Vigorous physical activity, incident heart disease, and cancer: how little is enough?

Abstract

Aims:
Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity levels. There is a very limited understanding of the minimal and optimal amounts of vigorous physical activity in relation to mortality and disease incidence.

Methods and results:
A prospective study in 71 893 adults [median age (IQR): 62.5 years (55.3, 67.7); 55.9% female] from the UK Biobank cohort with wrist-worn accelerometry. VPA volume (min/week) and frequency of short VPA bouts (≤2 min) were measured. The dose-response associations of VPA volume and frequency with mortality [all-cause, cardiovascular disease (CVD) and cancer], and CVD and cancer incidence were examined after excluding events occurring in the first year. During a mean post-landmark point follow-up of 5.9 years (SD ± 0.8), the adjusted 5-year absolute mortality risk was 4.17% (95% confidence interval: 3.19%, 5.13%) for no VPA, 2.12% (1.81%, 2.44%) for >0 to <10 min, 1.78% (1.53%, 2.03%) for 10 to <30 min, 1.47% (1.21%, 1.73%) for 30 to <60 min, and 1.10% (0.84%, 1.36%) for ≥60 min. The 'optimal dose' (nadir of the curve) was 53.6 (50.5, 56.7) min/week [hazard ratio (HR): 0.64 (0.54, 0.77)] relative to the 5th percentile reference (2.2 min/week). There was an inverse linear dose-response association of VPA with CVD mortality. The 'minimal' volume dose (50% of the optimal dose) was ∼15 (14.3, 16.3) min/week for all-cause [HR: 0.82 (0.75, 0.89)] and cancer [HR: 0.84 (0.74, 0.95)] mortality, and 19.2 (16.5, 21.9) min/week [HR: 0.60 (0.50, 0.72)] for CVD mortality. These associations were consistent for CVD and cancer incidence. There was an inverse linear association between VPA frequency and CVD mortality. 27 (24, 30) bouts/week was associated with the lowest all-cause mortality [HR: 0.73 (0.62, 0.87)].

Conclusion:
VPA of 15-20 min/week were associated with a 16-40% lower mortality HR, with further decreases up to 50-57 min/week. These findings suggest reduced health risks may be attainable through relatively modest amounts of VPA accrued in short bouts across the week.

Full text

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Vigorous physical activity, incident heart
disease, and cancer: how little is enough?
Matthew N. Ahmadi
1
*, Philip J Clare
1,2,3
, Peter T. Katzmarzyk
4
,
Borja del Pozo Cruz
5
, I-Min Lee
6,7
, and Emmanuel Stamatakis
1
1
Charles Perkins Centre, School of Health Sciences, Faculty of Medicine and Health, The University of Sydney, NSW, Australia;
2
Prevention Research Collaboration, School of Public Health,
Faculty of Medicine and Health, The University of Sydney, NSW, Australia;
3
National Drug and Alcohol Research Centre, UNSW Sydney, NSW, Australia;
4
Population and Public Health
Sciences, Pennington Biomedical Research Center, Baton Rouge, LA, USA;
5
Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark;
6
Division of Preventive Medicine, Brigham & Women’s Hospital, Harvard Medical School, Boston, USA; and
7
Department of Epidemiology, Harvard T.H. Chan School of Public Health,
Boston, MA, USA
Received 4 February 2022; revised 22 August 2022; accepted 28 September 2022
Abstract
Aims Vigorous physical activity (VPA) is a time-efficient way to achieve recommended physical activity levels. There is a very lim-
ited understanding of the minimal and optimal amounts of vigorous physical activity in relation to mortality and disease
incidence.
Methods
and results
A prospective study in 71 893 adults [median age (IQR): 62.5 years (55.3, 67.7); 55.9% female] from the UK Biobank cohort
with wrist-worn accelerometry. VPA volume (min/week) and frequency of short VPA bouts (≤2 min) were measured. The
dose–response associations of VPA volume and frequency with mortality [all-cause, cardiovascular disease (CVD) and can-
cer], and CVD and cancer incidence were examined after excluding events occurring in the first year. During a mean post-
landmark point follow-up of 5.9 years (SD ±0.8), the adjusted 5-year absolute mortality risk was 4.17% (95% confidence
interval: 3.19%, 5.13%) for no VPA, 2.12% (1.81%, 2.44%) for >0to<10 min, 1.78% (1.53%, 2.03%) for 10 to <30 min,
1.47% (1.21%, 1.73%) for 30 to <60 min, and 1.10% (0.84%, 1.36%) for ≥60 min. The ‘optimal dose’(nadir of the
curve) was 53.6 (50.5, 56.7) min/week [hazard ratio (HR): 0.64 (0.54, 0.77)] relative to the 5th percentile reference
(2.2 min/week). There was an inverse linear dose-response association of VPA with CVD mortality. The ‘minimal’volume
dose (50% of the optimal dose) was ∼15 (14.3, 16.3) min/week for all-cause [HR: 0.82 (0.75, 0.89)] and cancer [HR: 0.84
(0.74, 0.95)] mortality, and 19.2 (16.5, 21.9) min/week [HR: 0.60 (0.50, 0.72)] for CVD mortality. These associations were
consistent for CVD and cancer incidence. There was an inverse linear association between VPA frequency and CVD mor-
tality. 27 (24, 30) bouts/week was associated with the lowest all-cause mortality [HR: 0.73 (0.62, 0.87)].
Conclusion VPA of 15–20 min/week were associated with a 16–40% lower mortality HR, with further decreases up to 50–57 min/week.
These findings suggest reduced health risks may be attainable through relatively modest amounts of VPA accrued in short
bouts across the week.
* Corresponding author. Tel: +61 2 8627 8646, Email: matthew.ahmadi@sydney.edu.au
© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits
non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
European Heart Journal (2022) 00,1–14
https://doi.org/10.1093/eurheartj/ehac572
CLINICAL RESEARCH
Epidemiology and prevention
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Structured Graphical Abstract
What is the dose-response association of device-measured vigorous physical activity with mortality and incident cardiovascular disease
(CVD) and cancer?
15 minutes/week was associated with a 16% to 18% lower all-cause and cancer mortality, and 20 minutes/week was associated with 40%
Premature mortality and major chronic diseases may be lowered through relatively modest amounts of vigorous physical activity. Such
amounts are considerably lower than what questionnaire-based studies have proposed.
Key Question
Key Finding
Take Home Message
Vigorous exercise minutes/week
Percent
50 60 70 80
0.0
2.0
4.0
6.0
Age
0
0.75
Percent
Vigorous exercise minutes/week
1.25
1.75
10 20 30 40 50 60 70 80 90 100
10
8
6
4
2
0
none more than
0 to <10
10 to
<30
30 to
<60
60 or
more
Cumulative risk (%)
No vigorous physical activity
More than 0 to <10 minutes
30 to <60 minutes
60 or more minutes
10 to <30 minutes
Approximately 15 to 20 minutes of vigorous activity/week accrued through short bouts
were associated with substantially lower mortality and disease incidence
2 bouts/day up to 2
minutes each were
associated with 35%
lower CVD mortality
5-year risk of cardiovascular diseases incidenceCardiovascular disease mortality
15-20 min/week of vigorous
physical activity were associated
with 18-24% lower all-cause
mortality with an optimal dose
of 50-57 min/week
All-cause mortality
Approximately 15–20 min of vigorous activity/week accrued through short bouts were associated with lower mortality and disease incidence.
VPA =vigorous physical activity.
Keywords Physical activity •Mortality •Cardiovascular disease •Cancer •Vigorous intensity
Introduction
Based on existing prospective observational evidence, the 2020 World
Health Organization Physical activity and sedentary behaviour guide-
lines
1
and the physical activity guidelines for Americans, 2nd Edition
2
each recommended 150–300 min of moderate-to-vigorous physical ac-
tivity (MVPA), 75–150 min of vigorous physical activity (VPA), or a
combination of both a week. VPA, defined as physical activity at an en-
ergy expenditure rate of at least six metabolic equivalents (METs) is a
time-efficient way to achieve recommended physical activity levels
and can lead to rapid cardiorespiratory adaptations.
3
For the first
time, current physical activity guidelines
1,2,4,5
emphasize the value of
short bouts of intermittent physical activity (e.g. <5 min) for accumu-
lating the recommended amounts. Prior studies examining the health
2M.N. Ahmadi et al.
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benefits of VPA, which were limited by the inability of questionnaires to
capture shorter intermittent VPA sessions lasting under 10–15 min,
found that all-cause mortality (ACM) risk was lowered by approximate-
ly 10% when VPA contributed 30–50% of total MVPA time.
6,7
Findings
on cardiovascular disease (CVD) and cancer mortality showed similar
results.
8,9
Sixty to 90 min of weekly VPA accumulated through 10 to 15 min-
long bouts of exercise has been shown to be associated with a
3-year extension of life expectancy and a 4% lower risk of ACM for
every additional 15 min.
10,11
There is limited information on how low
volumes of VPA accumulated through short bouts are associated
with health and mortality. Such information is pertinent to improve
translation of research findings into clinical and public health interven-
tions involving accumulation of VPA through brief episodes throughout
the day.
Examining the dose-response of short and intermittent VPA bursts
requires device-based measurments.
9
Indeed, the World Health
Organization Guidelines Development Group recently indicated the
need for device-based studies to objectively assess the relationship of
physical activity with mortality and disease risk as a priority for re-
search.
12
The aim of this study was to examine the dose-response as-
sociation of device-measured VPA with mortality, and incident CVD
and cancer in the largest accelerometry cohort of UK adults. We hy-
pothesised inverse associations with mortality and incident CVD and
cancer exist through modest amounts of VPA accrued through short
bouts.
Methods
We reported this study as per the Strengthening the Reporting of
Observational Studies in Epidemiology (STROBE) guideline (Supplemental
STROBE Statement).
Study participants
Participants were included from the UK Biobank study, a prospective
cohort of 502 629 participants between 40–69 years. All participants
were enrolled between 2006–10 and provided informed written con-
sent. Ethical approval was provided by the UK National Health Service
(NHS), National Research Ethics Service (Ref 11/NW/0382).
Participants completed physical examinations by trained staff and
touchscreen questionnaires.
13
We excluded participants with prevalent
CVD or cancer (ascertained through self-report, hospital admission,
and cancer registry records), missing covariate data, or an event within
the first 12 months after the accelerometry measurements (landmark).
We considered the start of the landmark period as follow-up time on-
set (Supplementary material online, Figure 1).
Physical activity assessment
From 2013–15, 103,684 participants were mailed and wore an Axivity
AX3 accelerometer (Newcastle upon Tyne, UK) on their dominant wrist
for 24-h/day for 7 days to measure physical activity. Prior to being mailed,
the AX3 accelerometers were initialized to collect data with a sampling
frequency of 100 Hz and a dynamic range between ±8 g. Participants
returned the devices by mail and the data were calibrated and non-wear
periods were identified according to standard procedures.
14,15
Monitoring days were considered valid if wear time was greater than
16 h. To be included in analysis, participants were required to have at
least four valid monitoring days, with at least one of those days being a
weekend day (n=96459). Physical activity intensity was classified with
a validated accelerometer-based activity machine learning scheme cover-
ing VPA, moderate intensity physical activity, and light intensity physical
activity.
16
Briefly, this activity scheme uses features in the raw acceler-
ation signal to identify and quantify time spent in different activity types
and intensities in 10 s windows. A complete description is provided in
Supplementary material online, Text 1. To calculate physical activity vol-
ume, we summed time spent in each respective activity intensity band
across all valid wear days. Because 96% of VPA volume occurred in bouts
lasting up to 2 min, we did not carry out analyses of longer bouts.
Outcome ascertainment
Participants were followed up through 31 October 2021, with deaths
obtained through linkage with the NHS Digital of England and Wales or
the NHS Central Register and National Records of Scotland. Inpatient
hospitalization data were provided by either the Hospital Episode
Statistics for England, the Patient Episode Database for Wales, or the
Scottish Morbidity Record for Scotland. Cancer data linkage was ob-
tained through national cancer registries. For England and Wales, can-
cer diagnosis data were provided by the Medical Research Information
Service, based at the NHS Information Centre. For Scotland, cancer
diagnosis data were provided by the Information Services Division,
which is part of the NHS Scotland. Methods for the assessment of
CVD and cancer incidence are provided in Supplementary material
online, Table S1. In short, CVD was defined as diseases of the circulatory
system, excluding hypertension, diseases of arteries, and lymph. Cancer
was defined as neoplasms, excluding in situ, benign, uncertain, non-
melanoma skin cancer, or non-well-defined cancers. Due to the nature
of rolling updates for the data linkage, censoring dates varied between
resources (between September 2021 and October 2021).
Covariates
Based on the directed acyclic graph presented in Supplementary
material online, Figure 2, our selection of covariates included: age, sex,
accelerometer wear time, light intensity physical activity minutes, mod-
erate intensity physical activity minutes, smoking status, alcohol con-
sumption, sleep score based on five sleep indices (morning
chronotype, sleep duration, insomnia, snoring, and daytime sleepi-
ness),
17
fruit and vegetable consumption, discretionary screen-time de-
fined as time spent watching TV or using the computer outside of work,
highest attained education level, self-reported parental history of CVD
and cancer, and cholesterol, blood pressure, or diabetes medication
use. Complete covariate definitions are provided in Supplementary
material online, Table S2.
Analysis
We tabulated mortality and disease rate per 1000 person-years, the
crude risk,and age- and sex-adjusted incidence rate ratio within VPA vol-
ume groups (no VPA, >0to<10 min/week, 10 to <30 min/week, 30 to
<60 min/week, and ≥60 min/week). We calculated the dose–response
absolute risk between VPA volume and each outcome using Poisson re-
gression
18
(natural splines with knots at 10th, 50th, and 90th percen-
tiles
19
) to estimate the probability and the 95% confidence intervals
(CIs) of an event adjusting for all covariates. Further, we examined the
time-to-event dose-response associations of VPA volume, frequency
Vigorous activity, CVD, and cancer 3
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Table 1 Participant descriptive characteristics by quartiles of vigorous physical activity volume (min/week)
Vigorous physical activity (minutes/week)
Total
None 1 to <10 ≥10 to <30 ≥30 to <60 ≥60
n(%) 71 893 (100.0) 2532 (3.5) 18333 (25.5) 27 031 (37.6) 14 070 (19.6) 9927 (13.8)
Follow-up, years
a
5.9 (0.8) 5.8 (1.1) 5.9 (0.9) 5.9 (0.8) 5.9 (0.8) 5.9 (0.7)
Age, years, median (IQR) 62.5 (55.3, 67.7) 67.8 (62.9, 71.6) 65.2 (58.7, 69.4) 62.7 (55.7, 67.7) 60.3 (53.4, 66.2) 57.3 (51.4, 63.9)
Male sex, n(%) 31 678 (44.1) 805 (31.8) 6640 (36.2) 11678 (43.2) 6899 (49.0) 5656 (57.0)
Ethnicity, n(%)
White 69 568 (96.8) 2465 (97.4) 17 764 (96.9) 26 231 (97.0) 13 562 (96.4) 9546 (96.2)
Asian 825 (1.1) 25 (1.0) 205 (1.1) 297 (1.1) 168 (1.2) 130 (1.3)
Black 579 (0.8) 11 (0.4) 128 (0.7) 193 (0.7) 144 (1.0) 103 (1.0)
Mixed 387 (0.5) 10 (0.4) 94 (0.5) 128 (0.5) 92 (0.7) 63 (0.6)
Other 534 (0.7) 21 (0.8) 142 (0.8) 182 (0.7) 104 (0.7) 85 (0.9)
Smoking
history, n(%)
Never 41 159 (57.3) 1308 (51.7) 10 136 (55.3) 15 338 (56.7) 8273 (58.8) 6104 (61.5)
Previous 25 781 (35.9) 262 (10.3) 1474 (8.0) 1816 (6.7) 870 (6.2) 531 (5.3)
Current 4953 (6.9) 962 (38.0) 6723 (36.7) 9877 (36.5) 4927 (35.0) 3292 (33.2)
Alcohol intake
b
4.2 (1.2) 3.9 (1.2) 4.1 (1.2) 4.2 (1.1) 4.3 (1.1) 4.3 (1.1)
Sleep score
c
,n(%)
079 (0.1) 7 (0.3) 29 (0.2) 24 (0.1) 15 (0.1) 4 (0.0)
11328 (1.8) 79 (3.1) 429 (2.3) 495 (1.8) 211 (1.5) 114 (1.1)
26973 (9.7) 324 (12.8) 2060 (11.2) 2628 (9.7) 1225 (8.7) 736 (7.4)
319 178 (26.7) 761 (30.1) 5342 (29.1) 7306 (27.0) 3491 (24.8) 2278 (22.9)
427 382 (38.1) 897 (35.4) 6701 (36.6) 10301 (38.1) 5544 (39.4) 3939 (39.7)
516 953 (23.6) 464 (18.3) 3772 (20.6) 6277 (23.2) 3584 (25.5) 2856 (28.8)
Discretionary screen-time
d
4.6 (2.2) 5.0 (2.4) 4.9 (2.3) 4.6 (2.2) 4.4 (2.2) 4.2 (2.2)
Education, n(%)
College/University 31 529 (43.9) 1033 (40.8) 7568 (41.3) 11610 (43.0) 6336 (45.0) 4982 (50.2)
A/AS levels 9639 (13.4) 318 (12.6) 2409 (13.1) 3701 (13.7) 1870 (13.3) 1341 (13.5)
O levels 14 684 (20.4) 514 (20.3) 3804 (20.7) 5692 (21.1) 2921 (20.8) 1753 (17.7)
CSE 2843 (3.9) 66 (2.6) 685 (3.7) 1046 (3.9) 589 (4.2) 457 (4.6)
Continued
4M.N. Ahmadi et al.
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Table 1 Continued
Vigorous physical activity (minutes/week)
Total
None 1 to <10 ≥10 to <30 ≥30 to <60 ≥60
NVQ/HND/HNC 3861 (5.4) 147 (5.8) 992 (5.4) 1441 (5.3) 758 (5.4) 523 (5.3)
Other 9337 (12.9) 454 (17.9) 2875 (15.7) 3541 (13.1) 1596 (11.3) 871 (8.8)
Diet
e
8.1 (4.3) 8.0 (4.1) 8.0 (4.2) 8.1 (4.4) 8.0 (4.2) 8.3 (4.5)
Family history of CVD, n(%) 39 337 (54.7) 1519 (60.0) 10 744 (58.6) 14 842 (54.9) 7338 (52.2) 4894 (49.3)
Family history of cancer, n(%) 17 915 (24.9) 667 (26.3) 4732 (25.8) 6833 (25.3) 3388 (24.1) 2295 (23.1)
Medication, n(%)
Cholesterol 10 052 (14.0) 664 (26.2) 3522 (19.2) 3747 (13.9) 1425 (10.1) 694 (7.0)
Blood pressure 11 748 (16.3) 832 (32.9) 4189 (22.8) 4360 (16.1) 1581 (11.2) 786 (7.9)
Diabetes 458 (0.6) 37 (1.5) 177 (1.0) 142 (0.5) 63 (0.4) 39 (0.4)
Wear-time, days 6.7 (0.7) 6.7 (0.9) 6.7 (0.7) 6.7 (0.7) 6.7 (0.6) 6.7 (0.6)
Total activity, median (IQR) 854.1 (643.8, 1144.7) 500.1 (333.5, 696.0) 677.3 (498.5, 878.3) 848.0 (668.5, 1089.0) 1012.3 (763.2, 1286.2) 1215.5 (928.3, 1518.8)
Light activity, median (IQR) 530.7 (341.5, 793.0) 336.6 (190.5, 500.0) 430.5 (256.5, 639.8) 526.2 (355.3, 788.8) 614.3 (428.3, 892.3) 671.3 (476.3, 971.0)
Moderate activity, median (IQR) 199.2 (106.8, 379.3) 97.4 (36.3, 196.0) 154.50 (68.7, 306.5) 196.00 (104.7, 367.3) 235.00 (144.0, 423.1) 397.67 (196.0, 515.6)
Vigorous activity, median (IQR) 16.5 (8.3, 38.5) - 5.7 (3.7, 7.7) 15.7 (11.2, 20.7) 38.3 (32.5, 46.5) 88.5 (71.8, 96.2)
%VPA, median (IQR) 8.8 (3.8, 18.5) - 3.4 (1.6, 7.4) 8.1 (4.6, 14.7) 14.6 (8.7, 22.4) 19.9 (11.6, 25.6)
Vigorous bouts (up to 2 minutes), median (IQR) 13 (5, 25) - 3 (1, 5) 13 (9, 17) 29 (23, 35) 49 (34, 64)
Values represent mean (SD), unless specified otherwise.
a
Landmark period 12 months after primary exposure measurement.
b
Units/week (1 unit =8 grams of pure ethanol).
c
Sleep scores were determined using an established method (Huang B-H et al. BJSM 2021). In brief, participants were categorized by how many healthy sleep characteristics (morning chronotype, adequate sleep duration (7–8 hr/d), never or rare
insomnia, never or rare snoring, and infrequent daytime sleepiness) they displayed.
d
Discretionary screen-time composed of time spent/day watching TV and using a computer.
e
Fruit and vegetable servings/day.
Vigorous activity, CVD, and cancer 5
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(bouts/week), and the percentage contribution of VPA to total MVPA
volume (%VPA)with the five outcomes. For these analyses, we calculated
hazard ratios (HRs) using Cox proportional hazards (ACM) and
Fine-Gray subdistribution models for CVD and cancer outcomes (treat-
ing non-CVD or cancer deaths as competing risks as appropriate) with
knots at 10th, 50th, and 90th percentiles
19
and age as the timescale.
We also calculated the adjusted survival probability and 5-year risk.
Sequential hazards modelling for VPA volume included adjustments
for: sex (Model 1); Model 2 additionally adjusted for lifestyle and health
factors (smoking, alcohol, sleep quality score, discretionary screen-time,
diet, family history of CVD and cancer, and medication use); Model 3 add-
itionally adjusted for physical activity variables (light and moderate inten-
sity minutes,and accelerometer wear time), as well as mutual adjustment
for volume and frequency of VPA. We present Model 3 as the main ana-
lysis. The reference was set to 2.2 min/week, equivalent to the 5th per-
centile of the volume distribution, one bout/week for frequency analysis,
and 0.25% for %VPA analysis. Proportional hazards assumptions were as-
sessed using Schoenfeld residuals and no violations were observed (P>
0.05). For both absolute risk and HR analyses, departure from linearity
was assessed by a Wald test examining the null hypothesis that the co-
efficient of the second spline was equal to zero.
We calculated E-values to estimate the plausibility of bias from un-
measured confounding.
20
The E-values indicate the required magnitude
of the association unmeasured confounders to reduce findings to null.
Additional time-to-event analyses were performed to examine associa-
tions with mortality and incident disease across lifestyle and health vari-
able groups. To provide conservative point estimates for associations,
we assessed the minimal dose, defined as the volume of VPA associated
with 50% of the lowest HR (‘optimal dose’; nadir of the dose
curve).
21,22
We used bootstrapping with replacement (1000 iterations)
to calculate CIs for the optimal and minimal dose. We fit interaction
terms between VPA volume and light and moderate volume, separately.
The interaction term was not significant and did not improve model fit,
and therefore we do not present effect modification. To examine the
possibility of reverse causation, we excluded the second year from ac-
celerometry measurement baseline and those participants who were
on CVD medication or who had self-rated poor health.
To further assess robustness of our results to alternative analytic de-
cisions, we carried out the following sensitivity analyses: (i) we addition-
ally adjusted analyses for (body mass index-based) obesity strata; (ii) we
set the reference to zero minutes and 6.7 min/week (20th percentile of
volume distribution); (iii) we included participants with less than one
year of follow-up; (iv) we imputed missing data for covariates by using
multiple imputation using chained equations (five imputed data sets);
and (v) we assessed the dose-response of ACM with CVD and cancer
deaths treated as competing risks.
We performed all analysis using R statistical software with the rms
and survival packages.
23,24
Results
Our analytic sample for mortality included 71 893 participants [me-
dian age (IQR): 62.5 (55.3, 67.7) years; 55.9% female; characteristics
of excluded participants are shown in Supplementary material
online, Table S3) followed up for an averag e of 5.9 ±0.8 years (starting
from the landmark period 12 months after follow-up, or 6.9 years
from accelerometry measurement) with 1927 deaths (602 CVD
and 1150 cancer; Supplementary material online, Table S4). Our inci-
dent CVD sample included 71 049 participants with 4567 (3965 non-
fatal; Supplementary material online, Table S5) events. Our incident
cancer sample included 71 070 participants with 2854 (1704 non-fatal;
Supplementary material online, Table S5)events.MedianVPAand%
MVPA time was 16.5 (IQR =8.3, 38.5) minutes/week and 9.0%
(3.8%, 18.5%), respectively. The median frequency of VPA bouts/
week lasting up to 2-minutes was 13 (5, 25). Participants wore the ac-
celerometers for an average of 6.7 days and 22.8 h/day. Participant
characteristics by VPA volume are provided in Table 1. Within each
low-to-high quartile, median VPA time was 5.7, 15.7, 38.3, and
88.5 min/week, respectively.
Mortality and disease incidence risk
Tables 2 and 3present the crude event rates per 1000 person-years,
crude risk, and sex and age adjusted incidence rate ratios for mortality
and disease incidence by VPA volume groups. Compared to partici-
pants with zero minutes of VPA, the incidence rate ratio among parti-
cipants with 10 to 30 min/week was approximately one-third for
all-cause [0.35 (95% CI: 0.30, 0.42)] and CVD mortality [0.34 (0.26,
0.46)]. The rate was about one-half for 10–30 min/week for CVD
[0.58 (0.50, 0.67)] and cancer incidence [0.44 (0.34, 0.56)].
Figures 1–3show the adjusted absolute risk, adjusted 5-year risk, and
adjusted survival curves. Participants with zero minutes of VPA had an
absolute risk of 1.69% (1.45%, 1.99%) (5-year risk=4.17% (3.19%,
.................................................................................................................................
......................................................................................................................................................................................
Table 2 Mortality and disease incidence event rates per 1000 person-years
a
Vigorous physical activity (min/week)
b
Events
None >0to<10 ≥10 to <30 ≥30 to <60 ≥60
All-cause mortality 1927 13.4 (11.7, 15.4) 5.5 (5.1, 5.9) 3.8 (3.6, 4.1) 2.6 (2.3, 3.0) 1.8 (1.4, 2.1)
CVD mortality 602 4.4 (3.4, 5.6) 1.9 (1.7, 2.2) 1.2 (1.0, 1.4) 0.7 (0.5, 0.9) 0.3 (0.2, 0.5)
Cancer mortality 1150 5.5 (4.4, 6.9) 2.6 (2.3, 2.9) 1.9 (1.7, 2.1) 1.4 (1.2, 1.7) 1.0 (0.8, 1.4)
CVD incidence 4567 22.5 (20.1, 25.1) 14.5 (13.9, 15.2) 10.8 (10.3, 11.3) 8.8 (8.2, 9.4) 7.4 (6.7, 8.1)
Cancer incidence 2854 13.2 (11.4, 15.2) 8.0 (7.5, 8.5) 6.1 (5.8, 6.5) 5.2 (4.7, 5.7) 3.9 (3.4, 4.5)
a
Unadjusted estimates.
b
Groupings are based on quartiles of vigorous physical activity volume with zero minutes/week as its own group.
CVD included ICD-10 codes: I0, I11, I13, I20-I51, I60-I69.
Cancer included ICD-10 codes: C0-C9, excluding basal and squamous cell carcinoma.
6M.N. Ahmadi et al.
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5.13%) for all-cause mortality. In comparison, 10 to <30 min/week of
VPA was associated with a risk of 1.35% (1.18%, 1.55%) [5-year risk =
1.78% (1.53%, 2.03%)], 30 to <60 min/week had a risk of 1.06%
(0.90%, 1.24%) [5-year risk =1.47% (1.21%, 1.73%)], and ≥60 min/
week had a risk of 1.05% (0.87%, 1.27%) [5-year risk =1.10% (0.84%,
1.36%)]. For CVD incidence, corresponding results were 4.96%
(4.50%, 5.47%) [5-year risk =7.64% (6.46%, 8.81%), 4.08% (3.75%,
4.45%)] [5-year risk =4.65% (4.26%, 5.04%)], 3.32% (3.02%, 3.65%)
[5-year risk =4.26% (3.84%, 4.68%)], and 3.29% (2.95%, 3.68%) [5-year
risk =4.02% (3.53%, 4.51%)], respectively. For cancer incidence, they
were 2.34% (2.08%, 2.66%) [5-year risk =7.30% (5.90%, 8.68%)],
1.94% (1.78%, 2.13%) [5-year risk =4.79% (4.30%, 5.28%)], 1.84%
(1.68%, 2.03%) [5-year risk =4.82% (4.22%, 5.42%)], and 1.86%
(1.60%, 2.24%) [5-year risk =4.36% (3.67%, 5.05%)]. Supplementary
material online, Table S6 presents the absolute risk estimates in five mi-
nute increments for all mortality and disease incidence outcomes.
......................................................................................................................................................................................
Table 3 Crude risk, and sex and age adjusted incidence rate ratio by vigorous physical activity groups
Vigorous activity (min/week)
a
Crude risk (%) Incidence rate ratio
All-cause mortality
None 10.23 (8.77, 11.70) Reference
>0to<10 4.02 (3.78 4.35) 0.45 (0.39, 0.54)
≥10 to <30 2.66 (2.49, 2.82) 0.35 (0.30, 0.42)
≥30 to <60 1.82 (1.63, 2.01) 0.27 (0.22, 0.33)
≥60 1.23 (1.03, 1.42) 0.20 (0.16, 0.26)
Cardiovascular disease mortality
None 3.47 (2.58, 4.36) Reference
>0to<10 1.41 (1.27, 1.54) 0.51 (0.39, 0.67)
≥10 to <30 0.82 (0.73, 0.91) 0.34 (0.26, 0.46)
≥30 to <60 0.47 (0.37, 0.57) 0.22 (0.15, 0.31)
≥60 0.21 (0.12, 0.29) 0.11 (0.06, 0.19)
Cancer mortality
None 4.94 (3.89, 5.99) Reference
>0to<10 2.21 (2.04, 2.39) 0.55 (0.43, 0.71)
≥10 to <30 1.62 (1.49, 1.75) 0.44 (0.34, 0.56)
≥30 to <60 1.21 (1.06, 1.37) 0.37 (0.28, 0.50)
≥60 0.90 (0.73, 1.06) 0.31 (0.22, 0.44)
Cardiovascular disease incidence
None 15.52 (13.77, 17.27) Reference
>0to<10 9.78 (9.43, 10.13) 0.73 (0.64, 0.84)
≥10 to <30 7.21 (6.94, 7.48) 0.58 (0.50, 0.67)
≥30 to <60 5.92 (5.58, 6.25) 0.50 (0.43, 0.58)
≥60 5.05 (4.64, 5.45) 0.47 (0.39, 0.55)
Cancer incidence
None 5.80 (4.36, 7.24) Reference
>0to<10 3.77 (3.49, 4.04) 0.53 (0.42, 0.68)
≥10 to <30 2.31 (2.10, 2.52) 0.44 (0.34, 0.56)
≥30 to <60 1.68 (1.41, 1.94) 0.40 (0.30, 0.53)
≥60 0.80 (0.51, 1.09) 0.38 (0.25, 0.56)
a
Groupings are based on quartiles of vigorous activity volume with zero minutes/week as its own group.
CVD included ICD-10 codes: I0, I11, I13, I20-I51, I60-I69.
Cancer included ICD-10 codes: C0-C9, excluding basal cell carcinoma and squamous cell carcinoma.
Vigorous activity, CVD, and cancer 7
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Multivariable-adjusted associations
with all-cause, cardiovascular
disease, and cancer mortality
Volume
We observed a non-linear (p
non-linear
<0.01) dose–response association
for VPA volume and ACM with the optimal dose (lowest HR) at 53.6
(50.5, 56.7) minutes/week [corresponding to an HR of 0.64 (0.54,
0.77)]compared with the referent 2.2 min/week (Figure 4A). The min-
imum dose of VPA was 14.9 [14.3, 15.4] min/week [0.82 (0.75, 0.89)]
with an E-value of 1.74 (lower 95% CI 1.49). There was an inverse linear
(p
non-linear
=0.42) dose-response association of VPA volume and CVD
mortality (Figure 4B). The minimum dose was 19.2 (16.5, 21.9)
min/week [0.60 (0.50, 0.72)] with an E-value of 2.73 (2.11). Higher
VPA volume was associated with decreased cancer mortality in a non-
linear (p
non-linear
=0.02) relationship with the optimal dose at 55.4
(54.0, 56.0) minutes/week [0.68 (0.52, 0.88)] (Figure 4C). The minimum
dose was 15.9 (15.5, 16.3) minutes/week [0.84 (0.74, 0.95) with an
E-value of 1.68 (1.29)]. Across lifestyle and health groups, we observed
lower mortality HR for the minimum dose of VPA with all
three mortality outcomes except for participants with a parental history
of cancer (Supplementary material online, Figures 3–5). Supplementary
material online, Figure 6 shows the sequential modelling results.
Percent contribution of vigorous activity
and frequency
There was a non-linear inverse dose–response (Supplementary material
online, Figure 7) association for %VPA and all three mortality outcomes.
The optimal dose was 8.4% (6.7%, 10.2%) and 8.1% (6.1%, 10.2%) for
ACM [0.54 (0.46, 0.63)] and CVD [0.42 (0.31, 0.55)], respectively.
Attenuation of the association for %VPA became pronounced at >11.0%
forCVDmortality.Forcancermortality,therewasnoappreciable(rateof
HR change <0.003) HR decrease beyond 15.0% [0.63 (0.45, 0.88)]. Bouts
lasting up to 2 min exhibited an inverse non-linear (p
non-linear
<0.01) associ-
ation with all-cause and cancer mortality, withthe optimal dose at 27 (24, 30)
bouts/week [0.73 (0.62, 0.87)] and 31 (27, 35) bouts/week [0.60 (0.49, 0.73)],
respectively. CVD mortality exhibited an inverse linear associ ation (p
non-linear
=0.38) with a minimum frequency dose of 14 (12, 16) bouts/week [0.65
(0.53, 0.80)] (Supplementary material online, Figure 8A–C).
Figure 1 Adjusted absolute risk estimates for mortality and disease incidence by vigorous physical activity volume (minutes/week). Adjusted for age, sex, wear
time, light intensity, moderate intensity, frequency of vigorous bouts, smoking history, alcohol consumption, sleep score, diet, discretionary screen-time, edu-
cation, self-reported parental history of CVD and cancer, and self-reported medication use (cholesterol, blood pres sure, and diabetes). The range was capped at
the 97.5 percentile to minimize the influence of sparse data. Mortality: n=71 893; events: all-cause =1,927, cardiovascular disease =602, cancer =1150.
Cardiovascular disease: n=71,049, events =4567. Cancer: n=71,070, events =2854.
8M.N. Ahmadi et al.
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Multivariable-adjusted associations
with cardiovascular disease, and
cancer incidence
Volume
Associations for CVD and cancer incidence were non-linear
(p
non-linear
<0.01) with the optimal dose at 56.5 (55.4, 55.6) min/
week [0.69 (0.63, 0.76)] and 46.3 (42.9, 49.7) min/week [0.67
(0.55, 0.82)] (Figure 5A–B). The minimal dose for CVD was 15.0
(14.3, 15.7) min/week [0.85 (0.81, 0.89); E-value=1.65 (1.51)], and
cancer was 12.0 (10.3, 13.7) min/week [0.83 (0.75, 0.93); E-value =
1.69 (1.36)]. Supplementary material online, Figure 9 shows the se-
quential modelling results.
Percent contribution of vigorous activity
and frequency
The dose–response curves for %VPA with CVD and cancer inci-
dence were non-linear (p
non-linear
<0.01) (Supplementary material
online, Figure 10). The optimal dose for CVD and cancer was 7.1%
(3.3%, 10.4%) and 9.1% (6.1%, 12.1%) corresponding to an HR of
0.66 (0.56, 0.79) and 0.61 (0.47, 0.80). The minimum frequency
dose for bouts lasting up to 2 min was 10 (7, 13) bouts/week for
CVD and cancer incidence corresponding to an HR of 0.84 (0.80,
0.89) and 0.83 (0.74, 0.92) (Supplementary material online,
Figure 8D–E).
Sensitivity and additional analyses
Our sensitivity analyses produced similar findings. For example, exclud-
ing the first 2 years of follow-up, participants with self-rated
poor health, or using CVD medication, there was an inverse linear
(p
non-linear
=0.10) dose–response association for CVD mortality, and
for ACM, the optimal and minimum dose was 56.0 (50.4, 61.4) min/
week [0.74 (0.59, 0.92)] and 16.0 (12.8, 19.2) min/week [0.87 (0.78,
0.97)] (Supplementary material online, Figure 11). Results were robust
when adjusting for obesity strata (results available upon request). Dose–
response associations were consistent for VPA volume when zero min,
or 6.7 min (20th percentile) was the reference (Supplementary material
online, Figure 12), or when multiple imputation of covariates was applied
(results available upon request). Including participants with an event in the
first year of follow-up showed similar HRs as the main analysis except for
CVD incidence where associations were more pronounced
(Supplementary material online, Figures 13 and 14). In the ACM analyses
treating CVD and cancer deaths as competing risk (Supplementary
material online, Figure 15) the optimal dose for bouts/week was 24 (20,
28) corresponding to an HR of 0.50 (0.36, 0.71). The optimal dose for
VPA volume was 52.2 (48.9, 55.5) min/week [0.41 (0.28, 0.61)] with a min-
imal dose of 12.8 (10.2, 15.4) min/week [0.70 (0.60, 0.82)].
Discussion
We observed a consistent non-linear inverse association between VPA
and all-cause and cancer mortality, and a linear dose-response associ-
ation for CVD mortality. The incident disease optimal and minimal
Figure 2 Adjusted 5-year risk for mortality and disease incidence by vigorous physical activity volume groups. Timescale was follow-up years. Adjusted
for age, sex, wear time, light intensity, moderate intensity, frequency of vigorous bouts, smoking history, alcohol consumption, sleep score, diet, dis-
cretionary screen-time, education, self-reported parental history of CVD and cancer, and self-reported medication use (cholesterol, blood pressure,
and diabetes). Mortality: n=71 893; events: all-cause =1,927, cardiovascular disease =602, cancer =1150. Cardiovascular disease: n=71,049, events =
4567. Cancer: n=71,070, events =2854.
Vigorous activity, CVD, and cancer 9
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dose results were broadly comparable with those from mortality, with
a steep gradient for 5-year CVD incidence risk. While acknowledging
that VPA guidelines were largely derived from questionnaire data,
our dose–response curves for all three mortality outcomes suggested
that levels well under the current recommended 75 min/week of
VPA were associated with the lowest risk.
We found ∼53 min/week of VPA was associated with 36% lower
ACM, with modest additional beneficial associations for more VPA.
Regarding minimum dose, ∼15 min/week was associated with a 16–
18% lower all-cause and cancer mortality risk, and 20 min/week was as-
sociated with a 40% lower CVD mortality risk (Structured Graphical
Abstract). These findings are important from a public health and clinical
Figure 3 Adjusted survival curves for mortality and disease incidence by vigorous physical activity volume groups. Timescale was age. Adjusted for sex,
wear time, light intensity, moderate intensity, frequency of vigorous bouts, smoking history, alcohol consumption, sleep score, diet, discretionary
screen-time, education, self-reported parental history of CVD and cancer, and self-reported medication use (cholesterol, blood pressure, and diabetes).
Mortality: n=71 893; events: all-cause =1,927, cardiovascular disease =602, cancer =1150. Cardiovascular disease: n=71,049, events =4567. Cancer:
n=71,070, events =2854.
10 M.N. Ahmadi et al.
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perspective, given that lack of time remains the most commonly cited
barrier to regular physical activity across age, sex, ethnicity, and health
status.
25–27
Only 20% of middle age to older adults report engaging in any VPA
for at least 15 continuous minutes.
28
Sustained participation in VPA
leisure-time physical activity requires considerable time and often mon-
etary commitment and can be physically challenging for people with
poor fitness or established cardiovascular and cancer risk factors
such as hypertension and obesity. Our results show accumulating
VPA in short bouts that last up to 2 min on average four times/day
was associated with substantially lower (27%) mortality risk.
Although not directly assessed in this study, our findings suggest that
short VPA bouts may be also embedded into regular activities of daily
living and accrued intermittently throughout a week.
3
The VPA volume
doses we identified as potentially beneficial were consistent across age,
sex, and many lifestyle and health risk factors. They are also consistent
with proof of concept trials showing demonstrable effects of short
VPA bouts on cardiorespiratory fitness in physically inactive
adults.
29,30
Findings from these trials suggest short VPA durations
can stimulate the cardiorespiratory system and lead to measurable
cardiovascular adaptations. This is particularly relevant for clinicians
and health practitioners who provide intervention to individuals
who may be unable or unwilling to engage in long blocks of sustained
exercise-based VPA. The latest European Society of Cardiology
guidelines identified physical activity as a modifiable risk factor that re-
mains challenging to address, even among patients considered to be at
high CVD risk.
31
Encouraging participation in VPA of any length
throughout the day provides additional options for adults of all
ages, which might facilitate engagement, long-term adherence, and
promote VPA opportunities.
Questionnaire-based studies have suggested 60–70 min/week of
VPA behaviour can attenuate mortality risk by 30%.
10,11,32,33
Our
device-based findings suggest that a minimal dose of 20 min/week of ac-
tual VPA provides similar levels of lower mortality risk. While acknow-
ledging that questionnaires and devices measure related but different
constructs, our study suggests a ∼3:1 equivalence of VPA time captured
by questionnaires and accelerometers.
Previous studies assessing %VPA reported much higher percentages
(30 to 50%) were associated with 10% lower mortality relative to no
VPA.
6,7
These previous %VPA findings may be affected by the suscep-
tibility of over-reporting due to social desirability bias from self-reports.
By using objective device-based measures of physical activity, we found
a contribution of 8% had the strongest association and lowered mortal-
ity risk by 45% to 53%. These findings suggest that relatively modest
Figure 4 Dose–response association between vigorous physical activity volume (minutes/week) and all-cause, cardiovascular disease, and cancer mor-
tality. Timescale was age. Adjusted for sex, wear time, light intensity, moderate intensity, frequency of vigorous bouts, smoking history, alcohol con-
sumption, sleep score, diet, discretionary screen-time, education, self-reported parental history of CVD and cancer, and self-reported medication
use (cholesterol, blood pressure, and diabetes). The range was capped at the 97.5 percentile to minimize the influence of sparse data. Sample =71
893; events: all-cause =1,927, cardiovascular disease =602, cancer =1150; reference=2.2 min/week. Linearity: ACM (P<0.01); CVD (P=0.42); can-
cer (P<0.01). Nadir: ACM [53.6 min/wk; HR =0.64 (0.54, 0.77)]; cancer [55.4 min/wk; HR =0.68 (0.52, 0.88)].
Vigorous activity, CVD, and cancer 11
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contributions of VPA relative to total MVPA are associated with sub-
stantively lower risk for mortality and incident disease, calling for pro-
motion of even small amounts of vigorous intensity activities. These
beneficial associations are more pronounced than previously reported
by studies using questionnaire-based data.
6–8
This may provide oppor-
tunities for improvement of CVD preventative strategies in
cardio-oncology where high-intensity activity has been shown to at-
tenuate the cardiotoxicity of cancer treatments.
34,35
Whilst our results
reflect associations that can be expected in the general population, the
health benefits from contributions of different %VPA proportions
should be considered in relation to a person’s capacity. Narrative re-
views
36
and meta-analyses
37,38
report mixed findings on the relative
contributions of moderate and vigorous activities. A recent review of
physical activity intensity
39
suggests that the balance of physical activity
intensities needs to be determined relative to a person’sfitness and
functional capacity, reflecting metabolic conditions above which physio-
logical homeostasis is challenged and adaptations occur.
Previous device-based studies
40–42
have used a lower resolution of
physical activity, measured in 1 minute intervals, which may mask short
VPA durations and lead to an under-estimation of VPA volume, and
over-estimation of VPA volumes associated with health outcomes.
Under-estimation of VPA volume would have contributed to low stat-
istical power, making it difficult to discern associations of VPA volume
and frequency with health outcomes. Using a higher resolution of phys-
ical activity measures (10 second interval), we found the majority (92%)
of VPA durations lasted 1 minute or less. This is consistent with a
study
43
in overweight postmenopausal women that reported significant
interval effects for estimated VPA time over 7 days for 10 s intervals
compared with 1 min intervals and a review in children that found
VPA volume decreased 4-fold when measurement intervals increased
from 5 s to 1 min using wearable devices.
44
Studies assessing the
association between CVD incidence and physical activity intensity vol-
ume with wrist-worn devices have reported an inverse linear associ-
ation.
45,46
We now further focus specifically on VPA and investigate
in depth not only the volume dose response but also the associations
of weekly frequency and the percentage contribution of VPA to total
MVPA time with mortality and incident disease risk. By using a two-step
activity recognition approach that considers activity type and inten-
sity,
47,48
our study provides translation-ready VPA findings for public
health guidelines and preventive care practice.
Strengths and limitations
Strengths of our study include the use accelerometers to objectively
measure physical activity in the largest resource to date with linkage
Figure 5 Dose–response association between vigorous physical activity volume (min/week) and incidence of cardiovascular disease (n=71 049;
events =3730) and cancer (n=71 070; events =1315). Timescale was age. Adjusted for sex, wear time, light intensity physical activity, moderate in-
tensity physical activity, frequency of vigorous bouts, smoking history, alcohol consumption, sleep score, diet, screentime, education, self-reported par-
ental history of CVD and cancer, and self-reported medication use (cholesterol, blood pressure, and diabetes). The range was capped at the 97.5
percentile to minimize the influence of sparse data. Cardiovascular disease: n=71,049, events =4567. Cancer: n=71,070, events =2854.
Reference =2.17 min/week. Linearity: CVD (P<0.01); cancer (P<0.01). Nadir: CVD (56.5 min/wk; HR =0.69 [0.63, 0.76]); cancer (46.3 min/wk;
HR =0.67 [0.55, 0.82]).
12 M.N. Ahmadi et al.
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to prospective outcomes.
49
The large sample size and long follow up
allowed us to reduce the risk of reverse causality by removing partici-
pants who had an event in the first two years, prevalence of major dis-
ease, self-rated poor health, or used CVD medication. Despite the
extensive precautionary measures, the potential for reverse causation
may still exist caused by low activity levels due to undiagnosed or pro-
dromal disease.
50
Due to the observational design, we cannot rule out
the presence of unmeasured confounding. However, our e-values indi-
cate an unmeasured confounder would have to have a strong associ-
ation between 1.65 and 2.73 with the exposure and outcome for the
observed relationship to be null. The UK Biobank had a very low re-
sponse rate, and participants in our sample were subject to additional
selection criteria and should be considered when interpreting our re-
sults. Although, evidence suggests that this and the subsequent unrep-
resentativeness to the target population does not affect estimates of
physical activity with mortality.
51
Conclusion
Approximately 15–20 min of vigorous activity per week accrued
through short bouts were associated with lower mortality, and CVD
and cancer incidence. Our findings suggest premature mortality and
major chronic disease may be lowered through relatively modest
amounts of VPA with further decreases up to 50–57 min/week.
These results may inform future physical activity recommendations
and, combined with effective intervention strategies, may improve
population health outcomes.
Supplementary material
Supplementary material is available at European Heart Journal online.
Acknowledgements
This research has been conducted using the UK Biobank Resource, a
major biomedical database, under application number 25813. The
authors would like thank all the participants and professionals contrib-
uting to the UK Biobank, and Dr. Bo-Huei Huang for his assistance with
an early version of this manuscript.
Funding
This study is funded by an Australian National Health and Medical Research
Council (NHMRC) Investigator Grant (APP 1194510).
Conflict of interest: None declared.
Data availability
The UK Biobank data that support the findings of this study can be accessed
by researchers on application (https://www.ukbiobank.ac.uk/register-apply/).
References
1. Bull FC, Al-Ansari SS, Biddle S, Borodulin K, Buman MP, Cardon G, et al. World health
organization 2020 guidelines on physical activity and sedentary behaviour. Br J Sports
Med 2020;54:1451–1462.
2. Piercy KL, Troiano RP, Ballard RM, Carlson SA, Fulton JE, Galuska DA, et al. The physical
activity guidelines for Americans. JAMA 2018;320:2020–2028.
3. Stamatakis E, Huang BH, Maher C, Thøgersen-Ntoumani C, Stathi A, Dempsey PC, et al.
Untapping the health enhancing potential of vigorous intermittent lifestyle physical ac-
tivity (VILPA): rationale, scoping review, and a 4-pillar research framework. Sport Med
2021;51:1–10.
4. Ross R, Chaput JP, Giangregorio LM, Janssen I, Saunders TJ, Kho ME, et al. Canadian
24-Hour Movement guidelines for adults aged 18–64 years and adults aged 65 years
or older: an integration of physical activity, sedentary behaviour, and sleep. Appl
Physiol Nutr Metab 2020;45:S57–S102.
5. Department of Health and Social Care. Physical Activity Guidelines: UK Chief Medical
Officers’Report; Department of Health and Social Care: London, UK, 2019. Available
online: https://www.gov.uk/government/publications/physical-activity-guidelines-uk-ch.
6. Wang Y, Nie J, Ferrari G, Rey-Lopez JP, Rezende LFM. Association of physical activity
intensity with mortality: a national cohort study of 403681 US adults. JAMA Intern
Med 2021;181:203–211.
7. Gebel K, Ding D, Chey T, Stamatakis E, Brown WJ, Bauman AE. Effect of moderate to
vigorous physical activity on all-cause mortality in middle-aged and older Australians.
JAMA Int Med 2015;175:970–977.
8. Rey Lopez JP, Gebel K, Chia D, Stamatakis E. Associations of vigorous physical activity
with all-cause, cardiovascular and cancer mortality among 64 913 adults. BMJ Open Sport
Exerc Med 2019;5:e000596.
9. Pablo J, Lopez R, Sabag A, Juan MM. Do vigorous-intensity and moderate- intensity phys-
ical activities reduce mortality to the same extent ? A systematic review and
meta-analysis. BMJ Open Sport Exerc Med 2020;0:e000775.
10. Wen CP, Wai JPM, Tsai MK, Yang YC, Cheng TYD, Lee MC, et al. Minimum amount of
physical activity for reduced mortality and extended life expectancy: a prospective co-
hort study. Lancet 2011;378:1244–1253.
11. Lee DC, Pate RR, Lavie CJ, Sui X, Church TS, Blair SN. Leisure-Time running reduces
all-cause and cardiovascular mortality risk. J Am Coll Cardiol 2014;64:472–481.
12. DiPietro L, Al-Ansari SS, Biddle SJH, Borodulin K, Bull FC, Buman MP, et al. Advancing
the global physical activity agenda: recommendations for future research by the 2020
WHO physical activity and sedentary behavior guidelines development group. Int J
Behav Nutr Phys Act 2020;17:1–11.
13. Allen N, Sudlow C, Downey P, Peakman T, Danesh J, Elliott P, et al. UK Biobank: current
status and what it means for epidemiology. Health Policy Technol 2012;1:123–126.
14. Sipos M, Paces P, Rohac J, Novacek P. Analyses of triaxial accelerometer calibration al-
gorithms. IEEE Sens J 2012;12:1157–1165.
15. Ahmadi MN, Nathan N, Sutherland R, Wolfenden L, Trost SG. Non-wear or sleep?
Evaluation of five non-wear detection algorithms for raw accelerometer data. J Sports
Sci 2020;38:399–404.
16. Pavey TG, Gilson ND, Gomersall SR, Clark B, Trost SG. Field evaluation of a random
forest activity classifier for wrist-worn accelerometer data. J Sci Med Sport 2017;20:
75–80.
17. Huang BH, Duncan MJ, Cistulli PA, Nassar N, Hamer M, Stamatakis E. Sleep and physical
activity in relation to all-cause, cardiovascular disease and cancer mortality risk. Br J
Sports Med 2022;56:718–724.
18. Zou G. A modified poisson regression approach to prospective studies with binary data.
Am J Epidemiol 2004;159:702–706.
19. Desquilbet L, Mariotti F. Dose-response analyses using restricted cubic spline functions
in public health research. Stat Med 2010;29:1037–1057.
20. Haneuse S, VanderWeele TJ, Arterburn D. Using the E-value to assess the potential ef-
fect of unmeasured confounding in observational studies. JAMA 2019;321:602–603.
21. Ritz C, Baty F, Streibig JC, Gerhard D. Dose-response analysis using R. PLoS One 2015;
10:e0146021.
22. Rampinelli C, De Marco P, Origgi D, Maisonneuve P, Casiraghi M, Veronesi G, et al.
Exposure to low dose computed tomography for lung cancer screening and risk of can-
cer: secondary analysis of trial data and risk-benefit analysis. BMJ 2017;356:j347.
23. Harrell Jr FE. RMS: Regression Modeling Strategies. R package version 4.0-0: Vanderbilt
University; 2017.
24. Therneau T, Lumley T. R survival package. 2013.
25. Trost SG, Owen N, Bauman AE, Sallis JF, Brown W. Correlates of adults’participation in
physical activity: review and update. 2003; (January).
26. Hoare E, Stavreski B, Jennings GL, Kingwell BA. Exploring motivation and barriers to
physical activity among active and inactive Australian adults. Sports 2017;5:47.
27. Cerin E, Leslie E, Sugiyama T, Owen N. Perceived barriers to leisure-time physical ac-
tivity in adults: an ecological perspective. J Phys Act Health 2010;7:451–459.
28. O’Donovan G, Lee IM, Hamer M, Stamatakis E. Association of “weekend warrior”and
other leisure time physical activity patterns with risks for all-cause, cardiovascular dis-
ease, and cancer mortality. JAMA Intern Med 2017;177:335–342.
29. Jenkins EM, Nairn LN, Skelly LE, Little JP, Gibala MJ. Do stair climbing exercise
“snacks”improve cardiorespiratory fitness? Appl Physiol Nutr Metab 2019;44:
681–684.
30. Allison MK, Baglole JH, Martin BJ, Macinnis MJ, Gurd BJ, Gibala MJ. Brief intense
stair climbing improves cardiorespiratory fitness. Med Sci Sports Exerc 2017;49:
298–307.
31. Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Bäck M, et al. 2021 ESC
guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J 2021;42:
3227–3337.
32. Chomistek AK, Cook NR, Flint AJ, Rimm EB. Vigorous-intensity leisure-time physical
activity and risk of major chronic disease in men. Med Sci Sports Exerc 2012;44:
1898–1905.
Vigorous activity, CVD, and cancer 13
Downloaded from https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac572/6771381 by guest on 30 October 2022

33. Leitzmann MF, Park Y, Blair A, Ballard-Barbash R, Mouw T, Hollenbeck AR, et al. Physical
activity recommendations and decreased risk of mortality. Arch Intern Med 2007;167:
2453–2460.
34. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M,
et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity devel-
oped under the auspices of the ESC committee for practice guidelines. Eur Heart J 2016;
37:2768–2801.
35. D’ascenzi F, Anselmi F, Fiorentini C, Mannucci R, Bonifazi M, Mondillo S. The benefits of
exercise in cancer patients and the criteria for exercise prescription in cardio-oncology.
Eur J Prev Cardiol 2021;28:725–735.
36. Eijsvogels TMH, Molossi S, Lee DC, Emery MS, Thompson PD. Exercise at the ex-
tremes: the amount of exercise to reduce cardiovascular events. J Am Coll Cardiol
2016;67:316–329.
37. Löllgen H, Bö ckenhoff A, Knapp G. Physical activity and all-cause mortality: an up-
dated meta-analysis with different intensity categories. Int J Sports Med 2009;30:
213–224.
38. Samitz G, Egger M, Zwahlen M. Domains of physical activity and all-cause mortality: sys-
tematic review and dose-response meta-analysis of cohort studies. Int J Epidemiol 2011;
40:1382–1400.
39. Iannetta D, Keir DA, Fontana FY, Inglis EC, Mattu AT, Paterson DH, et al. Evaluating the
accuracy of using fixed ranges of METs to categorize exertional intensity in a heteroge-
neous group of healthy individuals: implications for cardiorespiratory fitness and health
outcomes. Sports Med 2021;51:2411–2421.
40. Lee IM, Shiroma EJ, Kamada M, Bassett DR, Matthews CE, Buring JE. Association of step
volume and intensity with all-cause mortality in older women. JAMA Intern Med 2019;
179:1105–1112.
41. Ekelund U, Tarp J, Steene-johannessen J, Hansen BH, Jefferis B, Fagerland MW, et al.
Dose-response associations between accelerometry measured physical activity and
sedentary time and all cause mortality : systematic review and harmonised
meta-analysis. BMJ 2019;366:l4570.
42. Saint-Maurice PF, Troiano RP, Bassett DR, Graubard BI, Carlson SA, Shiroma EJ, et al.
Association of daily step count and step intensity with mortality among US adults.
JAMA 2020;323:1151–1160.
43. Gabriel KP, McClain JJ, Schmid KK, Storti KL, High RR, Underwood DA, et al. Issues in
accelerometer methodology: the role of epoch length on estimates of physical activity
and relationships with health outcomes in overweight, post-menopausal women. Int J
Behav Nutr Phys Act 2010;7:53.
44. Trost SG, Mciver KL, Pate RR. Conducting accelerometer-based activity assessments in
field-based research. Med Sci Sports Exerc 2005;37:S531–S543.
45. Ramakrishnan R, Doherty A, Smith-Byrne K, Rahimi K, Bennett D, Woodward M, et al.
Accelerometer measured physical activity and the incidence of cardiovascular disease:
evidence from the UK biobank cohort study. PLoS Med 2021;18:e1003487.
46. Cruz BDP, Ahmadi M, Inan-Eroglu E, Huang BH, Stamatakis E. Prospective associations of
accelerometer-assessed physical activity with mortality and incidence of cardiovascular disease
among adults with hypertension: the UK biobank study. JAmHeartAssoc2022;11:e023290.
47. Trost SG. Population-level physical activity surveillance in youngpeople: are accelerometer-
based measures ready for prime time? Int J Behav Nutr Phys Act 2020;17:28.
48. Rosenberger ME, Haskell WL, Albinali F, Mota S, Nawyn J, Intille S. Estimating activity
and sedentary behavior from an accelerometer on the hip or wrist. Med Sci Sports
Exerc 2013;45:964–975.
49. Doherty A, Jackson D, Hammerla N, Plotz T, Olivier P, Granat M, et al. Large scale
population assessment of physical activity using wrist worn accelerometers: the UK bio-
bank study. PLoS One 2017;12:e0169649.
50. Tarp J, Hansen BH, Fagerland MW, Steene-johannessen J, Anderssen SA, Ekelund U.
Accelerometer-measured physical activity and sedentary time in a cohort of US adults
followed for up to 13 years : the influence of removing early follow-up on associations
with mortality. Int J Behav Nutr Phys Act 2020;17:39.
51. Stamatakis E, Owen KB, Shepherd L, Drayton B, Hamer M, Bauman AE. Is cohort rep-
resentativeness passé? Poststratified associations of lifestyle risk factors with mortality
in the UK biobank. Epidemiology 2021;32:179–188.
14 M.N. Ahmadi et al.
Downloaded from https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac572/6771381 by guest on 30 October 2022