Curr Hypertens Rep (2014) 16:495

DOI 10.1007/s11906-014-0495-z

PEDIATRIC HYPERTENSION (JT FLYNN, SECTION EDITOR)

The Emerging Epidemic of Hypertension in Asian

Children and Adolescents
Chong Guk Lee

Published online: 11 October 2014

# Springer Science+Business Media New York 2014

Abstract Hypertension has become a serious global public

health burden because of its high incidence and concomitant
risk of cardiovascular disease. Many studies have verified that
risk factors, such as hypertension and obesity which are responsible for cardiovascular disease, start in early childhood.
In Asian countries, the prevalence of hypertension in the
pediatric age group has become more prevalent than ever
before with the increasing obesity epidemic. To tackle the
epidemic of cardiovascular disease, a leading cause of death
and disability of non-communicable diseases in Asian countries, population-based measures aiming at reducing harmful
environmental factors to blood pressure and body weight must
be applied to individuals in their early childhood, as early as
the fetal stage. This review focused on the prevalence of
pediatric hypertension in Asian countries and outlined several
considerations for accurate blood pressure (BP) measurement
and evaluation, along with an overview of pathophysiology of
fetal programming and obesity related with childhood
hypertension.

Keywords Non-communicable disease . Pediatric

hypertension . Asian children . Blood pressure measurement
devices . Mercurial sphygmomanometer . Oscillometric
device . Blood pressure reference tables . Secular trend .
Tracking phenomenon . Low birth weight . Fetal
programming . Obesity

This article is part of the Topical Collection on Pediatric Hypertension

C. G. Lee (*)
Division of Pediatric Nephrology, Department of Pediatrics, Ilsan
Paik Hospital, Inje University, 2280, Ilsanseo-gu, Goyang-si,
Gyeonggi-do 411-706, South Korea
e-mail: chonglee@paik.ac.kr

Introduction
The WHO global status report on non-communicable diseases
(NCDs) shows that NCDs are the leading causes of death in
the world, responsible for 63 % of deaths in 2008. The
majority of these deaths are attributed to cardiovascular diseases (48 %), cancers (21 %), chronic respiratory diseases
(12 %), and diabetes (2 %) [1, 2]. The leading risk factors
for this mortality are hypertension (responsible for 13 % of
deaths globally) and obesity (5 %), followed by tobacco use,
high blood glucose, and physical inactivity [3]. Alarmingly,
these risk factors are the major causes of death and disability
burden in nearly all countries, regardless of the extent of
economic development. In fact, NCD burden is increasing
more rapidly in Asian countries [4].
The prevalence of hypertension in adults in various regions
of the world has been widely reported [4, 5]. However, sufficient epidemiologic data on blood pressure (BP) in relation to
prevalence and absolute burden in children and adolescents
have not been compiled. Even though the prevalence, awareness, treatment, and control of hypertension in developing
countries are coming closer to those in developed countries
[6], their own accurate estimates of the prevalence of hypertension are essential for the rational planning of health services for their children and adolescents.
Hypertension used to be regarded as an adult disease with
no real relevance to children, because pediatric hypertension
was thought to be mostly attributed to secondary causes [7],
and because the economic impact of pediatric hypertension
was so trivial as compared to costs related to adult hypertension [8, 9]. If so, why should we be concerned about pediatric
hypertension in Asian countries? Reasons that justify the
recent increasing attention to pediatric hypertension can be
summarized as follows: (i) epidemiologic shift to primary
hypertension with increasing obesity epidemic [7, 10], (ii)
tracking phenomenon of BP from childhood to adulthood [11,

495, Page 2 of 9

12], (iii) target organ damage (TOD) related to primary

hypertension in children [1315], and (iv) high incidence of
childhood obesity and low birth weight (LBW) infant in Asian
countries [3, 16].
In this review, the uncertainty of BP reference tables for
Asian children and adolescents in making diagnosis of pediatric hypertension, the prevalence of pediatric hypertension in
Asian countries, and secular trends and tracking phenomenon
of primary hypertension in children and adolescents are described. Furthermore, an overview of programming of hypertension in LBW infants and the pathophysiology of hypertension with obesity are presented.

Curr Hypertens Rep (2014) 16:495

male

mmHg
160
140
120

SBP

100
80

DBP

60
40
20

The Diagnostic Uncertainty of BP Reference Tables for Asian

Children and Adolescents

0
8

BP is defined differently in children than in adults. As children

and adolescents grow into adult size, their BP normally exhibits
a gradual rise. A gender difference in adolescents in the normal
range of BP, with lower levels in female than in male, is also
noted. Therefore, childrens BP is categorized from thresholds
based on gender, age, and height. The fourth report from National H igh B lood Pressure Edu cation P rogram
(2004NHBPEP)s Working Group on High Blood Pressure in
Children and Adolescents defines hypertension as the average
systolic BP (SBP) or diastolic BP (DBP) that is greater than or
equal to the 95th percentile for gender, age, and height on at least
three separate occasions [17]. This statistical definition based on
the normative distribution of BP in healthy children lacks the
evidence-based findings found in adult guidelines [18].
Another limitation to using this percentile definition is the
need to account for the secular trend of body size and accompanying change in BP which may vary in children and adolescents from different countries, because the socioeconomic
environment of human populations are substantially different
among countries [5, 19, 20]. Therefore, it is uncertain whether the 2004NHBPEP BP reference table is applicable to children and adolescents in other countries, who have different
ethnic and biocultural backgrounds.
High BP (prehypertension and hypertension) in Asian
countries, namely China, Japan, and Korea, is defined by
either the SBP, DBP, or both values exceeding the 90th and
95th percentiles of the recommended BP reference cutoffs for
their own children. They are using their own BP reference
tables [21, 22]. Figure 1 is showing the differences in BP
levels of the 95th percentile in the BP reference tables of
Korea [21], China [22], and the USA [17], respectively. Only
the 95th BP levels of the 50th age-specific height percentile of
each age group were compared. The SBP of males across
different age groups was 58 mmHg greater in the Korean
population than that in the US population, but there was little
difference between SBP of the USA and China in the age
group of 714 years, with a 4 mmHg greater BP after 15 years

10

Age(years)

11

12

13

2007 Korea

14

15

16

2010 China

17

2004 USA

female

mmHg
140

120

SBP
100

80

DBP

60

40

20

0
7
Age(years)

10
2007 Korea

11

12

13

2010 China

14

15

16

17

2004 USA

Fig. 1 Comparison of the systolic and diastolic BP 95th percentile in

male (a) and female (b) between Korea (21), China (22), and the USA
(17) blood pressure reference tables

of age in the US population. SBPs in females showed a slight

difference of 15 mmHg among the three countries. However,
DBP of the Korean population demonstrated a much lower
level by 511 mmHg than that of the USA and by 26 mmHg
than that of China. These differences could be explained by
ethnic differences or differences in the BP measurement methodology. BP was measured using a mercury sphygmomanometer in China and the USA, but an oscillometric device
(Dinamap ProCare 300) in Korea.
Though the 2004NHBPEP recommends auscultation as the
preferred method of measuring BP in children, not specifically
a mercury sphygmomanometer [17], a mercury sphygmomanometer is mostly being used as the standard device for accurate BP measurement in children and adolescents.

Curr Hypertens Rep (2014) 16:495

However, because of environmental concerns about mercurial toxicity, alternate instruments are needed. Oscillometric
devices, widely being used, have advantages of their ease of
use and minimization of observer bias in BP measurements on
young children [23]. However, a major disadvantage is that
BP level measured by oscillometric devices does not always
match BP level obtained by a mercury sphygmomanometer
[24]. Oscillometric devices measure mean arterial BP and then
calculate SBP and DBP through algorithms which are proprietary and differ depending on the maker and device [25].
Therefore, oscillometric devices must be validated on a regular basis. Protocols for validation have been developed, but the
validation process is limited to adults of over 25 years old
[26]. BP measurement using oscillometric devices is based
on the principle that pulsatile blood flow through an artery
creates oscillations of the arterial wall, and these oscillations
are sensed to determine BP. Oscillations of blood vessels can
vary according to the state of their stiffness [27]. Therefore,
validation studies of oscillometric devices in children and
adolescents are needed.
When the two devices were compared, a mercury sphygmomanometer (Baumanometer Mercury Gravity Sphygmomanometer, W.A. Baum Co., Copiague, NY, USA) vs. an
oscillometric device (Dinamap ProCare 300, GE Medical
Systems, Milwaukee, WI, USA), the oscillometric device
showed a 1.85 1.65 mmHg greater SBP and a 4.41
3.53 mmHg lower DBP [28]. The difference of BP readings
measured by the oscillometric device and the mercurial device
in 290 children and adolescents in the clinical setting was 3.8
9.1 mmHg greater for SBP and 5.97.9 mmHg lower for
DBP, respectively, in the oscillometric device [29]. In comparison with the Omron 705 IT (Omron Healthcare, Inc.,
Bannockburn, IL, USA), another oscillometric device, the
mean SBP reading was 4.64.9 mmHg greater, and the mean
DBP reading was 3.35.4 mmHg lower [30]. In general,
oscillometric devices record slightly higher SBP levels, but
lower DBP levels compared to those measured by mercurial
devices in children and adolescents.
Accordingly, when BP readings are evaluated in children
and adolescents, the difference of BP level between the auscultation and oscillometric device is needed to be considered.
The 2004NHBPEP recommends that an elevated BP reading
obtained with an oscillometric device should be repeated by
using auscultation [17].
Prevalence of Hypertension in Asian Pediatric Age Group
The prevalence of pediatric hypertension vary greatly depending on the differences in the definition of high BP, normative
BP reference tables, BP measurement devices, and the number
of occasions on which BP is measured. Based on the use of
95th percentile to define hypertension, the prevalence of
hypertension is expected to be approximately 5 %. However,

Page 3 of 9, 495

due to the effects of accommodation and regression to the

mean with repeated measurements, the actual prevalence of
hypertension is lower than 5 % and had been reported to be 1
3 % after three separate BP measurements in children and
adolescents with an initial BP measurement in the 95th
percentile [31]. BP screening studies conducted in schools
show that many children with an initially high BP have normal
BP after repeated measurements [32]. This reduction in the
prevalence of hypertension after repeated measurements emphasizes that a single elevated BP is insufficient to make the
clinical diagnosis of hypertension in children and adolescents
[33]. A recent survey in community-based practices in the
USA showed that the prevalence of prehypertension and
hypertension was 12.7 and 5.4 %, respectively, at the first
visit, but it was 12.0 and 0.3 %, respectively, after two subsequent visits [34]. In view of those variables in determining the
prevalence of pediatric hypertension in a certain area, it seems
to be inappropriate to compare the prevalence rate in a country
with others. A standardized method for BP measurement and
evaluation should be uniformly applied to the surveillance
study of childhood BP.
The epidemiologic evidence to support an adverse impact
of childhood obesity on BP levels has been suggested. In
China, prevalence rates of prehypertension and hypertension
accounted for 7.2 and 3.1 %, respectively, according to the
criteria of recommended BP reference cutoffs for Chinese
children [22] in Changsha City. Being overweight or obese
was both markedly associated with an increased risk of hypertension and prehypertension. The proportions of adolescents with hypertension across the body mass index (BMI)
categories were, respectively, 1.0, 3.3, and 11.5 % in normal
weight, overweight, and obese girls and 2.6, 7.5, and 21.7 %
in normal weight, overweight, and obese boys [10]. Another
Chinese national survey in 2010 showed that the prevalence of
hypertension was 16.1 % for boys and 12.9 % for girls [35].
A perspective on the prevalence of hypertension in Korean
children and adolescents can be made using the results of
nationwide health examinations for school students aged 7
to 18 years. Hypertension was defined by BP over 95th
percentile of the Korean BP reference table by gender, age,
and height [21, 36]. Screening studies conducted in 7-, 10-,
13-, and 16-year-old children and adolescents of 87,253 in
2012 revealed the prevalence of hypertension after the first
screening to be 2.8, 4.6, 7.1, and 8.2 %, respectively [37]. It
surely does not represent the actual prevalence of hypertension in Korean children and adolescents. Repeated measurements, at least three times apart, will result in much lower
rates. The prevalence of obesity (BMI 95th percentile of the
2007 Korean growth chart) was around 10 % before the age of
11 years but increased abruptly to 22 % at the age of 17 to
18 years in males; however, it was 8 % before the age of
12 years and then reached 13.2 % at the age of 18 years in
females [37]. Another study showed that the overall

495, Page 4 of 9

prevalence of hypertension among 46,024 children and adolescents between the ages of 7 and 18 years in 2005 Korea
national survey was 10.6 % (12.9 % in male and 8.2 % in
female, respectively). The survey was based on single BP
measurements by using an oscillometric device and the
2004NHBPEP BP table. The proportions of hypertension
across the BMI categories were, respectively, 7.5, 17.7, and
28.8 % in normal weight, overweight, and obese children and
adolescents (unpublished data). The prevalence of obesity
(BMI 95th percentile) increased from 5.5 to 9.7 % in the
period of 10 years from 1995 to 2005 [38].
From numerous studies regarding the prevalence of childhood hypertension, it appears to have an overall prevalence of
2.53 % in children and adolescents and, of prehypertension,
a prevalence of 912 % after repeated measurements. Recent
studies have demonstrated that prevalence is generally similar
in different countries irrespective of socioeconomic conditions
in each country [7]. Also, many analyses have verified that
the population increase in BP among children and adolescents
is largely due to the increase incidence of obesity [31].
Secular Trends and Tracking Phenomenon of Primary
Hypertension in Children and Adolescents
It is well established that hypertension in childhood is frequently associated with obesity. Increasing obesity epidemic
all over the world, even in Asian countries, results in a high
prevalence of hypertension [7, 9, 10].
The National Health and Nutrition Examination Survey
(NHANES) in the USA showed that mean BP levels have
increased in children over the past decade. SBP and DBP were
found to increase by 1.4 and 3.3 mmHg from 19881994 to
19992000 [39]; also, during the same period, an overall
increase in the prevalence of hypertension from 2.7 % in the
19881994 survey to 3.7 % in the 19992002 survey was
reported [40]. A recent analysis of NHANES data revealed
that the prevalence of elevated BP increased from NHANES
III to NHANES 19992008 (boys, 15.8 to 19.2 %; girls, 8.2 %
to 12.6 %). Increased prevalence of elevated BP was independently associated with BMI [41]. In the cohort study
established in the USA, researchers tracked growth and BP
for 27 years. They reported that the rate of hypertension was
higher in children who were overweight or obese (14 and
26 %, respectively). Children classified as overweight or
obese had double and quadruple the risk to have a diagnosis
of hypertension in adulthood, respectively, as compared to
normal weight children [42]. A Japanese group assessed the
health report data between 1983 and 2007 to clarify the
relationship between long-term changes in BMI and BP levels
in children and adolescent. Through multiple regression analysis, they concluded that higher changes in BMI (BMI) over
the 6-year period were associated with higher SBP even in
children whose BMI was in the lowest tertile at baseline. They

Curr Hypertens Rep (2014) 16:495

insisted that growth during childhood should be carefully

monitored because steeper BMI increases during primary
school lead to adolescent increases in BP even if baseline
BMI is low [43]. A Chinese study showed a relationship
between the prevalence of hypertension or prehypertension
and BMI. Approximately 53.4 % of the hypertensive cases
were attributed to excess body weight, and the prevalence of
hypertension in obese females and males was more than 11and 8-fold greater, respectively, than that in normal weight
subjects [10]. A recent study in China also showed that BP
among Chinese children and adolescents was on the rise from
2005 to 2010 by 1.21.5 mmHg of SBP and 1.01.1 mmHg of
DBP, respectively, which were decreased by 40.5 and 26.9 %,
respectively, after adjusting for the differences in BMI in 2005
and 2010 [44]. A study of a school-based population in
Shanghai revealed that BMI and waist circumference (WC)
were positively correlated with SBP and DBP. Being overweight or obese greatly increased the risk of hypertension in
Chinese children and adolescents, in which WC, denoting
central obesity, was considered as a more sensitive indicator
than BMI [45].
Even though a contradictory finding that neither the mean
nor high BP levels increased during the period in which the
prevalence of obesity increased almost threefold was reported
[46], in general, most studies have clearly showed that the
increase in absolute mean BP levels and the prevalence of
hypertension seem to be related to the obesity epidemic and
that the secular trend of BP in children and adolescents is
closely related to the increased prevalence of obesity. The
recent upward trend of childhood obesity in Asian countries
following the socioeconomic development attributes to the
rising rates of childhood high BP.
Meta-analysis of data from diverse populations showed
that BP tracks from childhood to adulthood and that an elevated BP in childhood is likely to predict adult hypertension
[12]. Tracking of BP over time has been an intriguing subject
as a way of identifying one of the high risk factors, hypertension, for cardiovascular disease. It is clear that hypertension
begins in childhood, and high BP in the young predicts future
high BP in the adult. Therefore, identifying children with
elevated BP and hypertension and starting early treatment or
prevention of hypertension may have an important impact on
the long-term outcome of cardiovascular disease [47].
Low Birth Weight and Hypertension
Many studies have identified various risk factors that are
attributable to the development of hypertension in childhood,
such as genes, dietary intake, physical activity, and environmental factors. Recent epidemiologic data showed that fetal
and perinatal events appear to exert effects on certain chronic
diseases, such as hypertension and chronic kidney disease
later in adulthood. The term of the Developmental Origin of

Curr Hypertens Rep (2014) 16:495

Health and Disease (DOHaD) emerged to describe the association between fetal and postnatal growth and, later, chronic
adult diseases. DOHaD should be viewed as a part of a
broader biological mechanism of plasticity by which organisms, in response to cues such as nutrition or hormones, adapt
their phenotype to the environment [48, 49].
Developmental plasticity, defined as the ability of an organism to develop in various ways, depending on the particular environment or setting [50], provides a conceptual basis
for DOHaD. This concept was first reported by Barker [51,
52], who showed a link between nutritional deficiency during
fetal growth and adult diseases, hypertension and obesity. This
Barkers hypothesis was extended to an important paradigm, DOHaD, in a multidisciplinary field. Further extension of this idea developed into what became known
as fetal origins of adult disease (FOAD). FOAD contends that environmental influences during fetal life can
influence adult health and transgenerational inheritance
of non-genomic information through various mechanisms, including epigenetics [50, 53, 54].
Birth weight is an indicator of nutrient availability in fetuses, and LBW is a marker of poor fetal growth. In the case of
in utero stress caused by maternal undernutrition, the developing fetus senses the adverse environment and reprograms
the genome, which favors immediate survival but results in
predisposition to hypertension and obesity in adult life. When
there is deprivation followed by plenty, catch-up growth occurs which predisposes the fetus to hypertension and obesity
[55]. Fetal programming by maternal malnutrition results in
LBW and reduction in nephron number, increasing the risk for
hypertension and renal diseases [56]. A kidney with fewer
nephrons was postulated to have a diminished filtration surface area, resulting in the limitation of sodium excretion,
leading to raised BP and reduction of renal adaptive capacity
in the setting of injury. A high prevalence of hypertension and
renal disease in populations with an increased frequency of
LBW (less than 2.5 kg) was recognized, whereby LBW and
prematurity were shown as the most consistent clinical surrogates for a low nephron number and were associated with an
increased risk of hypertension in later life [57].
Globally, 15.5 % of live newborn babies born weigh less
than 2.5 kg, as LBW infants, suggesting that they are at risk of
hypertension and kidney disease in later life [58]. The incidence of LBW in Asian countries was reported to be around
18.3 %, with India contributing to 40 % of the developing
worlds LBW population. In China, 1.1 million LBW infants
were born in 2004 [58]; South Korea reported 25,900 LBW
infants, which comprised 5 % of total live births in 2012 [59].
We, therefore, are sure that a quite large number of Asian
children of LBW are vulnerable to hypertension and renal
diseases. In fact, findings of a systematic review showed that,
in preterm babies born at a mean gestational age of 30.2 weeks
with a mean birth weight of 1.28 kg, BP in later life was

Page 5 of 9, 495

2.5 mmHg higher than in those born at term [60]. In another

study, a 2.28 mmHg increase in SBP was recorded in individuals whose birth weight was less than 2.5 kg, compared with
those heavier than 2.5 kg [61].
The precise mechanism for fetal programming of adult
disease is still unclear. Accumulating evidence suggests that
environmental factors during early life might also program the
development of obesity and hypertension [62, 63], but these
aspects are beyond the scope of this review.
Pathophysiology of Hypertension in Obesity
Although the mechanism of hypertension associated with
obesity is still an area of research, inappropriate activation of
the sympathetic nervous system life (SNS) and reninangiotensin system (RAS), the roles of adipokines and inflammatory cytokines, and endothelial dysfunction are suggested
as main attributable factors [64].
White adipose tissue in visceral fat is regarded as the largest
endocrine organ of the body that produce a variety of bioactive factors called adipokines and pro-inflammatory cytokines
which are clearly risk factors for hypertension [65].
Recent studies have shown that increased renal sympathetic nerve activity (RSNA) and RAS, which contribute to altered renal function, such as increased sodium reabsorption
and impaired pressure natriuresis, play key roles in obesity
hypertension. In fact, among several mediators of SNS activation, leptin functions as a promising mediator of obesityinduced SNS activation [66]. It is well known that the level of
leptin is increased in obesity and associated with elevated BP
[67]. Normally, leptin binds to its receptors in the central
nervous system (CNS), where it activates neural pathways
that decrease appetite and increase SNS activity and energy
expenditure. Increased leptin in obesity stimulates proopiomelanocortin (POMC) neurons in the hypothalamus and
brain stem, and the subsequent activation of the melanocortin
4 receptor (MC4R) leads to SNS activation. Chronic activation of the CNS POMC-MC4R pathway induced by increased
leptin is essential for SNS activation and hypertension in
obesity [66, 68]. In addition, leptin causes endothelial dysfunction and enhances the effects of angiotensin II on BP
through SNS activation, which contributes to vascular stiffness and hypertension in obesity [69].
Adiponectin, another main adipokine, is mainly synthesized in adipose tissue and produces the beneficial effects on
the vascular system. A recent clinical study demonstrated that
the lowest serum levels of adiponectin were found in subjects
who were both hypertensive and obese [70]. Some evidence
suggests that the detrimental effects of increased SNS outflow
in obesity lead to the downregulation of adiponectin levels
[71]. Adiponectin has insulin-sensitizing anti-inflammatory
and anti-atherogenic effects that protect against cardiovascular
disease. Briefly, adiponectin inhibits TNF- production and

495, Page 6 of 9

other inflammatory pathways in adipocytes and macrophages.

It reduces oxidative stress by decreasing ROS production in
endothelial cells and stimulates NO production in the vascular
endothelium. All these effects protect the vascular system
against endothelial dysfunction. Therefore, significant decreases in adiponectin levels in obesity contribute to the
pathogenesis of obesity-related hypertension [72].
Many studies have confirmed that human adipose tissue
synthesizes all the components of RAS: angiotensinogen,
renin, angiotensin-converting enzymes (ACEs) 1 and 2, and
Ang II receptors 1 and 2 [73]. Increased amount of these
components in adipose tissue might contribute to obesityinduced hypertension. Indeed, circulating RAS components
are elevated in human obesity, and weight loss reduces RAS
levels in plasma and in adipose tissue [74]. Moreover, increased Ang II in obesity may exacerbate the hypertensive
state via increased secretion of several proinflammatory cytokines (TNF- and IL-6) and decreased adiponectin secretion
and stimulation of leptin production in human adipocytes
[65]. All of these findings suggest that the adipose RAS has
a significant physiological role in the regulation of blood
pressure.
There is growing evidence that elevated SNS activity in
obesity contributes to the development and progression of
target organ damage irrespective of the presence of hypertension. Several studies documented that sympathetic nerve traffic was the major determinant of early structural and functional cardiovascular abnormalities in human obesity. The studies
showed that the association between adrenergic overdrive and
vascular, cardiac, and renal organ damage was not limited to
the hypertensive state but occurred in the obese normotensive
state as well [75, 76]. A recent study also showed that
disturbed circadian BP and heart rate rhythmicity, conditions
causing increased cardiovascular risk, in a group of obese
adolescent boys with primary hypertension did not normalize
after antihypertensive therapy despite BP lowering. These
findings underline the importance of visceral adipose tissue
for its role of SNS activation in the pathogenesis of hypertension and the establishment of treatment strategies. The therapy
should focus not only on BP lowering but also on reducing
visceral adipose tissue [77, 78].

Curr Hypertens Rep (2014) 16:495

overnutrition) accompanying the rapid socioeconomic progress over the past few decades.
Hypertension and obesity are major modifiable risk factors
for cardiovascular disease in adulthood. Therefore, it is of
considerable importance to assess BP and BMI of children
and adolescents properly and adopt appropriate preventive
strategies to obviate a future epidemic of adult cardiovascular
disease before the development of obesity.

Compliance with Ethics Guidelines

Conflict of Interest Chong Guk Lee declares no conflict of interest.
Human and Animal Rights and Informed Consent This article does
not contain any studies with human or animal subjects performed by any
of the authors.

References
Papers of particular interest, published recently, have been
highlighted as:
Of importance
Of major importance
1.

2.

3.

4.

5.

6.

7.

Conclusions
It should be clear that pediatric hypertension has emerged as
an important public health problem in Asian countries with
increasing obesity epidemic. The increasing prevalence of
high BP among children and adolescents is closely related to
increasing incidence of obesity. The causes of obesity epidemic in Asian countries are most frequently ascribed to a great
change of lifestyle (i.e., decrease in physical activity and

8.

9.

WHO. Global status report on non-communicable diseases 2010.

Geneva, World Health Organization, 2011. http://www.who.int/
nmh/publications/ncd_report_full_en.pdf. Accessed 10 Nov 2013
Alwan A, MacLean DR, Riley LM, d'Espaignet ET, Mathers CD,
Stevens GA, et al. Monitoring and surveillance of chronic noncommunicable diseases: progress and capacity in high-burden
countries. Lancet. 2010;376:18618.
WHO. Global health risks: mortality and burden of disease attributable to selected major risks. Geneva, World Health Organization,
2009. http://www.who.int/healthinfo/global_burden_disease/
GlobalHealthRisks_report_full.pdf. Accessed 10 Nov 2013.
WHO. Non-communicable diseases country profiles. Geneva,
World Health Organization, 2011. http://www.who.int/nmh/
publications/ncd_profiles_report.pdf. Accessed 10 Nov 2013.
Danaei G, Finucane MM, Lin JK, Singh GM, Paciorek CJ, Cowan
MJ, et al. National, regional, and global trends in systolic blood
pressure since 1980: systematic analysis of health examination
surveys and epidemiological studies with 786 country-years and
54 million participants. Lancet. 2011;377:56877.
Pereira M, Lunet N, Azevedo A, Barros H. Differences in prevalence, awareness, treatment and control of hypertension between
developing and developed countries. J Hypertens. 2009;27:96375.
Flynn J. The changing face of pediatric hypertension in the era of
the childhood obesity epidemic. Pediatr Nephrol. 2013;28:1059
66. This review presented updated data on the prevalence of hypertension in children and adolescents, the impact of the childhood
obesity epidemic on hypertension prevalence, and epidemiologic
shifts to primary hypertension in childhood.
Tran CL, Ehrmann BJ, Messer KL, Herreshoff E, Kroeker A,
Wickman L, et al. Recent trends in healthcare use among children
and adolescents with hypertension in the United States. Hypertens.
2012;60:296302.
Samuels J. The increasing burden of pediatric hypertension.
Hypertens. 2012;60:2767.

Curr Hypertens Rep (2014) 16:495

10. Cao ZQ, Zhu L, Zhang T, Wu L, Wang Y. Blood pressure and
obesity among adolescents: a school-based population study in
China. Am J Hypertens. 2012;25:57682. Informations regarding
the prevalence of hypertension and prehypertension as well as the
epidemical situation of the associated risk factor, obesity, in adolescents in China are available. Also, characteristics of the Chinese
blood pressure reference standards for children and adolescents are
described.
11. Bao W, Threefoot T, Srinivasan SR, Berenson GS. Essential hypertension predicted by tracking of elevated blood pressure from
childhood to adulthood: the Bogalusa Heart Study. Am J
Hypertens. 1995;8:65765.
12. Chen X, Wang Y. Tracking of blood pressure from childhood to
adulthood: a systematic review and meta-regression analysis.
Circulation. 2008;117:317180. A meta-analysis conducted on 50
cohort studies. Data from diverse populations revealed the strong
evidence for BP tracking from childhood into adulthood.
13. Seeman T, Pohl M, Palyzova D, John U. Microalbuminuria in
children with primary and white-coat hypertension. Pediatr
Nephrol. 2012;27:4617.
14. Kupferman JC, Lande MB, Adams HR, Pavlakis SG. Primary
hypertension and neurocognitive and executive functioning in
school-age children. Pediatr Nephrol. 2013;28:4018. doi:10.
1007/s00467-012-2215-8.
15. McNiece KL, Gupta-Malhotra M, Samuels J, Bell C, Garcia K,
Poffenbarger T, et al. Left ventricular hypertrophy in hypertensive
adolescents: analysis of risk by 2004 national high blood pressure
education program working group staging criteria. Hypertens.
2007;50:3925.
16. de Gusmao Correia ML, Volpato AM, Aguila MA, Mandarim-deLacerda CA. Developmental origins of health and disease: experimental and human evidence of fetal programming for metabolic
syndrome. J Hum Hypertens. 2012;26:40519. doi:10.1038/jhh.
2011.61.
17. National High Blood Pressure Education Program Working Group
on High Blood Pressure in Children and Adolescents. The fourth
report on the diagnosis, evaluation, and treatment of high blood
pressure in children and adolescents. Pediatr. 2004;114:55576.
18. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA,
Izzo Jr JL, et al. Seventh report of the Joint National Committee on
Prevention, Detection, Evaluation, and Treatment of High Blood
Pressure. Hypertens. 2003;42:120652.
19. Cole TJ. Secular trends in growth. Proc Nutr Soc. 2000;59:31724.
This paper aimed to consider the basic concept of secular trend in
child height, weight, birth weight, and growth tempo over the last
two centuries and to discuss its causation. The author insisted that
the secular change reflects the varying health and affluence of
populations over time, and it also highlights inequalities of health
and wealth within populations.
20. Berg GVD, Eijsden MV, Galindo-Garre F, Vrijkotte TGM, Gemke
RJBJ. Explaining socioeconomic inequalities in childhood blood
pressure and prehypertension. ABCD Study Hypertens. 2013;61:
3541.
21. Lee CG, Moon JS, Choi JM, Nam JM, Lee SY, Oh KW, et al.
Normative blood pressure references for Korean children and adolescents. Korean J Pediatr. 2008;51:3341.
22. Jie MI, Tian-you W, Ling-hui M, Guang-jin Z, Shao-mei H, Yan Z,
et al. Development of blood pressure reference standards for
Chinese children. Chin J Evid Based Pediatr. 2010;5:414.
23. Pickering TG. What will replace the mercury sphygmomanometer?
Blood Press Monit. 2003;8:235.
24. Park MK, Menard SW, Yuan C. Comparison of auscultatory and
oscillometric blood pressures. Arch Pediatr Adolesc Med.
2001;155:503.
25. O'Brien E, Waeber B, Parati G, Staessen J, Myers MG, on behalf of
the European Society of Hypertension Working Group on Blood

Page 7 of 9, 495

26.

27.
28.

29.

30.

31.
32.

33.

34.

35.

36.

37.

38.

39.

40.

41.

42.

Pressure Monitoring. Blood pressure measuring devices: recommendations of the European Society of Hypertension. BMJ.
2001;322:5316.
OBrien E, Atkins N, Stergiou G, Karpettas N, Parati G, Asmar R,
et al. European Society of Hypertension International Protocol
revision 2010 for the validation of blood pressure measuring devices in adults. Blood Press Monit. 2010;15:2338. Because of the
increasing ban on the use of mercury-containing sphygmomanometers, there is a need for an equivalent standard device that does not
contain mercury. This paper is giving an introduction of the recently
revised protocol of validation study by the European Society of
Hypertension.
van Montfrans GA. Oscillometric blood pressure measurement:
progress and problems. Blood Press Monit. 2001;6:28790.
Lee CG, Park HM, Shin HJ, Moon JS, Hong YM, Kim NS, et al.
Validation study of the Dinamap ProCare 200 upper arm blood
pressure monitor in children and adolescents. Korean J Pediatr.
2011;54:4639.
Lee CG. A comparison study between blood pressure measurement
devices to evaluate cut-off values of hypertension in Korean children and adolescents. The report of Korea Center for Disease
Control & Prevention, Oct. 2010
Van den Berg G, Van Eijsden M, Galindo-Garre F, Gemke R.
Explaining socioeconomic inequalities in childhood blood pressure
and prehypertension: the ABCD study. Hypertens. 2013;61:3541.
Falkner B. Hypertension in children and adolescents: epidemiology
and natural history. Pediatr Nephrol. 2010;25:121924.
Moore WE, Eichner JE, Cohn EM, Thompson DM, Kobza CE,
Abbott KE. Blood pressure screening of school children in a multiracial school district: the Healthy Kids Project. Am J Hypertens.
2009;22:3516.
Sorof JM, Lai D, Turner J, Poffenbarger T, Portman RJ.
Overweight, ethnicity, and the prevalence of hypertension in
school-aged children. Pediatr . 2004;113:47582.
Lo JC, Sinaiko A, Chandra M, Daley MF, Greenspan LC, Parker
ED, et al. Prehypertension and hypertension in community-based
pediatric practice. Pediatr. 2013;131:e41524.
Dong B, Ma J, Wang HJ, Wang ZQ. The association of overweight
and obesity with blood pressure among Chinese children and adolescents. Biomed Environ Sci. 2013;26:43744. doi:10.3967/08953988.2013.06.004.
Moon JS, Lee SY, Nam JM, Choi JM, Choe BK, Seo JW, et al. 2007
Korean national growth charts: review of developmental process
and an outlook. Korean J Pediatr. 2008;51:125.
Park SW, Park JH, Kim JH. The result of nationwide health examination for school students in primary, middle school and high
school. Korea Educational Development Institute. 2012. https://
www.kedi.re.kr/khome/main/research/selectPubForm.do.
Accessed 14 Nov 2013
Oh KW, Jang MJ, Lee NY, Moon JS, Lee CG, Yoo MH, et al.
Prevalence and trends in obesity among Korean children and adolescents in 1997 and 2005. Korean J Pediatr. 2008;51:9505.
Munter P, He J, Cutler JA, Wildman RP, Whelton PK. Trends in
blood pressure among children and adolescents. JAMA. 2004;291:
210713.
Din-Dzietham R, Liu Y, Bielo M-V, Shamsa F. High blood pressure
trends in children and adolescents in national surveys, 1963 to
2002. Circulation. 2007;116:148896.
Rosner B, Cook NR, Daniels S, Falkner B. Childhood blood
pressure trends and risk factors for high blood pressure: the
NHANES Experience 19882008. Hyperten. 2013;62:24754.
Watson SE, Hannon TS, Eckert GJ, Pratt JH, Rosenman M, Tu W.
Adult hypertension risk is more than quadrupled in obese children.
Abstract No. 36 of High Blood Pressure Research 2013 Scientific
Sessions, American Heart Association. 2013. http://my.
americanheart.org/idc/groups/ahamah- public/@wcm/@sop/@

495, Page 8 of 9
scon/documents/downloadable/ucm_455971.pdf. Accessed 16
Nov 2013
43. Kuwahara E, Asakura K, Nishiwaki Y, Komatsu H, Nakazawa A,
Ushiku H, Maejima F, Nishigaki Y, Hasegawa T, Okamura T,
Takebayashi T. Steeper increases in body mass index during childhood correlate with blood pressure elevation in adolescence: a longterm follow-up study in a Japanese community. Hypertens Res.
2013. doi: 10.1038/hr.2013.109. http://www.ncbi.nlm.nih.gov/
pubmed/24026043. Accessed 16 Nov 2013
44. Dong B, Wang HJ, Wang Z, Liu JS, Ma J. Trends in blood pressure
and body mass index among Chinese children and adolescents from
2005 to 2010. Am J Hypertens. 2013;26:9971004. doi:10.1093/
ajh/hpt050. This paper is showing the association between obesity
and high blood pressure in Chinese children and adolescents.
45. Lu X, Shi P, Luo CY, Zhou YF, Yu HT, Guo CY, et al. Prevalence of
hypertension in overweight and obese children from a large schoolbased population in Shanghai. China BMC Publ Health. 2013;13:
24. doi:10.1186/1471-2458-13-24. http://www.ncbi.nlm.nih.gov/
pubmed/?term=BMC+Public+Health+2013%3B13%3A24.
Accessed 18 Dec 2013.
46. Freedman DS, Goodman A, Contreras OA, Das Mahapatra P,
Srinivasan SR, Berenson GS. Secular trends in BMI and blood
pressure among children and adolescents: the Bogalusa Heart
Study. Pediatr. 2012;130:e15966. Contrary to the results of other
studies, there was no increase in systolic or diastolic blood pressure
levels despite increases in obesity in Bogalusa cohort study.
Authors insisted that it should not be assumed that trends in high
blood pressure have paralleled those for obesity.
47. Flynn JT. Pediatric hypertension update. Curr Opin Nephrol
Hypertens. 2010;19:2927.
4 8 . H a n s on M , G l uc k m a n P. D e v e l o p m e n t a l or i g i n s o f
noncommunicable disease: population and public health implications. Am J Clin Nutr. 2011;94(6 Suppl):1754S8S.
49. Lakshmy R. Metabolic syndrome: role of maternal undernutrition
and fetal programming. Rev Endocr Metab Disord. 2013;14:229
40. The concept of developmental origins of health and disease is
provided through the review of recent experimental and epidemiological studies providing evidence for the fetal programming associated with the development of metabolic syndrome and related
diseases. Roles of maternal macro- and micronutrients on fetal
programming during pregnancy are explained.
50. Gluckman PD, Hanson MA, Cooper C, Thornburg K. Effect of in
utero and early-life conditions on adult health and disease. N Engl J
Med. 2008;359:6173. In this review, they explained that the developmental plasticity requires stable modulation of gene expression, which is mediated by epigenetic processes such as DNA
methylation and histone modification. Thus, both the genome and
the epigenome interactively influence the mature phenotype and
determine sensitivity to later environmental factors and the subsequent risk of disease.
51. Barker DJ, Osmond C. Low birth weight and hypertension. Br Med
J. 1988;297:1345.
52. Barker DJP. Maternal and fetal nutrition and disease in later life.
Nutrition. 1997;13:80713.
53. Gluckman P, Hanson M, Beedle AS. Non-genomic
transgenerational inheritance of disease risk. Bioessays. 2007;29:
14554.
54. Patti ME. Intergenerational programming of metabolic diseases:
evidence from human populations and experimental animal models.
Cell Mol Life Sci. 2013;70:1597608.
55. Gluckman PD, Hanson MA, Beedle AS, Spencer HG. Predictive
adaptive responses in perspective. Trends Endocrinol Metab.
2008;19:10910.
56. Vaccari B, Mesquita FF, Gontijo J AR, Boer PA. Fetal kidney
programming by severe food restriction: effects on structure, hormonal receptor expression and urinary sodium excretion in rats. J

Curr Hypertens Rep (2014) 16:495

RAAS 2013. doi: 10.1177/1470320313481081. http://jra.sagepub.
com/content/early/2013/03/12/1470320313481081. Accessed 25
Nov 2013.
57. Luyckx VA, Bertram JF, Brenner BM, Fall C, Hoy WE, Ozanne SE,
et al. Effect of fetal and child health on kidney development and
long-term risk of hypertension and kidney disease. Lancet.
2013;382:27383. They described how low birth weight and prematurity affect kidney development and risk of disease, hypertension, and kidney disease.
58. UNICEF and WHO. Low birthweight: country, regional and global
estimates. UNICEF; 2004. p. 27.
59. Korean Statistical Information Service (KOSIS). Statistical
database/vital statistics. http://kosis.kr/wnsearch/totalSearch.jsp
60. de Jong F, Monuteaux MC, van Elburg RM, Gillman MW, Belfort
MB. Systematic review and meta-analysis of preterm birth and later
systolic blood pressure. Hypertens. 2012;59:22634.
61. Mu M, Wang SF, Sheng J, Zhao Y, Li HZ, Hu CL, et al. Birth
weight and subsequent blood pressure: a meta-analysis. Arch
Cardiovasc Dis. 2012;105:99113.
62. Gluckman PD, Hanson MA, Buklijas P. A conceptual framework
for the developmental origins of health and disease. J DOHaD.
2010;1:618. doi:10.1017/S2040174409990171.
63. Demicheva E, Crispi F. Long-term follow-up of intrauterine growth
restriction: cardiovascular disorders. Fetal Diagn Ther. 2013;36:
14353. doi:10.1159/000353633.
64. Bucher BS, Ferrarini A, Weber N, Bullo M, Bianchetti MG,
Simonetti GD. Primary hypertension in childhood. Curr
Hypertens Rep. 2013;15:44452.
65. Vlasova M, Purhonen AK AK, Jarvelin MR, Rodilla E, Pascual J,
Herzig KH. Role of adipokines in obesity-associated hypertension.
Acta Physiol. 2010;200:10727. It is well known that increased
amounts of most of the adipokines and the decreased adiponectin
levels in obesity affect the regulation of vascular tone. This article is
showing major effects of different adipokines on structural and
functional changes in the cardiovascular system.
66. Hall JE, da Silva AA, do Carmo JM, Dubinion J, Hamza S,
Munusamy Smith SG, et al. Obesity-induced hypertension: role
of sympathetic nervous system, leptin, and melanocortins. J Biol
Chem. 2010;285:172716. Role of CNS melanocortins and the
POMC-MC3/4R pathway in mediating obesity-induced SNS activation and blood pressure effects of leptin is reviewed.
67. Grontved A, Steene-Johannessen J, Kynde I, Franks PW, Helge JW,
Froberg K, et al. Association between plasma leptin and blood
pressure in two population-based samples of children and adolescents. J Hypertens. 2011;29:1093100.
68. Harlan SM, Rahmouni K. Neuroanatomical determinants of the
sympathetic nerve responses evoked by leptin. Clin Auton Res.
2013;23:17.
69. Wang J, Wang H, Luo W, Guo C, Wang J, Chen YE, et al. Leptininduced endothelial dysfunction is mediated by sympathetic nervous system activity. J Am Heart Assoc. 2013;2:e000299. doi:10.
1161/JAHA.113.000299.
70. Brambilla P, Antolini L, Street ME, Giussani M, Galbiati S,
Valsecchi MG, et al. Adiponectin and hypertension in normal-weight and obese children. Am J Hypertens. 2013;26:
25764.
71. Delporte ML, Funahashi T, Takahashi M, Matsuzawa Y, Brichard
SM. Pre- and post-translational negative effect of beta-adrenoceptor
agonists on adiponectin secretion: in vitro and in vivo studies.
Biochem J. 2002;367:67785.
72. Zhu W, Cheng KK, Vanhoutte PM, Lam KS, Xu A. Vascular effects
of adiponectin: molecular mechanisms and potential therapeutic
intervention. Clin Sci. 2008;114:36174.
73. Achard V, Boullu-Ciocca S, Desbriere R, Nguyen G, Grino M.
Renin receptor expression in human adipose tissue. Am J Physiol
Regul Integr Comp Physiol. 2007;292:R27482.

Curr Hypertens Rep (2014) 16:495

74.

Engeli S, Bohnke J, Gorzelniak K, Janke J, Schling P, Bader M,

et al. Weight loss and the renin-angiotensin-aldosterone system.
Hypertens. 2005;45:35662.
75. Grassi G, Seravalle G, DllOro R. Sympathetic activation in obesity: a noninnocent bystander. Hypertens. 2010;56:33840.
76. Lambert E, Sari CI, Dawood T, Nguyen J, McGrane M, Eikelis N,
et al. Sympathetic nervous system activity is associated with
obesity-induced subclinical organ damage in young adults.
Hypertens. 2010;56:3518. They evaluated the early signs of organ
damage associated with hypertension in obese young adults to
document their possible relationship to sympathetic nervous activity. They found that excess weight in young individuals was associated with subclinical alterations in renal and endothelial function
as well as in the structure of the heart, even in the absence of

Page 9 of 9, 495
hypertension. Sympathetic activity seemed to be closely associated
with cardiovascular and renal alterations observed in subjects with
obesity.
77. Niemirska A, Litwin M, Feber J, Jurkiewicz E. Blood pressure
rhythmicity and visceral fat in children with hypertension.
Hypertens. 2013;62:7828. Their findings support the central role
of the sympathetic nervous system in the pathophysiology of childhood hypertension and underscore the importance of visceral adiposity as not only an influence on sympathetic nervous system
activity but also as a potential target for prevention of adult cardiovascular disease.
78. Grassi G, Quarti-Trevano F, DllOro R, Mancia G. Essential hypertension and the sympathetic nervous system. Neurol Sci. 2008;29:
S336.

Reproduced with permission of the copyright owner. Further reproduction prohibited without
permission.