Evaluation
of hypertension in children and adolescents
N
S Mani MD Professor, Pediatrics, 9645151883
INTRODUCTION — It has become clear that hypertension
(HTN) begins in childhood and adolescence and that it contributes to the early
development of cardiovascular disease (CVD). The supporting data include
clinical studies that demonstrate cardiovascular structural and functional
changes in children with HTN and autopsy studies that have shown an association
of BP with atherosclerotic changes in the aorta and heart in children and young
adults
In hypertensive
adults, multiple randomized trials have shown that reduction of BP by
antihypertensive therapy reduces cardiovascular morbidity and mortality. The
magnitude of the benefit increases with the severity of the HTN
Based upon these
observations, identifying children with HTN and successfully treating their HTN
should have an important impact on long-term outcomes of CVD. One of the most
important components of the successful management of childhood HTN is
determining whether or not there is an underlying cause that is amenable to
treatment.
DEFINITION — In children, the
following definitions based upon the 2004 National High Blood Pressure
Education Program Working Group (NHBPEP) are used to classify BP measurements
in the United States. BP percentiles are based upon gender, age, and height.
The systolic and diastolic BP are of equal importance; if there is a disparity
between the two, the higher value determines the BP category. The age- and
height-specific blood pressure percentiles may be determined using calculators
for boys or for girls.
Normal BP – Both
systolic and diastolic BP <90th percentile.
· Prehypertension – Systolic and/or diastolic BP ≥90th percentile
but <95th percentile or if BP exceeds
120/80 mmHg (even if <90th percentile for age, gender, and
height).
· Hypertension – HTN is defined as either systolic
and/or diastolic BP ≥95th percentile measured upon three or
more separate occasions. The degree of HTN is further delineated by the two
following stages.
· Stage 1 HTN
– Systolic and/or diastolic BP between the 95th percentile and
5 mmHg above the 99th percentile.
· Stage 2 HTN
– Systolic and/or diastolic BP ≥99th percentile plus 5 mmHg.
OVERVIEW — The goals of the initial evaluation of
the hypertensive child or adolescent are to:
· Identify secondary HTN (ie, an underlying cause of
hypertension), which may be cured, avoiding the need for prolonged drug therapy
(table 3).
· Identify other comorbid risk factors (eg, obesity
and dyslipidemia) for cardiovascular disease (CVD) or diseases associated with
an increased risk for CVD (eg, diabetes mellitus.
· Identify children who should be treated with
antihypertensive drug therapy.
· Most hypertensive children, particularly those who
are likely to have secondary HTN, should be referred to a pediatric
nephrologist or other physician with experience in childhood HTN.
Primary
versus secondary hypertension — An
important initial step in the assessment of hypertensive children is
distinguishing between primary (without an identifiable cause) and secondary
HTN. Correction of the underlying disorder may cure the HTN in children with
secondary causes.
The following factors
can help differentiate secondary from primary HTN:
· Prepubertal children generally have some form of
secondary HTN while adolescents and postpubertal children usually have primary
HTN.
· Severe HTN (defined as stage 2 HTN) is usually
associated with secondary HTN, while primary HTN is associated with mild or
stage 1 HTN.
· Diastolic and/or nocturnal HTN detected by
ambulatory BP monitoring is more likely to be associated with secondary HTN than
primary HTN [3-5].
· Primary HTN is associated with overweight and/or a
positive family history of HTN.
· Symptoms or signs suggestive of an underlying
disorder indicate secondary HTN. As an example, symptoms of sympathetic
overactivity (catecholamine excess), such as tachycardia and flushing, raise
the possibility of pheochromocytoma, while edema, elevations in serum
creatinine, and/or an abnormal urinalysis are consistent with underlying renal
disease.
Comorbid
risk factors and diseases — HTN is
one of several risk factors that increase the risk of premature atherosclerosis
in childhood and of cardiovascular disease (CVD) in adults. These risk factors
(eg, HTN, overweight/obesity, dyslipidemia, and a family history of premature
CVD) do not generally occur in isolation but are usually found concurrently,
which further increases the likelihood of premature atherosclerosis and CVD. In
addition, several childhood diseases such as type 1 and type 2 diabetes
mellitus, and chronic kidney disease are associated with accelerated
atherosclerosis and CVD.
Current
recommendations by the National High Blood Pressure Education Program Working
Group (NHBPEP) are to target BP goals below the 90th percentile
for age, height, and gender in children and adolescents with one or more of the
following:
· Presence of other CVD risk factors (ie,
overweight/obesity, family history of premature CVD, or dyslipidemia).
· Evidence of target-organ damage (eg, left
ventricular hypertrophy, proteinuria, renal scarring, or retinopathy).
· Diseases with high risk of early atherosclerosis
(eg, type 1 and 2 diabetes mellitus, chronic kidney disease, and Kawasaki
disease).
The presence of
another CVD risk factor or disease associated with a high-risk of CVD may
impact on the timing and choice of intervention. As a result, the evaluation of
childhood HTN needs to systematically identify the presence of these factors
and diseases.
INITIAL
EVALUATION — The initial evaluation of
the child with HTN includes history, physical examination, and laboratory tests
and procedures. It is, as discussed above, primarily focused upon the
following:
· Differentiate primary from secondary HTN by looking
for signs and symptoms that are associated with specific underlying etiologies
for HTN
· Identify comorbid CVD risk factors or diseases
associated with a risk of CVD.
· Identify patients with stage 2 HTN or with
evidence of end-organ injury so that pharmacologic therapy can be initiated.
The age- and height-specific blood pressure percentiles may be determined using
calculators for boys .
History
and physical examination — Symptoms
consistent with hypertensive emergencies include headache, seizures, changes in
mental status, focal neurologic complaints, visual disturbances, and
cardiovascular complaints indicative of heart failure (such as chest pain,
palpitations, cough, or shortness of breath). These children require emergent
evaluation and treatment.
The blood pressure
should be accurately measured and the severity of HTN should be determined.
Pharmacologic therapy should be initiated without delay in children with stage
2 HTN or those who may have a hypertensive emergency.
Secondary
versus primary hypertension — Secondary
hypertension should be suspected in children with one or more of the following
findings:
· Prepubertal, particularly younger than 10 years of
age.
· A thin child with a negative family history for
HTN.
· An acute rise in BP above a previously stable
baseline.
· Severe HTN defined as stage 2 HTN (BP >5 mmHg
above the 99th percentile) The
age- and height-specific blood pressure percentiles may be determined using
calculators for boys or for girls
· Stage 1 HTN (BP ≥95th percentile
but less than stage 2) with finding(s) on history or physical examination that
suggests systemic disease or a specific secondary etiology of HTN
· Specific ambulatory blood pressure patterns, such
as sustained diastolic hypertension, nocturnal hypertension, and/or blunted
nocturnal dipping.
· Past history of urinary tract infection, especially
pyelonephritis, or underlying congenital kidney or urologic anomalies raises
the possibility of renal scarring.
· Symptoms suggestive of catecholamine excess include
headache, sweating, and tachycardia in addition to HTN. Pheochromocytoma,
neuroblastoma, or use of sympathomimetic drugs including phenylpropanolamine
(over-the-counter decongestant), cocaine, amphetamines, phencyclidine,
epinephrine, phenylephrine,
and terbutaline, and the combination of a monoamine
oxidase (MAO) inhibitor plus ingestion of tyramine-containing foods are
possible etiologies.
· Ambiguous genitalia may be suggestive of congenital
adrenal hyperplasia with excess endogenous secretion of androgens and
mineralocorticoids. Children with mineralocorticoid excess may develop
hypokalemia.
· Edema and hematuria may be indicative of renal
parenchymal disease. Initial laboratory testing demonstrating an abnormal
urinalysis or elevated serum creatinine add further support for an intrinsic
renal disease process.
· Patients with glomerulonephritis due to systemic
disorders such as Henoch-Schönlein purpura or systemic lupus erythematosus have
other clinical findings including arthritis, rash, and abdominal pain (the
latter especially in Henoch-Schönlein purpura
· A family history of chronic or congenital renal
disease (such as polycystic kidney disease), or other genetic conditions that
are associated with HTN, such as neurofibromatosis or tuberous sclerosis.
· Medication history (eg, glucocorticoids, anabolic
steroids, or oral contraceptives).
· History of umbilical arterial catheterization (UAC)
as a neonate. UAC is a predisposing factor for renovascular disease.
· The presence of an abdominal bruit raises the
possibility of renovascular disease, but its absence does not exclude the
diagnosis.
· The findings of hypertension in the upper
extremities and low or unobtainable blood pressure in the lower extremities,
significant difference between right and left arm BP, and diminished or delayed
femoral pulses are suggestive of coarctation of the aorta, the primary cardiac
cause of hypertension. The diagnosis is confirmed by echocardiogram.
CVD
risk factors — The history and physical
examination should assess for other cardiovascular disease (CVD) risk factors
or diseases associated with CVD in addition to hypertension.
· Family history of premature CVD and/or strokes.
· Identify overweight and obese children by
calculating body mass index (BMI) defined as the weight in kg divided by height
in m2. BMI and BMI percentiles may be determined using calculators for boys (calculator 3)
or for girls (calculator 4).
Weight classes based upon BMI are as follows .
Weight classes based upon BMI are as follows .
· Normal: BMI less than 25 kg/m2
· Overweight: BMI between 25 to 29.9 kg/m2
· Obese: BMI between 30 to 39.9 kg/m2
· Markedly obese: BMI greater than 40 kg/m2
· History of smoking.
· History of type 1 or 2 diabetes mellitus, chronic
kidney disease, organ transplantation, cardiac disease, Kawasaki disease,
autoimmune disease, familial hypercholesterolemia, and cancer.
· History of sleep disorders. Sleeping disorders,
especially sleep apnea, are associated with HTN and CVD in adults. In children,
data also suggest an association between sleep-disordered breathing and HTN [6-9].
Based upon this information, the NHBPEP Working Group recommends that a sleep
history should be obtained in a child with HTN, especially if he or she is
overweight. If a history of either sleep apnea or loud and frequent snoring is
obtained, polysomnography should be considered to identify a sleep disorder
Evidence of target-organ damage — The physical examination should
include a retinal examination to detect any retinal vascular changes due to HTN
. Cardiac heave or laterally displaced PMI may indicate left ventricular
hypertrophy (LVH).
Laboratory
evaluation — Initial laboratory
evaluation in all children with persistent HTN is directed at determining the
etiology of HTN, identifying other CVD risk factors, and detecting target-organ
damage. The following approach is recommended by the 2004 National High Blood
Pressure Education Program Working Group (NHBPEP):
· Measurement of serum BUN, creatinine, and
electrolytes, and collection of urine for urinalysis. These tests permit quick
assessment of renal function and abnormalities in glucose (eg, diabetes
mellitus) or potassium homeostasis (eg, chronic kidney disease or congenital
adrenal hyperplasia). An abnormal urinalysis and/or an elevation in serum
creatinine are suggestive of underlying renal disease.
· Complete blood count, looking for anemia that may
reflect chronic diseases such as vasculitis and chronic kidney disease.
· Measurement of fasting plasma glucose and lipids to
identify children with diabetes mellitus and dyslipidemia. These tests should
also be performed in prehypertensive children who are obese, have a family
history of premature CVD, or have chronic kidney disease.
· An echocardiogram to identify children with left
ventricular hypertrophy (LVH) because clinical parameters, such as the severity
of HTN, and electrocardiography do not accurately predict LVH. LVH is the most
prominent manifestation of target-organ damage from HTN. LVH has been reported
in 30 to 40 percent of children and adolescents with HTN and if present,
is an indication to initiate or intensify antihypertensive therapy.
Echocardiography should also be performed in prehypertensive children with obesity, hyperlipidemia, diabetes mellitus, or chronic kidney disease. Of note, left ventricular mass increases with higher BMI, and in the general pediatric population in the United States, LVM appears to be rising due to higher BMI.
Echocardiography should also be performed in prehypertensive children with obesity, hyperlipidemia, diabetes mellitus, or chronic kidney disease. Of note, left ventricular mass increases with higher BMI, and in the general pediatric population in the United States, LVM appears to be rising due to higher BMI.
· Renal ultrasonography is used to determine the
presence of both kidneys and presence of any other congenital anomaly, or
disparate renal size.
FURTHER
EVALUATION — Based upon the initial
history, physical examination, and laboratory evaluation, the clinician should
be able to establish whether the HTN is primary or secondary. This distinction
will determine whether further evaluation is performed for a potentially
reversible cause of secondary HTN.
Primary
hypertension — Hypertensive children who
fit the primary HTN profile may need no further laboratory evaluation beyond
the initial testing cited above .
The NHBPEP recommends
renal ultrasonography for all hypertensive children and adolescents. Although
we continue to obtain renal ultrasounds in all our patients with HTN, other
institutions do not routinely perform this study in patients who strongly fit
the profile of primary HTN defined as a post-pubertal adolescent who has stage
1 HTN, is overweight/obese, has a strong family history of primary HTN, and has
no sign or symptom suggestive of secondary HTN after completion of the initial
evaluation.
Among obese children
with primary HTN, measurement of hemoglobin A1c may be indicated, particularly
if there is a strong family history of type 2 diabetes mellitus.
There are little data
on the usefulness of plasma levels of uric acid, homocysteine, and
lipoprotein(a) in the evaluation of pediatric primary HTN. Elevation of these
substances has been reported to be associated with an increased risk of
cardiovascular disease in adults. The NHBPEP does not recommend these studies
unless there is a strong family history of an abnormality .
Secondary
hypertension — Further evaluation is
required in patients with findings suggestive of secondary HTN to determine the
underlying cause.
The following
diagnostic studies may be performed in hypertensive children with a high degree
of suspicion that an underlying disorder is present
Renal
imaging — As discussed previously,
renal ultrasound is useful to determine the presence of both kidneys or
presence of any congenital anomaly, or disparate renal size. The NHBPEP
recommends renal ultrasonography for all hypertensive children and adolescents.
In patients with a
strong suspicion for renal scarring from the history or with a suggestive but
indeterminant finding on renal ultrasound, a 99mTc–dimercaptosuccinic acid (DMSA) renal scan
can be performed, since it is a more sensitive study to detect renal cortical
loss and scarring
Plasma
renin activity — Plasma renin activity
(PRA) may be useful in patients suspected to have one of the following
conditions:
· Excess mineralocorticoids (eg, aldosterone)
secretion – Patients with mineralocorticoid excess are usually hypokalemic,
have metabolic alkalosis, and their PRA is low and often unmeasurable.
Congenital adrenal hyperplasia is a frequent cause of excess mineralocorticoid secretion in children. Affected patients may also present as a neonate with ambiguous genitalia due to the excess secretion of androgens
Aldosterone-secreting tumors are rare in children. Primary hypersecretion of aldosterone may also result from the rare genetic disorder glucocorticoid-remediable hyperaldosteronism. Hypokalemia is absent in more than one-half of these patients. In the absence of hypokalemia at presentation, the diagnosis may be suspected from the family history of early HTN (before age 21 years) and the frequent development of marked hypokalemia after the administration of a thiazide diuretic.
Congenital adrenal hyperplasia is a frequent cause of excess mineralocorticoid secretion in children. Affected patients may also present as a neonate with ambiguous genitalia due to the excess secretion of androgens
Aldosterone-secreting tumors are rare in children. Primary hypersecretion of aldosterone may also result from the rare genetic disorder glucocorticoid-remediable hyperaldosteronism. Hypokalemia is absent in more than one-half of these patients. In the absence of hypokalemia at presentation, the diagnosis may be suspected from the family history of early HTN (before age 21 years) and the frequent development of marked hypokalemia after the administration of a thiazide diuretic.
· Renin-secreting tumor – Renin-secreting tumors are
rare both in children and adults. Patients generally present with severe HTN,
hypokalemia, metabolic alkalosis, and markedly elevated renin levels
· Renovascular disease – The plasma renin activity
may be elevated in children with renovascular HTN but, as is true in adults, it
is a relatively insensitive test. Approximately 15 percent of children with
arteriographically evident renal artery stenosis have normal plasma renin
activity
Plasma
and urine catecholamines — Patients
with HTN due to disorders with catecholamine excess such as pheochromocytoma
and neuroblastoma will have elevated levels of both plasma and urine
catecholamines and metabolites. In addition to HTN, affected patients may
present with headache, sweating, and tachycardia. In patients with symptoms of
catecholamine excess and elevated plasma and urine catecholamines, further
evaluation is required.
Renovascular
imaging — In our practice,
renovascular imaging is considered, especially when infants and children have
known predisposing factors or findings associated with renal artery stenosis
such as prior umbilical artery catheter placements, family history or findings
for neurofibromatosis, an abdominal bruit, or a significant size discrepancy on
renal ultrasonography. In addition, we consider renovascular imaging in
patients with stage 2 HTN when no other cause has been identified since, as
noted above, children with renovascular disease typically have markedly
elevated BP. Standard intraarterial
angiography is the current gold standard for evaluating renovascular disease in
children. In adults, the following noninvasive tests are used to screen for
renal vascular diseases:
· Magnetic resonance angiography (MRA)
· Computed tomographic angiography (CTA)
· Duplex Doppler ultrasonography
In children, these
procedures are not universally available. In addition, there are considerations
that must be taken in account when these tests are performed in small children
and infants.
· The need for conscious sedation or general
anesthesia when performing MRA.
· The need to modify CT dosing to minimize
unnecessary radiation exposures.
If renovascular
evaluation is required, a radiological center with pediatric experience in
these screening techniques should be chosen. The selection of the screening
modality is dependent upon the expertise of the clinical staff and the
availability of appropriate equipment.
Our
approach — In our practice, the
initial evaluation includes measurement of serum BUN, creatinine, electrolytes,
a complete blood count, urinalysis, renal ultrasonography (unless done
previously), and an echocardiogram to evaluate left ventricular mass. Other
studies are performed based upon the likelihood that the cause of HTN is
secondary. Thus, more extensive evaluation is reserved for prepubertal children
(usually less than 10 years of age), and those with stage 2 HTN and/or findings
indicative of a specific underlying cause:
· Plasma renin and aldosterone are obtained in all
prepubertal children, any patient with stage 2 HTN, and any patient with hypokalemia
and/or metabolic alkalosis.
· Plasma and urine catecholamines are obtained in
patients who exhibit symptoms of catecholamine excess (eg, headache, sweating,
and/or tachycardia) or are at risk of pheochromocytoma, such as in patients
with neurofibromatosis.
· Screening for renovascular disease is performed in
any patient with stage 2 HTN if no other cause is identified, or if there are
predisposing risk factors (eg, prior umbilical artery catheterization,
neurofibromatosis, or abdominal bruit).
· A 99mTc-dimercaptosuccinic acid (DMSA) renal scan is performed in patients
with a strong suspicion for renal scarring based upon the history (ie,
recurrent urinary tract infection) and who have a normal renal ultrasound. A
DMSA scan is also obtained to clarify or confirm a suggestive but indeterminant
finding on renal ultrasound. (See 'Renal imaging' above.)
SUMMARY
AND RECOMMENDATIONS
· Hypertension (HTN) in childhood and adolescence
contributes to premature atherosclerosis and the early development of
cardiovascular disease (CVD).
· Childhood HTN is divided into two categories:
primary HTN (no identifiable cause is found), and secondary HTN (an underlying
cause is identified).
· The goals of the initial evaluation of a child or
adolescent with HTN include:
· Identify the child with secondary HTN who may have
a curable disease
· Identify other comorbid risk factors (eg, obesity
and dyslipidemia) for cardiovascular disease (CVD) or diseases associated with
an increased risk for CVD (eg, diabetes mellitus).
· Identify children who should be treated with
antihypertensive drug therapy.
· Most hypertensive children, particularly those who
are likely to have secondary HTN, should be referred to a pediatric
nephrologist or other physician with experience in childhood HTN for evaluation
and management.
· The initial evaluation includes a history, physical
examination, and laboratory testing including measurement of serum BUN,
creatinine, and electrolytes, and complete blood count, urinalysis, renal
ultrasonography, and an echocardiogram to evaluate left ventricular mass.
· Based upon the initial history, physical
examination, and laboratory evaluation, the clinician should be able to
establish whether the HTN is primary or secondary. Further evaluation is
performed to identify any potentially reversible cause of secondary HTN and
includes other renal imaging studies (eg, renal scans or arteriogram) and
measurement of plasma renin and aldosterone, and plasma and urine
catecholamines. Evaluation for renovascular disease in children should be
performed in a radiological center with pediatric experience in screening for
these disorders
