0021-972X/00/$03.00/0
The Journal of Clinical Endocrinology & Metabolism
Copyright © 2000 by The Endocrine Society
Vol. 85, No. 3
Printed in U.S.A.
Respiratory Fitness, Free Living Physical Activity, and
Cardiovascular Disease Risk in Older Individuals:
A Doubly Labeled Water Study*
ROMAN V. DVORAK, ANDRÉ TCHERNOF, RAYMOND D. STARLING,
PHILIP A. ADES, LORETTA DIPIETRO, AND ERIC T. POEHLMAN
Divisions of Clinical Pharmacology and Metabolic Research (R.V.D., A.T., R.D.S., E.T.P.) and
Cardiology (P.A.A.), Department of Medicine, University of Vermont, Burlington, Vermont 05405; and
The John D. Pierce Laboratory and Department of Epidemiology and Public Health, Yale University
School of Medicine (L.D.), New Haven, Connecticut 06519
ABSTRACT
The objective of this study was to examine the importance of cardiorespiratory fitness vs. physical activity energy expenditure on selected cardiovascular disease risk factors in older individuals. One
hundred and seventeen older individuals, 53 men (68 ⫾ 9 yr) and 63
women (67 ⫾ 7 yr), participated in the study. This cohort was divided
into 4 groups: 1) high cardiorespiratory fitness and high physical
activity, 2) high cardiorespiratory fitness and low physical activity, 3)
low cardiorespiratory fitness and high physical activity, and 4) low
cardiorespiratory fitness and low physical activity. Cardiorespiratory
fitness (VO2max) was determined from a graded exercise test, physical
activity energy expenditure was measured by doubly labeled water
and indirect calorimetry, body composition was determined by dual
energy x-ray absorptiometry, and dietary practices were determined
by a 3-day recall. Cardiorespiratory fitness exerted greater effects on
the cardiovascular disease risk profile than physical activity. That is,
older individuals with higher levels of cardiorespiratory fitness, regardless of their physical activity levels, showed lower levels of fasting
insulin (P ⬍ 0.01), triglycerides (P ⬍ 0.05), total cholesterol (P ⬍ 0.05),
total to high density lipoprotein cholesterol ratio (P ⬍ 0.05), low
density lipoprotein (P ⬍ 0.05), and lower waist circumference (P ⬍
0.01). Moreover, individuals with a high cardiorespiratory fitness but
low physical activity energy expenditure displayed a more favorable
cardiovascular disease risk profile than individuals with low cardiorespiratory fitness and high physical activity energy expenditure. The
results suggest that higher levels of cardiorespiratory fitness have
greater cardioprotective effects than higher levels of free living physical activity in older individuals. Although these findings do not discount the health benefits of being physically active, it is possible that
greater emphasis should be placed on aerobic exercise to increase
cardiorespiratory fitness in the elderly. (J Clin Endocrinol Metab 85:
957–963, 2000)
T
HERE IS CONSIDERABLE controversy regarding the
type and duration of exercise to enhance health benefits in the elderly. Despite recent public health recommendations to increase physical activity in the general population
(1), it is unclear whether high levels of cardiorespiratory
fitness (i.e. VO2max) or high levels of physical activity energy
expenditure (kilojoules per day) yield greater cardiovascular
and metabolic benefits in older individuals. Both greater
cardiorespiratory fitness (2–5), and leisure-time physical activity (6 – 8) are associated with a lower risk of cardiovascular
disease (CVD) and all-cause mortality, but these results may
not be generalizable to older individuals.
Cardiorespiratory fitness, a physiological attribute, quantifies the ability of the body to transport and use oxygen. It
is determined principally by training status and, to some
extent, by genetic predisposition (9). On the other hand,
physical activity is a behavioral attribute and comprises the
energy expenditure from volitional and nonvolitional activity throughout the day. Physical activity has also been shown
to be genotype dependent (10). Although there is shared
biological variance between these two phenotypes, they may
interact in a unique and independent manner to improve
metabolic and cardiovascular risk factors in older people.
Unfortunately, data on both cardiorespiratory fitness and
physical activity levels are seldom available for older
individuals.
Controversy regarding the effects of cardiorespiratory fitness and physical activity energy expenditure on cardiovascular health in older individuals may be partially due to
limitations in their assessment. Whereas cardiorespiratory
fitness can be directly and accurately quantified with graded
exercise tests by measuring oxygen consumption, the measure of physical activity energy expenditure has relied on
cruder methods, such as self-reports, motion detectors (i.e.
Caltrac) (11), or structured interviews (12). Although these
proxy measures of physical activity may be useful for detecting broad health trends or ranking the relative physical
activity levels in epidemiological investigations, they may
lack the precision and validity necessary to predict health
outcomes in individuals. For example, our laboratory has
recently shown, using doubly labeled water as the criterion
Received August 10, 1999. Revision received October 21, 1999. Accepted November 11, 1999.
Address all correspondence and requests for reprints to: Eric T.
Poehlman, Ph.D., Clinical Pharmacology and Metabolic Unit, Department of Medicine, Given Building C-247, University of Vermont, Burlington, Vermont 05405. E-mail: [email protected].
* This work was supported by the General Clinical Research Center
(RR-00109) from the University of Vermont; fellowships from the American Heart Association (to A.T. and R.V.D.), an Individual National
Research Science Award (AG-05791; to R.D.S.), and grants from the NIA
(KO4-AG-00564 and RO1-AG-07857) and the American Association of
Retired Persons (to E.T.P.).
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DVORAK ET AL.
method, that both uniaxial motion detectors and various
physical activity recall questionnaires underestimate physical activity energy expenditure in older individuals by as
much as 50% (13). These results raise questions regarding
whether physical activity was accurately assessed in previous investigations (6, 7).
The methodological assessment of physical activity energy
expenditure has been advanced in recent years with the use
of doubly labeled water. This method, which relies on the
administration of stable isotopes of oxygen and hydrogen
(2H218O), is objective, unobtrusive, and measures physical
activity energy expenditure over an extended period of time
in free living older individuals (14). Thus, this approach
becomes a powerful technique to increase our understanding
of the impact of free living physical activity on health outcomes in the elderly, which has not previously been possible.
To this end, we directly measured both cardiorespiratory
fitness (VO2max) and physical activity energy expenditure
using doubly labeled water in a relatively large sample of
older men and women. We identified older individuals with
high levels of VO2max, but low levels of physical activity
energy expenditure. We compared their metabolic risk profile to older individuals with low levels of VO2max, but high
levels of physical activity energy expenditure. This approach
permits an investigation of the relative importance of cardiorespiratory fitness vs. physical activity energy expenditure on selected CVD risk factors in older individuals.
Subjects and Methods
Subjects
Healthy older Caucasian men and women [53 men (68 ⫾ 9 yr) and
63 women (67 ⫾ 7 yr)] were recruited for the study from the greater
Burlington, VT, area from local advertisements and radio announcements. Subjects were clinically screened, and exclusion criteria included
1) hypertension (resting systolic/diastolic blood pressure, ⬎140/90 mm
Hg), 2) diabetes, 3) coronary heart disease (ST segment depression, ⬎1
mm at rest or during exercise), 4) smoking, 5) major orthopedic limitations, 6) thyroid disorders, and 7) medications that influence energy
expenditure, lipid metabolism, or cardiovascular function (lipid-lowering drugs, ␤-blockers, etc.). Women receiving hormone replacement
therapy were also excluded from the study. Each subject signed a consent form approved by the institutional review board at the University
of Vermont before participating in the study.
Testing protocol
All subjects were tested during an overnight stay in the General
Clinical Research Center at the University of Vermont. On the first day,
body composition was determined with dual energy x-ray absorptiometry (DXA), abdominal adiposity was estimated from waist circumference and trunk fat mass, and each subject was treated with doubly
labeled water to measure total daily energy expenditure (TEE) over the
subsequent 10 days. The morning after treatment, following an overnight fast, the resting metabolic rate was determined from indirect
calorimetry, and a blood sample was obtained to measure fasting concentrations of plasma insulin and lipids. Specific details of all procedures
are provided below.
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kg/min) were a respiratory exchange ratio greater than 1.0 and a heart
rate at or above the age-predicted maximum [220 ⫺ age (years)]. At least
one of these criteria was reached by 93% of the volunteers. Test-retest
conditions for nine older subjects (on two occasions, spaced 1 week
apart) yielded an intraclass correlation of 0.94 and a coefficient of variation of 3.8% in our laboratory.
Physical activity energy expenditure (PAEE)
We used doubly labeled water in combination with indirect calorimetry to measure free living physical activity energy expenditure. TEE
was determined over a 10-day period. Each subject was treated with a
1 g/kg body mass dose of 2H218O using the method of Schoeller and van
Santen (14), as previously described (16). Briefly, a baseline urine sample
was collected before treatment. The following morning, two additional
urine samples were collected, and two more samples were collected 10
days later. Urine samples were stored frozen in Vacutainers at ⫺20 C
until analyzed for 2H and 18O enrichments by isotope ratio mass spectrometry. 18O isotopic enrichment was determined from the carbon
dioxide (CO2) equilibration technique, and 2H enrichment was determined by the zinc catalyst method (17). The daily rate of CO2 production
(moles per day) was calculated using the equation of Speakman et al.
(18): rCO2 ⫽ N/2.196 ⫻ (cOkO ⫺ cHkH), where kO and kH are the
elimination rates of 18O and 2H tracers from the body, and cO and cH
are the dilution spaces for 18O and 2H tracers as recommended by Racette
et al. (19). Assuming a respiratory quotient of 0.85 for the food consumed
(20), total CO2 production was converted to TEE (kilojoules per day)
using the Weir formula (21).
The resting metabolic rate (RMR) was determined from 45 min of
indirect calorimetry using the ventilated hood technique, as previously
described (22). Respiratory gas analysis was performed using a Deltatrac
metabolic cart (Sensormedics, Yorba Linda, CA). The RMR (kilojoules
per day) was then calculated from the Weir equation (21). We previously
reported an intraclass correlation of 0.90 and a coefficient of variation of
4.3% for the measurement of RMR in 17 older volunteers who were
tested on 2 different occasions, 1 week apart. Assuming a thermic effect
of feeding of 10% in older individuals (23), total PAEE was then calculated from the equation: PAEE ⫽ (TEE ⫻ 0.90) ⫺ RMR.
Body composition and abdominal adiposity
Body composition was measured by DXA using a DPX-L densitometer (Lunar Corp., Madison, WI). A total body scan was completed in
30 – 40 min and provided measures of total lean tissue mass (kilograms),
fat mass (kilograms), and trunk lean and fat masses (kilograms). Abdominal adiposity was also assessed from the waist circumference taken
between the xiphoid process and the superior anterior iliac crest (24). The
waist circumference has demonstrated a strong correlation (r ⬎ 0.84)
with visceral fat mass, as determined from computed tomography in
middle-aged (25) and older subjects (26). Coefficients of variation for
repeat measurements of body composition by DXA and waist circumference were 1.7% and 4%, respectively, in our laboratory.
Cardiovascular and metabolic risk factors
Plasma insulin concentrations were determined by RIA as previously
described (27). Plasma cholesterol, triglyceride, and high density lipoprotein cholesterol (HDL-C) concentrations were determined from
standard enzymatic techniques at the nationally accredited laboratory of
the Fletcher Allen Medical Center. The interassay coefficients of variation for the measurement of total and HDL-C were 3.35% and 1.15%,
respectively. Low density lipoprotein cholesterol (LDL-C) was determined from the Friedewald equation (28).
Dietary intake
Cardiorespiratory fitness
Maximum aerobic capacity (VO2max) was determined from an incremental exercise test on a bicycle ergometer to volitional exhaustion, as
previously described (15). Cycling cadence was 50 rpm with a workload
of 25 and 50 watts during the first 3 min for women and men, respectively. Thereafter, workload was increased 25 watts every 2 min until the
test was terminated. The criteria for achieving VO2max (milliliters per
Dietary intake was measured for 3 days (1 weekend day and 2 weekdays), as previously described (29). Participants were instructed by
registered dietitian and encouraged to maintain their usual diet. Moreover, they were provided with dietary scales and measuring cups and
spoons to further increase the precision of the data obtained. Diets were
analyzed using the Nutritionist III software version 4.0 (N-Squared
Computing, Salem, OR).
CARDIORESPIRATORY FITNESS AND PHYSICAL ACTIVITY
Statistical analysis
We divided our sample into four groups based on the median cut-off
points for the sex-specific distributions of both cardiorespiratory fitness
and physical activity energy expenditure: 1) high cardiorespiratory fitness and high physical activity, 2) high cardiorespiratory fitness and low
physical activity, 3) low cardiorespiratory fitness and high physical
activity, and 4) low cardiorespiratory fitness and low physical activity.
We used a two-way ANOVA to test the main effects of cardiorespiratory
fitness, physical activity, and interactions on the physical characteristics
of our sample of older individuals. No interactions were found, so main
effects are presented. To examine the effects of cardiorespiratory fitness,
physical activity, and gender on selected CVD risk factors, we employed
a three-way analysis of covariance with age as a covariate. To examine
the contribution of body composition and body fat distribution variables
on the effects of cardiorespiratory fitness, physical activity, and gender
on CVD risk factors, we used a three-way analysis of covariance with
age, gender, waist circumference, trunk fat, and body fat percentage as
covariates. Statistical significance was accepted at ␣ ⬍ 0.05.
Results
Subject assignment into groups
Values for VO2max and physical activity energy expenditure for the four groups with high and low cardiorespiratory
fitness and with high and low physical activity energy expenditure are presented in Table 1. The median cut-off points
were VO2max of 27.7 and 21.7 mL/kg䡠min for men and
women, respectively, and the physical activity energy expenditure was 3449 kJ/day for men and 2742 kJ/day for
women. The VO2max values in the high cardiorespiratory
fitness groups reflect population norms for older people who
are considered fit (30). Furthermore, physical activity energy
expenditure values for individuals in all four groups exceeded the recommended level of daily exercise energy expenditure in older individuals (⬃849 kJ/day) (1). Thus, our
volunteer sample represented a physically active cohort of
older individuals. In the present sample of older, healthy
individuals, we found a modest association between cardiorespiratory fitness and physical activity energy expenditure
(r ⫽ 0.37; P ⬍ 0.01).
Physical and dietary characteristics
The physical characteristics of our cohort are presented in
Table 2. We found a significant main effect of cardiorespiratory fitness on age, body mass, body mass index, fat mass,
body fat percentage, and waist circumference. That is, older
individuals with high cardiorespiratory fitness were slightly
younger (P ⬍ 0.01); had lower body mass (P ⬍ 0.01), body
mass index (P ⬍ 0.01), fat mass (P ⬍ 0.01), body fat percent-
959
age (P ⬍ 0.01), and trunk fat mass (P ⬍ 0.01); and had smaller
waist circumference (P ⬍ 0.01) than older individuals with
low cardiorespiratory fitness. There was no significant effect
of cardiorespiratory fitness on fat-free mass in our cohort of
older individuals. Analysis of dietary habits revealed no
significant effect of cardiorespiratory fitness on total energy
intake, macronutrient composition (Table 2), or daily intake
of saturated fat and cholesterol (data not shown in table
form).
There was a trend for individuals who had greater physical activity energy expenditure to be younger (P ⫽ 0.08). We
observed a significant main effect of physical activity on
body mass index and body mass. In other words, older
individuals with high levels of physical activity energy expenditure showed higher body mass (P ⫽ 0.04) and body
mass index (P ⫽ 0.02) than older individuals with low levels
of physical activity energy expenditure. We found no differences in fat mass, fat-free mass, body fat percentage, trunk
fat mass, and waist circumference between individuals with
higher and lower physical activity energy expenditures in
our sample of older volunteers. Analysis of dietary practices
showed no differences between high vs. low physical activity
groups in the macronutrient composition of diet (Table 2),
saturated fat, and cholesterol intake (data not shown in table
form). However, as expected, we found that more active
individuals had significantly greater total daily energy intake
than their less active counterparts (Table 2).
Cardiovascular disease risk factors
Cardiovascular disease and metabolic risk factors were
examined with age as a covariate (Fig. 1, A and B). We
observed a significant main effect of cardiorespiratory fitness
on total cholesterol, LDL-C, total cholesterol to HDL-C ratio,
fasting insulin levels, and triglycerides. That is, older individuals with high cardiorespiratory fitness, regardless of
their physical activity level, showed lower total cholesterol
levels (P ⬍ 0.01), lower fasting LDL levels (P ⬍ 0.05), lower
total cholesterol to HDL-C ratio (P ⬍ 0.05), lower fasting
insulin levels (P ⬍ 0.01), and lower fasting triglycerides levels
(P ⬍ 0.05). We found no effect of physical activity on HDL
cholesterol levels. Also, we found no effect of gender on any
variable examined.
When examining the effects of physical activity, we found
a significant main effect of this variable on LDL levels, e.g.
older individuals with high levels of physical activity displayed lower levels of LDLs than individuals with low levels
TABLE 1. Cardiorespiratory fitness and physical activity energy expenditure (PAEE) for each group
High cardiorespiratory fitness
VO2max
mL/kg䡠min
L/min
PAEE (kJ/day)
Low cardiorespiratory fitness
High PAEE
(n ⫽ 34; 14f/20m; group 1)
Low PAEE
(n ⫽ 23; 15f/8m; group 2)
High PAEE
(n ⫽ 26; 18f/8m; group 3)
Low PAEE
(n ⫽ 34; 16f/18m; group 4)
33.2 ⫾ 8.0a
2.3 ⫾ 0.7a,b
4594 ⫾ 1397c
30.1 ⫾ 7.6a
1.9 ⫾ 0.6a
2364 ⫾ 732
19.5 ⫾ 3.2
1.5 ⫾ 0.4
4347 ⫾ 900c
20.8 ⫾ 4.3
1.5 ⫾ 0.5
1787 ⫾ 900
Values are presented as the mean ⫾ SD. The cut-off points based on median values for VO2max were 27.7 and 21.7 ml/kg䡠min for men and
women, respectively, and the physical activity energy expenditure was 3449 kJ/day for men and 2742 kJ/day for women.
a
P ⬍ 0.01 for the difference from group 3 and 4.
b
P ⬍ 0.01 for the difference from group 2.
c
P ⬍ 0.01 for the difference from groups 2 and 4.
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TABLE 2. Physical characteristics and dietary practices for each subgroup
High cardiorespiratory fitness
Age (yr)
Body mass (kg)
Body mass index (kg/m2)
Fat-mass (kg)
Fat-free mass (kg)
% body fat (%)
Trunk fat mass (kg)
Waist circumference (cm)
Energy intake (MJ/day)
Carbohydrate intake (%)
Fat intake (%)
Protein intake (%)
Main effect; P value
(3 ⫻ 2 ANOVA)
Low cardiorespiratory fitness
High PAEE
(group 1)
Low PAEE
(group 2)
High PAEE
(group 3)
High PAEE
(group 4)
CardioR fitness
PAEE
63 ⫾ 2
69 ⫾ 11
24 ⫾ 3
17 ⫾ 7
49 ⫾ 10
25 ⫾ 10
8.4 ⫾ 3.5
83 ⫾ 10
8.9 ⫾ 1.9
55 ⫾ 10
26 ⫾ 8
16 ⫾ 3
65 ⫾ 2
63 ⫾ 10
23 ⫾ 2
18 ⫾ 5
43 ⫾ 10
30 ⫾ 8
9.5 ⫾ 4.0
80 ⫾ 8
7.2 ⫾ 2.8
59 ⫾ 10
24 ⫾ 10
16 ⫾ 4
69 ⫾ 1
75 ⫾ 15
27 ⫾ 5
27 ⫾ 10
44 ⫾ 9
38 ⫾ 9
14.1 ⫾ 5.0
91 ⫾ 14
8.0 ⫾ 1.9
54 ⫾ 8
28 ⫾ 7
16 ⫾ 3
72 ⫾ 1
72 ⫾ 12
25 ⫾ 3
22 ⫾ 7
47 ⫾ 9
32 ⫾ 8
12.0 ⫾ 4.5
91 ⫾ 10
7.7 ⫾ 1.9
55 ⫾ 7
26 ⫾ 5
17 ⫾ 4
⬍0.01
⬍0.01
⬍0.01
⬍0.01
0.76
⬍0.01
⬍0.01
⬍0.01
0.55
0.23
0.32
0.58
0.08
0.04
0.02
0.15
0.39
0.72
0.59
0.40
0.01
0.18
0.09
0.83
Values are presented as the mean ⫾ SD.
PAEE, Physical activity energy expenditure.
of physical activity (P ⬍ 0.05). The absence of a main effect
of physical activity on other cardiovascular risk factors suggests that regardless of whether an individual has high or
low physical activity energy expenditure, the level of cardiorespiratory fitness is a stronger correlate of a more favorable CVD risk profile. This finding is particularly evident
when individuals with high cardiorespiratory fitness but low
physical activity energy expenditure (group 2) are compared
with individuals with high physical activity energy expenditure but low cardiorespiratory fitness (group 3). That is,
group 2 consistently displayed a more favorable CVD risk
profile than group 3 despite significant differences in physical activity energy expenditure levels.
Total and regional adiposity
We assessed the association of body composition and fat
distribution with the effects of cardiorespiratory fitness and
physical activity on CVD risk factors using analyses of covariance. The rationale underlying this approach is that individuals with a high cardiorespiratory fitness, independent
of their levels of physical activity energy expenditure,
showed lower levels of body weight, total body fat, fat mass,
trunk fat mass, and waist circumference (see Table 2). Therefore, we statistically controlled for waist circumference,
trunk fat mass, or body fat percentage using analysis of
covariance. We found that the inclusion of waist circumference, trunk fat mass, or body fat percentage as covariates
eliminated all of the differences among groups for all CVD
risk factors. Fat mass-adjusted marginal means were: for
cholesterol levels, 5.2 ⫾ 0.2, 5.6 ⫾ 0.2, 5.7 ⫾ 0.2 and 5.6 ⫾ 0.2
mmol/L; for LDL-C levels, 3.5 ⫾ 0.2, 3.7 ⫾ 0.2, 3.7 ⫾ 0.2, and
3.9 ⫾ 0.2 mmol/L; for HDL-C levels, 1.6 ⫾ 0.1, 1.5 ⫾ 0.1, 1.5 ⫾
0.1, and 1.5 ⫾ 0.1 mmol/L; for the total/HDL-C ratio, 3.4 ⫾
0.2, 3.8 ⫾ 0.2, and 3.9 ⫾ 0.2, 3.9 ⫾ 0.2 mmol/L; for fasting
insulin levels, 64.3 ⫾ 10.4, 69.5 ⫾ 10.2, and 84.9 ⫾ 10.4, 87.5 ⫾
9.5 pmol/L; and for triglyceride levels, 1.3 ⫾ 0.2, 1.7 ⫾ 0.2,
1.9 ⫾ 0.2, and 1.6 ⫾ 0.2 mmol/L for groups 1– 4 respectively.
Waist circumference- and trunk fat-adjusted values were
similar (not shown).
Discussion
To our knowledge, this is the first study to directly compare the effects of both cardiorespiratory fitness (VO2max)
and free living physical activity energy expenditure on several CVD risk factors in older people using doubly labeled
water methodology. The major finding of our study is that
high levels of cardiorespiratory fitness, independent of differences in physical activity levels, were associated with a
more favorable CVD risk profile in older individuals.
The cardioprotective benefits of cardiorespiratory fitness
vs. free living physical activity in older individuals are controversial. In our opinion, this is partially due to 1) the use
of proxy and often inaccurate assessments of physical activity (13), and 2) the failure to measure both cardiorespiratory
fitness and physical activity in older individuals. The present
study addresses these limitations by directly measuring both
variables using criterion measures (graded exercise test and
doubly labeled water) in older individuals. Moreover, our
relatively large sample size permitted the identification of
four groups of older individuals that differed in cardiorespiratory fitness and physical activity levels. This approach
allowed us to estimate whether older individuals with high
cardiorespiratory fitness (but low physical activity energy
expenditure) exhibited a more favorable CVD risk profile
than individuals with high physical activity energy expenditure, but low cardiorespiratory fitness.
We found that older men and women with high cardiorespiratory fitness, regardless of their physical activity levels,
showed lower concentrations of total cholesterol, LDL-C levels, the total to HDL cholesterol ratio, fasting insulin, and
triglycerides, than individuals with low cardiorespiratory
fitness. This point is particularly highlighted by the comparison of group 2 (high cardiorespiratory fitness, but low
physical activity) vs. group 3 (low cardiorespiratory fitness,
but high physical activity). Despite the fact that individuals
in group 2 had lower levels of physical activity than those in
group 3, their CVD risk profile was more favorable. Our
results are particularly striking when one considers the
healthy nature of our cohort.
How physiologically distinct are cardiorespiratory fitness
CARDIORESPIRATORY FITNESS AND PHYSICAL ACTIVITY
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FIG. 1. A, Total cholesterol, LDL-C, and HDL-C values among subjects with high or low cardiorespiratory fitness (VO2max) and either high or
low PAEE. Subgroups were defined using the 50th percentile of the distribution of each variable, for each gender (see and Materials and
Methods). B, Total to HDL-C ratio, fasting insulin, and triglyceride levels among subjects with high or low cardiorespiratory fitness (VO2max)
and either high or low PAEE. Subgroups were defined using the 50th percentile of the distribution of each variable, for each gender (see Materials
and Methods). Values are presented as the mean (adjusted for age and gender) ⫾ SEM.
and physical activity? Although one may hypothesize a
strong positive association between these two phenotypes
(e.g. individuals with a high physical activity level have high
cardiorespiratory fitness and vice versa), this relationship is
not straightforward. To address this point, we examined the
relationship between VO2max and physical activity energy
expenditure. We found a low order correlation between these
two variables (r ⫽ 0.37) in our cohort of 117 older individuals.
That is, only 13% of shared variance between these two
variables was found. This finding supports the idea that
these variables may act in a unique and independent manner
to improve cardiovascular and metabolic health in older
individuals.
There is limited evidence in the literature regarding the
relative influence of cardiorespiratory fitness vs. physical
activity on health outcomes in the elderly. It has been documented that individuals with higher cardiorespiratory fitness (3–5), and higher levels of physical activity (6, 7, 31) have
both lower CVD and overall mortality. However, previous
studies that assessed the relationship between physical activity and mortality may be questioned given recent data
suggesting that physical activity questionnaires significantly
underestimate true physical activity levels in older individuals (13). Moreover, few studies have examined both the
effects of cardiorespiratory fitness and free living physical
activity on CVD risk factors using doubly labeled water
methodology. Hein et al. (32) found that the effect of cardiorespiratory fitness level on ischemic heart disease was de-
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pendent on the level of leisure-time activity in a middle-aged
Danish population. Among sedentary men, cardiorespiratory fitness was not related to ischemic heart disease; however, among moderately or highly active men, there was a
strong inverse relationship between the level of cardiorespiratory fitness and ischemic heart disease risk. However,
other investigators (33–37) reported that a number of CVD
risk factors showed a stronger association with measures of
cardiorespiratory fitness than with physical activity levels in
populations of younger to middle-aged adults. The present
study extends the findings of previous investigations by
directly measuring both physical activity energy expenditure
and cardiorespiratory fitness using criterion measures in
older individuals, a population that is particularly susceptible to the comorbidities associated with low fitness and low
physical activity.
How does cardiorespiratory fitness exert greater cardioprotective effects than physical activity energy expenditure?
These findings are unlikely to be due to differences in dietary
habits. We found no differences in dietary intake among
groups, except for the higher total energy intake in more
physically active individuals compared with less active individuals. On the other hand, several investigators have suggested that favorable effects of exercise or high physical
activity on CVD risk factors may be mediated through differences in body composition or total and visceral body fatness (38 – 42). To examine this question, we statistically controlled for body composition (body fat percentage) and
visceral adiposity measures (waist circumference, trunk fat),
which are predictors of CVD risk factors (38). As described
in Results, we found no effect of cardiorespiratory fitness on
the CVD risk profile variables after this analysis was performed. Taken together, these findings support the hypothesis that the effects of cardiorespiratory fitness on CVD risk
profile may be mediated through lower levels of total and/or
central adiposity. In support of this idea, Hunter and colleagues (43) recently reported that vigorous physical activity
is effective in reducing total and abdominal adiposity. These
investigators suggested that the exercise-induced reduction
in total and regional adiposity may be mediated not only by
the direct caloric cost of exercise, but also by the increase in
postexercise RMR and greater appetite suppression. Furthermore, Tremblay and colleagues (44) reported a preferential
mobilization of visceral adipose tissue with higher intensity
exercise training in younger adults. Thus, it seems reasonable
to suggest that older individuals may accrue greater health
benefits from exercise prescriptions that stimulate cardiorespiratory fitness with concomitant reduction in total and
central adiposity.
The strengths of our study are the use of two precise and
direct measures to determine both cardiorespiratory fitness
(graded exercise test) and free living physical activity energy
expenditure (doubly labeled water) in the same older population. Furthermore, we considered the possible influence
of dietary habits on CVD risk factors examined. By stratifying
the sample into four groups based on their cardiorespiratory
fitness and physical activity energy expenditure levels, we
were able to examine the unique effects of cardiorespiratory
fitness vs. physical activity on various CVD risk factors. The
limitations of the present investigation include the cross-
sectional design, which precludes any idea regarding causal
relationships, and the fact that all of our volunteers were
Caucasian. Thus, our results cannot be extrapolated to other
ethnic groups. Moreover, it could be argued that a selective
mortality effect was operative in which healthy older survivors volunteered for our study. These individuals may
possess a cluster of favorable metabolic and CVD phenotypes. This could be attributable in part or in totality to
genotypes that are responsible for both higher cardiorespiratory fitness and a favorable CVD risk profile, such as low
total cholesterol, high HDL-C, low accumulation of visceral
fat, high insulin sensitivity, and low blood pressure (9, 10).
Our results are not intended to discount the importance of
a physically active lifestyle for maintaining health and physical function in aging (45). Indeed, substantial health benefits
can be achieved through physical activity levels that are not
associated with discernible changes in cardiorespiratory fitness (1, 46). Rather, we suggest that our findings underscore
the probable importance of vigorous physical activity in
which levels of cardiorespiratory fitness are increased. This
point was most recently supported by the findings of Erikssen and colleagues (47), who showed a significant decrease
in mortality in individuals who improved their cardiorespiratory fitness.
In conclusion, we found that high levels of cardiorespiratory fitness appear to have greater cardioprotective effects
than high levels of physical activity in older men and women.
It is possible that greater emphasis should be placed on
exercise interventions to increase cardiorespiratory fitness in
the elderly.
Acknowledgments
We extend our gratitude to all participants in this study. Furthermore,
the expert technical help of the staff at the General Clinical Research
Center is greatly appreciated.
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