Original Research Article
Frequency, Type, and Volume of Leisure-Time
Physical Activity and Risk of Coronary Heart
Disease in Young Women
Editorial, see p 300
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BACKGROUND: The inverse association between physical activity and
coronary heart disease (CHD) risk has primarily been shown in studies of
middle-aged and older adults. Evidence for the benefits of frequency, type,
and volume of leisure-time physical activity in young women is limited.
Andrea K. Chomistek,
ScD
Beate Henschel, MPH
A. Heather Eliassen, ScD
Kenneth J. Mukamal, MD,
MPH
Eric B. Rimm, ScD
METHODS: We conducted a prospective analysis among 97 230 women
aged 27 to 44 years at baseline in 1991. Leisure-time physical activity was
assessed biennially by questionnaire. Cox proportional hazards models
were used to examine the associations between physical activity frequency,
type, and volume, and CHD risk.
RESULTS: During 20 years of follow-up, we documented 544 incident CHD
cases. In multivariable-adjusted models, the hazard ratio (95% confidence
interval) of CHD comparing ≥30 with <1 metabolic equivalent of taskhours/wk of physical activity was 0.75 (0.57–0.99) (P, trend=0.01).
Brisk walking alone was also associated with significantly lower CHD risk.
Physical activity frequency was not associated with CHD risk when models
also included overall activity volume. Finally, the association was not
modified by body mass index (kg/m2) (P, interaction=0.70). Active women
(≥30 metabolic equivalent of task-hours/wk) with body mass index<25 kg/
m2 had 0.52 (95% confidence interval, 0.35–0.78) times the rate of CHD in
comparison with women who were obese (body mass index≥30 kg/m2) and
inactive (physical activity <1 metabolic equivalent of task-hours/wk).
CONCLUSIONS: These prospective data suggest that total volume of
leisure-time physical activity is associated with lower risk of incident CHD
among young women. In addition, this association was not modified by
weight, emphasizing that it is important for normal weight, overweight, and
obese women to be physically active.
Correspondence to: Andrea K.
Chomistek, ScD, Department of
Epidemiology and Biostatistics,
School of Public Health, Indiana University Bloomington, 1025 E 7th St,
Rm C101, Bloomington, IN 47405.
E-mail [email protected]
Sources of Funding, see p 298
Key Words: epidemiology ◼
exercise ◼ myocardial infarction
◼ women
© 2016 American Heart
Association, Inc.
290
July 26, 2016
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
Physical Activity and CHD in Young Women
Clinical Perspective
What Is New?
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What Are the Clinical Implications?
• For patients who are currently inactive and find joining a gym intimidating, emphasizing the benefits of
walking may help them get active.
• Findings from this study indicate that the frequency
of physical activity is not as important as the total
volume; thus, patients can achieve the recommended 150 minutes of moderate- to vigorousintensity physical activity per week in as many or as
few sessions as they wish.
• Our results suggest that previously inactive women
who become physically active can still decrease
their risk of CHD.
• It is important for normal weight, overweight, and
obese women to be physically active.
L
eisure-time physical activity is associated with an
≈30% lower risk of coronary heart disease (CHD)
in women.1,2 The majority of studies, however, have
been conducted in middle-aged and older populations
because cardiovascular disease morbidity and mortality
rates are low in women <55 years.3 Manson et al4 reported an inverse association between physical activity
and cardiovascular disease in 3 separate age groups
of women in the Women’s Health Initiative Observational
Study, with the youngest group including women 50 to
59 years of age at baseline. However, evidence for the
benefits of exercise for CHD in younger women is very
limited.
Although CHD morbidity and mortality rates are low
in younger women, the CHD mortality rate among US
women aged 25 to 54 years has shown minimal improvement in the past 2 decades, in contrast to rates
in older adults that have consistently declined.5 A potential explanation may be the increases in the prevalence
of diabetes mellitus and obesity.6,7 In addition, younger
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
METHODS
Study Population
The NHSII (Nurses’ Health Study II) is an ongoing cohort
study that was established in 1989 and included 116 430
predominantly white registered nurses aged 25 to 42 years.
Participants completed a baseline self-administered questionnaire used to collect information on lifestyle factors, including physical activity, health behaviors, and medical history.
Follow-up biennial questionnaires were sent to participants to
collect updated information on potential risk factors and newly
diagnosed diseases. Biennial response rates are >90%. This
study was approved by the Institutional Review Board at the
Harvard T.H. Chan School of Public Health. Informed consent
was implied by completion of the questionnaire.
Participants first reported on the frequency of physical
activity and completed a semiquantitative food frequency
questionnaire 12 in 1991, which served as the baseline for
this analysis. Women were excluded if they did not complete
the baseline physical activity questionnaire (n=15 418) or
reported an inability to walk at baseline (n=69). After exclusion
of women with cardiovascular disease, cancer, or diabetes
mellitus before 1991 (n=3713), 97 230 women were included
in the analysis.
Assessment of Physical Activity
Leisure-time physical activity was assessed in 1991, 1997,
2001, 2005, and 2009 through questions on average total
July 26, 2016
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ORIGINAL RESEARCH
ARTICLE
• Findings from this study indicate that physical activity is associated with lower risk of coronary heart
disease (CHD) in young women.
• Exercise did not have to be strenuous to have such
associations; moderate-intensity physical activity,
including brisk walking, was associated with lower
risk of CHD.
• In addition, we found that frequency of physical activity was not associated with CHD risk after adjusting
for total volume of physical activity.
• We found no association between physical activity
earlier in life and CHD risk in adulthood.
• Finally, the associations between physical activity
and lower CHD risk were evident regardless of body
mass index.
women differ from older women with regard to their lipid
profiles, and psychosocial risk factors, as well, which
may potentially impact the association between physical activity and CHD.8,9 We have recently shown that a
healthy lifestyle that includes a healthy diet, not smoking,
normal weight, and at least 2.5 hours per week of moderate- to vigorous-intensity exercise is associated with
substantially lower CHD risk in younger women.10 Nonetheless, physical activity is a complex exposure because
of its many dimensions, intensity, type, and frequency,
all of which may be important for the prevention of CHD
in younger women.
The purpose of this study was to assess the relationship between the volume of total leisure-time physical
activity (in metabolic equivalent of task [MET]-hours/wk)
and CHD in young women, while also examining moderate- and vigorous-intensity activity separately. In addition,
we examined whether frequency and type of exercise
were important attributes to general measures of overall
activity in relation to CHD risk. Because rises in obesity
may be a reason for the lack of decline in CHD mortality rates in young women, we investigated whether high
levels of physical activity could eliminate the adverse association between excess weight and CHD risk. Finally,
given the high prevalence of inactivity among adolescent
girls,11 we also investigated the associations between
activity during adolescence and young adulthood and
CHD during adulthood.
Chomistek et al
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time per week spent on various activities over the previous year.
The questions included on the 2009 NHS2 questionnaire can
be accessed at the Nurses’ Health Study website.13 Walking
pace, categorized as casual (<2 mph), normal (2–2.9 mph),
brisk (3–3.9 mph), or striding (≥4 mph), was also assessed. A
MET score was assigned to each activity based on its energy
cost.14 To calculate the amount of energy expended, the time
spent at each activity in hours per week was multiplied by its
MET score, then summed over all activities to yield total METhours/wk. Moderate activities (3 ≤ METs < 6) included brisk
walking, outdoor work, yoga (beginning in 2001), and weight
training (beginning in 2001). Vigorous activities, defined as
requiring MET values ≥6, were jogging (>10 minutes/mile),
running (≤10 minutes/mile), bicycling, lap swimming, tennis/
squash/racquetball, and other aerobic exercise.
The validity and reproducibility of the physical activity questionnaire have been reported in detail elsewhere.15 In brief, the
Pearson correlation between 4 one-week diaries and the questionnaire was 0.62 for moderate and vigorous recreational activity.
In addition to time per week spent on physical activity, frequency of exercise was assessed in 1991, 1993, 1995, 2005,
and 2009. This was assessed by using a single question that
read, “How many times per week do you engage in physical
activity long enough to perspire heavily (including swimming)?”
The responses provided were less than once/wk, once/wk, 2
to 3 times/wk, 4 to 6 times/wk, and ≥7 times/wk.
In 1997, participants were asked about their walking and
leisure-time activity during 5 age periods: grades 7 to 8, grades
9 to 12, ages 18 to 22, ages 23 to 29, and ages 30 to 34. For
each period, participants reported the average hours per week
they engaged in each of 3 activity categories, with examples
given for each: strenuous recreational activity (eg, running,
aerobics, swimming laps), moderate recreational activity (eg,
hiking, walking for exercise, casual cycling, and yard work), and
walking to and from school or work. Seven categories were
provided for responses ranging from 0 to 11+ hours per week.
Outcome Ascertainment
The primary end point was incident CHD, which included nonfatal myocardial infarction and fatal CHD. Self-reported MIs
were confirmed by medical records according to World Health
Organization criteria that included symptoms plus either diagnostic ECG changes or elevated cardiac-specific enzymes.16
Fatal CHD was confirmed by hospital or autopsy records or if
CHD was listed as the cause of death on the death certificate
and evidence of previous CHD was available.
Statistical Analysis
All analyses were performed using SAS statistical software,
version 9.3 (SAS Institute Inc, Cary, NC). Each eligible participant contributed person-time from the return of the 1991
questionnaire (or 1997 questionnaire for analysis of adolescent physical activity) until the date of diagnosis of the first
CHD event, death, or June 2011.
Analysis of Total, Moderate-Intensity, and
Vigorous-Intensity Physical Activity
Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CHD
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July 26, 2016
outcomes. Physical activity was modeled as a time-varying
exposure where simple updated levels of physical activity,
using the most recent value of activity reported, were used.
For example, events and person-time accrued between 1991
and 1997 were categorized according to exposures reported
on the 1991 questionnaire; events and person-time accrued
between 1997 and 2001 were categorized according to
exposures reported on the 1997 questionnaire; and so forth.
Participants were divided into quintiles (<1, 1–5.9, 6–14.9,
15–29.9, and ≥30 MET-hours/wk) for total leisure-time physical activity. For moderate- and vigorous-intensity activity, categories were based on the distribution of these variables as
well as informative cut points. For example, 3 MET-hours/wk
corresponds to 1 hour of moderate or 0.5 hours of vigorous
activity and 7.5 MET-hours/wk corresponds to 2.5 hours of
moderate or 1.25 hours of vigorous activity (the current recommendations based on the Physical Activity Guidelines for
Americans).3 Tests for linear trend were computed by using
the medians for categories modeled as a continuous variable.
Analysis of Individual Types of Physical Activity
In addition, we examined each individual activity separately
while adjusting for all other activity using categories of 0, 0.1
to 0.9, and 1+ hours per week (except for walking, where categories were 0, 0.1–0.9, 1–2.4, and 2.5+ hours per week due
to a larger number of women reporting walking compared to
other types of activities). For this analysis we used hours rather
than MET-hours to be able to use the same categories for all
activities, both those requiring more METs (eg, running) and
fewer METs (eg, yard work). Yoga and weight training were not
assessed until 2001; as such, we did not have enough power
to look at these individually.
Covariables
The multivariable models were stratified by age (in months) and
calendar year and included parental history of myocardial infarction before 60 years of age (yes/no), smoking (never, former,
current: 1–15 cigarettes/d, current: ≥15 cigarettes/d), hours
per week of television watching (quartiles), Alternative Healthy
Eating Index-2010 diet score (quintiles), aspirin use (yes/no),
menopausal status (pre/postmenopausal), postmenopausal
hormone use (never, past, current), parity (none, 1–2 children,
3–4 children, 5+ children), oral contraceptive use (never, past,
current), and history of hypertension (yes/no) or hypercholesterolemia (yes/no) at baseline. All covariables were updated
over time, except for hypertension and hypercholesterolemia
because the incidence of these conditions may be in the causal
pathway relating physical activity to CHD. Information from previous questionnaires was used when covariable data in a given
cycle were missing.
Sensitivity Analyses
To minimize bias attributable to reverse causation in situations where preclinical cardiovascular disease may limit the
ability to exercise, in the main analysis, we stopped updating
physical activity when an individual reported difficulty climbing a flight of stairs or walking. In addition, we performed
sensitivity analyses with a 2- and 4-year lag to exclude preclinical cases at baseline. For example, in a 2-year lag analysis, physical activity reported in 1991 would be used for the
1993 to 1995 follow-up period.
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
Physical Activity and CHD in Young Women
In addition to using simple updated levels of physical
activity, we also conducted a secondary analysis where we
calculated the cumulative average of physical activity levels
from all available questionnaires up to the start of each 2-year
follow-up interval to represent long-term levels of exercise.17
Analysis of Joint Association and Effect
Modification
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RESULTS
The mean (SD) age of the study population at baseline
was 36.6 (4.6) years. During 20 years of follow-up, 544
Table 1. Age-Standardized Characteristics According to Physical Activity at Baseline (1991), Nurses’ Health
Study II
Categories of Physical Activity, MET-h/wk (1991)
1 (<1)
(n=19 129)
2 (1–5.9)
(n=21 107)
3 (6–14.9)
(n=20 968)
4 (15–29.9)
(n=18 697)
5 (≥30)
(n=17 329)
Ptrend
Age, y
37.2 (4.6)
36.7 (4.6)
36.5 (4.6)
36.3 (4.7)
36.1 (4.7)
<0.0001
Total physical activity, MET-h/wk
0.0 (0.1)
4.0 (2.1)
10.0 (3.9)
20.2 (6.6)
46.0 (28.8)
–
Vigorous activity, MET-h/wk
0.0 (0.0)
0.4 (1.4)
5.9 (6.1)
15.0 (10.5)
30.4 (28.6)
–
Moderate activity, MET-h/wk
0.0 (0.0)
2.7 (4.4)
4.5 (7.6)
7.2 (10.0)
15.6 (28.8)
–
Body mass index, kg/m2
25.8 (6.3)
25.3 (5.7)
24.5 (5.0)
23.9 (4.5)
23.3 (4.1)
<0.0001
Hypercholesterolemia, %
16.1
15.1
14.4
13.4
13.0
<0.0001
Hypertension, %
7.3
6.6
6.0
5.3
5.4
<0.0001
Family history of myocardial infarction, %
22.4
21.8
21.8
21.7
21.1
0.006
Current smoker, %
13.8
13.3
11.8
10.9
10.8
<0.0001
AHEI-2010* score
44.7 (10.3)
46.3 (10.2)
48.5 (10.5)
50.5 (10.8)
53.4 (11.2)
<0.0001
Aspirin use, %
10.6
11.1
11.2
11.5
11.3
0.08
Current oral contraceptive user, %
9.8
10.3
10.3
11.4
11.8
<0.0001
Menopausal hormone therapy use, %
4.5
4.6
4.6
4.2
4.4
0.22
Postmenopausal, %
3.3
3.2
3.1
3.1
3.3
0.80
Parous, %
79.0
77.2
74.5
71.7
65.7
<0.0001
9.9 (9.7)
9.1 (8.6)
8.6 (8.1)
8.4 (7.8)
7.8 (7.8)
<0.0001
T.V. watching, hrs/wk
All values are means (SD) for continuous variables or frequencies for categorical variables, adjusted for age (except for age), except for physical activity
variables which are medians (IQR). AHEI-2010 indicates Alternative Healthy Eating Index-2010; IQR, interquartile range; MET, metabolic equivalent of task;
and SD, standard deviation.
*The AHEI-2010 includes 11 components: high intake of vegetables, fruits, whole grains, nuts and legumes, long-chain (n-3) fats (EPA+DHA), and
polyunsaturated fatty acids; moderate intake of alcohol; and low intake of sugar-sweetened beverages and fruit juice, red and processed meat, trans fat,
and sodium. The AHEI-2010 score ranges from 0 to 110 with higher scores representing better adherence.
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
July 26, 2016
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Finally, we assessed the joint association of leisure-time
physical activity and body mass index (BMI) with risk of CHD.
Participants were cross-classified into 15 groups according
to the levels of physical activity (<1, 1–5.9, 6–14.9, 15–29.9,
and ≥30 MET-hours/wk) and BMI (<25, 25–29.9, and ≥30 kg/
m2). The interaction was assessed using the likelihood ratio
test between the models with and without the cross-classified
physical activity–BMI variables. Potential effect modification
between physical activity and other cardiovascular risk factors (smoking, age, alcohol, and diet) was similarly assessed.
women developed documented incident CHD of which
254 cases occurred in women <50 years of age. We
examined total leisure-time physical activity in relation to
other potential risk factors for CHD at baseline (Table 1).
Women who reported more physical activity were younger, had lower BMI, were less likely to smoke, watched
less television, and had a higher Alternative Healthy Eating Index-2010 - diet score.
In multivariable-adjusted models, women reporting
the highest amount of leisure-time physical activity (≥30
MET-hours/wk) were at significantly lower risk of CHD in
comparison with women who were the least active (<1
MET-hour/wk; hazard ratio [HR], 0.75; 95% confidence
interval [CI], 0.57–0.99, P for trend=0.01) (Table 2).
When examined separately, moderate- and vigorousintensity physical activity were both inversely associated
with CHD risk. In comparison with women reporting 0
MET-hours/wk of moderate-intensity physical activity,
women reporting ≥15 MET-hours/wk of moderate activity had a 33% lower risk of CHD (HR, 0.67; 95% CI,
0.51–0.87; P for trend=0.01). Similarly, women reporting ≥15 MET-hours/wk of vigorous activity had a 23%
lower risk of CHD (HR, 0.77; 95% CI, 0.57– 1.03) in
Chomistek et al
Table 2. Hazard Ratios (95% CI) of Coronary Heart Disease According to Quintiles of Leisure-Time Physical
Activity, 1991 to 2011, Nurses’ Health Study II
Total physical
activity
Cases
Quintiles of Physical Activity, MET-h/wk
1 (<1)
2 (1–5.9)
3 (6–14.9)
4 (15–29.9)
5 (≥30)
P Value for
Linear Trend
182
119
101
67
75
Person-years
419 667
368 957
394 283
363 488
365 102
Age-adjusted
1.00
0.86 (0.68–1.08)
0.66 (0.52–0.84)
0.48 (0.36–0.63)
0.53 (0.41–0.70)
<0.0001
Multivariable*
1.00
0.96 (0.76–1.21)
0.80 (0.63–1.03)
0.63 (0.47–0.83)
0.75 (0.57–0.99)
0.01
1 (0)
2 (0.1–2.9)
3 (3–7.4)
4 (7.5–14.9)
5 (≥ 15)
P Value for Linear
Trend
61
103
60
86
Moderate-intensity physical activity
Cases
234
Person-years
550 036
247 575
438 299
301 637
373 950
Age-adjusted
1.00
0.60 (0.45–0.79)
0.61 (0.48–0.77)
0.47 (0.35–0.62)
0.49 (0.38–0.63)
<0.0001
Multivariable*
1.00
0.65 (0.49–0.87)
0.68 (0.54–0.87)
0.59 (0.44–0.80)
0.67 (0.51–0.87)
0.01
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Vigorous-intensity physical activity
313
73
62
36
60
Person-years
825 520
246 624
259 780
186 773
392 800
Age-adjusted
1.00
0.97 (0.75–1.25)
0.77 (0.59–1.01)
0.63 (0.44–0.88)
0.51 (0.38–0.67)
<0.0001
Multivariable*
1.00
1.16 (0.89–1.51)
0.99 (0.75–1.31)
0.89 (0.63–1.27)
0.77 (0.57–1.03)
0.04
Cases
AHEI-2010 indicates Alternative Healthy Eating Index-2010; CI, confidence interval; and MI, myocardial infarction.
*The models were stratified by age (in months) and time period and included parental history of MI at or before age 60 years, smoking, TV
watching, oral contraceptive use, aspirin, AHEI-2010 score, postmenopausal status, menopausal hormone therapy use, parity, preexisting disease
(diagnosis of hypertension or hypercholesterolemia at baseline). Models for moderate- and vigorous-intensity activity include both types of activity
simultaneously.
comparison with women reporting no vigorous activity
(P for trend=0.04). When the analysis was repeated with
a 2- and 4-year lag, results for total leisure-time activity and moderate activity were attenuated and no longer
statistically significant, whereas results for vigorous activity were similar and remained significant. In secondary analysis, when we used cumulative average physical
activity instead of simple updated activity, similar results
were obtained although the hazard ratios in the highest
2 categories were slightly attenuated (online-only Data
Supplement Table I).
We also examined the association between frequency
of exercise and risk of CHD (Table 3). In comparison
with women reporting exercise less than once per week,
the age-adjusted HR for women reporting exercise 4+
times per week was 0.60 (95% CI, 0.46–0.78; P for
trend=0.0001). However, the correlation between frequency and volume of exercise ranged from 0.41 to
0.44 in the questionnaire cycles where both were asked
(1991, 2005, 2009). In the multivariable model that included volume of physical activity, the association between exercise frequency and CHD risk was attenuated
and no longer significant (HR comparing extreme categories, 0.94; 95% CI, 0.70–1.26, P for trend=0.84),
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July 26, 2016
whereas the association for volume of physical activity
was nearly identical to that above (HR, 0.76; 95% CI,
0.56–1.02 comparing ≥30 with <1 MET-hours/wk).
Table 4 shows the association between individual
activities and CHD risk. In multivariable-adjusted analyses where each activity was modeled separately, but
adjusted for total volume of all other activity, aerobics,
outdoor work, and brisk walking were each significantly
inversely associated with CHD (P for trend=0.04, 0.04,
and 0.001, respectively) (Table 4). Engaging in aerobics ≥1 hour/wk was associated with a 26% CHD risk
reduction (HR, 0.74; 95% CI, 0.55-0.99) and outdoor
work with a 16% CHD risk reduction (HR, 0.84; 95%
CI, 0.68–1.04) in comparison with women not participating in these activities (Table 4). Brisk walking for
≥2.5 hours/wk was associated with a 35% risk reduction (HR, 0.65; 95% CI, 0.48–0.87) in comparison with
women who reported no brisk walking. In addition, increasing speed of usual walking pace was associated
with lower CHD risk. After adjusting for hours per week
of walking, other physical activity, and covariables, the
HRs for easy/casual pace (<2 mph), normal/average
pace (2–2.9 mph), brisk pace (3–3.9 mph), and very
brisk/striding pace (≥4 mph) were: 1.00, 0.81 (95% CI,
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
Physical Activity and CHD in Young Women
Table 3. Hazard ratios (95% CI) of Coronary Heart Disease According to Frequency of Physical Activity,
1991 to 2001, Nurses’ Health Study II
Frequency of Physical Activity
<1 Time/wk
Cases
1 Time/wk
2–3 Times/wk
≥4 Times/wk
P Value for
Linear Trend
101
173
75
590 006
354 486
636 471
324 241
Age-adjusted
1.00
0.87 (0.68–1.10)
0.79 (0.64–0.97)
0.60 (0.46–0.78)
0.0001
Multivariable*
1.00
0.91 (0.71–1.16)
0.94 (0.76–1.16)
0.81 (0.61–1.07)
0.17
Multivariable* + MET-h/wk of
physical activity
1.00
0.95 (0.74–1.22)
1.05 (0.84–1.30)
0.94 (0.70–1.26)
0.84
AHEI-2010 indicates Alternative Healthy Eating Index-2010; CI, confidence interval; MET, metabolic equivalent of task; and MI, myocardial infarction.
*The models were stratified by age (in months) and time period and included parental history of MI at or before age 60 years, smoking, TV watching,
oral contraceptive use, aspirin, AHEI-2010 score, postmenopausal status, menopausal hormone therapy use, parity, preexisting disease (diagnosis of
hypertension or hypercholesterolemia at baseline).
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0.66–0.98), 0.57 (95% CI, 0.44–0.73), and 0.33 (95%
CI, 0.17–0.65). Finally, results for running and tennis
also suggested an inverse association with incidence
of CHD but, most likely because of the small number of
cases in the upper categories, reductions in risk were
not statistically significant.
The joint association of physical activity and BMI on
risk of CHD is shown in the Figure. As the interaction
between physical activity and BMI was not statistically
significant (P for interaction=0.70), the inverse association between physical activity and CHD was not modified by BMI category. In comparison with obese women
reporting <1 MET-hour/wk of physical activity, the HR
of CHD for normal weight women reporting ≥30 METhours/wk was 0.52 (95% CI, 0.35–0.78). Furthermore,
among women in the highest category of exercise, those
with normal BMI had lower CHD risk than women who
were overweight or obese.
We additionally examined the association between
physical activity recalled from earlier in life and CHD
risk in adulthood (online-only Data Supplement Table
II). There was no association between physical activity during ages 12 to 22 years and risk of CHD; the
multivariable-adjusted HR comparing the highest with
the lowest category was 1.12 (95% CI, 0.83–1.52). We
also assessed physical activity measured at baseline
only (1991) in relation to events occurring throughout
the 20 years of follow-up, which differs from the primary
analysis where physical activity levels were updated every 4 to 6 years during follow-up. Similar to early-life
activity, the association between baseline physical activity and risk of CHD was null; the multivariable-adjusted
HR comparing the highest with lowest quintile was 0.98
(95% CI, 0.74–1.29) (online-only Data Supplement Table
III). These results suggest that the favorable association
between physical activity and CHD may be best documented with levels proximal to the date of CHD incidence for young and middle-aged women.
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
Finally, we evaluated whether the inverse association
between physical activity and CHD was modified by other
cardiovascular risk factors (online-only Data Supplement
Table IV). Physical activity was associated with lower CHD
risk for women <50 years of age and for women ≥50
years of age, as well. In addition, there was no evidence
of effect modification by smoking, Alternative Healthy
Eating Index-2010 diet score, or alcohol intake.
DISCUSSION
In this large, prospective study of young US women, individuals in the highest category (≥30 MET-hours/wk) of
leisure-time physical activity were at a 25% lower risk
of incident CHD. In addition, both moderate-intensity
physical activity (eg, brisk walking) and vigorous-intensity
activity were associated with reduced CHD risk. Importantly, physical activity was associated with lower CHD
risk regardless of BMI group.
The mean age at baseline of participants in this study
was 36.6 years, providing a unique opportunity to examine physical activity and CHD in younger women. According to a recent review, the median or mean ages of
subjects in studies included in the 2008 Physical Activity
Guidelines primarily ranged from 45 to 60 years.18 Thus,
this article is a valuable contribution to the existing literature on modifiable lifestyle factors that could prevent
CHD in younger women. Primordial prevention of CHD in
this group is critical because recent data suggest that
the CHD mortality rate in women aged 25 to 54 years
may not be declining as it is in other groups, possibly
because of the increases in the prevalence of obesity
and type 2 diabetes mellitus.5–7
We found no association between recalled physical
activity during adolescence or early adulthood and risk
of CHD in adulthood. This finding is similar to that of
Conroy et al19 who found that, although physical activity during high school and ages 18 to 22 was associJuly 26, 2016
295
ORIGINAL RESEARCH
ARTICLE
195
Person-years
Chomistek et al
Table 4. Hazard Ratios (95% CI) for Coronary Heart Disease Associated With Average Weekly
Hours of Individual Activities Adjusted for All Other Activity, 1991 to 2011, Nurses’ Health Study II
Hours/Week Spent in Individual Activities
0
0.1–0.9
≥ 1.0
Cases
508
22
14
Age-adjusted
1.00
0.74 (0.48–1.13)
0.76 (0.45–1.31)
0.24
Multivariable*
1.00
0.88 (0.57–1.36)
0.97 (0.56–1.67)
0.84
Cases
534
7
3
Age-adjusted
1.00
0.61 (0.29–1.29)
0.27 (0.09–0.85)
0.02
Multivariable*
1.00
0.71 (0.34–1.51)
0.40 (0.13–1.26)
0.11
Cases
415
84
45
Age-adjusted
1.00
1.04 (0.82–1.32)
0.90 (0.65–1.23)
0.51
Multivariable*
1.00
1.16 (0.92–1.48)
1.01 (0.74–1.39)
0.88
Cases
492
35
17
Age-adjusted
1.00
1.11 (0.79–1.57)
1.10 (0.67–1.78)
0.64
Multivariable*
1.00
1.13 (0.80–1.60)
1.08 (0.66–1.77)
0.67
Cases
534
5
5
Age-adjusted
1.00
0.57 (0.24–1.38)
0.46 (0.19–1.11)
0.06
Multivariable*
1.00
0.67 (0.28–1.61)
0.57 (0.24–1.39)
0.18
Cases
432
57
55
Age-adjusted
1.00
0.96 (0.72–1.26)
0.64 (0.48–0.85)
0.002
Multivariable*
1.00
1.04 (0.78–1.37)
0.74 (0.55–0.99)
0.04
Cases
327
87
130
Age-adjusted
1.00
0.70 (0.55–0.89)
0.89 (0.72–1.09)
Multivariable*
1.00
0.72 (0.57–0.91)
0.84 (0.68–1.04)
P for Trend
Vigorous activities
Jogging
Running
Bicycling
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
Swimming
Tennis
Aerobics
Moderate activities
Outdoor work
0.08
0.04
P for Trend
Hours/Week Spent in Individual Activities
0
0.1–0.9
1–2.4
≥2.5
427
29
35
53
Brisk walking
Cases
Age-adjusted
1.00
0.54 (0.37–0.79)
0.61 (0.43–0.86)
0.51 (0.38–0.68)
<0.0001
Multivariable*
1.00
0.65 (0.44–0.95)
0.77 (0.54–1.09)
0.65 (0.48–0.87)
0.001
AHEI-2010 indicates Alternative Healthy Eating Index-2010; CI, confidence interval; and MI, myocardial infarction.
*The models were stratified by age (in months) and time period and included total volume of other physical activity, parental history
of MI at or before age 60 years, smoking, TV watching, oral contraceptive use, aspirin, AHEI-2010 score, postmenopausal status,
menopausal hormone therapy use, parity and preexisting disease (includes a diagnosis of hypertension or hypercholesterolemia at
baseline).
296
July 26, 2016
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
Physical Activity and CHD in Young Women
0.90
1
0.8
0.6
0.92
0.85
0.78
0.78
0.76
0.66*
0.59*
0.49*
0.56*
0.4
0.44*
0.38*
0.52*
0.2
<1
1 - 5.9
6 - 14.9
15 - 29.9
≥ 30
Physical Activity (MET-hrs/wk)
Figure. Multivariable-adjusted hazard ratios (HRs) for
coronary heart disease (CHD) for the joint association
between physical activity and body mass index (BMI).
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
The models were stratified by age and period and included
parental history of myocardial infarction at or before age 60
years, smoking, TV watching, oral contraceptive use, aspirin
use, AHEI-2010 score, postmenopausal status, menopausal
hormone therapy use, parity, and preexisting disease (includes a diagnosis of hypertension or hypercholesterolemia
at baseline). *Indicates values significant at P=0.05. P for
interaction=0.70. AHEI-2010 indicates Alternative Healthy Eating Index-2010; and MET, metabolic equivalent of task.
ated with meeting physical activity recommendations in
middle adulthood, it was not associated with the risk of
CHD during middle age and older. Furthermore, when
we performed the analysis lagged 2 and 4 years, the
association between total physical activity and CHD risk
was attenuated. Taken together, these findings suggest
that associations between physical activity and CHD prevention may be driven by most recent levels. This is consistent with evidence suggesting that exercise has acute
effects on cardiovascular disease risk factors such as
blood lipids, blood pressure, and glucose control.20
Specifically, physical activity is correlated with lower triglycerides, lower apolipoprotein B, higher high-density
lipoprotein, change in low-density lipoprotein particle
size, and lower coronary artery calcium.21 Therefore, an
important message to communicate to the public is that,
regardless of how inactive you may be, it is possible to
experience cardiovascular benefits soon after becoming physically active. Nonetheless, physical activity early
in life should be encouraged because it has important
health benefits for children and adolescents, including
improved cardiovascular and metabolic health.3,22,23 Furthermore, in this same cohort of women, there was a
suggestive inverse association between physical activity
during ages 14 to 22 years and risk of premenopausal
breast cancer.24 Previous studies have also indicated
that past physical activity is associated with physical activity later in life.19,25 Thus, engaging in regular exercise
is important for young and old as physical activity has
important health benefits throughout life.
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
In the current study, there was no association between weekly frequency of physical activity and CHD
risk once adjusted for volume of physical activity. This
is in contrast to a recent finding from the Million Women
Study, which showed that, in comparison with women
reporting strenuous activity 2 to 3 times per week, those
reporting strenuous physical activity daily were at higher
risk of CHD.26 This inconsistency could be explained, in
part, by differences in analysis methods. In the Million
Women Study, the analysis for frequency of physical activity did not adjust for total volume of activity because
the duration of activity was not assessed until 3 years
after baseline. With the exception of activity frequency,
however, findings from the current study are similar to
those of the Million Women Study among women 50 to
64 years of age, in particular, with regard to the benefits
of moderate physical activity for CHD.
Our results suggest that both moderate- and vigorous-intensity physical activity are associated with CHD
risk reduction, similar to other studies.27–30 Nonetheless, these previous studies in older men and women
indicate a greater magnitude of association for vigorous activity compared with moderate,27–30 whereas we
saw a modestly stronger association for moderate over
vigorous activity. The result in the present study may
be a consequence of the physical activity questionnaire
used. We were unable to include an assessment of the
intensity at which a participant performed many of the
activities. So, although we categorized activities like bicycling and swimming as vigorous, some participants
may actually perform these activities at a much lower
intensity. Thus, the inability to distinguish between the
same activity performed at a truly vigorous intensity versus a lower intensity could have contributed random error and attenuated our assessment. This is further supported by the activity-specific hazard ratios where the
traditional vigorous activities such as running, tennis,
and aerobics were more strongly inversely associated
with CHD than activities like swimming, biking, and jogging that likely have a much broader range of intensity.
Furthermore, walking pace was assessed in the current
study and found to be strongly inversely associated with
risk of CHD.
Importantly, our study suggests that leisure-time physical activity is associated with a reduction in CHD risk in
younger women who are normal weight, overweight, or
obese. Although this finding has been reported in previous studies among middle-aged and older men and
women, it is worth emphasizing, given the high prevalence of overweight and obesity in young and middleaged US women (58.5% for women 20–39 years of age,
71.7% for women 40–59 years of age).31–33 An elevated
BMI is still a significant risk factor for development of
CHD, but the increased risk associated with being overweight or obese is attenuated, although not completely,
by engaging in physical activity.
July 26, 2016
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≥ 30
25 - 29.9
< 25
0
BMI (kg/m2)
1.2
HR for CHD
1.12
1 (ref)
Chomistek et al
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Strengths of this study include its prospective design,
the detailed information on physical activity collected
multiple times during follow-up, the large number of confirmed CHD cases despite the relatively young age of
study participants, and minimal loss to follow-up.
Our study also has several limitations that should be
considered. Our study population, consisting of predominantly white nurses, is not representative of the general
population. Thus, we cannot necessarily generalize our results to men or other populations with different educational levels, incomes, or distributions of race and ethnicity.
Physical activity was self-reported, but this questionnaire
has been previously validated in this population.15 Moreover, measurement error is unlikely to bias our results because physical activity was assessed prospectively so any
reporting errors would be nondifferential with respect to
subsequent disease status. Nonetheless, the lack of association between physical activity during adolescence and
CHD during adulthood may be a consequence of measurement error as participants had to recall physical activity
levels from 20 to 35 years earlier. As in any observational
study, the possibility of residual confounding by other lifestyle characteristics must be considered; however, we
were able to adjust for many known CHD risk factors.
In conclusion, this study indicates that physical activity is associated with a lower risk of CHD in young
women. Furthermore, exercise did not have to be strenuous to have such associations; moderate-intensity physical activity, including brisk walking, was associated with
lower risk of CHD. There was no association between
physical activity earlier in life and CHD risk in adulthood,
suggesting that previously inactive women who become
physically active can still decrease their risk of CHD. Finally, the favorable associations between physical activity and lower CHD risk were evident regardless of BMI,
emphasizing that it is important for normal weight, overweight, and obese women to be physically active.
SOURCES OF FUNDING
This study was supported by National Institute of Health grants
UM1 CA176726 and R01 CA050385. Dr Chomistek was supported by an institutional training grant (DK007703) from the
National Institute of Diabetes and Digestive and Kidney Diseases.
DISCLOSURES
None.
AFFILIATIONS
From the Department of Epidemiology and Biostatistics, School
of Public Health, Indiana University, Bloomington (A.K.C., B.H.);
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (A.H.E., E.B.R.); Channing Division of
298
July 26, 2016
Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (A.H.E.,
E.B.R.); Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (K.J.M.); and Department of Nutrition,
Harvard T.H. Chan School of Public Health, Boston, MA (E.B.R.).
FOOTNOTES
Received January 14, 2016; accepted June 16, 2016.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/lookup/suppl/doi:10.1161/
CIRCULATIONAHA.116.021516/-/DC1.
Continuing medical education (CME) credit is available for
this article. Go to http://cme.ahajournals.org to take the quiz.
Circulation is available at http://circ.ahajournals.org.
REFERENCES
1. Sattelmair J, Pertman J, Ding EL, Kohl HW III, Haskell W, Lee IM.
Dose response between physical activity and risk of coronary
heart disease: a meta-analysis. Circulation. 2011;124:789–795.
doi: 10.1161/CIRCULATIONAHA.110.010710.
2. Li J, Siegrist J. Physical activity and risk of cardiovascular disease–
a meta-analysis of prospective cohort studies. Int J Environ Res
Public Health. 2012;9:391–407. doi: 10.3390/ijerph9020391.
3. Physical Activity Guidelines Advisory Committee. Physical Activity
Guidelines Committee Report, 2008. Washington, DC: US Department of Health and Human Services; 2008:683.
4.Manson JE, Greenland P, LaCroix AZ, Stefanick ML, Mouton CP,
Oberman A, Perri MG, Sheps DS, Pettinger MB, Siscovick DS.
Walking compared with vigorous exercise for the prevention of
cardiovascular events in women. N Engl J Med. 2002;347:716–
725. doi: 10.1056/NEJMoa021067.
5.Wilmot KA, O’Flaherty M, Capewell S, Ford ES, Vaccarino V.
Coronary heart disease mortality declines in the United States
from 1979 through 2011: evidence for stagnation in young
adults, especially women. Circulation. 2015;132:997–1002. doi:
10.1161/CIRCULATIONAHA.115.015293.
6.Ford ES, Capewell S. Coronary heart disease mortality among
young adults in the U.S. from 1980 through 2002: concealed leveling of mortality rates. J Am Coll Cardiol. 2007;50:2128–2132.
doi: 10.1016/j.jacc.2007.05.056.
7.Yang Q, Cogswell ME, Flanders WD, Hong Y, Zhang Z, Loustalot F, Gillespie C, Merritt R, Hu FB. Trends in cardiovascular
health metrics and associations with all-cause and CVD mortality
among US adults. JAMA. 2012;307:1273–1283. doi: 10.1001/
jama.2012.339.
8.Matthews KA, Crawford SL, Chae CU, Everson-Rose SA, Sowers MF, Sternfeld B, Sutton-Tyrrell K. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol.
2009;54:2366–2373. doi: 10.1016/j.jacc.2009.10.009.
9. Mehta LS, Beckie TM, DeVon HA, Grines CL, Krumholz HM, Johnson MN, Lindley KJ, Vaccarino V, Wang TY, Watson KE, Wenger
NK; American Heart Association Cardiovascular Disease in
Women and Special Populations Committee of the Council on
Clinical Cardiology, Council on Epidemiology and Prevention,
Council on Cardiovascular and Stroke Nursing, and Council on
Quality of Care and Outcomes Research. Acute myocardial infarction in women: a scientific statement from the American Heart
Association. Circulation. 2016;133:916–947. doi: 10.1161/
CIR.0000000000000351.
10. Chomistek AK, Chiuve SE, Eliassen AH, Mukamal KJ, Willett WC,
Rimm EB. Healthy lifestyle in the primordial prevention of car-
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
Physical Activity and CHD in Young Women
Circulation. 2016;134:290–299. DOI: 10.1161/CIRCULATIONAHA.116.021516
23.Owen CG, Nightingale CM, Rudnicka AR, Sattar N, Cook DG,
Ekelund U, Whincup PH. Physical activity, obesity and cardiometabolic risk factors in 9- to 10-year-old UK children of white
European, South Asian and black African-Caribbean origin: the
Child Heart And health Study in England (CHASE). Diabetologia.
2010;53:1620–1630. doi: 10.1007/s00125-010-1781-1.
24. Boeke CE, Eliassen AH, Oh H, Spiegelman D, Willett WC, Tamimi
RM. Adolescent physical activity in relation to breast cancer risk.
Breast Cancer Res Treat. 2014;145:715–724. doi: 10.1007/
s10549-014-2919-5.
25.Lee IM, Paffenbarger RS Jr, Hsieh CC. Time trends in physical
activity among college alumni, 1962-1988. Am J Epidemiol.
1992;135:915–925.
26. Armstrong ME, Green J, Reeves GK, Beral V, Cairns BJ; Million Women
Study Collaborators. Frequent physical activity may not reduce vascular disease risk as much as moderate activity: large prospective
study of women in the United Kingdom. Circulation. 2015;131:721–
729. doi: 10.1161/CIRCULATIONAHA.114.010296.
27.Chomistek AK, Cook NR, Flint AJ, Rimm EB. Vigorous-intensity
leisure-time physical activity and risk of major chronic disease in
men. Med Sci Sports Exerc. 2012;44:1898–1905. doi: 10.1249/
MSS.0b013e31825a68f3.
28. Lee IM, Sesso HD, Oguma Y, Paffenbarger RS Jr. Relative intensity
of physical activity and risk of coronary heart disease. Circulation.
2003;107:1110–1116.
29. Tanasescu M, Leitzmann MF, Rimm EB, Willett WC, Stampfer MJ,
Hu FB. Exercise type and intensity in relation to coronary heart
disease in men. JAMA. 2002;288:1994–2000.
30.Swain DP, Franklin BA. Comparison of cardioprotective benefits of vigorous versus moderate intensity aerobic exercise. Am J Cardiol. 2006;97:141–147. doi: 10.1016/j.amjcard.2005.07.130.
31.Weinstein AR, Sesso HD, Lee IM, Rexrode KM, Cook NR, Manson JE, Buring JE, Gaziano JM. The joint effects of physical
activity and body mass index on coronary heart disease risk in
women. Arch Intern Med. 2008;168:884–890. doi: 10.1001/
archinte.168.8.884.
32.Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of childhood and adult obesity in the United States, 2011-2012. JAMA.
2014;311:806–814. doi: 10.1001/jama.2014.732.
33.Li TY, Rana JS, Manson JE, Willett WC, Stampfer MJ, Colditz GA,
Rexrode KM, Hu FB. Obesity as compared with physical activity in
predicting risk of coronary heart disease in women. Circulation.
2006;113:499–506. doi: 10.1161/CIRCULATIONAHA.105.574087.
July 26, 2016
299
ORIGINAL RESEARCH
ARTICLE
Downloaded from http://circ.ahajournals.org/ by guest on June 16, 2017
diovascular disease among young women. J Am Coll Cardiol.
2015;65:43–51. doi: 10.1016/j.jacc.2014.10.024.
11.Mozaffarian D. Dietary and policy priorities for cardiovascular
disease, diabetes, and obesity: a comprehensive review. Circulation. 2016;133:187–225. doi: 10.1161/CIRCULATIONAHA.
115.018585.
12. Willett WC, Sampson L, Stampfer MJ, Rosner B, Bain C, Witschi
J, Hennekens CH, Speizer FE. Reproducibility and validity of a
semiquantitative food frequency questionnaire. Am J Epidemiol.
1985;122:51–65.
13.Nurses’ Health Study. http://www.nurseshealthstudy.org/sites/
default/files/questionnaires/2009long.pdf.
14. Ainsworth BE, Haskell WL, Leon AS, Jacobs DR Jr, Montoye HJ,
Sallis JF, Paffenbarger RS Jr. Compendium of physical activities:
classification of energy costs of human physical activities. Med
Sci Sports Exerc. 1993;25:71–80.
15.Wolf AM, Hunter DJ, Colditz GA, Manson JE, Stampfer MJ, Corsano KA, Rosner B, Kriska A, Willett WC. Reproducibility and validity of a self-administered physical activity questionnaire. Int J
Epidemiol. 1994;23:991–999.
16 .Rose GA BH, Gillum R, Prineas RJ. Cardiovascular survey methods. WHO monograph series no. 56. 1982:162–165.
17.Hu FB, Stampfer MJ, Rimm E, Ascherio A, Rosner BA, Spiegelman D, Willett WC. Dietary fat and coronary heart disease: a
comparison of approaches for adjusting for total energy intake
and modeling repeated dietary measurements. Am J Epidemiol.
1999;149:531–540.
18.Shiroma EJ, Lee IM. Physical activity and cardiovascular health:
lessons learned from epidemiological studies across age, gender, and race/ethnicity. Circulation. 2010;122:743–752. doi:
10.1161/CIRCULATIONAHA.109.914721.
19. Conroy MB, Cook NR, Manson JE, Buring JE, Lee IM. Past physical activity, current physical activity, and risk of coronary heart
disease. Med Sci Sports Exerc. 2005;37:1251–1256.
20. Thompson PD, Crouse SF, Goodpaster B, Kelley D, Moyna N, Pescatello L. The acute versus the chronic response to exercise. Med
Sci Sports Exerc. 2001;33(6 suppl):S438–S445; discussion S452.
21. Ahmed HM, Blaha MJ, Nasir K, Rivera JJ, Blumenthal RS. Effects
of physical activity on cardiovascular disease. Am J Cardiol.
2012;109:288–295. doi: 10.1016/j.amjcard.2011.08.042.
22.Hay J, Maximova K, Durksen A, Carson V, Rinaldi RL, Torrance
B, Ball GD, Majumdar SR, Plotnikoff RC, Veugelers P, Boulé NG,
Wozny P, McCargar L, Downs S, Lewanczuk R, McGavock J. Physical activity intensity and cardiometabolic risk in youth. Arch Pediatr
Adolesc Med. 2012;166:1022–1029. doi: 10.1001/archpediatrics.2012.1028.
Frequency, Type, and Volume of Leisure-Time Physical Activity and Risk of Coronary
Heart Disease in Young Women
Andrea K. Chomistek, Beate Henschel, A. Heather Eliassen, Kenneth J. Mukamal and Eric B.
Rimm
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Circulation. 2016;134:290-299
doi: 10.1161/CIRCULATIONAHA.116.021516
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Data Supplement (unedited) at:
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SUPPLEMENTAL MATERIAL
Supplemental Table 1. Hazard ratios (95% CI) of coronary heart disease according to categories of cumulative
average physical activity, 1997 – 2011, Nurses’ Health Study II
Total
Physical Activity
Cases
1
(< 1)
99
Categories of Cumulative Average Physical Activity, MET-hrs/wk
2
3
4
5
(1 – 5.9)
(6 – 14.9)
(15 – 29.9)
(≥ 30)
159
130
86
70
Person-years
250,780
434,577
489,027
410,155
326,958
Age-adjusted
1.00
0.84
(0.65, 1.08)
0.61
(0.47, 0.80)
0.50
(0.37, 0.67)
0.55
(0.40, 0.75)
Multivariable*
1.00
p-value for
linear trend
<.0001
0.91
0.75
0.67
0.80
0.16
(0.71, 1.18)
(0.57, 0.98)
(0.50, 0.91)
(0.58, 1.11)
*The models were stratified by age (in months) and time period and included parental history of MI at or before age 60 years,
smoking, T.V. watching, oral contraceptive use, aspirin, AHEI-2010 score, postmenopausal status, menopausal hormone therapy use,
parity, pre-existing disease (diagnosis of hypertension or hypercholesterolemia at baseline).
Supplemental Table 2. Hazard ratios (95% CI) of coronary heart disease according to quartiles of early life
physical activity, 1997 – 2011, Nurses’ Health Study II
1
(< 24.6)
Ages 12 – 22 years
Cases / Person-years
Quartiles of Physical Activity, MET-hrs/wk
2
3
4
(24.7 – 41.4)
(41.5 – 65.1)
(> 65.1)
p-value for
linear trend
86 / 263,565
82 / 261,719
95 / 266,141
87 / 260,872
Age-adjusted
1.00
1.02
(0.75, 1.38)
1.21
(0.90, 1.62)
1.17
(0.86, 1.57)
0.23
Multivariable*
1.00
1.00
(0.73, 1.35)
1.17
(0.87, 1.57)
1.06
(0.78, 1.43)
0.58
MV* + adult PA
1.00
1.21
(0.90, 1.63)
3
(32.1 – 50.8)
1.12
(0.83, 1.52)
4
(> 50.8)
0.37
1
(< 17.5)
1.02
(0.75, 1.39)
2
(17.6 – 32)
103 / 263,019
85 / 263,144
68 / 263,586
94 / 262,548
Age-adjusted
1.00
0.89
(0.66, 1.18)
0.71
(0.52, 0.97)
0.97
(0.73, 1.29)
0.82
Multivariable*
1.00
0.96
(0.72, 1.28)
0.82
(0.60, 1.11)
1.10
(0.83, 1.46)
0.55
MV* + adult PA
1.00
Ages 23-34 years
Cases / Person-years
p-value for
linear trend
1.01
0.90
1.23
0.18
(0.76, 1.36)
(0.65, 1.23)
(0.92, 1.65)
*The models were stratified by age (in months) and time period and included parental history of MI at or before age 60 years,
smoking, T.V. watching, oral contraceptive use, aspirin, AHEI-2010 score, postmenopausal status, menopausal hormone therapy use,
parity, pre-existing disease (diagnosis of hypertension or hypercholesterolemia at baseline).
Supplemental Table 3. Hazard ratios (95% CI) of coronary heart disease according to quintiles of adult physical
activity at baseline, 1991 – 2011, Nurses’ Health Study II
Quintiles of Physical Activity, MET-hrs/wk
2
3
4
(1 – 5.9)
(6 – 14.9)
(15 – 29.9)
Baseline Physical Activity
1
(< 1)
5
(≥ 30)
Cases
151
118
115
74
86
Person-years
374,822
415,010
412,445
368,308
340,912
Age-adjusted
1.00
0.75
(0.59, 0.96)
0.76
(0.59, 0.97)
0.56
(0.42, 0.74)
0.72
(0.55, 0.94)
Multivariable*
1.00
p-value
for linear
trend
0.03
0.81
0.91
0.72
0.98
0.93
(0.63, 1.03)
(0.71, 1.17)
(0.54, 0.95)
(0.74, 1.29)
*The models were stratified by age (in months) and time period and included covariates at baseline only: parental history of MI at or
before age 60 years, smoking, oral contraceptive use, aspirin, AHEI-2010 score, postmenopausal status, menopausal hormone therapy
use, parity, and pre-existing disease (includes a diagnosis hypertension or hypercholesterolemia at baseline).
Supplemental Table 4. Hazard ratios (95% CI) of coronary heart disease according to quintiles of physical activity, stratified by cardiovascular risk
factors, 1991 – 2011, Nurses’ Health Study II
1
(< 1)
Non-smoker
Cases / Person-years
Multivariable*
Quintiles of Physical Activity, MET-hrs/wk
2
3
4
(1 – 5.9)
(6 – 14.9)
(15 – 29.9)
5
(≥ 30)
127 / 374,451
80 / 332,313
77 / 359,410
52 / 334,768
61 / 337,713
1.00
0.87 (0.66, 1.16)
0.80 (0.60, 1.06)
0.61 (0.44, 0.85)
0.78 (0.57, 1.07)
p-value for
linear trend
P for interaction
0.09
0.58
Current smoker
Cases / Person-years
Multivariable*
Age < 50
Cases / Person-years
Multivariable*
Age ≥ 50
Cases / Person-years
Multivariable*
Non-drinkers
Cases / Person-years
Multivariable*
Drinkers
Cases / Person-years
Multivariable*
AHEI < 49
Cases / Person-years
Multivariable*
AHEI ≥ 49
Cases / Person-years
55 / 45, 214
39 / 36,644
24 / 34,874
15 / 28,721
14 / 27,389
1.00
1.28 (0.83, 1.97)
0.83 (0.50, 1.38)
0.58 (0.32, 1.05)
0.60 (0.32, 1.12)
80 / 289,467
64 / 276,621
46 / 286,590
32 / 261,886
32 / 257,087
1.00
1.02 (0.73, 1.42)
0.77 (0.53, 1.11)
0.63 (0.42, 0.96)
0.70 (0.46, 1.07)
0.02
0.04
0.94
102/ 130, 200
55 / 92,335
55 / 107,693
35 / 101,602
43 / 108,015
1.00
0.90 (0.65, 1.26)
0.83 (0.60, 1.16)
0.62 (0.42, 0.91)
0.80 (0.55, 1.15)
93 / 193,741
55/ 153,732
48 / 145,660
28 / 120,912
27 / 108,210
1.00
1.00 (0.71, 1.41)
0.91 (0.64, 1.30)
0.69 (0.45, 1.06)
0.75 (0.48, 1.17)
89 / 225,926
64 / 215,225
53 / 248,623
39 / 242,576
48 / 256,892
1.00
0.97 (0.70, 1.34)
0.75 (0.53, 1.06)
0.62 (0.42, 0.91)
0.78 (0.54, 1.13)
119 / 253,259
73 / 207,693
60 / 193,130
35 / 151,760
29 / 118,223
1.00
1.01 (0.75, 1.36)
0.88 (0.64, 1.21)
0.68 (0.46, 0.99)
0.74 (0.49, 1.12)
51 / 149, 983
39 / 148,173
38 / 188,469
29 / 200,559
40 / 235,144
0.15
0.10
0.94
0.14
0.05
0.98
Multivariable*
1.00
0.95 (0.62, 1.45)
0.75 (0.49, 1.15)
0.59 (0.37, 0.94)
0.70 (0.46, 1.06)
0.08
*The models were stratified by age (in months) and time period and included parental history of MI at or before age 60 years, smoking, T.V. watching, oral contraceptive use,
aspirin, AHEI-2010 score, postmenopausal status, menopausal hormone therapy use, parity, pre-existing disease (diagnosis of hypertension or hypercholesterolemia at baseline).
Carolyn:
Welcome to Circulation on the Run, your weekly podcast summary and backstage pass
to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor from the National
Heart Centre and Duke National University of Singapore. I am so excited to be joined in
just a moment by Dr. Andrea [inaudible 00:00:21] and Dr. Wendy Post to discuss the
feature paper this week about leisure-time physical activity and the risk of coronary
heart disease in young women. First, here's the summary of this week's issue.
The first paper, by Dr. Bohula and colleagues at the TIMI Study Group at Brigham and
Women's Hospital in Boston, Massachusetts, aim to test the hypothesis that an
atherothrombotic risk stratification tool may be useful to identify high-risk patients who
have the greatest potential for benefit from more intensive secondary preventive
therapy such as treatment with Vorapaxar following a myocardial infarction. As a
reminder, Vorapaxar is a first-in-class anti-platelet agent that inhibits thrombinmediated activation of platelets via the protease activator receptor 1. The authors
studied almost 8,600 stable patients with a prior myocardial infarction followed for a
median of two and a half years.
In the thrombin receptor antagonist and secondary prevention of athrothrombotic
ischemic events, TIMI 50 trial. They identified nine independent risk predictors which
were age, diabetes, hypertension, smoking, peripheral artery disease, prior stroke, prior
coronary bypass grafting, heart failure and renal dysfunction. A simple integer-based
scheme using these predictors showed a strong graded relationship with the rates of
cardiovascular death, myocardial infarction or ischemic stroke. Moreover, the net
clinical outcome was increasingly favorable with Vorapaxar across the risk groups.
In summary, this paper provides a practical strategy that could be used by clinicians to
assist with risk stratification and therapeutic decision-making regarding Veropaxar use
for secondary prevention after myocardial infarction.
The next paper is by first author Dr. [inaudible 00:02:40] and corresponding authors, Dr.
[Gerstein 00:02:43] from the Beth Israel Deaconess Medical Center and Dr. [Carr
00:02:47] from the Broad Institute of Harvard and MIT, who look at aptamer-based
proteomic profiling. Now DNA aptamers are [alu 00:02:57] nucleotides of approximately
50 base pairs in length selected for their ability to bind proteins with high specificity and
affinity. They therefore holds considerable promise for biomarker and pathway
discovery in cardiovascular diseases.
These authors applied a novel technology that uses single-stranded DNA aptamers to
measure over 1,100 proteins in a single blood sample. They applied this to a model of
planned myocardial injury and that is patients undergoing septal ablation for
hypertrophic cardiomyopathy, and they found that 217 proteins were significantly
changed in the peripheral vein blood after planned myocardial injury in this derivation
cohort. They validated 79 of these proteins in an independent cohort. Furthermore,
among 40 validated proteins that increase within one hour after myocardial injury, 23
were also elevated in patients with spontaneous myocardial infarction.
Finally, the authors applied this to archive samples from the Framingham heart study
and showed 156 significant protein associations with the Framingham risk score. This
study is so exciting because it highlights any merging proteomics tool that captures a
large number of low abundance analytes with high sensitivity and precision, thus
providing important proof of principle for future clinical applications and this is
discussed in an excellent editorial that accompanies this paper by doctors Graham
[Malini 00:04:37], [Lau Enleui 00:04:39] from the University of Ottawa Heart Institute.
The next paper is by Dr. [Anter 00:04:51] and colleagues from the Beth Israel Deaconess
Medical Center in Boston, Massachusetts, who looked at post infarction, reentrant
ventricular tachycardia and addressed the problem that in vivo descriptions of
ventricular tachycardia circuits are currently limited by insufficient spatiotemporal
resolution. The authors therefore utilize a novel, high resolution mapping technology to
characterize the electrophysiological properties of these reentrant circuits in 15 swine.
The main finding was that the zones of slow conduction within the reentrant circuits
with the inward and outward curvatures while conduction velocity in the comment
channel isthmus itself was nearly normal. The authors further demonstrated that
entrainment mapping over estimated the true size of the isthmus. Thus, the conclusion
was that high resolution activation mapping of ventricular tachycardia may better guide
ablation therapy and ablation at zones of high curvature may be an attractive target for
ablation.
The final papers from first author, Dr. [Tang 00:06:08] and corresponding author Dr.
[Fitzgerald 00:06:10] from the University of Pennsylvania Perlman School of Medicine in
Philadelphia. These authors studied the cardiovascular consequences of prostanoid Ireceptor deletion in microsomal prostaglandin E synthase-1 deficient hyperlipidemic
mice. The clinical background to this research question is that inhibitors of
cyclooxygenase-2 or Cox-2 are well-known to relieve pain, fever and inflammation by
suppressing biosynthesis of prostacyclin and prostaglandin E2.
However, suppression of these prostaglandins particularly prostacyclin by Cox-2
inhibitors or deletion of the I-prostanoid receptor for prostacyclin is known to accelerate
atherogenesis and enhance thrombogenesis in mice. In contrast, deletion of the
microsomal prostaglandin E synthase1 has been shown to suppress PGE2 but increase
biosynthesis of prostacyclin. It therefore confers analgesia while attenuating
atherogenesis and does not predispose mice to thrombogenesis. Therefore, possibly
contributing to cardiovascular efficacy.
In this particular study, therefore, the authors sought to determine the relative
contribution of suppressing PGE2 versus augmenting prostacyclin to the impact of
depletion of microsomal prostaglandin E synthase-1 in hyperlipidemic mice. The main
findings were that augmentation of prostacyclin is the dominant contributor to the
favorable thrombogenic profile of microsomal prostaglandin E synthase-1 depletion in
these atherosclerotic mice while suppression of PGE2 accounted for the protective
effects in atherosclerosis and the exciting clinical take-home message is that inhibitors
of the microsomal prostaglandin E synthase-1 may be less likely to cause cardiovascular
adverse effects than NSAIDS or specific inhibition of Cox-2. Those were the highlights of
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this week. Now for our feature paper.
Our feature paper today is entitled "The frequency, [type 00:08:41] and volume of
leisure time physical activity and risk of coronary heart disease in young women" and I
am so excited to be joined by two lovely ladies today to discuss this paper. First, the first
and corresponding author Dr. Andrea [Comastick 00:08:58] from the School of Public
Health of Indiana University Bloomington and Dr. Wendy Post, associate editor from the
Johns Hopkins University. Welcome Andrea and Wendy.
Andrea:
Hi. Thanks.
Wendy:
Thank you so much for having us.
Carolyn:
I am just so excited that we are talking about a paper about women being discussed by
women. What more could you ask for? I have to say this is a first for Circulation on the
Run, which is why I’m just so excited, so let’s get straight into it.
Andrea, maybe I could just ask you to start by sharing the story of how you and your
team came up with some new questions and new data because I’m sure a lot of
listeners are thinking there’s a lot of data on exercise and how good it is for
cardiovascular health in women already.
Andrea:
Yeah, that's a great question. When we started talking about conceptualizing this paper,
the first thing was to focus on younger women. Most of the previous work on physical
activity and heart disease has been in older adults and that's primarily because it's older
adults that have heart attacks. It’s hard to get a large enough study of young women
that has enough coronary heart disease events to be able to study this. We were
fortunate where we had a large cohort in the nurses health study too of women and
because it’s been followed for over 20 years, we had enough events to be able to
examine this association.
We did want to think about, "Okay, what can we add?" because there’s a lot of
information about just overall physical activity and health, so what can we do
differently? I’m pretty familiar with the physical activity guidelines and really tried to
look at what in the guidelines currently and then what could we add? What could be of
interest when they start revising the guidelines which is actually going to happen very
soon.
That was when we started focusing on, "Okay, instead of looking at just overall activity,
look at intensity, comparing moderate and vigorous." We also wanted to look at
frequency of physical activity and looking at frequency but also adjusted for a total time
or total amount of physical activity that somebody does. Then we are also, the third
thing was that we thought was important was looking at adolescent physical activity.
We know that kids, unfortunately as they get older and get into their teenage years,
their activity declines quite a bit. Looking at how this physical activity during
adolescence earlier life impact coronary heart disease risk in adulthood. Those were the
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three main things that we were focusing on when we first conceptualized the paper.
Carolyn:
Nice. Tell us, what did you find?
Andrea:
We did find that exercise is just as beneficial in younger woman as it is in older adults,
which is great. We also found that moderate intensity exercise is just as beneficial as
vigorous intensity exercise, which I think is a really important message to get out there. I
think a lot of people, especially those that are really inactive to begin with are
completely intimidated about the fact of trying to think about going to a gym or trying
to jog or run a marathon or something like that.
I think really emphasizing that moderate intensity activity is beneficial and we found
that walking was actually the most beneficial activity that we looked at in our study, that
brisk walking was really really good for everybody and really lowered risk of coronary
heart disease.
Carolyn:
Hooray.
Andrea:
Yeah, and the other thing we found which might be of interest for those that are also
extremely busy, especially this target population where a lot of people are moms and
working was that frequency didn't seem to matter, that as long as people were
exercising for a couple hours a week that they should be that they could accumulate it in
a couple times a week or they could do it more frequently, four or five times a week. It
didn't seem to matter.
Carolyn:
That’s cool. You know what? I think a lot of these things we'll also discuss at the Editorial
Board when we're looking at this paper. Wendy, we promised that we would give a
backstage pass to the Editorial Board and The Journal, so could you share a little bit
about what we talked about there?
Wendy:
Well, the Editorial Board was really excited about this paper. We loved the emphasis on
young women and the important public health message about how we need to get out
there and move and exercise to reduce our risk for cardiovascular disease. As was
mentioned, there have been previous studies that also show the benefit of exercise but
the Editorial Board especially liked the large sample size, the long duration of follow-up,
the number of events that had been accrued that allowed for sophisticated analyses,
adjustment for confounders and the very rigorous study design and excellent statistical
methods that have been used in this study and so many other studies from the nurses
health study, but I think we particularly just loved the message. The message was great.
We need to get out there and move. We need to tell our patients, especially young
women, that now we have data that if you start exercising now, it will help in the future
but also the study showed that if you hadn't exercised much in early life that’s starting
to exercise more proximal to the event was also important as well.
Carolyn:
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Thank you Wendy. I also remember that we talked about the lack of interaction with
body mass index, and I thought that was a great message. Andrea, could you maybe
Page 4 of 6
share a little bit about that?
Andrea:
Yeah, this is something that previous investigators have looked at the interaction
between body mass index and exercise. Unfortunately, we’ve all found the same thing
so it doesn’t seem to matter whether women are normal weight or overweight or obese
that they still get benefit when they exercise, and I think that’s really encouraging. I
know a lot of people might start to exercise because they really want to drop some
weight but just trying to emphasize even if the numbers on the scale aren't changing,
that exercise still has all these really great benefits for heart disease and also for many
other diseases.
Carolyn:
Exactly. Can I just ask both of you and maybe I’ll start with Andrea, what will you do
different now both as a woman and as a clinician seeing women now that you know
what you do from your data?
Andrea:
Well, I’m not a clinician. I’m an epidemiologist so unfortunately I don’t get to see
patients and counsel them although I do try to talk to community members as a public
health person and really get in the community on board with what we’re talking about. I
just try to tell people, I actually talked to a group of people last week, and just trying to
say, "Anything is better than nothing and just trying to even start with some short
walks." Again, just emphasizing you don’t have to go to a gym or you don’t have to be
doing anything that's super strenuous but just do stuff that feels good and just try to get
your heart rate up a little bit like going out for a brisk walk. I think that's my main
message that I try to tell everybody is at least start with something and get moving a
little bit.
Carolyn:
I love that. Wendy?
Wendy:
I like to emphasize the data about brisk walking. I thought that was great because many
of our patients don’t want to join a gym, don’t have the time to join a gym so just
getting out and walking is fabulous exercise and now we have the data here that in
young women that after 20 years of follow-up, brisk walking was associated with I think
it was a 35% reduction in risk for cardiovascular disease during follow-up.
In addition, I liked the message about the total amount of time that you spend
exercising in a week is what’s important. It doesn’t matter whether you divide that into
seven days a week to get to that same amount of time or whether you do it in bursts of
three days a week, and I think that’s particularly important for the many women who
have so many different responsibilities and may not have time every day to go out and
exercise. The days that you do have time, just exercise a little bit more those days, so
lots of really important messages for our patients and for ourselves.
Carolyn:
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I really couldn’t agree more and just from my point of view, because I see a lot of
patients in Asia and I do acknowledge just like you did, Andrea, in your paper that your
data are predominantly in white populations. Still one of the messages I like to get out
to the women I see is we have very skinny women and when I see younger women, and
I really like emphasizing that, "Hey, just because you’re not struggling with an obesity
Page 5 of 6
issue or just because you’re young, it doesn’t mean you don’t need to exercise and that
we all should just get moving." Thank you very, very much for that Andrea.
Andrea:
Oh, no. It's my pleasure and thank you for having me come on today and talk about this.
Carolyn:
Thank you too, Wendy. Do you have any other comments?
Wendy:
No, but congratulations on your publication, Andrea.
Andrea:
Oh, thank you so much, Wendy. I was really happy to get the message that guys were
excited about it. Thank you so much.
Carolyn:
You’ve been listening to Circulation on the Run. Thank you for joining us this week and
please tune in next week.
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