ORIGINAL RESEARCH
published: 31 January 2020
doi: 10.3389/fphys.2020.00030
Edited by:
Hassane Zouhal,
University of Rennes 2, France
Reviewed by:
Ajmol Ali,
Massey University, New Zealand
Martin Burtscher,
University of Innsbruck, Austria
*Correspondence:
Yifan Lu
luyifan@bsu.edu.cn
Specialty section:
This article was submitted to
Exercise Physiology,
a section of the journal
Frontiers in Physiology
Received: 23 October 2019
Accepted: 15 January 2020
Published: 31 January 2020
Citation:
Li F, Nie J, Zhang H, Fu F, Yi L,
Hopkins W, Liu Y and Lu Y (2020)
Effects of Matched Intermittent
and Continuous Exercise on Changes
of Cardiac Biomarkers in Endurance
Runners. Front. Physiol. 11:30.
doi: 10.3389/fphys.2020.00030
Effects of Matched Intermittent and
Continuous Exercise on Changes of
Cardiac Biomarkers in Endurance
Runners
Feifei Li1,2, Jinlei Nie3, Haifeng Zhang1,4, Frank Fu5, Longyan Yi6, Will Hopkins7,
Yang Liu1,4 and Yifan Lu2*
1 College of Physical Education, Hebei Normal University, Shijiazhuang, China, 2 College of Sports Medicine
and Rehabilitation, Beijing Sport University, Beijing, China, 3 School of Health Sciences and Sports, Macao Polytechnic
Institute, Macao, China, 4 Provincial Key Lab of Measurement and Evaluation in Human Movement and Bio-information,
Hebei Normal University, Shijiazhuang, China, 5 Dr Stephen Hui Research Centre for Physical Recreation and Wellness,
Hong Kong Baptist University, Hong Kong, China, 6 Institute of Sport and Health Sciences, Beijing Sport University, Beijing,
China, 7 College of Sport and Exercise Science, Victoria University, Melbourne, VIC, Australia
Purpose: Endurance runners training with high-intensity intermittent exercise might
experience damage to cardiac muscle. We have therefore compared changes of cardiac
biomarkers after workload-matched intermittent and continuous exercise.
Methods: Twelve endurance runners [11 males, 1 female; means ± SD ˙VO2max,
62.4 ± 5.4 ml kg−1 min−1; velocity of ˙VO2max (v ˙VO2max), 17.1 ± 1.4 km h−1] completed
an intermittent and continuous exercise trial in random order. Intermittent exercise
consisted of running at 90% v˙VO2max for 2 min followed by 50% v˙VO2max for 2 min,
repeated for 92 min. Continuous exercise was performed at 70% v˙VO2max for 92 min.
Blood samples were drawn before and 0, 2, 4, 24, and 48 h after exercise for assay
of various cardiac biomarkers. Changes in concentration of biomarkers were averaged
for the comparison of intermittent with continuous exercise after adjustment for baseline
concentration and exercise intensity expressed as percent of heart-rate reserve (%HRR);
magnitudes were assessed by standardization.
Results: There were moderate and large increases in high-sensitivity cardiac troponin-I
and -T respectively following exercise. The differences between the increases adjusted
to the mean intensity of 78 %HRR were trivial, but at 85 %HRR the increases for cardiac
troponin-I and -T were moderately higher for intermittent compared with continuous
exercise (factor difference, ×/÷90% conﬁdence limits: 3.4, ×/÷1.9 and 2.1, ×/÷1.8
respectively). Differences in the changes in other cardiac biomarkers were trivial.
Conclusion: Prolonged intermittent exercise is potentially more damaging to cardiac
muscle than continuous exercise of the same average running speed at higher average
heart rates in endurance runners.
Keywords: high-intensity intermittent exercise, intensity, biomarkers, cardiac troponin, marathon runners
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Exercise-Induced Cardiac Biomarkers Elevation
INTRODUCTION
There is increasing evidence that an acute bout of intense
exercise can induce a minor and temporary elevation of cardiac-
speciﬁc biomarkers, including various kinds of cardiac troponin,
markers diagnostic of myocardial infarction (Thygesen et al.,
2012; Eijsvogels et al., 2016). The elevation of cardiac troponin
is aﬀected by exercise intensity (Fu et al., 2009), exercise duration
(Eijsvogels et al., 2010), baseline level (Legaz-Arrese et al., 2011),
training experience of the participants and age (Tian et al., 2012),
gender (Kong et al., 2017), cardiovascular risk factors (Vilela
et al., 2014), and environment (Li et al., 2016a). A transient
increase in myocardial membrane permeability appears to be
responsible, but the mechanism is still under debate (Nie et al.,
2010, 2016; Li et al., 2016b). Eijsvogels et al. (2016) concluded that
exercise intensity was the strongest single predictor of exercise-
induced cardiac troponin elevation, and Richardson et al. (2018)
found that cardiac troponin was associated with both mean and
peak heart rate during exercise. Gresslien and Agewall (2016)
hypothesized that there might be a threshold exercise intensity
where cardiac troponin release became more marked.
Athletes experience transiently high intensities of exercise
when they perform interval training to enhance performance but
the impact of such exercise on the heart in comparison with
continuous exercise is unclear (Billat, 2001; George et al., 2012;
Tschakert and Hofmann, 2013). Continuous exercise resulted
in a greater cardiac troponin concentration than intermittent
in sedentary men in a study by Ranjbar et al. (2017) whereas
Nie et al. (2018) reported no diﬀerence between the eﬀects
of intermittent and continuous exercise on cardiac troponin
changes in sedentary women. In two studies of endurance
athletes, intermittent running produced greater increases in
cardiac troponin than continuous running, but the exercise
intensity and duration were not carefully manipulated and
matched (Stewart et al., 2016; Weippert et al., 2016). Other
markers of cardiac muscle damage, including N-terminal pro
brain natriuretic peptide (NT-pro-BNP) could also provide
information on the relative eﬀects of intermittent and continuous
exercise (Scherr et al., 2011). The purpose of this study was
therefore to compare the changes of cardiac biomarkers after
workload-matched high-intensity intermittent and continuous
exercise on experienced endurance runners. It was hypothesized
that prolonged intermittent exercise potentially induced more
perturbations of cardiac biomarkers in endurance runners.
MATERIALS AND METHODS
Participants
After approval of this study by the local Ethical Committee, 12
(11 males and 1 female) endurance runners [means ± standard
deviation (SD): age, 23.5 ± 5.5 years; body mass, 63.3 ± 3.9 kg;
height, 170.5 ± 5.5 cm; %body fat, 12.6 ± 3.9%; ˙VO2max,
62.4 ± 5.4 ml kg−1 min−1; velocity of ˙VO2max (v ˙VO2max),
17.1 ± 1.4 km h−1; peak heart rate, 192 ± 9 min−1] were
recruited from the Department of Physical Education at a local
university. They had no history of disease or cardiac symptoms,
none were smokers, none were vegetarians or had any special
dietary habits and none had taken any drugs or antioxidant
supplements in the month before the study. Training history
(5.4 ± 3.4 years), training volume (44 ± 25 km week−1), and
personal best time in a recent marathon race (186 ± 16 min)
were self-reported. An initial medical screening and examination
were performed by a team of medical doctors and technicians.
All of the participants had normal resting blood pressures
and electrocardiographic results. All participants provided their
written consent and were fully informed about the purposes,
procedures, and potential cardiovascular risks of this study. The
study took place in the local sports science research center
between October and December in the afternoon. Conditions
were similar for each test, with small variations in temperature
(20.7 ± 2.3◦C), humidity (49 ± 13%). All of the participants
refrained from intense exercise and alcohol 48 h before
and after each trial and were allowed to ingest pure water
freely during tests.
Study Design
The design was a randomized-order crossover. On their ﬁrst visit
to the laboratory, the runners performed a test for estimation of
˙VO2max and corresponding v ˙VO2max. On two subsequent visits,
the runners completed either intermittent or continuous exercise.
The order in which each participant completed the two trials was
selected at random and separated by at least 7 days, during which
they trained normally. Blood samples were drawn pre-exercise
(−1.5 h), immediately post-exercise (0 h), and at four later time
points (2, 4, 24, and 48 h) for measurement of biomarkers.
Determination of the ˙VO2max and v˙VO2max
A treadmill (H/p/cosmos Pulsar 4.0, H/p/cosmos Sports and
Medical gmbh, Nussdorf-Traunstein, Germany) with a 2% slope
was used in the determination of ˙VO2max (Max-1, Physio-Dyne
Instrument, NY, United States) and in the exercise trials. After a
general 5- to 10-min warm-up with self-set speed, the participants
ran at an initial speed of 12 km h−1, which was increased by
1 km h−1 every 3 min without any pause between stages. When
the respiratory exchange ratio reached 1.00, the stages were
shortened to 2 min. The test stopped either when the increase
in oxygen consumption ( ˙VO2) was less than 2.1 ml kg−1 min−1
while the respiratory exchange ratio was greater than or equal
to 1.15, or when exhaustion was reached. ˙VO2max was recorded
as the highest 30-s average value of the recorded ˙VO2. The
corresponding v ˙VO2max was recorded at the minimal speed at
which ˙VO2max was reached, as long as this speed was sustained
for at least 1 min.
Exercise Trials
Each participant completed a 1000-m warm-up at their own pace
prior to each trial. In the intermittent trial, each bout consisted
of a hard run of 90% v ˙VO2max for 2 min, followed by an easy
run of 50% v ˙VO2max for 2 min, 23 bouts and 92 min in total. In
the continuous trial, participants ran at 70% v ˙VO2max for 92 min.
Running velocities for intermittent trial were 15.4 ± 1.3 and
8.4 ± 0.8 km h−1, hard and easy rung respectively; for continuous
trial was 12.0 ± 0.9 km h−1.
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Exercise-Induced Cardiac Biomarkers Elevation
Measurements
Heart rate (S810, Polar, Finland) were recorded every 2 min
during each exercise trial. Rating of perceived exertion on Borg’s
scale (Borg, 1982) was recorded at 30, 32, 58, 60, 90, and 92 min
during each trial. Venous blood samples of 5 ml were dropped
from the antecubital vein by venous punctures, clotted at room
temperature and centrifuged at 3000 × g for 15 min. The
separated serum was then drawn and stored at −80◦C for further
analysis. These laboratory methods are the standard methods
used by the local Hospital Clinical Chemistry Laboratory and
have been validated.
The high-sensitivity cardiac troponin-I was analyzed using a
commercially available high-sensitive immunochemistry STAT
assay from Abbott Diagnostics on an Architect i2000SR (Abbott
Diagnostics, Chicago, IL, United States) with the detection
limit of 1.6 pg ml−1 and 99th percentile of the assay was
26 pg ml−1. The high-sensitivity cardiac troponin-T analysis
method was based on the new electrochemiluminescence
technology and using Elecsys 2010 automated batch analysers
(Roche Diagnostics, Mannheim, Germany). The measurement
range was 3–1000 pg ml−1. The 99th percentile cutoﬀ
concentration was 14 pg ml−1. NT-pro-BNP was determined
by an Elecsys pro-BNP ECLIA on the Modular Analytics E170
analyzer (Roche Diagnostic, Mannheim, Germany) with the
analytical range 5–35,000 pg ml−1. The corresponding upper
reference limit was 125 pg ml−1. C-reactive protein (CRP)
was measured by immunoturbidometric assay from Sekisui
Diagnostics (Tokyo, Japan) on an AU2700 analyzer (Olympus
Germany, Beckman Coulter, Krefeld, Germany). The cutoﬀ point
was set as 3 mg L−1. Serum creatine kinase-MB (CK-MB) and
creatine kinase (CK) were detected by DC800 analyzer (Beckman
Coulter, Krefeld, Germany) using commercial kit according to
electrochemiluminescence technology with cutoﬀ values 25 and
195 U L−1, respectively.
Statistical Analysis
Raw data were presented as means mean ± SD unless otherwise
stated. All variables were log-transformed for analysis then
back-transformed to express eﬀects as factors, after adjustment
for the modifying eﬀects of the pre-exercise concentration
and either exercise intensity expressed as percent of heart-
rate reserve (%HRR) or training volume, using a spreadsheet
(Hopkins, 2017). Changes between the two modes of exercise
were compared for the average of post-exercise 0, 1, 4, and 24 h
for all biomarkers except for CRP, which was the average of
24 and 48 h. In the absence of thresholds for acute changes in
cardiac biomarkers associated with substantial increased risk of
morbidity or mortality in endurance athletes, the magnitudes of
the changes were assessed using threshold standardized changes
of 0.20, 0.60, 1.20, 2.0, and 4.0 for small, moderate, large, very
large, and extremely large, respectively (Hopkins et al., 2009;
Hopkins, 2019a).
Uncertainty in the estimates of eﬀects are presented as
90% compatibility limits. Probabilistic decisions about true
(large-sample) magnitudes accounting for the uncertainty were
based on one-sided hypothesis tests of substantial (at least
small) eﬀects followed by Bayesian inference. The p-value for
rejecting an hypothesis of a substantial eﬀect magnitude of
a given sign was the area of the sampling distribution of
the eﬀect with substantial values of that sign (Lakens et al.,
2018), evaluated via log transformation. Eﬀects were considered
decisive with a p-value threshold of <0.05. If an hypothesis
of a substantial magnitude of a given sign was rejected, the
p-value for the hypothesis of the other sign was interpreted as
evidence for that hypothesis, since the p-value corresponds to
the posterior probability of the magnitude of the true eﬀect
in a reference Bayesian analysis with a minimally informative
prior (Hopkins and Batterham, 2016; Hopkins, 2019b). This
p-value is reported qualitatively using the following scale:
0.25–0.75, possibly; 0.75–0.95, likely; 0.95–0.995, very likely;
>0.995, most likely (Hopkins et al., 2009). If neither hypothesis
was rejected, the magnitude of the eﬀect was considered to be
unclear, and the magnitude of the eﬀect is shown without a
probabilistic qualiﬁer.
RESULTS
No runners reported any cardiac symptoms during or after
the exercises. Heart rate during the intermittent trial was
160 ± 12 min−1 (176 ± 12 min−1 for the hard running and
145 ± 13 min−1 for the easy running); during the continuous trial
heart rate was 162 ± 11 min−1. The intensities were 78 ± 6 and
79 ± 5 %HRR for intermittent and continuous trials, respectively,
or 83 ± 4 and 84 ± 4 %peak heart rate. Rating of perceived
exertion during intermittent and continuous trials was 14 ± 3
and 12 ± 3, respectively. Values for pre-exercise concentration of
biomarkers are shown in Table 1, and values for high-sensitivity
cardiac troponin-I pre- and post-exercise are shown in Figure 1.
The baseline level of high-sensitivity cardiac troponin-I in three
runners exceeded the upper reference limit of 26 pg ml−1,
and after intermittent and continuous exercises this limit was
exceeded by 11 and 10 runners, respectively.
The mean and factor SD for the individual averaged changes in
concentrations of biomarkers for the intermittent and continuous
trials are presented in Table 2. These changes were large for
high-sensitivity cardiac troponin-T, moderate for high-sensitivity
TABLE 1 | The pre-exercise concentrations of biomarkers.
Raw
Back-trans.
(mean ± SD)
(mean ×/÷ SD)
High-sensitivity cardiac troponin I
(hs-cTnI, pg ml−1)
70 ± 180
8.6 ×/÷ 6.2
High-sensitivity cardiac troponin T
(hs-cTnT, pg ml−1)
8 ± 10
5.3 ×/÷ 2.0
N-terminal pro brain natriuretic peptide
(NT-pro-BNP, pg ml−1)
28 ± 26
18 ×/÷ 2.6
C-reactive protein (CRP, mg L−1)
1.1 ± 1.1
0.7 ×/÷ 2.9
Creatine kinase-MB (CK-MB, U L−1)
3.9 ± 2.8
3.3 ×/÷ 1.8
Creatine kinase (CK, U L−1)
350 ± 250
289 ×/÷ 1.9
Back-trans.:
back-transformed
mean
and
factor
SD
of
the
log-transformed concentrations.
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Exercise-Induced Cardiac Biomarkers Elevation
FIGURE 1 | Back-transformed means of log-transformed concentrations of
high-sensitivity cardiac troponin I (hs-cTnI) 1.5 h before and 0–48 h after
continuous and intermittent exercise. Error bars are standard deviations.
cardiac troponin-I and CK-MB, and small for NT-Pro-BNP,
CRP, and CK. The individual changes following intermittent and
continuous exercise, with regression lines showing prediction by
baseline concentration, training volume and exercise intensity,
are shown in Figure 2 for one of the biomarkers, high-
sensitivity cardiac troponin-I. The ﬁgure shows apparently
similar modifying eﬀects of baseline concentration and training
volume on high-sensitivity cardiac troponin-I, but a marked
diﬀerence in the modifying eﬀect of exercise intensity.
Comparisons of the changes in high-sensitivity cardiac
troponin-I and in the other biomarkers adjusted to the mean
values of the modiﬁers and to approximately 1 SD above the
mean values are shown in Table 2. In summary, there were
trivial diﬀerences between the two modes of exercise at the mean
values of the modiﬁers, although the diﬀerences were not clear
for some measures (high-sensitivity cardiac troponin-T, CK-MB,
CK). Eﬀects of 1 SD of baseline concentration of the marker
and of training volume had at most small observed eﬀects,
and true values for the clear eﬀects were at most only possibly
substantial. However, intensity approximately 1 SD above the
mean of heart-rate reserve (85 %HRR) had clear moderate
eﬀects on high-sensitivity cardiac troponin-I and -T, with high
likelihoods that the true change with intermittent was greater
than that with continuous exercise. With the other biomarkers
only CRP showed a clear diﬀerence at 85 %HRR (a small,
possibly substantial increase with intermittent compared with
continuous), eﬀects on the other biomarkers being trivial or
small and unclear.
DISCUSSION
To our knowledge, this is the ﬁrst study to explore the eﬀect
of intermittent exercise on cardiac biomarker concentrations by
comparing workload-matched continuous exercise in endurance
runners. Our novel ﬁndings suggest that there was little diﬀerence
in the eﬀect of exercise mode on cardiac-troponin elevation
at typical training intensity, but for runners exercising at
higher relative heart rates, prolonged intermittent exercise is
potentially more damaging to cardiac muscle than comparable
continuous exercise.
Referring to the mean values of high sensitivity cardiac
troponin-I in Figure 1 and Table 1, there was a similar eﬀect
of two forms of exercise. Of course, as markers for diagnosis of
acute myocardial injury in clinical settings, the actual magnitude
of individual cardiac troponin level itself should be considered.
The peak level of high-sensitivity cardiac troponin-I exceeded
the upper reference limit of 26 pg ml−1 in most runners after
both forms of exercise. Others have noted that cardiac troponin
TABLE 2 | Changes in concentration of biomarkers following continuous and intermittent exercise, with magnitude-based decisions for the comparison of the changes
adjusted to mean values of potential modiﬁers and to 1 SD above baseline concentration, to approximately 1 SD above mean Tvol (67 km week−1), and to
approximately 1 SD above mean exercise intensity (85% HRR).
Factor change scoresa
Effect for intermittent/continuousb
(mean ×/÷ SD)
(mean, ×/÷90CL) and magnitude-based decisionc
Continuous
Intermittent
At mean valuesd
At baseline + 1 SDd
At 67 km week−1
At 85 %HRR
hs-cTnI
4.4 ×/÷ 2.4
4.4 ×/÷ 1.8
1.0, ×/÷1.4 trivial, ↔00
1.7, ×/÷1.7 small, ↑*
1.8, ×/÷2.0 small,↑*
3.4, ×/÷1.9 moderate,↑***
hs-cTnT
3.0 ×/÷ 2.1
3.2 ×/÷ 1.4
1.0, ×/÷1.4 trivial
1.1, ×/÷1.7 trivial, ↔0 ↑*
1.3, ×/÷1.6 trivial, ↔0 ↑*
2.1, ×/÷1.8 moderate,↑**
NT-pro-BNP
1.8 ×/÷ 1.3
1.7 ×/÷ 1.2
1.0, ×/÷1.2 trivial, ↔00
1.1, ×/÷1.3 trivial, ↔0 ↑*
0.9, ×/÷1.4 trivial
1.1, ×/÷1.4 trivial
CRP
1.3 ×/÷ 1.7
1.6 ×/÷ 1.4
1.2, ×/÷1.3 trivial, ↔0 ↑*
1.1, ×/÷1.4 trivial, ↔0 ↑*
1.1, ×/÷1.3 trivial, ↔00
1.3, ×/÷1.4 small, ↑*
CK-MB
1.6 ×/÷ 1.5
1.7 ×/÷ 1.6
1.1, ×/÷1.5 trivial
1.0, ×/÷1.9 trivial
1.0, ×/÷2.0 trivial
1.0, ×/÷1.9 trivial
CK
1.4 ×/÷ 1.4
1.5 ×/÷ 1.5
1.0, ×/÷1.4 trivial
1.2, ×/÷1.6 small, ↑
1.0, ×/÷1.5 trivial
1.1, ×/÷1.7 small, ↑
SD, standard deviation; 90CL, 90% conﬁdence limits as factors; Tvol, training volume, km week−1; %HRR, percent of heart-rate reserve; hs-cTnI, high-sensitivity cardiac
troponin I, pg ml−1; hs-cTnT, high-sensitivity cardiac troponin T, pg ml−1; NT-pro-BNP, N-terminal pro brain natriuretic peptide, pg ml−1; CRP, C-reactive protein, mg L−1;
CK-MB, creatine kinase-MB, U L−1; CK, creatine kinase, U L−1. aChanges, adjusted to overall mean values of baseline concentration and intensity, are for the mean
of 0, 1, 4, and 24 h post-exercise, except for CRP, which is the change for the mean of 24 and 48 h post-exercise. bAll effects are adjusted for baseline concentration.
cThe qualitative magnitude shown is derived by standardization for the observed effect. For clear effects, likelihood of a true substantial increase (↑) is indicated as
*possible; **likely; ***very likely. Likelihood of a true trivial change (↔) is indicated as follows: 0possible; 00likely. dMeans and SD are shown in Table 1. These effects are
adjusted for intensity.
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FIGURE 2 | Individual factor changes of high-sensitivity cardiac troponin-I (hs-cTnI) averaged over 0–24 h following intermittent and continuous exercise, with
regression lines showing prediction by baseline concentration, training volume and exercise intensity. Horizontal dotted lines indicate no change in concentration;
vertical dotted lines indicate mean values of the predictors.
often exceeds the upper reference limit following exercise (Vilela
et al., 2014; Gresslien and Agewall, 2016). Although strongly
needed, there are no agreed thresholds for acute changes in
cardiac troponin associated with substantial increased risk of
morbidity or mortality in athletes, as the clinical relevance of
exercise-induced cardiac troponin is still under debate (Skadberg
et al., 2017; Nie, 2018). It has been argued previously that cardiac
troponin is not randomly elevated after vigorous exercise but
increases in certain “susceptible” individuals (Nie et al., 2011;
Tian et al., 2014; Legaz-Arrese et al., 2015). We discuss below
the extent to which resting concentration of cardiac troponin
and level of training are two characteristics that modify release
of cardiac troponin following exercise in our study.
Our ﬁndings for the eﬀect of intensity of intermittent
exercise are consistent with other studies, reviewed in the
Introduction, showing greater elevation of cardiac biomarkers
with higher intensity
exercise.
In
particular,
it obtained
pronounced high-sensitivity cardiac troponin-T elevation after
intermittent exercise with average heart rate of 160 min−1, which
was similar to the mean heart rate of our runners (Richardson
et al., 2018). Stewart et al. (2016) suggested that a heart rate
of 145 min−1 was a threshold for the elevation of cardiac
troponin. Gresslien and Agewall (2016) and Nie et al. (2018)
also presented evidence for a threshold exercise intensity. With
the prolonged exercise of trained runners in our study, there is
evidence of a threshold heart rate for intermittent exercise, but
not for continuous exercise (Figure 2, right-hand scatterplot).
The greater increase in cardiac troponin concentrations with
intermittent compared with continuous exercise at high relative
intensities is obviously due to the higher peak heart rates
during the on-phase of each interval; the lower heart rates
during the oﬀ-phase do not compensate for the on-phase for
high relative intensities, but they more than compensate for
low relative intensities, on average. Clearly, however, there are
individual diﬀerences in the response to both types of exercise
that are not explained by relative exercise intensity across the
range of intensities.
As shown in Figure 2, the baseline level of cardiac troponin
and training volume can explain some of the individual
diﬀerences in response to the intermittent and continuous
exercise. The three participants with the highest baseline
concentrations of cardiac troponin-I experienced absolutely no
increase with either form of exercise, so any cardiac pathology
represented by the concentration of this marker is apparently not
exacerbated by exercise in these participants. In the analysis that
included all participants with adjustment for intensity, there was
only a small or trivial mean increase with intermittent compared
with continuous exercise at high baseline concentrations of
either form of cardiac troponin, and the true increases were
only possibly substantial. We therefore do not consider that
intermittent exercise is a concern for runners with high baseline
values of cardiac troponin, at least with this sample: if anything,
baseline concentration had a protective eﬀect for exercise-
induced increases. There was a similar protective eﬀect for
training volume, again with only a possibly small relative mean
increase for intermittent compared with continuous exercise for
participants with high training volumes.
We found small increases in NT-pro-BNP after both forms
of exercise, with little diﬀerence between two exercise modes.
NT-pro-BNP is a marker of cardiac stress elicited from volume
or pressure overload in clinical settings of myocardial injury
(Kociol et al., 2010). The magnitude of increase in NT-pro-BNP
is primarily dependent on exercise duration as well as basal
concentration, but not exercise intensity (Scharhag et al., 2008;
Legaz-Arrese et al., 2011; Serrano-Ostariz et al., 2011). There
seems a “ceiling eﬀect” that NT-pro-BNP is maximized at a low
exercise intensity so that further increase requires accumulation
over time (Legaz-Arrese et al., 2011). We also observed small
increases in CRP after intermittent and continuous exercise and
possible small eﬀect of exercise mode at 85 %HRR. CRP and
other inﬂammatory markers have been reported to increase 24–
74 h after endurance exercise (Scherr et al., 2011). Stewart et al.
(2016) also observed CRP increased to a greater extent with
intermittent exercise accompanying cardiac troponin elevations.
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Although this marker is not cardiac-speciﬁc, inﬂammatory
cytokines related to cardiac injury have been reported to aﬀect the
release of cardiac troponin after exercise (La Gerche et al., 2015).
Inﬂammation may therefore have contributed to the exercise-
induced cardiac troponin elevation via a transient increase in
myocardial membrane permeability. Further research is needed
to address this issue.
LIMITATIONS AND PERSPECTIVE
The unclear comparisons of exercise mode and some of the
unclear moderating eﬀects for the markers other than cardiac
troponin need resolving with a larger sample size, which
would also improve the precision of the estimates of the eﬀect
with cardiac troponin. Other factors that may contribute to
the individual variation of exercise-induced cardiac troponin
elevation have not been veriﬁed for the small sample size.
Competing at similar intensity, younger age predicts cardiac
troponin elevation among endurance runners (Eijsvogels et al.,
2015). Sex eﬀect may also inﬂuence the individual variation as
one female runner was included in the present study. Exercise-
induced cardiac troponin elevation occurred in both male
and female runners, lower in female (Kong et al., 2017), but
not exactly the case in a meta-analysis (Shave et al., 2007).
Furthermore, core temperature, diet and ﬂuid intake, which may
have impact on the performance of endurance runners were not
monitored between the two trial.
Cardiac troponin, a biomarker to diagnosis acute myocardial
infarction is moderately to largely increased after typical long
hard training in endurance runners. Some runners training with
high-intensity intermittent exercise for improved performance
may be at increased risk of cardiac stress. Baseline concentration
of cardiac biomarkers and training volume have protective eﬀects
for cardiac stress of endurance runners participating with high
training volumes. Training can be a potentially precondition to
better cardiomyocyte tolerance to intense exercise.
CONCLUSION
Intermittent and continuous exercise at similar mean heart rates
have similar mean eﬀects on elevation of cardiac troponins in
marathon runners performing long hard training. Elevation of
cardiac troponins is greater at higher intensities and less at lower
intensities with intermittent but not continuous exercise. Baseline
level of cardiac troponin and training volume can explain some
of the individual diﬀerences in response to intermittent and
continuous exercise.
DATA AVAILABILITY STATEMENT
All datasets generated for this study are included in the
article/supplementary material.
ETHICS STATEMENT
The studies involving human participants were reviewed and
approved by the Beijing Sport University (BSUIRB, 2019003H).
The patients/participants provided their written informed
consent to participate in this study.
AUTHOR CONTRIBUTIONS
FL, JN, HZ, FF, LY, and YLu conceived and designed the study. FL,
LY, WH, YLi, and YLu performed the experiments and analyzed
the data. All authors drafted the manuscript.
FUNDING
Financial support was from a research grant received from the
Hebei Normal University (No. L062018B14) and Fundamental
Research
Funds
for
the
Central
Universities
of
China
(No. 2018GJ018).
ACKNOWLEDGMENTS
We acknowledge the Institute of Sport and Health Sciences and
the Key Laboratory of Exercise Stress and Adaptation of Beijing
Sport University for the data collection.
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Conﬂict of Interest: The authors declare that the research was conducted in the
absence of any commercial or ﬁnancial relationships that could be construed as a
potential conﬂict of interest.
The handling Editor and reviewer AA declared their involvement as co-editors in
the Research Topic, and conﬁrm the absence of any other collaboration.
Copyright © 2020 Li, Nie, Zhang, Fu, Yi, Hopkins, Liu and Lu. This is an open-access
article distributed under the terms of the Creative Commons Attribution License
(CC BY). The use, distribution or reproduction in other forums is permitted, provided
the original author(s) and the copyright owner(s) are credited and that the original
publication in this journal is cited, in accordance with accepted academic practice. No
use, distribution or reproduction is permitted which does not comply with these terms.
Frontiers in Physiology | www.frontiersin.org
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Effects of Matched Intermittent and Continuous Exercise on Changes of Cardiac Biomarkers in Endurance Runners.
Li, Feifei,Nie, Jinlei,Zhang, Haifeng,Fu, Frank,Yi, Longyan,Hopkins, Will,Liu, Yang,Lu, Yifan