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Indian J Pediatr (August 2012) 79(8):10561061

DOI 10.1007/s12098-012-0777-x

SYMPOSIUM ON PEDIATRIC NEPHROLOGY

Hypertension and Obesity: Epidemiology, Mechanisms


and Clinical Approach
Lauren J. Becton & Ibrahim F. Shatat & Joseph T. Flynn

Received: 2 April 2012 / Accepted: 3 May 2012 / Published online: 5 June 2012
# Dr. K C Chaudhuri Foundation 2012

Abstract Obesity-related hypertension in pediatric patients Introduction


is becoming more prevalent around the world as a conse-
quence of the childhood obesity epidemic. Hypertension The importance of abnormal blood pressure among pediatric
and the metabolic abnormalities associated with obesity will patients is becoming clearer, with numerous recent studies
significantly increase the health risks for these children as adding to our understanding of its prevalence and possible
they grow into adulthood. The pathophysiology of obesity- consequences [1]. In a study of data from national health
related hypertension is complex, and multiple potential mech- surveys examining high blood pressure trends in children
anisms likely contribute to the development of higher blood and adolescents in the United States (US), the authors found
pressure in obese children. These include hyperinsulinemia, the prevalence of pre-hypertension and hypertension among
activation of the renin-angiotensin-aldosterone system, stim- children and adolescents to be increasing among all ethnic
ulation of the sympathetic nervous system, abnormalities in groups in parallel with the increase in obesity, especially
adipokines such as leptin, direct effects of perinephric fat on among African American and Mexican American youth.
the renal parenchyma, and cytokines acting at the vascular They found a prevalence of hypertension of 3.7 % overall,
endothelial level. As in any child with elevated blood pressure, but up to 9 % in some groups [2]. Other studies have found
diagnostic evaluation should focus on confirmation of hyper- prevalence rates of hypertension as high as 15 %, especially
tension, determine if an underlying cause can be identified and among American racial minorities and in overweight or
whether hypertensive target organ damage is present. Therapy obese children [1, 3]. The variation in exact prevalence rates
should begin with lifestyle modifications, but will often need to reported in these studies is due to differences in study design
include one or more antihypertensive medications. as well as how blood pressure was measured and whether
repeated or average measurements were reported. Further
Keywords Blood pressure . Hypertension . Obesity discussion and recommendations regarding these issues can
be found below.
The epidemiologic data not only demonstrate an increase in
overall blood pressure values and prevalence of hypertension
L. J. Becton
and pre-hypertension, but also show an alarming rate of
Department of Pediatrics, MUSC Childrens Hospital,
Charleston, SC, USA progression and tracking of elevated blood pressure into
adulthood [4]. Falkner and colleagues reported the rate of
I. F. Shatat (*) progression from prehypertension to hypertension at 7 % per
Division of Pediatric Nephrology and Hypertension,
year. In that study, initial body mass index (BMI) and changes
MUSC Childrens Hospital,
96 Jonathan Lucas Street, CSB-428, in BMI had significant effect on blood pressure changes over
Charleston, SC 29425, USA time [5]. In a more recent study, Redwine and colleagues also
e-mail: shatat@musc.edu reported that elevated blood pressure increases the risk for the
development of hypertension during adolescence. In their
J. T. Flynn
Division of Nephrology, Seattle Childrens Hospital, study, students with pre-hypertension by the 2004 Task Force
Seattle, WA, USA definition developed hypertension at a rate of 1.1 %/year
Indian J Pediatr (August 2012) 79(8):10561061 1057

(hazard ratio 2.98; 0.7711.56) [6]. Among those with hyper- al. also found a correlation between higher BMI and higher
tension, it will persist in many children after 2 y of follow-up systolic blood pressure [17]. In the study by Muntner et al.
[7]. This was also the conclusion of the systematic review and [18], blood pressure levels correlated with BMI and waist
meta-regression analysis by Chen and Wang; they showed that circumference. Among obese adolescents in the US, the
the evidence of blood pressure tracking from childhood to prevalence of hypertension has been estimated to be at least
adulthood is strong, that elevated childhood blood pressure 10 % and strong associations have been found in younger
is associated with elevated blood pressure later in life, and that children as well [3, 18]. Data from European and Indian
early intervention is important to reduce future cardiovascular cohorts show higher rates of hypertension, with up to 35 %
risk [8]. The take-home message from these data is that of overweight or obese children having hypertension in each
blood pressure elevation in children or adolescents will population [14].
progress over time, so youth with blood pressure even in the Clearly, obesity-associated hypertension has become an
pre-hypertensive range merit intervention and long-term important pediatric health problem and predicts an expected
follow-up. increase in adult cardiovascular disease in the future. Hy-
pertension in adolescents has been shown to significantly
increase the risk of adult hypertension [19]. Based on cur-
Relationship Between Obesity and Hypertension rent data, some extrapolated estimates show an increase in
coronary artery disease among adults to increase by 515 %
The increasing burden of pediatric hypertension is undoubt- over the next 25 y. In the US, for example, this corresponds
edly related to the worldwide childhood obesity epidemic, to >100,000 extra cases that will be attributable solely to
which shows no signs of slowing. Defining obesity as a childhood obesity [7]. Data from Egypt not only demon-
BMI 95th percentile for age and gender, the prevalence of strate the relationship between obesity and hypertension, but
obesity among US children and adolescents is 17 % [7]. A also development of the metabolic syndrome, including
recent meta-analysis in India of studies performed over the last hypertriglyceridemia and insulin resistance [20]. In summa-
decade found the prevalence rate of overweight (BMI 85th ry, the significant rise in the prevalence of obesity over this
and <95th percentile) to be over 12 % and that of obesity to be last decade has been accompanied by a corresponding in-
over 3 %. Some suggest that this may even be an underesti- crease in the prevalence of hypertension.
mation since charts used to define percentiles are based on
normative data from the US and United Kingdom [9]. Among
Indian children from higher socioeconomic classes, the rates Pathophysiology
are even higher, with overweight rates of 1619 % and obesity
rates of 56 % [10]. There are several pathophysiological mechanisms that proba-
Higher socioeconomic status is associated with obesity in bly contribute to the development of hypertension in obesity
several developing African countries as well, in contrast to (Fig. 1). Insulin resistance and hyperinsulinemia are indepen-
developed nations, where higher socioeconomic status dent activators of the renal sympathetic nervous system. This
appears to be protective [11]. A quickly increasing rate of causes vasoconstriction and reduced renal blood flow, which is
overweight and obesity among children has been found in a trigger for renin release. The end result of this activation of
many other countries, including Thailand, China, Brazil and the renin-angiotensin-aldosterone system is sodium and water
South Africa [12, 13]. Worldwide, the overall prevalence of retention, which raises blood pressure. Also contributing to the
overweight and obesity in children increased by 2.5 % be- reduced renal blood flow is direct compression of the paren-
tween 1990 and 2010. That year, the estimated prevalence chyma by perinephric fat, which encourages sodium reabsorp-
among the worlds children was 6.7 %. At the current rate of tion and higher blood pressure. This phenomenon occurs even
increase, it is expected to exceed 9 % by 2020 [14]. Other in the absence of signs of sclerosis or chronic kidney disease.
estimates already exceed 10 % [11]. In addition to the alarm- Higher levels of leptin, a hormone produced by adipose
ing rate of rise in overweight and obesity, the rates of co- tissue, are associated with elevated blood pressure, a rela-
morbities such as type 2 diabetes mellitus (with India demon- tionship that is mediated by BMI and effects on sympathetic
strating one of the highest rates in the world) and the metabolic nervous system [21]. Conversely, obese individuals produce
syndrome are also increasing [15]. less adiponectin, an anti-atherogenic, cardioprotective hor-
While the presence of obesity or hypertension does not mone made in adipose tissue, which inversely correlates
necessarily predict the other, there is a clear correlation with blood pressure in obese children and adolescents
between the two. For example, Robinson et al. found a [22]. The proinflammatory cytokines and oxidative stress
positive correlation between increased BMI and primary produced in obesity probably contribute to vascular endo-
hypertension as well as presentation of hypertension at a thelial dysfunction, impairing the local vasodilatory re-
younger age among those with increased BMI [16]. Flynn et sponse, thereby increasing peripheral resistance.
1058 Indian J Pediatr (August 2012) 79(8):10561061

Fig. 1 Mechanisms of obesity-related hypertension

Obese children with sleep-disordered breathing (apnea, Patient Evaluation


hypopnea) are at even higher risk of developing hyperten-
sion, especially at night. Furthermore, sympathetic activa- Evaluation of a patient with hypertension should first confirm
tion via multiple other mechanisms and morbidities may the diagnosis of hypertension, then seek an underlying cause
contribute to a higher blood pressure in obese children; and finally screen for any end-organ effects [26]. A complete
these include but are not limited to the proinflammatory history is obtained, including diet and exercise habits and
state created by cytokines such as increased IL-6 produc- family history of hypertension, cardiovascular disease or her-
tion, which in turn results in an acute phase response. In itable diseases. Family history should be updated periodically
addition, the sympathetic nervous system plays a role in as it may change over time. Past medical history should be
energy balance and metabolic syndrome as fasting sup- taken, beginning with perinatal history, including birth weight
presses, and meal ingestion induces sympathetic activity and umbilical artery catheterization, and a history of symp-
[23]. Weight loss reduces sympathetic overactivity in obe- toms of other medical conditions associated with increased
sity, which may partly explain the lower blood pressure in risk of hypertension. This includes a history of renal malfor-
response to dieting [24]. Central fat distribution is associated mations, urinary tract infections, acute kidney injury, cardiac,
with disturbances in the hypothalamic-pituitary-adrenal axis, endocrine or neurologic diseases or a history of solid organ or
suggesting that a disturbed axis may be implicated in the bone marrow transplant.
development of the metabolic syndrome [25]. Symptoms of the disorders listed above may suggest an
Finally, there is often a history of poor nutrition in over- underlying cause of hypertension that has not yet been diag-
weight and obese patients. Calorie dense foods are often nosed. These include virilization, polydipsia and polyuria, he-
also high in sodium and obese patients with hypertension maturia, weight loss, palpitations or temperature intolerance. A
are more likely to have salt-sensitive blood pressure than careful sleep history as well as other parts of the social history
their normal weight counterparts. Related to this may be the may also suggest a secondary cause, including life stressors,
impact of stress on blood pressure and the phenomenon of smoking, alcohol and the intake of any medications, including
stress-eating, which may compound an individuals risk of those that are prescribed, over-the-counter or illicit substances.
both obesity and hypertension [14]. Finally, any clinical symptoms of end-organ damage are
Indian J Pediatr (August 2012) 79(8):10561061 1059

important to identify as this may change the subsequent eval- for hypertensive target organ damage. There is no role
uation, including headaches, dizziness or vertigo, visual for routine chest x-rays or electrocardiograms in pediatric
changes, nausea or vomiting, epistaxis, nerve palsies and patients with hypertension unless there is a suspicion for
dyspnea. underlying cardiac disease. Because of the correlation be-
The physical examination should include vital signs, tween obesity, hypertension and the metabolic syndrome,
height, weight and BMI, all reported as percentiles using patients with obesity and abnormal blood pressure should be
accepted population curves. Skin manifestations of underlying screened for additional components of the metabolic syn-
diseases, such as neurofibromatosis and insulin resistance drome as recommended.
should be looked for. Cardiovascular exam includes pulses Depending on the history and the results of screening
and blood pressure measurement in all extremities and the studies, additional evaluation may be required, including
auscultation for bruits and murmurs. Palpation of the abdomen drug screen, polysomnography, plasma renin activity and
may reveal hepatosplenomegaly or other masses related to aldosterone levels, urine and plasma catecholamines and
renal or oncologic disease. Neurologic examination should steroid measurements, ultrasonography with Doppler, radio-
be completed, including fundoscopy, cranial nerve testing nuclide (DMSA) scan, CT or MRI, angiography and genetic
and evaluation for any focal defect suggesting stroke. studies to evaluate for monogenic sodium transport abnor-
Blood pressure should be measured with an appropriately malities causing hypertension (e.g., Liddle syndrome) [31].
sized cuff and repeated on several occasions to confirm the The interested reader should consult detailed references for
diagnosis of hypertension. The cuff size is considered ap- guidance regarding further evaluation [26].
propriate if the width of the inflatable bladder covers at least
40 % of the arm circumference at about midway between the
olecranon and acromion. The length of the bladder should Treatment
cover 80100 % of the arm circumference. Similarly, if the
original measurement was taken using an oscillometric device, Therapy for obesity related hypertension should begin
it should be confirmed by auscultation [2729]. Normative by addressing the childs weight and implementing non-
data tables published by the US National High Blood Pressure pharmacologic lifestyle modifications. Dietary recommenda-
Education Program [27] have been endorsed for wide use tions include avoiding excess sugar, soft drinks, saturated fat
by the European Hypertension Association Guidelines [28]. and salt, while increasing the intake of dietary fiber in the form
Recent research has highlighted the importance of using of fruits, vegetables and whole grains. Implementation of the
ambulatory blood pressure monitoring (ABPM) in the diag- DASH-style diet has been shown to be associated with lower
nosis and management of childhood hypertension [29]. blood pressure [32]. Increased physical activity and limitation
ABPM uses a portable device worn by the patient that of time spent in sedentary activities is also an important part of
measures and records blood pressure during the patients the treatment of obesity. The clinician should recognize that
daily activities and therefore has the ability to diagnose lifestyle changes are difficult and should involve the whole
masked hypertension, including nocturnal hypertension. family to be successful [7, 27]. Ongoing support in the form of
Obese children and adolescents have been shown to have nutritional counseling as well as frequent follow-up with the
more blood pressure variability, and those with sleep- primary care provider may be very useful to continue to
disordered breathing often have reduced normal nocturnal encourage efforts to lose weight.
dipping. Both masked and white-coat hypertension are shown Pharmacological antihypertensive treatment should be
to contribute to development of hypertensive target organ started when these efforts fail, though the lifestyle changes
damage. In adult studies, ABPM has been shown to better should continue even after beginning a medication. Children
predict cardiovascular outcomes than clinic blood pressures, who are able to lose weight may later be able to stop their
since it more accurately records blood pressure during normal medication and control their hypertension solely with life-
daily activities. The accurate use of ABPM requires some style measures. Other indications for starting a medication
expertise in the reading and interpretation of data. This may are symptomatic hypertension, secondary causes as well as
not be a practical option in some areas without easily acces- specific underlying diseases such as diabetes mellitus that
sible specialists [2730]. are independent cardiovascular risk factors, or evidence of
Recommendations for routine laboratory investigation vary target organ damage, such as elevated left ventricular mass
only slightly among authors and most recommend the follow- by echocardiogram [27].
ing for all hypertensive children and adolescents: blood Pediatric studies on specific antihypertensive drugs and
counts, serum electrolytes, urea, creatinine, fasting glucose drug classes have increased and there is a growing base of
and lipid panel, and urinalysis with culture. All patients with experience with many agents. In general, therapy should be
confirmed hypertension should have a renal ultrasound to rule started with a single drug at the lowest recommended dose
out underlying renal disease and echocardiography to assess and increased until the blood pressure goal is achieved or
1060 Indian J Pediatr (August 2012) 79(8):10561061

the highest dose is reached. The choice of antihypertensive 7. Expert panel on integrated guidelines for cardiovascular health and
risk reduction in children and adolescents: summary report. Na-
medication will depend on any underlying co-morbid con- tional Heart, Lung, and Blood Institute, National Institutes of
ditions, e.g., angiotensin-converting enzyme inhibitors are Health, Bethesda, Maryland. Pediatrics. 2011; 128:S144.
the initial choice for a child with diabetes and hypertension. 8. Chen X, Wang Y. Tracking of blood pressure from childhood to
Detailed discussion of the indications for antihypertensive adulthood: a systematic review and meta-regression analysis. Cir-
culation. 2008;117:317180.
medications in children and adolescents, as well as guide- 9. Midha T, Nath B, Kumari R, Rao YK, Pandey U. Childhood
lines for how to prescribe antihypertensive medications in obesity in India: a meta-analysis. Indian J Pediatr. 2011; Oct 15
the young can be found elsewhere [33]. [Epub ahead of print].
Close follow-up after making a diagnosis of hypertension is 10. Marwaha RK, Tandon N, Singh Y, Aggarwal R, Grewal K, Mani K.
A study of growth parameters and prevalence of overweight and
necessary. Home and repeat ambulatory monitoring of blood obesity in school children from Delhi. Indian Pediatr. 2006;43:943
pressure is recommended to ensure adequate control. Home 52.
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12. Wang Y, Lobstein T. Worldwide trends in childhood overweight
up visits every 36 mo are recommended for overweight and and obesity. Int J Pediatr Obes. 2006;1:1125.
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Childhood obesity in Asian Indians: a burgeoning cause of insulin
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morbidities contribute to high blood pressure. The workup of Nutr. 2008;17:1725.
16. Robinson RF, Batisky DL, Hayes JR, Nahata MC, Mahan JD.
the obese child with high blood pressure should include screen- Body mass index in primary and secondary pediatric hypertension.
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Conflict of Interest None.
20. Sliem HA, Ahmed S, Nemr N, El-Sherif I. Metabolic syndrome in
the middle east. Indian J Endocr Metab. 2012;16:6771.
21. Grontved A, Steene-Johannessen J, Kynde I, et al. Association be-
Role of Funding Source None. tween plasma leptin and blood pressure in two population-based
samples of children and adolescents. J Hypertens. 2011;29:1093
100.
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