ORIGINAL

ARTICLES
Left Ventricular Diastolic Dysfunction Among Youth with Obesity and
History of Elevated Blood Pressure
Jareatha N. Abdul-Raheem, BS3, Edem Binka, MD1, Jennifer Roem, MS4, Christy B. Turer, MD, MHS5,6,
Elaine M. Urbina, MD, MS7, and Tammy M. Brady, MD, PhD2

Objective To assess prevalence of and factors associated with left ventricular diastolic dysfunction (LVDD) in
youth with obesity and elevated blood pressure (BP).
Study design This was a cross-sectional analysis of baseline and follow-up visits of 83 youth, 5-21 years, eval-
uated for overweight/obesity and elevated BP in a multidisciplinary clinic. LVDD was defined according to estab-
lished adult criteria (LVDDadult; E/A < 1, E/e0 > 14, or e0 /a0 < 0.8) and pediatric criteria (LVDDpeds; E/A <10th
percentile, E/e0 >99th percentile, or e0 /a0 <1st percentile) based on data from 103 age-sex matched healthy controls.
Baseline factors associated with LVDDpeds were examined using Wilcoxon rank sum and c2 tests. Multiple logistic
regression analyses using generalized estimating equations to account for repeated measures evaluated the asso-
ciations of adiposity and BP with LVDDpeds.
Results The prevalence of LVDD ranged from 1.2% to 2.7% when we used adult criteria and 19% to 28% when we
used pediatric criteria. Those with LVDDpeds were older, predominantly male, and non-African American and had
greater weight, BP, BP medication use, and non–high-density lipoprotein cholesterol than those without LVDDpeds.
Diastolic BP z score was associated with LVDDpeds by E/A (OR 1.95, 95% CI 1.15-3.32, P = .014) after we adjusted
for age, sex, race, BP medications, and body mass index z score.
Conclusions LVDD was present in a substantial proportion of youth with overweight/obesity and elevated BP us-
ing pediatric criteria. Those with LVDDpeds had significantly greater measures of adiposity and BP compared with
those without LVDDpeds, and diastolic BP z score was an independent predictor of LVDDpeds by E/A. These
data emphasize the importance of prevention and treatment of cardiovascular disease risk factors in childhood.
(J Pediatr 2021;235:130-7).

T
here is an epidemic rise in the prevalence of obesity among children and adolescents, with a concomitant rise in cardio-
vascular disease (CVD) risk factors among these at-risk youth, with up to 25% of youth with obesity also having comor-
bid hypertension.1-3 Fortunately, children and adolescents do not typically experience hypertensive symptoms or
sequelae such as myocardial infarction or heart failure in their youth. Instead, children and adolescents with obesity and hy-
pertension become adults with these conditions, developing heart disease and experiencing cardiovascular (CV) events in
adulthood.4-6
Left ventricular diastolic dysfunction (LVDD) predicts the development of heart failure and therefore serves as an interme-
diate marker of CVD events in adults.7-10 LVDD signifies poor cardiac relaxation and filling and is associated with hypertension
and obesity in adults.7-10 As such, echocardiography often is conducted in at-risk adults to screen for LVDD and facilitate sec-
ondary and tertiary prevention of heart failure.11 Youth with hypertension also undergo echocardiography, primarily to screen
for left ventricular hypertrophy (LVH), a form of structural target organ damage also associated with CV events in adults.12-15
Although assessing for LVH by echocardiography is standard of care for hypertension management in children, concurrent
assessment of diastolic function is not performed consistently, leaving the burden
of this intermediate risk factor in youth without preexisting structural or func-
tional heart disease largely unknown. Further complicating the assessment of
1
From the Divisions of Pediatric Cardiology and
left ventricular (LV) function in children is the lack of universally established 2 3
Pediatric Nephrology, Johns Hopkins University
clinical cut points to define pediatric LVDD. Therefore, the aim of the present School of Medicine, Baltimore, MD; Department of 4

Epidemiology, Johns Hopkins Bloomberg School of

study was to estimate both the prevalence of LVDD in children and adolescents Public Health, Baltimore, MD; Departments of
5 6
Pediatrics and Internal Medicine, UT Southwestern
with obesity and elevated blood pressure (BP) and to identify predictors of 7
Medical Center, Dallas, TX; and Division of Cardiology,
Cincinnati Children’s Hospital Medical Center,
Cincinnati, OH
Supported by the National Institutes of Health/National
Heart, Lung, and Blood Institute, United States (R56-HL-
BMI Body mass index LV Left ventricular 139620 [to T.B.] and T32 HL125239 [to E.B.]). These
funding sources had no role in study design; collection,
BP Blood pressure LVDD Left ventricular diastolic analysis, and interpretation of data; writing the report; or
CKD Chronic kidney disease dysfunction the decision to submit the report for publication. The
CV Cardiovascular LVH Left ventricular hypertrophy authors declare no conflicts of interest.

CVD Cardiovascular disease LVMI Left ventricular mass index Portions of this study were accepted for the Pediatric
Academic Society annual meeting, 2020 (canceled).
DBP Diastolic blood pressure non-HDL Non–high-density lipoprotein
HTN Hypertension cholesterol 0022-3476/$ - see front matter. ª 2021 Elsevier Inc. All rights reserved.
https://doi.org/10.1016/j.jpeds.2021.03.066

130

LVDD in this at-risk pediatric population. To achieve these
aims, we established pediatric thresholds for abnormal dia-
stolic function from a cohort of healthy controls and also
describe the prevalence of abnormal diastolic function using
conventional adult thresholds.
Methods
The ReNEW Cohort
This is a cross-sectional analysis of the baseline and follow-up
visits of 83 children and adolescents, aged 5-21 years, with over-
weight/obesity and a history of elevated BP who were referred to
a multidisciplinary obesity, hypertension clinic (ReNEW
Clinic) at Johns Hopkins University. Children and adolescents
seen in the ReNEW clinic are evaluated by a pediatric nephrol-
ogist, a behavioral psychologist, a physical therapist, and a die-
tician and undergo echocardiography every 6-12 months.
Youth and their families are invited to provide informed con-
sent and assent to have their demographic and clinical data
included in a longitudinal patient registry (ReNEW clinic
cohort study; NCT03816462). Children and adolescents who
had an initial clinic visit between February 1, 2015, and January
31, 2020, and had an echocardiogram conducted at their initial
visit were included in this study.
The control group consisted of 103 healthy children and ad-
olescents 7-21 years of age with body mass index (BMI) percen-
tile <85% (or <25 kg/m2 if 20 years of age or older), no history
of hypertension (HTN), and no personal or family history of
CVD. The control group was generated by selecting eligible
youth from the Johns Hopkins Hospital pediatric cardiology
echocardiographic imaging database who were matched for
age and sex with the ReNEW clinic cohort participants. Chil-
dren and adolescents without significant medical history who
were referred by their primary care provider for evaluation of
a heart murmur, underwent echocardiography between
January 2013 and January 2020, and had no structural or func-
tional cardiac abnormalities identified were eligible for inclu-
sion in the control group. When needed, chart review of
potential control participants confirmed inclusion criteria
were met. The Johns Hopkins University School of Medicine
institutional review board approved this study.
All anthropometric measurements were measured in a stan-
dardized fashion by a research dietician. Height was measured
to the nearest 0.1 cm with a wall-mounted stadiometer, and
weight was measured to the nearest 0.1 kg (wearing light
clothing) by a calibrated standing balance scale. BMI was calcu-
lated (in kg/m2). Age-sex specific height, weight, BMI percen-
tiles, and z scores were calculated using Centers for Disease
Control and Prevention normative growth data.16 For patients
younger than 20 years of age, overweight was defined as BMI
³85th to <95th percentile and obesity as BMI ³95th percentile.
For those ³20 years, overweight and obesity were defined as
BMI 25 to 29.9 and ³30 kg/m2, respectively.
BP was manually auscultated in the right upper arm using
a calibrated aneroid sphygmomanometer per standard
methods, including individualized cuff selection based on
Volume 235  August 2021
measured mid-arm circumference.17 Three BP measure-
ments were obtained after an initial rest period of 5 minutes,
with the average of these measures used as the composite
measurement for the visit. BP percentiles for all participants
were determined using normative data from the 2017 Amer-
ican Academy of Pediatrics Hypertension Clinical Practice
Guidelines.17 BP index (average measured BP/age-height-
sex specific 95th percentile BP for children <13 years, 130/
80 mm Hg for ³13 years) was calculated to standardize BP
comparisons between children. For HTN diagnosis, the
2017 American Academy of Pediatrics Hypertension Clinical
Practice Guidelines definitions were used.17 In addition, BP z
scores were determined to allow for additional comparisons.
Dietary intake was assessed at baseline using either a 3-day
diet record that was completed before the visit to the clinic
and reviewed in detail by the dietitian during the clinic visit
or via a 24-hour guided dietary recall completed with the die-
titian during the clinic visit. Nutrition Data System for
Research (University of Minnesota Nutrition Coordinating
Center), versions 2014 and 2015, were used for dietary anal-
ysis, including potassium, sodium, and omega-3 fatty acids
(Recommended Dietary Allowances; Food and Nutrition
Board, Institute of Medicine, National Academies).
Laboratory data obtained within 6 months of the initial
visit were collected by chart review. Laboratory assessments
included lipid panel analysis (total cholesterol, low-density
lipoprotein cholesterol, non–high-density lipoprotein
cholesterol [non-HDL], triglycerides; all mg/dL) and hemo-
globin A1c (%).
A complete echocardiographic study was performed on each
participant using GE Vivid E95 (GE Vingmed Ultrasound) or
Philips EPIQ 7 (Philips Medical Systems) systems with the
participant supine or in the left decubitus position. All images
were secondarily reviewed by a study cardiologist to obtain
the measures included in this study. Standardized 2-
dimensional–guided M-mode echocardiography recordings of
the LV dimensions and function were obtained. The measure-
ments included interventricular septal and posterior wall thick-
ness and LV diameter at the end of diastole. LV mass was
calculated from the Devereux formula.18 Left ventricular mass
index (LVMI) was calculated as LVM (g)/height (m2.7). For
each participant, LVH was assessed using 2 different definitions:
LVMI ³95th percentile and LVMI ³51 g/m2.7.19
For the evaluation of diastolic function, several measures were
obtained using conventional Doppler tracings of the mitral and
the tricuspid valve from an apical 4-chamber view. Mitral filling
was assessed with the peak velocity of the transmitral early filling
wave (E) and the peak velocity of atrial late filling (A), and the
ratio of both (E/A). Pulse wave tissue Doppler imaging was
used to measure the mitral annulus velocity during early (e0 )
and late (a0 ) diastole in the assessment of diastolic function.
The E/e0 value (the ratio of E and the average of the diastolic
annular velocity [e0 ]) and e0 /a0 value (the ratio of early to late dia-
stolic annular velocity) were calculated.
Due to the lack of clear definitions for LVDD in the pedi-
atric population,20-24 the presence of LVDD in the study
131
THE JOURNAL OF PEDIATRICS  www.jpeds.com Volume 235

population was determined by 2 different methodologies.

Results
First, LVDD was defined by applying the following cutoffs
that have been used to diagnose LVDD in adults (LVDDadult):
The study population consisted of 83 children and adoles-
E/A < 1, E/e0 > 14, or e0 /a0 < 0.8.25 Second, we defined LVDD
cents (35 female) with obesity and a history of elevated BP
based on the distribution of the same measures in our age-
who contributed 139 visits with echocardiography over
and sex-matched control population (LVDDpeds): E/A
5 years of follow-up. Fifty-three (64%) youth contributed
<10th percentile, E/e0 >99th percentile, or e0 /a0 <1st percen-
data from 1 visit, 18 (22%) contributed data from 2 visits,
tile. E/A cutoff measures were defined as below the 10th
and 12 (14%) contributed data from more than 2 visits dur-
percentile (and not <1st percentile) based on the distribution
ing the follow-up period. Between 125 and 127 visits had
of measurements in the study population to ensure enough
concurrent echocardiography with all covariates and out-
data points for statistical analyses.
comes of interest, with 75 participants contributing 125 visits
Demographic and clinical variables were compared be-
with E/A; 78 contributing 127 visits with E/e0 ; and 78 contrib-
tween those in the ReNEW clinic cohort and those in the con-
uting 125 visits with e0 /a0 . The median age at the initial visit
trol group using data from the initial ReNEW clinic visit.
was 14 years (range: 5-21 years). Baseline clinical characteris-
Additional initial clinic visit characteristics including demo-
tics of the study population and the age- and sex-matched
graphics, adiposity and CV measures, medical history, and
controls are shown in Table I. As expected, there was a
laboratory and dietary assessments were compared between
statistically significant difference between the study
ReNEW study participants with and without LVDDpeds. Cat-
population and controls in regard to weight, BMI, BMI z
egorical variables were compared using c2 tests, and contin-
score, systolic BP, systolic BP z score, LVMI, LVH [LVMI
uous variables were compared using Wilcoxon rank sum test
>95th percentile and LVMI >51 g/m2.7], E/A, E/e0 , and e0 /
for non-normally distributed data.
a0 . The 2 populations were similar in age and sex by design.
To incorporate all available data from both the initial and any
The distribution of each measure of diastolic function
follow-up clinic visits with a concurrent echocardiogram, gener-
(E/A, E/e0 , e0 /a0 ) in the control population is presented in
alized estimating equations were used to account for repeated
Table II with the chosen cutoffs for defining LVDDpeds
measures provided by study participants. Univariate and multi-
highlighted in bold. As there was only 1 child (1%) in the
variable analyses evaluated the association between CVD risk
study population with E/A <1st percentile (1.18) and only
factors (BMI z score, systolic blood pressure z score, diastolic
8 (10%) with E/A <5th percentile (1.36), for this outcome
blood pressure [DBP] z score, and HTN status) and LVDDpeds
we chose the 10th percentile as the LVDDpeds cutoff to
defined by each of the 3 echocardiographic measures. Multivari-
allow for meaningful comparisons in the ReNEW cohort.
able regression models adjusted for age, sex, race, and CVD risk
Among the children in the study population, the prevalence
factors to determine the independent association of each risk
of LVDDadult across all available clinic visits with an echocardio-
factor on LVDDpeds. For BP risk factors, an additional multivari-
gram was 2% by E/A (E/A < 1), 1% by E/e0 (E/e0 > 14), and 2%
able model also adjusted for the use of antihypertensive medica-
by e0 /a0 (e0 /a0 < 0.8). The prevalence of LVDDpeds across the same
tions. A 2-sided P value <.05 was considered statistically
clinic visits was 23% by E/A (E/A <10th percentile [E/A < 1.62]),
significant. Statistical analyses were conducted using R 4.0.0.
19% by E/e0 (E/e0 >99th percentile [E/e0 > 8.54]), and 28% by e0 /
Data were managed using REDCap (Research Electronic Data
a0 (e0 /a0 <1st percentile [e0 /a0 < 1.64]).
Capture) hosted at Johns Hopkins University.

Table I. Baseline clinical characteristics of youth with obesity and elevated BP (ReNEW Cohort) compared with a
healthy pediatric population (control)
Characteristics* ReNEW cohort (n = 83) Control (n = 103) P value
Age, y 14 [11, 16] 14 [12, 16] .32
Female sex, % (No.) 42 (35) 51 (53) .21
Weight, kg 99.5 [79.9, 126.2] 49.8 [37.1, 57.1] <.001
BMI, kg/m2 36.8 [32.3, 43.9] 18.5 [17.0, 20.2] <.001
BMI z score 2.60 [2.42, 2.81] 0.18 [–0.61, 0.31] <.001
Systolic BP 124 [114, 135] 112 [105, 118] <.001
Systolic BP z score† 1.48 [0.67, 2.05] 0.33 [–0.29, 0.97] <.001
DBP 65 [58, 72] 64 [57, 68] .10
DBP z score† 0.13 [–0.51, 0.82] 0.05 [–0.64, 0.43] .07
LVMI, g/m2.7 44.8 [39.5, 56.8] 29.7 [26.0, 34.3] <.001
LVH, LVMI>51 g/m2.7, % (No.) 37 (30) 0 (0) <.001
E/A 1.95 [1.64, 2.21] 2.23 [1.84, 2.68] <.001
E/e0 7.69 [6.37, 8.37] 5.77 [4.75, 6.65] <.001
e0 /a0 1.90 [1.60, 2.31] 2.71 [2.30, 3.25] <.001

Missing data include BMI z score: n = 6; LVM: n = 4; E/A: n = 4; E/e0 : n = 2; e0 /a0 : n = 3.

Values in bold are statistically significant with a P < .05.
*Continuous characteristic represented as median [IQR] and categorical characteristics as % (No.).
†Based on 2017 guidelines age, sex, and height-specific cutoffs.

132 Abdul-Raheem et al
August 2021 ORIGINAL ARTICLES

definitions. Although only 1%-2% of the children and ado-

Table II. Distribution of each measure of diastolic lescents in this study had LVDD by adult criteria, this is
function among 103 healthy, normotensive children in notable when one considers that studies of pediatric patients
the control population with chronic kidney disease (CKD), systemic lupus erythe-
Statistical threshold E/A E/e0 e0 /a0 matosus, and end-stage renal disease have not reported echo-
Mean (SD) 2.39 (0.80) 5.81 (1.30) 2.83 (0.74) cardiographic evidence of LVDD based on adult LVDD
2 SD 0.79 3.21 1.35 thresholds.20-23 Also noteworthy is that one-fifth to one-
+2 SD 3.99 8.41 4.31
Percentile
quarter of our study population had diastolic function mea-
1st 1.18 3.57 1.64 sures more extreme than the 1st and 99th percentile of values
5th 1.36 4.03 1.80 obtained in a healthy, control population. As hypothesized,
10th 1.62 4.45 1.98
25th 1.84 4.75 2.30
youth with LVDD using these pediatric thresholds
50th 2.23 5.77 2.71 (LVDDpeds) had greater measures of adiposity and greater
75th 2.69 6.65 3.25 BP than those without. Further, DBP z score was an indepen-
90th 3.34 7.37 3.84
95th 3.89 7.76 4.09
dent predictor of LVDDpeds using E/A criteria, with each 1-
99th 4.92 8.54 4.88 unit increase in z score associated with a 2 times greater
odds of diastolic dysfunction.
Values in bold indicate pediatric cutoffs chosen to indicate diastolic dysfunction in the study
population. In adults, LVDD is an important intermediate outcome
because it is independently associated with the development
Table III shows the clinical characteristics at the initial clinic of heart failure, CV outcomes, and mortality.7-11 The hall-
visit of the study population with and without LVDDpeds. mark of diastolic dysfunction is impaired relaxation during
Weight, systolic and DBP (mm Hg), index, and z score, HTN, diastole, leading to incomplete cardiac filling.26 Over time,
BP medication use, and non-HDL cholesterol were all the cardiac muscle becomes progressively hypertrophied
significantly greater among youth with LVDDpeds by E/A; they with decreased elasticity and adaptive remodeling which ul-
were also more likely to be older and male. The group with timately becomes pathological and leads to heart failure.26
LVDDpeds defined using e0 /a0 had significantly greater systolic Early detection and intervention in asymptomatic adults
and DBP, DBP index, diabetes, and non-HDL cholesterol. lead to substantial improvement in morbidity and a reduc-
Only BP medication use was significantly associated with tion in CV events and mortality.27 There are several different
LVDDpeds when defined using E/e0 . and complementary ways by which LV diastolic function can
Results from the regression analyses of specific CVD risk fac- be assessed. This includes measuring the E/A ratio, which as-
tors and LVDDpeds are shown in Table IV. In both unadjusted sesses the velocity of LV blood flow during early diastole
and adjusted analyses, DBP z score was associated with a (passive flow during cardiac relaxation) and late diastole
greater odds of LVDDpeds when defined using E/A. (flow during atrial contraction); the e0 /a0 ratio, which mea-
Specifically, with each 1-unit increase in DBP z score, there sures the velocity of mitral annular movement during early
was 2.18 times greater odds of having LVDDpeds defined by E/ diastole (e0 ) and during atrial contraction (a0 ); or by
A (95% CI 1.33-3.59, P = .002). This finding persisted after measuring E/e0 , which is an estimate of LV filling pressures
adjusting for age, sex, race, BP medication use, and BMI z during diastole.25,28-31 Based on these different approaches
score: each 1-unit increase in DBP z score was associated with to LV diastolic function assessment, we opted to measure
an almost 2 times greater odds of LVDDpeds defined by E/A all 3 in our study, particularly as each is considered a signif-
(aOR 1.95, 95% CI 1.15-3.32, P = .014). DBP z score was also icant predictor of mild-to-severe diastolic dysfunction.25,28
significantly associated with LVDDpeds, defined by e0 /a0 in This is consistent with conventional approaches, as each
univariate analyses (OR 1.63, 95% CI 1.02-2.62; P = .04). measure has strengths and limitations and are often not as-
However, after adjustment, although the point estimate was sessed independently. For example, although E/A provides
similar (OR 1.68), this association was only borderline prognostic information in adults, it is a load-dependent mea-
statistically significant (95% CI 0.98-2.88; P = .06). Similarly, surement that can be altered by hydration status and high
in unadjusted analyses hypertension was significantly systolic BP.25,28 Interestingly, this was the only outcome in
associated with LVDDpeds defined by E/A (OR 2.20, 95% CI our study that was independently associated with CVD risk
1.01-4.79, P = .048), but the association was not significant factors in our cohort of youth with extreme adiposity. This
after multivariable adjustment. Neither BMI z score nor significant association might be explained by increased
systolic blood pressure z score was associated with LVDDpeds sodium and water retention, as is commonly observed in in-
in any of the models. dividuals with overweight/obesity, leading to increased intra-
vascular volume and elevated BP, particularly DBP.32 The e0 /
a0 and E/e0 ratios are not load dependent.25 However, it is
Discussion important to note that e0 decreases with age and E/e0 does
not provide a reliable estimate of LV filling pressures in
In this group of high-risk youth with obesity and elevated BP, normal individuals nor in individuals with mitral valve dis-
we found a significant prevalence of target organ damage ease.25 These characteristics are possible reasons why we
including LVDD using both adult and pediatric-based did not observe a significant association with these measures
Left Ventricular Diastolic Dysfunction Among Youth with Obesity and History of Elevated Blood Pressure 133
134

THE JOURNAL OF PEDIATRICS

Table III. Characteristics of participants with overweight/obesity and elevated blood pressure, with and without diastolic dysfunction*
Measures of LV diastolic function
E/A (septal/medial), n = 79 E/e0 (average), n = 81 e0 /a0 (septal/medial), n = 80
Characteristics† Overall, N = 83‡ E/A >1.62, n = 61 E/A <1.62, n = 18 P value E/e0 <8.54, n = 65 E/e0 >8.54, n = 16 P value e0 /a0 >1.64, n = 55 e0 /a0 <1.64, n = 25 P value
Demographic features
Age, y 14 [11, 16] 13 [10, 15] 15 [14, 17] .04 14 [12, 16] 11 [8, 16] .09 13 [10, 16] 14 [12, 15] .31
Female sex 42 (35) 52 (32) 17 (3) .01 42 (27) 44 (7) .87 45 (25) 32 (8) .26
African American race 76 (63) 82 (50) 56 (10) .02 77 (50) 69 (11) .50 84 (46) 60 (15) .02
Adiposity measures
Weight, kg 99.5 [79.9, 126.2] 95 [68, 125] 113 [100, 145] .02 104 [84, 127] 88 [55, 105] .09 99 [69, 126] 102 [89, 125] .43
BMI, kg/m2 36.8 [32.3, 43.9] 36.1 [30.9, 44.1] 40.6 [35.5, 44.4] .10 37.6 [32.5, 44.1] 34.2 [31.7, 39.4] .22 36.8 [32.3, 44.2] 37.4 [34.3, 43.7] .57
BMI z score 2.60 [2.42, 2.81] 2.60 [2.39, 2.77] 2.69 [2.50, 2.90] .26 2.60 [2.41, 2.80] 2.62 [2.54, 2.99] .23 2.60 [2.44, 2.79] 2.61 [2.41, 2.87] .93
CV measures
Systolic
BP 124 [114, 135] 121 [110, 130] 132 [125, 145] <.01 124 [113, 134] 124 [119, 135] .69 121 [111, 134] 128 [124, 139] .03
BP z score§


1.48 [0.67, 2.05] 1.34 [0.61, 1.88] 2.05 [1.31, 2.33] .02 1.40 [0.67, 1.88] 1.65 [1.22, 2.33] .11 1.34 [0.63, 1.97] 1.88 [1.40, 2.33] .08
BP index{ 0.98 [0.88, 1.04] 0.97 [0.86, 1.03] 1.03 [0.96, 1.10] .01 0.97 [0.87, 1.04] 1.02 [0.95, 1.04] .29 0.97 [0.87, 1.04] 1.00 [0.97, 1.04] .18

www.jpeds.com
Diastolic
BP 65 [58, 72] 64 [58, 71] 72 [63, 83] .01 65 [58, 72] 63 [58, 75] .69 64 [58, 71] 72 [60, 79] .06
BP z score‡ 0.13 [-0.51, 0.82] 0.00 [-0.52, 0.67] 0.74 [-0.20, 1.35] .05 0.02 [-0.71, 0.81] 0.15 [-0.36, 0.82] .44 0.02 [-0.51, 0.64] 0.71 [-0.67, 1.18] .13
BP index{ 0.79 [0.61, 0.90] 0.74 [0.58, 0.88] 0.90 [0.77, 1.04] <.01 0.79 [0.67, 0.90] 0.71 [0.38, 0.94] .73 0.73 [0.56, 0.89] 0.86 [0.75, 0.98] .02
HTN** 51 (42) 43 (26) 72 (13) .03 48 (31) 62 (10) .29 47 (26) 64 (16) .17
BP medications 36 (30) 30 (18) 56 (10) .04 31 (20) 62 (10) .02 38 (21) 36 (9) .85
LVMI, g/m2.7 44.8 [39.5, 56.8] 44.5 [39.5, 57.2] 49.5 [38.0, 57.9] .56 44.8 [39.5, 55.9] 50.8 [39.6, 59.0] .53 46.3 [39.5, 56.8] 43.9 [37.5, 58.5] .85
LVH
LVMI ³95th %ile 72 (59) 73 (44) 72 (13) .93 71 (46) 80 (12) .47 74 (40) 64 (16) .36
LVMI >51 g/m2.7 37 (30) 37 (22) 44 (8) .55 35 (23) 47 (7) .42 39 (21) 36 (9) .81
Medical history
Diabetes†† 20 (13) 17 (8) 29 (5) .30 23 (12) 8 (1) .25 12 (5) 35 (8) .04
Prediabetes‡‡ 34 (23) 35 (17) 25 (4) .44 35 (19) 25 (3) .50 36 (15) 26 (6) .43
Obstructive sleep apnea§§ 64 (49) 66 (37) 59 (10) .59 66 (39) 62 (10) .79 65 (34) 68 (15) .82
Laboratory assessments
HbA1c (%) 5.6 [5.5, 6.1] 5.7 [5.5, 6.1] 5.6 [5.4, 7.3] .88 5.6 [5.4, 6.3] 5.6 [5.5, 5.8] .92 5.5 [5.4, 6.0] 5.7 [5.6, 6.1] .12
Non-HDL cholesterol, mg/dL 114 [93, 132] 109 [90, 127] 132 [117, 146] .02 109 [91, 130] 129 [105, 132] .29 109 [89, 129] 129 [108, 139] .03
Total cholesterol, mg/dL 158 [143, 175] 155 [141, 170] 175 [155, 189] .07 156 [142, 174] 166 [153, 176] .44 155 [140, 173] 165 [153, 179] .15
LDL cholesterol, mg/dL 97 [79, 109] 92 [75, 106] 103 [89, 122] .16 95 [75, 109] 98 [80, 106] .92 95 [74, 108] 103 [88, 113] .12
Triglycerides, mg/dL 96 [74, 137] 86 [70, 119] 137 [80, 184] .10 89 [68, 133] 132 [75, 143] .27 87 [74, 135] 100 [69, 151] .39
Dietary assessments
Potassium, mg/d 1747 [1356, 2263] 1741 [1224, 2174] 1939 [1651, 2775] .09 1742 [1299, 2158] 1951 [1732, 3087] .05 1747 [1332, 2213] 1875 [1396, 2438] .59
Sodium, mg/d 3072 [2353, 3650] 3051 [2372, 3711] 3391 [2444, 3616] .98 3027 [2116, 3666] 3434 [3243, 3616] .09 3101 [2354, 3600] 3036 [2364, 4199] .96
Omega 3 fatty acids, g/d 1.6 [0.7, 2.2] 1.7 [1.2, 2.2] 0.7 [0.5, 0.9] .06 1.6 [0.6, 2.2] 1.2 [0.9, 2.2] .93 1.7 [0.9, 2.2] 1.3 [0.4, 2.0] .50

HbA1c, hemoglobin A1c; LDL, low-density lipoprotein.

Values in bold are statistically significant with a P < .05.
*Diastolic dysfunction defined as <10th percentile for E/A, >99th percentile for E/e0 , and <1st percentile for e0 /a0 based on measures obtained in a healthy control pediatric population. E/A cutoff measures were defined <10th percentile (and not <1st percentile) based
Abdul-Raheem et al

on the distribution of measurements in the study population to ensure enough data points for statistical analyses.
†Continuous characteristics represented as median [IQR] and categorical characteristics as % (No.).
‡Missing data include BMI z score: n = 5; LVM: n = 1; diabetes: n = 17; prediabetes: n = 15; obstructive sleep apnea: n = 6; HbA1c: n = 18, non-HDL: n = 17; total cholesterol: n = 17; LDL: n = 18; triglycerides: n = 18; potassium: n = 12; sodium: n = 11; omega 3:

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n = 43.
§Based on 2017 guidelines age, sex, and height-specific cutoffs.
{BP index (systolic or diastolic) calculated as the average of 3 manual BPs/95th percentile value for a given child’s age, sex, and height for <13 years, 130 mm Hg systolic for ³13 years, 80 mm Hg diastolic for ³13 years; BP index ³1 indicates a hypertensive BP.
**HTN defined as systolic or diastolic blood pressure ³95th percentile for age <13 years or blood pressure ³130/80 mm Hg for age ³13 years.
††Diabetes based on a medical history of diabetes or hemoglobin >6.4%.
‡‡Prediabetes defined as hemoglobin between >5.7% and <6.4%.
§§Obstructive sleep apnea based on a medical history of diabetes or obstructive sleep apnea screen >0.3.
August 2021 ORIGINAL ARTICLES

Table IV. Predictors of LVDD defined using pediatric cutoffs* among children with overweight/obesity and elevated
BP
E/A (septal/medial) < 1.62 E/e0 (average) > 8.54 e0 /a0 (septal/medial) < 1.64
(n = 125 visits from 75 (n = 127 visits from 78 (n = 125 visits from 78
participants) participants) participants)
CVD risk factors OR 95% CI P value OR 95% CI P value OR 95% CI P value
BMI z score
Unadjusted 2.52 0.73-8.73 .146 2.04 0.36-11.65 .423 0.94 0.25-3.48 .920
Adjusted for age, sex, race, SBPz 3.54 0.90-13.85 .069 2.29 0.44-11.76 .322 1.14 0.28-4.72 .854
Adjusted for age, sex, race, DBPz 3.28 0.82-13.12 .093 2.18 0.36-13.09 .394 1.00 0.21-4.70 .997
Adjusted for age, sex, race, HTN 3.42 0.90-12.97 .070 2.34 0.43-12.65 .322 1.15 0.28-4.70 .845
Systolic BP z score†
Unadjusted 1.28 0.77-2.14 .339 1.37 0.76-2.46 .297 1.63 0.95-2.81 .078
Adjusted for age, sex, race, BMIz 1.10 0.65-1.86 .733 1.50 0.79-2.85 .218 1.54 0.89-2.67 .121
Adjusted for age, sex, race, BMIz, BP medications 0.95 0.57-1.58 .847 1.25 0.65-2.40 .495 1.58 0.93-2.68 .093
Diastolic BP z score†
Unadjusted 2.18 1.33-3.59 .002 1.46 0.91-2.35 .115 1.63 1.02-2.62 .041
Adjusted for age, sex, race, BMIz 2.08 1.20-3.62 .009 1.44 0.90-2.32 .129 1.66 0.97-2.83 .065
Adjusted for age, sex, race, BMIz, BP medications 1.95 1.15-3.32 .014 1.32 0.82-2.13 .257 1.68 0.98-2.88 .059
HTN‡
Unadjusted 2.20 1.01-4.79 .048 1.53 0.59-3.96 .381 1.98 0.86-4.60 .110
Adjusted for age, sex, race, BMIz 1.71 0.70-4.17 .236 1.86 0.68-5.06 .224 1.82 0.73-4.52 .195
Adjusted for age, sex, race, BMIz, BP medications 1.41 0.6-3.31 .433 1.42 0.49-4.11 .516 1.85 0.75-4.58 .184

SPB, systolic blood pressure.

Values in bold are statistically significant with a P < .05.
*LVDD was defined as <10th percentile for E/A, >99th percentile for E/e0 , and <1st percentile for e0 /a0 based on the control population.
†Based on 2017 guidelines age, sex, and height-specific cutoffs.
‡HTN defined as systolic or DBP ³95th percentile for age <13 years or blood pressure ³130/80 mm Hg for age ³13 years.

in our pediatric population, a population that has not had
decades of exposure to CVD risk factors known to affect
valvular function and ventricular filling.
Among adults, E/A and E/e0 are used more often than e0 /a0
for clinical diagnosis of LVDD. Predictors of LVDD in adults
include increasing age, obesity, HTN, and diabetes, similar to
what we found in our study population.7-10,33 Notably, we
found increased DBP z score to be an independent predictor
of LVDD. This is not necessarily surprising, as DBP, like dia-
stolic function, is measured during cardiac relaxation. In
adults, elevated DBP is a stronger predictor of coronary heart
disease risk than systolic BP in patients younger than
50 years.34,35 In addition, diastolic HTN independently pre-
dicts the risk of adverse CV outcomes that include myocar-
dial infarction, ischemic stroke, and hemorrhagic stroke in
adults.36 Elevated DBP may therefore play an important
role in assessing CV outcomes in pediatric patients.
Consistent with other pediatric assessments of CVD risk,
the LVDDpeds cutoff criteria employed in this study was
determined using epidemiologic thresholds based on data
from a healthy cohort. We adopted this approach due to
the lack of universally established thresholds by which to
define LVDD by E/A, E/e0 , or by e0 /a0 in youth, recognizing
that diastolic function may be influenced by body size, vessel
caliber, and linear growth, making use of adult cutoffs less
ideal for use in children.37 Our approach to identifying the
LVDDpeds values were similar to approaches used by other in-
vestigators.20-23 A 2013 study evaluating LVDD in pediatric
CKD defined LVDD as >2 SDs greater than the mean E/e0
measured in a healthy control population.20 Using this cut-
off, they described a LVDD prevalence of 38.5% for patients
with CKD and 42.9% for patients after renal transplant.20 In a
Left Ventricular Diastolic Dysfunction Among Youth with Obesity and History of Elevated Blood Pressure
2019 study evaluating diastolic function in pediatric-onset
SLE, z scores of >2 for E/e0 and <–2 for E/A obtained from
a healthy control population identified LVDD in 24% of their
population based on E/e0 and 0% based on E/A.23 What is
most striking about these results is that the burden of
LVDD in these high-risk populations is similar to the burden
observed in our population of youth considered to be at a
lower tier of CVD risk. We are not the first to describe the
role of adiposity on LVDD; Dusan et al demonstrated that
almost 2% of children with obesity as their sole CVD risk fac-
tor had LVDD based on E/A using adult criteria.24 Although
the American Heart Association has categorized children
with severe obesity and confirmed hypertension to be at
moderate CVD risk,38 these findings underscore the impor-
tance of being vigilant in the prevention and treatment of
these risk factors in children and adolescents.
There are several limitations of this study that should be kept
in mind when considering our results. These include its rela-
tively smaller sample size and cross-sectional design, preventing
an inference of causality. In addition, we employed epidemio-
logic cutoffs for defining pediatric LVDD, thresholds obtained
from 103 healthy controls and not yet known to be associated
with clinical outcomes. This is also a relatively small population
from which to derive control data, and does not include data
from children under age 7 years.
With the known tracking of BP and target organ damage
from childhood to adulthood, and the known association
of LVDD with CV outcomes in adulthood, these results sug-
gest an elevated CVD risk profile of children with obesity
related hypertension. Continued efforts aimed at prevention
and treatment of these risk factors in children remain of para-
mount importance. n
135
THE JOURNAL OF PEDIATRICS  www.jpeds.com
Submitted for publication Dec 21, 2020; last revision received Mar 25, 2021;
accepted Mar 29, 2021.
Reprint requests: Tammy M. Brady, MD, PhD, Johns Hopkins School of
Medicine, The David M. Rubenstein Child Health Building, 200 North Wolfe St,
Room 3062, Baltimore, MD 21287. E-mail: tbrady8@jhmi.edu
References
1. Lakshman R, Elks CE, Ong KK. Childhood obesity. Circulation
2012;126:1770-9.
2. Cheung PC, Cunningham SA, Narayan KMV, Kramer MR. Childhood
obesity incidence in the United States: a systematic review. Child Obes
2016;12:1-11.
3. Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ. Overweight,
ethnicity, and the prevalence of hypertension in school-aged children.
Pediatrics 2004;113:475-82.
4. Brady TM, Appel LJ, Holmes KW, Fivush B, Miller ER 3rd. Association
between adiposity and left ventricular mass in children with hyperten-
sion. J Clin Hypertens (Greenwich) 2016;18:625-33.
5. Li X, Li S, Ulusoy E, Chen W, Srinivasan SR, Berenson GS. Childhood
adiposity as a predictor of cardiac mass in adulthood: the Bogalusa Heart
Study: the Bogalusa heart study. Circulation 2004;110:3488-92.
6. Baker JL, Olsen LW, Sørensen TIA. Childhood body-mass index and the
risk of coronary heart disease in adulthood. N Engl J Med 2007;357:
2329-37.
7. Kane GC, Karon BL, Mahoney DW, Redfield MM, Roger VL, Burnett JC,
et al. Progression of left ventricular diastolic dysfunction and risk of
heart failure. JAMA 2011;306:856-63.
8. Redfield MM, Jacobsen SJ, Burnett JC Jr, Mahoney DW, Bailey KR,
Rodeheffer RJ. Burden of systolic and diastolic ventricular dysfunction
in the community appreciating the scope of the heart failure epidemic.
ACC Curr J Rev 2003;12:50-1.
9. Ammar KA, Redfield MM, Mahoney DW, Johnson M, Jacobsen SJ,
Rodeheffer RJ. Central obesity: association with left ventricular dysfunc-
tion and mortality in the community. Am Heart J 2008;156:975-81.
10. Schillaci G, Pasqualini L, Verdecchia P, Vaudo G, Marchesi S, Porcellati C,
et al. Prognostic significance of left ventricular diastolic dysfunction in essen-
tial hypertension. J Am Coll Cardiol 2002;39:2005-11.
11. Barbosa JA, Rodrigues A, Mota C, Barbosa, Simoes e Silva A. Cardiovascular
dysfunction in obesity and new diagnostic imaging techniques: the role of
noninvasive image methods. Vasc Health Risk Manag 2011;7:287-95.
12. Daniels SD, Meyer RA, Loggie JM. Determinants of cardiac involvement
in children and adolescents with essential hypertension. Circulation
1990;82:1243-8.
13. Hanevold C, Waller J, Daniels S, Portman R, Sorof J. International Pedi-
atric Hypertension Association. The effects of obesity, gender, and ethnic
group on left ventricular hypertrophy and geometry in hypertensive chil-
dren: a collaborative study of the International Pediatric Hypertension
Association. Pediatrics 2004;113:328-33.
14. Brady TM, Fivush B, Flynn JT, Parekh R. Ability of blood pressure to pre-
dict left ventricular hypertrophy in children with primary hypertension.
J Pediatr 2008;152:73-8. 78.e1.
15. Rosner B, Cook NR, Daniels S, Falkner B. Childhood blood pressure
trends and risk factors for high blood pressure: the NHANES experience
1988-2008. Hypertension 2013;62:247-54.
16. Kuczmarski RJ, Ogden CL, Guo SS, Grummer-Strawn LM, Flegal KM,
Mei Z, et al. 2000 CDC growth charts for the United States: methods
and development. Vital C Stat 11 2002;246:1-190.
17. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE,
Daniels SR, et al. Clinical practice guideline for screening and manage-
ment of high blood pressure in children and adolescents. Pediatrics
2017;140:e20171904.
18. Jafary FH. Devereux formula for left ventricular mass—be careful to use
the right units of measurement. J Am Soc Echocardiogr 2007;20:783.
136
Volume 235
19. Khoury PR, Mitsnefes M, Daniels SR, Kimball TR. Age-specific reference
intervals for indexed left ventricular mass in children. J Am Soc Echocar-
diogr 2009;22:709-14.
20. Lindblad YT, Axelsson J, Balzano R, Vavilis G, Chromek M, Celsi G, et al.
Left ventricular diastolic dysfunction by tissue Doppler echocardiogra-
phy in pediatric chronic kidney disease. Pediatr Nephrol 2013;28:
2003-13.
21. Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ,
Khoury PR, et al. Impaired left ventricular diastolic function in children
with chronic renal failure. Kidney Int 2004;65:1461-6.
22. Mitsnefes MM, Kimball TR, Border WL, Witt SA, Glascock BJ,
Khoury PR, et al. Abnormal cardiac function in children after renal
transplantation. Am J Kidney Dis 2004;43:721-6.
23. Chang JC, White BR, Elias MD, Xiao R, Knight AM, Weiss PF, et al.
Echocardiographic assessment of diastolic function in children with
incident systemic lupus erythematosus. Pediatr Cardiol 2019;40:
1017-25.
24. Dusan P, Tamara I, Goran V, Gordana M-L, Amira P-A. Left ventricular
mass and diastolic function in obese children and adolescents. Pediatr
Nephrol 2015;30:645-52.
25. Nagueh SF, Smiseth OA, Appleton CP, Byrd BF, Dokainish H,
Edvardsen T, et al. Recommendations for the evaluation of left ventric-
ular diastolic function by echocardiography: an update from the Amer-
ican society of echocardiography and the European association of
cardiovascular imaging. J Am Soc Echocardiogr 2016;29:277-314.
26. Federmann M, Hess OM. Differentiation between systolic and diastolic
dysfunction. Eur Heart J 1994;15(suppl D):2-6.
27. Kossaify A, Nasr M. Diastolic dysfunction and the new recommenda-
tions for echocardiographic assessment of left ventricular diastolic func-
tion: Summary of guidelines and novelties in diagnosis and grading.
J Diagn Med Sonogr 2019;35:317-25.
28. Mitter SS, Shah SJ, Thomas JD. A test in context: E/A and E/e0 to assess
diastolic dysfunction and LV filling pressure. J Am Coll Cardiol 2017;69:
1451-64.
29. Thomas JD, Weyman AE. Echocardiographic Doppler evaluation of left
ventricular diastolic function. Physics and physiology. Circulation
1991;84:977-90.
30. Morrissey C. Echo for diastology. Ann Card Anaesth 2016;19(suppl):
S12-8.
31. Kloch-Badelek M, Kuznetsova T, Sakiewicz W, Tikhonoff V, Ryabikov A,
Gonzalez A, et al. Prevalence of left ventricular diastolic dysfunction in
European populations based on cross-validated diagnostic thresholds.
Cardiovasc Ultrasound 2012;10:10.
32. Brady TM. Obesity-related hypertension in children. Front Pediatr
2017;5:197.
33. Wan S-H, Vogel MW, Chen HH. Pre-clinical diastolic dysfunction. J Am
Coll Cardiol 2014;63:407-16.
34. Li Y, Wei F-F, Wang S, Cheng Y-B, Wang J-G. Cardiovascular risks asso-
ciated with diastolic blood pressure and isolated diastolic hypertension.
Curr Hypertens Rep 2014;16:489.
35. Franklin SS, Larson MG, Khan SA, Wong ND, Leip EP, Kannel WB, et al.
Does the relation of blood pressure to coronary heart disease risk change
with aging? The Framingham Heart Study: the Framingham heart study.
Circulation 2001;103:1245-9.
36. Flint AC, Conell C, Ren X, Banki NM, Chan SL, Rao VA, et al. Effect of
systolic and diastolic blood pressure on cardiovascular outcomes. N Engl
J Med 2019;381:243-51.
37. Dragulescu A, Mertens L, Friedberg MK. Interpretation of left ventricu-
lar diastolic dysfunction in children with cardiomyopathy by echocardi-
ography: problems and limitations. Circ Cardiovasc Imaging 2013;6:
254-61.
38. de Ferranti SD, Steinberger J, Ameduri R, Baker A, Gooding H, Kelly AS,
et al. Cardiovascular risk reduction in high-risk pediatric patients: a sci-
entific statement from the American Heart Association. Circulation
2019;139:e603-34.
Abdul-Raheem et al
August 2021 ORIGINAL ARTICLES

50 Years Ago in THE JOURNAL OF PEDIATRICS

Our Evolving Understanding of Pediatric Malnutrition
Fischhoff J, Whitten CF, Pettit MG. A Psychiatric Study of Mothers of Infants with Growth Failure Secondary to Maternal
Deprivation. J Pediatr 1971;79:209-15.

P ediatric malnutrition has been defined as the negative imbalance between what is required for a child’s healthy
growth and development and what is delivered effectively.1 This 1971 article by Fischhoff et al describes 16
full-term infants who were found to be malnourished at 3-24 months after birth. These children had no evidence
of organic cause for failure to thrive and showed marked improvement after a period of adequate food provision.
The study evaluated the psychological status of the mothers of these infants, and determined that the infants were
malnourished owing to inadequate nutritional intake associated with maternal deprivation, rather than defects in their
absorption or their metabolism of nutrients.
Fifty years later, although childhood neglect remains a potential etiology for pediatric malnutrition, our understanding
of physiologic and hormone-related changes during periods of decreased intake continues to evolve. It has now been
determined that a child’s nutritional status plays an important role on the growth hormone-insulin-like growth factor-
1 (IGF-1) axis. Insufficient food intake leads to a catabolic state in which the body develops lower levels of IGF-1 (a hor-
mone produced by the liver), leading to lower muscle bulk and linear growth.2 IGF binding protein-3 is a protein that
regulates the transport of IGF-1 in the blood circulation, controlling delivery of the hormone to body tissues.2 IGF binding
protein-3 has been found to act in parallel to levels of IGF-1 during periods of malnutrition, with levels decreasing during
periods of inadequate nutrition and recovering during refeeding.3 It has been suggested that this serum protein is a more
sensitive marker for nutritional status than IGF-1.4 Scientific investigation over the last several decades has also deter-
mined that children in a catabolic state have low baseline insulin and leptin levels with elevated growth hormone, cortisol,
and ghrelin levels, directing the body toward fat catabolism and glucose production, rather than energy storage and
growth.5 These hormonal imbalances reverse with adequate caloric intake.
Malnutrition in children is associated with illness-related catabolic states and can also occur in non-illness-related sit-
uations such as neglect, environmental instability (food insecurity, low socioeconomic status), and in behavioral condi-
tions (oral aversion, disordered eating patterns). Thought to be under-recognized, the American Society for Parenteral
and Enteral Nutrition guidelines now recommend 5 key domains to evaluate for adequate nutritional assessment: anthro-
pometrics, growth patterns, chronicity, etiology, and functional status.1 With advancement in our understanding of pe-
diatric malnutrition, protein markers and hormone levels are becoming increasingly important components of the
nutritional evaluation. We expect that our field of knowledge will continue to evolve as we learn more about the intricate
biochemical pathways of the human body.
Rachel E. Herdes, DO
Division of Pediatric Gastroenterology
Hepatology and Nutrition
Stanford University
Lucile Packard Children’s Hospital
Palo Alto, California

Stephanie B. Oliveira, MD, CNSC

Division of Pediatric Gastroenterology
Hepatology and Nutrition
Cincinnati Children’s Hospital Medical Center
Cincinnati, Ohio
References

1. Mehta NM, Corkins MR, Lyman B, Malone A, Goday PS, Carney LN, et al. Defining pediatric malnutrition: a paradigm shift toward etiology-
related definitions. JPEN J Parenter Enteral Nutr 2013;37:460-81.
2. Haspolat K, Ece A, Gurkan F, Atamer Y, Tutanç M, Yolbaş I. Relationships between leptin, insulin, IGF-1 and IGFBP-3 in children with energy
malnutrition. Clin Biochem 2007;40:201-5.
3. Livingstone C. The insulin-like growth factor system and nutritional assessment. Scientifica (Cairo) 2012;2012:768731.
4. Ozen M, Cokugras H, Ozen H, Camcioglu Y, Akcakaya N. Relation between serum insulin-like growth factor-I and insulin-like growth factor-
binding protein-3 levels, clinical status and growth parameters in prepuberal cystic fibrosis patients. Pediatr Int 2004;46:429-35.
5. Bartz S, Mody A, Hornik C, Bain J, Muehlbauer M, Kiyimba T, et al. Severe acute malnutrition in childhood: hormonal and metabolic status at
presentation, response to treatment, and predictors of mortality. J Clin Endocrinol Metab 2014;99:2128-37.

Left Ventricular Diastolic Dysfunction Among Youth with Obesity and History of Elevated Blood Pressure 137