Stroke

ORIGINAL CONTRIBUTION

Association Between Excess Leisure Sedentary

Time and Risk of Stroke in Young Individuals
Raed A. Joundi , MD, DPhil; Scott B. Patten , MD, PhD; Jeanne V.A. Williams , Msc; Eric E. Smith, MD, MPH

BACKGROUND AND PURPOSE: The association between physical activity (PA) and lower risk of stroke is well established, but the
relationship between leisure sedentary time and stroke is less well studied.

METHODS: We used 9 years of the Canadian Community Health Survey between 2000 and 2012 to create a cohort of healthy
individuals without prior stroke, heart disease, or cancer. We linked to hospital records to determine subsequent hospitalization
or emergency department visit for stroke until December 31, 2017. We quantified the association between self-reported leisure
sedentary time (categorized as <4, 4 to <6, 6 to <8, and 8+ hours/day) and risk of stroke using Cox regression models and
competing risk regression, assessing for modification by PA, age, and sex and adjusting for demographic, vascular, and social factors.

RESULTS: There were 143 180 people in our cohort and 2965 stroke events in follow-up. Median time from survey response
to stroke was 5.6 years. There was a 3-way interaction between leisure sedentary time, PA, and age. The risk of stroke with
8+ hours of sedentary time was significantly elevated only among individuals <60 years of age who were in the lowest PA
quartile (fully adjusted hazard ratio, 4.50 [95% CI, 1.64–12.3]). The association was significant across multiple sensitivity
analyses, including adjustment for mood disorders and when accounting for the competing risk of death.

CONCLUSIONS: Excess leisure sedentary time of 8+ hours/day is associated with increased risk of long-term stroke among individuals
<60 years of age with low PA. These findings support efforts to enhance PA and reduce sedentary time in younger individuals.
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GRAPHIC ABSTRACT: An online graphic abstract is available for this article.

Key Words: epidemiology ◼ exercise ◼ risk factors ◼ sedentary behavior ◼ stroke

T
he association between physical activity (PA) and
lower risk of stroke is a well-known and robust find-
ing across a broad range of epidemiological stud-
ies.1–9 More recent cohort studies and meta-analyses
have identified excess sedentary time as a risk factor for
cardiovascular disease (CVD) and death, independent of
PA.10–12 However, the risk of CVD and mortality is only
significantly increased after 9 or 10 hours of daily sed-
entary time.11,12 In addition, this risk can be attenuated or
eliminated with higher levels of PA.13,14
Sedentary time has increased over the past 2
decades in the United States and Canada, particularly
in the young,15,16 raising the importance of characteriz-
ing its effect on long-term health. Studies to date have
addressed the association between sedentary time and
risk of CVD as a composite measure that may include
ischemic heart disease, stroke, and CVD-related mortal-
ity. Two studies specifically evaluating stroke risk were
focused on post-menopausal women and television
viewing time only.17,18 A better understanding of the risk
of sedentary time specific to stroke may be important for
public health campaigns to reduce sedentary behavior.
We used a large cohort of healthy individuals from the
Canadian Community Health Survey (CCHS) and linked
to administrative databases to determine whether excess
leisure sedentary time is associated with elevated risk of
long-term stroke, whether the risk is greater in the young,
and whether the risk is modified by PA.

 
Correspondence to: Raed A. Joundi, MD, DPhil, University of Calgary, Health Sciences Bldg, 3330 Hospital Dr, NW Calgary, AB T2N 4N1. Email raed.joundi@ucalgary.ca
This manuscript was sent to Emmanuel Touzé, Guest Editor, for review by expert referees, editorial decision, and final disposition.
The Data Supplement is available with this article at https://www.ahajournals.org/doi/suppl/10.1161/STROKEAHA.121.034985.
For Sources of Funding and Disclosures, see page XXX.
© 2021 American Heart Association, Inc.
Stroke is available at www.ahajournals.org/journal/str

Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034985 October 2021   1

 Joundi et al
Original Contribution
Nonstandard Abbreviations and Acronyms
CCHS Canadian Community Health Survey
CVD cardiovascular disease
HR hazard ratio
ICH intracerebral hemorrhage
MET metabolic equivalent
PA physical activity
METHODS
The dataset from this study is held securely in coded form at
the Research Data Centre (Statistics Canada). Access to data
may only be granted within the Research Data Centre after
approval by Statistics Canada.
Study Sample—CCHS
The CCHS is an annual cross-sectional survey, represent-
ing 97% of the Canadian household population aged ≥12
years.19 The survey randomly samples households nationwide
and selects one respondent per household. The CCHS col-
lects information about health status, health determinants, and
health care utilization of the household population. Interviews
were conducted using computer-assisted personal and tele-
phone interview software. Before releasing the CCHS for use,
data are assessed for quality and compared with previous
cycles to avoid errors. The 3% of the general population that
is excluded from the survey target population includes those
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living on Indigenous reserves, those living in foster care, full
time members of the Canadian Armed Forces, the institutional-
ized population, and the remote Région du Nunavik and Région
des Terres-Cries-de-la-Baie-James. Data were collected by
Statistics Canada using a multistage sample allocation strategy
to support estimation at the health region and provincial level.
Administrative Linkages
CCHS Sharelink is a CCHS subsample with ≈85% of total
respondents, who agreed to have their responses linked to
administrative records. Statistics Canada created sample weights
for CCHS Sharelink to retain population representativeness.
CCHS Sharelink resembles CCHS in sociodemographic char-
acteristics. Linkages were performed by Statistics Canada and
included the Canadian Institutes of Health Discharge Abstract
Database for hospitalizations and the National Ambulatory
Care Reporting System for emergency department visits.20 We
linked the CCHS survey to the Discharge Abstract Database
and National Ambulatory Care Reporting System to determine
stroke events after the survey response until December 31,
2017. All participants had a minimum of 5 years of full follow-up
for events and were censored if alive on December 31, 2017.
Cohort
We used CCHS years 2000, 2003, 2005, and 2007 to 2012 to
capture data on sedentary time and other baseline covariates.
The sedentary activity module uptake differed by region in each
year.16 We excluded those under the age of 40 years and those
2   October 2021
Sedentary Time and Stroke Risk
with a self-reported history of heart disease or cancer, or prior
stroke (either self-reported or captured with administrative
data; see Figure I in the Data Supplement for patient flowchart).
Exposure
Our main exposure was self-reported leisure sedentary time.
Sedentary time was measured by adding the number of hours
spent on a computer, reading, and watching TV per week, then
dividing by 7 to obtain daily sedentary time. The sedentary
time module in the CCHS does not include time at school or
work. We categorized leisure sedentary time as <4, 4 to <6, 6
to <8, and ≥8 hours/day, with excess sedentary time defined
as ≥8 hours/day. As we captured leisure sedentary time only,
our prespecified upper threshold of ≥8 hours is lower than the
typical upper threshold of 10 to 12 hours for the overall daily
sedentary time.17,21–25 The upper threshold of ≥8 hours was
also higher than previous studies on TV viewing only or leisure
sedentary time,22,24,26 although we included computer use and
reading, and sedentary behavior has increased over time.15
Covariates
Covariates were obtained from the CCHS, including age, sex,
rural residence, and self-report of ethnicity, education level, total
household income, marital status, alcohol consumption, body
mass index, smoking status, hypertension, diabetes, heart dis-
ease, cancer, migraine, arthritis, chronic obstructive pulmonary
disease, and asthma. Categorization of the variables can be
seen in Table I in the Data Supplement. Due to known biases in
self-report of body mass index, we used a correction developed
by the CCHS.27
Leisure-time PA was measured as weekly energy expendi-
ture and was calculated using the frequency and duration of
each type of PA and the metabolic equivalent (MET) value of the
activity. The MET is a value of metabolic energy cost expressed
as a multiple of the resting metabolic rate. Energy expenditure
is obtained with the following formula: (N)×(D)×(MET value),
where N is the number of times a respondent engaged in an
activity over a 3-month period, D is the average duration in hours
of the activity, and MET is the energy cost of the activity (kilo-
calories expended per kilogram of body weight per hour). Three-
month average energy expenditure was calculated for leisure
PA then divided by 12 to obtain MET-hours/week. As CCHS
interviews are distributed fairly evenly throughout the year, there
was no seasonal bias in self-reported sedentary time or PA.
Outcome
Our primary outcome was acute stroke (ischemic stroke or intra-
cerebral hemorrhage [ICH]) at any time in follow-up until cen-
soring on December 31, 2017, using the International Statistical
Classification of Diseases and Related Health Problems, Tenth
Revision, Canada, codes (ischemic stroke: I63.x, I64.x, H34.1;
ICH: I61.x) and International Statistical Classification of Diseases
and Related Health Problems, Ninth Revision, codes (ischemic
stroke: 434.01, 434.11, 434.91, 436; ICH: 431).
Analysis
We used Cox proportional regression models to obtain the haz-
ard of stroke by category of leisure sedentary time. We first
Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034985
 Joundi et al Sedentary Time and Stroke Risk

assessed for the presence of modification of the sedentary We conducted multiple sensitivity analyses. First, we

time stroke association by PA level. As effect modification of
the association only occurred between the lowest and second
lowest quartiles of PA, we dichotomized PA as the lowest quar-
tile of activity  (low PA; equivalent to 3.5 MET-hours/week or
less) versus quartiles 2 to 4 (high PA). We also assessed for
modification by age group (40–59, 60–79, and 80+ years)
and sex, with P threshold of 0.05. As there was evidence of
modification by age and PA level, we created models specific
to these groups.
In our simple model, we adjusted for sex only. In our vascu-
lar model, we adjusted for sex, body mass index, hypertension,
diabetes, and smoking. In our full model, we adjusted for the
above in addition to income quartile, rural residence, educa-
tion, ethnicity, marital status, alcohol consumption, and other
comorbidities (migraine, arthritis, chronic obstructive pulmonary
disease, and asthma). We evaluated the proportional hazards
assumption by assessing the significance (P<0.05) of an inter-
action term of sedentary time category and follow-up time.
We further explored the modification of sedentary time
stroke risk by PA in 2 ways. First, we created a variable with 8
levels comprising every combination of leisure sedentary time
category and PA category, and used this variable as the main
exposure in the age-stratified Cox model. Second, we created
a variable for uncompensated sedentary time, by subtracting 1
hour of daily leisure sedentary time for each 1 hour of daily lei-
sure energy expenditure equivalent to walking (3 MET-hours).
We then categorized uncompensated sedentary time again as
<4, 4 to <6, 6 to <8, and ≥8 hours and used this as the main
exposure in the age-stratified Cox models.
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Original Contribution
excluded reading time to assess the association between
screen time only (computer and TV) and stroke. Second, we
repeated the analysis with a maximum follow-up time of 5
years rather than the full follow-up period. Third, we assessed
the risk of ischemic stroke only. Fourth, we additionally adjusted
for mood disorders (presence of depression, bipolar disor-
der, mania, or dysthymia, diagnosed by a health professional)
or depressive symptoms (≥2 weeks of feeling sad, blue, or
depressed in the past 12 months) in the subset of individuals
in which these variables were available. Fifth, we defined meet-
ing minimal PA guidelines as 10 MET-hours/week as per the
World Health Organization28 and determined whether reaching
this threshold modified the risk of stroke with excess sedentary
time. Sixth, we changed the upper category of leisure sedentary
time to ≥7 or ≥6 hours instead of ≥8 hours/day.
Lastly, as excess sedentary time has previously been
associated with all-cause mortality, we conducted competing
risk regression to confirm that the risk of stroke was elevated
while accounting for the competing risk of death using the
Fine and Gray subdistribution hazard models29–31 and gener-
ated cumulative incidence functions to assess the cumulative
risk of stroke over 15 years. We adjusted for the same fac-
tors as in previous full models.
Our study conformed to STROBE guidelines. Data were
missing in <1% for all variables except body mass index and
income which had <10% missing. Missing data were excluded
from the models through listwise deletion. Analyses were done
in the Prairie Regional Research Data Centre at the University
of Calgary using Stata 16.0 (College Station, TX). Threshold of

Figure 1. Association between categories of sedentary time and risk of stroke, shown separately by physical activity (PA) level
and age group.
Hazard ratios from the Cox model are shown from A to C and subdistribution hazard ratios from competing risk models shown from D to F. There
is a higher hazard of stroke only in those with low PA and 8+ h of sedentary time per day among those <60 y of age (A and C) but not 60 to 79
(B and E) or 80+ (C and F). aHR indicates adjusted hazard ratio; and aSHR, adjusted subdistribution hazard ratio.

Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034985 October 2021   3

 Joundi et al Sedentary Time and Stroke Risk

significance for P was <0.05. Under Tri-Council guidelines, this stratified the Cox model jointly by age and PA level. There
Original Contribution

analysis did not require approval by a research ethics board.
RESULTS
Our total cohort comprised 143 180 people with self-
reported leisure sedentary time and without prior heart
disease, cancer, or stroke. During a median follow-up
time of 9.4 years (interquartile range, 6.3–12.5), there
was a total of 2965 stroke events (88.2% ischemic). The
median time from survey response until stroke was 5.6
years (interquartile range, 3.2–9.2).
Baseline characteristics of the cohort weighted to the
Canadian population are shown in Table I in the Data
Supplement. The proportion of individuals <60 years of
age was 67%. Mean daily leisure sedentary time was
4.08 hours (95% CI, 3.93–4.23), with slightly greater
sedentary time at older age (mean, 3.9 hours for age
<60 years, 4.4 hours for age 60–79 years, and 4.3 hours
for age 80+ years) and among women (mean, 4.0 hours
among men and 4.2 hours among women).
Weighted percentages of stroke events in follow-up are
shown in Table II in the Data Supplement and stratified by
subgroup. The greatest relative difference in risk of stroke
associated with excess leisure sedentary time occurred
among individuals <60 years of age with low PA (2.97%
over a median of 9.4 years of follow-up) compared with
high PA (0.59%). In the Cox regression model, there was a
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was no violation of the proportional hazards assumption.
In the simple model, the hazard ratio (HR) for stroke
with excess leisure sedentary time ≥8 hours was only ele-
vated in individuals <60 years of age with low PA (HR, 4.21
[95% CI, 1.74–10.2]). The association was consistent in
the vascular model (HR, 3.67 [95% CI, 1.33–10.2]) and
the full model (HR, 4.50 [95% CI, 1.64–12.3]; Figure 1A;
Table III in the Data Supplement). This pattern was also
consistent across analyses combining sedentary time and
PA categories in a single variable and when evaluating
uncompensated sedentary time (Figure 2; Table III in the
Data Supplement) and in all sensitivity analyses (Table IV
in the Data Supplement). There was no significant asso-
ciation between any sedentary time category and risk of
stroke among individuals 60 to 79 or 80+ years of age
(Figure 1; Tables III and IV in the Data Supplement).
Lastly, competing risk regression and cumulative inci-
dence functions demonstrated a significantly elevated
risk of stroke with excess leisure sedentary time in those
<60 years of age and low PA after accounting for the
competing risk of death (subdistribution HR, 4.10 [95%
CI, 1.46–11.5]; Figures 1 and 3; Table V in the Data
Supplement).
DISCUSSION
We demonstrate that excess daily leisure sedentary time
≥8 hours is associated with increased long-term risk of

significant 3-way interaction between sedentary time cat-

egory, PA category, and age (Pint=0.028). Therefore, we stroke among young individuals under 60 years of age but

Figure 2. Association between alternate categories of sedentary time and risk of stroke.
Adjusted hazard ratios (aHR) for stroke with combined sedentary and physical activity categories (A, simple model; B, vascular model; C, full model)
and with uncompensated sedentary time categories (D, simple model; E, vascular model; F, full model) in those <60 y of age. Hazard ratios are from
analysis with Cox regression models. Uncompensated sedentary time is calculated by subtracting 1 h of sedentary time for every 3 MET-hours of
activity (equivalent to 1 h of walking). HP indicates high physical activity (quartiles 2-4); and LP, low physical activity (lowest quartile).

4   October 2021 Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034985

 Joundi et al
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Figure 3. Sedentary time and cumulative incidence of stroke.
Cumulative incidence functions for stroke (proportion) over 15 y of follow-up for categories of sedentary time among individuals who have low
physical activity (PA) (lowest quartile; A, C, and E) or high PA (quartiles 2–4; B, D, and F). There is a large elevation in cumulative incidence of
stroke with excess sedentary time and low PA only for those <60 y (A and B).
only in those with low levels of PA. The results remained
significant after adjustment for potential vascular and
social confounders, after multiple sensitivity analyses, and
when accounting for the competing risk of death.
While PA and body mass index have known associa-
tions with CVD,1 recent attention has turned to sedentary
time as an independent risk factor for greater risk of CVD.32
In cohort studies and meta-analyses of self-reported and
objectively measured sedentary time, the risk of CVD
(defined as stroke, myocardial infarction, or cardiovascular-
related mortality) was elevated with >9 hours of sedentary
time11,12 but attenuated with higher PA.10,13,14,17,33,34 In our
cohort, excess leisure sedentary time is specifically associ-
ated with increased risk of stroke among individuals <60
years of age who participate in minimal PA.
Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034985
Sedentary Time and Stroke Risk
Original Contribution
The reason for the age-specific risk is unclear and may
relate to longer follow-up in the younger population, selec-
tive survival in the older population, or accumulated con-
founding throughout the life span. As our objective was to
determine risk of stroke, we did not include major cardiac
events and mortality in our analysis, which will have reduced
the number of adverse events in follow-up in the older pop-
ulation compared with other studies. Nevertheless, prior
studies have shown the associations between vascular
risk factors such as obesity or diabetes, and adverse out-
comes are also greater at younger age,35,36 and sedentary
time is associated with increased waist circumference and
metabolic risk.37,38 Potential mechanisms of excess sed-
entary time elevating cardiovascular risk include reduction
in blood flow, reduction in NO, and increase in endothelin
October 2021   5
 Joundi et al
production, insulin resistance, and inflammatory changes
Original Contribution
leading to vascular dysfunction.39 CVD-related and inflam-
matory biomarkers increase with sedentary time and
decrease with PA.40 As low-grade inflammation naturally
increases with age,41 it is possible that the specific impact
of inflammatory dysregulation related to sedentary behav-
ior is greater at younger compared with older ages leading
to a higher relative risk of stroke and CVD, although this
is speculative. Our findings may have public health impli-
cations due to rising sedentary behavior15,16 and stroke
incidence42–45 in the younger population. There is modest
evidence that interventions can lower sedentary time in
adults and should be the target of future research.46,47
There were some limitations to this study. First, we
could not capture occupational sedentary time, and so
our analysis was specific to leisure sedentary time only.
Younger individuals likely have higher occupation sed-
entary time, which was unaccounted for and may have
influenced the effect modification by age. However, lei-
sure time spent sitting is important as it may be associ-
ated with other unhealthy behaviors, such as greater food
consumption leading to elevated risk of metabolic syn-
drome.48,49 Television viewing is associated with greater
risk of CVD and mortality compared with occupational
sitting, and, therefore, reducing screen time may be the
most effective target for lowering cardiovascular risk.50
Second, the CCHS did not specifically ask about newer
technology such as mobile devices in the included years,
and thus sedentary time may have been underrepre-
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sented. Third, self-reported sedentary time was used,
which may be subject to recall bias and generally under-
estimates actual sedentary time compared with objective
measures.51 Fourth, the presence of interactions resulted
in a need for stratification and increased risk of type I
error, although the results were plausible and consistent
across multiple sensitivity analyses. Fifth, while the results
were robust for ischemic stroke alone, there were insuffi-
cient number of ICH events for producing reliable regres-
sion models. Therefore, we could not determine whether
excess sedentary time is associated with increased risk
of ICH. Lastly, despite adjustment for a variety of poten-
tial confounders, there remains the possibility of residual
measured and unmeasured confounding. For example,
we did not have information on peripheral artery disease
or long-term use of antiplatelet therapy, although the
prevalence of these factors is expected to be low in this
young population without prior heart disease or stroke.
In conclusion, high sedentary time with low PA is
associated with higher risk of stroke in young individuals.
Public health efforts to increase PA, as well as reduce
high sedentary time in the young, may contribute to low-
ering the long-term risk of stroke in this population.
ARTICLE INFORMATION
Received March 8, 2021; final revision received June 3, 2021; accepted June
21, 2021.
6   October 2021
Sedentary Time and Stroke Risk
Affiliations
Departments of Clinical Neurosciences (R.A.J., E.E.S.) and Community Health
Sciences (S.B.P., J.V.A.W., R.A.J., E.E.S.), Cumming School of Medicine, University
of Calgary, Canada.
Acknowledgments
The analysis was conducted at the Prairie Regional Research Data Centre (RDC),
which is part of the Canadian Research Data Centre Network. The services and
activities provided by the Canadian Research Data Centre Network are made
possible by the financial or in-kind support of the Social Sciences and Humani-
ties Research Council, the Canadian Institutes of Health Research, the Canadian
Foundation for Innovation, Statistics Canada, and participating universities whose
support is gratefully acknowledged. The views expressed in this article do not nec-
essarily represent those of the Canadian Research Data Centre Network or that
of its partners. We thank Stephanie Cantlay for her assistance in the Prairie RDC.
Sources of Funding
Dr Joundi is supported by a fellowship grant from the Canadian Institutes of
Health Research (funding reference number MFE-164702).
Disclosures
None.
Supplemental Materials
Online Tables I–V
Online Figure I
REFERENCES
1. Lear SA, Hu W, Rangarajan S, Gasevic D, Leong D, Iqbal R, Casanova A,
Swaminathan S, Anjana RM, Kumar R, et al. The effect of physical activity
on mortality and cardiovascular disease in 130 000 people from 17 high-
income, middle-income, and low-income countries: the PURE study. Lancet.
2017;390:2643–2654. doi: 10.1016/S0140-6736(17)31634-3
2. O’Donnell MJ, Chin SL, Rangarajan S, Xavier D, Liu L, Zhang H, Rao-
Melacini P, Zhang X, Pais P, Agapay S, et al; INTERSTROKE Investigators.
Global and regional effects of potentially modifiable risk factors associated
with acute stroke in 32 countries (INTERSTROKE): a case-control study.
Lancet. 2016;388:761–775. doi: 10.1016/S0140-6736(16)30506-2
3. Willey JZ, Moon YP, Paik MC, Boden-Albala B, Sacco RL, Elkind MS. Physical
activity and risk of ischemic stroke in the Northern Manhattan Study. Neurol-
ogy. 2009;73:1774–1779. doi: 10.1212/WNL.0b013e3181c34b58
4. Wendel-Vos GC, Schuit AJ, Feskens EJ, Boshuizen HC, Verschuren WM, Saris
WH, Kromhout D. Physical activity and stroke. A meta-analysis of observa-
tional data. Int J Epidemiol. 2004;33:787–798. doi: 10.1093/ije/dyh168
5. Lee CD, Folsom AR, Blair SN. Physical activity and stroke risk: a
meta-analysis. Stroke. 2003;34:2475–2481. doi: 10.1161/01.STR.
0000091843.02517.9D
6. Agnarsson U, Thorgeirsson G, Sigvaldason H, Sigfusson N. Effects of
leisure-time physical activity and ventilatory function on risk for stroke
in men: the Reykjavík Study. Ann Intern Med. 1999;130:987–990. doi:
10.7326/0003-4819-130-12-199906150-00006
7. Hu FB, Stampfer MJ, Colditz GA, Ascherio A, Rexrode KM, Willett
WC, Manson JE. Physical activity and risk of stroke in women. JAMA.
2000;283:2961–2967. doi: 10.1001/jama.283.22.2961
8. Kiely DK, Wolf PA, Cupples LA, Beiser AS, Kannel WB. Physical activity and
stroke risk: the Framingham Study. Am J Epidemiol. 1994;140:608–620.
doi: 10.1093/oxfordjournals.aje.a117298
9. Gillum RF, Mussolino ME, Ingram DD. Physical activity and stroke incidence
in women and men. The NHANES I Epidemiologic Follow-up Study. Am J
Epidemiol. 1996;143:860–869. doi: 10.1093/oxfordjournals.aje.a008829
10. Biswas A, Oh PI, Faulkner GE, Bajaj RR, Silver MA, Mitchell MS, Alter DA.
Sedentary time and its association with risk for disease incidence, mor-
tality, and hospitalization in adults. Ann Inter Med. 2015;162:123–32. doi:
10.7326/M14-1651
11. Pandey A, Salahuddin U, Garg S, Ayers C, Kulinski J, Anand V, Mayo H,
Kumbhani DJ, de Lemos J, Berry JD. Continuous Dose-Response Association
between sedentary time and risk for cardiovascular disease: a meta-analy-
sis. JAMA Cardiol. 2016;1:575–583. doi: 10.1001/jamacardio.2016.1567
12. Ekelund U, Tarp J, Steene-Johannessen J, Hansen BH, Jefferis B,
Fagerland MW, Whincup P, Diaz KM, Hooker SP, Chernofsky A, et al. Dose-
response associations between accelerometry measured physical activity
and sedentary time and all cause mortality: systematic review and harmon-
ised meta-analysis. BMJ. 2019;366:l4570. doi: 10.1136/bmj.l4570
Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034985
 Joundi et al
13. Ekelund U, Steene-Johannessen J, Brown WJ, Fagerland MW, Owen N,
Powell KE, Bauman A, Lee IM; Lancet Physical Activity Series 2 Execu-
tive Committe; Lancet Sedentary Behaviour Working Group. Does physi-
cal activity attenuate, or even eliminate, the detrimental association of
sitting time with mortality? A harmonised meta-analysis of data from
more than 1 million men and women. Lancet. 2016;388:1302–1310. doi:
10.1016/S0140-6736(16)30370-1
14. Ekelund U, Brown WJ, Steene-Johannessen J, Fagerland MW, Owen N,
Powell KE, Bauman AE, Lee IM. Do the associations of sedentary behaviour
with cardiovascular disease mortality and cancer mortality differ by physi-
cal activity level? A systematic review and harmonised meta-analysis of
data from 850 060 participants. Br J Sports Med. 2019;53:886–894. doi:
10.1136/bjsports-2017-098963
15. Yang L, Cao C, Kantor ED, Nguyen LH, Zheng X, Park Y, Giovannucci EL,
Matthews CE, Colditz GA, Cao Y. Trends in sedentary behavior among
the US population, 2001-2016. JAMA. 2019;321:1587–1597. doi:
10.1001/jama.2019.3636
16. Prince SA, Melvin A, Roberts KC, Butler GP, Thompson W. Sedentary behav-
iour surveillance in Canada: trends, challenges and lessons learned. Int J
Behav Nutr Phys Act. 2020;17:34. doi: 10.1186/s12966-020-00925-8
17. Chomistek AK, Manson JE, Stefanick ML, Lu B, Sands-Lincoln M, Going
SB, Garcia L, Allison MA, Sims ST, LaMonte MJ, et al. Relationship of seden-
tary behavior and physical activity to incident cardiovascular disease: results
from the Women’s Health Initiative. J Am Coll Cardiol. 2013;61:2346–2354.
doi: 10.1016/j.jacc.2013.03.031
18. McDonnell MN, Hillier SL, Judd SE, Yuan Y, Hooker SP, Howard VJ. Associ-
ation between television viewing time and risk of incident stroke in a general
population: results from the REGARDS study. Prev Med. 2016;87:1–5.
19. Government of Canada SC. Canadian Community Health Survey - Annual
Component (CCHS) [Internet]. 2019. Cited Febrary 13, 2020. Accessed
June 29, 2021. https://www23.statcan.gc.ca/imdb/p2SV.pl?Function=get
Survey&SDDS=3226
20. Sanmartin C, Decady Y, Trudeau R, Dasylva A, Tjepkema M, Finès P, Burnett
R, Ross N, Manuel DG. Linking the Canadian Community Health Survey and
the Canadian Mortality Database: an enhanced data source for the study of
mortality. Health Rep. 2016;27:10–18.
21. Matthews CE, Cohen SS, Fowke JH, Han X, Xiao Q, Buchowski MS,
Hargreaves MK, Signorello LB, Blot WJ. Physical activity, sedentary behav-
Downloaded from http://ahajournals.org by on September 3, 2021
ior, and cause-specific mortality in black and white adults in the South-
ern Community Cohort Study. Am J Epidemiol. 2014;180:394–405. doi:
10.1093/aje/kwu142
22. Matthews CE, George SM, Moore SC, Bowles HR, Blair A, Park Y, Troiano
RP, Hollenbeck A, Schatzkin A. Amount of time spent in sedentary behaviors
and cause-specific mortality in US adults. Am J Clin Nutr. 2012;95:437–
445. doi: 10.3945/ajcn.111.019620
23. Bjørk Petersen C, Bauman A, Grønbæk M, Wulff Helge J, Thygesen
LC, Tolstrup JS. Total sitting time and risk of myocardial infarc-
tion, coronary heart disease and all-cause mortality in a prospective
cohort of Danish adults. Int J Behav Nutr Phys Act. 2014;11:13. doi:
10.1186/1479-5868-11-13
24. Kim Y, Wilkens LR, Park SY, Goodman MT, Monroe KR, Kolonel LN. Asso-
ciation between various sedentary behaviours and all-cause, cardiovascular
disease and cancer mortality: the Multiethnic Cohort Study. Int J Epidemiol.
2013;42:1040–1056. doi: 10.1093/ije/dyt108
25. Borodulin K, Kärki A, Laatikainen T, Peltonen M, Luoto R. Daily sedentary
time and risk of cardiovascular disease: the National FINRISK 2002 study.
J Phys Act Health. 2015;12:904–908. doi: 10.1123/jpah.2013-0364
26. Patel AV, Bernstein L, Deka A, Feigelson HS, Campbell PT, Gapstur SM,
Colditz GA, Thun MJ. Leisure time spent sitting in relation to total mortality
in a prospective cohort of US adults. Am J Epidemiol. 2010;172:419–429.
doi: 10.1093/aje/kwq155
27. Shields M, Connor Gorber S, Janssen I, Tremblay MS. Bias in self-reported
estimates of obesity in Canadian health surveys: an update on correction
equations for adults. Health Rep. 2011;22:35–45.
28. World Health Organization. Global recommendations on physical activ-
ity for health [Internet]. Cited December 13, 2020. https://www.who.int/
publications-detail-redirect/9789241599979
29. Austin PC, Lee DS, Fine JP. Introduction to the analysis of survival data
in the presence of competing risks. Circulation. 2016;133:601–609. doi:
10.1161/CIRCULATIONAHA.115.017719
30. Lau B, Cole SR, Gange SJ. Competing risk regression models for epidemio-
logic data. Am J Epidemiol. 2009;170:244–256. doi: 10.1093/aje/kwp107
31. Austin PC, Fine JP. Practical recommendations for reporting Fine-Gray
model analyses for competing risk data. Stat Med. 2017;36:4391–4400.
doi: 10.1002/sim.7501
Stroke. 2021;52:00–00. DOI: 10.1161/STROKEAHA.121.034985
Sedentary Time and Stroke Risk
32. Lavie CJ, Ozemek C, Carbone S, Katzmarzyk PT, Blair SN. Sedentary behav-
Original Contribution
ior, exercise, and cardiovascular health. Circ Res. 2019;124:799–815.
33. Katzmarzyk PT, Church TS, Craig CL, Bouchard C. Sitting time and mortality
from all causes, cardiovascular disease, and cancer. Med Sci Sports Exerc.
2009;41:998–1005. doi: 10.1249/MSS.0b013e3181930355
34. Stamatakis E, Gale J, Bauman A, Ekelund U, Hamer M, Ding D. Sitting
time, physical activity, and risk of mortality in adults. J Am Coll Cardiol.
2019;73:2062–2072. doi: 10.1016/j.jacc.2019.02.031
35. Rawshani A, Rawshani A, Franzén S, Sattar N, Eliasson B, Svensson AM,
Zethelius B, Miftaraj M, McGuire DK, Rosengren A, et al. Risk factors, mortal-
ity, and cardiovascular outcomes in patients with type 2 diabetes. N Engl J
Med. 2018;379:633–644. doi: 10.1056/NEJMoa1800256
36. Peter RS, Mayer B, Concin H, Nagel G. The effect of age on the shape
of the BMI–mortality relation and BMI associated with minimum all-cause
mortality in a large Austrian cohort. Int J Obes. 2015;39:530–534.
37. Healy GN, Wijndaele K, Dunstan DW, Shaw JE, Salmon J, Zimmet PZ, Owen
N. Objectively measured sedentary time, physical activity, and metabolic risk:
the Australian Diabetes, Obesity and Lifestyle Study (AusDiab). Diabetes
Care. 2008;31:369–371. doi: 10.2337/dc07-1795
38. Sjöros T, Vähä-Ypyä H, Laine S, Garthwaite T, Lahesmaa M, Laurila SM,
Latva-Rasku A, Savolainen A, Miikkulainen A, Löyttyniemi E, et al. Both sed-
entary time and physical activity are associated with cardiometabolic health
in overweight adults in a 1 month accelerometer measurement. Sci Rep.
2020;10:20578. doi: 10.1038/s41598-020-77637-3
39. Carter S, Hartman Y, Holder S, Thijssen DH, Hopkins ND. Sedentary behav-
ior and cardiovascular disease risk: mediating mechanisms. Exerc Sport Sci
Rev. 2017;45:80–86. doi: 10.1249/JES.0000000000000106
40. Elhakeem A, Cooper R, Whincup P, Brage S, Kuh D, Hardy R. Physical activ-
ity, sedentary time, and cardiovascular disease biomarkers at age 60 to 64
years. J Am Heart Assoc. 2018;7:e007459.
41. Woods JA, Wilund KR, Martin SA, Kistler BM. Exercise, inflammation and
aging. Aging Dis. 2012;3:130–140.
42. Kissela BM, Khoury JC, Alwell K, Moomaw CJ, Woo D, Adeoye O, Flaherty
ML, Khatri P, Ferioli S, De Los Rios La Rosa F, et al. Age at stroke: tem-
poral trends in stroke incidence in a large, biracial population. Neurology.
2012;79:1781–1787. doi: 10.1212/WNL.0b013e318270401d
43. Rosengren A, Giang KW, Lappas G, Jern C, Torén K, Björck L.
Twenty-four-year trends in the incidence of ischemic stroke in Swe-
den from 1987 to 2010. Stroke. 2013;44:2388–2393. doi: 10.1161/
STROKEAHA.113.001170
44. Madsen TE, Khoury JC, Leppert M, Alwell K, Moomaw CJ, Sucharew H, Woo
D, Ferioli S, Martini S, Adeoye O, et al. Temporal trends in stroke incidence
over time by sex and age in the GCNKSS. Stroke. 2020;51:1070–1076.
doi: 10.1161/STROKEAHA.120.028910
45. Joundi RA, Smith EE, Yu AYX, Rashid M, Fang J, Kapral MK. Temporal and
age-specific trends in acute stroke incidence: a 15-year population-based
study of administrative data in Ontario, Canada. Can J Neurol Sci. 2020;1–
5. doi: 10.1017/cjn.2020.257
46. Martin A, Fitzsimons C, Jepson R, Saunders DH, van der Ploeg HP,
Teixeira PJ, Gray CM, Mutrie N; EuroFIT Consortium. Interventions
with potential to reduce sedentary time in adults: systematic review and
meta-analysis. Br J Sports Med. 2015;49:1056–1063. doi: 10.1136/
bjsports-2014-094524
47. Gardner B, Smith L, Lorencatto F, Hamer M, Biddle SJ. How to reduce
sitting time? A review of behaviour change strategies used in sedentary
behaviour reduction interventions among adults. Health Psychol Rev.
2016;10:89–112. doi: 10.1080/17437199.2015.1082146
48. Hu FB, Li TY, Colditz GA, Willett WC, Manson JE. Television watch-
ing and other sedentary behaviors in relation to risk of obesity and
type 2 diabetes mellitus in women. JAMA. 2003;289:1785–1791. doi:
10.1001/jama.289.14.1785
49. Thorp AA, McNaughton SA, Owen N, Dunstan DW. Independent and
joint associations of TV viewing time and snack food consumption
with the metabolic syndrome and its components; a cross-sectional
study in Australian adults. Int J Behav Nutr Phys Act. 2013;10:96. doi:
10.1186/1479-5868-10-96
50. Garcia JM, Duran AT, Schwartz JE, Booth JN, Hooker SP, Willey JZ,
Cheung YK, Park C, Williams SK, Sims M, et al. Types of sedentary behavior
and risk of cardiovascular events and mortality in blacks: the Jackson
Heart Study. J Am Heart Assoc. 2019;8:e010406. doi: 10.1161/JAHA.
118.010406
51. Prince SA, Cardilli L, Reed JL, Saunders TJ, Kite C, Douillette K, Fournier K,
Buckley JP. A comparison of self-reported and device measured sedentary
behaviour in adults: a systematic review and meta-analysis. Int J Behav Nutr
Phys Act. 2020;17:31. doi: 10.1186/s12966-020-00938-3
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