Journal of the American College of Cardiology
© 2009 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 54, No. 25, 2009
ISSN 0735-1097/09/$36.00
doi:10.1016/j.jacc.2009.08.030
QUARTERLY FOCUS ISSUE: PREVENTION/OUTCOMES
Atherosclerosis Markers and Physical Activity in Children
Physical Activity Reduces Systemic Blood
Pressure and Improves Early Markers of
Atherosclerosis in Pre-Pubertal Obese Children
Nathalie J. Farpour-Lambert, MD,* Yacine Aggoun, MD,* Laetitia M. Marchand, MS,*
Xavier E. Martin, MS,* François R. Herrmann, MD, MPH,† Maurice Beghetti, PD*
Geneva, Switzerland
Objectives
The aim of this study was to determine the effects of physical activity on systemic blood pressure (BP) and early
markers of atherosclerosis in pre-pubertal obese children.
Background
Hypertension and endothelial dysfunction are premature complications of obesity.
Methods
We performed a 3-month randomized controlled trial with a modified crossover design: 44 pre-pubertal obese
children (age 8.9 ⫾ 1.5 years) were randomly assigned (1:1) to an exercise (n ⫽ 22) or a control group (n ⫽ 22).
We recruited 22 lean children (age 8.5 ⫾ 1.5 years) for baseline comparison. The exercise group trained 60 min
3 times/week during 3 months, whereas control subjects remained relatively inactive. Then, both groups trained
twice/week during 3 months. We assessed changes at 3 and 6 months in office and 24-h BP, arterial intimamedia thickness (IMT) and stiffness, endothelial function (flow-mediated dilation), body mass index (BMI), body
fat, cardiorespiratory fitness (maximal oxygen consumption [VO2max]), physical activity, and biological markers.
Results
Obese children had higher BP, arterial stiffness, body weight, BMI, abdominal fat, insulin resistance indexes, and
C-reactive protein levels, and lower flow-mediated dilation, VO2max, physical activity, and high-density lipoprotein
cholesterol levels than lean subjects. At 3 months, we observed significant changes in 24-h systolic BP (exercise
⫺6.9 ⫾ 13.5 mm Hg vs. control 3.8 ⫾ 7.9 mm Hg, ⫺0.8 ⫾ 1.5 standard deviation score [SDS] vs. 0.4 ⫾ 0.8
SDS), diastolic BP (⫺0.5 ⫾ 1.0 SDS vs. 0 ⫾ 1.4 SDS), hypertension rate (⫺12% vs. ⫺1%), office BP, BMI z-score,
abdominal fat, and VO2max. At 6 months, change differences in arterial stiffness and IMT were significant.
Conclusions
A regular physical activity program reduces BP, arterial stiffness, and abdominal fat; increases cardiorespiratory fitness; and delays arterial wall remodeling in pre-pubertal obese children. (Effects of Aerobic Exercise Training on Arterial Function and Insulin Resistance Syndrome in Obese Children: A Randomized Controlled Trial; NCT00801645)
(J Am Coll Cardiol 2009;54:2396–406) © 2009 by the American College of Cardiology Foundation
The rising prevalence of childhood obesity represents a
major public health crisis, because it is associated with
considerable risks to the child’s present and future health
(1). The appearance of pediatric forms of chronic diseases
such as hypertension (HTN), early signs of atherosclerosis,
or type 2 diabetes contributes to increased risks in adult life
(2– 4). Hypertension is indeed considered the most impor-
From the *Pediatric Cardiology Unit, Department of Child and Adolescent, and
†Biostatistics, Department of Rehabilitation and Geriatrics, University Hospitals of
Geneva and University of Geneva, Geneva, Switzerland. This work was supported by
the Swiss National Science Foundation (#3200B0-103853), Bern, and the Geneva
University Hospitals Research and Development Fund.
Manuscript received April 25, 2009; revised manuscript received July 27, 2009,
accepted August 6, 2009.
tant cardiovascular disease (CVD) risk factor worldwide,
contributing to one-half of the coronary heart disease and
approximately two-thirds of the cerebrovascular disease
burdens (5).
See page 2407
In children and adolescents, body mass index (BMI) is
strongly related to high blood pressure (BP) (6 – 8), and the
prevalence of HTN ranges from 47% to 62% in obese
pediatric patients (9 –11). Several factors are believed to
contribute to increased vascular tone in obese individuals,
including activation of the sympathetic nervous system
(12–15), insulin resistance (16,17), and endothelial and
smooth muscle cell dysfunctions (18 –21).
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
The structure and function of large arteries can now be
assessed by noninvasive, high-resolution ultrasound, and
endothelial dysfunction is considered an early marker of
atherosclerosis that precedes the plaque formation (19,22).
We and others demonstrated impaired arterial endothelial
and smooth muscle cell functions and the presence of
arterial stiffness in obese children and adolescents (18 –20,
23). Vascular dysfunction develops even before puberty, in
association with elevated systemic BP (21), whereas increased intima-media thickness (IMT) appears later during
puberty. The appearance of HTN and first signs of atherosclerosis in young obese children forecasts a major health
burden and a need for early intervention strategies.
The benefits of physical activity in the prevention and
treatment of cardiovascular diseases have been very well
described in adults (24). Individuals who perform regular
physical activity have a lower risk of HTN (25), and both
acute and chronic physical activity lower BP in patients with
HTN, including those who are obese (26). On the contrary,
low cardiorespiratory fitness is associated with a 1.3- and
2.6-fold increased risk for HTN in lean and overweight
young adults, respectively (27). In children, a recent
population-based study demonstrated that higher levels
of physical activity were associated with lower BP, and
results suggested that the volume was more important
than the intensity (28). However, the cross-sectional
design did not allow establishing the causality.
Obese children usually spend less time in moderate and
vigorous physical activities and have lower cardiorespiratory
fitness that their non-obese counterparts (29). The treatment usually includes exercise, dietary, and behavioral interventions. However, most randomized controlled trials
were designed to assess the effects of combined lifestyle
changes in obese youth (23,30), and only a few authors
investigated the impact of exercise alone (31–36). In obese
adolescents, they reported significant changes in body fat or
visceral fat, endothelial function, IMT, parasympathetic
nervous activity, lipids profile, and insulin resistance indexes. However, the effects of physical activity on systemic
BP remain controversial, and to our knowledge, there is no
information in children before puberty.
Therefore, the primary purpose of this study was to
determine the effects of a physical activity program on
systemic BP and early markers of atherosclerosis (endothelial and smooth muscle cell functions, IMT, and arterial
stiffness) in pre-pubertal obese children.
Methods
Study design and subjects. We performed a randomized
controlled trial including 44 pre-pubertal obese children
ages 6 to 11 years. All patients were recruited at the Obesity
Clinic of the Children’s Hospital of Geneva, if their BMI
was over the 97th age- and sex-specific percentile (37). To
allow baseline comparison, we recruited 22 lean volunteers
among 165 children in a local elementary school, if their
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
2397
BMI was within the normal
Abbreviations
and Acronyms
range. During the first visit, we
assessed pubertal stage by clinical
ANCOVA ⴝ analysis of
examination according to the
covariance
method of Tanner, and subjects
ANOVA ⴝ analysis of
with a stage above 1 were exvariance
cluded. With these restrictive exBMI ⴝ body mass index
clusion criteria, we do not have
CVD ⴝ cardiovascular
to consider the effect of sex on
disease
body fat gain at the time of
DBP ⴝ diastolic blood
puberty, generally observed in
pressure
adolescent girls (38). Subjects
Einc ⴝ incremental elastic
were excluded if they: 1) were
modulus
involved in any weight control,
FMD ⴝ flow-mediated
dilation
physical activity, or behavioral
therapy; 2) had a familial history
HDL-C ⴝ high-density
lipoprotein cholesterol
of dyslipidemia or essential
HOMA-IR ⴝ homeostasis
HTN; 3) took any medications
assessment model of
or hormones that might influinsulin resistance
ence cardiovascular function,
HTN ⴝ hypertension
body composition, or lipid or
IMT ⴝ intima-media
glucose metabolism; 4) had an
thickness
orthopedic affection limiting
LDL-C ⴝ low-density
physical activity; 5) had a genetic
lipoprotein cholesterol
disorder or a chronic disease; or
NTGMD ⴝ nitroglycerin6) followed a therapy for psychimediated dilation
atric problems.
SBP ⴝ systolic blood
The Mother and Child Ethics
pressure
Committee of the University HosSDS ⴝ standard deviation
pitals of Geneva approved this
score
study, and informed written conTC ⴝ total cholesterol
sent was obtained from both parTG ⴝ triglyceride
ent and child.
VO2max ⴝ maximal oxygen
Intervention. After the initial
consumption
evaluation, the 44 eligible obese
subjects were randomly assigned
(1:1) to an exercise (EX, n ⫽ 22) or control (CON, n ⫽ 22)
group (Fig. 1). We used closed envelopes containing 50%
exercise and 50% control group assignments. The randomization process resulted in a similar girl/boy ratio in each
group.
The 3-month intervention consisted of a physical activity
program including 3 60-min sessions/week after school
hours (total 180 min/week in addition to physical education
135 min/week), without any dietary intervention. Training
sessions were supervised by 2 experienced physical education
teachers and consisted of 30 min of aerobic exercise (fast
walking, running, ball games, or swimming) at a heart rate
corresponding to 55% to 65% of individual maximal cardiorespiratory fitness (based on baseline maximal oxygen consumption [VO2max] measures by treadmill test), followed
by 20 min of strengthening exercises and 10 min of
stretching and cool-down. Children wore a heart rate
monitor (Polar S610, Kempele, Finland) during each training session, and watch alarms warned them if the heart rate
was too low (⬍55% VO2max) or too high (⬎65%
2398
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
55 obese children assessed for eligibility
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
165 lean children assessed for eligibility
143 Excluded
141 Declined Study Participation
2 Did Not Meet Inclusion Criteria
11 Excluded
8 Declined Study Participation
3 Did Not Meet Inclusion Criteria
44 obese children randomized
Figure 1
22 Randomized to
Exercise Group
22 Randomized
to Control Group
Status at 3-mo follow-up
22 Received Intervention
as Assigned
Status at 3-mo follow-up
19 Received Intervention
as Assigned
3 Dropped-out
2 Lost Interest
1 Transportation
Status at 6-mo follow-up
18 Continued Intervention
as Assigned
4 Dropped-out
2 Transportation
1 Lost interest
1 Family Issue
Status at 6-mo follow-up
18 Started Exercise
4 Dropped-out
1 Too Hard to Adhere
2 Transportation
1 Lost interest
22 included in analysis
22 included in analysis
22 lean children
for baseline comparison
Flowchart for Enrollment, Randomization, and Follow-Up of Study Participants
VO2max). The aerobic period was followed by strengthening exercises of the arms, legs, and trunk (2 to 3 series of 10
to 15 repetitions), with the resistance being provided by the
child’s own body weight and elastic bands. Subject compliance to training was determined as the proportion of
attended sessions, and adherence was determined as the
proportion of subjects who completed all training and
testing sessions. The CON group did not participate in any
intervention and was asked to maintain the current level of
physical activity during the first 3 months. After the
3-month intervention, the EX group was invited to continue to exercise twice/week for a total of 6 months. The
CON group was also asked to start a similar training
program (twice/week) after the 3-month control period
(modified crossover design), to avoid a long waiting period
before receiving treatment.
Procedures. At baseline, participants visited the Children’s
Hospital from 8:00 AM to 12:00 AM. Obese and lean subjects
underwent identical testing, and the protocol was repeated
twice at 3 and 6 months in obese patients only. Observers
were blinded to subject grouping. We measured body
weight to the nearest 0.1 kg with light clothes with an
electronic scale (Seca 701, Hamburg, Germany) and height
to the nearest 0.1 cm with a Harpenden stadiometer. We
calculated BMI as weight/height squared (kg ⫻ m⫺2) and
determined BMI z-scores (37). Total body and abdominal
fat mass and fat-free mass (kg) were assessed with dualenergy X-ray absorptiometry (DXA, GE Lunar Prodigy,
Lunar Corp., Madison, Wisconsin). Manual analysis, with
the “regions of interest” feature, was performed on total
body scans to assess abdominal fat. The upper border was
defined as the distal margin of the lower ribs, and the lower
border was defined as just superior to the supra-iliac crest.
The lateral margins were placed outside the body, so that all
abdominal but no arm tissue was included (39). The
intra-class correlation for repeated measurements of body
fat mass was 0.998 in our laboratory.
The brachial resting BP was measured 3 times at a 2-min
interval after 10 min of rest in supine position with the back
supported, with a validated automated device (Colin PressMate BP 8800C, San Antonio, Texas). The cuff covered at
least two-thirds of the length of the upper arm, with the
length of the bladder wrapping the arm circumference. The
average BP was calculated, and HTN was defined as BP
⬎95th sex-, age-, and height-specific percentiles (40).
We also performed a 24-h ambulatory BP monitoring
with an automatic monitor and a standing position captor
(Dyasis Integra II, Physicor S.A., Paris, France) that has
been validated by the British Hypertension Society. This
method is considered the gold standard for BP assessment
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
in children (41,42). Measures were taken on the nondominant arm with previously published methods (11). We
obtained valid recordings in 42 obese and 15 lean children.
The BP analysis was performed off-line after the intervention, without knowing the subject group assignment or
time. We calculated the 24-h mean BP and BP standard
deviation scores (SDS) (43). Hypertension was defined as
24-h BP over the 95th age- and sex-specific percentile and
a BP load over 25%.
Noninvasive measurements of the IMT at the common
carotid artery and the endothelial and smooth muscle cell
functions at the brachial artery were performed by the same
investigator (Y.A.) with a real-time B-mode ultrasound
imager (Vingmed CFM800C System Ltd., Hovik, Norway)
with a 10-MHz linear high-resolution vascular probe
(19,22). All off-line measurements of IMT were performed
with an automated computerized program (Iôtec System,
Iôdata Processing, Paris, France). The pulse wave of the
radial artery was assessed with an applanation tonometry
probe (SphygmoCor, Atcor Medical Ltd., West Ryde,
Australia) to estimate central aortic pressure noninvasively.
This parameter allowed determination of arterial stiffness
with the incremental elastic modulus (Einc) (44). After 30
min of rest in a recumbent position, we measured endothelial (flow-mediated dilation [FMD]) and smooth muscle
(nitroglycerin-mediated dilation [NTGMD]) functions of
the right brachial artery with the same echographic vascular
linear probe (19,44).
Cardiorespiratory fitness was measured as VO2max assessed
by direct gas analysis (Vmax Spectra, Vyasis Healthcare, GE,
Yorba Linda, California) during a multistage treadmill test
(Marquette 2000, GE, Milwaukee, Wisconsin). After a sufficient warm-up, the subject walked or ran on the treadmill at a
constant speed, which varied by age and physical capacity
(from 5 to 9 km ⫻ h⫺1) (45). The grade of the treadmill was
increased by 2.5% every 2 min until the subject was exhausted
and reached the VO2max criteria.
We measured physical activity count before the intervention and at 3 and 6 months with a validated uniaxial
accelerometer (Actigraph MT 6471, MTI, Pensacola, Florida) (46), worn at the right waist during a 7-day period
(school week, 24 h/day, outside training periods), except
during bathing or swimming. The monitor used a 1-min
cycle, and at the end of each cycle, the summed value was
stored in memory. The Excel software (Microsoft, Redmond, Washington) was used for data reduction and analysis. Only periods between 8:00 AM and 9:00 PM were
analyzed. The “zero activity” periods of 20 min or longer
were interpreted as being due to unworn accelerometers
and were removed from the total activity count. Subject’s
data were taken into account if total daily counts/min
were under 4,000 and if the monitor was worn during at
least 4 days (including 1 weekend day). Leisure-time
physical activity in the previous 12 months was assessed
with the Modifiable Physical Activity Questionnaire for
Adolescents (47).
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
2399
Nutrition was assessed with a self-reported 3-day food
record (2 weekdays and 1 weekend day successively) filled
out by the parents. We provided a kitchen scale (precision
1 g, Seca Culina 852) to perform home measures. We
calculated the total energy (kcal) and macronutrients intakes.
Blood samples were collected via venipuncture after a
10-h overnight fast. Total cholesterol (TC), high-density
lipoprotein cholesterol (HDL-C), and triglyceride (TG)
levels (mmol ⫻ l⫺1) were determined by standard automotive techniques (SYNCHRON LX20, Beckman
Coulter, Fullerton, California). Low-density lipoprotein
cholesterol (LDL-C) was calculated with the Friedewald’s formula. Plasma insulin concentrations were measured by radioimmunoassay (Access ultrasensitive insulin,
Beckman Coulter Ireland, Inc., Galway, Ireland), and
insulin resistance was assessed by using the homeostasis
model assessment (HOMA-IR), according to the equation: HOMA-IR ⫽ fasting insulin (␮U ⫻ ml⫺1) ⫻ fasting
glucose (mmol ⫻ l⫺1)/22.5. High-sensitive C-reactive protein levels were assessed by nephelometry (Beckman Coulter
Ireland, Inc.). Results were considered abnormal if: TC
⬎5.2 mmol ⫻ l⫺1, LDL-C ⬎3.4 mmol ⫻ l⫺1, HDL-C
ⱕ0.9 mmol ⫻ l⫺1, TG ⬎1.7 mmol ⫻ l⫺1, glucose ⱖ5.6
mmol ⫻ l⫺1, and insulin ⬎15 ␮U ⫻ ml⫺1, according to
recent pediatric guidelines (48,49).
Sample size and statistical analysis. The calculation of
sample size was based on the assessment of systemic BP as
the primary end point. In adults, a reduction of 5 mm Hg in
diastolic BP is associated with a reduction of at least 35% of
stroke and 21% of congenital heart disease (50). In obese
adolescents, a 6-month exercise training program resulted in
a reduction of systolic blood pressure (SBP) of 8 mm Hg
(effect size 0.6) (36). Therefore, with an anticipated effect
size of 0.6, a sample size of 22 subjects in each group could
detect statistically significant differences at p ⬍ 0.05 with a
statistical power of 80%. On the basis of previous studies,
this sample size was also sufficient to identify differences in
endothelial function parameters.
Data were screened for normality, with skewness and
kurtosis tests. The following variables were transformed
and successfully normalized: office SBP (square), total
and LDL-C (reciprocal); and insulin, Einc, FMD, and
NTGMD (square-root). Data were expressed as mean and
SD or median and interquartile range (25th to 75th percentile), when appropriate. At baseline, we compared means
of each continuous variable of obese and lean groups by
analysis of variance (ANOVA) with Bonferroni post hoc
tests and analysis of covariance (ANCOVA), while adjusting for sex and age entered into the model as a continuous
variable. We also compared the shapes of distributions with
Mann-Whitney U tests. Except for physical activity count,
there were no age and sex effects in ANCOVA, and
Mann-Whitney U tests yielded similar results. The associations between continuous variables were determined with
2400
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
Pearson correlation coefficient. To assess the relationships
between changes in BP and body fat, we also performed
univariate and multivariate linear regression analysis.
Then, ANOVA with a repeated-measure design was used
to evaluate parameter changes over time (2 or 3 visits) in
obese subjects while assessing the effects of intervention.
From baseline to 3 months (randomized controlled trial),
we performed a per-protocol analysis (n ⫽ 41) and an
intention-to-treat (n ⫽ 44) analysis, which yielded the same
results. For 3 subjects in the obese CON group with no
follow-up results at 3 months, we carried forward their
baseline values for all the studied parameters (n ⫽ 44). We
also adjusted the same models for age, sex, and baseline
outcome with repeated-measure design ANCOVA, but
results were not different, except for physical activity count.
We also completed an efficacy analysis including subjects
who met the criteria for exposure to the intervention (⬎60%
attendance). As groups differed in age- and sex-ratio after
excluding subjects who did not meet criteria for exposure,
these variables were entered in the computation.
From 3 to 6 months, we performed a per-protocol
analysis only (n ⫽ 38), because it was an open study. We
used the statistical software program Stata release 9.2 (Stata
Corp., College Station, Texas). Differences were considered
significant when p ⬍ 0.05.
Results
Comparison between obese and lean subjects at baseline.
Recruitment and randomization procedures are summarized
in Figure 1. Randomization produced similar distributions
of baseline characteristics and biological markers in the 2
obese groups (Table 1). Compared with the lean group, the
2 obese groups had significantly higher body weight, BMI,
BMI z-score, percent of total and abdominal fat, fat-free
mass, fasting insulin, and HOMA-IR and C-reactive protein levels, as well as lower HDL-C, physical activity level,
and VO2max. The proportion of obese children who had
dyslipidemia or increased insulin resistance indexes compared with normative references was as follows: TC (14%),
HDL-C (19%), LDL-C (15%), and fasting insulin (22%
between 15 and 28 ␮U ⫻ ml⫺1). None of the obese subjects
had increased glucose or TG, and all lean children had
normal values. Nutrition analysis (energy and macronutriments) was not possible due to insufficient filling-out
of the food record in more than 50% of cases.
Blood pressure, cardiorespiratory fitness, and vascular
parameter results at baseline are presented in Table 2. Obese
children had significantly higher 24-h SBP and DBP, BP
SDS, and arterial stiffness, as well as lower VO2max, FMD,
and NTGMD compared with lean subjects. Office BP was
significantly higher in EX than lean children. Moderate
systolic HTN was present in 20 of 42 obese subjects
(47.6%), and both systolic and diastolic HTN was present in
12 of 42 subjects (28.6%). The proportion of children with
systolic HTN was similar between obese EX (50%) and
CON (45%).
Effects of the 3-month exercise intervention in obese
children. The compliance averaged 83% of the 36 scheduled exercise sessions in the obese EX group. The adherence
was high; 19 of 22 obese subjects (86%) participated in 3
Markers in
Baseline
Characteristics,
the
Obese Characteristics,
Groups
Physical
Compared
Activity,
With
and
the
Biological
Lean Group
Baseline
Physical
Activity,
and Biological
Table 1
Markers in the Obese Groups Compared With the Lean Group
Parameters
Female/male, n
Age, yrs
Height, cm
Obese Exercise
(n ⴝ 22)
Obese Control
(n ⴝ 22)
Lean Group
(n ⴝ 22)
13/9
15/7
16/6
9.1 (1.4)
8.8 (1.6)
0.8
0.4
135.5 (10.2)
134.9 (9.5)
Body weight, kg
50.6 (11.8)
47.1 (14.4)
28.4 (5.4)
BMI, kg ⫻ m⫺2
25.4 (4.6)
25.1 (4.7)
15.5 (1.6)
⬍0.0001
2.3 (0.6)
2.3 (0.6)
⫺0.5 (0.9)
⬍0.0001
BMI z-score
140.4 (7.9)
8.5 (1.5)
p Value
0.1
⬍0.0001
Whole body fat, %
42.6 (6.9)
42.4 (7.1)
20.1 (8.1)
⬍0.0001
Abdominal fat, %
49.7 (8.0)
49.7 (8.0)
19.6 (8.3)
⬍0.0001
Fat-free mass, kg
7-day physical activity, cpm
Past year physical activity, min ⫻ week⫺1
Total cholesterol, mmol ⫻ l⫺1*
27.5 (4.9)
26.0 (5.3)
21.8 (3.8)
306.7 (34.2)
329.4 (79.1)
420.6 (83.7)
41.1 (80.8)
48.2 (55.1)
116.5 (103.1)
4.3 (3.7–4.8)
4.1 (3.9–4.4)
4.3 (4.0–4.6)
LDL-cholesterol, mmol ⫻ l⫺1*
2.9 (2.4–3.4)
2.9 (2.5–3.2)
2.8 (2.3–3.0)
HDL-cholesterol, mmol ⫻ l⫺1
1.2 (0.2)
1.0 (0.3)
1.4 (0.3)
Triglycerides, mmol ⫻ l⫺1
0.6 (0.3)
0.7 (0.3)
0.6 (0.2)
Fasting glucose, mmol ⫻ l⫺1
4.8 (0.4)
4.8 (0.4)
4.8 (0.4)
Fasting insulin, mU ⫻ l⫺1*
12.0 (7.8–17.1)
10.0 (7.6–13.8)
0.0003
⬍0.0001
0.005
0.8
0.3
⬍0.0001
0.4
0.9
3.3 (2.8–6.6)
⬍0.0001
HOMA-IR
2.5 (2.2)
2.2 (1.6)
0.7 (0.9)
⬍0.0001
hsCRP, mmol ⫻ l⫺1
3.4 (5.3)
4.7 (4.2)
1.6 (1.6)
0.04
Results are shown as mean (SD), unless otherwise indicated. The p values indicate significant differences among the 3 groups (analysis of variance).
The 2 obese groups were not different. *Median and interquartile range (25th to 75th percentile).
BMI ⫽ body mass index; HDL ⫽ high-density lipoprotein; HOMA-IR ⫽ homeostasis assessment model of insulin resistance; hsCRP ⫽ high-sensitive
C-reactive lipoprotein; LDL ⫽ low-density lipoprotein.
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
2401
Arterial Parameters
Baseline
Blood
Pressure,
inBlood
Obese
Cardiorespiratory
Groups Compared
Fitness,
Withand
theFitness,
Lean Group
Baseline
Pressure,
Cardiorespiratory
and
Table 2
Arterial Parameters in Obese Groups Compared With the Lean Group
Parameters
Office SBP, mm Hg*
Office DBP, mm Hg
Obese Exercise
(n ⴝ 22)
Obese Control
(n ⴝ 22)
Lean Group
(n ⴝ 22)
107.0 (103.0–117.0)
101.0 (94.0–117.0)
101.5 (97.0–106.0)†
56.3 (8.6)
51.8 (5.9)
24-h SBP, mm Hg
127.6 (13.3)
121.9 (15.0)
24-h DBP, mm Hg
50.7 (3.1)†
p Value
0.01
0.01
104.7 (9.2)
⬍0.0001
73.5 (6.9)
72.0 (7.9)
62.1 (4.3)
⬍0.0001
24-h SBP-SDS
2.3 (1.6)
1.7 (1.6)
⫺0.4 (1.2)
⬍0.0001
24-h DBP-SDS
1.4 (1.3)
1.1 (1.5)
⫺0.7 (0.8)
⬍0.0001
Systolic HTN, n (%)
11 (50)
9 (45)
0 (0)
9 (41)
3 (15)
0 (0)
⬍0.0001
34.4 (5.0)
36.9 (7.1)
49.1 (5.7)
⬍0.0001
47.8 (3.1)
Systolic-diastolic HTN, n (%)
VO2max, ml ⫻ kg⫺1 ⫻ min⫺1
IMT of CCA, mm ⫻ 10⫺2
48.7 (2.8)
48.2 (3.1)
Einc, mm Hg ⫻ 102*
13.1 (9.73–16.2)
12.6 (11.5–14.3)
FMD, %*
5.1 (3.7–7.7)
NTGMD, %*
20.3 (8.9)
4.1 (3.7–4.8)
17.1 (7.6)
⬍0.0001†
0.6
9.3 (6.5–13.4)
0.8
7.8 (7.1–9.5)
0.007
25.0 (6.9)
0.006
Results are shown as mean (SD), unless otherwise indicated. The p values indicate significant differences among the 3 groups at baseline (analysis
of variance). The 2 obese groups were not different. *Median and interquartile range (25th to 75th percentile). †Lean group was different from the
obese exercise group only (p ⬍ 0.05).
CCA ⫽ common carotid artery; DBP ⫽ diastolic blood pressure; Einc ⫽ incremental elastic modulus; FMD ⫽ flow-mediated dilation; HTN ⫽
hypertension; IMT ⫽ intima-media thickness; NTGMD ⫽ nitroglycerin-mediated dilation; SBP ⫽ systolic blood pressure; SDS ⫽ standard deviation
score; VO2max ⫽ cardiorespiratory fitness.
sessions/week. Three of 22 obese CON (14%) subjects did
not attend the second visit, but there were no drop-outs in
the EX group.
Changes and treatment effects at 3 months are shown in
Tables 3 and 4 (intention-to-treat analysis, n ⫽ 44). In the
EX group, BMI z-score (⫺5.5%), whole body (⫺3.6%) and
abdominal fat (⫺4.2%), TC (⫺3.7%), LDL-C (⫺4.2%),
HDL-C (⫺5.3%), office SBP (⫺2.0%) and DBP (⫺4.1%),
and 24-h SBP (⫺4.9%) and DBP (⫺3.2%) significantly
decreased, whereas fat-free mass (⫹4.6%) and VO2max
(⫹6.0%) increased during the intervention (p ⬍ 0.05).
Mean systolic BP also decreased during the night (⫺7.1 ⫾
10.2 mm Hg, p ⫽ 0.03).
We found opposite results in the CON group, where
BMI (⫹1.1%), whole body fat (⫹2.2%), abdominal fat
(⫹2.1%), and office (⫹4.3%) and 24-h SBP (⫹3.6%)
increased, whereas VO2max (⫺4.3%) and physical activity
count (⫺11.6%) decreased (p ⬍ 0.05). Body weight, height,
insulin, and HOMA-IR significantly augmented in the 2
obese groups.
The change differences between the obese EX and CON
groups (treatment effect) in BMI, BMI z-score, whole body
During thein3-Month
Changes
Body
Composition,
Exercise
Physical
in Activity,
Obese
Children
andActivity,
Biological
(Intention-to-Treat
Markers
Changes
in Body Program
Composition,
Physical
and
BiologicalAnalysis)
Markers
Table 3
During the 3-Month Exercise Program in Obese Children (Intention-to-Treat Analysis)
Parameters
Body weight, kg
Obese Exercise
(n ⴝ 22)
1.0 (2.4)†
Obese Control
(n ⴝ 22)
Treatment Effect*
p Value
1.6 (1.5)‡
⫺0.9
0.3
0.06
BMI, kg ⫻ m⫺2
⫺0.1 (1.0)
0.3 (0.7)†
⫺0.4
BMI z-score
⫺0.1 (0.1)‡
0.0 (0.1)
⫺0.1
0.04
Whole body fat, %
⫺1.5 (1.7)‡
0.8 (1.6)†
⫺2.4
⬍0.0001
Abdominal fat, %
⫺2.1 (2.5)‡
0.7 (2.4)‡
⫺2.9
0.0007
Fat-free mass, kg
1.2 (1.3)‡
⫺0.1 (2.8)
1.4
0.03
Physical activity, cpm
1.1 (86.3)
⫺41.1 (71.2)†
48.1
0.05§
⫺4.0 (551.9)
⫺343.8
Total energy intake, kcal
⫺347.8 (224.6)‡
0.1
Total cholesterol, mmol ⫻ l⫺1
⫺0.22 (0.53)†
⫺0.14 (0.46)
⫺0.08
0.6
LDL-cholesterol, mmol ⫻ l⫺1
⫺0.18 (0.44)†
⫺0.17 (0.55)
0.01
0.9
HDL-cholesterol, mmol ⫻ l⫺1
⫺0.06 (0.11)‡
⫺0.03 (0.13)
⫺0.05
0.3
0.12 (0.43)
⫺0.04
0.6
Triglycerides, mmol ⫻ l⫺1
0.04 (0.31)
Glucose, mmol ⫻ l⫺1
0.15 (0.33)†
⫺0.01 (0.26)
0.15
0.09
Insulin, mU ⫻ l⫺1
3.81 (4.28)‡
3.0 (5.1)‡
0.85
0.6
HOMA-IR
0.99 (1.04)‡
0.62 (1.20)†
0.37
0.3
0.04
0.9
hsCRP, mmol ⫻ l⫺1
⫺0.13 (4.53)
⫺0.17 (3.76)
Results are shown as mean (SD). *Treatment effect defined as the change in obese exercise group compared with control group. †Significant
within-group change between baseline and 3 months (p ⬍ 0.05). ‡Significant within-group change between baseline and 3 months
(p ⬍ 0.01). §Adjusted for age and sex.
Abbreviations as in Table 1.
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Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
During the
Changes
in Blood
3-Month
Pressure,
Exercise
Cardiorespiratory
Program Cardiorespiratory
in Obese
Fitness,
Children
and Arterial
(Intention-to-Treat
Function
Parameters
Analysis)
Changes
in Blood
Pressure,
Fitness,
and Arterial
Function
Parameters
Table 4
During the 3-Month Exercise Program in Obese Children (Intention-to-Treat Analysis)
Parameters
Obese Exercise
(n ⴝ 22)
Obese Control
(n ⴝ 22)
Treatment Effect*
p Value
Office SBP, mm Hg
⫺1.9 (11.8)†
4.4 (10.3)†
⫺6.9
0.003
Office DBP, mm Hg
⫺1.3 (9.7)
4.7 (7.0)‡
⫺6.7
0.009
24-h SBP, mm Hg
⫺6.9 (13.5)†
3.8 (7.9)†
⫺10.7
24-h DBP, mm Hg
⫺2.6 (5.0)†
24-h SBP SDS
⫺0.8 (1.5)†
24-h DBP SDS
⫺0.5 (1.0)†
VO2max, ml ⫻ kg⫺1 ⫻ min⫺1
IMT of CCA, mm ⫻ 10⫺2
Einc, mm Hg ⫻ 10⫺2§
1.9 (3.5)†
⫺0.09 (3.75)
1.81 (10.68)
⫺0.2 (7.0)
0.4 (0.8)†
⫺0.0 (1.4)
0.007
⫺2.3
0.3
⫺1.1
0.01
⫺0.5
⫺1.6 (4.6)†
3.5
0.02
0.007
1.13 (4.40)
⫺1.22
0.2
⫺0.54 (6.18)
2.34
0.4
FMD, %
⫺0.59 (3.13)
0.13 (2.61)
⫺0.72
0.4
NTGMD, %
⫺1.01 (9.04)
0.64 (9.42)
⫺1.64
0.6
Results are shown as mean (SD). *Treatment effect defined as the change in the obese exercise group compared with the control group. †Significant
within-group change between baseline and 3 months (p ⬍ 0.05). ‡Significant within-group change between baseline and 3 months
(p ⬍ 0.01). §Normalized (square root).
Abbreviations as in Tables 1 and 2.
and abdominal fat, fat-free mass, office and 24-h SBP and
DBP, VO2max, and physical activity count were all significant (p ⬍ 0.05). The prevalence of HTN reduced in EX
(⫺12%) compared with CON (⫺1%) subjects. In hypertensive EX subjects (11 of 22), the reduction of 24-h SBP
(⫺9.9 ⫾ 14.5 mm Hg, ⫺1.3 ⫾ 1.5 SDS) was significantly
greater than in nonhypertensive EX subjects. Changes in
24-h SBP correlated with changes in abdominal fat only
(r ⫽ 0.42, p ⫽ 0.02). We did not observe any changes in
biological or arterial function parameters. The efficacy
analysis, after excluding the 3 obese EX subjects who
participated in ⬍60% of sessions, showed similar results.
Only 18 of 44 obese subjects had valid food records before
and after the intervention (9 EX and 9 CON). We did not
observe any significant between-group differences in the
total energy intake either before (EX 1,813.0 ⫾ 306.6 kcal
vs. CON 1,614.0 ⫾ 382.5 kcal) or after the intervention
(EX 1,465.2 ⫾ 298.0 kcal vs. CON 1,610.0 ⫾ 468.2 kcal).
Exercise training was associated with a decrease in total
energy intake in the EX group but not in the CON group
(Table 3). The EX–CON effect was not significant, and the
percentage of total kilocalories from fat, protein, or carbohydrate did not change in either the EX or the CON group.
To assess the relationships between changes in BP and
body fat, we performed univariate and multivariate regression analysis including all subjects (n ⫽ 44). We observed
associations between 24-h SBP and BMI changes (coefficient 4.8%, p ⫽ 0.05), total body fat (coefficient 2.2%, p ⫽
0.02) and abdominal fat (coefficient 2.0%, p ⫽ 0.003), as
well as 24-h DBP and abdominal fat changes (coefficient
0.8%, p ⫽ 0.003). However, after introducing intervention
and disease in the model, the intervention remained the
only significant determinant of BP changes. We then
adjusted the model for sex and age (or used 24-h SBP SDS
as dependent variable) and found similar results. Office BP
changes were not related to BMI or body fat changes.
Evaluation at 6 months. After the 3-month intervention,
we encouraged obese EX participants to continue to train
twice/week for a total of 6 months. Four of 22 subjects
dropped-out, 19 continued, and 16 of them participated
regularly (⬎60% of sessions) (Fig. 1). The CON group was
invited to start a similar exercise program for 3 months. One
of 19 obese subjects dropped-out, 18 started training, and
12 of them trained regularly.
From 3 to 6 months, we observed further changes in the
EX group (n ⫽ 18) (Fig. 2) in BMI z-score (⫺0.03 ⫾ 0.05,
p ⫽ 0.01), whole body fat (⫺0.5 ⫾ 1.1%, p ⫽ 0.02), fatfree mass (0.5 ⫾ 0.9 kg, p ⫽ 0.02), glucose (⫺0.2 ⫾ 0.3
mmol ⫻ l⫺1, p ⫽ 0.003), and HOMA-IR (⫺0.96 ⫾ 1.02,
p ⫽ 0.0003). In the CON group (n ⫽ 18), the exercise
intervention also resulted in reduced BMI z-score (⫺0.08 ⫾
0.14, p ⫽ 0.009), whole body fat (⫺1.1 ⫾ 2.0%, p ⫽ 0.02),
abdominal fat (⫺1.0 ⫾ 2.0%, p ⫽ 0.05), and office DBP
(⫺4.4 ⫾ 8.2 mm Hg, p ⫽ 0.02) and increased fat-free mass
(1.1 ⫾ 0.5 kg, p ⬍ 0.0001), physical activity count (77.5 ⫾
107.9, p ⫽ 0.03), and HDL-C (0.06 ⫾ 0.15, p ⫽ 0.05).
Body weight and height significantly increased in both
groups.
From baseline to 6 months (Fig. 2), change differences
between EX and CON groups were significant for SBP
(⫺1.8 SDS, p ⫽ 0.04), DBP (⫺1.5 SDS, p ⫽ 0.047),
arterial stiffness (⫺470.0 mm Hg ⫻ 102, p ⫽ 0.049), IMT
(⫺0.02 mm, p ⫽ 0.045), and VO2max (⫹2.8, p ⫽ 0.02).
Discussion
Hypertension and first signs of atherosclerosis develops
before puberty in obese children, and therefore it is urgent
to identify effective strategies to prevent the spread of CVD
in this population. To our knowledge, we demonstrate for
the first time that a regular physical activity program results
in a significant reduction of systemic BP after 3 months and
a decrease of arterial stiffness as well as a stabilization of the
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
Figure 2
2403
Changes in BMI, Body Fat, Systolic BP, Cardiorespiratory Fitness,
Arterial Stiffness, and IMT at 3 and 6 Months in Obese Children
Obese exercise group (solid circles); obese control group (open circles). Asterisks indicate significant treatment effect (exercise vs. control group) at 3 and 6
months: *p ⬍ 0.05; **p ⬍ 0.01. BMI ⫽ body mass index; BP ⫽ blood pressure; Einc ⫽ incremental elastic modulus; IMT ⫽ intima-media thickness; SDS ⫽
standard deviation score; VO2max ⫽ maximal oxygen consumption.
IMT after 6 months in pre-pubertal obese children. These
changes are independent of body weight or fat reduction
and are of greater magnitude in hypertensive subjects. We
also show that our exercise intervention has beneficial effects
on whole body and abdominal fat, fat-free mass, and
cardiorespiratory fitness in obese children.
Systemic HTN is a common complication of childhood
obesity. In a recent study, we reported an increased prevalence of HTN in pre-pubertal obese children, assessed by
ambulatory BP monitoring (11). Elevated BP was associated with endothelial and smooth muscle cell dysfunction,
arterial stiffness (21), and increased left ventricular mass
(11). In this present study, we observed a significant
decrease in systolic and diastolic office and 24-h BP after 3
months of exercise training. The effects on BP were clinically relevant, ranging from ⫺7 to ⫺12 mm Hg for SBP
and from ⫺2 to ⫺7 mm Hg for DBP, as previously shown
in adolescents (36) and adults (26). In addition, 24-h SBPand DBP-SDS treatment effects were ⫺1.2 and ⫺0.5 at 3
months, respectively. These changes were significantly
greater in hypertensive subjects compared with nonhypertensive subjects. In the EX group, the proportion of
children with HTN reduced significantly from 50% to 37%
at 3 months and to 29% at 6 months. If we hypothesize that
these changes translate into those of similar magnitude in
adulthood, these finding could be of public health significance. For example, in adult population a reduction of 5 mm
Hg in diastolic BP is associated with a decrease of at least
35% of stroke and 21% of congenital heart disease (50). For
pediatricians or general practitioners, the diagnosis of systemic HTN in young obese children might raise the critical
question of whether they should prescribe antihypertensive
medications or promote lifestyle modifications. Because
HTN is a consequence of obesity and physical inactivity, we
suggest encouraging regular exercise.
Systemic HTN in obese children might be due to
impaired endothelial function or activation of the sympathetic nervous system or insulin resistance (12–21). At
baseline, we showed impaired arterial endothelial and
smooth muscle cell functions, increased local arterial stiffness, and insulin resistance indexes in obese compared with
lean children, without significant evidence of arterial remodeling (IMT). Surprisingly, the changes in BP that we
observed during the 3-month intervention were not associated with improved endothelial or smooth muscle cell
functions or arterial stiffness in obese subjects. After 6
months, however, we found a significant reduction in
arterial stiffness as well as a stabilization of IMT in the EX
compared with the CON group. Some authors previously
reported improved endothelial function after an 8-week
aerobic exercise program in a small cohort of 14 adolescents,
even in absence of changes in subcutaneous fat, body
weight, or BMI (51). However, subjects with HTN were
excluded from that study. More recently, Meyer et al. (36)
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Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
demonstrated increased endothelial function (⫹57%) and
decreased SBP, IMT, and insulin resistance indexes after a
6-month moderate exercise training program (3 sessions/
week, 210 min total) in obese adolescents. Baseline SBP was
elevated, similarly to our study, whereas FMD was lower
compared with lean subjects. Another trial investigated the
effects of a 6-week physical activity program combined with
a dietary restriction in 10-year-old children and found
improved endothelial function (52). However, children had
normal BP at baseline. Our intervention seems to be
insufficient to improve endothelial or smooth muscle function in a cohort of patients with a high prevalence of HTN.
A longer program might be needed to detect changes at very
early stages of atherosclerosis.
Insulin resistance has been incriminated in the development of HTN in obese patients (16,17). During the first 3
months of intervention, we did not observe any reduction in
glucose and insulin levels or HOMA-IR. From 3 to 6
months, however, we reported a significant decrease of
insulin resistance indexes in both groups. These findings
suggest that exercise might have variable effects in young
children, probably because their insulin levels are only
slightly increased, close to the normal range. In addition, we
found the opposite within-group differences for HDL-C in
the EX group from baseline to 3 months compared with the
CON group from 3 to 6 months (crossover). However,
between-group differences were not significant. Because
dyslipidemia was present in only a small proportion of
children, we might hypothesize that our sample size was too
small to detect such changes. To date, the effects of lifestyle
modifications on markers of the metabolic syndrome remain
controversial. Only 2 studies showed significant responses to
moderate physical activity (32,36) or behavioral intervention
in adolescents (30), but no studies have demonstrated effects
of exercise on biological markers in obese children before
puberty.
In obese patients, HTN might also be due to altered
autonomous system activity (12–15), although we did not
measure these parameters in our study. Gutin et al.
(14,31,32,53) completed a 4-month moderate aerobic exercise randomized controlled trial in children ages 7 to 11
years and reported significant changes in cardiac parasympathetic activity as well as in fasting insulin.
The main objective of the treatment of childhood obesity
is to stabilize body weight during growth, in order to reduce
BMI, body fat, and comorbidities. Therapeutic programs
are generally multidisciplinary and include nutritional, exercise, and behavioral components. Our baseline results
confirm that physical activity level, sports participation, and
cardiorespiratory fitness are significantly lower in obese
compared with lean children. Our intervention included
various types of activities, such as ball games, walking, and
swimming, and participants showed great enthusiasm during sessions. The absence of drop-out and the high compliance and adherence rates as well as the number of
children who decided to continue training suggest that our
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
program was adapted and attractive. We assessed the
physical activity level before and during the week after the
3-month intervention, which started in September and
ended in December. We found that the level remained
stable in the EX group, whereas it decreased in the CON
group. Physical activity level usually decreases during autumn and winter in Europe, but the obese children who did
the intervention maintained their level after the program,
despite seasonal variations. We also observed a significant
increase in cardiorespiratory fitness in the exercise group
and might hypothesize that patients improved their functional capacity as well as their pleasure in participating in
daily activities. We conclude that physical activity programs
for obese children might be an interesting approach to
increase their physical activity level and motivate them in
the first phase of treatment.
We found significant changes in BMI z-scores and whole
body and abdominal fat, despite an increase in body weight.
These results might be explained by the gain in fat-free mass
that we observed in the EX compared with the CON group.
Indeed, BMI does not assess body composition, and care
should be taken in using this measure as the main outcome
of treatment. Gutin et al. also reported reduced percent
body fat and visceral and subcutaneous abdominal adipose
tissue after exercise training, whereas others did not (35,36).
Savoye et al. (30) performed a family-based behavioral
intervention in obese children and adolescents and found
changes of similar magnitude compared with our results.
Because visceral fat deposition is closely associated with
CVD risk factors and type 2 diabetes, we suggest that future
pediatric intervention studies assess changes on central
adiposity parameters (e.g., waist circumference, visceral fat)
instead of BMI.
Study strengths and limitations. This study has several
strengths. We used a randomized controlled trial design,
which allowed us to determine the effects of an exercise
training program during 3 months. The compliance and
adherence were high and the drop-out rate was low in the
EX group. However, our study had also several limitations.
We chose a modified crossover design because we felt that
it was unethical to leave obese children without treatment
for more than 3 months. This design did not permit
assessing EX–CON treatment effects over the 6-month
period. In addition, we assessed the energy intake by a
self-reported food record and obtained only 18 of 44 valid
datasets. Although the differences were not statistically
significant between groups, the sample sizes (9 in each
group) were small. The CON group changed little in overall
calorie intake, but the EX group decreased their intake by
348 calories/day. We hypothesize that subjects who participate in a physical activity program 3 times/week spend less
time at home and therefore decrease their food intake.
Changes in diet could therefore be responsible for some of
the changes attributed solely to exercise, suggesting that our
intervention could have had an unintended but beneficial
effect on diet. This could have important clinical implica-
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
tions but also indicates that physical activity change alone
might not have the desired results without a related change
in diet. However, nutritional results should be interpreted
with caution, because subjects with valid diet records might
be more motivated to make lifestyle changes and might not
be representative of the entire group. Our study also shows
that the decrease in systemic BP during the intervention is
independent of body weight or fat changes, supporting a
direct effect of exercise on HTN reduction.
Conclusions
Our study demonstrates that a regular physical activity
program, including mixed aerobic and strengthening exercises at least 60 min 3 times/week (180 min total) during 3
months, significantly reduces systemic BP, BMI z-score,
and total and abdominal adiposity and increases fat-free
mass and cardiorespiratory fitness in obese pre-pubertal
children. Changes in BP are greater in hypertensive subjects
and independent of body fat reduction. The continuation of
the exercise intervention during 6 months leads to a further
decrease in BP, a reduction of arterial stiffness and a
stabilization of the IMT. However, exercise has no effects
on endothelial or smooth muscle cell functions.
We conclude that participation in physical activity programs should be encouraged in young obese children to
reduce systemic BP and prevent the premature development
of atherosclerosis. Future research should investigate the
volume, intensity, and duration of physical activity that is
needed to improve endothelial and smooth muscle functions
in children with obesity.
Acknowledgments
The authors thank the subjects for volunteering for the
study, Sophie Bucher Della Torre (dietician), and the staff
of the Pediatric Policlinic and the Nuclear Medicine Unit
for their assistance.
Reprint requests and correspondence: Dr. Nathalie J. FarpourLambert, Pediatric Cardiology Unit, Department of Child and
Adolescent, University Hospitals of Geneva, 6 rue Willy-Donze,
1211 Geneva 14, Switzerland. E-mail: nathalie.farpourlambert@
hcuge.ch
REFERENCES
1. Ebbeling CB, Pawlak DB, Ludwig DS. Childhood obesity: publichealth crisis, common sense cure. Lancet 2002;360:473– 82.
2. McCarron P, Smith GD, Okasha M, McEwen J. Blood pressure in
young adulthood and mortality from cardiovascular disease. Lancet
2000;355:1430 –1.
3. Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation
of overweight to cardiovascular risk factors among children and
adolescents: the Bogalusa Heart Study. Pediatrics 1999;103:1175– 82.
4. Srinivasan SR, Myers L, Berenson GS. Predictability of childhood
adiposity and insulin for developing insulin resistance syndrome
(syndrome X) in young adulthood: the Bogalusa Heart Study. Diabetes
2002;51:204 –9.
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
2405
5. Whitworth JA. 2003 World Health Organization (WHO)/
International Society of Hypertension (ISH) statement on management of hypertension. J Hypertens 2003;21:1983–92.
6. Sorof J, Daniels S. Obesity hypertension in children: a problem of
epidemic proportions. Hypertension 2002;40:441–7.
7. Paradis G, Lambert M, O’Loughlin J, et al. Blood pressure and
adiposity in children and adolescents. Circulation 2004;110:1832– 8.
8. Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic
syndrome in children and adolescents. N Engl J Med 2004;350:
2362–74.
9. Lurbe E, Alvarez V, Liao Y, et al. The impact of obesity and body fat
distribution on ambulatory blood pressure in children and adolescents.
Am J Hypertens 1998;11:418 –24.
10. Stabouli S, Kotsis V, Papamichael C, Constantopoulos A, Zakopoulos
N. Adolescent obesity is associated with high ambulatory blood
pressure and increased carotid intimal-medial thickness. J Pediatr
2005;147:651– 6.
11. Maggio AB, Aggoun Y, Marchand LM, et al. Associations among
obesity, blood pressure, and left ventricular mass. J Pediatr 2008;152:
489 –93.
12. Rocchini AP, Katch V, Schork A, Kelch RP. Insulin and blood
pressure during weight loss in obese adolescents. Hypertension 1987;
10:267–73.
13. Daniels SR, Kimball TR, Khoury P, Witt S, Morrison JA. Correlates
of the hemodynamic determinants of blood pressure. Hypertension
1996;28:37– 41.
14. Gutin B, Barbeau P, Litaker MS, Ferguson M, Owens S. Heart rate
variability in obese children: relations to total body and visceral
adiposity, and changes with physical training and detraining. Obes Res
2000;8:12–9.
15. Rabbia F, Silke B, Conterno A, et al. Assessment of cardiac autonomic
modulation during adolescent obesity. Obes Res 2003;11:541– 8.
16. Kanai H, Matsuzawa Y, Tokunaga K, et al. Hypertension in obese
children: fasting serum insulin levels are closely correlated with blood
pressure. Int J Obes 1990;14:1047–56.
17. Lambert M, Paradis G, O’Loughlin J, Delvin EE, Hanley JA, Levy E.
Insulin resistance syndrome in a representative sample of children and
adolescents from Quebec, Canada. Int J Obes Relat Metab Disord
2004;28:833– 41.
18. Celermajer DS, Sorensen KE, Gooch VM, et al. Non-invasive
detection of endothelial dysfunction in children and adults at risk of
atherosclerosis. Lancet 1992;340:1111–5.
19. Tounian P, Aggoun Y, Dubern B, et al. Presence of increased stiffness
of the common carotid artery and endothelial dysfunction in severely
obese children: a prospective study. Lancet 2001;358:1400 – 4.
20. Meyer AA, Kundt G, Steiner M, Schuff-Werner P, Kienast W.
Impaired flow-mediated vasodilation, carotid artery intima-media
thickening, and elevated endothelial plasma markers in obese children:
the impact of cardiovascular risk factors. Pediatrics 2006;117:1560 –7.
21. Aggoun Y, Farpour-Lambert NJ, Marchand LM, Golay E, Maggio
AB, Beghetti M. Impaired endothelial and smooth muscle functions
and arterial stiffness appear before puberty in obese children and are
associated with elevated ambulatory blood pressure. Eur Heart J
2008;29:792–9.
22. Aggoun Y, Szezepanski I, Bonnet D. Noninvasive assessment of
arterial stiffness and risk of atherosclerotic events in children. Pediatr
Res 2005;58:173– 8.
23. Woo KS, Chook P, Yu CW, et al. Overweight in children is associated
with arterial endothelial dysfunction and intima-media thickening. Int
J Obes Relat Metab Disord 2004;28:852–7.
24. Thompson PD, Buchner D, Pina IL, et al. Exercise and physical
activity in the prevention and treatment of atherosclerotic cardiovascular disease: a statement from the Council on Clinical Cardiology
(Subcommittee on Exercise, Rehabilitation, and Prevention) and the
Council on Nutrition, Physical Activity, and Metabolism (Subcommittee on Physical Activity). Circulation 2003;107:3109 –16.
25. Pescatello LS, Franklin BA, Fagard R, Farquhar WB, Kelley GA, Ray
CA. American College of Sports Medicine position stand. Exercise
and hypertension. Med Sci Sports Exerc 2004;36:533–53.
26. Hagberg JM, Park JJ, Brown MD. The role of exercise training in the
treatment of hypertension: an update. Sports Med 2000;30:193–206.
27. Carnethon MR, Gidding SS, Nehgme R, Sidney S, Jacobs DR Jr., Liu
K. Cardiorespiratory fitness in young adulthood and the development
of cardiovascular disease risk factors. JAMA 2003;290:3092–100.
2406
Farpour-Lambert et al.
Obesity, Hypertension, and Exercise in Children
28. Leary SD, Ness AR, Smith GD, et al. Physical activity and blood
pressure in childhood: findings from a population-based study. Hypertension 2008;51:92– 8.
29. Trost SG, Kerr LM, Ward DS, Pate RR. Physical activity and
determinants of physical activity in obese and non-obese children. Int
J Obes Relat Metab Disord 2001;25:822–9.
30. Savoye M, Shaw M, Dziura J, et al. Effects of a weight management
program on body composition and metabolic parameters in overweight
children: a randomized controlled trial. JAMA 2007;297:2697–704.
31. Ferguson MA, Gutin B, Le NA, et al. Effects of exercise training and
its cessation on components of the insulin resistance syndrome in obese
children. Int J Obes Relat Metab Disord 1999;23:889 –95.
32. Gutin B, Owens S. Role of exercise intervention in improving body fat
distribution and risk profile in children. Am J Human Biol 1999;11:
237– 47.
33. Gutin B, Barbeau P, Owens S, et al. Effects of exercise intensity on
cardiovascular fitness, total body composition, and visceral adiposity of
obese adolescents. Am J Clin Nutr 2002;75:818 –26.
34. Kang HS, Gutin B, Barbeau P, et al. Physical training improves insulin
resistance syndrome markers in obese adolescents. Med Sci Sports
Exerc 2002;34:1920 –7.
35. Watts K, Beye P, Siafarikas A, et al. Exercise training normalizes
vascular dysfunction and improves central adiposity in obese adolescents. J Am Coll Cardiol 2004;43:1823–7.
36. Meyer AA, Kundt G, Lenschow U, Schuff-Werner P, Kienast W.
Improvement of early vascular changes and cardiovascular risk factors
in obese children after a six-month exercise program. J Am Coll
Cardiol 2006;48:1865–70.
37. Kromeyer-Hauschild K, Zellner K. Trends in overweight and obesity
and changes in the distribution of body mass index in schoolchildren
of Jena, East Germany. Eur J Clin Nutr 2007;61:404 –11.
38. Luo ZC, Cheung YB, He Q, Albertsson-Wikland K, Karlberg J.
Growth in early life and its relation to pubertal growth. Epidemiology
2003;14:65–73.
39. Kamel EG, McNeill G, Han TS, et al. Measurement of abdominal fat
by magnetic resonance imaging, dual-energy X-ray absorptiometry and
anthropometry in non-obese men and women. Int J Obes Relat Metab
Disord 1999;23:686 –92.
40. National High Blood Pressure Education Program Working Group
on High Blood Pressure in Children and Adolescents. The fourth
report on the diagnosis, evaluation, and treatment of high blood
pressure in children and adolescents. Pediatrics 2004;114:555–76.
41. Graves JW, Althaf MM. Utility of ambulatory blood pressure monitoring in children and adolescents. Pediatr Nephrol 2006;21:1640 –52.
JACC Vol. 54, No. 25, 2009
December 15/22, 2009:2396–406
42. Urbina E, Alpert B, Flynn J, et al. Ambulatory blood pressure
monitoring in children and adolescents: recommendations for standard
assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee
of the council on cardiovascular disease in the young and the council
for high blood pressure research. Hypertension 2008;52:433–51.
43. Wuhl E, Witte K, Soergel M, Mehls O, Schaefer F. Distribution of
24-h ambulatory blood pressure in children: normalized reference
values and role of body dimensions. J Hypertens 2002;20:1995–2007.
44. Aggoun Y, Sidi D, Levy BI, Lyonnet S, Kachaner J, Bonnet D.
Mechanical properties of the common carotid artery in Williams
syndrome. Heart 2000;84:290 –3.
45. Blimkie CJ, Cunningham DA, Nichol PM. Gas transport capacity and
echocardiographically determined cardiac size in children. J Appl
Physiol 1980;49:994 –9.
46. Ekelund U, Sjostrom M, Yngve A, et al. Physical activity assessed by
activity monitor and doubly labeled water in children. Med Sci Sports
Exerc 2001;33:275– 81.
47. Aaron DJ, Kriska AM, Dearwater SR, Cauley JA, Metz KF, LaPorte
RE. Reproducibility and validity of an epidemiologic questionnaire to
assess past year physical activity in adolescents. Am J Epidemiol
1995;142:191–201.
48. Daniels SR, Greer FR. Lipid screening and cardiovascular health in
childhood. Pediatrics 2008;122:198 –208.
49. Williams CL, Hayman LL, Daniels SR, et al. Cardiovascular health in
childhood: a statement for health professionals from the Committee
on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY)
of the Council on Cardiovascular Disease in the Young, American
Heart Association. Circulation 2002;106:143– 60.
50. MacMahon S, Peto R, Cutler J, et al. Blood pressure, stroke, and
coronary heart disease. Part 1, Prolonged differences in blood pressure:
prospective observational studies corrected for the regression dilution
bias. Lancet 1990;335:765–74.
51. Watts K, Beye P, Siafarikas A, et al. Exercise training normalizes
vascular dysfunction and improves central adiposity in obese adolescents. J Am Coll Cardiol 2004;43:1823–7.
52. Woo KS, Chook P, Yu CW, et al. Effects of diet and exercise on
obesity-related vascular dysfunction in children. Circulation 2004;109:
1981– 6.
53. Owens S, Gutin B, Allison J, et al. Effect of physical training on total
and visceral fat in obese children. Med Sci Sports Exerc 1999;31:
143– 8.
Key Words: atherosclerosis y child y hypertension y obesity y physical
activity.