European Heart Journal Advance Access published March 24, 2015

European Heart Journal REVIEW

doi:10.1093/eurheartj/ehv089

Obesity and metabolic syndrome

Lifetime risk: childhood obesity and cardiovascular

risk
Julian Ayer1,2, Marietta Charakida3, John E. Deanfield3, and David S. Celermajer1,2,4*
1
The Heart Centre for Children, The Children’s Hospital at Westmead, Sydney, Australia; 2Sydney Medical School, University of Sydney, Sydney, Australia; 3Institute of Cardiovascular
Sciences, University College London, London, UK; and 4Royal Prince Alfred Hospital, Sydney, Australia

Received 22 December 2014; revised 2 March 2015; accepted 9 March 2015

In a recent report, the worldwide prevalence of childhood obesity was estimated to have increased by 47% between 1980 and 2013. As a result,
substantial concerns have been raised about the future burden of cardiovascular (CV) disease that could ensue. The purpose of this review is
to summarize and interpret (i) the evidence linking early life obesity with adverse changes in CV structure and function in childhood, (ii) the
lifetime risk for CV disease resulting from obesity in childhood, and (iii) the potential effects of lifestyle interventions in childhood to ameliorate
these risks.
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Keywords Obesity † Cardiovascular risk

Prevalence and trends Definitions of childhood obesity

The prevalence of childhood overweight and obesity has increased
dramatically, in both developed and developing countries, over the
last 30 years. A recent report, which combined many sources of
data, estimated that the worldwide prevalence of childhood
obesity had increased by 47.1% between 1980 and 2013.1 The
most marked rise occurred in developed countries; in 1980, 16.9%
of boys and 16.2% of girls were classed as overweight or obese but
this had increased to 23.8 and 22.6%, respectively, by 2013. An im-
portant increase in this prevalence has also been occurring in the
developing world, from 8.1 to 12.9% in boys and 8.4 to 13.4% in
girls, over the corresponding time. This high and increasing preva-
lence of childhood overweight and obesity mirrors trends in adults.
Despite lower prevalence rates than in many Western countries,
populous ‘emerging’ countries such as China and India face a major
burden of childhood obesity now and potentially into the future.
Data from recent U.S. national surveys suggest a recent plateau of
the prevalence of childhood overweight and obesity.2 However,
even here, the overall levels remain disturbingly high and there is sig-
nificant geographical variation in the trends.3 Furthermore, the
prevalence of childhood overweight and obesity is related to
poverty and ethnicity,4 making the imperative to reduce obesity
prevalence in childhood an issue of social justice, as well as a
medical and health economics problem.
Obesity is characterized by an excess of body fat which confers an
increased risk of adverse health outcomes. Body fat may be estimated
by a number of techniques (Table 1), each with different strengths and
limitations. Percent body fat (%BF) may be estimated by dual energy
X-ray absorptiometry (DXA). As DXA is not widely available
outside a research setting, the association of other, more easily obtain-
able, measures with %BF and their cut-points with health risks have
been evaluated. In children, skin fold thickness (SFT) correlates reason-
ably strongly with %BF but its reproducibility is poor, particularly for
single SFT measurements. Body mass index (BMI, kg/m2), although a
more practical and reproducible measure and the most widely
reported estimate of adiposity, is relatively insensitive in discriminating
between lean body mass and fat mass. In children, the association
between BMI and %BF is better for girls and young boys and less
accurate for older boys. Furthermore, the association between BMI
and %BF is dependent upon race/ethnicity and may not account for
other factors that influence weight-for-height, such as prior under-
nutrition. Definitions and estimates of prevalence rates of childhood
overweight and obesity are based upon comparison with BMI refer-
ence values, which are available, for example, from the World
Health Organization, U.S. Centres for Disease Control and Prevention
and The International Obesity Taskforce (IOTF). The ability of any
of the various childhood BMI cut-offs to predict the presence of

* Corresponding author. Tel: +61 2 95157110, Fax: +61 2 9550 6262, Email: david.celermajer@email.cs.nsw.gov.au; celermajer@bigpond.com
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2015. For permissions please email: journals.permissions@oup.com.
Page 2 of 8 J. Ayer et al.

Table 1 Methods of estimating body fat with potential clinical use

Technique Principle Strengths Weaknesses

...............................................................................................................................................................................
DXA Low energy X-rays are differentially
absorbed by different tissues
BIA Impedance to electric current
estimates total body water with
fat-free mass determined from
prediction equations
SFT Regional measurement of
subcutaneous fat as an indicator of
total fat
WC Measurement of waist using a flexible
tape measure in reference to
anatomical landmarks
WHtR Measurement of waist using a flexible
tape measure in reference to
anatomical landmarks and standard
measures of height
BMI A measure of weight relative to height
[weight (kg)/height squared (m2)]
Estimate fat free and fat mass and regional body
composition
Quick, inexpensive, and safe
Inexpensive, relatively easy to perform
Inexpensive, easy to perform, reflects total and
abdominal fat, association with cardiovascular
risk factors in children
Inexpensive, easy to perform, reflects total and
abdominal fat, does not require reference to
centile charts, associated with cardiovascular
risk factors in children and provides additional
information about cardiovascular risk over and
above BMI percentile
Quick, inexpensive, easy to perform
Expensive, time consuming, difficult to access,
the body size of the severely obese may
exceed the scanning area
Variability in devices and prediction equations,
inaccurate for prediction of fat mass in
individuals and better suited to determining
the direction of changes
Poor accuracy in the obese
In children requires reference to centile charts
In children requires reference to centile charts,
cannot discriminate between fat-free and fat
mass, variable cut-offs in children to define
overweight and obesity, variable reference
data

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adult cardiovascular (CV) risk factors or disease remains largely
unknown, although longitudinal data suggest low sensitivity of IOTF
overweight and obesity cut-offs in predicting adult hypertension and
hyperlipidaemia.5
Excessive visceral adipose tissue (VAT) rather than subcutaneous
adipose tissue appears to convey the highest cardio-metabolic risk in
adults.6 Waist circumference (WC) appears to contribute to the pre-
diction of abdominal fat, to a similar degree as BMI.7 In children, the
waist : height ratio (WHtR) may be a more practical measure than
WC, as it does not require conversion to a percentile. Waist circum-
ference and WHtR have been shown to predict cardio-metabolic risk
over and above BMI in some but not all studies of children and these
measures may help to define a metabolic healthy group of overweight
and obese youth.8 – 10 Despite these current uncertainties, it would
seem reasonable to include WC measurement and WHtR calcula-
tion in the routine assessment of overweight or obese children.
CV effects of obesity in children
Endothelial function and arterial stiffness
Endothelial dysfunction is a key early step in the development of CV
disease and may be assessed non-invasively using techniques such as
brachial artery flow-mediated dilatation (FMD). Increased arterial
stiffness, associated with an increased risk of CV disease in adults,
occurs with aging itself but may also be a result of higher levels of
certain CV risk factors. An indication of arterial stiffness may be
gained by measurements of the compliance or distensibility of an
arterial segment, the speed of transit of the pulse wave (pulse wave
velocity, PWV) or the timing and magnitude of wave reflection
(pulse wave analysis). Several smaller studies have demonstrated
reduced FMD and increased arterial stiffness in obese compared
with lean children and adolescents.11 – 21 These studies have largely
compared FMD and arterial stiffness between either severely (BMI
z-score .2.0) and/or older (.10 years) obese children and lean con-
trols.
In a large study of children and young adults (age range 10–24 years)
referred to a hospital clinic, Urbina et al. measured endothelial function
and arterial stiffness in lean controls (n ¼ 241) and obese subjects
without (n ¼ 234) and with (n ¼ 241) type 2 diabetes.22 There was a
progressive deterioration in endothelial function and arterial stiffness
from lean; to obese; to obese with type 2 diabetes, which remained
after adjustment for CV risk factors. In a large cohort of 10 and 11
year olds in the Avon Longitudinal Study of Parents and Children (n ¼
6576, 80% normal weight, 16% overweight, and 4% obese by IOTF cri-
teria), overweight and obese children had worse metabolic profiles,
better endothelial function and reduced arterial stiffness compared with
normal weight children.23 The overweight and obese children had a
higher heart rate, greater resting and reactive hyperaemic blood flow,
and larger brachial artery diameter, suggesting an adaptive hyperaemic
state in response to pre-pubertal adiposity. However, when over-
weight/obese (n ¼ 28) and lean (n ¼ 14) subjects were studied at age
14 and again at 19 years, there was a significantly greater increase in
PWV over 5 years in the overweight/obese (25% compared with 3%
in the lean adolescents) despite similar baseline PWV.24
Taken together, it is possible to speculate that there is an early
stage of ‘vascular adaptation’ that may be overcome with either
more severe or longer duration of obesity, the influence of pubertal
Childhood obesity and cardiovascular risk
development or the onset of type 2 diabetes. The effects of these
interactions remain to be clarified.
Arterial wall thickness
Structural changes in the arterial wall may be assessed on ultrasound
by measurement of intima-media thickness (IMT). In adults, IMT is
correlated with coronary and carotid atherosclerosis and is a signifi-
cant predictor of future CV events. In children, IMT is increased in
children at high risk for future CV disease, such as those with familial
hypercholesterolemia and type 1 diabetes mellitus.
Several studies have reported higher IMT in obese compared with
lean children and adolescents.11,16 – 19,21,25 Once again these studies
have largely been in older children and adolescents and in the signifi-
cantly obese. Other studies have not demonstrated a difference in
IMT despite changes in endothelial function or arterial stiffness.14,20
A cumulative burden of childhood obesity and/or interaction with
aging, puberty, and other CV risk factors may be required to
produce differences in arterial structure.
Furthermore, whether childhood obesity is independently asso-
ciated with arterial wall thickness in adulthood is uncertain. For
example, longitudinal data from the Young Finns Study demonstrated
an association between childhood BMI and adult IMT, which was sig-
nificantly attenuated or abolished after adjustment for adult BMI.26 – 28
As with effects on endothelial function and arterial stiffness,
arterial wall remodelling in obesity may be influenced by the dura-
tion and severity of obesity, the interaction of ‘obesity’ with other
CV/metabolic risk factors and also by pubertal development.
Cardiac structure
Left ventricular mass (LVM), a quantitative assessment of the thickness
of left ventricular muscle, is an independent risk factor for CV morbid-
ity and mortality.29 A number of studies have demonstrated increased
LVM in obese children and adolescents compared with normal weight
controls30 – 32 and increasing LVM with increasing childhood BMI.33
Although both LVM and BMI track from childhood into adulthood,
the strength of the association between BMI and LVM appears to
increase with age.33 Furthermore, in a study of 467 young adults, Li
et al. found that the significant independent determinants of adult
LVM were childhood BMI, current BMI, and systolic BP and the ‘cumu-
lative burden’ of BMI from childhood to adult life.34 The influence on
LVM of body composition (lean vs. fat mass) remains controversial
and may differ in overweight/obese compared with normal weight
children and may also vary by gender.35 – 37 A central distribution of
fat appears to be more highly correlated with LVM in children.30,38
Left atrial size is independently associated with a higher risk of atrial
fibrillation, stroke, heart failure, and death in adults.39 Several studies
have demonstrated an association between BMI and left atrial (LA)
size in childhood.40 – 42 and higher LA size in overweight/obese
than normal weight children.43 Tracking of LA size from childhood
to adult life and the strength of the association between childhood
BMI and adult LA size adjusted for adult BMI remain to be determined.
Evaluation of atrial phasic function with atrial strain has not been
reported in obese children. The relationship, however, between
LA size and obesity may relate to abnormalities in ventricular
mechanics, particularly diastolic dysfunction, which has been docu-
mented in asymptomatic obese adults44,45 and children.46 – 48 The
Page 3 of 8
degree of tracking of these abnormalities in ventricular mechanics
from childhood into adulthood also remains to be determined.
Taken together, these data suggest that childhood obesity has an
important effect on cardiac structure which persists into adult life
and may accentuate the cardiac effects of adult obesity.
Risk factor clustering in obesity
A number of studies have demonstrated that risk factors for CV
disease, such as high blood pressure, cholesterol, diabetes, and over-
weight/obesity, cluster together in children and adolescents and are
significantly inter-correlated.49 The statistical techniques of principal
components analysis reduce these risk factors into a smaller number
of summary factors, while retaining as much variance as possible in
the original variables. This appears to be a valid way to evaluate the
underlying determinants of CV disease risk. For example, in a study
of 1578 adolescents, Goodman et al. describe four such uncorrelated
summary risk factors: adiposity (including BMI, waist, fibrinogen, and
insulin), cholesterol (including low density lipoprotein- and total
cholesterol), carbohydrate-metabolic (including glucose, insulin,
high density lipoprotein (HDL)-cholesterol, and triglycerides), and
blood pressure (including systolic and diastolic BP).49 Such principal
components analyses suggest that obesity (and perhaps to a lesser
extent hyperinsulinaemia) is the most important correlate for
being at high risk for each of these summary factors.
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A particular pattern of risk factor clustering characterises the meta-
bolic syndrome (MetS). Although a standard definition for paediatric
MetS has been lacking until recently, some combination of increased
WC plus 2 or more of elevated triglycerides, low HDL-cholesterol,
hypertension, and glucose intolerance has been included in most
studies. Does a definition of MetS in youth help with defining CV
risk, over and above an analysis of the independent risk factors for
CV disease? Some50 – 52 but not all53 studies have demonstrated
greater alterations of CV structure and function in obese children
with MetS compared with obese children without MetS. Although
paediatric MetS predicts adult MetS and increased adult IMT, it is no
better at doing so than childhood BMI54 Furthermore, childhood.-
MetS which resolves in adulthood does not convey an increased
risk of high adult carotid IMT or type 2 diabetes.55
Longitudinal data from four large prospective cohorts indicate that
adult IMT increases with the number of childhood CV risk factors
measured after age 9 years.28 However, further data from long-term
cohort studies are required on whether risk factor clustering in child-
hood predicts the development of CVD in adults. Available data
support the notion that consideration of risk factor clustering in
children is important for determining future CV risk.
Mechanisms of CV dysfunction in
childhood obesity
The cumulative burden of ‘traditional’ CV risk factors that accompany
obesity may alter early steps in atherosclerosis (endothelial function,
arterial stiffness, adhesion molecule expression, foam cell formation,
and smooth muscle proliferation) as well as later changes (plaque
rupture and thrombosis). However, recent studies have focussed
on novel mediators of CV dysfunction in obesity. Dysfunctional
VAT (as part of an ‘adiposopathy’), in particular, may be an important
Page 4 of 8
source of mediators of inflammation, oxidative stress, and angiogen-
esis (Figure 1). These mediators, known as adipocytokines, may act
locally in an autocrine or paracrine manner or more distantly, in an
endocrine fashion. Although a detailed discussion is beyond the
scope of this review, there is a growing body of evidence linking
various adipocytokines, including leptin, resistin, adiponectin,
interleukin-6, and tumour necrosis factor-a, to different steps in
the development of CV disease. Much work has been done to
define the role of athero-inflammation of adiponectin, a 244-amino
acid protein which is produced principally by white adipose tissue
and which is paradoxically found in lower levels in obese compared
with non-obese subjects.56,57 Physiological levels of adiponectin
inhibit monocyte adhesion to human aortic endothelial cells, down-
regulate the expression of adhesion molecules on these endothelial
cells,58 suppress human aortic smooth muscle cell proliferation and
migration,59 inhibit macrophage foam cell transformation,60 and
increase the production of tissue inhibitor of metalloproteinase-1
(an important regulator of extracellular matrix degradation and
atherosclerotic plaque rupture).61 Apo-E deficient mice treated
with recombinant adenovirus that expresses human adiponectin
show significantly less atherosclerosis than control Apo-E deficient
mice.62 In human studies, low adiponectin levels have been associa-
ted with greater levels of hs-CRP,63 endothelial dysfunction in
adults and children,64 greater progression of coronary artery calcifi-
cation,65 thicker carotid IMT in adolescents,66,67 and women.68 These
studies have shown that actions of adiponectin are consistently
anti-atherosclerotic.
Figure 1 Schematic of the complex pathophysiology of CVD in ‘adiposopathy’ of obesity.
J. Ayer et al.
Reversibility of adverse CV effects
of childhood obesity
Intensive lifestyle interventions, of healthy eating, exercise, and redu-
cing sedentary activity, are the cornerstones of treatment of obesity
in childhood and adolescence. Clinical trials of lifestyle interventions
in adults report a weight-loss efficacy of between 5 and 10%, often
resulting in important improvements in CV risk factors. However,
such efficacy is rarely seen in the primary care setting and long-term
weight maintenance remains a problem. Paediatric lifestyle inter-
vention trials have also reported improvements in body composition
and metabolic parameters. Several paediatric studies have shown
improvements in FMD and/or IMT with diet alone,69 exercise
alone12,13,70 – 73 or diet and exercise (Table 2).69
A recent review of adult outcomes after bariatric surgery supported
a benefit on CV mortality and morbidity. Several studies have reported
benefits of bariatric surgery on CV risk factors, endothelial function,
IMT progression, LV mass and function. In adolescents, bariatric
surgery has been recommended as an adjunct to lifestyle interventions
with BMI .40 kg/m2 plus a severe co-morbidity or BMI .50 kg/m2
and a less severe co-morbidity.74 Although bariatric surgery has
been show to reverse the metabolic complications and cardiac struc-
tural and functional changes of severe adolescent obesity, few other
reports of its long-term effects on CV health in youth have been
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reported.75
A number of weight-loss drug therapies have been approved
for use in adults worldwide, including orlistat, lorcaserin, and
Childhood obesity and cardiovascular risk Page 5 of 8

phentermine plus topiramate-ER. The evidence of the impact of
these medications in children and adolescents on weight loss is
limited and little, if any, data are available on their CV effects at this
age. Metformin appears to improve insulin resistance and other meta-
bolic markers in obese adolescents.
Childhood obesity and lifetime CV
risk
Estimating the lifetime risk for obese children has been challenging as
most of the information is derived from observational studies. In a
cohort of children born in Denmark a higher BMI in childhood was
associated with increased risk for coronary heart disease in adult-
hood. A 55-year follow-up of the Harvard Growth Study showed
that being overweight in adolescence resulted in a 2-fold higher
risk of coronary heart disease mortality which was independent
of adult weight. A British study that involved a 57-year follow-up of
a cohort also confirmed that all-cause and CV mortality were
increased when childhood BMI was higher than the 75th centile.
More recently, in the Bogalusa Heart Study elevated blood pressure
and adiposity from childhood onwards had an adverse effect on LVM
and geometry in 1061 subjects.76 Even if the prevalence of obesity
in the young can be reduced, a substantial number of children who
are currently overweight or obese will grow up to be obese adults.
obesity also appears to confer an increased lifetime risk for CV
disease. These data highlight the major CV health opportunities
that are likely to arise from the development and implementation
of strategies that reduce the prevalence of childhood overweight
and obesity.
Appropriately, the greatest medical focus will be on the develop-
ment of ‘treatments’ for severely obese children and adolescents
with the highest future CV risk and most abnormal CV structure
and function. However, the greatest population burden of CV
disease will be driven by those with lesser degrees of excess adiposity.
Here, the development of unifying strategies to address both child-
hood and adult obesity will be made harder by environmental, cul-
tural, and economic factors that promote increased caloric intake
and sedentary lifestyles. Recently, strategies for the prevention and
management of obesity in early life have been the subject of several
national public health guidelines. Implementation of these guidelines
will require a concerted effort of many stakeholders, which will
include politicians, infrastructure planners, physicians, scientists,
and other professionals to convey the ‘lifetime risk’ message to fam-
ilies and to support the early management of childhood obesity.
Future directions
There remain substantial gaps in our understanding of the develop-

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Achieving sustained weight loss is a challenge. The predicted
increased lifetime burden of CV morbidity and mortality in these sub-
jects can however be attenuated by reduction in risk factors such as,
cholesterol and blood pressure even if weight cannot be optimized.77
Clinical implications
Current data indicate that obesity unfavourably alters CV structure
and function during childhood and adolescence itself. Childhood
ment of CV disease in children and adolescents who are overweight
or obese. It remains uncertain how best to measure clinically the CV
risk in the young. What measurements undertaken at what time
points in childhood best predict CV disease in adult life? Other
than LVM, clinical measurements of adverse CV alterations are not
yet available and it is unclear whether routine assessment of endothe-
lial function, arterial stiffness, ventricular wall thickness, or mechanics
will help to stratify risk in children and whether those measures will
support more aggressive therapy, including weight-loss medication

Table 2 Studies examining the effects of interventions to reduce obesity on cardiovascular structure and function in
children

First author, tear Type(s) of Number(s) in Number in Age Intervention Cardiovascular effects:
(Ref. no.) intervention (s) intervention non-intervention (years) duration intervention vs.
group (s) group (month) non-intervention
...............................................................................................................................................................................
Farpour-Lambert, Exercise 22 22 8.9 + 1.5 3 + further 3 BP, fat, fitness (3
200912 open label months) BP, IMT,
arterial stiffness, no
effect on FMD (6 months)
Woo, 200419,69 Diet only or 41 – 9.9 + 1.0 1.5 FMD
diet + exercise 41 –  FMD
Kelly, 200472 Exercise 10 10 2 FMD
Watts, 200413,71 Exercise 19 19 14.3 + 1.5 2 FMD
Meyer, 200611,70 Exercise 33 34 14.7 + 2.2 6 FMD, IMT
Watts, 200413,71 Exercise 14 14 8.9 + 0.4 2 FMD
Ippisch, 200873 Bariatric surgery 38 – 16 + 1.0 10 BP, LVM,  diastolic
function
Mitchell, 200273 Exercise 20 15 13– 16 8 No effect on LVM

BP, blood pressure; IMT, intima-media thickness; FMD, flow-mediated dilatation; LVM, left ventricular mass.
Page 6 of 8
or bariatric surgery. Larger cross-sectional measurements of these
parameters in healthy children to derive population norms will be
helpful. Although childhood obesity appears to convey a lifetime
risk for CV disease, it remains unclear as to what factors during the
passage through childhood into adult life may influence this risk.
Large-scale multi-ethnic longitudinal studies, undertaken preferably
from birth but certainly from early childhood, are required to study
these factors. Measurements should preferably include more
detailed assessments of body composition and fat distribution and
pubertal development. Some lifestyle intervention studies have indi-
cated reversibility of adverse CV structure and function over a short
or intermediate time frame. The long-term effects on CV risk and
disease of lifestyle interventions, drug therapies, and bariatric
surgery in children and adolescents remain to be determined.
Conclusions
Considerable evidence exists for adverse effects of childhood obesity
on CV structure and function. Evidence also exists for childhood
obesity conferring an increased lifetime risk for CV disease. Further
research is required on factors which may interact with obesity to
alter this risk. However, sufficient information is available to be con-
cerned about the future burden of CV disease that childhood obesity
entails. Such data support the call to arms to develop better therapies
to manage childhood obesity and society wide changes to reduce its
prevalence.
Conflict of interest: none declared.
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