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Influence of Body Composition, Hemoglobin Concentration, and Cardiac


Size and Function of Gender Differences in Maximal Oxygen Uptake in
Prepubertal Children

Article in Chest · November 2003


DOI: 10.1378/chest.124.4.1494 · Source: PubMed

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Influence of Body Composition,
Hemoglobin Concentration, and Cardiac
Size and Function of Gender
Differences in Maximal Oxygen Uptake
in Prepubertal Children*
Agnès Vinet, PhD; Stéphane Mandigout, PhD; Stéphane Nottin, PhD;
LongDang Nguyen, MD; Anne-Marie Lecoq, MD; Daniel Courteix, PhD; and
Philippe Obert, PhD

Objective: To determine the relative contribution of the gender difference in body composition,
blood hemoglobin concentration, and cardiac dimension and function at rest and exercise of the
gender difference in maximal oxygen uptake (V̇O2max) in 10- to 12-year-old children.
Subjects: Thirty-five healthy children (17 girls and 18 boys; mean ! SD age, 10.5 ! 0.4 years).
Experimental design: An anthropometric evaluation (body surface area, body fat content, and lean
body mass [LBM]), assessment of hemoglobin concentration, echocardiographic evaluation at
rest (left ventricular dimensions, and diastolic and systolic indexes at rest), and cardiovascular
evaluation during a maximal cycle exercise (stroke volume [SV], total peripheral resistance).
Results: The boys exhibited a higher mass-relative V̇O2max than the girls (47.9 mL/kg/min vs 40.9
mL/kg/min, respectively); but when normalized for LBM (allometric equation), the difference
totally disappeared (19.0 mL/kg LBM1.33/min vs 18.9 mL/kg LBM1.33/min, respectively). No
significant gender differences were seen in maximal heart rate and arteriovenous oxygen
difference; however, maximal SV (SVmax) was significantly higher in boys than in girls, but when
expressed relative to LBM, the difference was no longer significant.
Conclusions: These findings demonstrate that contrary to adults, the sole limiting factor of V̇O2
that distinguished boys from girls was a lower SVmax in the latter; however, this gender
difference totally disappeared when normalized for LBM. Consequently, the gender difference
in heart size and cardiac function during exercise should be interpreted as only one aspect of the
lower LBM in girls and not as reflective of a more basic functional gender difference.
(CHEST 2003; 124:1494 –1499)

Key words: cardiac size; children; maximal oxygen uptake; stroke volume

Abbreviations: A ! peak velocity of atrial contraction filling; BSA ! body surface area; DAVO2 ! arteriovenous
oxygen difference; E ! peak velocity of early diastolic rapid inflow; EF ! ejection fraction; HR ! heart rate;
IVST ! interventricular septal thickness; LBM ! lean body mass; LVID ! left ventricular end-diastolic dimension;
LVM ! left ventricular mass; PWT ! posterior wall thickness; Q ! cardiac output; SF ! shortening fraction;
SV ! stroke volume; SVmax ! maximal stroke volume; TPR ! total peripheral resistance; V̇o2 ! oxygen uptake;
V̇o2max ! maximal oxygen uptake; VTI ! velocity curve over time

*From Laboratoire de Physiologie des Adaptations Cardiovascu-


laires à l’exercice (Drs. Vinet, Nottin, and Obert), Avignon;
I (V̇o
n the exercising human, maximal oxygen uptake
max) can be potentially limited by each step
2

Laboratoire de la Performance Motrice (Drs. Mandigout and


of the oxygen pathway from the atmosphere to the
Courteix), Orléans; and Laboratoire d’Exploration Fonctionnelle mitochondria: (1) the pulmonary diffusing capacity,
Respiratoire (Drs. Nguyen and Lecoq), Orléans, France. (2) the cardiovascular system, (3) the oxygen-carry-
Manuscript received April 30, 2002; revision accepted March 27, ing capacity of the blood, and (4) the muscle oxida-
2003.
Reproduction of this article is prohibited without written permis- tive characteristics. Of particular importance is the
sion from the American College of Chest Physicians (e-mail: cardiac system (function and/or size).1
permissions@chestnet.org). In adults, gender difference in V̇o2max is usually
Correspondence to: Agnès Vinet, PhD, Laboratoire de Physiologie reported with higher values in men than in women
des adaptations cardio-vasculaires à l’exercice, Département
STAPS, Faculté des Sciences, 33 Rue Louis Pasteur, 84000 whether V̇o2max is expressed in absolute terms or
Avignon, France; e-mail: agnes.vinet@univ-avignon.fr relative to body mass. Expressing V̇o2max relative

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to fat-free mass or lean body mass (LBM) re- Materials and Methods
duces but does not eliminate this difference.2
Other factors mainly linked to the oxygen-carrying Subjects
capacity and cardiac size have been shown to Thirty-five healthy children (17 girls and 18 boys) participated
contribute significantly to this gender-related dif- in the entire experiment. All were volunteers from a local school
ference.2–5 who were examined clinically on the day of the test, and their
In prepubertal children, results in the literature pubertal status was assessed.14 Any child exhibiting signs of
pubertal development was excluded from taking part. This study
are much more controversial than in adults. When received approval from the local ethics committee, and written
body size is taken into account, few studies re- informed consent was obtained from all the children’s parents.
ported similar V̇o2max in boys and girls6; however, All children were active but not participating in formal training or
V̇o2max was reported as being lower in the lat- organized sports.
ter.7–9 A difference in body composition and espe- Experimental Procedures
cially in body fat mass content could explain these
results. Sunnegardh and Bratteby10 and Rowland Firstly, an anthropometric evaluation, a capillary blood sample
for the measurement from blood hemoglobin concentration, and
et al9 reported V̇o2max relative to fat-free mass M-mode, two-dimensional, and pulsed-wave Doppler echocardi-
(estimated from the indirect method of skinfold ography analyses were conducted at rest in the supine position.
thickness) statistically higher in boys than in girls. Then, cardiovascular and bioenergetic data were evaluated dur-
Whether the same factors as those reported in ing an upright maximal exercise test.
Anthropometric Variables: Body height and mass were mea-
adults in order to explain the gender-related dif- sured with a wall stadiometer and a calibrated foot balance,
ference in V̇o2max are involved in children re- respectively. In addition, percentages of body fat mass and LBM
mains to be elucidated. According to the Fick were assessed by means of dual radiograph absorptiometry on a
equation, gender differences must be explained by Hologic QDR-1000/W (Hologic; Waltham, MA).
Doppler Echocardiographic Measurements: At rest, the chil-
variance in heart rate (HR), stroke volume (SV), dren were examined by M-mode, two-dimensional, and Doppler
and arteriovenous oxygen difference (DAVO2). echocardiographic analyses on a Kontron Sigma HVD44 ultra-
Cardiac output (Q̇) at a given submaximal work sound imaging system (Kontron Medical; Plaisir, France), incor-
rate has been reported to be higher,11 lower,12 or porating a 3.5-MHz annular array transducer. Investigations were
performed at rest with subjects in a supine position. Subjects
the same6,13 in boys compared to girls. Most remained in this position for at least 15 min prior to the
literature studies reported that SV was higher and examination. All echocardiographic measurements and calcula-
HR was lower in boys than in girls at a given tions were obtained according to standard procedures recom-
absolute submaximal rate. At maximal exercise, mended by the American Society of Echocardiography, using the
leading-edge-to-leading-edge method. Methodology used was
only SV differentiated boys from girls.6,9 Such a previously described in Obert et al.15 The echocardiographic
gender effect was attributed by certain authors to parameters measured or derived included the following: left
a higher left ventricular mass (LVM) in boys,6 ventricular end-diastolic dimension (LVID), posterior wall thick-
whereas others9 did not observe any difference in ness (PWT) at end diastole, interventricular septal thickness
(IVST) at end diastole, left ventricular shortening fraction (SF),
resting echocardiographic measures. To the best and ejection fraction (EF). LVM was calculated according to the
of our knowledge, only Rowland et al9 focused on formula of Devereux et al.16
the impact of cardiac function and size as well as Moreover, the following measurements and calculations were
body composition on the gender-related differ- made: peak velocity of early diastolic rapid inflow (E), peak
velocity of atrial contraction filling (A), and E/A ratio. Where
ence in V̇o2max in children. These authors showed appropriate, measurements were expressed relative to the indi-
that cardiac functional capacity (ie, SV) as well as vidual subject’s body surface area (BSA)17 according to the
body composition account for the differences in recommendation of Daniels et al.18 The maximal systolic diam-
V̇o2max between prepubertal boys and girls. eter of the ascending aorta was also measured at rest before each
test by two-dimensional echocardiography in the parasternal
Thus, it is not clear how the gender differences in long-axis view with the subject in a pedaling position. The
overall cardiac dimension are related to the gender measurement was recorded from inner to inner edge at the level
difference in V̇o2max, and it is unknown whether of the insertion of the aortic valve leaflets. The resting value,
heart size differences between boys and girls reflects assuming not to change during exercise, was used for all resting
and exercise SV calculations.19
only the general body size (in particular of LBM), or During exercise, SV and Q̇ were estimated using the standard
if more fundamental functional differences exists. Doppler echocardiography technique, according to the method-
This study was therefore designed to determine the ologic procedure used by Rowland et al.20 The feasibility and
relative contribution of the potential gender differ- accuracy of this technique as a method for noninvasively mea-
ence in body composition, blood hemoglobin con- suring SV and Q̇ during exercise was previously investigated in
children in our laboratory.21 Briefly, SV was estimated as the
centration, and cardiac dimension and function at product of the aortic root area and integral of ascending blood
rest and exercise to the gender difference in V̇o2max velocity and time. The velocity of blood in the ascending aorta
in 10- to 12-year-old children. was recorded with a 2.0-MHz continuous-wave Doppler trans-

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ducer (Pedof; Kontron Medical) directly from the suprasternal (mass, BSA or LBM), and a is a constant multiplier. To obtain b,
notch. The outline contour of the velocity curve over time (VTI) log transformation of both the Y and the X was performed,
was traced manually. The end of each VTI was taken as the and least-squares regression identified b in the equation
observed closure of the aortic valve. Values for VTI were log(Y) ! log(a) ' blog(X). Differences between maximal cardio-
averaged from five to seven curves, with the highest values vascular variables were determined by analysis of covariance with
demonstrating crisp spectral envelopes. The cross-sectional area LBM as covariate. The comparison of cardiac variables in the
of the ascending aorta was calculated from the mean diameter, boys and the girls during rest and exercise was performed by a
considering the aorta to be circular. The following derived two-way analysis of variance (sex, intensity) with repeated mea-
variables were calculated from primary measurements: sures. When a significant interaction was found, a post hoc
SV ! VTI " aortic root area; Q̇ ! SV " HR. DAVO2 was calcu- Scheffe test was used. Regression equations between Q̇ and V̇o2
lated as V̇o2Q̇. were calculated from submaximal values, and the differences in
All records were analyzed blindly on 2 separate days by an terms of the slopes and intercepts were evaluated by a covariance
experienced operator as well as on another day by a different of heterogeneous regression lines (SPSS; Chicago, IL). Statistical
cardiologist in order to assess intraobserver and interobserver significance for all analyses was defined as p # 0.05.
variability, respectively. Since both intraobserver and interob-
server variability for the overall cardiac variables were low
(# 6%), values presented were those obtained by the first
cardiologist. Results
Maximal Exercise Protocol: Each child performed a continuous
and progressive exercise test to exhaustion on a bicycle ergometer
The physical characteristics of the children are
(Ergomeca; Toulon, France). During the test, the pedaling rate reported in Table 1. No significant differences were
was maintained constant at 70 revolutions per minute. After a observed between the boys and girls in height and
resting period sitting on the bicycle and a 3-min, 35-W warm-up body mass. Girls tended to have higher body fat mass
period, 17.5-W increments were applied in 3-min stages until the content, but the difference failed to reach statistical
pedaling rate could no longer be sustained. Cardiovascular
evaluation was performed during the final minute of each
significance; however, LBM was higher in the boys
workload and during the last minute of the test. During the first than in girls. Hemoglobin concentration was similar
30 s of the final minute of each workload, BP was measured. in both groups.
Then, during the following 30 s, Q was assessed by the Doppler Resting echocardiographic data are outlined in
technique. Table 2. The aortic diameter was higher in the boys
Expired Gas Analysis: Oxygen uptake (V̇o2), ventilation, and
respiratory exchange ratio were determined continuously by
than in the girls, but when expressed relative to
means of a gas analysis system (MedGraphics CPXD; Medical LBM0.208, the difference was no longer significant
Graphics Corporation; St. Paul, MN); inspired and expired gas between groups. The systolic function index, as
flow were monitored by means of a pneumotachograph con- estimated from SF and EF, and the diastolic func-
nected to a MedGraphics respiratory flow transducer. Gas con- tion index, as evaluated from E and A, and E/A ratio
centrations were evaluated using rapidly responding gas analyz-
ers. Before each test, the gas analyzers were calibrated against
were similar in the two groups. The boys had
precision analyzed gas mixture (CO2, 4%; O2, 15%; precision, significantly higher LVID, PWT, IVST, and LVM
0.1% certified by the manufacturer). V̇o2max was achieved when expressed in absolute terms and relative to BSA than
three of the following criteria were respected: (1) a HR at a value the girls; however, when expressed relative to LBM
close to the theoretical maximal HR (210 $ 0.65 " age), (2) the (allometric equation), all the above variables were no
stability of V̇o2 in spite of the increase in workload, (3) the
impossibility for the subject to maintain the pedaling rate, and
longer significantly different between groups.
(4) a respiratory exchange ratio % 1.1. Physiologic variables at maximal exercise are pre-
BP Measurements: Auscultatory cuff BP was obtained in sented in Table 3. No significant differences were
the left arm using manual sphygmomanometry according to the observed either in maximal HR, maximal DAVO2, and
report of the second task force on BP control in children.22 The maximal TPR between the boys and girls. Mean
first Korotkoff sounds defined systolic pressure, and the fourth
Korotkoff sounds (muffling of the sound) defined diastolic pres-
V̇o2max expressed in absolute terms and relative to
sure. Mean arterial pressure was calculated as one third of the body mass were significantly higher in the boys than in
pulse pressure plus the diastolic pressure. Total peripheral
resistance (TPR) was calculated as the quotient of mean arterial
pressure divided by Q̇.
Table 1—Physical Characteristics of the Subjects
Statistical Analysis Boys (n ! 17) Girls (n ! 18)

The results are presented as mean & SD. Two submaximal Variables Mean SD Mean SD
exercise intensities were chosen at approximately 60% and 80%
Age, mo 126.9 3.8 126.6 5
of V̇o2max. Nonparametric test comparisons of physical charac-
Height, cm 143.6 4.6 139 5.8
teristics and cardiovascular variables between boys and girls were
Body mass, kg 37.9 5.4 34.5 5.5
performed after values were adjusted to body size by traditional
Body fat mass, % 20.05 7.9 23.4 5.8
anthropometric measures (body mass, BSA) and by allometric-
LBM, kg 30.5* 1.9 25.7 2.8
derived anthropometric variables calculated from these specific
BSA, m2 1.22 0.12 1.19 0.12
subject populations. In the latter analysis, the scaling exponent b
Hemoglobin, g/dL 13.4 1.5 13.9 1.3
was identified in the allometric equation Y ! aXb, where Y is the
physiologic variable, X is the anthropometric scaling variable *Significant difference (p # 0.05) between boys and girls.

1496 Clinical Investigations

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Table 2—Echocardiographic Data* Table 3—Physiologic Variables at Maximal Exercise

Boys Girls Boys Girls

Variables Mean SD Mean SD Variables Mean SD Mean SD

Aortic diameter HR, beats/min 200 8 203 6


mm 16.5† 0.7 15.8 0.8 V̇o2
mm BSA0.5 18.3† 1.3 17.0 1.3 mL/min 1801* 279 1422 273
mm/kg 8.2 0.3 8.1 0.4 mL/kg/min 47.9* 7 41.7 7.4
LBM0.208 mL/kg LBM/min 58.7 8 55.1 6.7
LVIDd mL/kg LBM1.33/min 19.0 2.5 18.9 2.2
mm 43† 3 40.3 2 SV
mm BSA0.5 37.5† 1.5 38.8 1.6 mL 64.1* 10.1 53.9 6.8
mm/kg 11.1 0.5 10.9 0.5 mL/m2 52.1* 6.1 47 6.6
LBM0.401 mL/kg LBM0.792 4.4 0.6 4.2 0.4
IVSTd Q̇
mm 6.8† 1.1 5.8 0.7 L/min 12.8* 2.3 10.9 1.4
mm BSA0.5 6.1† 0.9 5.4 0.7 L/min/m2 10.4* 1.4 9.5 1.4
mm/kg 0.9 0.1 0.9 0.1 L/min/kg LBM0.763 0.97 0.16 0.94 0.1
LBM0.572 DAVO2, mL/100 mL 14.2 2.2 13 2.1
PWTd TPR, U 7.1 1.1 7.4 1.1
mm 6.3† 0.7 5.5 0.8
*Significant difference (p # 0.05) between boys and girls.
mm BSA0.5 5.7† 0.6 5.1 0.7
mm/kg 0.7 0.1 0.6 0.1
LBM0.651
LVM
g 83.1† 20.8 61.5 10.4 SV kinetics from rest to maximal exercise are pre-
g BSA1.5 55.1† 11.1 42.0 9.1 sented in Figure 1. For both boys and girls, SV
g/kg 0.59 0.1 0.54 0.1 increased significantly from rest to moderate intensity
LBM1.455 and then reached a plateau; however, the SV pattern in
EF, % 72.1 5.8 71.9 5.04
SF, % 35.0 5.0 34.7 4.1
boys was displaced upward when compared to girls.
E, cm/s 93.4 9.1 96.3 15 Moreover, the maximal SV (SVmax)/SV at rest ratio was
A, cm/s 46.4 1.1 48.3 8.4 similar in the two groups (boys, 1.39 & 0.19; girls,
E/A ratio 2.1 0.1 2.04 0.4 1.40 & 0.21; not significant). The regression equations
TVI-T, cm/s 21.5 3.1 20.9 4.2 between Q̇ (liters per minute) and V̇o2 (liters per
*LVIDd ! left ventricular internal diameter in diastole; minute) were as follows:
IVSTd ! IVST at end diastole; PWTd ! posterior wall thickness at
end distaole; TVI-T ! TVI of the total diastolic filling period. Boys Q̇ ! 3.04 ' (6.14 " V̇o2)
†Significant difference (p # 0.05) between boys and girls.
Girls Q̇ ! 2.27 ' (7.12 " V̇o2)
The slopes as well as the intercepts of these two
the girls. When normalized to LBM, V̇o2max was no relationships were not significantly different be-
longer significantly different between groups. More- tween the two groups.
over, when LBM was statistically controlled as covari-
ate, mean absolute V̇o2max was similar in both groups.
At rest, the boys and the girls exhibited similar Q Discussion
with, however, higher HR and lower SV in girls than
in boys. Moreover, when HR was statistically con- The major finding of the present study was that
trolled as covariate, SV was still significantly different gender differences in V̇o2max in children were due
between the boys and girls. principally to absolute SV differences given that HR
During exercise, whatever the relative intensity and DAVO2 were similar in boys and girls. However,
(ie, 60%, 80%, and maximum), the boys demon- allometric normalization of absolute SV for LBM
strated larger absolute and BSA relative values for totally eliminated this gender difference, and accord-
SV than girls; however, HR values were similar in ing to power calculation the group size was suffi-
the two groups. Consequently, absolute and BSA- cient. Consequently, gender difference in V̇o2max in
relative Q̇ at high intensity (ie, 80%) and maximal children only appears to be a reflection of differ-
intensities were higher in boys than in girls. When ences in body composition but not in cardiac func-
expressed relative to LBM (allometric equation), tional capacity.
both SV and Q̇ were no longer different between the The magnitude of gender difference in aerobic
boys and girls. Such results were confirmed by the fitness in this sample of subjects reflects that ob-
analysis of covariance using LBM as covariate. served in previous studies in children. The boys

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Figure 1. Mean (SD) SV at rest, and during submaximal and maximal exercise in boys and girls.
*Significant difference (p # 0.05) between boys and girls.

exhibited a higher mass-relative V̇o2max than girls impact of body composition and cardiac size and
(47.9 mL/kg/min vs 40.9 mL/kg/min, respectively). function in prepubertal boys and girls.9 Rowland et
Higher V̇o2max in 11- to 12-year-old boys than in al9 also reported that gender-related difference in
girls was already reported by Miyamura and Honda23 V̇o2max in children was only a reflection of higher
(46.8 mL/kg/min vs 41.6 mL/kg/min, respectively) and SVmax in boys than in girls. They reported, however,
by Rowland et al9 (47.2 mL/kg/min vs 40.4 mL/kg/min, that cardiac functional capacity as well as body
respectively) on cycle testing. In the present study, composition account for the differences in V̇o2max
differences in body composition were essentially between prepubertal children. Indeed, differences
responsible for this gender difference. Indeed, after between boys and girls regarding SVmax were re-
allometric normalization of absolute V̇o2max for duced but still persisted after body size and compo-
LBM (Table 3), differences between our boys and sition (ie, fat-free mass) were taken into account,
girls totally disappeared (1%, not significant). Such which disagree therefore with the results of our
an influence of body composition on gender differ- experiment.
ences in V̇o2max has been already reported in SV depends largely on cardiac size and function.
previous studies.9,10 In our study, girls exhibited reduced cardiac dimen-
In the present work, among the limiting physio- sions (LVID, IVST, and PWT) and LVM when
logic factors of V̇o2max, only SV was significantly compared to boys. Similar results were reported by
different in the boys and girls. Indeed, hemoglobin Turley and Wilmore6 (78.8 g vs 66 g, respectively). In
concentration was similar between both genders our work, LVM was moreover significantly corre-
(13.4 g/dL and 13.9 g/dL, respectively), which agrees lated with SVmax (r ! 0.44, p # 0.05). Thus, it is
with previous studies in children6,12 and could ex- likely that differences in cardiac size may mainly
plain in part the similar submaximal and maximal contribute to the lower SV at rest and during exercise
DAVO2 in these two groups. Maximal HR was in girls. The reduced cardiac size in our girls,
similar in the boys and girls; consequently, the however, seems to be principally a reflection of their
gender difference in SVmax was responsible for reduced overall body size and especially LBM. In-
virtually all of the effect of gender on maximal Q̇ and deed, when SV, left ventricular dimensions, and
then V̇o2max. These results differ from those in LVM were expressed relative to LBM (allometric
adults showing that both central cardiac factors and equation), differences between boys and girls were
peripheral ones, mainly associated with the dimin- no longer significant. Batterham et al5 already re-
ished oxygen-carrying capacity in women, are in- ported reduced but still significant differences in
volved in order to explain the gender-related differ- LVM values when expressed relative to LBM (allo-
ence in V̇o2max.2 However, our results are in metric equation) in adults. Rowland et al9 did not
accordance with the only study9 that investigated the observe any differences in resting left ventricular

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