be discussed when counseling both habitual
sedentary individuals and also the exercise enthusiasts.
The inherent risks and benefits of high‑dose exercise
should be made clear.[27] This is especially more
relevant for patients with established stable CAD. The
marathon running may be looked upon as thrilling or
adventure sport and not as ideal workout for maximal
health benefit.
The importance of gradual increment in training
should be emphasized in middle‑aged runners to
avoid precipitation of SCD,[28] acute coronary events,
or musculoskeletal injury. A gradually incremental and
long‑term training schedule may reduce the risk of SCD
substantially in the habitual sedentary cases.[10] The
frequency of physical activity (not the intensity) should
be emphasized as the initial goal. The previously
inactive person should start with brisk walking
3–4 times a week and then upgrade to light pace
jogging at 50%–75% of age‑predicted maximum heart
rate (MHR), and finally to moderate pace running at
70%–85% of age‑predicted MHR. Each stage should last
for 6–8 weeks.[10] As described earlier, exercise‑induced
cardiac adaptive remodeling is a slow process and
takes 9–12 months of training to reach its maximal
potential.[17]
The amateur runners should be instructed to observe
even mild symptoms of chest pain, dizziness, small
decrements in exercise capacity, or new onset
fatigability and should seek physician’s consult.[27] This
must be especially more emphasized in patients with
established stable CAD. The amateur runners should
be made aware of the importance of cross training to
achieve maximal aerobic fitness and avoid overuse
injury.[1] The amateur runners must be instructed
to stick to the healthy lifestyle including healthy
dietary choices, quitting smoking, and excess alcohol
consumption.[27] Although statins are prescribed
for eligible patients in accordance with 2015 ACC/
AHA guidelines, the statin‑induced myalgia is often
more troublesome in the runners.[10] The use of
low‑dose aspirin (75–100 mg) as primary prevention
in middle‑aged runners with traditional coronary risk
factors is uncertain,[54] but the benefit may outweigh
the risk.[10]
wIsdoM of hIPPocrAtes
After reviewing the of emerging data of exercise and its
effects on health, the following quote from Hippocrates
appears to be more relevant than ever.[75]
“If we could give every individual the right amount
of nourishment and exercise, not too little and not
too much, we would have found the safest way to
health.”
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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