Cardiovascular Mechanisms of the Occupational Physical Activity Health Paradox: 24-hour Physical Activity, Blood Pressure, and Heart Rate
Conditions: Occupational Diseases, Cardiovascular Diseases, Cardiovascular Risk Factor, Occupational Exposure
Sponsor: University of Pittsburgh

Cover Page 
 
 
 
Cardiovascular Mechanisms of the Occupational Physical 
Activity Health Paradox: 24-hour Physical Activity, Blood 
Pressure, and Heart Rate 
 
NCT04075279 
 
9/26/2019 
 

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OPA have different occupational responsibilities and activity levels that may
adversely affect cardiovascular health. Indeed, occupation is known to explain much
of the overall variation in physical activity accumulation.14,15 While the population
average of the energy expenditure of work activities has decreased over the past 50
years,1 Tudor-Locke et al. reported that approximately 21% of the United States
population still remains in occupations requiring moderate or vigorous intensity
activities regularly.16 Steeves et al. recently used 2005-6 National Health and
Nutrition Examination Survey (NHANES) data to report great variation in total
uniaxial accelerometry counts per minute (cpm) in high-activity occupations (>400
cpm) compared to low-activity occupations (<300 cpm).15 High-activity occupations
include categories such as ‘farming, fishing, forestry’, ‘building & ground cleaning’,
‘construction, extraction’, and ‘food preparation, serving’ while low-activity
occupations include categories such as ‘community, social services’, ‘legal’, ‘health
care support’, and ‘office, administrative support’.15 Overall, it is known that
occupation in a strong determinant of activity pattern across individuals. Although
the physical activity health paradox has been attributed to these differences in
activity pattern, gaps in the literature remain explaining the health implications of
OPA specifically.
Epidemiological research suggests the cardiovascular health implications are
different across occupational populations with varying amounts and patterns of OPA
and LTPA. Specifically, those with high OPA have increased all-cause mortality risk
and those with high LTPA have decreased mortality risk.7,17 Furthermore, the
increased mortality risk associated with high OPA seem to be ameliorated by high
amounts of LTPA.7 While these relationships have been identified, the literature in
this field is greatly limited. Almost all studies use self-reported activity data collected
at a single time point, are observational and likely affected by biases such as
uncontrolled confounding (e.g., socio-economic status) and selection (e.g., the
healthy worker effect), are restricted to mainly male samples, and do not study
mechanisms. Even still, the consistency of observational findings may justify a re-
evaluation of physical activity recommendations in the presence of high volume OPA
accumulation. Moreover, occupational health and safety regulations regarding
allowable working times for highly active occupations may need to consider
potentially detrimental effects of high OPA accumulation on cardiovascular health. 
Prior to recommending changes to physical activity recommendations or OPA
regulations and standards, better understanding of the mechanisms that explain the
physical activity health paradox in workers with high accumulated OPA is needed.
Holtermann recently proposed six hypotheses to explain this paradox: 1) OPA does
not improve cardiorespiratory fitness because it is of too low intensity or of too long
duration18; 2) OPA may increase 24-hour heart rate (HR)19; 3) OPA may increase
24-hour blood pressure (BP); 4) OPA does not allow for adequate recovery time20;

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5) workers have limited autonomy over the OPA performed; and 6) OPA increases
inflammation.13,21 More specifically for the purposes of this proposal, while acute
bouts of physical activity of moderate or vigorous intensity (LTPA) increase HR and
BP during exercise, the resulting 24-hour cardiovascular load is decreased due to a
compensatory hypotensive response. However, when considering the typical pattern
of OPA, it is hypothesized that low intensity activity for a long duration with little
recovery results in elevated 24-hour HR and BP which are known to be positively
related to all-cause mortality.19 Furthermore, autonomic dysfunction, which is
closely related to cardiovascular regulation, has been proposed to occur as a result
of high OPA and is may be a pathway by which OPA elevates cardiovascular risk.22
Lastly, low task autonomy and high psychological job strain are commonly found in
occupational settings and can result in few recovery breaks or days of rest,
negatively impacting cardiovascular health.13 These effects have also been found to
potentially differ across individuals with high versus low fitness levels.8 However,
these hypothesized deleterious cardiovascular effects of increased 24-hour HR and
BP and autonomic dysfunction resulting from high OPA remain untested.
Furthermore, effect modification of these proposed mechanisms by fitness level or
job strain are largely unexplored in studies designed for this purpose. 
The current study aims to address this knowledge gap using an innovative within-
subject design and best practice assessments of objective physical activity,
sedentary behavior, and field-based cardiovascular testing of HR, BP, and
autonomic function. The intention of the proposed research is to expand
understanding of the biological plausibility behind the physical activity health
paradox with the long-term goal to inform activity guidelines or occupational
regulations for individuals achieving high levels of OPA. 7,8,10,13,22,23
 

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measurement is ≥150 mmHg systolic or ≥95 mmHg diastolic, the participant will be
determined to be ineligible for the study and the assessment will be discontinued. If
average systolic BP is >140 mmHg or diastolic BP >90, we will provide a safety alert
letter encouraging participants to follow up with their primary care provider. If
average systolic BP is >180 mmHg or diastolic BP is >110 mmHg, we will provide an
urgent alert letter encouraging participants to follow up with their primary care
provider immediately. BP >180/110 mmHg with symptoms will prompt emergency
response procedures. (See attachments)
3. Medical history (medications, smoking status, known disease, physical limitations
using a standard medical history form)
4. Demographics (age, race/ethnicity, sex) and occupational status/history.
5. Measurements of anthropometry (height and weight) will be completed using a
calibrated digital scale (WB-110A, Tanita Corporation of America, Arlington Heights,
Illinois) to the nearest 0.1 kg and stadiometer (HM200P, Charder, Tiachung City,
Tiawan) measured to the nearest 0.1 cm. Each participant will be asked to remove
their shoes and anything in their pockets prior to the anthropometry measurements.
Two measurements of each will be taken and a third measurement will be taken if
the two measurements differ by >0.2 kg and >0.5 cm in weight and height,
respectively. The average of all measurements will be used for both anthropometric
measurements and will be used to calculate BMI as kg/m2.
6. Each participant will complete a submaximal treadmill test using the 
Balke protocol up to 80% age-predicted HRmax (80% age-predicted HRmax = 0.80
x (208 – (0.7 x age)) to estimate cardiorespiratory fitness level (25, 126). Each test
will be completed with a constant speed of 3.3 mph and increasing incline by 1%
each minute, starting at 0% for the first minute. During the exercise test, heart rate
will be recorded from the polar heart rate strap/watch during the last 10 seconds of
each minute and blood pressure will be recorded during the last 45 seconds of every
2nd minute (e.g. 2, 4, 6, etc.). Ratings of Perceived Exertion (RPE) will be measured
using the Borg Rating of Perceived Exertion Scale (6=No exertion at all to
20=Maximal exertion) every two minutes during the exercise test and immediately
after the last stage of the test to rate the final perceived effort of the individual. HR
will be measured continuously throughout the submaximal exercise test using a
Polar HR strap (H7 Bluetooth, Polar). When the participant’s HR reaches their 80%
age-predicted HRmax, the test will be terminated and the participant will be asked to
walk slowly on the treadmill (1.0-2.0 mph and 0% grade) until their HR returns to
below 100 beats per minute. The final test duration, final test heart rate, and final

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test RPE will be recorded following the test termination. The observed HR trajectory
will be used to estimate each participant’s work rate at their age-predicted maximal
HR which will then be used to predict maximal oxygen uptake (VO2max). Estimated
VO2max will be used as estimated fitness level in the analytical analyses.
If at any point throughout the exercise test, any of the following criteria are met, the
exercise test will be terminated to ensure participant safety:
1. Onset of angina-like symptoms
2. Drop in SBP of 10 mm Hg with an increase in work rate or if SBP decreases
below the value obtained in the same position prior to testing
3. Excessive rise in BP: systolic pressure ≥220 mm Hg and/or diastolic pressure
≥100 mm Hg
4. Shortness of breath, wheezing, leg cramps, or claudication
5. Signs of poor perfusion: light-headedness, confusion, ataxia, pallor, cyanosis,
nausea, or cold and clammy skin
6. Subject requests to stop
7. Physical or verbal manifestations of severe fatigue
8. Failure of the testing equipment
The staff who will be performing the exercise test and blood pressure measurements
will hold a master’s degree or greater in exercise physiology and have prior
experience and training in taking exercising blood pressures.
If the exercise test is terminated prior to the participant achieving 80% of the
predicted maximal heart rate, the participant will be considered ineligible for further
participation in the study and all research activities will be discontinued.
Objective Physical Activity Monitoring
Following all baseline measurements, each participant will be fitted with physical
activity (inclinometer and tri-axial accelerometer) and ambulatory cardiovascular
monitors (heart rate strap and ambulatory blood pressure monitor) to wear for 7
complete days. After 7 days, monitors will be returned by the participant to the
research laboratory at a pre-scheduled return time. Physical activity will be
monitored for 7 days using gold standard, research grade methods: 1) inclinometer
(activPAL, PAL Technologies, Glasgow) and 2) tri-axial accelerometer (GT3X-BT,
Actigraph, Pensacola, Fl). These two measurements have been validated and used
extensively to measure physical activity patterns in a free-living environment (127,
128). In addition to the physical activity monitoring, each participant will be asked to
complete a paper diary of their working times, sleeping times, monitor wear, and
daily job strain. This diary will be used to characterize all activity categories into total

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time, work time, non-work time, or sleep.
The activPAL will be affixed to the right thigh using a transparent adhesive dressing
(Tegaderm, 3M) for 7 days to measure 24-hour activity, posture (sitting or standing),
and stepping throughout the day. Participants will be asked to wear the ActivPAL for
7 days to estimate weekly, habitual activity. The participants will be encouraged to
wear the ActivPAL monitor for 24 hours per day from 7 days and only asked to
remove the device prior to swimming and placing it back on immediately after.
ActivPal data will exported as event-type data and will be classified as sedentary
behavior, stepping, and standing based on proprietary algorithms. Time spent in
sedentary behavior, standing, and stepping will be averaged across all wear days as
well as averaged work time and non-work time. All self-reported nap and sleep
periods will be coded as sleep and will be removed from the calculation of sedentary
time. Self-reported non-wear will also be removed from the sedentary time
calculation. Further data reduction will estimate time spent in prolonged bouts of
sedentary behavior (e.g., <30 consecutive minutes: SED<30 and ≥30 consecutive
minutes: SED≥30) or standing (e.g., ≥60 minutes) and averaged across all valid
wear days. Averages will also be calculated during work and non-work days.
The Actigraph GT3X-BT will be worn over the right hip using an elastic belt to
measure pattern and intensity of activity (light, moderate, or vigorous) for 7 days.
Each participant will be instructed to take the monitor off only for water activities
(e.g., showering, swimming). They will also be asked to record the corresponding
times of monitor removal and application in their paper diary each day.
Accelerometry counts will be calculated as sedentary time, light activity, or moderate
to vigorous activity using previously described algorithms across all valid wear time
as well as for work time and non-work time. Data will be collected as 1-minute
epochs, downloaded using ActiLife software (Actigraph, Pensacola, Fl) and
considered valid if data is collected for ≥4 days of ≥10 hours per day. Wear time will
be defined as 24 hours minus non-wear time, defined using the Choi algorithm.
Daily mean activity counts (cpm) and duration of all activity intensity categories
(minutes/day) will be averaged across all valid wear days. Moderate to vigorous
physical activity will be derived from the triaxial vector magnitude data using
Freedson vector magnitude cutpoints. Moderate to vigorous physical activity will be
further separated into long bouts (≥10 consecutive minutes with allowance for 2
consecutive minutes below the 100 cpm, MVPA≥10) and then short bout moderate
to vigorous physical activity (<10 minutes, MVPA<10) (129, 130).
Combining activPAL and Actigraph data, we will calculate time spent in five clinically
relevant activity categories: SED≥30, SED<30, light activity, MVPA<10, and
MVPA≥10. These categories reflect the recent expert call for research examining the
health impacts of light physical activity and prolonged versus sporadic sedentary
time and moderate to vigorous physical activity (4).

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Ambulatory Cardiovascular Measurement
24-hour heart rate measurement
A Bluetooth enabled HR monitor strap (H7 Bluetooth, Polar) will continuously
measure HR for 7 days and provide a measurement of average 24-hour HR for
every day during the 7-day period. Each participant will be instructed to wear the HR
strap directly below their nipple line for the duration of the 7-day monitoring period,
only removing it during bathing or during water activities (e.g., swimming). Any time
the monitor is removed, the participants will be instructed to record the time and
reason in the provided paper diary. The HR monitor will be paired via Bluetooth with
the Actigraph accelerometer upon activation so that the continuously measured HR
data at a beat to beat resolution of 1 millisecond and will be stored on the Actigraph
device throughout the monitoring period. HR data will be downloaded as interbeat
R-R intervals using ActiLife software (Actigraph, Pensacola, Fl). Average 24-hour
HR will be calculated for all wear days where the beginning and end of each 24-hour
day is defined as the average reported wake-up time for each participant. Average
24-hour HR will then be calculated for work days or non-work days separately. 
Heart rate variability measurement
Nocturnal heart rate variability (HRV) will be measured on every night of the 7-day
monitoring period using the Bluetooth HR strap described above to examine
autonomic function. A previous systematic review concluded that telemetric-derived
measures (Polar heart rate monitor) of HRV provide a valid alternative to
electrocardiogram measurement. Data collection will be done at a sampling beat to
beat resolution of 1 millisecond. HR data will be downloaded as interbeat R-R
intervals using ActiLife software (Actigraph, Pensacola, Fl) which will then be
imported into Kubios HRV software version 3.2 (Kubios HRV v.3.2, Kubios, Kuopio,
Eastern Finland) for HRV data analysis. The entire reported sleep duration will be
separated into valid 5-minute periods. Nocturnal HRV will be defined in two ways. 1)
All valid 5-minute segments will be averaged across the whole self-reported nights
sleep, resulting in a 5-minute average of all HRV metrics 2) Three 5-minutes periods
with the highest R-R intervals (lowest HR) will be determined for each sleep interval
and averaged. Both of these selection methods have been previously used to
evaluate nocturnal HRV. For each sleep interval detected, mean HRV values will be
determined using both methods and averaged across the night for each work day
and non-work day. HRV values that will be calculated for these time periods are: root
mean square successive difference (RMSSD), high frequency (0.15 – 0.4 Hz) (HF),
low frequency (0.04 – 0.15 Hz) (LF), very low frequency (0.003 – 0.04 Hz) (VLF),
and low frequency to high frequency ratio (LF/HF). Both time (RMSSD) and

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frequency (LF/HF) HRV domains will be used in statistical comparisons (134, 135).
All HRV values will be calculated using Kubios HRV software version 3.2.
Ambulatory blood pressure measurement
Each participant will be asked to wear the ambulatory BP monitor (ABPM) (Oscar 2,
SunTech Medical, Morrisville, NC) on their non-dominant arm for 24-hours on two
occasions throughout the monitoring period (one work day and one non-work day).
The participants will only be asked to wear the ABPM on two days during the 7-day
monitoring period to limit participant burden. These two days will be determined with
the participant and study staff on the day of the baseline assessment. Ideally, the
work day monitoring will be done with one work day prior and at least 48 hours after
the baseline assessment to limit any influence from the sub-maximal fitness test (i.e.
ABPM on a Wednesday when Tuesday was a work day and baseline assessment
was on a Monday). Similarly, the non-work day monitoring is ideally done with one
non-work day prior and at least 48 hours after the baseline assessment visit (i.e.
ABPM on Sunday if Saturday is a non-work day and baseline assessment was on a
Monday). Ambulatory BP will be measured using established protocols including
every 30 minutes during the day and every 60 minutes during sleep using self-
reported sleep and wake times (136). Participants will be given the ABPM upon
completion of the baseline assessment and be shown how to properly wear the
monitor. They will also be given standardized instructions on monitor wear, how to
start/end the monitoring, and when to wear the monitor (137). The participants will
be required to start and stop the monitor on their prescribed ABPM wear days.
However, phone call and email reminders will additionally encourage proper wear
time per protocol. ABPM data will be downloaded using Accuwin Pro software
(Suntech Medical, Morrisville, NC) and edited using the Verdecchia criteria for
physiologic BP readings and notable error codes (e.g., artifact or erratic oscillotertic
signal) given in the AccuWin pro software (138). Daily averages of BP and HR to be
compared across work and non-work days will be computed as 24-hour, daytime,
and nocturnal based on diary reported sleep and wake time.
Job Strain Measurement
Job strain will be measured once daily to quantify the level of psychological stress
that the participant is burdened with each day across the entire work day. This
measurement will be used to examine potential differences in cardiovascular
responses in participants with high versus low average job strain (Specific Aim III). A
previous study mentioned above found job strain to be associated with increased
HR and BP during work (116). Measurement of job strain will be completed at the
end of each work day in the provided paper dairy using the 8-item Stress in General
scale which has been extensively validated to measure work related stress (139).

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5) Answering questions/questionnaires: questionnaires are limited to those that
provide essential scientific information for this study, and this will reduce the time
requirements for completing these questionnaires.
6) Treadmill exercise will be limited to only those qualified for the study and
therefore are considered at low risk for a cardiovascular event. Specifically, any
individual with measured resting blood pressure of ≥150 mmHg systolic or ≥95
mmHg diastolic during the baseline assessment will be considered ineligible for
participation in the study. This method follows the American College of Sports
Medicine recommendations for safe exercise in those who do not report exercising
regularly. Heart rate, blood pressure, rating of perceived exertion, and participant
reported signs and symptoms of cardiovascular abnormality will be monitored
throughout the test. If any abnormal cardiovascular responses are observed by the
trained staff member running the exercise test, the test will be discontinued.
Furthermore, the exercise test will be prematurely terminated if any of the following
indications are met:
1. Onset of angina-like symptoms
2. Drop in SBP of 10 mm Hg with an increase in work rate or if SBP decreases
below the value obtained in the same position prior to testing
3. Excessive rise in BP: systolic pressure ≥220 mm Hg and/or diastolic pressure
≥100 mm Hg
4. Shortness of breath, wheezing, leg cramps, or claudication
5. Signs of poor perfusion: light-headedness, confusion, ataxia, pallor, cyanosis,
nausea, or cold and clammy skin
6. Subject requests to stop
7. Physical or verbal manifestations of severe fatigue
8. Failure of the testing equipment
The exercise test will also be conducted by an exercise physiologist trained to
recognize and respond to any emergencies. This individual is holds a master’s
degree in exercise physiology as well as is trained in American Heart Association
Advanced Cardiac Life Support (ACLS) to ensure appropriate response
qualifications in the case of an emergency. Furthermore, during all exercise tests, a
second person will be present in the room to assist as needed in the case of a
response. Finally, a faculty member of the department of health and physical activity
will be present in the building during the exercise test to assist in case of any
emergency situation.
3. Financial risks - will the subject or insurer be charged for any research
required procedures?

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
A. Have a financial interest (aggregated value of equity and remuneration
during the past or next twelve months) in a publicly-traded entity that either
sponsors this research or owns the technology being evaluated or developed
that exceeds a 5% ownership interest or a current value of $10,000?

B. Receive remuneration (during the past or next twelve months) from a non-
publicly traded entity that either sponsors this research or owns the technology
being evaluated or developed that exceeds $10,000?

C. Have equity in a non-publicly traded entity that either sponsors this research
or owns the technology being evaluated or developed?

D. Have rights as either the author or inventor of intellectual property being
evaluated or developed in this research and for which you are receiving
royalties, milestone fees, or other proceeds that have or will exceed $10,000 in
any 12-month period (include payments through the University of Pittsburgh,
the Veterans Administration Pittsburgh Healthcare System, UPMC, and
University of Pittsburgh Physicians)?

E. Have an officer or management position with a company that either
sponsors this research or owns the technology being evaluated or developed?

F. Receive compensation of any amount when the value of the compensation
would be affected by the outcome of this research, such as compensation that
is explicitly greater for a favorable outcome than for an unfavorable outcome or
compensation in the form of an equity interest in the entity that either sponsors
this research or owns the technology being evaluated or developed?

None of the above options apply and there are no other financial conflicts of
interest in the conduct of this research.
5. Provide the name of the investigator(s) and describe the nature of the
Significant Financial Interest(s):
Dr. Barone Gibbs discloses grant funding from the Agency for Healthcare Quality
Research, the American Heart Association, the National Institutes of Health, and the
Tomayko Fund.