Journal of the American College of Cardiology Vol. 62, No.

15, 2013
 2013 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00
Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2013.07.042

STATE-OF-THE-ART PAPER

Childhood Obesity and

Cardiovascular Dysfunction
Anita T. Cote, PHD, Kevin C. Harris, MD, Constadina Panagiotopoulos, MD,
George G. S. Sandor, MD, Angela M. Devlin, PHD
Vancouver, British Columbia, Canada

Obesity-related cardiovascular disease in children is becoming more prevalent in conjunction with the rise in
childhood obesity. Children with obesity are predisposed to an increased risk of cardiovascular morbidity and
mortality in adulthood. Importantly, research in children with obesity over the last decade has demonstrated that
children may exhibit early signs of cardiovascular dysfunction as a result of their excess adiposity, often independent
of other obesity-related comorbidities such as dyslipidemia and insulin resistance. The clinical evidence is
accumulating to suggest that the cardiovascular damage, once observed only in adults, is also occurring in obese
children. The objective of this review is to provide a synopsis of the current research on cardiovascular abnormalities
in children with obesity and highlight the importance and need for early detection and prevention programs to
mitigate this potentially serious health problem. (J Am Coll Cardiol 2013;62:1309–19) ª 2013 by the American
College of Cardiology Foundation

Noncongenital cardiovascular disease (CVD) should be rare
among children yet is becoming more prevalent in con-
junction with the rise in childhood obesity (1). Obesity in
children is defined as a body mass index (BMI) at or above
the 95th percentile for age and sex (2). Recent estimates
from 2007 to 2008 report that 16.9% of children are obese
and 31.6% are overweight in the United States (3,4),
a concern as many of these children will become obese adults
with enhanced risk for CVD (5–8). In fact, in 2007 it was
predicted that in the United States, the number of additional
cardiovascular (CV) events attributable to excess weight in
adolescence is expected to be >100,000 by 2035 (9). Most
disturbing, however, are the recent reports that childhood
obesity is often accompanied by concurrent CV abnormali-
ties, suggesting the problem is not only one of future or
long-term CVD risk but rather, one requiring immediate
attention to prevent progressive CV damage in childhood.
The goal of this review is to describe the spectrum of CV
abnormalities observed in children with obesity, with
From the Department of Pediatrics, University of British Columbia, Child and Family
Research Institute, Vancouver, British Columbia, Canada. This work is supported by
grants from the Canadian Institutes of Health Research (Dr. Devlin), Natural Sciences
and Engineering Research Council (Dr. Devlin), and British Columbia Mental
Health and Addiction Services (Drs. Devlin and Panagiotopoulos). Dr. Cote is sup-
ported by a MITACS Elevate postdoctoral fellowship. Dr. Panagiotopoulos is sup-
ported by Clinician Scientist awards from the Canadian Diabetes Association and
Child and Family Research Institute. Dr. Devlin is supported by an Investigator
Award from the Child and Family Research Institute. Drs. Harris and Sandor have
reported that they have no relationships relevant to the contents of this paper to
disclose.
Manuscript received June 20, 2013; revised manuscript received July 19, 2013,
accepted July 22, 2013.
a specific focus on cardiac and vascular structure and func-
tion and autonomic function.
Cardiac Structure and Function
Obesity is associated with increased metabolic demand due
to greater adipose tissue and lean mass, increasing blood
volume, and as such, increased preload to the heart (10). In
addition, vascular alterations impacting arterial stiffness and
resistance increase afterload to the heart (10). Both eccentric
and concentric hypertrophy have been noted in adults with
obesity and are impacted by the degree and duration of the
obesity and whether there is hypertension (11). Children
with obesity present with alterations analogous to that of
middle-age adults.
Cardiac structure. Studies of children, ranging in sample
size from 10 to 233 subjects (Table 1), have reported that left
atrial (12–16) and left ventricular (LV) (12,13,15–22)
dimensions are significantly greater in children with
obesity compared with children with a healthy BMI. Several
investigations have also reported greater LV mass in children
with obesity compared with lean controls (12,15,16,18–25),
and this has been detected as early as 2 years of age (26).
Greater epicardial fat has also been reported in children
with obesity compared with sex-matched children with
a healthy BMI, and is positively associated with LV mass
(15). Furthermore, a positive relationship between cardiac
size and BMI (14,24), insulin resistance (24), and waist-
to-height ratio (25) has been reported in children with
obesity.
1310 Cote et al. JACC Vol. 62, No. 15, 2013
Cardiovascular Effects of Childhood Obesity October 8, 2013:1309–19

Abbreviations Epicardial fat. Epicardial adi- 4.1 mm or greater determined insulin resistance (as assessed
and Acronyms pose tissue deposited around the by the homeostasis model assessment–estimated insulin
heart between the pericardium resistance [HOMA-IR] index) with 90% sensitivity and
BMI = body mass index
and outer wall of the myocardium 61% specificity, leading these researchers to propose that
CIMT = carotid intima-media
(27) is proposed to be a CVD this cut-off value could be used as a simple, inexpensive,
thickness
risk predictor (28). Quantification and noninvasive screening tool to predict cardiometabolic
CV = cardiovascular
of epicardial adipose tissue by dysfunction in obese children (30). Another study reported
CVD = cardiovascular
echocardiography is reported to that epicardial fat was positively associated with body
disease
be associated with visceral adipose weight, waist circumference, percent total fat mass as quan-
FMD = flow-mediated
dilation
tissue deposition (29). Some de- tified by dual-energy x-ray absorptiometry, visceral and
gree of epicardial fat deposition is subcutaneous adipose tissue deposition as quantified by
LV = left ventricular
observed in healthy subjects, but magnetic resonance imaging, and systolic blood pressure (27).
PWV = pulse wave velocity
upper limit values for the healthy Impaired cardiac function. Altered cardiac morphology
range have yet to be established. However, a recent study may be a precursor to impaired cardiac function, or alter-
proposed 4.1 mm as the upper limit cut-off value in children natively, cardiac dysfunction may elicit changes in chamber
(30). Epicardial fat deposition is positively associated with morphology. Studies of children and adolescents with obesity
insulin resistance (31), coronary artery disease (32), carotid have reported altered cardiac mechanics (Table 1) including
intima-media thickness (CIMT) (33), and arterial stiffness diastolic dysfunction (12,16,17,19,20,22,23,35–38) and
(34) in adults and may be a useful clinical tool for assessing systolic dysfunction at rest (36,37) and during exercise (22).
CVD risk in children. The abnormalities in diastolic function, and to a lesser
Greater epicardial fat deposition has been reported in degree, systolic function, are compelling evidence of the
children with obesity compared with sex- and age-matched association between obesity and CVD in children. Currently,
children with a healthy BMI (15,27,30). These investiga- it is unclear how this diminished cardiac function will
tions reported that epicardial fat was positively associated progress over time, and correlations of such changes in
with LV mass (15) and BMI and CIMT (30) in children childhood with outcomes in adulthood are lacking. In adults,
with obesity but not in lean children. Abaci et al. (30), re- despite evidence of cardiac enlargement and systolic
ported significantly higher epicardial fat in pubertal lean dysfunction, several studies have found that LV ejection
and obese children compared with pre-pubertal children, fraction is normal or even supranormal in many obese
illustrating the effects of puberty on epicardial fat deposition. subjects (39). However, even with normal ejection fraction,
They further demonstrated that epicardial fat deposition of myocardial contractile abnormalities may still exist, and

Table 1 Studies Investigating Effects of Obesity on Ventricular Mass, Dimensions, and Function in Children and Adolescents

Obese Control

First Author, Year (Ref. #) n Female Age (yrs) n Female Age (yrs) LVM LVd LVf
Harada, 2001 (35) 21 NR 10.3 98 NR 10.9 [ [ Y
Chinali, 2006 (20) 223 65% 17.7 114 39% 16.8 [ [ Y
Di Salvo, 2006 (42) 150 56% 12.0 150 56% 12.0 [ [ Y
Sharpe, 2006 (23) 28 50% 12.4 15 47% 13.3 [ 4 Y
Yu, 2006 (14) 22 27% 13.4 18 39% 13.4 [ [ 4
Lorch, 2007 (38) 33 24% 13.3 115 50% 13.9 4 Y
Di Bonito, 2008 (25) 111 52% 10.6 30 50% 10.8 [ 4 4
Van Putte-Katier, 2008 (19) 49 55% 11.2 45 51% 11.5 [ [ Y
Mehta, 2009 (12) 17 24% 13.3 32 41% 13.3 [ [ Y
Schuster, 2009 (22) 18 0% 11.6 17 0% 11.6 [ [ 4
Ingul, 2010 (37) 10 40% 14.8 10 40% 14.9 Y Y
Ozdemir, 2010 (15) 106 44% 11.4 62 42% 11.8 [ [
Pac, 2010 (77) 37 41% 13.9 30 43% 13.1 Y
Atabek, 2011 (24) 208 57% 11.9 50 48% 11.4 [
Dhuper, 2011 (16) 213 50% 13.8 130 39% 13.8 [ [ Y
Saltijerl, 2011 (21) 30 60% 13.3 42 40% 13.9 [ [ Y
Harris, 2012 (17) 61 44% 13.8 55 60% 13.8 [ Y
Koopman, 2012 (13) 21 19% 14.2 27 19% 13.9 [ [ Y
Mahfouz, 2012 (36) 56 30% 13.8 40 38% 13.4 Y
Ozcetin, 2012 (18) 42 57% 10.1 36 61% 9.8 4 [ Y

LVd ¼ left ventricular dimension; LVf ¼ left ventricular function; LVM ¼ left ventricular mass; NR ¼ not reported; [ ¼ greater compared to control; Y ¼ lower compared to control; 4 ¼ no difference between
control and obese.
JACC Vol. 62, No. 15, 2013
October 8, 2013:1309–19
are typically highlighted with more sensitive measures such
as tissue Doppler, strain and strain rate analyses (40,41).
Indeed, digital tagging by magnetic resonance imaging or
speckle tracking imaging with echocardiography, have
identified reductions in LV strain (13,21,38,42) and strain
rate (42), and right ventricular strain and strain rate (42) in
children with obesity. Impaired contractility as demon-
strated by these techniques could be missed with more
conventional, limited evaluations, and as such the extent
of cardiac dysfunction in childhood obesity may be
underestimated.
Applicability of the tissue Doppler imaging extends to the
ability to estimate LV filling pressures in obese subjects.
The ratio of early diastolic filling to mitral annular tissue
velocity (E/E0 ) is a well-validated index of pulmonary
capillary wedge pressure (43). This surrogate for filling
pressure has been reported to be higher in obese children
(12,18,19,23,37) although still within the normal range
and below that shown in children with other CV conditions
(44). The use of tissue Doppler and strain analysis were
reported to detect pre-clinical changes in LV systolic func-
tion before conventional changes in ejection fraction (45),
deeming these techniques potentially valuable in early
detection of obesity-related CV consequences.
Vascular Structure and Function
It is well known that atherogenesis begins in early life.
Autopsies on children (2 to 15 years of age) who died from
circumstances unrelated to CVD report fatty streaks and
fibrous plaque lesions in the aorta (46,47). Furthermore,
childhood BMI is positively associated with CVD risk in
adulthood (6), suggesting arterial wall damage may begin
during childhood. There is evolving evidence that clinical
indicators of atherosclerosis such as intima-media thickness,
arterial stiffness, and endothelial dysfunction are altered in
children with obesity, although the strength of the associa-
tions and mechanisms by which these effects are mediated
have not been fully elucidated.
Carotid intima-media thickness. The assessment of
CIMT is a sensitive clinical marker of atherosclerosis and is
predictive of CV morbidity and mortality in the general
adult population and in at-risk persons (48). Currently,
normative values have been established for adolescents 10 to
20 years of age (49), but not for younger children. Several
groups have reported that children and adolescents (ages
10 to 14 years) with obesity (Table 2) have greater CIMT
compared with children and adolescents with a healthy BMI
(13,18,50–57). In contrast, others have reported no differ-
ence in CIMT, despite impaired endothelial function
(58,59) and greater arterial stiffness (59), in children (ages
8.9 to 12 years) with obesity. Conflicting findings in these
studies may be due to differences in the degree of arterial
wall remodeling responsible for greater arterial stiffness,
and in some cases, it is not advanced to a point that pro-
duces intima-media thickening (58). Further, it is unclear
Cote et al. 1311
Cardiovascular Effects of Childhood Obesity
whether age may be a factor in the development of
CIMT, as it is in adults (60). A recent investigation re-
ported that age was a predictor of CIMT in children (61),
but the effect of age could not be distinguished from the
effects of pubertal development and exposure to CV risk
factors in this study. Furthermore, the severity of obesity
and body fat distribution may also contribute to the
progression of CIMT (18). Further research is required to
ascertain how obesity, body fat distribution, and/or expo-
sure to CV risk factors affect atherosclerotic progression in
children.
Vascular age. An interesting clinical application of the use
of CIMT is the concept of vascular age. Vascular age eval-
uates the CIMT measurement against the percentile charts
for the race- and sex-matched adult population (62), and
is supported for use to classify CVD risk in adults (63). After
the assessment of 70 children (ages 6 to 19 years; 89%
European; 49% male) with obesity and atherosclerosis-
promoting risk factors (dyslipidemia, hypertension, insulin
resistance, and smoke exposure), Le et al. (64) reported
that 75% of these children had advanced vascular age, similar
to what would be expected for a 45-year-old adult. The
average CIMT was 0.07 mm higher in the children with
advanced vascular age compared with children categorized as
normal vascular age, which is greater than the estimated 0.01
mm per year increase in CIMT reported for age-related
progression in healthy adults (64). With the establishment
of normative values in children, vascular age could serve
as an effective clinical tool for predicting CVD risk in
children.
Arterial stiffness. It is well established that greater vascular
stiffness is associated with increased CVD risk in adults
(65). An elastic vascular system reduces cardiac demand
(66), increases coronary artery perfusion (67), and is asso-
ciated with reduced atherosclerotic progression (68). Central
pulse wave velocity (PWV) is most strongly correlated with
CVD (69) and is predictive of both CV morbidity and all-
cause mortality in adults (70). Reference values of aortic
PWV have recently been reported for healthy children ages 3
to 18 years in which aortic stiffness remains stable up to
approximately 8 years of age, and then gradually increases in
both sexes with age (71). Arterial compliance increases with
age as arteries become larger during childhood growth and
development (72), and may temper age-associated increases
in arterial stiffness in young subjects (73).
Greater arterial stiffness has been reported in children
with obesity (Table 2) at the carotid artery (18,53,59) and in
central measures of PWV (13,36,52,74–76). In addition, we
and others (17,36,77) have reported abnormal biophysical
properties in the aorta of children with obesity, indicating
loss of aortic elasticity. The effects of obesity on arterial
properties has also been demonstrated in the pulmonary
artery (36). Increased pulmonary stiffness is thought to play
a role in the development and progression of pulmonary
hypertension, and can be identified before any clinical
evidence of pressure elevations (78).
 1312
Cardiovascular Effects of Childhood Obesity
Cote et al.
Table 2 Studies Investigating Effects of Obesity on Vascular Structure and Function in Children and Adolescents

Obese Control

First Author, Year (Ref. #) n Female Age (yrs) n Female Age (yrs) Tanner* FMD CIMT AC CAC CAS AS PWVc PWVp
Tounian, 2001 (59) 48 58% 12.6 27 41% 12.0 Yes Y 4 [ [
Iannuzzi, 2004 (53) 100 39% 10.0 47 21% 10.0 No [ [
Woo, 2004 (55) 36 58% 10.3 36 58% 10.3 Yes Y [
Zhu, 2005 (56) 43 46% 12.0 28 40% 12.0 No Y [
Kapiotis, 2006 (54) 145 48% 12.0 54 44% 12.0 No Y [
Meyer, 2006 (50) 32 53% 13.7 20 60% 14.7 Yes Y [
Meyer, 2006b (91) 96 51% 14.2 35 51% 14.7 Yes Y
Pena, 2006 (95) 58 48% 13.3 53 55% 14.1 No Y
Reinehr, 2006 (57) 96 54% 11.0 25 56% 11.0 Yes [
Lee, 2007 (75) 126 0% 14.6 130 0% 14.9 No [
Aggoun, 2008 (58) 48 67% 8.9 23 69% 8.3 Yes Y 4
Dangardt, 2008 (80) 33 61% 13.9 18 61% 14.3 No Y
Karpoff, 2009 (51) 12 0% 11.6 13 0% 11.6 No Y [ 4
Mahmud, 2009 (94) 26 39% 13.4 51 41% 14.0 Yes Y
Sakuragi, 2009 (76) 191 49% 10.1 0 Yesy [
Bhattacharjee, 2010 (93) 55 51% 8.6 50 40% 8.0 No Y
Pac, 2010 (77) 37 41% 13.9 30 43% 13.1 No [
Urbina, 2010 (74) 234 70% 18.1 241 61% 17.8 No [ 4
Yilmazer, 2010 (52) 77 47% 11.5 40 43% 9.8 Yesy Y [ Y
Chalmers, 2011 (81) 34 53% 13.6 33 39% 13.2 Yesy [
Ciccone, 2011 (92) 93 47% 10.9 No Y
Harris, 2012 (17) 61 44% 13.8 55 60% 13.8 No [
Koopman, 2012 (13) 21 19% 14.2 27 19% 13.9 No 4 [ [
Lurbe, 2012 (79) 284 44% 12.0 79 56% 13.4 No Y
Mahfouz, 2012 (36) 56 30% 13.8 40 38% 13.4 No [
Ozcetin, 2012 (18) 42 57% 10.1 36 61% 9.8 No [ [
Tryggestad, 2012 (82) 63 52% 13.9 61 49% 13.3 Yesy 4 [

*Tanner staging of pubertal status. yHigher Tanner stage in children with obesity.
AC ¼ arterial compliance; AS ¼ aortic stiffness; CAC ¼ carotid artery compliance; CAS ¼ carotid artery stiffness; CIMT ¼ carotid intima-media thickness; FMD ¼ flow-mediated dilation; PWVc ¼ central pulse wave velocity (carotid-femoral); PWVp ¼ peripheral pulse wave
velocity (carotid-radial or femoral-foot); [ ¼ greater than control; Y ¼ lower than control; 4 ¼ no difference between control and obese.

JACC Vol. 62, No. 15, 2013

October 8, 2013:1309–19
JACC Vol. 62, No. 15, 2013
October 8, 2013:1309–19
In contrast to the reports that show increased arterial
stiffness in children with obesity, some recent investiga-
tions have reported lower measures of arterial stiffness
(79,80) or increased arterial compliance (81,82) in children
with obesity compared with healthy BMI controls. Inter-
estingly, in some of these studies, the enhanced arterial
properties in children with obesity was accompanied by
cardiometabolic dysfunction such as elevated blood pres-
sure (80,81), greater insulin resistance, and elevated plasma
triglycerides, total cholesterol, and C-reactive protein
concentrations (82). Technical considerations may be res-
ponsible for these discrepant results. The reduced periph-
eral PWV (80) and increased arterial compliance (81,82) in
children with obesity may be a reflection of increasing
arterial diameter, which occurs naturally during develop-
ment, and may be altered (greater) in children with obesity.
The increased arterial diameters and/or large vessel elas-
ticity that occurs with growth and development may be
adequate to compensate for increased arterial pressures
(71). When tension in the aortic wall surpasses the point of
natural adaptation, aortic stiffness would subsequently rise,
differentiating arterial stiffness in children with and
without obesity. In support of this, Dangardt et al. (80)
reported lower carotid-to-radial PWV in 14-year-old
obese adolescents compared with age-matched lean ado-
lescents; however, in a recent follow-up, they reported that
at age 19 years of age, those with obesity now had a higher
PWV compared with those with a healthy BMI (83).
These researchers found that over the 5-year study period,
arterial stiffness increased 25% in adolescents with obesity
compared with 3% in adolescents with a healthy BMI.
Furthermore, the degree of increase in arterial stiffness at
the 5-year follow-up was positively associated with BMI z-
score at baseline. Thus, it may be difficult to disassociate
the natural adaptations that occur with growth from the
pathological developments of obesity on arterial stiffness
during adolescence.
An important consideration when interpreting arterial
stiffness and compliance findings are that many do not
control for sex and pubertal status, which are important
factors known to influence arterial wall properties (84).
Developmental adaptations in systemic compliance and
central and peripheral arterial stiffness during the pre-
pubertal, pubertal, and post-pubertal stages have been
described. For example, pre-pubertal girls display greater
arterial stiffness and lower systemic compliance than boys;
however, post-pubertal girls display similar compliance and
central artery stiffness and lower peripheral arterial stiffness
than boys (84), likely the result of differences in sex steroid
hormones, such as estrogens, which are known to influence
arterial structure and function (85). Furthermore, a recent
investigation reported that the steep increase in PWV,
which occurs normally during development, was observed
almost 2 years earlier in girls than in boys (71). As such,
caution must be made when comparing findings from
studies conducted in children that differ in terms of sex and
Cote et al. 1313
Cardiovascular Effects of Childhood Obesity
pubertal stage, and adjustments for both of these factors
should be considered in the data analyses.
Endothelial function. The vascular endothelium plays
a key role in the progression of atherosclerosis (86). Damage
to the endothelium, assessed by brachial artery flow-
mediated dilation (FMD), is an early clinical indicator of
atherosclerosis and vascular damage (87,88). A recent meta-
analysis suggested that FMD might only be a useful indi-
cator of CVD in populations at low risk (89). Considering
many children with obesity may not present with additional
metabolic or clinical risk factors, FMD may be useful in
identifying those children with early signs of atherosclerotic
development.
Several studies (Table 2) have reported that children with
obesity have lower FMD compared with children with
a healthy BMI (50–52,54–56,58,59,90–95). Only 2 studies
have reported similar FMD in children with obesity
compared with children with a healthy BMI (13,82). There
is some evidence to suggest that the presence of car-
diometabolic risk factors affect the relationship between
obesity and FMD in children. For example, Pena et al. (95)
reported a negative relationship between low-density lipo-
protein cholesterol and FMD (95). Furthermore, Bhatta-
charjee et al. (93) demonstrated that the degree of delay in
post-ischemia recovery was positively correlated with the
degree of dyslipidemia in nonhypertensive children with and
children without obesity. In the later study, the children with
obesity were free of obstructive sleep apnea, which is known
to interact with obesity to amplify CV morbidity (96).
Autonomic function. Impaired cardiac autonomic function
is related to all-cause mortality and sudden cardiac events in
adults (97). Specifically, a reduction in vagal activity has been
associated with the development of CVD and mortality (98),
and baroreflex sensitivity is considered a prognostic factor in
cardiology (99). Furthermore, depressions in autonomic
activity may precede the overt signs of CVD (100), deeming
autonomic assessment a potential useful clinical tool in early
identification of children and youth at risk.
Several reports have provided evidence of autonomic
dysfunction in children with obesity (101–110) (Table 3).
Indications of reduced vagal or parasympathetic activity of heart
rate variability are most commonly reported (102–105,110)
with some reports of a concurrent decrease in sympathetic
activity (105,108). The low frequency to high frequency
ratio may also be increased in children with obesity
(102,103,107,110), a marker of sympathovagal imbalance
(111). In addition, diminished baroreflex sensitivity has also
been reported (106,109). Given that the baroreflex is important
for regulating blood pressure (112), the assessment of cardiac
baroreceptor sensitivity incorporates both afferent and efferent
signaling in cardiac vagal activity and may be more sensitive
than heart rate variability to identify autonomic dysfunction in
children (106,113).
Some investigations have categorized children as lean
(healthy BMI), overweight (BMI 85th percentile for age
and sex), and obese. Two independent studies have reported
1314 Cote et al. JACC Vol. 62, No. 15, 2013
Cardiovascular Effects of Childhood Obesity October 8, 2013:1309–19

Table 3 Studies Investigating the Effects of Obesity on Autonomic Function in Children and Adolescents

Obese Control

First Author, Year (Ref. #) n Female Age (yrs) n Female Age (yrs) LF HF LF/HF BRS
Yakinci, 2000 (101) 33 30% 9.5 30 40% 10.1 Y
Martini, 2001 (102) 32 47% 13.8 13 46% 13.1 4 Y [
Riva, 2001 (110) 23 NR 13.9 14 NR 12.9 [ Y [
Nagai, 2004 (108) 48 35% 9.4 48 35% 9.5 Y Y
Kaufman, 2007 (103) 16 50% 11.5 10 50% 11.5 [ Y [
Tonhajzerova, 2008 (104) 20 60% 14.8 20 60% 14.8 Y
Lazarova, 2009 (109) 20 60% 14.9 20 60% 15.1 Y
Vanderlei, 2010 (105) 56 55% 10.0 65 51% 10.4 Y Y 4
Dangardt, 2011 (106) 120 49% 11.0 148 53% 13.6 Y
Rodriquez-Colon, 2011 (107) 91 52% 9.0 420 50% 8.8 [ Y [

BRS ¼ baroreflex sensitivity; HF ¼ high frequency; LF ¼ low frequency; LF/HF ¼ low frequency to high frequency ratio; NR ¼ not reported; PNS ¼ parasympathetic nervous system activity; SNS ¼ sympathetic
nervous system activity; [ ¼ greater than control; Y ¼ lower than control; 4 ¼ no difference between control and obese.

autonomic distinctions between lean and obese children,
with overweight children presenting similar autonomic
indices compared with lean children (103,106). Further-
more, in a study of children (n ¼ 91) at 9 years of age with
obesity, a positive relationship between BMI percentile and
impaired autonomic function was reported (107). In healthy
children and adolescents, puberty is reported to influence
autonomic function, although a recent study in obese chil-
dren and adolescents controlled for pubertal status and
determined baroreflex function is independent of age and
sex (106).
Mechanisms of Cardiovascular Dysfunction in
Childhood Obesity
The mechanisms responsible for CV dysfunction in children
with obesity are difficult to ascertain in the absence of
longitudinal data. The cascade of events leading to CVD
may vary in response to genetic and environmental factors as
well as the presence or absence of other comorbidities such
as hypertension or dyslipidemia (39). We have summarized
some of the important factors, which have been identified
(Fig. 1); however, many of the specific mechanisms and
interactions are incompletely understood in children and
likely involves a complex interaction between the presented
factors. For example, autonomic function is sensitive to
changes in adiposity (114), yet may continue to be altered as
atherosclerosis-related structural changes in large arteries
impede vagal input (115). Furthermore, metabolic
dysfunction accompanying obesity, such as leptin or insulin
resistance, may alter the sympathovagal balance via effects on
vascular smooth muscle (116). However, the relevance of
these factors during childhood obesity remains to be
determined.
It has been proposed that the duration of obesity is
a major factor that determines the likelihood of developing
systolic dysfunction and heart failure (14). Indeed obesity in
older individuals appears to pose less of a mortality risk than
it does in younger subjects (117). Given the structural and
functional changes have been reported in obese children, the
reports of increased morbidity and mortality with obesity in
adolescence (118) may be underestimated. Longitudinal
studies in children with obesity are required to delineate the
progression of CV abnormalities and the long-term health
consequences.
Cardiovascular Effects of Interventions in
Childhood Obesity
Indications for clinical interventions to prevent CVD in
overweight and obese children are not well defined. Current
clinical guidelines advocate lifestyle, dietary, and exercise
interventions for the prevention and management of obesity
and use BMI as an outcome measure of treatment success
(119,120), with more aggressive approaches such as phar-
macotherapy and bariatric surgery considered for severely
obese adolescents with serious complications who have failed
other, more conventional therapies (121). The efficacy of the
various obesity treatment options for children is a complex
topic and may be reviewed elsewhere (122,123). The most
common interventions for childhood obesity include eating
a healthy diet, increasing moderate-to-vigorous physical
activity, and reducing sedentary activities.
Exercise programs have positive effects on BMI and
measures of adiposity over short-term (i.e., 10 weeks) (124)
and moderate (4 months) timeframes (125). However, not
all studies have demonstrated reductions in BMI despite
other beneficial outcomes such as improved endothelial
function (126,127). Exercise may alter body composition
although body weight remains constant (128); thus, BMI as
a primary outcome measure may underestimate the effec-
tiveness of the intervention, particularly with respect to CV
risk. Reductions in central adiposity, determined using dual-
energy x-ray absorptiometry, were reported after only
8 weeks of circuit training despite no change in BMI or
waist circumference (129), highlighting the potential
underestimation of an intervention’s success when BMI is
the primary outcome measure.
JACC Vol. 62, No. 15, 2013 Cote et al. 1315
October 8, 2013:1309–19 Cardiovascular Effects of Childhood Obesity

Figure 1 Obesity-Related Mechanisms of Cardiovascular Dysfunction in Children

A simplistic schematic of a complex problem. The progression of cardiovascular dysfunction in children with obesity is not completely understood and is likely influenced by a variety
of genetic and environmental factors. The presence or absence of co-morbidities adds further complexity to understanding the mechanisms of obesity-related cardiovascular
dysfunction. AC ¼ arterial compliance; BP ¼ blood pressure; CO ¼ cardiac output; SNS ¼ sympathetic nervous system activity; SVR ¼ systemic vascular resistance.

Interventions designed to assess changes in CV structure
and/or function are limited. Reports of improved cardiac
function (37) and vascular function (91,126,129–132) with
exercise, as well as improved diastolic function after 6 months
of dietary intervention (133), are promising. Exercise-
induced improvements in FMD in children with obesity are
shown to be reversed after only 6 weeks of inactivity
(126,129), advocating exercise as a useful method of both
prevention and treatment. Given the energy demands on the
growing body in youth, vigorous physical activity has been
proposed to be more effective in the prevention of obesity than
restriction of energy intake (134). In contrast with these
results, 1 study reported reductions in BMI, waist circum-
ference, systolic blood pressure, and low-density lipoprotein
cholesterol after 10 weeks of aerobic or circuit training
(combination of aerobic and resistance exercises), in the
absence of improved arterial stiffness (124). Another study
found reductions in body fat and BMI that were not accom-
panied by improved endothelial function (135). In morbidly
obese adolescents, bariatric surgery improved cardiac
geometry and diastolic function (assessed at 10  3 months
post-operative) (136). Further, bariatric surgery was reported
to be associated with a decrease in epicardial fat (137).
Longitudinal randomized control studies with long-term
follow-up are required to evaluate the most effective
interventions.
Clinical Considerations
The research to date illustrates that obesity during childhood
and adolescence is associated with various measurable
alterations in CV structure and function. Interpretation of
research findings is complex, given the variation in the type
and number of CV risk factors present in children with
obesity. Our understanding of the cumulative effects of
multiple risk factors, the weighted importance of the risk
factor, and the effect of the length of exposure to the risk
factors is limited.
In the clinical setting, the measures discussed in this review
are not routinely performed, with the exception of quantifying
1316 Cote et al.
Cardiovascular Effects of Childhood Obesity
LV mass. Thus, the extent of obesity-related CV changes are
likely under-recognized and therefore under-managed. A
standardized clinical approach to the CV evaluation of chil-
dren with obesity is required. Importantly, this approach
should include early detection and evaluation of subclinical
cardiac dysfunction, given the potential for reversibility.
However, incorporating these assessments into clinical prac-
tice is challenging when specialized equipment and/or
personnel may be required. Furthermore, there is a lack of
adequate normative data with which to compare the individual
patient, and acquisition of these data is paramount to estab-
lishing clinical guidelines.
For the clinician, monitoring CV biomarkers is an attrac-
tive option for individual patient care as lipid screening
is already part of routine assessment and monitoring in
children with obesity. Biomarkers may indicate the progres-
sion of disease but causality cannot be assumed. Despite the
interest in the use of biomarkers to assess children at risk,
a recent review of CVD biomarkers in children concluded
there are insufficient data to recommend the use of any 1
biomarker in screening pediatric populations for CVD (138).
Future Directions
Considering the effects of aging on arterial stiffness and LV
relaxation patterns, obesity-related advancements in vascular
age and cardiac dysfunction during childhood will accelerate
the progression of CVD (12). What is most apparent from
the collective findings in this review is that childhood obesity
not only increases CV risk in adulthood, but is also associ-
ated with CV damage during childhood. As such, there is
an urgent need for prevention and treatment programs de-
signed specifically for children with obesity. Given the
paucity of interventional studies in this population, the
indications for intervention and the most effective therapy
for obese children with CV abnormalities have not been
adequately elucidated.
To advance our understanding of the CVD risk in
children with obesity, long-term comprehensive studies are
required that will provide standard normative values on
measures of CV function throughout childhood and take
into account adaptive changes associated with growth and
development. These normative values are required to dis-
tinguish the adaptive changes that occur during healthy
development from the maladaptive or pathological changes
occurring as a consequence of obesity. Furthermore, iden-
tifying biomarkers associated with adaptive changes in CV
function through growth and development and how these
biomarkers change with obesity-related CVD may provide
alternative cost-effective measures that can be used to
screen children for CV dysfunction. In addition, future
research should incorporate more clinically important
endpoints for evaluating the success of an intervention,
such as body composition in place of BMI or weight loss.
Despite the costs associated with imaging, percentage of
body fat quantified by dual-energy x-ray absorptiometry,
JACC Vol. 62, No. 15, 2013
October 8, 2013:1309–19
or magnetic resonance imaging to quantify visceral
adiposity and epicardial fat, will provide a more valid
assessment of the effectiveness of an intervention, in
addition to depicting CV risk more accurately than tradi-
tional anthropometrics.
Conclusions
Early identification of cardiac dysfunction in children with
obesity is warranted to mitigate long-term complications.
Longitudinal studies designed to track the progression of
CVD as well as those evaluating comprehensive treatment
interventions will guide clinical assessment choices and
ultimately permit risk stratification and optimal treatment
with evidence-based care guidelines.
Reprint requests and correspondence: Dr. Angela Devlin,
Department of Pediatrics, University of British Columbia, Chil-
dren and Family Research Institute, 272-950 West 28th Avenue,
Vancouver, British Columbia V5Z 4H4, Canada. E-mail:
adevlin@cfri.ubc.ca.
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Key Words: cardiac function - children - obesity - vascular dysfunction.