EURO PEAN
SO CIETY O F
CARDIOLOGY ®
Original scientific paper
Cardiopulmonary fitness is a function
of lean mass, not total body weight: The
DR’s EXTRA study
European Journal of Preventive
Cardiology
2015, Vol. 22(9) 1171–1179
! The European Society of
Cardiology 2014
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DOI: 10.1177/2047487314557962
ejpc.sagepub.com
Benno Krachler1,2, Kai Savonen1,3, Pirjo Komulainen1,
Maija Hassinen1, Timo A Lakka1,4 and Rainer Rauramaa1,3
Abstract
Background: Division by total body weight is the usual way to standardise peak oxygen uptake (peak VO2) for body
size. However, this method systematically underestimates cardiopulmonary fitness in obese individuals. Our aim was to
analyse whether lean-mass is a better base for a body mass-independent standard of cardiopulmonary fitness.
Methods: A population based sample of 578 men (body mass index (BMI) 19–47 kg/m2) and 592 women (BMI 16–49 kg/m2)
57–78 years of age. Peak VO2 was assessed by respiratory gas analysis during a maximal exercise test on a cycle
ergometer. We studied the validity of the weight-ratio and the lean mass-ratio standards in a linear regression model.
Results: The weight-ratio standard implies an increase of peak VO2 per additional kg body weight with 20.7 ml/min (95%
confidence interval (CI): 20.3–21.1) in women and 26.9 ml/min (95% CI: 26.4–27.5) in men. The observed increase per kg
is only 8.5 ml/min (95% CI: 6.5–10.5) in men and 10.4 ml/min (95% CI: 7.5–13.4) in women. For the lean mass-ratio
standard expected and observed increases in peak VO2 per kg lean mass were 32.3 (95% CI: 31.8–32.9) and 34.6 (95%
CI: 30.0–39.1) ml/min for women and 36.2 (95% CI: 35.6–36.8) and 37.3 (95% CI: 32.1–42.4) ml/min in men. The lean
mass-ratio standard is a body mass-independent measure of cardiopulmonary fitness in 100% of women and 58% of men;
corresponding values for the weight-ratio standard were 11% and 16%.
Conclusions: For comparisons of cardiopulmonary fitness across different categories of body mass, the lean mass-ratio
standard should be used.
Keywords
Exercise capacity, cardiopulmonary fitness, cardiorespiratory fitness, exercise physiology, exercise testing, body
composition
Received 22 June 2014; accepted 13 October 2014
Introduction
Poor cardiopulmonary fitness is an independent risk
factor for cardiovascular and metabolic diseases in
the general population.1,2 The most commonly used
measure of cardiopulmonary fitness is peak oxygen
uptake (peak VO2) in a maximal exercise test, which
shows excellent reproducibility in both health and disease.3,4 Since peak VO2 is dependent on body size, it
needs to be standardised in order to obtain a measure
of cardiopulmonary fitness that allows comparisons
across categories of body size. Comparing group-means
of peak VO2 (mean standard) and adjusting peak VO2
for body weight (adjusted standard) as well as dividing
1
Kuopio Research Institute of Exercise Medicine, Finland
Department of Public Health and Clinical Medicine, Umeå University,
Sweden
3
Department of Clinical Physiology and Nuclear Medicine, Kuopio
University Hospital, Finland
4
Institute of Biomedicine/Physiology, University of Eastern Finland,
Finland
2
Part of this work was presented as a poster at the 2013 American
Medical Society for Sports Medicine (AMSSM) 22nd Annual Meeting.
Corresponding author:
Benno Krachler, Kuopio Research Institute of Exercise Medicine,
Haapaniementie 16, FIN-70100 Kuopio, Finland.
Email: [email protected]
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European Journal of Preventive Cardiology 22(9)
by body weight (weight ratio standard) are commonly
used methods. As cardiopulmonary performance does
not increase in linear proportion to body size, dividing
peak VO2 by body weight raised to the power of 0.7 has
been recommended based on allometric modelling.5
However, allometric scaling is rarely used in a clinical
or epidemiological context. Instead, a simple weight
ratio, i.e. dividing peak VO2 by body weight is the
most commonly used reference standard in exercise
physiology, cardiovascular prevention and current clinical guidelines.6–9 We recently demonstrated that dividing peak VO2 by body weight introduces a bias
against obese subjects and distorts associations
between cardiopulmonary fitness and co-morbidities
of obesity.10
Given the shortcomings of the weight-ratio standard
and the need for a reference population for the adjusted
standard, other ways to account for body size have been
explored. A ratio based on lean mass compared favourably to the weight-ratio standard as a measure of fitness
in adolescents11 and has been suggested in assessment of
dyspnoea in adults.12,13 Fat mass has been shown not to
influence peak aerobic capacity.14 Estimating cardiopulmonary fitness independent of obesity has been shown
to improve the accuracy of fitness as a determinant of
cardiac function.15 Moreover, physiological models
based on allometric scaling support the notion that
peak VO2 is a linear function of lean mass with a
mass exponent equal to –1.16 However, these results
were observed in selected groups of subjects, rather
than population based samples, nor has the degree of
bias introduced by the weight-ratio been demonstrated
explicitly which might explain why it is still the most
common reference standard of cardiorespiratory fitness.
Since simple ratios are the preferred way of standardising peak VO2 in clinical and epidemiological practice, we intend to contrast the weight-ratio standard
with a lean mass-ratio standard in a population based
sample of elderly subjects. If the lean mass-ratio standard, i.e. dividing peak VO2 by lean mass is equivalent
to adjustment for lean mass, it would provide a simple
way of standardising for body size without introducing
a bias against obese subjects.
Methods
Design and participants
We used cross-sectional data collected at the two-year
follow-up visits of the Dose-Responses to Exercise
Training Study (DR’s EXTRA, Clinical Trial
Registration
URL:
http://www.clinicaltrials.gov,
Unique Identifier: isrctn 45977199) which is a four-year
randomised controlled trial on the health effects of
regular physical exercise and diet: an age-stratified
sample of 1500 men and 1500 women aged 55–74
years was randomly selected from the population register of the city of Kuopio, a municipality of about
100,000 inhabitants in Eastern Finland. Every potential
participant was invited by mail in 2003. After the run-in
period and after exclusions 1479 individuals were eligible for the baseline examinations in 2005–2006. The
exclusion criteria were conditions that inhibit safe
engagement in exercise training, malignant diseases,
and conditions considered to prevent cooperation.
The present study population consists of 1170 individuals (578 men and 592 women) aged 59–80 years at
two-year follow-up when body composition was estimated by bioimpedance. The Research Ethics
Committee Hospital District of Northern Savo has
approved the research protocol. Written informed consent has been obtained from all participants.
Assessment of cardiopulmonary fitness
Cardiopulmonary fitness was assessed during a symptom-limited maximal exercise stress test on an electrically braked cycle ergometer (Ergoline, Bitz, Germany).
The tests were supervised by physicians according to a
standardised test protocol with a warm-up of 3 min at
20 W and a 20 W increase in the workload per minute.
Participants were verbally encouraged to maximal exertion. Oxygen consumption was measured directly by
the breath-by-breath method using the VMax pulmonary gas analyser (SensorMedics, Yorba Linda,
California, USA). Peak VO2 was defined as the mean
of the three highest values of the averaged oxygen consumption measured consecutively over 20-second intervals. A total of 99% of the subjects achieved the
respiratory exchange ratio of 1.1.
Assessment of habitual physical activity
Physical activity. Physical activity was assessed using the
12-month leisure-time physical activity questionnaire as
described previously.17 Briefly, for each activity performed, the subject was asked to record the frequency
(number of sessions per month), average duration (hours
and minutes per session), and intensity (scored as 0 for
recreational activity, 1 for conditioning activity, 2 for
brisk conditioning activity, 3 for competitive, strenuous
exercise). A trained nurse checked and completed the
questionnaire in an interview. The intensity of physical
activity was expressed in MET hours (Metabolic
Equivalent of Task with 1 METh ¼ reference value of
1kcal *kg1 *h1). METh/week were standardised using
the direct method as follows: reported METh/week
values were multiplied by the individual’s total body
weight and divided by sex-specific population mean
weight. Weight-standardised METh/week were divided
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Krachler et al.
1173
by the individual’s lean mass and multiplied by the sexspecific population mean lean mass.
9.2, SAS Institute, Cary, North Carolina, USA) for all
statistical evaluations.
Body composition. Body composition was assessed by
multifrequency bioimpedance analysis using the
InBody 720 device (Biospace, Seoul, Korea). We used
the device-specific software provided by the manufacturer to assess lean mass. Manufacturer-instructions
regarding standardisation of measurement were
followed.
A sensitivity analysis was performed to explore
potential bias introduced by assessing body composition with bioimpedance instead of dual-energy X-ray
absorptiometry (DXA). Based on the findings in
another population of Finns with similar age18 we calculated obesity-category specific correction factors for
estimates of lean mass. Based on the corrected estimates
of lean mass, differences between observed associations
of peak VO2 and lean mass and those implied by the
lean mass-ratio standard narrowed slightly in women
(predicted 34.9 ml/min/kg lean mass; observed 35.5
(95% CI: 30.8–40.2)) and widened slightly in men (predicted 38.3 ml/min/kg lean mass; observed 34.9 (95%
CI: 29.8–40.1)).
Results
Statistical analyses
As a measure of cardiopulmonary fitness, we calculate
expected normal peak VO2 in ml/min for every participant according to three different standards (compare
Figures 1 and 2): (a) mean: sex specific population
mean; (b) weight-ratio standard: mean ml/kg/min¼ each subject’s body weight multiplied with sex-specific mean peak VO2 in ml/kg/min; (c) lean mass-ratio
standard: mean ml/kg lean mass/min ¼ each subject’s
lean-mass multiplied with sex-specific mean peak VO2
in ml/kg lean mass/min. Standards (b) and (c) are compared to the actually observed associations between
peak VO2 and body weight and lean-mass, respectively
by linear regression analyses.
Confounding by body mass for the respective standard is estimated by plotting residuals (standard-specific
expected peak VO2 – observed peak VO2) against body
mass index (BMI). Trends in bias are estimated by
linear regression of residuals vs BMI. The intersection
of the regression line with zero defines the BMI-level
with minimum confounding by body mass.
Intersections of regression lines’ upper and lower 95%
confidence limits with zero define the BMI-interval of
unbiased estimation of cardiopulmonary fitness.
Proportions of individuals within and outside that
bias-free BMI-interval are used to compare the different
standards’ performance.
All reported p values are two-sided. We used the
Statistical Analysis System (SAS for Windows, version
Characteristics of subjects according to sex and BMIcategory are shown in Table 1. Mean peak VO2
increases with increasing BMI. Cardiopulmonary fitness expressed as peak VO2 per kg body weight
decreases markedly with increasing BMI in both men
and women. Peak VO2 per kg lean mass decreases
slightly with increasing BMI in men, whereas there is
no such trend over BMI-categories in women. There is
a trend towards lower physical activity in both men and
women. After standardisation for body mass and body
composition, a weak negative association between
activity and body mass remains, only in men.
Associations between peak VO2 and total body
weight for men are given in Figure 1(a). The
observed increase per kg (linear regression) is
10.4 ml/min (95% CI 7.5–13.4). The mean standard
(mean ml/min) implies no change in peak VO2 with
increasing body weight. The weight-ratio standard
(mean ml/min/kg) implies an increase of peak VO2
with 26.9 ml/min (95% CI: 26.4–27.5) per additional
kg body weight. Figure 1(b) is a plot of peak VO2
against lean mass. The increase in peak VO2 implied
by lean mass-ratio standard (36.2 ml/min/kg lean
mass, 95% CI: 35.6–36.8) is close to the observed
increase of peak VO2 with increasing lean-mass
(slope of linear regression: 37.3 ml/min (95% CI:
32.1–42.4). Figure 1(c) is a plot of residuals of the
mean standard (ignoring body weight). There is a
positive trend both with increasing body weight
(upper panel) and with increasing BMI. Figure 1(d)
is a plot of residuals for the weight-ratio standard.
Mean residuals are positive in light individuals and
negative in heavier subjects, both in terms of body
weight and BMI. Average residuals for the peak VO2
divided by lean mass (Figure 1(e)) are close to 0
across the whole range of lean-mass. There is a
slight negative trend for residuals with increasing
BMI.
Figure 2 depicts respective values for women. As in
men, the regression line of peak VO2 and total body
weight (Figure 2(a)) has a positive slope, but not as
steep as implied by division of peak VO2 with total
body weight: the weight-ratio standard (mean ml/min/
kg) implies an increase in peak VO2 of 20.7 ml/min
(95% CI: 20.3–21.1) per additional kg body weight.
The true increase per kg (linear regression) is only
8.5 ml/min (95% CI: 6.5–10.5). Dividing peak VO2
with lean-mass (mean ml/min/kg lean mass) is almost
equivalent to the linear regression with predicted and
observed increase of peak VO2 by 32.3 ml/min (95%
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1174
European Journal of Preventive Cardiology 22(9)
(a)
Expected Peak VO 2 vs. Lean mass in men
(b)
Expected Peak VO 2 vs. weight in men
4000
4000
3500
3500
3000
3000
2500
2500
2000
Mean
ml/min
2000
Mean
ml/min/kg
Linear
regression
1000
100
130
1500
1000
500
40
50
60
70
80
80
110
120
140
Mean
ml/min
1500
Mean
ml/min/kg
lean mass
500
150
30
40
50
Total weight, kg
Residuals:
Mean standard
mean ml/min
(c)
1250
1000
750
500
250
0
-250
-500
-750
1500
1500
1250
1250
1000
1000
750
750
500
500
250
250
0
0
-250
-250
-500
-750
-750
-1000
-1250
-1500
90
Lean mass-rao
mean ml/min/kg lean mass
-1000
-1250
80
(e)
Weight-rao
mean ml/min/kg
-500
-1000
70
Lean mass, kg
(d)
1500
60
Linear
regression
-1250
-1500
-1500
40
50
60
70
80
80
100
110
120
130
140
150
40
50
60
70
80
80
100
110
120
130
140
150
30
1500
1500
1500
1250
1250
1250
1000
1000
1000
750
750
750
500
500
500
250
250
250
0
0
0
-250
-250
-250
-500
-500
-500
-750
-750
-750
-1000
-1000
-1000
-1250
-1250
-1250
-1500
-1500
15
20
25
30
35
40
40
50
60
70
80
90
-1500
15
Linear trend
20
25
30
35
40
15
20
25
30
35
40
95% CI
Figure 1. Differences between expected and observed cardiopulmonary fitness in men: (a) comparison of trend in peak oxygen
uptake (peak VO2) per kg total weight implied by the weight-ratio standard (mean ml/min/kg) and actually observed values;
(b) comparison of trend in peak VO2 per kg lean mass implied by the lean mass-ratio standard (mean ml/min/kg lean mass) and actually
observed values. Residuals difference between observed peak VO2–peak VO2 expected by the respective standard plotted by basis for
the respective standard (upper panel) and body mass index (BMI) (lower panel); (c) mean standard, comparison of peak VO2 without
regarding body mass; (d) weight-ratio, comparisons based on peak VO2 divided by kg total weight; (e) lean mass-ratio, comparisons
based peak VO2 divided by kg lean mass. CI: confidence interval.
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Krachler et al.
Expected Peak VO 2 vs. Weight
in women
Peak VO 2 ml/min
(a)
1175
(b)
Expected Peak VO 2 vs. Lean Mass
in women
Mean
Mea
ml/min
Mean
Mea
ml/min
Mean
ml/min/kg
Mean
ml/min/kg
lean mass
Linear
regression
Total weight, kg
Linear
regression
Lean mass, kg
Residuals:
Mean standard
mean ml/min
(d)
Weight-rao
mean ml/min/kg
(e)
Lean mass-rao
mean ml/min/kg lean mass
Peak VO 2 ml/min
(c)
Lean mass, kg
BMI, kg/m 2
BMI, kg/m 2
Linear trend
BMI, kg/m 2
95% CI
Figure 2. Differences between expected and observed cardiopulmonary fitness in women: (a) comparison of trend in peak oxygen
uptake (peak VO2) per kg total weight implied by the weight-ratio standard (mean ml/min/kg) and actually observed values;
(b) comparison of trend in peak VO2 per kg lean mass implied by the lean mass-ratio standard (mean ml/min/kg lean mass) and actually
observed values. Residuals difference between observed peak VO2–peak VO2 expected by the respective standard plotted by basis for
the respective standard (upper panel) and body mass interval (BMI) (lower panel); (c) mean standard, comparison of peak VO2 without
regarding body mass; (d) weight-ratio, comparisons based on peak VO2 divided by kg total weight; (e) lean mass-ratio, comparisons
based peak VO2 divided by kg lean mass. CI: confidence interval.
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1176
European Journal of Preventive Cardiology 22(9)
Table 1. Characteristics of men by body mass index (BMI) category.
18.5–25
<18.5
25–30
Mean
SD
n ¼ 179
69
70
173
23
56
178
2054
29
37
44.0
39.9
n ¼ 295
5
68
7
82
7 173
1
27
6
60
44 182
485 2219
6
27
7
37
30
41.6
27
41.4
Women
n¼6
n ¼ 232
Age, years
66
4
68
Weight, kg
48
3
59
Height, cm
165
6 160
BMI, kg/m2
18
1
23
Lean-mass, kg
41
1
41
Workloadmax, W
97
28 115
VO2max, ml/min
1142 262 1333
VO2max, ml/min/kgd
24
6
23
VO2max, ml/min/kg lean masse
28
6
32
f
METh/week, raw
33.0 22
32.9
METh/week, standardisedg
23.9 15
29.3
n ¼ 223
69
70
160
27
44
115
1421
20
32
29.6
29.6
BMI
Men
n¼0
Age, years
Weight, kg
Height, cm
BMI, kg/m2
Lean-mass, kg
Workloadmax, W
VO2max, ml/min
VO2max, ml/min/kgd
VO2max, ml/min/kg lean masse
METh/week, rawf
METh/week, standardisedg
5
6
6
2
4
30
278
5
6
21
18
Mean
>35
30–35
Linear trenda
All
SD
bb
pc
n ¼ 82
n ¼ 22
n ¼ 578
5
67
5
66
5
68
7
98
8 118
13
82
6 175
6 174
7 174
1
32
1
39
4
27
6
65
6
69
7
60
47 177
43 151
48 179
523 2278 494 2144 353 2174
6
23
5
18
3
27
7
35
7
31
4
36
29
31.1 24
27.7 18
40.4
28
34.4 27
34.1 22
39.7
5
14
6
4
7
46
508
6
7
29
28
0.76
14.68
0.50
4.69
4.37
4.16
83.45
3.26
1.09
5.73
2.09
0.008
< 0.001
0.131
<0.001
<0.001
0.094
0.002
<0.001
0.006
<0.001
0.162
n ¼ 98
n ¼ 33
n ¼ 592
69
5
66
5
68
81
7
97
9
69
159
5 158
5 160
32
1
39
3
27
45
4
48
4
43
116
28 110
26 115
1493 300 1484 309 1399
18
3
15
3
21
33
6
31
6
32
25.5 18
25.3 31
30.0
28.5 19
32.1 40
29.4
5
12
6
5
5
31
320
5
6
21
21
0.14
11.85
0.80
4.92
2.19
0.08
70.07
2.28
0.02
3.07
0.34
0.553
<0.001
0.003
<0.001
<0.001
0.954
<0.001
<0.001
0.944
0.002
0.717
SD
5
6
6
1
5
34
353
5
7
21
20
Mean
SD
Mean
SD
Mean
Peak VO2: peak oxygen uptake; SD: standard deviation.
a
Linear trend over BMI categories. bSlope of regression line. cp-Value for hypothesis of no linear trend. dPeak VO2 in ml/min divided by kg total body
weight ( ¼ weight-ratio standard). ePeak VO2 in ml/min divided by kg lean mass ( ¼ lean mass-ratio standard). fMetabolic Equivalent of Task hours;
1 METh ¼ reference value of 1 kcal *kg1 *h1. gStandardised for body composition.
CI: 31.8–32.9) and 34.6 ml/min (95% CI: 30.0–39.1),
respectively per kg lean mass. Residual analyses show
that neither mean nor weight-ratio standard are independent of body weight, whereas the lean-mass-ratio
standard is independent of lean mass.
Standard-wise comparisons are shown in Table 2.
The mean standard yields an unbiased estimate of cardiopulmonary fitness in 59% of men and 31% of
women. The mean standard is superior to the weightratio standard (p < 0.001). Dividing peak VO2 by body
weight gives an unbiased estimate in 16% of men and
11% of women, respectively. The weight-ratio standard
is inferior to both mean- and lean-mass-ratio standards
(p < 0.001). Dividing peak VO2 by lean-mass estimates
cardiopulmonary fitness without bias for body mass in
58% of men and 100% of women. It is superior to both
mean- and weight-ratio standards in women
(p < 0.001). In men it is superior to the weight-ratio
standard (p < 0.001) and not significantly different
from the mean standard.
Discussion
In our population, dividing peak VO2 by lean mass
implies an association between peak VO2 and kg lean
mass that is very close to the actually observed association. The lean mass-ratio standard, thus, is equivalent to adjusting for lean mass. Obesity, the other
component of the body mass bias, is ruled out as
only lean mass is used as a basis. Therefore, the
remaining trend to lower fitness with increasing BMI
in men represents – strictly speaking – not a bias, but
a true positive association between overweight and
lack of fitness.
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Krachler et al.
1177
Table 2. Standards of cardiorespiratory fitness and their respective bias by body mass.
Unbiased est., %c
n
Men
578
578
578
Women 592
592
592
Unbiased
BMI-intervalb
Standarda
Mean, peak VO2, ml/min
24.2 – 29.9
Weight-ratio, ml/min/kg
26.0 – 27.2
Lean-mass-ratio, ml/min/kg FFM 24.5 – 30.1
24.9 – 28.8
Mean, peak VO2, ml/min
Weight-ratio, ml/min/kg
25.5 – 26.8
Lean-mass-ratio, ml/min/kg FFM 16.8 – 46.5
Unbiased, nd
Comparisone
Correct Overest. Underest. Correct Biased pmod ¼ ref pmod ¼ ref
59
16
58
31
11
100
18
41
17
29
42
0
22
43
24
39
47
0
343
94
338
186
68
592
235
484
240
406
524
0
ref
<0.001
0.765
ref
<0.001
<0.001
<0.001
ref
<0.001
<0.001
ref
<0.001
BMI: body mass index; est.: estimate; FFM: fat-free mass; peak VO2: peak oxygen uptake.
a
Measure, on which comparison of cardiorespiratory fitness is based. bBMI-interval in which 95% confidence interval of mean residuals ( ¼ observedexpected peak VO2) includes zero. cPercentage of study population within/above/below the BMI-interval of unbiased estimate of cardiorespiratory
fitness. dNumber of individuals with correct/biased estimates of cardiorespiratory fitness. eTesting the hypothesis of no difference between current
standard and reference. Based on number of individuals with correct and biased estimate of cardiorespiratory fitness.
Comparison with previous findings
Our findings are in accordance with Batterham et al.16
who, in a study of 1314 adult men, found a linear relationship between lean mass and peak VO2, but not
total body mass. The same conclusion was reached in
a study of 94 young women.19 In contrast to our results,
in a study of 845 men and women,20 regression-based
and lean mass-ratio based values were different. A
likely explanation is the fact that this population was
two decades younger and had therefore a higher peak
VO2 per kg lean mass. This results in steeper slopes for
both regression line and lean mass-ratio, which in turn
increases the distortion caused by the fact that every
ratio is forced through the origin.
Practical relevance
In a clinical context, both prevention and care of cardiopulmonary disease are affected by use of correct standards of cardiopulmonary fitness: Physical activity on
prescription based on assessment of cardiopulmonary
fitness with peak VO2 in ml/min/kg would result in
>80% of the patients being recommended faulty training programmes; either setting unrealistically high goals
– with potentially detrimental effects on motivation and
compliance – or misleading both patients and attending
physicians to believe that little can be gained by further
improvement of cardiopulmonary fitness. For example,
in our population, a training stimulus of 80% of maximal
workload estimated on the base of population means per
kg total weight for men (women) would amount to 203
(127) W and 120 (77) W for subjects with BMI >35 and
BMI 18.5–25, respectively. Corresponding lean mass
based values are 162 (101) W and 132 (86) W. In other
words, ignoring body composition levies a penalty of 41
(26) W on class II obese subjects and grants a bonus of 11
(9) W to normal weight subjects.
Exercise training in diastolic dysfunction,21 timing of
transplantation in heart failure15 and resection of lung
cancer,9 are further examples of effective interventions
depending on correct assessment of cardiopulmonary
fitness. Furthermore, use of peak VO2 cut-offs in ml/
min/kg to identify functional disability6 may result in
misallocation of public funds. Finally, in occupations,
such as the military or fire-fighters, promotion based on
biased fitness tests may be favouring subjects with suboptimal performance.22 Thus, there is a wide range of
practical applications where unbiased assessment of
cardiopulmonary fitness is crucial.
Weight-bearing exercise testing
A potential criticism of the lean-mass approach is its
disregard of performance in weight-bearing exercise.
This is a valid point, if the purpose of measuring fitness
is prediction of performance in weight-bearing exercise.
If, however, fitness is measured to assess an individuals’
health status, ignoring body composition by dividing
peak VO2 with total body weight results in a mixture
of obesity and fitness that precludes valid conclusions
about the role of either.10,15 This applies also to treadmill-based protocols for indirect assessment of peak
VO2, e.g.,23 as current tables for conversion of treadmill time into estimated peak VO2 ignore body-composition and thus penalise obese subjects.
Study limitations and strengths
Our study has a number of limitations: it is concerned
with clinical and epidemiological practice, rather than
physiological theory. Both the weight ratio-standard
and the lean mass ratio-standard imply linear associations. Therefore, we restricted our analyses to comparisons in linear models, rather than modelling the
‘ideal’ association of peak VO2 with weight and lean
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1178
European Journal of Preventive Cardiology 22(9)
mass, respectively. Bioimpedance is not a reference
method for estimation of body composition.
However, a sensitivity analysis, based on the systematic
bias compared to DXA-measurements in a similar
population altered our results only slightly. Numbers
are given in the methods section.
To our knowledge, this is one of the largest population-based samples with objectively measured peak
VO2 and estimation of body composition in the literature. Direct measurement of oxygen consumption
during an incremental exercise stress test is the most
accurate method to determine peak VO2.24,25 BMI is
the most widely used measure of body mass, but has a
number of shortcomings.26,27 In our analysis BMI is
used to compare the obesity-related bias introduced
by the weight-ratio and lean mass-ratio standards.
Using percentage body fat as a measure of obesity
would have favoured the lean mass-ratio standard
even more.
Implications for further research
As body composition is a potential confounder, examples of tables of normal fitness28 should be complemented by lean-mass standardised data. Also,
simplified protocols for estimating peak VO2 that are
based on examples of validations in populations with
uniform (normal-weight) body mass23 need to be revalidated for populations with a wider range of body
composition. Further, examples of observations of joint
effects of fatness and fitness29 need to be re-evaluated,
as most of the evidence is based on measures of fitness
that are not standardised for body composition and
thus preclude conclusions about differential effects of
fitness and obesity.
Conclusion
Dividing peak VO2 by total body weight standardises
only for differences in body size. This may be adequate
in lean athletes but in a general population measures of
fitness need to be standardised for body composition.
Funding
The DR’s EXTRA study was supported by grants from the
Ministry of Education of Finland (116/722/2004, 134/627/
2005, 44/627/2006, 113/627/2007, 41/627/2008), the
Academy of Finland (104943, 211119, 123885), the
European
Commission
FP6
Integrated
Project
(EXGENESIS: LSHM-CT-2004-005272), the City of
Kuopio, the Finnish Diabetes Association, the Finnish
Foundation for Cardiovascular Research, Kuopio
University Hospital, Päivikki and Sakari Sohlberg
Foundation, and the Social Insurance Institution of
Finland. B Krachler was supported by grants from Bruno
Krachler and the Swedish Council for Working Life and
Social Research. K Savonen was supported by a grant from
the Finnish Medical Foundation. None of the above-mentioned funding bodies had any influence on study design,
data collection, analysis or interpretation, nor on the writing
process or the decision to submit the manuscript for
publication.
Conflict of interest
The authors declare that there is no conflict of interest.
References
1. Mark DB and Lauer MS. Exercise capacity: The prognostic variable that doesn’t get enough respect.
Circulation 2003; 108: 1534–1536.
2. Franklin BA, Lavie CJ, Squires RW, et al. Exercise-based
cardiac rehabilitation and improvements in cardiorespiratory fitness: Implications regarding patient benefit. Mayo
Clin Proc 2013; 88: 431–437.
3. Skinner JS, Wilmore KM, Jaskolska A, et al.
Reproducibility of maximal exercise test data in the
HERITAGE family study. Med Sci Sports Exerc 1999;
31: 1623–1628.
4. Barron A, Dhutia N, Mayet J, et al. Test-retest repeatability of cardiopulmonary exercise test variables in
patients with cardiac or respiratory disease. Eur J Prev
Cardiol 2014; 21: 445–453.
5. Vanderburgh PM. Body mass bias in exercise physiology.
In: Zaslav K (ed.) An international perspective on topics in
sports medicine and sports injury. 2012, pp.99–112.
InTech. Available at: http://www.intechopen.com/
books/an-international-perspective-on-topics-in-sportsmedicine-and-sports-injury.
6. Leon AS. Interaction of aging and exercise on the cardiovascular system of healthy adults. Am J Lifestyle Med
2012; 6: 368–375.
7. Heil DP. Body mass scaling of peak oxygen uptake in 20to 79-yr-old adults. Med Sci Sports Exerc 1997; 29:
1602–1608.
8. Balady GJ, Arena R, Sietsema K, et al. Clinician’s guide
to cardiopulmonary exercise testing in adults: A scientific
statement from the American Heart Association.
Circulation 2010; 122: 191–225.
9. Arena R and Sietsema KE. Cardiopulmonary exercise
testing in the clinical evaluation of patients with heart
and lung disease. Circulation 2011; 123: 668–680.
10. Savonen K, Krachler B, Hassinen M, et al. The current
standard measure of cardiorespiratory fitness introduces
confounding by body mass: the DR’s EXTRA study. Int
J Obes (Lond) 2012; 36: 1135–1140.
11. Ekelund U, Franks PW, Wareham NJ, et al. Oxygen
uptakes adjusted for body composition in normalweight and obese adolescents. Obes Res 2004; 12:
513–520.
12. Milani RV, Lavie CJ and Mehra MR. Cardiopulmonary
exercise testing: How do we differentiate the cause of
dyspnea? Circulation 2004; 110: e27–e31.
Downloaded from cpr.sagepub.com at PENNSYLVANIA STATE UNIV on May 18, 2016
Krachler et al.
1179
13. Milani RV, Lavie CJ, Mehra MR, et al. Understanding
the basics of cardiopulmonary exercise testing. Mayo Clin
Proc 2006; 81: 1603–1611.
14. Goran M, Fields DA, Hunter GR, et al. Total body fat
does not influence maximal aerobic capacity. Int J Obes
Relat Metab Disord 2000; 24: 841–848.
15. Osman AF, Mehra MR, Lavie CJ, et al. The incremental
prognostic importance of body fat adjusted peak oxygen
consumption in chronic heart failure. J Am Coll Cardiol
2000; 36: 2126–2131.
16. Batterham AM, Vanderburgh PM, Mahar MT, et al.
Modeling the influence of body size on V(O2) peak:
Effects of model choice and body composition. J Appl
Physiol 1999; 87: 1317–1325.
17. Laukkanen JA, Rauramaa R, Makikallio TH, et al.
Intensity of leisure-time physical activity and cancer mortality in men. Br J Sports Med 2011; 45: 125–129.
18. Volgyi E, Tylavsky FA, Lyytikainen A, et al. Assessing
body composition with DXA and bioimpedance: Effects
of obesity, physical activity, and age. Obesity (Silver
Spring) 2008; 16: 700–705.
19. Vanderburgh PM and Katch FI. Ratio scaling of
VO2max penalizes women with larger percent body fat,
not lean body mass. Med Sci Sports Exerc 1996; 28:
1204–1208.
20. Toth MJ, Goran MI, Ades PA, et al. Examination of
data normalization procedures for expressing peak VO2
data. J Appl Physiol 1993; 75: 2288–2292.
21. Sandri M, Kozarez I, Adams V, et al. Age-related effects
of exercise training on diastolic function in heart failure
with reduced ejection fraction: The Leipzig Exercise
22.
23.
24.
25.
26.
27.
28.
29.
Intervention in Chronic Heart Failure and Aging
(LEICA) Diastolic Dysfunction Study. Eur Heart J
2012; 33: 1758–1768.
Leahy GD. Body mass bias, allometric scaling and military fitness tests. TSAC Report 2011 18.5–18.7 (National
Strength and Conditioning Association).
Pollock ML, Bohannon RL, Cooper KH, et al. A comparative analysis of four protocols for maximal treadmill
stress testing. Am Heart J 1976; 92: 39–46.
American Thoracic Society/ American College of Chest
Physicians. ATS/ACCP Statement on cardiopulmonary
exercise testing. Am J Respir Crit Care Med 2003; 167:
211–277.
Palange P, Ward SA, Carlsen KH, et al.
Recommendations on the use of exercise testing in clinical practice. Eur Respir J 2007; 29: 185–209.
Okorodudu DO, Jumean MF, Montori VM, et al.
Diagnostic performance of body mass index to identify
obesity as defined by body adiposity: A systematic review
and meta-analysis. Int J Obes (Lond) 2010; 34: 791–799.
Norgan NG. Population differences in body composition
in relation to the body mass index. Eur J Clin Nutr 1994;
48: S10–S25; discussion S6–S7.
Hakola L, Komulainen P, Hassinen M, et al.
Cardiorespiratory fitness in aging men and women: The
DR’s EXTRA study. Scand J Med Sci Sports 2011; 21:
679–687.
Barry VW, Baruth M, Beets MW, et al. Fitness vs. fatness
on all-cause mortality: A meta-analysis. Prog Cardiovasc
Dis 2014; 56: 382–390.
Downloaded from cpr.sagepub.com at PENNSYLVANIA STATE UNIV on May 18, 2016