Evaluation of hypertension in children and adolescents

Evaluation of hypertension in children and adolescents

N S Mani MD Professor, Pediatrics, 9645151883

drnsmanimd@gmail.com

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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 <90^th percentile.

· Prehypertension – Systolic and/or diastolic BP ≥90^th percentile but <95^th percentile or if BP exceeds 120/80 mmHg (even if <90^th percentile for age, gender, and height).

· Hypertension – HTN is defined as either systolic and/or diastolic BP ≥95^th 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 95^th percentile and 5 mmHg above the 99^th percentile.

· Stage 2 HTN – Systolic and/or diastolic BP ≥99^th 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 90^th 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 99^th percentile)   The age- and height-specific blood pressure percentiles may be determined using calculators for boys   or for girls  

· Stage 1 HTN (BP ≥95^th 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 .

· 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.

· 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.  

· 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