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Physical Activity and Heart Failure Risk in a Prospective Study of Men
JACC: HEART FAILURE
VOL.
ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
-, NO. -, 2015
ISSN 2213-1779/$36.00 http://dx.doi.org/10.1016/j.jchf.2015.05.006
Physical Activity and Heart Failure Risk in a Prospective Study of Men Iffat Rahman, PHD, Andrea Bellavia, MSC, Alicja Wolk, DRMEDSCI, Nicola Orsini, PHD
ABSTRACT OBJECTIVES This study investigated if total physical activity, as well as different types of physical activity, were associated with heart failure risk. BACKGROUND Physical activity has shown to be associated with reduced risks of coronary heart disease and stroke. Studies have also suggested that physical activity is associated with heart failure development. METHODS A study population of 33,012 men was followed from beginning of 1998 until the end of 2012. First event of heart failure was ascertained through linkage to the Swedish National Patient Register and Cause of Death Register. The data were analyzed by using Cox proportional hazards regression and Laplace regression. RESULTS During a mean follow-up of 13 years, we ascertained a total of 3,609 first events of heart failure. The average age at study baseline was 60 9 years of age. When examining the entire study population, a U-shaped association between total physical activity and heart failure risk was detected, with both extremely high (57 metabolic equivalent [MET] h/day) and extremely low (38 MET h/day) levels of total physical activity associated with an increased risk of heart failure. When investigating different types of physical activity, we found that walking/bicycling at least 20 min/day was associated with 21% lower risk of heart failure (95% confidence interval: 0.72 to 0.87); corresponding to a the median age at heart failure 8 months later for those who had actively walked or biked daily. When looking at long-term behavior of walking/bicycling, the results suggested a trend toward more recent active behavior being more related to heart failure protection than past physical activity levels. CONCLUSIONS This study suggests that both low levels and high levels of total physical activity, in comparison with moderate levels, could increase heart failure risk in men and that certain types of physical activity are associated with a protective effect on heart failure in men. When examining different types of physical activity, walking/bicycling at least 20 min per day was associated with the largest risk reduction of heart failure. (J Am Coll Cardiol HF 2015;-:-–-) © 2015 by the American College of Cardiology Foundation.
H
eart failure (HF) is a large public health
investigated the shape of association between total
issue with a substantial effect on the dis-
PA and HF modeling the exposure as a continuous
ease burden in developed countries, partic-
variable using flexible spline modeling. Neither has
ularly among the elderly (1). In the United States,
long-term behavior regarding PA in relation to HF
more than 5.8 million people suffer from HF, and
risk been investigated previously.
the number of HF sufferers worldwide is around
Moreover, previous studies have presented their
23 million (1). The lifetime risk for development of
results by relying only on relative measures of asso-
HF is around 20% (2).
ciation. These popular risk measures that lack a time
Physical activity (PA) has been shown to be asso-
unit may be complemented by estimating differences
ciated with reduced risks of coronary heart disease
in the percentiles of survival time, presenting results
(3–5) and stroke (3,5–8). Studies have also suggested
in the metric of time (i.e., days, months) (15).
that PA is associated with HF development (9–14).
We therefore examined how total PA and 5
To the best of our knowledge, no previous study has
different domains of PA are associated with the
From the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. All authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received February 17, 2015; revised manuscript received May 11, 2015, accepted May 16, 2015.
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Physical Activity and Heart Failure
ABBREVIATIONS
development of HF in a population-based
home/household work w2.5 MET; watching TV/
AND ACRONYMS
prospective cohort study of men, examining
reading w1.2 MET; sleep w0.9 MET. Total daily
both relative risks and survival percentiles.
physical activity (TPA) score was then estimated by
We also investigated if changes of PA at
multiplying the intensity score of each type of PA for
different time points were associated with
its reported duration and then adding all specific
HF risk.
activities together. The intensity of an activity was
CI = confidence interval COSM = Cohort of Swedish Men
HF = heart failure
METHODS
HR = hazard ratio MET = metabolic equivalent
STUDY POPULATION. The study participants
PA = physical activity TPA = total physical activity
belonged to the Cohort of Swedish Men (COSM), a population-based cohort estab-
lished between 1997 and 1998. All men born between 1914 and 1948 residing in Örebro and Västmanland counties in Sweden were asked to complete an extensive questionnaire regarding PA, diet, anthropometric traits, and other lifestyle factors. We excluded individuals with prevalent HF or myocardial infarction (n ¼ 3,350) from the baseline population, based on linkage of the cohort to the
based on the rate of the work and did not take into account the physiological capacity of an individual. Implausible self-reported 24 h were corrected either by adding missing hours or subtracting over-reported hours. The correction time was multiplied by an intensity of 2.0 MET, which corresponded to the average of walking at home (2.5 MET) and sitting (eating, transportation etc. 1.5 MET). The questions on TPA in COSM have been validated by a previous study on a subpopulation of COSM. The study found that the correlation comparing selfreported TPA with records (7 days of PA diaries) was 0.56 (17), which suggests reasonable validity.
Swedish National Patient Register and the Swedish
ASCERTAINMENT OF HF EVENTS. Dates of incident
Cancer Register. This effort was made because the
HF hospitalization as well as dates of deaths from HF
previously mentioned diseases may affect both
were ascertained from January 1, 1998, to December
traditional HF risk factors and HF development. We
31, 2012, through linkage to the Swedish National
also excluded individuals with missing information
Patient Register and the Causes of Death Register.
on total PA (n ¼ 9,923) from the study sample. The
The Swedish National Patient Register represents the
final study population consisted of 33,012 men.
inpatient register, which includes all hospital admis-
The questionnaire included information on partici-
sions that entailed at least 1 overnight stay, and the
pants’ educational attainment, smoking and alcohol
outpatient register, which covers diagnoses registered
consumption, presence of hypertension, family his-
during outpatient care. HF events were identified
tory of myocardial infarction, diagnosis of diabetes
by using International Classification of Diseases-10
(which was complemented with information from the
codes I50 (HF) and I11.0 (hypertensive heart disease
diabetes register and the Swedish National Patient
with HF). We included the first HF event recorded in
Register), weight, and height. Information on history
the registers listed as either the primary or secondary
of stroke and angina was obtained from the Swedish
diagnosis of hospitalization or death.
National Patient Register.
STATISTICAL ANALYSES. Data handling and gener-
The study has been approved by the Regional
ation of descriptive statistics were performed in SAS
Ethical Review Board at Karolinska Institutet.
(version 9.2, SAS Institute, Inc, Cary, North Car-
ASSESSMENT OF PHYSICAL ACTIVITY. Study par-
olina). Stata software version 12.1 (StataCorp LP,
ticipants were asked to report how their level of ac-
College Station, Texas) was used to fit Cox propor-
tivity at work, home/housework, walking/bicycling,
tional hazards regression and Laplace regression.
and exercise, had been in the year before study
Hazard ratios (HR) and 95% confidence intervals (CI)
enrollment and at 30 years of age. Questions
were estimated using Cox proportional hazards
regarding inactivity (watching television or reading)
regression models with attained age as the under-
and an open question about hours per day of sleeping
lying time scale. Start of follow-up was January 1, 1998,
and sitting or lying down were also included in the
and follow-up was censored at the date of first event of
questionnaire. Each type of PA was assigned an in-
HF, death, or December 31, 2012, whichever occurred
tensity score defined as metabolic equivalent (MET)
first. TPA was modeled as a continuous variable by
hours per day, deriving the intensity score from the
means of restricted cubic splines with 3 knots of
compendium of physical activities (16). The mean
the distribution (at 36, 41, and 48 MET h/day) using
MET values assigned for the different types of
the median level of 41 MET h/day as the reference
PAs were as follows: walking/bicycling w3.6 MET;
value. We examined the linearity of the dose-response
exercise w5.0 MET; work occupation w1.3 MET for
by testing the null hypothesis that the coefficient of
mostly sitting down to 3.9 for heavy manual work;
the second spline was equal to zero. The top 1% and
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bottom 1% of TPA levels were removed to diminish influence from potential outliers. We then graphed
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Physical Activity and Heart Failure
T A B L E 1 Age-Standardized Baseline Characteristics of the Study Population of the
Cohort of Swedish Men by Categories of Physical Activity
the dose-response association between TPA and HF Quartiles of Total Physical Activity (MET hr/day)
incidence. Additionally, we evaluated the different domains
<38 (n ¼ 7,927)
$38 to <42 (n ¼ 7,981)
$42 to <45 (n ¼ 7,619)
$45 (n ¼ 7,614)
of TPA: exercise, walking/bicycling, work occupation,
Mean age at study entry,* yrs
59
59
61
60
home/household work, and physical inactivity. To
Ever smoker, %
64
62
62
62
examine if the results were inflicted by reverse cau-
Obesity, %
47
46
45
45
sality, we conducted a sensitivity analysis in which
Diabetes, %
6
5
5
5
study participants who developed HF during the first
Hypertension, %
26
22
22
19
3 years of follow-up time were excluded.
University education, %
25
24
15
8
Current drinker, %
93
93
92
91
History of stroke, %
3
2
1
2
History of angina, %
5
3
3
3
34
34
36
36
Laplace regression was next used to evaluate HF-free survival according to levels of PA and adjusting for potential confounders (15,18,19). We focused on the 50th percentile of attained age at first
Family history of MI before 60 yrs of age, %
HF event; attained age being also used as the under-
Self-reported health status
lying time scale in the Cox regression models, and
Heavy manual work, %
30
82
99
100
Exercise >1 h/week, %
63
83
81
84
Walking/bicycling $20 min/day
75
90
90
93
Home/household work >1 h/day, %
46
62
63
68
9
14
14
17
estimated multivariable-adjusted differences in the median age at first HF event between men who were active and inactive on the different domains of PA (walking/bicycling, exercise, work occupation, household work, and reading/watching TV). We also investigated the relationship between
Inactivity (watching television/reading) $3 h/day, %
Values are standardized to the age distribution of the study population. *Value is not age adjusted. MI ¼ myocardial infarction.
long-term behavior regarding walking/bicycling and the incidence of HF. This was done by combining information on levels of walking/bicycling ($20 min/
We found evidence of non-linearity (p < 0.001).
day vs. <20 min/day) at 30 years of age and in 1997,
Compared with participants with the median TPA level
examining if the level of walking/bicycling changed
(41 MET h/day), lower levels of TPA (beginning from
or remained the same. Walking/bicycling less than
40 MET h/day) were progressively associated with
20 min/day both at age 30 and in 1997 served as the
higher HF risk, with up to 44% higher risk for partici-
reference category.
pants with the lowest TPA (HR: 1.44; 95% CI: 1.24 to
Covariates included in the multivariable-adjusted
1.68). High levels of TPA (starting from 47 MET h/day)
model were age at study entry, educational attain-
were also associated with increased risk of HF, and
ment (primary school, high school, university), smok-
men who had the highest level of TPA (57 MET h/day)
ing (never/past/current [#10, >10 cigarettes/day]),
had an increased risk of HF (HR: 1.25; 95% CI: 1.03 to
alcohol consumption (never/past/current [<5, $5
1.53) compared with men with the median TPA level
g/day]), family history of myocardial infarction before
(Figure 1).
50 years of age, history of stroke, history of angina,
SPECIFIC
hypertension, diabetes, and body mass index (<18.5,
examining the different domains of activities that
18.5 to 24.9, 25 to 29.9, $30 kg/m 2). The proportional
constituted TPA, we found certain types of PA to
hazards assumption was examined by investigating
be associated with a reduced risk of HF (Table 2).
Schoenfeld’s residuals.
Walking/bicycling than 20 min/day was associated
RESULTS
TYPES
OF
PHYSICAL
ACTIVITY. When
with an HR of 0.79 (95% CI: 0.72 to 0.87). Exercising more than 1 h/week was associated with HF risk reduction with an HR of 0.86 (95% CI: 0.79 to 0.94) in
During a mean follow-up of 13 years (450,523 person-
the multivariable-adjusted model. Work occupation,
years), we ascertained a total of 3,609 HF events
household work, and physical inactivity were not
including 3,190 first events of HF hospitalizations and
significantly associated with HF development.
419 HF deaths. The average age at study entry among
Table 2 also shows the absolute differences in the
study participants was 60 years of age. Baseline
median age at first HF event between groups of
characteristics of the cohort according to quartiles of
moderate to high versus low levels of different types
TPA are presented in Table 1.
of PA estimated with Laplace regression. Moderate to
TOTAL PHYSICAL ACTIVITY. We modeled TPA as a
high levels of walking/bicycling and exercise were
continuous predictor using restricted cubic splines.
significantly associated with longer HF-free survival
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Physical Activity and Heart Failure
F I G U R E 1 Multivariable-Adjusted HRs for Incident HF Depending on Daily Total Physical Activity
2 1.8 1.6 1.4 1.2 40
1
30 .8
20
.6
10
Percent
Multivariable−adjusted Hazard Ratios
4
0 30
34
38 42 46 50 54 Total physical activity, MET hours/day
58
Hazard ratios (HRs) were adjusted for educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, and BMI (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2). Solid curve represents the restricted cubic spline and dashed-dotted line represents the 95% CI.
compared to low levels of the corresponding PA
in walking/bicycling with incidence of HF (Table 3).
types. The largest difference was detected for
Compared with men who had been inactive at both
walking/bicycling. By looking at the median age at HF
time points the HR was lower for men who had gone
event, HF cases who had engaged at least 20 min/day
from being inactive in this PA domain at age 30 to
in this activity had the HF event 8 months later than
active in 1997 (HR: 0.77; 95% CI: 0.58 to 1.02) and also
HF cases who had engaged in this activity less than
for men who had been active at both time points (HR:
20 min/day (50th percentile difference ¼ 230 days;
0.84; 95% CI: 0.69 to 1.03). The results, however, did
95% CI: 144 to 317 days).
not reach statistical significance (Table 3).
We further investigated if age at study entry or educational level differed significantly between men walking/bicycling at least 20 min/day versus men walking/bicycling less than 20 min/day. We did not find any significant difference on age or level of education between the 2 groups (data not shown).
DISCUSSION In this prospective population-based study, we found moderate levels of TPA to be associated with a lower risk of future HF. Compared with the median level of TPA, both extremely low and extremely high levels of
SENSITIVITY ANALYSIS. In the sensitivity analysis,
TPA were associated with an increased risk of HF.
in which we excluded study participants who devel-
However, the association was larger for lower levels
oped HF in the 3 first years of follow-up (n ¼ 104), to
of TPA. When investigating which domains of TPA
account for potential reverse causality, the results
were associated with a reduced risk of HF, we found
remained similar to the main analysis. The associa-
that engaging in walking or biking at least 20 min per
tion between walking/bicycling at least 20 min/day
day and exercising during leisure time at least 1 h per
and HF risk was comparable with the results from
week were associated with reduced HF risk.
the main model (HR: 0.77; 95% CI: 0.69 to 0.86) in
When examining long-term behavior regarding
the sensitivity analysis.
walking or biking and HF risk, the results suggested
LONG-TERM WALKING/BICYCLING. We also exam-
that more recent active behavior in this PA domain
ined the relationship between long-term behaviors
may be more important for HF protection than past
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T A B L E 2 Hazard Ratios of HF and Differences in Median Age at HF Event (50th PD), With 95% CI, According to Different Types of
Physical Activity Hazard Ratio (95% CI)*
Hazard Ratio (95% CI)†
50th PD (95% CI), days‡
Walking/bicycling, $20 min/day vs. <20 min/day
Type of Physical Activity
0.75 (0.68 to 0.82)
0.79 (0.72 to 0.87)
230 (144 to 317)
Exercise, $1 h/week vs. <1 h/week
0.80 (0.74 to 0.87)
0.86 (0.79 to 0.94)
125 (51 to 200)
Work occupation, active vs. mostly sitting
0.88 (0.81 to 0.96)
0.93 (0.85 to 1.01)
49 (–27 to 126)
Home/household work, $1 h/day vs. <1 h/day
0.97 (0.91 to 1.04)
0.95 (0.89 to 1.02)
3 (56 to 61)
1.01 (0.89 to 1.15)
0.99 (0.87 to 1.12)
33 (–79 to 146)
Inactivity (watching television/reading), <3 h/day vs. $3 h/day
*Hazard ratios adjusted for educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, and body mass index (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2). †Hazard ratios additionally mutually adjusted for all types of physical activity. ‡Estimates were obtained by fitting a Laplace regression model on the 50th percentile of age at heart failure (HF) event, and adjusted for age at baseline, educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, and body mass index (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2). All types of physical activity were mutually adjusted for. CI ¼ confidence interval; HF ¼ heart failure; PD ¼ percentile difference.
PA levels. Being active at age 30 but turning inactive
could potentially be attributed to increased oxidative
in 1997 was not found to be associated with decreased
stress, arterial stiffness, and coronary artery calcifica-
risk of HF.
tion (25). Moreover, it is possible that very heavy
Previous studies have shown that low levels of
manual work causes a great deal of stress, which in
PA increase the risk of HF (20). One former study
turn has adverse effects on cardiovascular health.
investigating the effect of different types of PA on HF
Another potential explanation could be that extremely
risk in a Finnish population found leisure time PA to
heavy manual work occupations are correlated with
have the largest inverse association with HF (13).
unhealthy lifestyle factors that exert increased risk of
A previous study by Lee et al. (21) showed that
HF, factors which were not accounted for in this study.
running from 5 to 10 min per day at low speed was
It is also interesting to note that a recent study
associated with a markedly HF risk reduction. In our
investigating the relationship between TPA and HF in
study, we observed the largest inverse association
women, using the same TPA construct, did not detect
with moderate levels of walking/bicycling and leisure
an increased risk of HF with very high levels of TPA
time exercise. Hence our results are in line with the
(26). Hence, the effects of PA might be different
results from the previous studies.
for men and women. A randomized controlled study
The biological link between PA and cardiovascular
examining the effects of exercise training on mortal-
disease is not fully understood. Several biological
ity and hospitalization reported that exercise training
explanations for potential cardioprotective effects
in individuals with HF was associated with a larger
exerted by PA have been suggested. For example, it
risk reduction of all-cause mortality and hospital stay
has been suggested that the beneficial effects could
in women compared with men (27).
be mediated through reductions in inflammatory and
STUDY STRENGTHS AND LIMITATIONS. To the best
hemostatic biomarkers, and to some extent blood
of our knowledge, the majority of previous studies
pressure, lipids, and body mass index (22). In a recent
have not investigated the dose-response association
study, it was shown that moderate levels of PA were
between PA and HF by using flexible tools such
associated with lower levels of sensitive troponin T
as splines. We also had information on long-term
and N-terminal pro–B-type natriuretic peptide and
PA behavior and could show that more recent PA
also lower risk of HF (23). In contrast to other studies, we also found extremely high levels of TPA to be associated with an
T A B L E 3 Hazard Ratios of HF, With 95% CI, According to Long-Term Behavior in
Walking/Bicycling
increased risk of HF. It is important to bear in mind that Walking/Bicycling in 1997
TPA was a construct encompassing various types of PAs, with work occupation being the biggest contributor. Some studies have suggested that heavy physical exercise, such as intense long-distance running, is associated with adverse cardiovascular outcomes (24,25). It is possible that substantial increase of pumping of blood by the heart could damage the cardiac muscle fibers, causing damage in the myocardium. Moreover, adverse cardiovascular outcomes
Walking/bicycling at 30 years of age
Inactive (<20 min/day)
Active ($20 min/day)
Inactive (<20 min/day)
1.00 reference
0.77 (0.58–1.02)
Active ($20 min/day)
1.01 (0.92–1.32)
0.84 (0.69–1.03)
Multivariable-adjusted hazard ratio (95% confidence interval [CI]) adjusted for age at baseline, educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, body mass index (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2), and other types of physical activity. Abbreviations as in Table 2.
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Physical Activity and Heart Failure
activity levels is associated with decreased risk of
be able to extrapolate our findings to other ethnic-
HF compared with past PA levels.
ities, younger age groups, or women.
Furthermore, we complemented our main results by reporting the association between PA domains and HF risk in terms of time differences, by estimating survival percentiles. This approach allows for an easier interpretation of the results and might facilitate the presentation of scientific results to the general public (15). Laplace regression, the method we used for this analysis, directly estimates differences in survival percentiles and enables adjustment for potential confounders (18). It is important to note that we cannot infer on causality based on our study results. It is possible that the association between PA and risk of future HF could have been due to unmeasured confounders or residual confounding both at baseline and during the follow-up period. Education level varied according to level of TPA in a strong negative fashion and it is
CONCLUSIONS This study shows that certain types of PA are associated with a protective effect on HF in men. Walking or biking at least 20 min each day and leisure time PA were in particular found to be associated with a risk reduction of HF. In addition, this study suggests that both extremely low and extremely high levels of TPA could elevate the risk of developing HF in men. Public awareness of specific types of PA as well as sufficient amount and duration of PA required for HF protection could potentially reduce the HF burden in society. Further studies unraveling the duration of PA and specific types of PA that are most beneficial for HF protection are therefore needed.
thus possible that residual confounding of education
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
was present. It could also be that educational level
Andrea Bellavia, Unit of Nutritional Epidemiology,
is correlated with income level/socioeconomic status
Institute of Environmental Medicine, Karolinska
and therefore with better health care services. These
Institutet, Box 210, 17177 Stockholm, Sweden. E-mail:
potential limitations could be particularly pertinent to
[email protected].
the positive association observed between very high levels of TPA at baseline and HF risk, as there was an inverse association between TPA and education. Moreover, we did not have information on medication use and objective measurements of risk factors such as blood pressure, variables that could have exerted confounding effects. We also lacked information on whether PA levels among the study participants changed during the course of the follow-up period. We used self-reported PA data, and therefore it is possible that PA levels were misclassified. It would have been desirable to include objective measures of PA, such as accelerometer data. However, our study was a prospective cohort study and such, recall bias is not expected to be an issue. Potential misclassification of PA should be independent of the outcome status and could have attenuated the association between PA and HF risk. The generalizability of this study might also be limited. This study population comprised middle-
PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: Among men, both high and low extremes of total physical activity were associated with an increased risk of heart failure. The domain of total physical activity that was associated with the largest risk reduction in heart failure was walking/bicycling at least 20 min/day. TRANSLATIONAL OUTLOOK: Prospective studies should carefully study nonlinear relationships between total physical activity and heart failure risk in men, as well as look deeper into what types of physical activity actually have a protective effect on heart failure. Certain types of physical activity, such as walking or biking 20 min daily, can be promoted in heart failure risk prevention strategies.
aged and elderly white men, so that we might not
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16. Ainsworth BE, Haskell WL, Herrmann SD, et al. 2011 Compendium of Physical Activities: a second update of codes and MET values. Med Sci Sports Exerc 2011;43:1575–81. 17. Norman A, Bellocco R, Bergstrom A, Wolk A. Validity and reproducibility of self-reported total physical activity—differences by relative weight. Int J Obes Relat Metab Disord 2001;25:682–8. 18. Bellavia A, Discacciati A, Bottai M, et al. Using Laplace Regression to model and predict percentiles of age at death when age is the primary time scale. Am J Epidemiol 2015 June 20 [E-pub ahead of print]. 19. Bottai M, N. Orsini. A command for Laplace regression. Stata J 2013;13:302–14. 20. Wen CP, Wai JP, Tsai MK, et al. Minimum amount of physical activity for reduced mortality and extended life expectancy: a prospective cohort study. Lancet 2011;378:1244–53.
events: potential mediating mechanisms. Circulation 2007;116:2110–8. 23. deFilippi CR, de Lemos JA, Tkaczuk AT, et al. Physical activity, change in biomarkers of myocardial stress and injury, and subsequent heart failure risk in older adults. J Am Coll Cardiol 2012; 60:2539–47. 24. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators. N Engl J Med 1993; 329:1677–83. 25. O’Keefe JH, Lavie CJ. Run for your life . at a comfortable speed and not too far. Heart 2013; 99:516–9. 26. Rahman I, Bellavia A, Wolk A. Relationship between physical activity and heart failure risk in women. Circ Heart Fail 2014;7:877–81. 27. Piña IL, Bittner V, Clare RM, et al. Effects of exercise training on outcomes in women with heart failure: analysis of HF-ACTION (Heart Failure-A Controlled Trial Investigating Outcomes of Exercise TraiNing) by sex. J Am Coll Cardiol HF
21. 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;64:472–81.
2014;2:180–6.
22. Mora S, Cook N, Buring JE, Ridker PM, Lee IM. Physical activity and reduced risk of cardiovascular
KEY WORDS physical activity, heart failure, epidemiology
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ª 2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER INC.
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ISSN 2213-1779/$36.00 http://dx.doi.org/10.1016/j.jchf.2015.05.006
Physical Activity and Heart Failure Risk in a Prospective Study of Men Iffat Rahman, PHD, Andrea Bellavia, MSC, Alicja Wolk, DRMEDSCI, Nicola Orsini, PHD
ABSTRACT OBJECTIVES This study investigated if total physical activity, as well as different types of physical activity, were associated with heart failure risk. BACKGROUND Physical activity has shown to be associated with reduced risks of coronary heart disease and stroke. Studies have also suggested that physical activity is associated with heart failure development. METHODS A study population of 33,012 men was followed from beginning of 1998 until the end of 2012. First event of heart failure was ascertained through linkage to the Swedish National Patient Register and Cause of Death Register. The data were analyzed by using Cox proportional hazards regression and Laplace regression. RESULTS During a mean follow-up of 13 years, we ascertained a total of 3,609 first events of heart failure. The average age at study baseline was 60 9 years of age. When examining the entire study population, a U-shaped association between total physical activity and heart failure risk was detected, with both extremely high (57 metabolic equivalent [MET] h/day) and extremely low (38 MET h/day) levels of total physical activity associated with an increased risk of heart failure. When investigating different types of physical activity, we found that walking/bicycling at least 20 min/day was associated with 21% lower risk of heart failure (95% confidence interval: 0.72 to 0.87); corresponding to a the median age at heart failure 8 months later for those who had actively walked or biked daily. When looking at long-term behavior of walking/bicycling, the results suggested a trend toward more recent active behavior being more related to heart failure protection than past physical activity levels. CONCLUSIONS This study suggests that both low levels and high levels of total physical activity, in comparison with moderate levels, could increase heart failure risk in men and that certain types of physical activity are associated with a protective effect on heart failure in men. When examining different types of physical activity, walking/bicycling at least 20 min per day was associated with the largest risk reduction of heart failure. (J Am Coll Cardiol HF 2015;-:-–-) © 2015 by the American College of Cardiology Foundation.
H
eart failure (HF) is a large public health
investigated the shape of association between total
issue with a substantial effect on the dis-
PA and HF modeling the exposure as a continuous
ease burden in developed countries, partic-
variable using flexible spline modeling. Neither has
ularly among the elderly (1). In the United States,
long-term behavior regarding PA in relation to HF
more than 5.8 million people suffer from HF, and
risk been investigated previously.
the number of HF sufferers worldwide is around
Moreover, previous studies have presented their
23 million (1). The lifetime risk for development of
results by relying only on relative measures of asso-
HF is around 20% (2).
ciation. These popular risk measures that lack a time
Physical activity (PA) has been shown to be asso-
unit may be complemented by estimating differences
ciated with reduced risks of coronary heart disease
in the percentiles of survival time, presenting results
(3–5) and stroke (3,5–8). Studies have also suggested
in the metric of time (i.e., days, months) (15).
that PA is associated with HF development (9–14).
We therefore examined how total PA and 5
To the best of our knowledge, no previous study has
different domains of PA are associated with the
From the Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden. All authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received February 17, 2015; revised manuscript received May 11, 2015, accepted May 16, 2015.
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Physical Activity and Heart Failure
ABBREVIATIONS
development of HF in a population-based
home/household work w2.5 MET; watching TV/
AND ACRONYMS
prospective cohort study of men, examining
reading w1.2 MET; sleep w0.9 MET. Total daily
both relative risks and survival percentiles.
physical activity (TPA) score was then estimated by
We also investigated if changes of PA at
multiplying the intensity score of each type of PA for
different time points were associated with
its reported duration and then adding all specific
HF risk.
activities together. The intensity of an activity was
CI = confidence interval COSM = Cohort of Swedish Men
HF = heart failure
METHODS
HR = hazard ratio MET = metabolic equivalent
STUDY POPULATION. The study participants
PA = physical activity TPA = total physical activity
belonged to the Cohort of Swedish Men (COSM), a population-based cohort estab-
lished between 1997 and 1998. All men born between 1914 and 1948 residing in Örebro and Västmanland counties in Sweden were asked to complete an extensive questionnaire regarding PA, diet, anthropometric traits, and other lifestyle factors. We excluded individuals with prevalent HF or myocardial infarction (n ¼ 3,350) from the baseline population, based on linkage of the cohort to the
based on the rate of the work and did not take into account the physiological capacity of an individual. Implausible self-reported 24 h were corrected either by adding missing hours or subtracting over-reported hours. The correction time was multiplied by an intensity of 2.0 MET, which corresponded to the average of walking at home (2.5 MET) and sitting (eating, transportation etc. 1.5 MET). The questions on TPA in COSM have been validated by a previous study on a subpopulation of COSM. The study found that the correlation comparing selfreported TPA with records (7 days of PA diaries) was 0.56 (17), which suggests reasonable validity.
Swedish National Patient Register and the Swedish
ASCERTAINMENT OF HF EVENTS. Dates of incident
Cancer Register. This effort was made because the
HF hospitalization as well as dates of deaths from HF
previously mentioned diseases may affect both
were ascertained from January 1, 1998, to December
traditional HF risk factors and HF development. We
31, 2012, through linkage to the Swedish National
also excluded individuals with missing information
Patient Register and the Causes of Death Register.
on total PA (n ¼ 9,923) from the study sample. The
The Swedish National Patient Register represents the
final study population consisted of 33,012 men.
inpatient register, which includes all hospital admis-
The questionnaire included information on partici-
sions that entailed at least 1 overnight stay, and the
pants’ educational attainment, smoking and alcohol
outpatient register, which covers diagnoses registered
consumption, presence of hypertension, family his-
during outpatient care. HF events were identified
tory of myocardial infarction, diagnosis of diabetes
by using International Classification of Diseases-10
(which was complemented with information from the
codes I50 (HF) and I11.0 (hypertensive heart disease
diabetes register and the Swedish National Patient
with HF). We included the first HF event recorded in
Register), weight, and height. Information on history
the registers listed as either the primary or secondary
of stroke and angina was obtained from the Swedish
diagnosis of hospitalization or death.
National Patient Register.
STATISTICAL ANALYSES. Data handling and gener-
The study has been approved by the Regional
ation of descriptive statistics were performed in SAS
Ethical Review Board at Karolinska Institutet.
(version 9.2, SAS Institute, Inc, Cary, North Car-
ASSESSMENT OF PHYSICAL ACTIVITY. Study par-
olina). Stata software version 12.1 (StataCorp LP,
ticipants were asked to report how their level of ac-
College Station, Texas) was used to fit Cox propor-
tivity at work, home/housework, walking/bicycling,
tional hazards regression and Laplace regression.
and exercise, had been in the year before study
Hazard ratios (HR) and 95% confidence intervals (CI)
enrollment and at 30 years of age. Questions
were estimated using Cox proportional hazards
regarding inactivity (watching television or reading)
regression models with attained age as the under-
and an open question about hours per day of sleeping
lying time scale. Start of follow-up was January 1, 1998,
and sitting or lying down were also included in the
and follow-up was censored at the date of first event of
questionnaire. Each type of PA was assigned an in-
HF, death, or December 31, 2012, whichever occurred
tensity score defined as metabolic equivalent (MET)
first. TPA was modeled as a continuous variable by
hours per day, deriving the intensity score from the
means of restricted cubic splines with 3 knots of
compendium of physical activities (16). The mean
the distribution (at 36, 41, and 48 MET h/day) using
MET values assigned for the different types of
the median level of 41 MET h/day as the reference
PAs were as follows: walking/bicycling w3.6 MET;
value. We examined the linearity of the dose-response
exercise w5.0 MET; work occupation w1.3 MET for
by testing the null hypothesis that the coefficient of
mostly sitting down to 3.9 for heavy manual work;
the second spline was equal to zero. The top 1% and
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bottom 1% of TPA levels were removed to diminish influence from potential outliers. We then graphed
3
Physical Activity and Heart Failure
T A B L E 1 Age-Standardized Baseline Characteristics of the Study Population of the
Cohort of Swedish Men by Categories of Physical Activity
the dose-response association between TPA and HF Quartiles of Total Physical Activity (MET hr/day)
incidence. Additionally, we evaluated the different domains
<38 (n ¼ 7,927)
$38 to <42 (n ¼ 7,981)
$42 to <45 (n ¼ 7,619)
$45 (n ¼ 7,614)
of TPA: exercise, walking/bicycling, work occupation,
Mean age at study entry,* yrs
59
59
61
60
home/household work, and physical inactivity. To
Ever smoker, %
64
62
62
62
examine if the results were inflicted by reverse cau-
Obesity, %
47
46
45
45
sality, we conducted a sensitivity analysis in which
Diabetes, %
6
5
5
5
study participants who developed HF during the first
Hypertension, %
26
22
22
19
3 years of follow-up time were excluded.
University education, %
25
24
15
8
Current drinker, %
93
93
92
91
History of stroke, %
3
2
1
2
History of angina, %
5
3
3
3
34
34
36
36
Laplace regression was next used to evaluate HF-free survival according to levels of PA and adjusting for potential confounders (15,18,19). We focused on the 50th percentile of attained age at first
Family history of MI before 60 yrs of age, %
HF event; attained age being also used as the under-
Self-reported health status
lying time scale in the Cox regression models, and
Heavy manual work, %
30
82
99
100
Exercise >1 h/week, %
63
83
81
84
Walking/bicycling $20 min/day
75
90
90
93
Home/household work >1 h/day, %
46
62
63
68
9
14
14
17
estimated multivariable-adjusted differences in the median age at first HF event between men who were active and inactive on the different domains of PA (walking/bicycling, exercise, work occupation, household work, and reading/watching TV). We also investigated the relationship between
Inactivity (watching television/reading) $3 h/day, %
Values are standardized to the age distribution of the study population. *Value is not age adjusted. MI ¼ myocardial infarction.
long-term behavior regarding walking/bicycling and the incidence of HF. This was done by combining information on levels of walking/bicycling ($20 min/
We found evidence of non-linearity (p < 0.001).
day vs. <20 min/day) at 30 years of age and in 1997,
Compared with participants with the median TPA level
examining if the level of walking/bicycling changed
(41 MET h/day), lower levels of TPA (beginning from
or remained the same. Walking/bicycling less than
40 MET h/day) were progressively associated with
20 min/day both at age 30 and in 1997 served as the
higher HF risk, with up to 44% higher risk for partici-
reference category.
pants with the lowest TPA (HR: 1.44; 95% CI: 1.24 to
Covariates included in the multivariable-adjusted
1.68). High levels of TPA (starting from 47 MET h/day)
model were age at study entry, educational attain-
were also associated with increased risk of HF, and
ment (primary school, high school, university), smok-
men who had the highest level of TPA (57 MET h/day)
ing (never/past/current [#10, >10 cigarettes/day]),
had an increased risk of HF (HR: 1.25; 95% CI: 1.03 to
alcohol consumption (never/past/current [<5, $5
1.53) compared with men with the median TPA level
g/day]), family history of myocardial infarction before
(Figure 1).
50 years of age, history of stroke, history of angina,
SPECIFIC
hypertension, diabetes, and body mass index (<18.5,
examining the different domains of activities that
18.5 to 24.9, 25 to 29.9, $30 kg/m 2). The proportional
constituted TPA, we found certain types of PA to
hazards assumption was examined by investigating
be associated with a reduced risk of HF (Table 2).
Schoenfeld’s residuals.
Walking/bicycling than 20 min/day was associated
RESULTS
TYPES
OF
PHYSICAL
ACTIVITY. When
with an HR of 0.79 (95% CI: 0.72 to 0.87). Exercising more than 1 h/week was associated with HF risk reduction with an HR of 0.86 (95% CI: 0.79 to 0.94) in
During a mean follow-up of 13 years (450,523 person-
the multivariable-adjusted model. Work occupation,
years), we ascertained a total of 3,609 HF events
household work, and physical inactivity were not
including 3,190 first events of HF hospitalizations and
significantly associated with HF development.
419 HF deaths. The average age at study entry among
Table 2 also shows the absolute differences in the
study participants was 60 years of age. Baseline
median age at first HF event between groups of
characteristics of the cohort according to quartiles of
moderate to high versus low levels of different types
TPA are presented in Table 1.
of PA estimated with Laplace regression. Moderate to
TOTAL PHYSICAL ACTIVITY. We modeled TPA as a
high levels of walking/bicycling and exercise were
continuous predictor using restricted cubic splines.
significantly associated with longer HF-free survival
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Physical Activity and Heart Failure
F I G U R E 1 Multivariable-Adjusted HRs for Incident HF Depending on Daily Total Physical Activity
2 1.8 1.6 1.4 1.2 40
1
30 .8
20
.6
10
Percent
Multivariable−adjusted Hazard Ratios
4
0 30
34
38 42 46 50 54 Total physical activity, MET hours/day
58
Hazard ratios (HRs) were adjusted for educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, and BMI (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2). Solid curve represents the restricted cubic spline and dashed-dotted line represents the 95% CI.
compared to low levels of the corresponding PA
in walking/bicycling with incidence of HF (Table 3).
types. The largest difference was detected for
Compared with men who had been inactive at both
walking/bicycling. By looking at the median age at HF
time points the HR was lower for men who had gone
event, HF cases who had engaged at least 20 min/day
from being inactive in this PA domain at age 30 to
in this activity had the HF event 8 months later than
active in 1997 (HR: 0.77; 95% CI: 0.58 to 1.02) and also
HF cases who had engaged in this activity less than
for men who had been active at both time points (HR:
20 min/day (50th percentile difference ¼ 230 days;
0.84; 95% CI: 0.69 to 1.03). The results, however, did
95% CI: 144 to 317 days).
not reach statistical significance (Table 3).
We further investigated if age at study entry or educational level differed significantly between men walking/bicycling at least 20 min/day versus men walking/bicycling less than 20 min/day. We did not find any significant difference on age or level of education between the 2 groups (data not shown).
DISCUSSION In this prospective population-based study, we found moderate levels of TPA to be associated with a lower risk of future HF. Compared with the median level of TPA, both extremely low and extremely high levels of
SENSITIVITY ANALYSIS. In the sensitivity analysis,
TPA were associated with an increased risk of HF.
in which we excluded study participants who devel-
However, the association was larger for lower levels
oped HF in the 3 first years of follow-up (n ¼ 104), to
of TPA. When investigating which domains of TPA
account for potential reverse causality, the results
were associated with a reduced risk of HF, we found
remained similar to the main analysis. The associa-
that engaging in walking or biking at least 20 min per
tion between walking/bicycling at least 20 min/day
day and exercising during leisure time at least 1 h per
and HF risk was comparable with the results from
week were associated with reduced HF risk.
the main model (HR: 0.77; 95% CI: 0.69 to 0.86) in
When examining long-term behavior regarding
the sensitivity analysis.
walking or biking and HF risk, the results suggested
LONG-TERM WALKING/BICYCLING. We also exam-
that more recent active behavior in this PA domain
ined the relationship between long-term behaviors
may be more important for HF protection than past
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T A B L E 2 Hazard Ratios of HF and Differences in Median Age at HF Event (50th PD), With 95% CI, According to Different Types of
Physical Activity Hazard Ratio (95% CI)*
Hazard Ratio (95% CI)†
50th PD (95% CI), days‡
Walking/bicycling, $20 min/day vs. <20 min/day
Type of Physical Activity
0.75 (0.68 to 0.82)
0.79 (0.72 to 0.87)
230 (144 to 317)
Exercise, $1 h/week vs. <1 h/week
0.80 (0.74 to 0.87)
0.86 (0.79 to 0.94)
125 (51 to 200)
Work occupation, active vs. mostly sitting
0.88 (0.81 to 0.96)
0.93 (0.85 to 1.01)
49 (–27 to 126)
Home/household work, $1 h/day vs. <1 h/day
0.97 (0.91 to 1.04)
0.95 (0.89 to 1.02)
3 (56 to 61)
1.01 (0.89 to 1.15)
0.99 (0.87 to 1.12)
33 (–79 to 146)
Inactivity (watching television/reading), <3 h/day vs. $3 h/day
*Hazard ratios adjusted for educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, and body mass index (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2). †Hazard ratios additionally mutually adjusted for all types of physical activity. ‡Estimates were obtained by fitting a Laplace regression model on the 50th percentile of age at heart failure (HF) event, and adjusted for age at baseline, educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, and body mass index (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2). All types of physical activity were mutually adjusted for. CI ¼ confidence interval; HF ¼ heart failure; PD ¼ percentile difference.
PA levels. Being active at age 30 but turning inactive
could potentially be attributed to increased oxidative
in 1997 was not found to be associated with decreased
stress, arterial stiffness, and coronary artery calcifica-
risk of HF.
tion (25). Moreover, it is possible that very heavy
Previous studies have shown that low levels of
manual work causes a great deal of stress, which in
PA increase the risk of HF (20). One former study
turn has adverse effects on cardiovascular health.
investigating the effect of different types of PA on HF
Another potential explanation could be that extremely
risk in a Finnish population found leisure time PA to
heavy manual work occupations are correlated with
have the largest inverse association with HF (13).
unhealthy lifestyle factors that exert increased risk of
A previous study by Lee et al. (21) showed that
HF, factors which were not accounted for in this study.
running from 5 to 10 min per day at low speed was
It is also interesting to note that a recent study
associated with a markedly HF risk reduction. In our
investigating the relationship between TPA and HF in
study, we observed the largest inverse association
women, using the same TPA construct, did not detect
with moderate levels of walking/bicycling and leisure
an increased risk of HF with very high levels of TPA
time exercise. Hence our results are in line with the
(26). Hence, the effects of PA might be different
results from the previous studies.
for men and women. A randomized controlled study
The biological link between PA and cardiovascular
examining the effects of exercise training on mortal-
disease is not fully understood. Several biological
ity and hospitalization reported that exercise training
explanations for potential cardioprotective effects
in individuals with HF was associated with a larger
exerted by PA have been suggested. For example, it
risk reduction of all-cause mortality and hospital stay
has been suggested that the beneficial effects could
in women compared with men (27).
be mediated through reductions in inflammatory and
STUDY STRENGTHS AND LIMITATIONS. To the best
hemostatic biomarkers, and to some extent blood
of our knowledge, the majority of previous studies
pressure, lipids, and body mass index (22). In a recent
have not investigated the dose-response association
study, it was shown that moderate levels of PA were
between PA and HF by using flexible tools such
associated with lower levels of sensitive troponin T
as splines. We also had information on long-term
and N-terminal pro–B-type natriuretic peptide and
PA behavior and could show that more recent PA
also lower risk of HF (23). In contrast to other studies, we also found extremely high levels of TPA to be associated with an
T A B L E 3 Hazard Ratios of HF, With 95% CI, According to Long-Term Behavior in
Walking/Bicycling
increased risk of HF. It is important to bear in mind that Walking/Bicycling in 1997
TPA was a construct encompassing various types of PAs, with work occupation being the biggest contributor. Some studies have suggested that heavy physical exercise, such as intense long-distance running, is associated with adverse cardiovascular outcomes (24,25). It is possible that substantial increase of pumping of blood by the heart could damage the cardiac muscle fibers, causing damage in the myocardium. Moreover, adverse cardiovascular outcomes
Walking/bicycling at 30 years of age
Inactive (<20 min/day)
Active ($20 min/day)
Inactive (<20 min/day)
1.00 reference
0.77 (0.58–1.02)
Active ($20 min/day)
1.01 (0.92–1.32)
0.84 (0.69–1.03)
Multivariable-adjusted hazard ratio (95% confidence interval [CI]) adjusted for age at baseline, educational attainment (primary school, high school, university), smoking (never, past, current [#10, >10 cigarettes/day]), alcohol consumption (never/past/current [<5, $5 g/day]), family history of myocardial infarction, history of stroke, history of angina, hypertension, diabetes, body mass index (<18.5, 18.5 to 24.9, 25 to 29.9, $30 kg/m2), and other types of physical activity. Abbreviations as in Table 2.
5
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Physical Activity and Heart Failure
activity levels is associated with decreased risk of
be able to extrapolate our findings to other ethnic-
HF compared with past PA levels.
ities, younger age groups, or women.
Furthermore, we complemented our main results by reporting the association between PA domains and HF risk in terms of time differences, by estimating survival percentiles. This approach allows for an easier interpretation of the results and might facilitate the presentation of scientific results to the general public (15). Laplace regression, the method we used for this analysis, directly estimates differences in survival percentiles and enables adjustment for potential confounders (18). It is important to note that we cannot infer on causality based on our study results. It is possible that the association between PA and risk of future HF could have been due to unmeasured confounders or residual confounding both at baseline and during the follow-up period. Education level varied according to level of TPA in a strong negative fashion and it is
CONCLUSIONS This study shows that certain types of PA are associated with a protective effect on HF in men. Walking or biking at least 20 min each day and leisure time PA were in particular found to be associated with a risk reduction of HF. In addition, this study suggests that both extremely low and extremely high levels of TPA could elevate the risk of developing HF in men. Public awareness of specific types of PA as well as sufficient amount and duration of PA required for HF protection could potentially reduce the HF burden in society. Further studies unraveling the duration of PA and specific types of PA that are most beneficial for HF protection are therefore needed.
thus possible that residual confounding of education
REPRINT REQUESTS AND CORRESPONDENCE: Dr.
was present. It could also be that educational level
Andrea Bellavia, Unit of Nutritional Epidemiology,
is correlated with income level/socioeconomic status
Institute of Environmental Medicine, Karolinska
and therefore with better health care services. These
Institutet, Box 210, 17177 Stockholm, Sweden. E-mail:
potential limitations could be particularly pertinent to
[email protected].
the positive association observed between very high levels of TPA at baseline and HF risk, as there was an inverse association between TPA and education. Moreover, we did not have information on medication use and objective measurements of risk factors such as blood pressure, variables that could have exerted confounding effects. We also lacked information on whether PA levels among the study participants changed during the course of the follow-up period. We used self-reported PA data, and therefore it is possible that PA levels were misclassified. It would have been desirable to include objective measures of PA, such as accelerometer data. However, our study was a prospective cohort study and such, recall bias is not expected to be an issue. Potential misclassification of PA should be independent of the outcome status and could have attenuated the association between PA and HF risk. The generalizability of this study might also be limited. This study population comprised middle-
PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: Among men, both high and low extremes of total physical activity were associated with an increased risk of heart failure. The domain of total physical activity that was associated with the largest risk reduction in heart failure was walking/bicycling at least 20 min/day. TRANSLATIONAL OUTLOOK: Prospective studies should carefully study nonlinear relationships between total physical activity and heart failure risk in men, as well as look deeper into what types of physical activity actually have a protective effect on heart failure. Certain types of physical activity, such as walking or biking 20 min daily, can be promoted in heart failure risk prevention strategies.
aged and elderly white men, so that we might not
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KEY WORDS physical activity, heart failure, epidemiology
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