ARTICLE

Relationships of Cardiovascular Phenotypes With

Healthy Weight, at Risk of Overweight, and
Overweight in US Youths
Haidong Zhu, MD, PhD, Weili Yan, MD, PhD, Dongliang Ge, MD, PhD, Frank A. Treiber, PhD, Gregory A. Harshfield, PhD,
Gaston Kapuku, MD, PhD, Harold Snieder, PhD, Yanbin Dong, MD, PhD

Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, Georgia

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

ABSTRACT
OBJECTIVE. This study aimed to evaluate comprehensively the cardiovascular pheno-
types of cardiovascular disease-free youths at risk of overweight, in comparison with
healthy weight and overweight. www.pediatrics.org/cgi/doi/10.1542/
peds.2006-3720
METHODS. Casual and ambulatory blood pressure measurements, noninvasive hemo- doi:10.1542/peds.2006-3720
dynamic profiles, pulse wave velocity, left ventricular structure and function, and Key Words
overnight sodium excretion were examined in a cohort of US black and white youths at risk of overweight, youths, blood
(n ⫽ 972; mean age: 17.6 ⫾ 3.3 years). pressure, arterial stiffness, hemodynamics,
left ventricular structure and function
RESULTS. The occurrence of at risk of overweight was ⬃17% in either black youths or Abbreviations
white youths. In white youths, there was a ⬃2-mm Hg increase in casual systolic CDC—Centers for Disease Control and
blood pressure for each increasing step in the 3 BMI categories (healthy weight, Prevention
BP— blood pressure
109.5 ⫾ 0.5 mm Hg; at risk of overweight, 111.5 ⫾ 0.6 mm Hg; overweight, 113.5 ⫾ PWV—pulse wave velocity
1.1 mm Hg). Ambulatory systolic blood pressure showed a similar increase with the SV—stroke volume
increase in BMI. A blunted nocturnal decline in ambulatory diastolic blood pressure HR— heart rate
SBP—systolic blood pressure
with the categorical BMI increase was observed in black youths. In both racial DBP— diastolic blood pressure
groups, cardiac output and stroke volume were significantly enhanced sequentially LVM—left ventricular mass
from healthy weight to at risk of overweight to overweight. In black youths, both Accepted for publication Jun 26, 2007
casual and ambulatory heart rate increased significantly with the increase in BMI. Address correspondence to Yanbin Dong, MD,
Moreover, there was a linear increase of left ventricular mass index from the PhD, Georgia Prevention Institute, Department
of Pediatrics, Medical College of Georgia,
healthy-weight group to the at risk of overweight group, with the overweight group Building HS-1640, Augusta, GA 30912-3715.
having the highest value. In white youths, carotid-dorsalis pedis pulse wave velocity E-mail: ydong@mcg.edu
increased significantly as the BMI increased. Regardless of race, overnight sodium PEDIATRICS (ISSN Numbers: Print, 0031-4005;
excretion showed a significant increase from healthy-weight subjects to overweight Online, 1098-4275). Copyright © 2008 by the
American Academy of Pediatrics
subjects, with at risk of overweight subjects having intermediate values.
CONCLUSIONS. Youths at risk of overweight, compared with healthy-weight youths, seem to have increased cardiovas-
cular risks. Our data suggest that the status of at risk of overweight already has clinical implications in youths.

B ODY FATNESS IN adults is associated with a clustering of cardiovascular risk factors, including increased vascular
tone, arterial stiffening, blood pressure (BP) elevation, and atherogenic vascular phenotypes.1–3 The significant
increase in the prevalence of overweight youths in the past decades has been well recognized.4 BMI, irrespective of
its limitations, is considered to provide a reliable indicator of body fatness.3 On the basis of the distribution approach,
the US Centers for Disease Control and Prevention (CDC) recently designated a new term for BMI, namely, at risk
of overweight. The BMI for individuals at risk of overweight falls between healthy weight and overweight, which
includes ⬎16% of the pediatric population 2 to 19 years of age.4
It is, however, still debatable whether this at risk of overweight category should be regarded as an arbitrary cutoff
point or a precursor for cardiovascular consequences. Simply, is there a “dose-response” relationship in cardiovas-
cular risks for the 3 BMI categories (healthy weight, at risk of overweight, and overweight)? It is well known that
overweight in adults is associated with cardiovascular disease, hypertension, and type 2 diabetes mellitus.3 Similarly,

PEDIATRICS Volume 121, Number 1, January 2008 115

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data are required to show whether at risk of overweight
status might predict elevated cardiovascular risk in car-
diovascular disease-free young individuals. We think
that a closer look at the antecedents of cardiovascular
disease in youths with regard to such an important BMI
category is warranted.
Therefore, this cross-sectional study aimed at compre-
hensively examining cardiovascular structure and func-
tion of the at risk of overweight status in a large cohort
of black and white US youths living in the same envi-
ronment and drawn from the Georgia Cardiovascular
Twin Study. Twin studies provide an efficient research
design for the study of genetic and environmental
influences underlying complex traits. Many studies
have shown that both quantitative and disease phe-
notypes for twins are similar to those of age-matched
subjects from the general population.5,6 Therefore,
twins are representative of singleton populations. In
particular, research on twins has proved to be a valid
epidemiologic tool for studying cardiovascular dis-
ease.5,6
METHODS
Study Population
Subject recruitment was described previously.7,8 In brief,
the twin pairs were recruited through announcements in
local media and flyers distributed to public middle and high
schools within 120 miles of the study location (Augusta,
GA). Zygosity of all same-gender pairs was determined by
DNA fingerprinting. Subjects were classified as black if (1)
both parents reported being of African heritage or (2) par-
ents considered themselves and their child to be black.
Subjects were classified as white if (1) both parents re-
ported being of European ancestry or (2) they considered
themselves and their child to be white and not of Hispanic,
Native American, or Asian descent. All subjects were ap-
parently healthy, on the basis of parental reports of the
child’s medical history. Informed consent was provided by
all subjects or their parents (if the subjects were ⬍18 years
of age). The institutional review board of the Medical Col-
lege of Georgia approved the study.
Body weight, height, and waist circumference were
evaluated by using established protocols.9 Triceps, sub-
scapular, and suprailiac skinfold thicknesses were mea-
sured with a Lange skinfold caliper (Cambridge Scientific
Products, Cambridge, MA), and the sum of the 3 skinfold
measurements was computed.
Casual BP and Hemodynamic Measurements
The testing procedure was described previously.10 Hemo-
dynamics and heart rate (HR) were measured by using a
Dinamap 1846 SX monitor (Criticon, Tampa, FL). Mea-
surements were taken at 11, 13, and 15 minutes during a
15-minute relaxation period in which subjects were in-
structed to relax as completely as possible while laying
supine on a hospital bed, with their heads resting on a
pillow. The averages of the 3 measurements were used to
represent resting hemodynamic data. Stroke volume (SV),
cardiac output, and total peripheral resistance were mea-
116 ZHU et al
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sured through bioimpedance cardiography (NCCOM-3;
BoMeD Medical Manufacturing, Irvine, CA).
Ambulatory BP Measurements
The procedures for ambulatory BP recordings were de-
scribed in detail previously.11 An ambulatory BP monitor
(model 90207; SpaceLabs, Redmond, WA) was fitted to
the nondominant arm. Measures were obtained every
20 minutes during the day (8 AM to 10 PM) and every 30
minutes during the night (midnight to 6 AM). Transi-
tional periods from 6 AM to 8 AM and from 10 PM to
midnight were not included in the analyses. Adequacy
of recordings was based on acceptable readings, using
previously established criteria,4 for ⱖ14 readings over
the 14 hours designated as daytime and ⱖ6 readings
over the 6 hours designated as nighttime, as suggested
by the European Society of Hypertension Working
Group on Blood Pressure Monitoring.12
Pulse Wave Velocity Measurements
Carotid-radial (radial) pulse wave velocity (PWV) and
carotid-dorsalis pedis (foot) PWV were measured non-
invasively with applanation tonometry (Millar Instru-
ments, Houston, TX)13 and commercially available ac-
quisition and analysis software (SphygmoCor; AtCor
Medical, Sydney, Australia). Pressure waves were re-
corded at the common carotid and radial arteries for the
radial PWV and at the common carotid and dorsalis pedis
arteries for the foot PWV. PWV was then calculated
automatically from measurements of pulse transit time
and the distance traveled by the pulse between the 2
recording sites (PWV ⫽ distance [in meters]/transit time
[in seconds]).13
Echocardiographic Measurements
Two D-directed, M-mode echocardiograms were per-
formed by using a Hewlett-Packard Sonos 1500 echocar-
diograph (Hewlett-Packard, Andover, MA). Left ventric-
ular posterior wall thickness in diastole, interventricular
septal thickness in diastole, and left ventricular internal
dimension in diastole were measured according to the
American Society of Echocardiography conventions.14
Left ventricular mass (LVM) was derived by using the
formula described by Devereux et al,15 which has been
validated for use in individuals with normal cardiac
function. On the basis of the recommendation of de
Simone et al,16 LVM was divided by height2.7 to adjust
for normal growth (LVM index). Relative wall thickness
⫽ (left ventricular posterior wall thickness in diastole ⫹
interventricular septal thickness in diastole)/left ventric-
ular internal dimension in diastole. Midwall fractional
shortening and midwall fractional shortening ratio were
calculated by using established formulas.9
Overnight Urinary Sodium Collection
Urine samples were collected from bedtime to time of
awakening the next morning, for the measurement of
overnight sodium excretion. Sodium concentrations
were measured, in equivalents per milliliter, with the
ion-selective electrode method by using a Nova 16 sys-
tem (Nova Biomedical, Boston, MA). The overnight uri-
nary sodium excretion rate was calculated as follows:
urinary sodium excretion rate (in milliequivalents per
hour) ⫽ sodium concentration ⫻ urine volume/1000
per hour.
Definitions of Healthy Weight, At Risk of Overweight, and
Overweight
Anthropometric data were measured with standard
methods and a Healthometer scale (Continental Scale,
Chicago, IL), by trained observers. Height was measured
with the subject standing without shoes and anything
that might interfere with direct horizontal contact with
the top of the head, and weight was measured with only
light clothing. BMI was calculated as weight (in kilo-
grams)/(height [in meters])2. For subjects ⬍18 years of
age, the exact BMI percentile was computed. According
to the CDC growth charts (www.cdc.gov/nchs/about/
major/nhanes/growthcharts/datafiles.htm), BMI of
ⱖ5th percentile and ⬍85th percentile was defined as
healthy weight, BMI of ⱖ85th percentile and ⬍95th
percentile was defined as at risk of overweight, and BMI
of ⱖ95th percentile was defined as overweight.17 For
subjects ⱖ18 years of age, BMI of ⱖ18.5 kg/m2 and ⬍25
kg/m2 was defined as healthy weight, BMI of ⱖ25 kg/m2
and ⬍30 kg/m2 was defined as at risk of overweight, and
BMI of ⱖ30 kg/m2 was defined as overweight.
Definitions of Prehypertension and Hypertension
For individuals ⬍18 years of age, prehypertension was
defined as an average BP of ⱖ90th percentile and sys-
tolic BP (SBP) or diastolic BP (DBP) of ⬍95th percentile,
according to age, gender, and height, or SBP was ⱖ120
mm Hg and DBP was ⱖ80 mm Hg; then hypertension
was defined as an average BP of ⱖ95th percentile for
SBP or DBP18 The height percentiles were determined
from the standard height charts derived from the 2000
CDC growth charts.19 For individuals ⱖ18 years of age,
according to the Seventh Report of the Joint National Com-
mittee on Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure, those with SBP of 120 to 139 mm Hg
and DBP of 80 to 89 mm Hg were considered prehyper-
tensive and those with SBP of ⱖ140 mm Hg and DBP of
ⱖ90 mm Hg were considered hypertensive.20
Statistical Analyses
The statistical analyses were performed with Stata 8.0
software (Stata, College Station, TX). The gender ratios
among healthy weight, at risk of overweight, and over-
weight were compared with a ␹2 test for black youths
and white youths separately. Values are presented as
adjusted mean ⫾ SE. Logarithmic transformation was
performed to obtain an approximation of normal distri-
bution when necessary. Ages among healthy weight, at
risk of overweight, and overweight were compared with
one-way analysis of variance. Differences in continuous
variables among healthy weight, at risk of overweight,
and overweight were compared with generalized esti-
mating equations, a regression technique that allows for
the relatedness within twins and yields unbiased SEs and
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P values.21 When the overall comparisons of phenotypes
among the 3 BMI categories showed a significant differ-
ence, generalized estimating equation analysis was per-
formed again, with the at risk of overweight group as the
reference group. All analyses were adjusted for possible
confounders, including age and gender. The differences
among healthy weight, at risk of overweight, and over-
weight were compared for black youths and white
youths separately. P ⬍ .05 was deemed statistically sig-
nificant.
RESULTS
Clinical Characteristics
Data for this study were available for 972 twins (44.6%
black youths) from the Georgia Cardiovascular Twin
Study, including 232 monozygotic and 254 dizygotic
pairs of same-gender or opposite-gender twins (mean
age: 17.6 ⫾ 3.3 years). In total, 539 white (269 male and
270 female) and 433 black (193 male and 240 female),
monozygotic or dizygotic twins were enrolled in the
study. As shown in Table 1, the occurrence of at risk of
overweight was consistent between black youths and
white youths (17.1% vs 16.9%), but overweight was
much more common in black youths than in white
youths (22.6% vs 12.1%; P ⬍ .001). Of interest, among
the subjects ⬍18 years of age, there were more over-
weight black youths than overweight white youths
(24.2% vs 9.2%), although the proportions at risk of
overweight were similar between white youths and
black youths (13.7% vs 13.4%). For both black youths
and white youths, skinfold thicknesses of the 3 regions
(triceps, subscapular, and suprailiac), the sum of the 3
skinfold measurements, and waist circumference in-
creased significantly in parallel with the weight catego-
ries.
Casual BP and Hemodynamic Profile
Table 2 shows that the presence of prehypertension and
hypertension combined was more common among the
at risk of overweight subjects than the healthy-weight
subjects, among both black youths and white youths. In
particular, in white youths, the rate of prehypertension
showed a gradient increase with weight gain. In white
youths, each increasing step in BMI category showed a
⬃2-mm Hg increase in casual SBP. In black youths only,
DBP declined slightly with increasing BMI category. In
either black youths or white youths, among the 3 BMI
categories, SV and cardiac output increased with BMI
gain, whereas total peripheral resistance decreased. In
black youths, HR increased significantly with BMI in-
creases. Gender was found to be a significant codetermi-
nant for most of the hemodynamic phenotypes stratified
according to the BMI categories.
Ambulatory BP and HR
As shown in Table 3, in either white youths or black
youths, 24-hour ambulatory SBP, ambulatory daytime
SBP, and ambulatory nighttime SBP increased in the
sequence of healthy weight to at risk of overweight to
overweight, but results reached statistical significance
PEDIATRICS Volume 121, Number 1, January 2008 117
 TABLE 1 Clinical Characteristics Among Healthy Weight, at Risk of Overweight, and Overweight Subjects
Phenotype White Black
HW AROW OW P HW AROW OW P
Age
Mean ⫾ SD, ya 17.6 ⫾ 3.3 18.5 ⫾ 3.3 18.5 ⫾ 3.3 .013 17.0 ⫾ 2.8 18.3 ⫾ 3.7 17.1 ⫾ 3.8 .007
⬍18 y, n (%) 242 (77.1) 43 (13.7) 29 (9.2) 173 (62.5) 37 (13.4) 67 (24.2)
ⱖ18 y, n (%) 141 (62.7) 48 (21.3) 36 (16.0) .001 88 (56.4) 37 (23.7) 31 (19.9) .021
Male/female, n 183/200 47/44 39/26 NS 128/133 30/44 35/63 NS
Overnight UNaV, mean ⫾ SE, mEq/hb,c 5.0 ⫾ 0.2 6.2 ⫾ 0.4 7.2 ⫾ 0.5d ⬍.001 5.6 ⫾ 0.3 6.6 ⫾ 0.3 7.5 ⫾ 0.5d .034
Waist circumference, mean ⫾ SE, cmb 73.9 ⫾ 0.4 87.5 ⫾ 0.5e 101.1 ⫾ 0.8d ⬍.001 70.4 ⫾ 0.5 84.1 ⫾ 0.4e 97.6 ⫾ 0.7d ⬍.001
Triceps skinfold, mean ⫾ SE, mmb,c 13.6 ⫾ 0.3 20.3 ⫾ 0.3e 26.9 ⫾ 0.6d ⬍.001 12.3 ⫾ 0.4 20.0 ⫾ 0.3e 27.7 ⫾ 0.5d ⬍.001
Subscapular skinfold, mean ⫾ SE, mmb,c 11.0 ⫾ 0.3 18.9 ⫾ 0.3e 26.8 ⫾ 0.6d ⬍.001 11.7 ⫾ 0.4 20.5 ⫾ 0.4e 29.4 ⫾ 0.6d ⬍.001
Suprailiac skinfold, mean ⫾ SE, mmb,c 13.4 ⫾ 0.4 21.8 ⫾ 0.4e 30.1 ⫾ 0.7d ⬍.001 10.0 ⫾ 0.4 19.8 ⫾ 0.3e 29.6 ⫾ 0.6d ⬍.001
Sum of the 3 skinfolds, mean ⫾ SE, mmb,c 38.1 ⫾ 0.8 60.9 ⫾ 0.9e 83.7 ⫾ 1.6d ⬍.001 33.9 ⫾ 1.0 60.4 ⫾ 1.0e 86.8 ⫾ 1.5d ⬍.001
HW indicates healthy weight; AROW, at risk of overweight; OW, overweight; UNaV, urinary sodium excretion rate; NS, not significant.
a Data are original mean ⫾ SD.

b Data are mean ⫾ SE after adjustment for age and gender.

c P values were based on the logarithmically transformed data.

d P ⬍ .05 between at risk of overweight and overweight.

e P ⬍ .05 between healthy weight and at risk of overweight.

only for white youths. In black youths, the 24-hour
ambulatory DBP decreased significantly with increasing
BMI category. The blunted decline of ambulatory DBP
from daytime to nighttime (“dipping”) with the increase
in BMI was statistically significant for black youths. In
both black youths and white youths, 24-hour ambula-
tory HR, daytime ambulatory HR, and nighttime ambu-
latory HR increased with the increase in BMI, although
these trends reached statistical significance only for black
youths. The gender effects are shown in Table 3.
Overnight Urinary Sodium Excretion
As shown in Table 1, for both black youths and white
youths, there was a linear increase in the overnight
urinary sodium excretion with increasing BMI category.
Cardiovascular Structure and Function
In white youths, foot PWV increased significantly from
healthy weight to overweight, with at risk of overweight
showing an intermediate value as described in Table 4.
In black youths, however, radial PWV decreased with
BMI increases across the 3 BMI categories. In both black
youths and white youths, interventricular septal thick-
ness in diastole, left ventricular internal dimension in
diastole, and left ventricular posterior wall thickness in
diastole increased significantly with increases in BMI.
The increase in relative wall thickness reached signifi-
cance (P ⬍ .001) only for black youths. Regardless of
race, the overweight group had the greatest value for
LVM index, the healthy-weight group had the lowest
value, and the at risk of overweight group had an inter-
mediate value. In black youths, the midwall fractional
shortening ratio decreased with BMI increases. The gen-
der effects are included in Table 4.
DISCUSSION
The present study provides additional evidence that
young individuals at risk of overweight whose BMI is
not within the optimal range but does not exceed the
overweight threshold may posses elevated cardiovascu-
lar risks. In this twin cohort, the occurrence of at risk of
overweight was ⬃17% in either black youths or white
youths, which is similar to the rate for Spanish school-
children (⬃16%)22 but less than the rate for American

TABLE 2 Casual BP and Hemodynamic Measurements Among Healthy Weight, At Risk of Overweight, and Overweight Subjects
Phenotype White Black
HW AROW OW P HW AROW OW P
(n ⫽ 383) (n ⫽ 91) (n ⫽ 65) (n ⫽ 261) (n ⫽ 74) (n ⫽ 98)
PHT and HT, n (%) 7.6 (6.8) 18.7 (17.6) 28.1 (25.0) ⬍.001 15.3 (11.5) 18.9 (17.6) 25.8 (14.4) NS
SBP, mean ⫾ SE, mm Hga 109.5 ⫾ 0.5 111.5 ⫾ 0.6b 113.5 ⫾ 1.1c .001 113.5 ⫾ 0.7 112.9 ⫾ 1.1 112.4 ⫾ 2.3 NS
DBP, mean ⫾ SE, mm Hga 58.1 ⫾ 0.3 57.7 ⫾ 0.4 57.2 ⫾ 0.7 NS 61.8 ⫾ 0.5 60.5 ⫾ 0.4b 59.2 ⫾ 0.7c .002
TPR, mean ⫾ SE, mm Hg/L per min 15.6 ⫾ 0.3 14.7 ⫾ 0.3 13.7 ⫾ 0.5c ⬍.001 17.1 ⫾ 0.4 15.8 ⫾ 0.3b 14.6 ⫾ 0.5 ⬍.001
SV, mean ⫾ SE, mL per beata 82.1 ⫾ 1.3 87.4 ⫾ 1.4 92.6 ⫾ 2.5 .001 79.6 ⫾ 1.5 84.1 ⫾ 1.3b 88.6 ⫾ 2.2 .001
Cardiac output, mean ⫾ SE, L/min 5.2 ⫾ 0.1 5.7 ⫾ 0.1 6.1 ⫾ 0.2 ⬍.001 5.1 ⫾ 0.1 5.4 ⫾ 0.1b 5.8 ⫾ 0.2 ⬍.001
HR, mean ⫾ SE, beats per mina 65 ⫾ 0 66 ⫾ 0 67 ⫾ 1 NS 64 ⫾ 1 65 ⫾ 1 67 ⫾ 1 .028
Data are mean ⫾ SE after adjustment for age and gender. All P values were based on logarithmically transformed data. HW indicates healthy weight; AROW, at risk of overweight; OW, overweight;
TPR, total peripheral resistance; NS, not significant; PHT, prehypertension; HT, hypertension.
a Gender showed a significant effect for white and black subjects (P ⬍ .001).

b P ⬍ .05 between healthy weight and at risk of overweight.

c P ⬍ .05 between at risk of overweight and overweight.

118 ZHU et al
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 TABLE 3 Ambulatory BP Measurements Among 3 BMI Groups for Black and White Subjects
Ambulatory BP White Black
HW AROW OW P HW AROW OW P
n 175 35 30 124 26 43
24-h SBP, mm Hga 113.1 ⫾ 0.6 114.8 ⫾ 0.6b 116.6 ⫾ 1.0 ⬍.001 115.1 ⫾ 0.7 116.8 ⫾ 0.7 118.6 ⫾ 0.9 NS
Day SBP, mm Hga 117.4 ⫾ 0.6 118.6 ⫾ 0.7b 120.4 ⫾ 1.0 ⬍.001 118.3 ⫾ 0.7 119.9 ⫾ 0.7 121.4 ⫾ 1.0 NS
Night SBP, mm Hga 105.1 ⫾ 0.7 106.9 ⫾ 0.7b 108.7 ⫾ 1.1 ⬍.001 109.6 ⫾ 0.8 111.4 ⫾ 0.7 113.2 ⫾ 1.1 NS
24-h DBP, mm Hg 65.6 ⫾ 0.5 65.2 ⫾ 0.5 64.8 ⫾ 0.7 NS 67.0 ⫾ 0.5 66.6 ⫾ 0.5b 66.2 ⫾ 0.7 .044
Day DBP, mm Hg 69.9 ⫾ 0.5 69.6 ⫾ 0.6 69.7 ⫾ 0.5 NS 70.3 ⫾ 0.6 70.2 ⫾ 0.6 70.1 ⫾ 0.6 NS
Night DBP, mm Hg 57.5 ⫾ 0.5 56.6 ⫾ 0.6 55.8 ⫾ 0.9 NS 60.8 ⫾ 0.6 59.9 ⫾ 0.6 59.0 ⫾ 0.8 NS
24-h HR, beats per mina 75.6 ⫾ 0. 8 77.7 ⫾ 0.8 79.8 ⫾ 1.2 NS 77.0 ⫾ 0.9 79.0 ⫾ 0.9b 81.1 ⫾ 1.2 .001
Day HR, beats per mina 81.1 ⫾ 0.9 82.9 ⫾ 0.9 84.7 ⫾ 1.4 NS 81.4 ⫾ 1.0 83.2 ⫾ 1.0b 85.0 ⫾ 1.3 .007
Night HR, beats per mina 66.5 ⫾ 0.8 68.5 ⫾ 0.9 70.6 ⫾ 1.3 NS 69.3 ⫾ 0.9 71.4 ⫾ 0.9b 73.4 ⫾ 1.3 .001
Dipping SBP, % 10.2 ⫾ 0.4 9.9 ⫾ 0.5 9.5 ⫾ 0.7 NS 7.5 ⫾ 0.5 7.1 ⫾ 0.5 6.7 ⫾ 0.7 NS
Dipping DBP, %a 4.4 ⫾ 1.2 0.9 ⫾ 1.3 ⫺2.5 ⫾ 2.0 NS 1.0 ⫾ 1.4 ⫺2.5 ⫾ 1.3b ⫺5.9 ⫾ 1.9c ⬍.001
Data are mean ⫾ SE after adjustment for age and gender. HW indicates healthy weight; AROW, at risk of overweight; OW, overweight; NS, not significant; Day, average of daytime; Night, average
of nighttime; Dipping ⫽ 关(daytime 14 h ⫺ nighttime 6 h)/daytime 14 h兴 ⫻ 100%.
a Gender showed a significant effect for white and black subjects (P ⬍ .001).

b P ⬍ .05 between healthy weight and at risk of overweight.

c P ⬍ .05 between at risk of overweight and overweight.

Indian adolescents (25%).23 Furthermore, overweight
was twice as common in black youths as in white
youths. From healthy weight to at risk of overweight to
overweight, there was an obvious gradient growth in
waist circumference and triceps, subscapular, and su-
prailiac skinfold thicknesses, indicating that young indi-
viduals at risk of overweight have greater than optimal
fatness and adipose tissue accumulation. In particular,
waist circumference has been advocated as an indicator
of abdominal fat content. Increased waist circumference,
in combination with or independent of BMI, may predict
cardiovascular risk factors among youths at risk of over-
weight.24,25
In either black youths or white youths, the occur-
rence of prehypertension and hypertension combined
increased with the increase in BMI category. In white
youths, the rate of prehypertension alone was signifi-
cantly higher for the at risk of overweight group than the
healthy-weight group, demonstrating that higher than
optimal weight is associated with higher than optimal
BP. A 2-mm Hg BP increase may not be of clinical sig-
nificance at the individual level, but it has a significant
impact on a population level, especially in the pediatric
population. BP elevation tracks from late childhood into
adulthood and follows a relatively consistent progres-
sion. BP elevation early in life places a cumulative bur-
den on the cardiovascular system.26,27 Ambulatory BP
measurements offer advantages over casual BP readings,
such as tracking of circadian BP patterns.12 More specif-
ically, only a few studies have addressed the impact of
weight gain on ambulatory BP levels in youths.28 Our
data for youths showed that ambulatory daytime SBP
and nighttime SBP increased in step with the weight
categories. These findings support the concept that the
risk for essential hypertension can be attributed directly
to excess weight in older adults.29 In particular, in white

TABLE 4 Cardiovascular Structure and Function Among Healthy Weight, at Risk of Overweight and Overweight Subjects
Phenotype White Black
HW AROW OW P HW AROW OW P
(n ⫽ 365) (n ⫽ 82) (n ⫽ 48) (n ⫽ 254) (n ⫽ 71) (n ⫽ 89)
Radial PWV, m/sa 6.3 ⫾ 0.1 6.3 ⫾ 0.1 6.3 ⫾ 0.1 NS 6.9 ⫾ 0.1 6.6 ⫾ 0.1 6.3 ⫾ 0.1b .001
Femoral PWV, m/sa 6.9 ⫾ 0.1 7.1 ⫾ 0.1 7.2 ⫾ 0.1 .004 7.1 ⫾ 0.1 7.2 ⫾ 0.1 7.2 ⫾ 0.1 NS
IVSD, cma,c 0.8 ⫾ 0.0 0.8 ⫾ 0.0d 0.9 ⫾ 0.0b ⬍.001 0.8 ⫾ 0.0 0.8 ⫾ 0.0d 0.9 ⫾ 0.0b ⬍.001
LVIDd, cma,c 4.7 ⫾ 0.0 4.9 ⫾ 0.0d 5.0 ⫾ 0.1b ⬍.001 4.6 ⫾ 0.0 4.7 ⫾ 0.0d 4.8 ⫾ 0.0 ⬍.001
LVPWD, cma,c 0.8 ⫾ 0.0 0.8 ⫾ 0.01d 0.9 ⫾ 0.0b ⬍.001 0.8 ⫾ 0.0 0.8 ⫾ 0.0d 0.9 ⫾ 0.0b ⬍.001
RWTa,c 0.3 ⫾ 0.0 0.3 ⫾ 0.0 0.4 ⫾ 0.0 NS 0.3 ⫾ 0.0 0.4 ⫾ 0.0d 0.4 ⫾ 0.0b ⬍.001
LVMIa,c 29.8 ⫾ 0.4 32.8 ⫾ 0.4d 35.9 ⫾ 0.8b ⬍.001 29.4 ⫾ 0.4 33.4 ⫾ 0.4d 37.4 ⫾ 0.6b ⬍.001
MFS, %a 21.1 ⫾ 0.2 20.9 ⫾ 0.2 20.6 ⫾ 0.3 NS 21.1 ⫾ 0.2 20.7 ⫾ 0.2 20.3 ⫾ 0.3 .023
MFS ratio 116.0 ⫾ 0.9 114.4 ⫾ 1.1 112.7 ⫾ 2.0 NS 115.9 ⫾ 1.1 113.7 ⫾ 1.1 111.4 ⫾ 1.9 .041
Ejection fractiona 0.7 ⫾ 0.0 0.7 ⫾ 0.0 0.7 ⫾ 0.0 NS 0.7 ⫾ 0.0 0.7 ⫾ 0.0 0.7 ⫾ 0.0 NS
Data are mean ⫾ SE after adjustment for age and gender. A total of 699 subjects had available PWV data, including 411 white subjects and 288 black subjects. HW indicates healthy weight; AROW,
at risk of overweight; OW, overweight; NS, not significant; IVSD, interventricular septal thickness in diastole; LVIDd, left ventricular internal dimension in diastole; LVPWD, left ventricular posterior wall
thickness in diastole; RWT, relative wall thickness; MFS, midwall fractional shortening; LVMI, LVM index.
a P values were based on the logarithmically transformed data.

b P ⬍ .05 between at risk of overweight and overweight.

c Gender showed a significant effect for white and black subjects (P ⱕ .01).

d P ⬍ .05 between healthy weight and at risk of overweight.

PEDIATRICS Volume 121, Number 1, January 2008 119

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youths, both ambulatory daytime SBP and nighttime
SBP were significantly greater in the at risk of over-
weight subjects than in the healthy-weight subjects, in-
dicating that early weight gain contributes to BP eleva-
tion.
Alexander et al30 characterized overweight as a state
in which elevated blood volume, enlarged vascular tree,
and increased cardiac output were all thought necessary
to sustain the demands of an expanded adipose tissue
mass. In the present study, SV and cardiac output were
increased in the at risk of overweight youths, especially
black youths, which suggests that the high-output state
may already be present in the early stage of weight gain.
Excess adipose tissue generates an increase in oxygen
consumption and subsequently requires an increase in
cardiac output.3 Total peripheral resistance was, how-
ever, decreased with BMI increases according to the
categories. This finding was in accordance with previous
reports in overweight hypertensive adults31 and might be
a result of compensatory widening of the vascular tree.
The absolute lowering of systemic resistance could be
inadequate in the presence of increased demands for
circulating volume. The elevation of cardiac output was
previously considered to be related primarily to increases
in SV rather than HR.32 In this study, casual HR and
24-hour HR (including daytime and nighttime) also in-
creased with the categorical weight increase, although
the increases were statistically significant only for black
youths. The acceleration of HR together with the eleva-
tion of SV contributes to the increase in cardiac output.
One explanation for the HR increase is that the demands
of excess adipose tissue might have exceeded the com-
pensatory capacity of SV alone. HR acceleration can also
be a sign of sympathetic hyperactivity, which is the
common feature of overweight in humans and in animal
models.33 Furthermore, increased HR variability was
found previously in overweight adolescents, which sug-
gests an altered balance between sympathetic and para-
sympathetic activity in relation to excess weight gain.34
Among both black youths and white youths, subjects
at risk of overweight showed increased LVM, lower left
ventricular contractility, and lower vascular compliance,
compared with healthy-weight individuals. This obser-
vation is in accordance with findings from the Strong
Heart Study, in which unfavorable alterations in cardiac
geometric features and function were shown for 460
American Indian adolescents.23 In white youths, we ob-
served a “staircase” increase of foot PWV across the 3
BMI categories, which suggests increased stiffness of the
arterial wall with increases in weight status.
Of interest, overnight urinary sodium excretion,
which might reflect dietary salt intake, exhibited a sig-
nificant “dose-response” increase in association with the
categorical BMI increase in both race groups. The Inter-
salt Study demonstrated that overweight adult individ-
uals usually ate more food than healthy-weight adults;
along with greater food intake, they also ingested more
sodium.35 Salt loading leads to extracellular volume ex-
pansion, high cardiac output, and BP elevation and con-
tributes to cardiac hypertrophy. In addition, weight gain
is associated with salt sensitivity, contributing to the
120 ZHU et al
Downloaded from pediatrics.aappublications.org at Florida International University, Medical Library on June 5, 2015
hyperdynamic circulation and cardiac load through the
renin-angiotensin-aldosterone system, sympathetic ner-
vous system, and intrarenal physical forces.29,34,36 Ideally,
the results need to be confirmed in an independent
cohort with 24-hour urinary sodium excretion measure-
ments, which are more-accurate measures of dietary salt
intake. The effects of at risk of overweight on the rela-
tionship between nocturnal sodium excretion and BP
deserves further investigation.37
There were 2 observations contrary to our hypothe-
ses. First, casual DBP and 24-hour ambulatory DBP were
decreased with the categorical BMI increase, especially
in black youths. However, this is in line with a few
previous findings in the literature. For instance, the
1999 to 2002 National Health and Nutrition Examina-
tion Survey demonstrated that lower DBP was associ-
ated with higher BMI in 4508 adolescents 12 to 19 years
of age.38 In the present study, a blunted nocturnal de-
cline in ambulatory DBP with the categorical BMI in-
crease was observed, especially in black youths. It is
known that individuals with a blunted nocturnal decline
in BP, referred to as “nondippers,” display the highest
cardiovascular risk, because such individuals are ex-
posed to a greater cardiovascular load each day.39 Sec-
ond, radial PWV was unchanged with the BMI increase
in white youths and decreased significantly with the
BMI increase in black youths. We found previously that
DBP was the most important hemodynamic predictor for
PWV; the variance explained by the DBP model alone
approached that for the full model for PWV.40 Because
DBP was correlated negatively with the BMI categories,
the inverse correlation between radial PWV and the BMI
categories should not be unexpected.
There were limitations of the present study. First, the
use of the dorsalis pedis as an alternative to the femoral
measurement site was considered less sensitive, al-
though more readily accepted by youths. Foot PWV
represents a mixture of both proximal elastic arteries and
distal muscular arteries. Some differences with other
reports, which typically measured carotid-femoral PWV,
are thus expected. However, the previous findings re-
vealed that foot PWV, as a combination of central and
peripheral measures, was correlated more strongly with
age than was radial PWV.40 This is quite comparable to
the characteristic of carotid-femoral PWV. In addition,
the genetic influences on foot PWV and radial PWV
differed significantly.40 Second, there is concern about
the accuracy of hemodynamic assessments, such as car-
diac output measurements, with impedance cardiogra-
phy. Nevertheless, this technique is noninvasive and
feasible for large population studies. Third, there may be
concerns regarding whether results from twin studies
can be generalized to the general population. We and
others demonstrated previously that twins are represen-
tative of singleton populations, and studies of twins are
valid epidemiologic tools for common diseases such as
hypertension.5,6 Fourth, this study is limited by the cross-
sectional design. Longitudinal follow-up monitoring
would indicate the dynamic changes in cardiovascular
structure and function caused by at risk of overweight
status. Lastly, there are limitations in the CDC defini-
tions of BMI and BP cutoff values. For example, ethnic/
racial differences in the development of body size and
height in adolescents were not included. Therefore, cau-
tion should be used in generalizing our results with US
youths to other adolescent populations.
Although there is a continuum of cardiovascular risk
across levels of BMI, our data suggest that a simple BMI
threshold, that is, at risk of overweight, already has
clinical implications in youths. This study suggests
strongly that a variety of adaptations and alterations in
cardiovascular structure and function are associated
with this higher than optimal weight status. Further-
more, the likelihood of clustering of cardiovascular risk
factors is enhanced in cardiovascular disease-free young
individuals at risk of overweight. Optimal approaches to
effective preventive strategies in youths should include
early recognition, dietary intervention, stress reduction,
prevention of weight gain, weight loss, and physical
activity.
ACKNOWLEDGMENT
This study was supported by grants from the National
Heart, Lung, and Blood Institute (HL56622, HL76723,
HL77230, HL85817 and HL69999) and the American
Heart Association (0430078N and 0435146N).
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THE ODYSSEY YEARS

“There used to be four common life phases: childhood, adolescence, adult-

hood and old age. Now, there are at least six: childhood, adolescence, odys-
sey, adulthood, active retirement and old age. Of the new ones, the least
understood is odyssey, the decade of wandering that frequently occurs be-
tween adolescence and adulthood. During this decade, 20-somethings go to
school and take breaks from school. They live with friends and they live at
home. They fall in and out of love. They try one career and then try another.
Their parents grow increasingly anxious. These parents understand that
there’s bound to be a transition phase between student life and adult life. But
when they look at their own grown children, they see the transition stretch-
ing five years, seven and beyond. The parents don’t even detect a clear sense
of direction in their children’s lives. They look at them and see the things that
are being delayed. They see that people in this age bracket are delaying
marriage. They’re delaying children. They’re delaying permanent employ-
ment. People who were born before 1964 tend to define adulthood by certain
accomplishments—moving away from home, becoming financially indepen-
dent, getting married and starting a family. In 1960, roughly 70 percent of
30-year-olds had achieved these things. By 2000, fewer than 40 percent of
30-year-olds had done the same. Yet with a little imagination it’s possible
even for baby boomers to understand what it’s like to be in the middle of the
odyssey years. It’s possible to see that this period of improvisation is a sensible
response to modern conditions.”
Brooks D. New York Times. October 9, 2007
Noted by JFL, MD

122 ZHU et al
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 Relationships of Cardiovascular Phenotypes With Healthy Weight, at Risk of
Overweight, and Overweight in US Youths
Haidong Zhu, Weili Yan, Dongliang Ge, Frank A. Treiber, Gregory A. Harshfield,
Gaston Kapuku, Harold Snieder and Yanbin Dong
Pediatrics 2008;121;115
DOI: 10.1542/peds.2006-3720
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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 © 2008 by the American Academy of Pediatrics. All
rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Florida International University, Medical Library on June 5, 2015
 Relationships of Cardiovascular Phenotypes With Healthy Weight, at Risk of
Overweight, and Overweight in US Youths
Haidong Zhu, Weili Yan, Dongliang Ge, Frank A. Treiber, Gregory A. Harshfield,
Gaston Kapuku, Harold Snieder and Yanbin Dong
Pediatrics 2008;121;115
DOI: 10.1542/peds.2006-3720

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/121/1/115.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 © 2008 by the American Academy
of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 1098-4275.

Downloaded from pediatrics.aappublications.org at Florida International University, Medical Library on June 5, 2015