2540
Physical Activity and 23-Year Incidence of
Coronary Heart Disease Morbidity and
Mortality Among Middle-aged Men
The Honolulu Heart Program
Beatriz L. Rodriguez, MD, PhD; J. David Curb, MD; Cecil M. Burchfiel, PhD;
Robert D. Abbott, PhD; Helen Petrovitch, MD; Kamal Masaki, MD; Darryl Chiu, MS
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Background The purpose of the study was to examine the
association between physical activity and 23-year incidence of
coronary heart disease morbidity and mortality. This cohort
study continues to follow 8006 Japanese-American men who
were 45 to 68 years of age and living on Oahu, Hawaii, in 1965,
for the development of coronary heart disease morbidity and
mortality.
Methods and Results The Framingham physical activity
index was calculated by summing the product of average hours
spent at each activity level and a weighting factor based on
oxygen consumption. Study subjects were divided into tertiles
of physical activity index at baseline. Relative risks and 95%
confidence intervals (CI) for incidence of coronary heart
disease morbidity and mortality were obtained using the Cox
model. After age adjustment and using the lowest physical
activity index tertile as a reference group, the relative risk for
coronary heart disease incidence for the highest tertile of
physical activity was 0.83 (CI, 0.70 to 0.99). After adjusting for
age, hypertension, smoking, alcohol intake, diabetes, cholesterol, and body mass index, the relative risk was 0.95 and CI
included 1 (CI, 0.80 to 1.14). For coronary heart disease
mortality, the age-adjusted relative risk was 0.74 (CI, 0.56 to
0.97) and 0.85 (CI, 0.65 to 1.13) after risk factor adjustment.
Conclusions The results suggest that the impact of physical activity index on coronary heart disease is mediated
through its effects on hypertension, diabetes, cholesterol,
and body mass index. These findings support the hypothesis
that physical activity is inversely associated with coronary
heart disease morbidity and mortality and suggest that
physical activity interventions in middle-aged men, by improving cardiovascular risk factor levels, may have significant
public health implications in the prevention of coronary
heart disease. (Circulation. 1994;89:2540-2544.)
Key Words * exercise * coronary heart disease *
Japanese-Americans * middle age
T he identification of factors that may prevent the
development of coronary heart disease is
clearly important because this condition continues to be the leading cause of death in Western
industrialized countries.' The inverse relation between
physical activity and coronary heart disease remains
controversial.23 Recently, a meta-analysis of 27 studies
that examined this relation presented convincing evidence that physical activity has a protective effect
against coronary heart disease. However, whether the
association between physical activity and coronary heart
disease is independent of other cardiovascular risk
factors is debatable.4
The Honolulu Heart Program provides the opportunity to investigate the association between physical
activity and incidence of coronary heart disease morbidity and mortality among men aged 45 to 64 years
during a follow-up period of up to 23 years in a cohort
of 8006 men of Japanese ancestry. A previous publication from the Honolulu Heart Program5 reported a
protective effect of physical activity on coronary heart
disease incidence during 12 years of follow-up. This
investigation extends the follow-up period to 23 years
and includes coronary heart disease mortality as an
outcome in addition to morbidity. It also provides
results adjusted for multiple risk factors simultaneously,
as opposed to adjustment for individual risk factors
separately. Few studies have been able to examine these
relations among middle-aged men with such a long
follow-up period.
Received December 22, 1993; revision accepted February 26,
1994.
From the Honolulu Heart Program, Kuakini Medical Center
(B.L.R., J.D.C., H.P., K.M., D.C.), Honolulu, Hawaii; John A.
Burns School of Medicine (B.L.R., J.D.C., H.P., K.M.), the
University of Hawaii at Manoa, Honolulu; the Honolulu Heart
Program, National Heart, Lung, and Blood Institute, National
Institutes of Health (C.M.B.), Honolulu; and the Division of
Biostatistics (R.D.A.), Department of Medicine, University of
Virginia School of Medicine, Charlottesville.
Correspondence and reprint requests to Beatriz L. Rodriguez,
MD, PhD, Honolulu Heart Program, 347 North Kuakini St,
Honolulu, HI 96817.
Methods
Study Population
The Honolulu Heart Program began in Oahu, Hawaii, in
1965 to 1968, following 8006 men of Japanese ancestry, then
aged 45 to 68 years, for the development of coronary heart
disease and stroke. Details of the selection process for this
cohort have been published previously.6 Prevalent cases of
coronary heart disease, stroke, and cancer were excluded from
these analyses. Also, participants aged 65 years or older were
eliminated because retirement may have a significant impact
on physical activity habits. A total of 7074 men were included
in the analyses.
Data Collection
Baseline Examination
During the first examination of this cohort in 1965, data on
cardiovascular risk factors were collected using a standard
Rodriguez et al The Honolulu Heart Program Study
2541
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protocol. Data collected included anthropometric measurements, blood pressure measurements, ECG, serum cholesterol
levels, behavioral characteristics such as smoking, alcohol
consumption, and physical activity, and medical history,
among other variables. An examination by a physician also was
conducted. The information on physical activity obtained at
the baseline examination included the average number of
hours spent per day in various levels of activity including no
activity such as sleeping or lying down, sedentary activity such
as sitting or standing, slight activity such as walking on level
ground, moderate activity such as gardening or light carpentry,
and heavy activity such as shoveling or digging. These data
were collected once as part of the first examination. Similar
questionnaires have been used by the Framingham7 and
Puerto Rico8-'0 heart studies.
TABLE 1. Mean Number of Hours per Day Spent in
Each Level of Physical Activity Among Men Ages 45 to
64 Years at Exam 1
Surveillance Methods
in the lower tertile spent 15 hours per day inactive or
sedentary and 0 hours in moderate or heavy activities.
In contrast, 90% of the men in the upper tertile spent 10
hours of the day inactive or sedentary and 5 hours
conducting moderate or heavy activities. Ninety percent
of the men in the middle tertile spent 11 hours per day
inactive or sedentary and 1 hour in moderate or heavy
activities.
Among men in the most active group, less than 1%
reported mostly sitting at work and 40% reported
mostly sitting at home. In contrast, 54% of the inactive
men reported mostly sitting at work and 72% reported
mostly sitting at home.
Age-adjusted mean levels (or percentages) of selected cardiovascular risk factors are shown by tertile of
physical activity index in Table 2. By design, the physical
activity index increased with increasing tertile of physical activity. Smoking and alcohol consumption did not
vary significantly across physical activity index tertiles.
Body mass index, serum cholesterol, and rates of hypertension and diabetes decreased significantly with increasing levels of physical activity.
During the 23 years of follow-up, 789 incident cases of
coronary heart disease were identified (fatal and nonfatal events). A significantly lower age-adjusted incidence rate was observed among men in the highest
tertile of physical activity index, 5.2 per 1000 personyears compared with 6.3 and 6.2 per 1000 person-years
in the middle and lowest tertiles, respectively. No
protective effect was observed at moderate levels of
physical activity. The test for trend was of borderline
significance (P=.06) (Fig 1).
During the follow-up period, 340 fatal coronary heart
disease events occurred. Age-adjusted mortality rates
for coronary heart disease were also lowest among men
in the highest tertile of physical activity, 1.9 per 1000person years compared with 2.9 and 2.6 per 1000 among
the middle and lowest physical activity index tertiles
(Fig 2). Again, no protective effect was evident for men
reporting moderate levels of activity. The test for trend
was also of borderline significance (P=.05).
Cox regression models were used to study the relation
of physical activity index and other risk factors to the
risk of total coronary heart disease incidence (Table 3).
No significant association was observed between intermediate levels of physical activity at baseline and 23year incidence of coronary heart disease. Participants in
the highest physical activity index tertile at baseline
showed a 17% reduction in 23-year coronary heart
disease incidence (relative risk, 0.83; 95% confidence
interval, 0.70 to 0.99) after adjusting for age. This
A surveillance system was established at the beginning of
the study and continues to identify cases of coronary heart
disease and stroke, based on selected discharge diagnoses at
the major medical facilities on the island of Oahu. The
ascertainment of death is primarily from obituaries in island
newspapers, supplemented with listings of death certificates
filed with the State Department of Health. The medical
records are then requested and reviewed by a panel of
Honolulu Heart Program physicians to identify incident cases
of heart disease and stroke as well as to determine the cause of
death, based on standardized criteria.1"'12 Incident cases of
coronary heart disease include fatal and nonfatal events as
well as sudden deaths within 1 hour among asymptomatic or
apparently healthy subjects. The out-migration rate from
Oahu for our study participants has been less than 1 in 1000
per year.
Data Analysis
To calculate a summary measure of physical activity, a
weighting factor based on the approximate oxygen consumption needed for each level of effort was multiplied by the
number of hours spent at each level of activity. The resulting
products of all levels of activity then were added to obtain a
physical activity index.5
The mean number of hours spent in each level of physical
activity was calculated for the population in the study. Subjects
then were divided into tertiles based on their physical activity
index level. Age-adjusted mean values (or percentages) for
selected risk factors and age-adjusted incidence rates per 1000
person-years for coronary heart disease morbidity and mortality were calculated by tertile of physical activity.13 To examine
the effect of physical activity on coronary heart disease morbidity and mortality and the potential mediating effects of other
risk factors on such a relation, Cox regression models were
used.'4 Estimates of relative risk were obtained using the
subjects in the lowest tertile of physical activity as the reference
group. Analyses were repeated excluding deaths that occurred
within the first 2 years of follow-up. Analyses were also conducted using the number of hours spent in various levels of
activity individually instead of using the composite physical
activity index. To address the possibility that the effect of
physical activity on the risk of coronary heart disease might be
altered as follow-up becomes further removed from when
physical activity was first assessed, the effect of physical activity
was allowed to change with time in the Cox regression model.
Results
Table 1 shows the mean number of hours per day
spent at each level of physical activity among participants in the study. On average, subjects spent 7.3 hours
per day inactive, 7.3 hours performing sedentary activities, 6.1 hours in slight activities, 3.1 hours in moderate
activities, and 0.2 hours conducting heavy activities.
The study population was divided into tertiles based
on the physical activity index. Ninety percent of the men
Level
Mean
SD
Range
No activity
1.1
7.3
3-23
7.3
Sedentary activity
3.1
1-19
2.7
Slight activity
6.1
0-19
Moderate activity
3.1
2.7
0-14
Heavy activity
0.2
0.8
0-9
Prevalent cases of coronary heart disease, cerebrovascular
disease, and cancer were excluded.
2542
Circulation Vol 89, No 6 June 1994
TABLE 2. Age-Adjusted Mean Risk Factor Levels by Tertile of Physical Activity Index Among
Men Aged 45 to 64 Years at Exam 1
Physical Activity Index Tertile
Low
Medium
High
(SD)
Mean
(SD)
Mean
Physical activity index
32
38
(1.1)
(1.2)*
17
17
18
Smoking, pack/yr
(24.6)
(24.2)
14
14
15
Alcohol, oz/mo
(24.4)
(24.5)
24.2
24.0
23.4
Body mass index
(3.1)
(3.2)*
220
218
217
Cholesterol, mg/dL
(38.7)
(37.6)
Hypertension
39%
(0.5)
36%
(0.5)*
33%
15%
Diabetes
13%
(0.4)
11%
(0.3)*
Prevalent cases of coronary heart disease, cerebrovascular disease, and cancer were excluded.
*P<.05, lowest tertile of physical activity index as reference.
Mean
29
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inverse relation between physical activity and risk of
coronary heart disease was also independent of smoking
and alcohol consumption. However, when each of the
variables hypertension, cholesterol, body mass index,
and diabetes were included separately in the model with
age, the 95% confidence intervals for the relative risk
for total coronary heart disease incidence among the
most active men included 1 in the various models. In a
separate regression that included all risk factors, the
relative risk of physical activity for total coronary heart
disease incidence was 0.95 (95% confidence interval,
0.80 to 1.14).
Similar analyses were conducted for coronary heart
disease mortality (Table 4). The findings observed were
consistent but of a larger magnitude compared with
total coronary heart disease incidence. Participants in
the highest tertile of physical activity index showed a
26% reduction in 23-year coronary heart disease mortality (relative risk, 0.74; 95% confidence interval, 0.56
to 0.97) after adjusting for age. In a Cox model that
included all risk factors, the relative risk of coronary
heart disease death for the most physically active tertile
was 0.85 (95% confidence interval, 0.65 to 1.13).
Analyses were repeated excluding deaths that occurred within the first 2 years of follow-up, and results
were unchanged. Analyses also were repeated using the
number of hours spent inactive or sedentary as well as
in moderate and heavy activities separately instead of
CHD incidence rate per 1000 peron years
6.2
_/
using the composite index. No additional insights were
available from these procedures. Although associations
tended to be weaker, the risk of coronary heart disease
increased with more hours spent inactive or sedentary
and decreased with more hours spent in moderate or
heavy activities. In general, the physical activity index
was a better predictor of the risk of coronary heart
disease, presumably because of the ability of the composite physical activity index to incorporate all information that comprises the overall metabolic output in a
24-hour period compared with the individual components of activity that define the physical activity index.
To test for a potential decline in the strength of the
association between physical activity and coronary heart
disease incidence as the number of years of follow-up
increases, the effect of physical activity on the risk of
coronary heart disease was allowed to change with time
from when the physical activity index was first measured
(1965 to 1968). Although the association of physical
activity with coronary heart disease seemed to decline
with increasing number of years into follow-up, the
decline was not statistically significant.
Discussion
The findings of this long-term epidemiologic study
suggest that among men of middle age, leading a
physically active lifestyle was associated with a significant reduction in the risk of coronary heart disease
CHD mortality rate per 1000 peron years
6.3
Middle
High
Physical activity Index tertile
FIG 1. Bar graph: Age-adjusted incidence rates for total coronary heart disease (CHD) by physical activity index tertile.
Low
(SD)
(3.8)*
(22.9)
(25.0)
(3.0)*
(38.0)*
(0.5)*
(0.3)*
Low
Middle
High
Physical activity index tertile
FiG 2. Bar graph: Age-adjusted coronary heart disease (CHD)
mortality rates by physical activity index tertile.
Rodriguez et al The Honolulu Heart Program Study
2543
TABLE 3. Relative Risks and 95% Confidence Intervals for Total Coronary Heart
Disease Incidence by Level of Physical Activity Index Among Men Aged 45 to 64 Years
at Exam 1 During a 23-Year Follow-up Period Adjusting for Selected Variables
Middle Tertile
Highest Tertile
Variables in the
Model
Age
Age, smoking
RR
(95% Cl)
RR
(95% Cl)
0.83
1.01
(0.86-1.19)
(0.70-0.99)*
0.82
(0.69-0.98)*
1.00
(0.85-1.18)
1.02
0.84
(0.86-1.20)
(0.70-0.99)*
Age, alcohol
0.87
(0.73-1.03)
1.04
(0.88-1.22)
Age, hypertension
0.86
(0.72-1.02)
1.03
(0.87-1.22)
Age, cholesterol
1.04
0.89
(0.75-1.06)
(0.88-1.23)
Age, body mass index
0.87
(0.73-1.03)
1.04
(0.88-1.23)
Age, diabetes
All variables above
0.95
(0.80-1.14)
1.07
(0.90-1.26)
Prevalent cases of coronary heart disease, cerebrovascular disease, and cancer were excluded.
Reference group was the lowest physical activity index tertile.
*95% confidence interval (Cl) for the relative risk (RR) excludes 1.
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morbidity and mortality. This effect appears to be
mediated through the effect of physical activity on other
cardiovascular risk factors such as hypertension, body
mass index, serum cholesterol, and diabetes. These
findings are consistent with other studies that have
shown that physical activity may offer protection against
coronary heart disease.4,5,7'9'10,15-32 This study also supports the hypothesis, at least cross-sectionally, that
physical activity is associated with a favorable profile of
cardiovascular disease risk factors27'33 and that this
association is related to the prediction of coronary heart
disease morbidity and mortality.
Although these results, based on 23 years of followup, show slightly weaker associations between physical
activity and coronary heart disease incidence compared
with those reported by Donahue et al,5 the latter using
only the first 12 years of follow-up, the differences are
not statistically significant. The present findings can only
suggest the potential for a decline in the strength of
association between physical activity and coronary heart
disease with increasing number of years of follow-up
after physical activity is assessed and that long-term
follow-up studies may warrant more frequent updating
of physical activity information to better characterize or
strengthen the associations that are reported here.
This study, like other observational investigations on
this matter, has various potential sources of bias.27'29
The measurement of physical activity used in this
investigation is a self-reported measure, which does not
obtain very detailed descriptions of activity, as do some
more recently developed instruments. Breaking down
the physical activity index into its individual components failed to identify a specific component of the
physical activity index that may have been responsible
for the overall association that was found between the
physical activity index and coronary heart disease. Also,
changes in physical activity habits may have occurred
during the follow-up period. Thus, we cannot rule out
the possibility of systematic misclassification among the
three physical activity groups. This type of misclassification could potentially increase or decrease the magnitude of the association observed between physical
activity and coronary heart disease.
In this investigation, a dose-response effect for coronary heart disease morbidity and mortality incidence
rates across tertiles of physical activity index was not
evident. Men in the middle tertile even showed slightly
higher coronary heart disease morbidity and mortality
rates compared with the most inactive group. The
TABLE 4. Relative Risks and 95% Confidence Intervals for Coronary Heart Disease
Mortality by Level of Physical Activity Index Among Men Aged 45 to 64 Years at Exam 1
During a 23-Year Follow-up Period Adjusting for Selected Variables
Middle Tertile
Highest Tertile
Variables in
RR
RR
(95% Cl)
(95% Cl)
the Model
0.74
1.12
(0.56-0.97)*
(0.88-1.44)
Age
1.12
0.72
(0.54-0.95)*
(0.88-1.44)
Age, smoking
0.74
1.13
(0.56-0.98)*
(0.88-1.45)
Age, alcohol
0.77
1.15
(0.59-1.02)
(0.90-1.48)
Age, hypertension
1.14
0.76
(0.58-1.00)
(0.89-1.47)
Age, cholesterol
0.79
1.15
(0.60-1.04)
(0.90-1.48)
Age, body mass index
0.79
1.17
(0.60-1.04)
(0.91-1.50)
Age, diabetes
0.85
All variables above
1.19
(0.65-1.13)
(0.93-1.53)
Prevalent cases of coronary heart disease, cerebrovascular disease, and cancer were excluded.
Reference group was the lowest physical activity index tertile.
*95% confidence interval (Cl) for the relative risk (RR) excludes 1.
2544
Circulation Vol 89, No 6 June 1994
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patterns of activity of men in the middle tertile, however, are more like those of men in the lower physical
activity tertile than the activity patterns of men in the
most active group. For example, 90% of the men in the
lower and middle tertile of physical activity spent 0 and
1 hours, respectively, conducting moderate or heavy
activities, compared with 5 hours for the top tertile. This
may explain why only the most active group showed
reduced incidence rates of coronary heart disease morbidity and mortality.
The major potential source of bias in this type of
investigation could be due to the possibility that subjects
who had low levels of physical activity at entry were
already sick, and illness was the cause rather than the
result of lack of physical activity. Efforts to reduce this
potential source of bias were made by eliminating all
prevalent cases of heart disease, stroke, and cancer from
these analyses. Analyses were also repeated after excluding deaths occurring during the first 2 years of
follow-up, and results did not change. It is also possible
that subjects who exercise may have adopted other
healthy habits besides physical activity, leading to confounding of the results. However, the physical activity
measure used in this study reflects the overall level of
activity of the subjects throughout the day rather than
only whether participants engage in sports, a behavior
potentially linked to other healthy habits. No doubt, a
randomized, controlled clinical trial of physical activity
would be the optimal way to assess the potential benefits
of physical activity on coronary heart disease incidence
and mortality and would allow the establishment of the
temporal relation between cause and effect. Unfortunately, this type of investigation may not be feasible
because of difficulty with long-term compliance and the
resources that a study of this nature would require.
Despite the problems of observational studies, the
evidence suggesting that lack of physical activity is a
potentially modifiable risk factor for coronary heart
disease morbidity and mortality continues to accumulate.4,5,7,9,10,15-32 These findings suggest that physical
activity interventions during middle age, by improving
cardiovascular risk factor levels, may have significant
public health implications for the prevention of coronary heart disease.
Acknowledgments
This research was supported by contract No. NO1-HC05102 from the National Heart, Lung, and Blood Institute,
Bethesda, Md.
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B L Rodriguez, J D Curb, C M Burchfiel, R D Abbott, H Petrovitch, K Masaki and D Chiu
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Circulation. 1994;89:2540-2544
doi: 10.1161/01.CIR.89.6.2540
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 1994 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the
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