Blood Pressure Response and Pulse Arrival Time During Exercise Testing in Well-Trained Individuals

Abstract

Introduction: There is a lack of data describing the blood pressure response (BPR) in well-trained individuals. In addition, continuous bio-signal measurements are increasingly investigated to overcome the limitations of intermittent cuff-based BP measurements during exercise testing. Thus, the present study aimed to assess the BPR in well-trained individuals during a cycle ergometer test with a particular focus on the systolic BP (SBP) and to investigate pulse arrival time (PAT) as a continuous surrogate for SBP during exercise testing.
Materials and Methods: Eighteen well-trained male cyclists were included (32.4 ± 9.4 years; maximal oxygen uptake 63 ± 10 ml/min/kg) and performed a stepwise lactate threshold test with 5-minute stages, followed by a continuous test to voluntary exhaustion with 1-min increments when cycling on an ergometer. BP was measured with a standard automated exercise BP cuff. PAT was measured continuously with a non-invasive physiological measurements device (IsenseU) and metabolic consumption was measured continuously during both tests.
Results: At lactate threshold (281 ± 56 W) and maximal intensity test (403 ± 61 W), SBP increased from resting values of 136 ± 9 mmHg to maximal values of 219 ± 21 mmHg and 231 ± 18 mmHg, respectively. Linear within-participant regression lines between PAT and SBP showed a mean r ² of 0.81 ± 17.
Conclusion: In the present study focusing on the BPR in well-trained individuals, we observed a more exaggerated systolic BPR than in comparable recent studies. Future research should follow up on these findings to clarify the clinical implications of the high BPR in well-trained individuals. In addition, PAT showed strong intra-individual associations, indicating potential use as a surrogate SBP measurement during exercise testing.

Full text

Blood Pressure Response and Pulse
Arrival Time During Exercise Testing in
Well-Trained Individuals
Sondre Heimark
1
,
2
*
†
, Ingrid Eitzen
3
†
, Isabella Vianello
3
,
4
, Kasper G. Bøtker-Rasmussen
3
,
Asgeir Mamen
5
, Ole Marius Hoel Rindal
3
, Bård Waldum-Grevbo
1
, Øyvind Sandbakk
6
and
Trine M. Seeberg
3
1
Department of Nephrology, Oslo University Hospital, Oslo, Norway,
2
Institute of Clinical Medicine, University of Oslo, Oslo,
Norway,
3
Department of Smart Sensors and Microsystems, SINTEF Digital, Oslo, Norway,
4
Department of Health Science and
Technology, Aalborg University, Aalborg, Denmark,
5
Kristiania University College, School of Health Sciences, Oslo, Norway,
6
Centre for Elite Sports Research, Department of Neuromedicine and Movement Science, Norwegian University of Science and
Technology, Trondheim, Norway
Introduction: There is a lack of data describing the blood pressure response (BPR) in well-
trained individuals. In addition, continuous bio-signal measurements are increasingly
investigated to overcome the limitations of intermittent cuff-based BP measurements
during exercise testing. Thus, the present study aimed to assess the BPR in well-trained
individuals during a cycle ergometer test with a particular focus on the systolic BP (SBP)
and to investigate pulse arrival time (PAT) as a continuous surrogate for SBP during
exercise testing.
Materials and Methods: Eighteen well-trained male cyclists were included (32.4 ±
9.4 years; maximal oxygen uptake 63 ± 10 ml/min/kg) and performed a stepwise
lactate threshold test with 5-minute stages, followed by a continuous test to voluntary
exhaustion with 1-min increments when cycling on an ergometer. BP was measured with a
standard automated exercise BP cuff. PAT was measured continuously with a non-
invasive physiological measurements device (IsenseU) and metabolic consumption was
measured continuously during both tests.
Results: At lactate threshold (281 ± 56 W) and maximal intensity test (403 ± 61 W), SBP
increased from resting values of 136 ± 9 mmHg to maximal values of 219 ± 21 mmHg and
231 ± 18 mmHg, respectively. Linear within-participant regression lines between PAT and
SBP showed a mean r
2
of 0.81 ± 17.
Conclusion: In the present study focusing on the BPR in well-trained individuals, we
observed a more exaggerated systolic BPR than in comparable recent studies. Future
research should follow up on these findings to clarify the clinical implications of the high
BPR in well-trained individuals. In addition, PAT showed strong intra-individual
associations, indicating potential use as a surrogate SBP measurement during exercise
testing.
Keywords: blood pressure response, continuous cuff-less measurement method, diastolic blood pressure (DBP),
endurance athletes, pulse arrival time (PAT), systolic blood pressure (SBP)
Edited by:
Martin Burtscher,
University of Innsbruck, Austria
Reviewed by:
Laurent Mourot,
Université Bourgogne Franche-
Comté, France
Isabella Tan,
Macquarie University, Australia
*Correspondence:
Sondre Heimark
sondhe@ous-hf.no
†
These authors share first authorship
Specialty section:
This article was submitted to
Exercise Physiology,
a section of the journal
Frontiers in Physiology
Received: 27 January 2022
Accepted: 08 June 2022
Published: 11 July 2022
Citation:
Heimark S, Eitzen I, Vianello I,
Bøtker-Rasmussen KG, Mamen A,
Hoel Rindal OM, Waldum-Grevbo B,
Sandbakk Ø and Seeberg TM (2022)
Blood Pressure Response and Pulse
Arrival Time During Exercise Testing in
Well-Trained Individuals.
Front. Physiol. 13:863855.
doi: 10.3389/fphys.2022.863855
Frontiers in Physiology | www.frontiersin.org July 2022 | Volume 13 | Article 8638551
ORIGINAL RESEARCH
published: 11 July 2022
doi: 10.3389/fphys.2022.863855

INTRODUCTION
Blood pressure (BP) measurement is included as a regular
component of exercise stress testing, in order to evaluate the
physiological status of the individual and detect subclinical
cardiovascular disease (CVD) (Schultz et al., 2012;Miyai et al.,
2021). The normal BP response (BPR) to an increase in intensity
during dynamic exercise includes a rise in systolic blood pressure
(SBP) as well as decreasing total peripheral resistance (TPR),
whereas the diastolic blood pressure (DBP) remains stable or
reveals a slight decrease (Bjarnason-Wehrens and Predel, 2020).
Exaggerated BPR to exercise has been reported as a prognostic
factor for incident hypertension or cardiovascular disease in the
general population (Schultz and Sharman, 2013;Caselli et al.,
2019;Mariampillai et al., 2020). This so-called hypertensive
response to exercise has been defined as an SBP ≥210 mmHg
for men and ≥190 mmHg for women (Schultz and Sharman,
2013). However, these thresholds and the subsequent clinical
interpretation of what should be regarded as a normal or
abnormal BPR during exercise are under debate (Bauer et al.,
2021), and The European Society of Cardiology states in its latest
guideline that there is currently no consensus on what is to be
defined as a ‘normal’BPR during exercise (Williams et al., 2018).
Thus, there is a strong need for information related to the clinical
value of exercise-related BP in the general population (Bjarnason-
Wehrens and Predel, 2020).
With regard to BPR to exercise in well-trained or athletic
populations, data are even more sparse, and ambiguity is
inherently even larger. Even though exercise testing plays a
pivotal role in sports cardiology, few studies have evaluated
the magnitude and distribution of exercise-induced BPR in
athletic populations. Due to the high cardiac output achieved
by athletes, the upper limit of ‘normal values’for peak exercise
SBP may differ from other populations. While an exaggerated
exercise BP is increasingly regarded as a risk factor for
cardiovascular disease in the general population (Schultz et al.,
2017), the clinical importance of exercise BPR in athletes remains
uncertain. A recent review by Richard et al. (2021) states that
existent guidelines cannot be adapted when evaluating BPR in
endurance-trained individuals and underlines that elevated SBP
in this population might reflect adaptive responses to training
rather than a pathological sign. Furthermore, comparison of
results from the studies involving athletes that do exist is
challenging, due to differences in reported exercise testing
methods and protocols, BP measurement methods, and
determinations of SBP at maximum or sub-maximum
workloads (Pressler et al., 2018;Caselli et al., 2019;Bauer
et al., 2020). Hence, a consensus on what is a normal BPR
response to exercise in well-trained individuals, as well as
direct causation linking high-graded exercise testing and SBP
to pathology, is lacking.
Another obstacle in estimating BPR during exercise is caused
by limitations in validated non-invasive measurement methods,
which are usually cuff-based and may be impractical,
intermittent, and give discomfort to patients (El-Hajj and
Kyriacou, 2020). As a result, cuff-less BP monitoring with
different bio-signal approaches has gained increasing attention
(Pandit et al., 2020;Welykholowa et al., 2020). One of the signals
regarded as promising for estimation of BP is the extraction of
pulse arrival time (PAT) (Lee et al., 2019). PAT measured using
an electrocardiography (ECG) sensor and a photo-
plethysmography (PPG) sensor and is calculated as the time
interval from an R-wave in an ECG signal to a fiducial point in a
peripheral PPG waveform (Welykholowa et al., 2020). PAT is
inversely related to pulse wave velocity (PWV) and the
relationship between PWV and BP has been recognized since
the late 19th century (Callaghan et al., 1984). When investigating
BPR during exercise, a continuous cuff-less approach would be
superior compared to cuff-based measurements, to avoid
discomfort and inaccuracy caused by movement. However,
PAT is a single parameter, and its relationship to different
parameters of BP is not yet fully understood (Heimark et al.,
2021). Still, the correlation coefficient (on an individual basis)
between PAT and SBP in a recent review by Welykholowa et al.
(2020) was shown to be r= 0.84 (range 0.42–0.98) in studies
utilizing the ECG + PPG modality. Thus, it is reasonable to assess
PAT as a potential cuff-less surrogate SBP measurement during
exercise testing in athletes.
The present study aimed to investigate the BPR in a
population of well-trained individuals during a lactate
threshold and maximal exercise test on a cycle ergometer,
utilizing both an auscultatory technique with an upper arm
inflatable cuff with an integrated microphone designed for
exercise, and a novel device aimed for cuff-less BP
measurements to extract PAT as a potential surrogate BP
measurement. The study will add to current knowledge on
BPR during exercise testing in an athletic population by
addressing the following two aims: 1) To investigate the
systolic BPR during a lactate threshold and maximal cycle
ergometer test in a population of well-trained male cyclists,
and 2) To assess whether PAT measured with a novel cuff-less
device can be used as a continuous SBP surrogate during exercise
testing in the athletic population.
MATERIALS AND METHODS
Participants
Well-trained male cyclists over 18 years of age, free of any chronic
and cardiovascular disease and not under any form of
pharmacological treatment, were eligible for inclusion.
Candidates were recruited from cycling clubs in Oslo and
surrounding areas. Qualifying performance criteria were;
experience in high-intensity bike exercise and a minimum of
8 hours of exercise per week, of which a minimum of 5 hours of
cycling. In line with the Helsinki declaration, all participants were
informed about the test procedure and signed a written informed
consent form before final inclusion. The participants were
instructed to be fully recovered on the test day, which
included avoiding training earlier on the same day and
accomplishing only light training on the day before. They
were further encouraged to ensure an adequate food and fluid
intake on the day before and earlier during the test day, and to
avoid intake of any food during the last hour and caffeine drinks
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Heimark et al. Blood Pressure Response During Exercise

the last 3 hours before the test. During the test, participants were
shirtless, wearing only padded cycling tights and cycling shoes. If
needed, the areas on which the electrodes were applied were
shaved free of hair.
Equipment
BP at rest and during the exercise test was measured utilizing an
auscultatory technique with an upper arm inflatable cuff with an
integrated microphone designed for exercise tests (Schiller BP-
200+, Schiller AG, Baar, Switzerland). The auscultatory technique
BP device was calibrated by certified service personnel the day
before the testing started (Diacor, Oslo, Norway), and the
following settings were used: max inflation pressure of
300 mmHg, and a deflation rate of 3 mmHg/s. This setup for
measuring BP also consists of a 3-channel ECG sensor (Schiller
Cardiovit AT-104 PC, Schiller AG, Baar, Switzerland) that were
used by Schiller BP-200 + to identify heart cycles (QRS triggering)
to provide more accurate BP measurements.
Respiratory variables were measured continuously during
the exercise test using a metabolic analyzer (Cosmed K5,
Cosmed srl, Rome, Italy, software Omnia 1.6.5) and data
was automatically synchronized with the Schiller ECG data.
Prior to each test, the metabolic analyzer was calibrated in
accordance with the user guide. This calibration included flow
calibration by a 3 L calibration syringe (Cosmed ref
C00600.01.11), CO
2
zeroing (shrubbery) and reference gas
calibration, O
2
= 16.0% and CO
2
= 4.0% (CareFusion,
Yorba Linda, CA, United States). Finally, blood lactate
concentration (BLa) was measured with Lactate Scout, a
portable analyzer (Lactate Scout+, EKF Diagnostics, Cardiff,
United Kingdom).
A Garmin sports watch (Garmin Forerunner 920XT, Olathe,
KS, United States) with a chest belt for measuring heart rate (HR)
was used to give real-time measures to the investigators during
the whole protocol. In addition, the Garmin device provided a
master timeline for the protocol.
A prototype, wearable device, IsenseU (SINTEF, Oslo,
Norway), capable of measuring a one-channel ECG, PPG,
impedance cardiography, and movements (3D-acceleration,
3D-angular rate) in the chest area was used to extract PAT
FIGURE 1 | Illustration of the test protocol. BP, Blood pressure.
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Heimark et al. Blood Pressure Response During Exercise

from the ECG signal to the PPG at chest level. The PPG sensor
was mounted on the case (12.5 cm × 4.5 cm) facing the body and
ECG was measured using two standard electrodes placed on the
anterior chest wall. Details on the devices have been published
previously (Seeberg et al., 2017). An upgraded version with a
higher sampling rate of 1,000 Hz was used in the present study.
Raw signals were inspected in real-time via bluetooth connection
to a custom-made software (SINTEF, Oslo, Norway).
Study Protocol
Set-Up and Subject Preparation
The test protocol is presented in Figure 1. All tests were
performed in an exercise laboratory (Kristiania University
College) on a cycle ergometer and comprehended a lactate
threshold test followed by a maximal intensity test. The test
protocol used in the present study is identical to the protocol
utilized by the Norwegian Olympic and Paralympic Committee
and Confederation of Sport at the time of planning the study.
Participants’anthropometric measurements (birth date, height,
weight, body mass index (BMI), and body fat percentage) were
recorded prior to the test. The cycle ergometer (Lode Excalibur
Sport, Lode B.V., Groningen, Netherlands) was calibrated
3 months before testing by certified personnel (Timik, Oslo),
and adjusted prior to each test subject in accordance with their
anthropometric data. The temperature in the laboratory was
20.1 ± 0.9°C.
The BP cuff was placed on the upper left arm of the subject (at
heart level), with bladder size adjusted to the arm circumference
and with the microphone positioned on the brachial artery. For
some participants, a towel was placed between the lower arm and
the handlebar so that the subject could be more comfortable. The
IsenseU sensor was kept fixed on the chest by an elastic chest belt
with three standard ECG electrodes positioned on the upper
chest, as described by Seeberg et al. (2017). The Garmin chest belt
HR monitor was positioned just below the IsenseU sensor.
Continuous HR was measured throughout the whole test
protocol. The 3-lead ECG was fitted with three standard
electrodes; two were placed below the clavicle at the right and
left upper part of the chest and the third at the lower left part of
the chest.
Pre-Exercise Resting Period
Prior to the exercise test, the participants rested for 10 min seated
in a chair while synchronized continuous data collection was
initialized for the IsenseU, Garmin watch, and the 3-lead ECG.
Resting BP was measured at the 5th, 7th, and 9th minute. The
lowest recorded value of the three was defined as the resting BP
value. After the last resting BP measurement, BLa at rest was
recorded.
Warm-Up
After rest measurements, the participants performed a 10-minute
warm-up period on the cycle ergometer at a controlled self-
selected intensity corresponding to a rate of perceived exertion
(RPE) of 10–11 on the Borg Scale (Borg, 1982). Two BP
measurements were recorded at the 3rd and 8th minute. The
warm-up period was followed by a short break, during which the
mask for the metabolic recording was placed and checked for
leakage (Hans Rudolph 7450 Series V2 mask with 2600 non-
rebreathing Y-valve; Hans Rudolph Inc, Shawnee, KS,
United States).
Lactate Threshold Test
Oxygen uptake was recorded throughout the test. The starting
intensity of the threshold test was set between 60 and 90 W below
the presumed lactate threshold at the nearest predefined unit with
30 W intervals. It was assumed that the participants knew their
approximate anaerobic threshold load (W). In case this was not
known, the starting load was at RPE of 11, with HR and RPE
feedback from the warm-up period. Cadence was kept at 85-95
revolutions per minute (RPM) throughout the test.
The lactate threshold test consisted of 5-minute steps with an
incremental increase in the workload of 30 W and an optimal
duration between three and five steps. The BLa was measured by a
finger capillary sample at the last 15 s of each increment. In cases
where the BLa had reached a level between 3 and 4 mmol/L, the
subsequent incremental increase was 15 W instead of 30 W.
When the BLa reached a level above or close to 4 mmol/L the
test was concluded. The reason for the conclusion at levels close to
4 mmol/L was that the addition of one more increment would
spike the BLa significantly above 4 mm/L and potentially disrupt
performance during the subsequent maximal incremental test. BP
was measured starting 1 min and 40 s prior to the end of each
incremental step and without pause in the test, in order to have an
adaptation of the BP to the exercise intensity.
Rest Period two
After completion of the threshold test, the mask was taken off and
all participants had a resting period of 10 min. Participants could
decide whether to sit still on the bike or to pedal at a very low
intensity to avoid an undesired stiffening of the legs. Two BP
measurements were taken at the 3rd and 8th minute.
VO
2max
Test
At the end of the break, the mask to measure the metabolic
consumption was re-mounted. The VO
2max
test started at the
same intensity as the threshold test in cases where the
anaerobic threshold was reached at the 4th or 5th
incremental step. Otherwise, it started at 30 W lower if the
threshold was reached earlier, or at 30 W higher if the
threshold was reached later. The optimal duration of the
VO
2max
test was between 6 and 10 min. The incremental
stepshadadurationof1minwithanincreaseof30W.
The cadence was kept at 85–95 RPM throughout the test.
The test continued until exhaustion was reached by the
subject; defined as a voluntary interruption or by the
cadence falling below 60 RPM, despite a strong
encouragement to hold on to the given intensity. After
completion, the mask was removed, and the metabolic
recording turned off. BLa was measured 1-minute post-
exercise. BP measurements during the test were recorded
starting from the first minute of exercise at every second
minute until exhaustion. IsenseU-data, metabolic capacity,
and HR were recorded throughout the test.
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Heimark et al. Blood Pressure Response During Exercise

Post-Exercise Resting Period
A post-exhaustion BP measurement was taken immediately after
completion of the VO
2max
test when the subject was recovering
seated on the cycle ergometer. Following the BP measurement,
participants were seated on a chair while five post-exercise BP
measurements were taken every second minute for 10 min.
Data Processing and Statistical Analyses
Synchronization of Sensor Data
First, the IsenseU-data was attached to the master-timeline (i.e. the
time of the Garmin watch) by using manually noted times for the
start/stop of the sensor. Then data from the metabolic analyzer
(which was automatically synchronized with the Schiller ECG data),
was synchronized to the master-timeline by accomplishing
maximum correlation of RR-peaks in the two ECG signals
(IsenseU and Schiller). Finally, the open-source software platform
Activity Presenter, a software module created to simplify the process
of visualizing, synchronizing, and organizing data and video from
multiple sources (Albrektsen et al., 2022), was used to fine-tune and
verify correct synchronization.
Performance Characteristic and Variation of
Physiological Measurements Between Participants
To be able to compare data across participants, five characteristic
physiological states were defined and the corresponding data at those
points were extracted from the dataset (presented in Figure 2):
•PRE: value at rest before the cycling. The measurement
point with the lowest SBP was used with the
corresponding HR.
•WU: value during warm-up. The last BP measurement
(after 8 min) was used as the subject-dependent intensity
was adjusted and the physiological parameters were
stabilized to the intensity demand.
•THR: values at 4.0 mmol/L as an indication of lactate
threshold. The last completed BP measurement with the
corresponding HR and watt values before passing BLa of
4.0 mmol/L was extracted.
•MAX = Watt at the last completed stage in the maximal test
and maximal HR reached in the test. For the BP
measurements, the point with the highest completed
FIGURE 2 | VO
2max
is presented as a box and whisker plot with median, interquartile range, and minimum and maximum value, otherwise Individual (dotted lines)
and mean (red line) values for workload, percentage of maximal heart rate (%HR), blood lactate (BLa), systolic blood pressure (SBP) and diastolic blood pressure (DBP)
during the protocol. PRE = values at rest before the cycling, WU = values during warm-up, THR = values at the threshold, MAX = values at maximal intensity (except for
BLa which was measured directly after the maximal intensity), POST = values measured 10 min after the test.
Frontiers in Physiology | www.frontiersin.org July 2022 | Volume 13 | Article 8638555
Heimark et al. Blood Pressure Response During Exercise

valid measurement was chosen. It should be noted that this
was lower than the maximal W reached during the max-test
because the BP measurement took longer than each
increment and it was difficult to obtain valid
measurements during maximal intensity. BLa was
measured directly after the maximal test.
•POST = SBP with the corresponding HR measured 10 min
after completion of the maximal test.
Calculation of PAT and SBP-Corresponding PAT
Values
PAT was calculated for each cardiac cycle from the R-peak in the
ECG signal to the foot in the PPG signal recorded from the skin
vasculature at chest level (Heimark et al., 2021). The PAT values
were filtered by applying a moving median filter with a window
size of 30 cycles, only keeping PAT values within 20% of the
median of the window. Subsequently, a second median filter was
applied to calculate the median PAT value from 10 cycles prior to
and after the corresponding SBP value. SBP values were noted
manually at the time of recording and synchronized to IsenseU as
described earlier. To ensure that the PAT was not calculated too
far away from its corresponding SBP measurement, PAT values
calculated more than 20 s apart from the SBP measurement were
discarded. If less than 5 valid PAT values existed in the window,
the PAT measurement was discarded. DBP was not considered in
the present analysis due to a lack of relationship between the two
variables (Heimark et al., 2021).
Participant Selection
All participants (n= 18) were included in the analysis of
performance and variation of physiological response during
the lactate threshold and maximal dynamic exercise test. For
the analysis of PAT, three subjects had to be excluded due to a low
signal-to-noise ratio in the PPG, and thus only 15 were available
for analyses of the relationship between PAT and SBP.
Statistical Analyses
Raw data processing and statistical analyses were performed
using the Python programming language with these packages;
NumPy (1.18.1), SciPy (1.4.1), NeuroKit2 (0.0.32), Pandas
(1.3.3), and Matplotlib (3.1.1) (Hunter, 2007;McKinney,
2010;Harris et al., 2020;Virtanen et al., 2020;Makowski
et al., 2021). Prior to the linear regression analysis, all PAT
SBPpairoutlierswerefiltered in the following way: If the
probability of the pair occurring was less than 2.5% based on
the normal Gaussian distribution from all samples from the
same subject, the measurement pair was considered an outlier
and removed from the data analysis. The 2.5% cut-off was
selected due to increasing levels of noise in both the raw
signals from the IsenseU and the BP cuff with increasing
levels of exercise intensity. The relationship between PAT
and SBP was analyzed using linear regression for each
subject. All valid measurement pairs for each participant
throughout the test protocol, including rest periods and
warm-up, were used. For the performance characteristics of
the five defined physiological states, mean and standard
deviations were calculated.
RESULTS
Participant Characteristics
General characteristics of the 18 participants were; mean age of
32.4 ± 9.4 years, height of 182.7 ± 6.6 cm, body mass of 75.4 ±
8.2 kg, BMI of 22.6 ± 1.5 kg/m
2,
and a body fat percentage of 9.3 ±
3.9%. The participants rode an average of 14,130 ± 7240 km/year
and had 7.9 ± 4.8 years of experience in active cycling.
Performance Characteristics and Blood
Pressure Response
To highlight the test protocol, physiological measurements for
one typical participant are displayed in Figure 3. Performance
parameters and BP response extracted from the pre-exercise
resting period (PRE), warm-up (WU), at threshold (THR), at
maximal intensity (MAX, except for BLa which was measured
directly after the maximal intensity), and 10 min after the test
(POST) are presented in Table 1. In brief, the participants had a
mean VO
2max
of 63 ± 10 ml/min/kg and maximum workload in
the maximal performance test at 403 ± 61 W. Resting BP was 136/
88 ± 9/7 mmHg and SBP at MAX was 231 ± 18 mmHg.
Individual data and mean values for performance and BP
characteristics for the participants during the protocol are
given in Figure 2.
Table 2 shows the results from the linear regression between SBP
and PAT. The mean r
2
of all individual regression analyses was
0.81 ± 0.17 with a mean of individual regression slopes of −0.72 ±
0.37 ms/mmHg.
DISCUSSION
At present, few studies have described the BPR in well-trained
individuals and athletes, and it is not known whether an
exaggerated BPR represents a warning sign, or rather is an
expression of adaptive responses to training in these populations
(Richard et al., 2021). The primary aim of this study was, therefore, to
add to the current knowledge by investigating the BPR during a
maximal cycle ergometer test in well-trained male cyclists. Our results
indicate, similarly to previous studies, that the systolic BPR during
maximal aerobic exercise in well-trained subjects is exaggerated
compared to normative values from a general population.
Notably, the SBP at peak aerobic intensity from our cohort was
even higher than in recent similar studies. Furthermore, cuff-less
approaches are suggested to overcome the current limitations of cuff
measurements during exercise testing. Thus, as a secondary aim, we
investigated PAT as a potential non-invasive cuff-less measurement
method. Here, our results strengthen previous findings of strong
associations between PAT and exercise SBP on an individual level.
Blood Pressure Response in Well-Trained
Individuals
In our study, the mean (SD) value for SBP at peak aerobic exercise
was 231 (18) mmHg, with a mean difference from baseline of
95 mmHg. There is no consensus on the exact definition for what
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Heimark et al. Blood Pressure Response During Exercise

should be regarded as an exaggerated BP response to exercise in
general, even though SBP at peak aerobic exercise exceeding
210 mmHg for men and 190 mmHg for women has frequently
been reported as exaggerated (Schultz and Sharman, 2013;
Sabbahi et al., 2018;Percuku et al., 2019). An alternative
suggested cut-off in several studies is a difference of 60 mmHg
between baseline (resting) and peak SBP for men and 50 mm Hg
for women (Percuku et al., 2019). Caselli et al. (2016) tried to
accommodate the shortcoming of reference values specifically for
the athletic population by assessing BPR in highly trained
Olympic athletes and suggested a cut-off for males of
220 mmHg peak SBP. From recent similar studies listed in
Table 3,Pressler et al. (2018),Caselli et al. (2019) and Bauer
et al. (2020) reported mean peak aerobic SBPs somewhat lower
than in the present study, but close to the suggested cut-off values
in athletes. As a consequence, a large number of athletes still have
an exaggerated systolic BPR. Importantly, the data from Caselli
et al. (2019) are extracted from a cohort also including 27%
women, and separate values for men were not given. As men
consistently are reported to reveal a more pronounced SBP
response than women (De Buyzere and Rietzschel, 2018;Song
et al., 2020), the value for men-only would likely be higher.
Comparably high maximum dynamic exercise BPR to our
findings has previously been reported in similar populations.
Karjalainen et al. (Table 3) reported a peak aerobic SBP of 228
(16) mmHg in elite male orienteers and long-distance runners
aged 26 (±3) (Karjalainen et al., 1997). Compared with age and
gender-matched normative data in apparently healthy general
FIGURE 3 | Physiological measurements during the experimental protocol, exemplified with data from one typical subject. PAT is inverted on the y-axis to better
visualize the co-variation with SBP. PAT, pulse arrival time (ms); SBP, systolic blood pressure (mmHg); DBP, diastolic blood pressure (mmHg); HR, heart rate (beats per
minute).
TABLE 1 | Mean values and standard deviation for workload, VO
2
, %VO
2
, HR, %HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), and blood lactate (BLa)
during the protocol.
PRE WU THR MAX POST
Mean (SD) Mean (SD) Mean (SD) Mean (SD) Mean (SD)
Workload [Watt] 174 (28) 281 (56) 403 (61)
VO2 [ml/min/kg] 49 (9) 63 (10)
%VO2 [of VO2max] 82 (12) 100 (0)
HR [bpm] 59 (11) 125 (12) 164 (10) 182 (9) 93 (18)
%HR [of HRmax] 32 (6) 69 (5) 90 (4) 100 (0) 51 (8)
SBP [mmHg] 136 (9) 201 (21) 219 (21) 231 (18) 134 (18)
DBP [mmHg] 88 (7) 88 (10) 89 (9) 91 (10) 88 (9)
BLa [mmol/L] 1.6 (0.4) 3.3 (0.5) 11.0 (2.5)
PRE = values at rest before the cycling, WU = values during warm-up, THR = values at the threshold,MAX = values at maximal (except for Bla which was measured directly after maximal
intensity), POST = values measured 10 min after the test
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Heimark et al. Blood Pressure Response During Exercise

population cohorts, Hedman et al. (2020b) reported a peak SBP
during exercise test of 202 (22) mmHg and Sabbahi et al. (2018)
179 (20) mmHg, with corresponding differences from baseline of
74 and 56 mmHg, respectively. In sum, our data indicate an
exaggerated BPR in well-trained individuals compared to the
general population and reflect an even higher peak SBP than in
recent comparable studies on athletic populations.
One possible explanation for the observed high peak SBP
values in our study compared to recent comparable studies is that
our participants had a higher mean age. It has been shown that
peak exercise SBP increases steadily with increasing age (Hedman
et al., 2020b). However, in the study by Karjalainen et al., which
demonstrated similarly high peak aerobic SBP, participant age
was lower compared to our study. Another possible explanation is
that cyclists compared to other athletes are shown to have a larger
BPR during a maximal cycle ergometry test (Richard et al., 2021),
and none of the other studies included cyclists-only. It is further
important to bear in mind that there is no accepted gold standard
exercise BP measurement method, which may impact the
comparability across studies, particularly if the number of
participants is small, as in our cohort. Another variable which
differentiated our results from the afore discussed studies, was the
higher achieved workload at peak aerobic exercise, presented in
Table 3. All four comparable studies had test protocols that
TABLE 2 | Linear regression between systolic blood pressure (SBP) and pulse arrival time (PAT) for participants with valid pulse arrival time (PAT) measuremen ts. The pvalue
indicates the test of the null hypothesis that the coefficients are equal to zero.
Participant number r
2
Slope (ms/mmHg) pvalue Number of measurement
pairs removed based
on poor signal
quality
1 0.91 −0.51 0.001 10/17
2 0.69 −0.66 0.005 13/22
3 0.97 −0.65 <0.001 1/20
4 0.84 −1.09 <0.001 3/22
5 0.32 −0.18 0.014 2/20
6 0.90 −0.79 <0.001 2/20
7 0.93 −0.76 <0.001 6/20
8 0.93 −1.00 <0.001 0/19
9 0.77 −1.59 <0.001 0/20
10 0.86 −0.73 <0.001 1/20
11 0.82 −0.44 <0.001 3/23
12 0.90 −0.93 <0.001 8/21
13 0.64 −0.69 <0.001 4/22
14 0.82 −0.59 <0.001 1/15
15 0.91 −0–86 <0.001 3/22
Mean ± SD 0.81 ± 0.17 −0.72 ± 0.37
n=15
TABLE 3 | Overview of similar studies.
Study Cohort, number of
participants, age (SD)
Peak
aerobic
SBP (SD),
mmHg
Maximal
workload
(SD),
Watt
Difference
from baseline,
mmHg
Exercise
method
BP measurement
method
Test protocol
Present study Well-trained male cyclists,
18, 32 (9.4)
231 (18) 403 (61) 95* Cycle
ergometry
Automated
electronic exercise
cuff
Threshold W followed by 30 W
increases every 1 min
Bauer et al.
(2020)
Male professional
handball and hockey
athletes, 142, 26 (5)
197 (20) 351 (79) 74 (20) Cycle
ergometry
Automated
electronic exercise
cuff
100 W followed by 50 W
increases every 2 min until
exhaustion
Pressler et al.
(2018)
Professional athletes,
2419 (663 female), 26 (12)
204 (22) 305 (59) 80 (20 Cycle
ergometry
Manual sphygmo-
manometry
Varying; usually starting load of
50-100 W with 20-50 W
increases and 3-minute
durations
Caselli et al.
(2019)
Male and female
professional athletes, 141,
26 (6)
208 (22) 262 (61) 87* Cycle
ergometry
Manual sphygmo-
manometry
0.5W/Kg with increases of
0.5W/Kg every 2 min
Karjalainen
et al. (1997)
Male orienteer and long
distance runners, 32,
26 (3)
228 (16) 333 (27) 97* Cycle
ergometry
Manual sphygmo-
manometry
50 W followed by 50 W
increase every 3 min
SBP, systolic blood pressure. SD, standard deviation. W, watt. *SD unknown
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Heimark et al. Blood Pressure Response During Exercise

consisted of cycle ergometry. Pressler et al. (2018),Caselli et al.
(2019) and Bauer et al. (2020) had considerably lower achieved
workloads. Also in the study by Karjalainen et al. (1997), which
had the most comparable BPR, the athletes achieved lower a
maximal workload; of 333 (27) W. Whether the maximum
workload is causal towards the higher peak SBPs by
physiological explanations such as differences in TPR, or a
result of well-trained cyclists performing a cycle-ergometer
test, is uncertain. However, novel approaches in interpreting
SBP response to peak aerobic exercise include indexing
maximum SBP to max achieved workload (Hedman et al., 2020a).
Interestingly, the suggested alternative cut-off of 60 mmHg
from rest to peak aerobic exercise is exceeded not only in our
study but also in all four comparable studies on athletes as well as
the normative data. The uncertainty of what should be regarded
as a potentially dangerous exaggerated response is further
complicated by the variance in prevalence of an exaggerated
BPR between studies, not only due to different definitions but also
because the BRP must be seen in relation to the characteristics of
different study populations (Schultz and Sharman, 2013). It is
further crucial to interpret values from the level of exercise
intensity. Both our findings and results from comparable
studies (Table 3) suggest that a cut-off of 60 mmHg increase
from rest to peak SBP for exaggerated BP response may be
inaccurate. Another factor that must be taken into
consideration when comparing findings between studies is
how they have defined measurements at “rest”. Body position
may affect the measurements (Eser et al., 2007), and the white-
coat effect should also be considered. For athletes, in particular,
exercise testing may entail expectations of performance, which
can lead to anxiety and an elevated stress level (Ford et al., 2017)
which may influence their baseline data; in this context
resting BP.
Although there is a growing body of studies indicating that an
exaggerated BPR in athletes is a matter of physiological adaptation,
there is a lack of longitudinal studies assessing if there is an
increased risk of hypertension or cardiovascular disease. Caselli
et al. (2019) showed that athletes with an exaggerated BPR
compared to normal BPR to maximal cycle ergometry [max
SBP 208 (22) mmHg vs. 185 (20) mmHg achieving maximal
workloads of 262 (61) W vs. 257 (62) W] had a 3.6-fold hazard
ratio of incident hypertension after 6.5 ± 2.8years of follow up.
These results highlight the need for future studies on athlete
populations to define cut-off values and risk assessment.
Is PAT a Potential Non-Invasive, Continuous
Surrogate Systolic Blood Pressure
Measurement in Athletic Populations?
Our results demonstrated that, on an individual level, PAT has a
strong association with SBP in well-trained individuals during a
threshold and VO
2max
test. This has not previously been
assessed in an athletic population with corresponding
exercise intensities. PAT has gained increasing interest in
non-invasive, cuff-less BP monitoring to overcome cuff
limitations. Gold standard BP measurements during exercise
are limited to the invasive method, which is not ethically
justifiable in routine exercise testing or even in most research
settings. Cuff-based methods, either manually or electronically
by using a microphone to detect Korotkoff sounds, are
considered acceptable but remain unable to produce high
precision non-invasive measurements. Cuff-based methods
are further limited due to intermittent sampling and
distortion caused by noise and motion artifacts. Previous
studies have, similar to our findings, demonstrated that PAT
is strongly correlated to SBP on an individual level during
dynamicexercise(Wibmer et al., 2015;Heimark et al., 2021).
However, the need for calibration against a cuff-measurement to
correct for the unknown length of the pulse wave propagation in
addition to other individual factors is still an unresolved
limitation in PAT-based approaches. Wibner et al. (2015)
achieved comparable coefficients of determination to our
results using regression analysis in 18 patients referred to
cardiopulmonary exercise testing, with a mean r
2
(SD) of
0.80 (0.22) vs. 0.81 (0.17) in our study. Wibner et al. further
translated PAT to absolute BP values using multipoint
calibration and achieved a Bland Altmann bias of –0.3 (12.4)
mmHg with limits of agreement from –24.7 to 24.1 mmHg
compared to the reference exercise BP cuff, which was
considerably better than simultaneously measured continuous
volume clamp method [bias 14.0 (28.5) mmHg)]. Thus, our
resultsindicatethatPATmaybeafeasiblecontinuousSBP
surrogate measurement also in an athletic population. However,
a major limitation to overcome, in addition to the need for at
least one static calibration to adjust for individual offsets, is the
significant between-individuals variation in the PAT/SBP slope.
Wibneretal.wereabletoproduceaccurateSBPvaluesfor
comparative purposes by multipoint calibration; however, this is
not a practical approach in everyday use. Future research should
focus on methods to predict the individual PAT/SBP slope.
Regarding DBP, no meaningful association with PAT was
observed as DBP during dynamic exercise changed very little,
which is expected from the underlying physiological adaptations.
Similar indications have been reported in previous studies
assessing PAT during dynamic exercise (Wibmer et al., 2015;
Heimark et al., 2021). Although many studies report strong
correlations between PAT and both SBP and DBP, we believe
that PAT as a single parameter cannot be generalized to both SBP
and DBP across various hemodynamic states.
It is an ongoing debate whether confounding ofthe pre-ejection
period (PEP) limits the application of PAT as a BP surrogate
measurement. PEP is defined as the electromechanical time delay
from the electrical onset of the systole (observable as the R-peak in
an ECG signal) to the actual opening of the aortic valve and true
onset of the pulse wave propagation in the arterial tree, defined as
pulse transit time (PTT). The PEP may not vary with the same
magnitude and direction as the PTT and corresponding change in
BP (Pour Ebrahim et al., 2019). However, during dynamic exercise,
PEP is previously shown to display an intensity-dependent
decrease from rest to exercise (Michael et al., 2017), potentially
minimizing the confounding effect during exercise testing
compared to non-exercise settings of BP measurement. Our
study is limited to PAT only, and the potential confounding
role of PEP should be clarified in future studies.
Frontiers in Physiology | www.frontiersin.org July 2022 | Volume 13 | Article 8638559
Heimark et al. Blood Pressure Response During Exercise

LIMITATIONS
The main limitations of the present study are the small study
sample containing only males, and the lack of a control group.
Most investigations examining exaggerated BPR during exercise
are derived from Caucasian middle-aged men, and there is a lack
of studies including younger individuals and specifically athletes
and/or well-trained individuals. There is further a lack of studies
including women. Our study only partly addresses this bias, as
our material consists of Caucasian men with a mean age of
32.4 years and a VO
2max
of 63 (10) ml/min/kg. In addition, peak
aerobic SBP suffers from varying test protocols with different
methods of BP measurements across and within studies. Thus,
the aforementioned limitations warrant caution when
interpreting the results and drawing conclusions in the context
of data from comparable studies. An important consideration
when assessing the BPR to exercise is the change in BP from
baseline values, of which the validity is dependent on true baseline
or resting values. We observed in the present study, despite sitting
rest for 5 min prior to baseline measurements, unreasonably high
resting BP values, which was the reason for choosing the lowest
value. The most likely explanation for this high resting BP is the
anticipation of the subsequent VO
2max
test. Our PAT analysis was
limited by significant amounts of noise in the PPG signal, which
was attributable to movement artifacts and clipping of high
amplitude PPG waveforms during exercise. However, strict
criteria were applied to measure PAT from valid signals
during high noise periods. A major challenge in future
developments in the PPG-sensor technology and signal
processing is improvements to account for noise.
CONCLUSION
The present study adds to existing data on the BPR in well-trained
populations. The results suggest an exaggerated BPR compared to
normative cut-off values and reveal a higher SBP at peak aerobic
exercise compared to most similar studies. Our findings indicate
that athletes may have different cut-off values than less trained
populations, which could be a result of physiological adaptations.
However, there is a need for more data to determine reliable cut-
off values in addition to considering any possible risk factors
associated with exaggerated SBP responses in athletic
populations. Furthermore, the results suggest that PAT may be
used as a potential non-invasive and cuff-less SBP surrogate
measurement on an individual level. However, a measurement
device with a more robust signal-to-noise ratio is required, and
the varying individual relationship between PAT and SBP
remains a challenge for future work.
DATA AVAILABILITY STATEMENT
The raw data supporting the conclusions of this article will be
made available by the authors, without undue reservation.
ETHICS STATEMENT
Ethical review and approval was not required for the study on
human participants in accordance with the local legislation and
institutional requirements. The patients/participants provided
their written informed consent to participate in this study.
AUTHOR CONTRIBUTIONS
Conceptualization: SH, IE, IV, ØS, BW-G, and TMS.
Methodology: SH, IV, TMS, IE, and ØS. Data acquisition: IV,
AM, and TMS. Software: OH and KGB-R. Formal analysis: SH,
OH, KGB-R, and TMS. Writing—Original draft: SH, IE, and
TMS. Writing—Review and editing: IV, KGB-R, AM, OH, BW-
G, and ØS. Final approval of submitted manuscript: All authors.
FUNDING
This study was supported by the AutoActive project (Project No.
270791), a research project in the IKTPLUSS program financed
by the Norwegian Research Council, and by the HyperSension
project (project number 282039), a research project in the BIA
program financed by the Norwegian Research Council.
ACKNOWLEDGMENTS
The authors would like to thank the cyclists for their willingness
to participate, Simen Seeberg-Rommetveit for his valuable
contribution to the data collection and Kristiania University
College for allowing us to use their facilities.
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