REVIEW ARTICLE

Pediatric Precursors of Adult Cardiovascular Disease:

Noninvasive Assessment of Early Vascular Changes in
Children and Adolescents
Judith A. Groner, MDa,b, Mandar Joshi, PhDb, John A. Bauer, PhDa,b
aDepartment of Pediatrics, Ohio State University College of Medicine, bCenter for Cardiovascular Medicine, Columbus Childrens Hospital Research Institute, Columbus
Childrens Hospital, Columbus, Ohio

The authors have indicated they have no nancial relationships relevant to this article to disclose.

ABSTRACT
BACKGROUND. Until recently, our understanding of the childhood antecedents of adult
cardiovascular disease was limited mainly to autopsy studies and pathologic findings in teens and young adults who died from accidental causes. Recent advances
in the understanding of atherosclerosis and new technologies allowing detection of
early events have made it possible to observe anatomic and physiologic evidence
of cardiovascular disease in young adults and children.
OBJECTIVES. The goal of this article was to introduce pediatricians to new methods for
noninvasive measurement of cardiovascular disease and its precursors, to describe
the potential application of these techniques in detecting childhood precursors of
adult cardiovascular disease, and to summarize knowledge gained from this approach.
METHODS. We conducted a computerized search of peer-reviewed articles listed in
PubMed and Medline from 1980 to April 2006. We reviewed 63 and 84 articles
from the adult and pediatric literature, respectively.
RESULTS. Reviewing the research on childhood antecedents of adult cardiovascular

disease is sobering. Vascular alterations in anatomy, physiology, mechanical properties, and proinflammatory and prothrombotic changes are present from a very
early age of childhood and are associated with the risk factors common in adult
cardiovascular disease. At the same time, this body of research supports the
concept that the vascular impairment from childhood may improve over time with
appropriate intervention.

www.pediatrics.org/cgi/doi/10.1542/
peds.2005-2992
doi:10.1542/peds.2005-2992
Key Words
cardiovascular disease, atherosclerosis,
ow-mediated dilation, intima-medial
thickness, arterial distensibility,
inammation, homocysteine, childhood
obesity
Abbreviations
CVD cardiovascular disease
IMTintima-medial thickening
FMDow-mediated dilation
CRPC-reactive protein
LDLlow-density lipoprotein
Accepted for publication May 15, 2006
Address correspondence to Judith A. Groner,
MD, Department of Pediatrics, Ohio State
University, Center for Cardiovascular Medicine,
Columbus Childrens Hospital Research
Institute, Columbus Childrens Hospital, 700
Childrens Dr, Columbus, OH 43205. E-mail:
jgroner@chi.osu.edu
PEDIATRICS (ISSN Numbers: Print, 0031-4005;
Online, 1098-4275). Copyright 2006 by the
American Academy of Pediatrics

CONCLUSIONS. The measurement tools and concepts described in this article offer
diagnostic and therapeutic opportunities for collaboration between clinical pediatricians and pediatric researchers. These partnerships will enable pediatricians to
contribute in an effort to reduce the burdens of cardiovascular disease to individuals, families, and society.

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DULT CARDIOVASCULAR DISEASE (CVD) begins and

progresses during childhood and adolescence.
Pediatricians are currently witnessing a pandemic of
childhood obesity, with concomitant secondary hypertension, hyperlipidemia, and the metabolic syndrome,
which are linked to CVD in adulthood. The atherosclerotic process develops silently for decades during childhood and adolescence before cardiovascular complications such as myocardial infarction and stroke occur in
adulthood. Until recently, our understanding of the
childhood antecedents of adult CVD was limited, having
been based on autopsy studies of pathologic findings in
teens and young adults who died of accidental causes.
However, recent advances in the conceptualization of
the process of atherosclerosis and the development of
new noninvasive technologies has made it possible to
detect early changes (anatomic, physiologic, mechanical,
proinflammatory, and prothrombotic) of CVD in adults
and children.
The blood vessel wall consists of 3 concentric layers:
intima, media, and adventitia. The intima, adjacent to
the blood vessel lumen, is composed of a monolayer of
endothelial cells with minimal underlying connective

tissue. Far from being inert, endothelial cells perform

crucial roles in regulating vascular tone and structure.1
These roles include providing a nonthrombotic surface,
maintaining vascular tone by releasing small molecules
such as nitric oxide, prostacyclin, and endothelin (which
modulate vasodilation or vasoconstriction), and providing a nonadherent surface of leukocytes.2 Endothelial
dysfunction was initially identified as impaired vasodilation to specific stimuli, but recent investigations
have broadened the term to also include a proinflammatory and prothrombotic state. Traditional risk factors for
CVD (hypercholesterolemia, hypertension, diabetes,
family history of CVD, and active smoking) and morerecently identified risk factors (inflammation, infection,
secondhand smoke exposure, homocystinemia, physical
inactivity, and obesity) are associated with endothelial
dysfunction in both adults and children (Fig 1).1,310 Dysfunction of the endothelium over time leads to measurable thickening of the intima and media of the vessel
wall of large- and medium-sized muscular arteries and
large elastic arteries such as the aorta, carotid, and iliac
arteries.11 This thickening is typically considered the earliest anatomic change of atherosclerosis.

FIGURE 1
The relationship between endothelial dysfunction and risk factors for CVD. (Adapted from Widlansky ME, Gokce N, Keaney JF Jr, Vita JA. J Am Coll Cardiol. 2003;42:1149 1160.)

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The role of inflammation in the development of CVD

has been appreciated in the past several years, and subsequent processes leading to increased cellular oxidation
have been implicated.3,12 Atherosclerosis, the main cause
of coronary artery disease, is now thought to be a
chronic inflammatory disease in which immune mechanisms interact with metabolic risk factors to initiate,
maintain, and activate arterial lesions.13 In this process,
immune cells dominate early atherosclerotic lesions, and
activation of inflammation can elicit acute coronary
symptoms.
The goal of this article is to introduce pediatricians to
the noninvasive methods for measurement of CVD and
to summarize knowledge gained from the application of
these techniques to pediatric populations. Understanding these advances will help pediatricians develop a
greater appreciation of their role in preventing, detecting, and ameliorating conditions in childhood that lead
to CVD later in life.
METHODS
We conducted a computerized search of articles in
PubMed and Medline from 1980 to April 2005 using
the search terms atherosclerosis, atherosclerosis and
children, cardiovascular disease, cardiovascular disease and children, intima-medial thickness, intimamedial thickness and children, flow-mediated dilation, flow-mediated dilation and children, arterial
distensibility, arterial distensibility and children, inflammation and atherosclerosis, inflammation and
atherosclerosis and children, homocysteine, and
homocysteine and children. Because our focus was on
pediatric populations, we selected only key review and
summary articles from the adult literature and reviewed
most of the articles from the pediatric literature. We
reviewed 63 and 84 articles from the adult and pediatric
literature, respectively.
RESULTS
Noninvasive Measurement of CVD in Adults
Anatomic Changes: Intima-Medial Thickness
The first morphologic changes of the arterial wall, thickening of the intima and media, can be imaged by Bmode, high-resolution ultrasound. Intima-medial thickening (IMT), which precedes clinical cardiovascular
events by decades, is considered a marker of generalized
atherosclerosis in adults. The arteries most commonly
examined in adults are the internal and common carotid
arteries in the vicinity of the carotid bulb and the carotid
bulb itself.14 Carotid IMT in adults is associated with
arteriographically documented lesions and subsequent
myocardial infarction and stroke and also with the
presence of known cardiovascular risk factors such as
diabetes and obesity.14,15 The routine use of IMT as an
outcome measure has been recommended for many ep-

idemiologic and interventional trials in adults dealing

with vascular disease.16 IMT measurement is currently
being integrated into the clinical practice of adult medicine.
Physiologic Changes: Flow-Mediated Dilation and
Endothelial Performance
Noninvasive ultrasound measurement of flow-mediated
dilation (FMD) was developed in the 1990s and has been
extensively used in adult cardiovascular research to assess endothelial functional integrity. This test is performed at the brachial artery and measures the vasodilator response to increased blood flow. The underlying
physiologic principle is a phenomenon known as shearstressinduced vasorelaxation. This response is known to
be endothelium mediated and is governed by the ability
of the endothelial monolayer to produce nitric oxide in
response to shear stress, which in turn causes smoothmuscle dilation.17,18 Studies on adults have shown a close
correlation between the endothelial function peripherally (at the brachial artery) and that of the coronary
circulation.19 In adults, endothelial dysfunction measured by FMD has been shown to be an independent
predictor of CVD events in both the short- and longterm.20
Mechanical Changes: Arterial Distensibility
Arterial distensibility or, conversely, arterial stiffness is a
measure of vascular elastic behavior.21 In addition to
reflecting the structural arrangement of the artery, endothelial function is also implicated in arterial distensibility by directly affecting the vascular tone through the
nitric-oxide pathway.21 Distensibility or stiffness can be
assessed noninvasively using B- or M-mode imaging by
measuring change in lumen diameter from systole to
diastole, coupled with the measure of the local pulse
pressure.22 An alternative measure, pulse-wave velocity,
has also been used to assess arterial distensibility. The
propagation of the pulse wave along the arteries is related to the elastic properties of the arterial wall.21 The
reproducibility of these measurements is adequate for
application in epidemiologic studies.22
The most prominent factor in increasing arterial stiffness is aging, which equally affects males and females.21
Pathologic reductions of arterial distensibility lead to
increased left ventricular afterload, decreased coronary
artery perfusion, increased systolic blood pressure, and
trauma to the vessel wall, which, in turn, leads to atherosclerotic vascular changes.23 Active smoking, hyperlipidemia, hypertension, congestive heart failure, and
diabetes (types 1 and 2) are all associated with decreased
arterial distensibility.23
The body of research on arterial stiffness as a risk
factor for CVD is not as extensive as that on IMT or FMD.
Despite substantial cross-sectional evidence, longitudinal
data on the relationship of arterial stiffness with future
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CVD is limited to patients with hypertension, patients

with end-stage renal disease, the elderly, and renal
transplant recipients.
Inflammatory Changes: C-Reactive Protein
Low-grade chronic inflammation, as indicated by C-reactive protein (CRP), prospectively defines the risk of
atherosclerotic complications, adding prognostic information to the traditional risk factors. In the mid-1990s,
immunoassays for CRP, with greater sensitivity than
those used previously, revealed that increased CRP values, even those within the range previously considered
normal, strongly predicted future coronary events.24 Recent studies have also suggested that CRP is not only a
predictor but also a mediator of endothelial injury. CRP,
at concentrations known to predict vascular disease, has
a direct effect in stimulating diverse early atherosclerotic
processes.25,26 Intensive statin therapy has been shown to
have a beneficial effect on the rate of progression of
coronary artery disease because of an independent effect
of lowering the CRP level in addition to the classic lowering of low-density lipoprotein (LDL) cholesterol.5
Measurement of CRP is currently emerging as a clinical
tool in adult medicine for risk-factor assessment and as a
marker of clinical improvement for patients on statin
therapy.
Inflammatory and Prothrombotic Changes: Homocysteine
The observed high frequency of premature occlusive
vascular disease among young people with homocystinuria, caused by a rare hereditary defect in homocysteine
metabolism, prompted the hypothesis that moderately
elevated homocysteine levels may be a risk factor for
CVD and stroke in the general population.27 Elevated
plasma total homocysteine may be a result of genetic
defects, vitamin deficiencies, or renal impairment.28 The
pathophysiology of the atherogenic propensity of homocysteine is hypothesized to be based on direct toxic endothelial cell damage generating potent reactive oxygen
species, which can induce oxidative damage to endothelial cells, in addition to directly decreasing endothelial
production of nitric oxide. This leads to impaired endothelial-dependent vascular reactivity, resulting in platelet activation and thrombus formation.10,29,30
Vitamins B6 and B12 and folate are involved in homocysteine metabolism. Because an elevated homocysteine level is treatable (hypothetically) with these
substances, there has been considerable interest in determining if, indeed, elevated homocysteine is an independent risk factor for CVD and if dietary changes could
produce significant clinical effects in decreasing both
homocysteine levels and the rate of CVD.31 Currently,
the importance of the contribution of a moderately
elevated homocysteine level to CVD in the general population is uncertain. Multiple prospective studies suggest an association of homocysteine with CVD, but the
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relationship is weaker than previously believed.29 The

American Heart Association,32 at present, does not recommend generalized population screening for homocysteine levels but does advocate targeted homocysteine
screening for adults at high risk. Recent reports indicate
that supplementation with B vitamins does not lower
the risk of recurrent CVD33 or reduce the risk of major
cardiovascular events in patients with preexisting vascular disease.34
Use of New Techniques: Childhood Antecedents of Adult
CVD
Information on the prevalence and extent of atherosclerotic changes in teens and young adults in the United
States comes from several large studies, both prospective
and cross-sectional. The Muscatine and Bogalusa studies
are relevant to this discussion because large cohorts of
subjects recruited and followed in these 2 studies became available as young adults for noninvasive imaging
studies. Researchers are now able to relate risk factors
measured during childhood to preclinical vascular
changes in young adults. The relationship between
childhood risk factors and adult vascular changes is complicated by the fact that some risk factors (eg, obesity)
tend to track from childhood to adulthood. Relationships
between childhood risk factors and vascular changes in
adulthood may be a result of the persistence of the
particular risk factor into adulthood. Complex statistical
analyses are required to determine the contribution of
risk factors present during childhood to adult vascular
changes. The large sample sizes involved in these cohort
studies makes such analyses possible.
The Muscatine study
Between 1971 and 1981, 14 000 schoolchildren
(aged 8 18 years, predominantly white) in Muscatine,
Iowa, underwent biennial examinations that assessed
their height, weight, blood pressure, triceps skinfold
thickness, and total cholesterol and triglyceride levels.
Every 10 years, a subset of the original sample underwent repeat testing, which included more advanced
noninvasive assessments that were not available at the
original recruitment time.35 In the late 1990s, a subset of
750 of the original participants (with equal proportions
of men and women) underwent repeat testing, including
measurement of carotid intima-medial thickness. This
assessment revealed that total cholesterol level, measured during childhood, was a significant independent
risk factor for carotid thickening during adulthood for
both men and women; elevated BMI during childhood
was also a significant independent risk factor for women
only.35
The Bogalusa Heart Study
This project is one of the longest and most detailed
prospective studies of children with a focus on the early
natural history of coronary artery disease and essential

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hypertension. The study began in 1973 in Bogalusa,

Louisiana, and is still ongoing. The original population
consisted of both white (65%) and black (35%) schoolaged children and young adults up to 35 years of age.
More than 16 000 individuals have participated, and
9500 have had multiple measurements of cardiovascular risk factors, including BMI, triceps skinfold thickness, lipid profile, and smoking status. Observations
from the Bogalusa Heart Study have shown that major
etiologies of adult CVD, atherosclerosis, coronary artery
disease, and essential hypertension begin in childhood,
with documented anatomic changes as early as 5 to 8
years of age.36
A recent examination of 500 young adults from the
Bogalusa Heart Study revealed that childhood risk factors were associated with adult carotid IMT. An elevated
LDL-cholesterol level and elevated BMI during childhood were found to be independent risk factors for
increased carotid thickening in young adulthood.37 Another analysis using the Bogalusa data set revealed that
adult obesity modified the association between childhood obesity and IMT; arterial thickening was seen only
among overweight children who became obese adults.
IMT was not present among nonobese adults who had
been overweight children or among obese adults who
had been nonoverweight children. These results emphasize the adverse, cumulative effects of childhood-onset
obesity that persist into adulthood.38
In addition to using the newer noninvasive measurements in adult cohorts who have been followed since
childhood, researchers have investigated vascular anatomy, physiology, and inflammation in both clinical and
population-based samples of children.

Application of New Measurement Modalities to Pediatric

Populations
Anatomic Changes: IMT
Investigators have used IMT measurements to study
children at high risk for development of atherogenesis
later in life. Children with familial hypercholesterolemia
were found to have higher IMT than age-matched
healthy children.39 IMT was associated directly with elevated total and LDL cholesterol and triglyceride levels
and inversely correlated with high-density lipoprotein
cholesterol levels in the affected children.6,39 Children
with hypertension have higher carotid IMT than normotensive children; these differences remained significant
even after controlling for gender, race, age, and BMI.40
Investigations of IMT in children with type 1 diabetes
have shown conflicting results, with some researchers
reporting no effect on IMT and others reporting IMT
related to the duration of diabetes.6,4143
Findings with clinical applicability to pediatricians include:

1. Overweight and obesity are related to vascular thickening. Obesity has been shown to be highly associated with IMT in several studies.7,44,45 Additional research has demonstrated that overweight alone,
without extreme obesity, was independently associated with arterial thickening in a population in whom
excess weight was not confounded by coexisting risk
factors such as hypertension and hyperlipidemia. A
group of 36 overweight but nonobese children was
found to have significant carotid thickening compared with age-matched nonoverweight controls.
The children were between the ages of 7 and 12 years
and were matched for age, gender, blood pressure,
and cholesterol and glucose levels.44
2. Carotid IMT is reversible. Investigators measured IMT
in overweight and obese children who were enrolled
in a clinical trial of lifestyle modification and assigned
to 1 of 3 groups: dietary modification alone for 1 year,
dietary modification for 1 year plus exercise for 6
weeks, and dietary modification plus exercise sustained for 1 year. There was no change detected in
IMT after 6 weeks in any of the 3 groups. However, at
1 year, children in the diet-only group and in the
diet-plus-sustained-exercise group showed significant regression in carotid IMT despite the fact that
there was no significant change in BMI in any of the
groups.45 The implication of this research is that, over
time, anatomic changes consistent with early atherosclerosis in children are modifiable by sustained diet
or sustained diet and exercise.
Physiologic Changes: FMD
FMD has been used in pediatric research since the 1990s.
To date, at least 19 studies using this technique in children have been published. Investigators have assessed
FMD in special populations of children such as those
with type 1 diabetes, familial dyslipidemias, hypertension, Kawasakis disease, and severe obesity.9,11,4650 This
body of research has confirmed that endothelial dysfunction is found in the childhood conditions that are
known to predispose to early atherogenesis.
Recently, investigations of endothelial function in
children have revealed findings with clinical applicability
for pediatric populations:
1. Obesity and overweight are related to FMD impairment and are reversible with exercise. Obese and
overweight children have been shown to have FMD
impairment that is reversible with exercise even in
the absence of weight loss. In the past 2 years, 3
research groups have reported on the effect of exercise training on FMD in overweight and obese children.44,45,51,52 In all of the studies, FMD impairment
was noted in the overweight or obese children that
subsequently improved after exercise training even in
the absence of weight loss. FMD was an additional
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outcome measurement in the clinical trial of lifestyle

modification described above. Investigators randomly
assigned overweight children to 1 of 3 interventions:
dietary modification alone for 1 year, dietary modification for 1 year plus exercise for 6 weeks, and dietary modification plus exercise sustained for 1 year.
Children in the diet-only and diet-plus-exercise
groups both showed FMD improvement in the shortterm (6 weeks), although there was no significant
change in BMI in either group. The improvement was
significantly greater in the diet-plus-exercise group.
Children who continued to exercise showed sustained improvement in FMD after 1 year, whereas
those in the diet-only group showed no sustained
improvement.45 These findings imply that, for children, sustained exercise even in the absence of
change in BMI in children has a protective effect on
their vascular physiology.

that arterial distensibility inversely correlates with BMI.

A relationship between obesity in childhood and increased arterial stiffness (as defined by decreased arterial
distensibility) has been described.47,59,60 This association
has been noted among severely obese children59,61,62 and
among those with the metabolic syndrome.62 The relationship remains even among normal children from
nonclinical samples. Whincup et al59 described a consistent independent inverse relationship between all measures of adiposity and arterial distensibility among nearly
500 children aged 13 to 15 years. It is interesting to note
that the research group had studied the same population
of children 2 years earlier and did not find the association between obesity and arterial stiffness. This finding
of a particular timing for the adverse effects of obesity on
arterial distensibility is intriguing and warrants further
investigation.

2. Regular physical activity in healthy children is associated with greater endothelial function. Investigators
measured habitual physical activity levels using a
well-validated technique in a group of healthy children (aged 510 years) in Australia. The level of
physical activity emerged as a strong and consistent
predictor of FMD.8 This research suggests that physical activity at a very young age may influence arterial
health.

Inflammatory Changes: CRP

The CRP level in children has been shown to correlate
most consistently with BMI.6365 Children and adolescents with the metabolic syndrome are 4 times more
likely than those without the syndrome to show evidence of low-grade inflammation as measured by the
CRP level.66 CRP levels seem to increase with the degree
of obesity65 along with other markers of inflammation.
There is conflicting evidence regarding the presence of a
direct relationship between elevated CRP and insulin
resistance in children.51,65 Key findings from research on
CRP in children include:

Mechanical Changes: Arterial Distensibility

Arterial distensibility during childhood can be measured
by assessing changes to vessel diameter during the cardiac cycle or by pulse-wave velocity53 and can be determined at either the carotid or brachial artery.54,55 Arterial
distensibility decreases from early childhood to adolescence.5658 Research in pediatric populations has shown
that early mechanical changes in the arterial wall may
precede the appearance of arterial structural changes.
Boys aged 10 to 19 years who have heterozygous familial hypercholesterolemia had decreased brachial artery
distensibility independent of their LDL or total cholesterol levels.54 None of the children had echographic evidence of atherosclerotic lesions, and no IMT was found.
The decreased distensibility may be a result of the effects
of endothelial dysfunction, via the nitric-oxide pathway,
rather than the effect of actual physical changes in the
arterial wall.
Arterial distensibility has been studied in a large population-based sample of almost 500 children aged 9 to 11
years.55 Total and LDL-cholesterol levels were inversely
related to arterial distensibility in this sample. This finding is intriguing, because the children were from a nonclinical population, with total and LDL-cholesterol levels
in the range of the general population.
In addition to these investigations, researchers have
focused on arterial distensibility and obesity and found
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1. Low-level inflammation is present in very young children and is related to BMI. Analysis of the National
Health and Nutrition Examination Survey from
1999 2000 showed that BMI had a strong independent association with CRP level for children in all age
groups from 3 to 17 years. This relationship was
noted even in the subgroup of very young children
between the ages of 3 and 7 years.66
2. Evidence of inflammation is associated with endothelial dysfunction. Recent research has demonstrated
that the relationship between inflammation and endothelial dysfunction emerges even during childhood. An elevated CRP level even among healthy
children has been shown to be associated with a
reduction in FMD.67 Recently, investigators have
shown impaired FMD in children with acute infection; children recovering from infections also showed
impairment but to a lesser degree.68 This research on
healthy children supports a potential role for previously unsuspected extrinsic inflammation in the
pathogenesis of CVD.
Inflammatory and Prothrombotic Changes: Homocysteine
Homocysteine levels in children are substantially lower
than those in adults, and increase with age.69 Levels are

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higher in boys than in girls after age 10.70 Homocysteine

levels in children seem to be inversely related to serum
folate levels.69,71,72 The role of homocysteine in the general pediatric population (without homocystinuria) as a
childhood antecedent of adult CVD is unclear. No relationships have been reported between lipid profile,
blood pressure, and BMI and homocysteine levels in
children.69 71 However, one research group reported that
homocysteine levels in children aged 10 to 19 were
independently correlated to carotid IMT in children.72
Homocysteine has been investigated as a serum
marker of risk in children from families with a history of
premature CVD, with conflicting findings.69,71 Tonstad et
al investigated 700 children aged 8 to 12 years and
reported that homocysteine was higher among children
whose father, grandfather, or uncle died at 55 of age as
a result of myocardial infarction or sudden cardiac arrest
than control children after adjusting for socioeconomic
status. Analysis of a subsample of children involved in
the Bogalusa study produced similar findings.71 Children
with a positive parental history of coronary artery disease had significantly greater age-adjusted homocysteine
levels than those without a positive history; this relationship was observed in each race and gender group.
However, analysis of another large data set from the
CATCH (Children and Adolescent Trial for Cardiovascular Health) cohort did not support these findings.67 Investigators found no relationship to the childs homocysteine level and family history of stroke or myocardial
infarction or premature CVD as defined by these events
in a relative younger than 60 years. It is possible that this
definition of family history of CVD was not sensitive
enough to capture the at-risk children.
IMPLICATIONS FOR PEDIATRICIANS
The measurement tools described here offer diagnostic
and therapeutic opportunities for collaboration between
clinical pediatricians and pediatric researchers. The
availability of adequate noninvasive measures of anatomic, functional, mechanical, proinflammatory, and
prothrombotic vascular changes during childhood will
greatly enhance our insight into causes, development,
and pathophysiologic mechanisms of CVD. In addition,
these tools will be essential in assessing treatment protocols for reversing or ameliorating these changes before
adulthood. For example, assessment of arterial thickness, distensibility, endothelial function, and the proinflammatory and prothrombotic state, alone or in combination, may offer a method for identifying children who
are the highest risk for CVD in adulthood and to form
specific treatment strategies. Children with hypercholesterolemia who have impaired FMD may benefit from
pharmacologic therapy (statins) more than those without endothelial dysfunction. Obese children with abnormally thickened arteries may be targeted for more intensive exercise and dietary modifications. Conversely,

children with a particular risk factor who have normal

endothelial function, normal CRP levels, and normal
FMD may be followed sequentially with less-aggressive
intervention.
Once identified, there is a role for repeat testing in
measuring the result of a particular intervention. The
research reviewed here has shown that obese children
showed improvement of endothelial function in the
short-term and reversed vascular change in the longterm via long-term sustained lifestyle modifications, although there was no actual reduction in their BMI.
Sequential measurements of FMD and IMT for children
who are undergoing intensive lifestyle modifications will
provide positive feedback for those who are actually
making the desired changes, even if BMI reduction is not
attained.
CONCLUSIONS
Reviewing the research on childhood antecedents of
adult CVD is sobering. Vascular alterations in anatomy,
physiology, mechanical properties, and proinflammatory and prothrombotic changes are present from a very
early age and are associated with the risk factors common in adult CVD: overweight and obesity, inflammation, hypertension, and abnormal lipid profiles. Many of
these risk factors are known to track into adulthood. For
at least 1 of the risk factors (obesity) there is evidence of
a cumulative negative impact on adult cardiovascular
health from its presence during both childhood and
adulthood. At the same time, this body of research supports the concept that the vascular changes in childhood
may improve over time with appropriate intervention.
Advances in this field will be made when clinical pediatricians collaborate with pediatric researchers. These
partnerships will enable pediatricians to contribute in an
effort to reduce the burdens of CVD to individuals, families, and society.
ACKNOWLEDGMENTS
This work was supported in part by National Institute of
Child Health and Human Development grant 1R21 HD
50944-01, Health Resources and Services Administration grant 5D52 HP007-05-00, the Flight Attendant
Medical Research Institute, and the American Diabetes
Association.
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1691

Pediatric Precursors of Adult Cardiovascular Disease: Noninvasive Assessment

of Early Vascular Changes in Children and Adolescents
Judith A. Groner, Mandar Joshi and John A. Bauer
Pediatrics 2006;118;1683
DOI: 10.1542/peds.2005-2992
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PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

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Pediatric Precursors of Adult Cardiovascular Disease: Noninvasive Assessment

of Early Vascular Changes in Children and Adolescents
Judith A. Groner, Mandar Joshi and John A. Bauer
Pediatrics 2006;118;1683
DOI: 10.1542/peds.2005-2992

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/118/4/1683.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2006 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

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