Critical thinking paper written for Syracuse University class, PPE 518, exploring the cardiovascular implications of marathon running. See SlideShare link above.

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Marathon running generates a considerable amount of media attention, especially
when seemingly healthy runners suffer from sudden cardiac death (SCD) and nonfatal
cardiac arrests during a race. There is no doubt that marathon-related cardiac arrests are
on the rise, causing many to question whether or not marathon running is harmful to
one’s cardiovascular health (2). However, marathon participants and marathon events are
also on the rise (2). In 2014, there was a record amount of over 550,000 marathon
finishers and more than 1,200 marathon events in the United States alone (8). Research
has shown that the increase in marathon-related cardiac arrests are proportional to the
increase in marathon participation and marathon races (2). With that said, the overall
incidence of exercise-induced SCD remains low, with an annual incidence of 1:185,000,
equating to 1 SCD per every 365 million hours of exertion (3). For marathon runners in
specific, the annual incidence rates are even lower with an annual incidence of 1:114,000,
typically occurring during the final mile or finish line of marathons (3). When compared
to other sport populations, cardiac risk associated with long-distance running is
equivalent, if not lower than, the risk associated with other vigorous physical activity (2).
SCD’s and nonfatal cardiac arrests during marathon races indubitably draw media
attention and public concern. While these events do adjure further investigation, current
research suggests that marathon running is more helpful than harmful to one’s
cardiovascular health.
To understand the implications of research related to cardiac risk associated with
long distance running, one must first understand the measurements of cardiac function,
primarily cardiac biomarkers. Cardiac biomarkers are substances that are released into the
blood when the heart is under stress (4). There are a number of cardiac biomarkers that

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correspond to physiological and pathological processes of the cardiovascular system (4).
Elevations of these biomarkers implicate myocardial ischemia, damage, or cardiac
dysfunction (4). Cardiac Troponins, Creatine Kinase, Creatine Kinase-Myoglobin, B-type
Natriuretic Peptide, and N-terminal Pro–B-type Natriuretic Peptide are among the many
cardiac biomarkers researched in marathon running associated cardiovascular studies.
Cardiac-specific troponins, cTnT and cTnI, are regulatory proteins that are
powerful markers of myocyte damage and considered the “gold standard” biomarkers in
diagnosis of myocardial necrosis (4). In patients with myocardial infarction, cTnT and
cTnI elevate within two to four hours of infarction, peak between 18 and 36 hours, and
can remain in the blood for up to 21 days (4). The American Heart Association (AHA)
defines myocardial infarction (MI) as “the elevation of cardiac troponins above the URL
combined with at least one of the following four criteria: 1) symptoms of ischemia, 2)
ECG changes indicative of new ischemia, 3) development of pathologic Q waves in the
ECG, or 4) imaging evidence of new loss of viable myocardium or new regional wall
abnormalities” (4). When elevated cardiac troponins are present without clinical evidence
of ischemia, the AHA recommends investigating other etiologies (4). It is important to
note that “extreme exertion” is listed as an etiology, suggesting that elevations in cTnT
and cTnI can occur without the presence of MI, due to strenuous exercise (4).
Creatine Kinase (CK), an intracellular enzyme, and Creatine Kinase-Myoglobin
(CK- MB), an isoenzyme of CK, are cardiac biomarkers used to differentiate skeletal
from cardiac muscle injury (7). CK-MB is mainly found in cardiac muscle and thus is
used to determine myocardial injury, whereas CK is found in skeletal muscle,
myocardium, brain, and other visceral tissues (7). CK-MB typically elevates within 4 to 6

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hours of a MI, peaks at 24 hours, and returns to normal level within 2 days (7). While
CK-MB does elevate in the presence of MI, it can also elevate following severe physical
exertion (7).
B-type Natriuretic Peptide (BNP) is a counter-regulatory hormone that reduces
myocardial wall stress through increasing natriuresis, vasodilation, and
sympathoinhibitory effects (4). N-terminal Pro–B-type Natriuretic Peptide (NT-proBNP)
is a cleaved inactive fragment of BNP (4). Both BNP and NT-proBNP elevations denote
increased myocardial wall stress due to volume or pressure overload on the heart and
cardiac dysfunction, chronic heart failure, cardiomyopathy, acute coronary syndromes, as
well as other cardiac diseases (4). Although BNP and NT-proBNP are present during
cardiac dysfunction, they have been shown to have cytoprotective and growth-regulating
properties (4).
There is much controversy on whether or not the elevation of cardiac biomarkers
in marathon runners is clinically significant of cardiovascular damage. One study
examined the increase in NT-proBNP and its relation to elevations in cTnT, cTnI, CK,
and CK-MB following prolonged strenuous exercise (5). This study tested 105 obviously
healthy athletes’ NT-proBNP, cTnT, and cTnI changes via blood samples taken from an
antecubital vein (5). Each participant’s blood was sampled 15 minutes before and three
hours after their participation in a marathon, 100 km run, or mountain bike marathon (5).
77 percent of athletes exceeded the upper reference limit (URL) of NT-proBNP post-
exercise (5). Athletes from all events demonstrated increases exceeding the URL of NT-
proBNP, with the largest increase shown in the 100-km runners (median increase of 200
ng/L) (5). Interestingly, the marathon runners exhibited a lower median increase (97

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ng/L) than the 100 km runners (5). Significant increases in CK and CK-MB were also
seen in all three events, with the largest increase again seen in the 100-km runners (5). 74
percent of subjects exhibited an increase in cTnI above the URL and 47 percent of
subjects exhibited an increase in cTnT above the URL (5).
While significant increases were seen for all cardiac biomarkers tested, there were
no correlations between CK, CK-MB, NT-proBNP, cTnT, and cTnI (5). However, a
correlation between NT-proBNP and exercise time was shown, representing a correlation
between NT-proBNP and exercise intensity (5). The results of this study conclude that
the exercise-induced increases in NT-proBNP, cTnT, and cTnI concentrations seem to be
independent and most likely have different underlying mechanisms (5). In summary, the
study demonstrates that, although biomarkers of cardiac damage in cardiovascular
patients, the previously stated exercise-induced increases are not necessarily indicative of
cardiac damage.
A follow-up study was done three months following the marathon, 100-km, and
mountain bike marathon events (6). In the second study, 21 of the 105 previously tested
athletes that had exhibited increased blood concentrations of cTnT and cTnI above the 99
percent upper reference values were retested through extensive cardiac examination (6).
The cardiac examination involved a blood analysis of cTnT, cTnI, NT-proBNP, CK, and
CK- MB (6). Resting blood pressure (BP) and ECG measurements were then taken for
each subject (6). Next, each subject participated in an exercise stress test on either a
treadmill or cycling ergometer with 6 precordial leads (6). All of the subjects achieved at
least 90 percent of their age-predicted max-HR values (6). All but one subject presented
no signs of persistent cardiac damage or cardiac abnormalities (6). The one subject that

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presented signs of cardiac damage had prior unknown coronary artery disease, unrelated
to the exercise activity (6). In summary, the two aforementioned studies suggest that, as
opposed to cardiovascular patients, exercise-induced elevations of cTnT and cTnI in
endurance athletes are not necessarily signs of irreversible myocardial injury or necrosis.
A more recent study attempted to identify correlations between BP and levels of
cardiac biomarkers in middle-aged marathon runners (3). The study tested 40 healthy
male marathon runners between the ages of 40 and 60 who had completed at least three
previous marathons (3). The subjects participated in an exercise stress test one week prior
to a marathon race using the Bruce protocol, 12-lead ECG, respiratory gas analyzer, an
automated BP, pulse oximeter, and treadmill (3). Resting HR and BP were measured
prior to the test (3). HR, BP, Rate of Perceived Exertion, Respiratory Exchange Ratio,
and oxygen consumption were recorded 1-minute prior to each step of the protocol (3). If
the subject qualified (no cardiovascular issues present during exercise stress test), blood
samples were collected from the subject 2 hours prior to and immediately following a
marathon race (3).
All subjects were healthy (no high BP, diabetes, CVD, or liver disorders), but all
exhibited exercise-induced high BP and cardiac biomarkers post-marathon (3). The
results of this study ultimately demonstrated no clear evidence that the exercise-induced
cardiac biomarkers were accompanied by myocardial injury (3). It did, however, indicate
that middle-aged marathon runners with potential ischemic CVD and excessive increases
in BP might experience increased myocardial ischemia due to increased oxygen demand,
which can then induce other cardiac events (3).

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Eijsvogels et al. conducted a study to research independent predictors of exercise-
induced cTnI elevation (7). Demographic data, health status, physical activity levels, and
marathon experience were obtained from 92 moderately to highly trained marathon
runners through an online questionnaire (7). Blood samples were taken from each subject
via antecubital vein pre- and post-marathon to record cTnI levels (7). Participants’ HR’s
were recorded via 2-channel ECG chest bands during the marathon event, allowing mean
HR to be determined (average HR between the start and finish of the race) (7). Each
participant was asked to report their fluid intake, use of analgesics, physical complaints,
and RPE throughout the marathon in a questionnaire given post-race (7).
The results demonstrated no statistical significance in previous marathon
experience, exercise intensity, and hydration status with cTnI levels (7). However, it did
produce statistical significance with lower age and longer duration of exercise as
independent predictors of cTnI elevation (7). Age of participants was inversely correlated
with cTnI elevation while longer exercise duration was directly proportional to cTnI
elevation (7). The results of this study imply that exercise-induced cTnI and cTnT are
more likely reflective of a physiological response than a pathological response, such as
myocardial damage (7).
A fifth research study observed the relationship of exercise-induced elevated cTnI
and BNP and cardiac dysfunction (9). 25 marathon runners who did not exhibit signs,
symptoms, or previous medical history of heart disease were tested (9). One to four
weeks prior to the marathon race, the subjects participated in an exercise-stress test using
the Bruce treadmill protocol and blood samples were taken to measure cTnI and BNP
levels (9). Blood samples and ECG measures were taken directly following the marathon

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race and blood samples were taken again 24 hours post-marathon (9). An advantage of
this study was the use of Cardiovascular Magnetic Resonance (CMR) imaging. CMR
imaging is superior to ECG in that it provides more fields of view and has excellent
spatial resolution (9). It also provides late gadolinium enhancement (LGE)
measurements, a tool used for scar detection and the diagnosis of cardiomyopathies (9).
Furthermore, CMR imaging capabilities allow for the most accurate measurement of the
right ventricle of the heart (9). CMR was performed on the subjects of this study pre- and
post-marathon (9).
As with other studies observed, the results demonstrated a significant rise in cTnI,
CK, CK-MB, and BNP immediately following the race (9). There were no ventricular
arrhythmias examined post-marathon and no signs or symptoms of MI or significant
exercise-induced arrhythmias observed during the exercise-stress testing (9). CMR
imaging results demonstrated that two-thirds of the subjects exhibited evidence of right
heart dysfunction with significant dilation of the right atria (RA) and right ventricle (RV),
along with hypokinesis of the RV immediately following the marathon with no
correlation to age, sex, cardiovascular fitness, or previous marathon experience (9).
However, there were no significant differences between the pre- and post-race CMR
measurements and there was no evidence of LGE to suggest MI or significant cardiac
arrhythmias (9). CMR imaging findings coincided with previous research, suggesting that
approximately one- third of marathon runners experience transient dilation of the RA,
RV, and a reduction in RV ejection fraction (9). The study suggested that those findings
are a result of increased preload and afterload, thus overworking the RV and making it
susceptible to extreme fatigue during a marathon race (9). Although changes in the right

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side of the heart were exhibited, they did not appear to cause ischemic injury (9). In
summary, the findings of this study further supported previous evidence that exercise-
induced changes in the heart during a marathon race do not always implicate myocardial
damage (9).
Further research still needs to be done to observe long-term effects of marathon
running and cardiovascular health; however, current research does not support marathon
training as a significant cardiovascular risk factor. Based on current research, the known
benefits of endurance exercise on cardiovascular health outweigh the risks associated
with marathon training. In fact, the annual risk of premature death is estimated to be 120
times higher during general living compared to the risk of running one marathon (3).
While benefits seem to outweigh risk, it is important to consider personal factors, such as
cardiovascular health history and physical activity level, before one begins training for a
marathon, as those factors contribute to risk of MI and other cardiac myopathies (1). In
conclusion, marathon running provides cardiovascular benefits and is not a significant
cardiovascular risk factor, so long as the runner makes safe decisions in regards to their
own health.

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Works Cited:
1.Kim YJ, Ahn JK, Shin KA, Kim CH, Lee YH, Park KM. Correlation of Cardiac
Markers and Biomarkers With Blood Pressure of Middle-Aged Marathon Runners. J Clin
Hypertens (Greenwich). 2015 Nov;17(11):868-73. doi: 10.1111/jch.12591. Epub 2015
Jun 13. PubMed PMID: 26073606.
2.Kim JH, Malhotra R, Chiampas G, d'Hemecourt P, Troyanos C, Cianca J, Smith RN,
Wang TJ, Roberts WO, Thompson PD, Baggish AL; Race Associated Cardiac Arrest
Event Registry (RACER) Study Group. Cardiac arrest during long-distance running
races. N Engl J Med. 2012 Jan 12;366(2):130-40. doi: 10.1056/NEJMoa1106468.
PubMed PMID: 22236223.
3. Day SM, Thompson PD. Cardiac risks associated with marathon running. Sports
Health. 2010 Jul;2(4):301-6. PubMed PMID: 23015951; PubMed Central PMCID:
PMC3445091.
4. Scharhag J, George K, Shave R, Urhausen A, Kindermann W. Exercise-associated
increases in cardiac biomarkers. Med Sci Sports Exerc. 2008 Aug;40(8):1408-15. doi:
10.1249/MSS.0b013e318172cf22. PubMed PMID: 18614952.
5. Scharhag J, Herrmann M, Urhausen A, Haschke M, Herrmann W, Kindermann W.
Independent elevations of N-terminal pro-brain natriuretic peptide and cardiac troponins
in endurance athletes after prolonged strenuous exercise. Am Heart J. 2005
Dec;150(6):1128-34. PubMed PMID: 16338248.
6. Urhausen A, Scharhag J, Herrmann M, Kindermann W. Clinical significance of
increased cardiac troponins T and I in participants of ultra-endurance events. Am J
Cardiol. 2004 Sep 1;94(5):696-8. PubMed PMID: 15342317.
7. Cummins P, Young A, Auckland ML, Michie CA, Stone PC, Shepstone BJ.
Comparison of serum cardiac specific troponin-I with creatine kinase, creatine kinase-
MB isoenzyme, tropomyosin, myoglobin and C-reactive protein release in marathon
runners: cardiac or skeletal muscle trauma? Eur J Clin Invest. 1987 Aug;17(4):317-24.
PubMed PMID: 3117569.
8. Running USA 2014 Statistics. http://www.runningusa.org/marathon-report-
2015?returnTo=annual-reports
9. Trivax JE, Franklin BA, Goldstein JA, Chinnaiyan KM, Gallagher MJ, deJong AT,
Colar JM, Haines DE, McCullough PA. Acute cardiac effects of marathon running. J
Appl Physiol (1985). 2010 May;108(5):1148-53. doi: 10.1152/japplphysiol.01151.2009.
Epub 2010 Feb 11. PubMed PMID: 20150567.