Over the last two decades, essential hypertension has become common in adolescents, yet remains under-diagnosed in absence of symptoms. Diagnosis is based on normative percentiles that factor in age, sex and height. Evaluation is more similar to adult essential hypertension than childhood secondary hypertension. Modifiable risk factors such as obesity, sodium consumption and low exercise should be addressed first. Many anti-hypertensive medications now have specific regulatory approval for children. Sports participation need not be limited in mild or well-controlled cases. Primary care physicians play an important role in reduction of cardiovascular mortality by early detection and referral when needed.
Key points
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Over the last two decades, essential hypertension has become common in children and adolescents, and it is related to the obesity epidemic.
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Hypertension is underrecognized in children and diagnosis is based on specific normative standards, including sex, age, and height.
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Modifiable risk factors for essential hypertension in children, such as obesity and sodium consumption, should be addressed during treatment.
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Primary care physicians may play an important role in reduction of cardiovascular mortality by early detection, appropriate management, and referral when needed.
Introduction
The current prevalence of hypertension in children is estimated at about 1% to 5%, with higher rates among minority adolescents. Primary hypertension (PH), also referred to as essential hypertension, previously considered a disease of adulthood, has now become increasingly common in the pediatric population largely due to the obesity epidemic. Obese children are three times more likely to develop hypertension than their nonobese counterparts. Therefore, this article focuses on obesity-related teenage hypertension. The article also discusses hypertension in nonobese teenagers, for which significant data exist.
The relationship between obesity and hypertension has been clearly defined in multiple studies across different ethnic and gender groups. The cause of obesity-related hypertension has been linked to sympathetic hyperactivity, insulin resistance, and vascular structure changes. Sorof and colleagues demonstrated the presence of sympathetic nervous system hyperactivity in obese school-age children, evidenced by increased heart rate and blood pressure (BP) variability, which contributed to the pathogenesis of isolated systolic hypertension in this cohort. Increased sodium content of the cerebrospinal fluid has been shown to increase sympathetic nervous system activity through activation of the renin-angiotensin-aldosterone pathway in the brain. Obese individuals have selective insulin resistance, which leads to increased sympathetic activity and alteration of vascular reactivity. The resultant sodium retention is evidenced by decreased urinary sodium excretion. The lessons learned from the study of obese hypertensive individuals can be largely applied to the diverse population of hypertensive children.
Introduction
The current prevalence of hypertension in children is estimated at about 1% to 5%, with higher rates among minority adolescents. Primary hypertension (PH), also referred to as essential hypertension, previously considered a disease of adulthood, has now become increasingly common in the pediatric population largely due to the obesity epidemic. Obese children are three times more likely to develop hypertension than their nonobese counterparts. Therefore, this article focuses on obesity-related teenage hypertension. The article also discusses hypertension in nonobese teenagers, for which significant data exist.
The relationship between obesity and hypertension has been clearly defined in multiple studies across different ethnic and gender groups. The cause of obesity-related hypertension has been linked to sympathetic hyperactivity, insulin resistance, and vascular structure changes. Sorof and colleagues demonstrated the presence of sympathetic nervous system hyperactivity in obese school-age children, evidenced by increased heart rate and blood pressure (BP) variability, which contributed to the pathogenesis of isolated systolic hypertension in this cohort. Increased sodium content of the cerebrospinal fluid has been shown to increase sympathetic nervous system activity through activation of the renin-angiotensin-aldosterone pathway in the brain. Obese individuals have selective insulin resistance, which leads to increased sympathetic activity and alteration of vascular reactivity. The resultant sodium retention is evidenced by decreased urinary sodium excretion. The lessons learned from the study of obese hypertensive individuals can be largely applied to the diverse population of hypertensive children.
Definition and classification of pediatric hypertension
Pediatric hypertension is usually asymptomatic and can easily be missed by healthcare professionals. The National Heart, Lung, and Blood Institute (NHLBI) of the National Institute of Health (NIH) commissioned the Task Force on Blood Pressure Control in Children to develop normative standards for BP. These standards were derived from the survey of more than 83,000 person-visits of infants and children. The percentile curves describe age-specific and gender-specific distributions of systolic and diastolic BP in infants and children adjusted for height ; these have been updated periodically.
Hypertension in children and adolescents is diagnosed based on specific references, including age, gender, and height. Hypertension is defined as systolic and/or diastolic BP greater than the 95th percentile for age, gender, and height on three or more separate occasions. BP greater than 90th percentile but less than the 95th percentile for age, sex, and height defines prehypertension, representing a category of patients at high risk for developing hypertension. It is crucial that healthcare providers be aware that the BP at the 90th percentile for an older child often exceeds the adult threshold for prehypertension of 120/80 mm Hg. As a result, beginning at 12 years of age, the BP range that defines prehypertension includes any BP reading of greater than 120/80 mm Hg, even if it is less than the 90th percentile. We now know that prehypertension may not be completely benign and the rate of progression to hypertension was reported at 7% per year over a 2-year interval. Stage I hypertension refers to systolic and/or diastolic BP greater than the 95th percentile but less than or equal to the 99th percentile plus 5 mm Hg. There are no data on the progression from stage I to stage II hypertension in children.
Stage II hypertension is defined as systolic and/or diastolic BP greater than the 99th percentile plus 5 mm Hg. This represents a more severe form of hypertension, commonly associated with target organ damage. An analysis by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents revealed an increased risk for left ventricular hypertrophy (LVH) in participants with stage II hypertension. Surprisingly, in some studies, children and adolescents with prehypertension also had a substantially increased left ventricular mass index with a twofold higher prevalence of LVH than their normotensive counterparts. Classification of hypertension is summarized in Table 1 .
| Normotensive children | Systolic and/or diastolic BP <90th percentile for sex, age, and height |
| Prehypertension | Systolic and/or diastolic BP greater than the 90th but less than the 95th percentile or BP >120/80 mm Hg but less than the 95th percentile |
| Stage I Hypertension | Systolic and/or diastolic BP greater than the 95th but less than the 99th percentile plus 5 mm Hg |
| Stage II Hypertension | Systolic and/or diastolic BP greater than the 99th percentile plus 5 mm Hg for sex, age, and height |
Primary and Secondary Hypertension
Based on the cause, hypertension can be categorized as PH or essential hypertension when there is no identifiable cause and as secondary hypertension (SH) when there is an underlying cause for hypertension. PH is now the most common cause of hypertension in adolescents and young adults. It is usually characterized by stage I (mild) hypertension and associated with a positive family history of hypertension. SH should be considered in very young children, those with stage II hypertension, and children with clinical features that suggest systemic diseases associated with hypertension. SH may be due to
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An underlying renal parenchymal disease
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Endocrine disease
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Vascular
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Neurologic condition.
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Diagnosis of pediatric hypertension is often missed due to the absence of symptoms.
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Hypertension is diagnosed based on specific references, including age, gender, and height.
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Three stages of hypertension are
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Prehypertension
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Stage I hypertension
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Stage II hypertension.
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Based on cause, hypertension can be either primary (no identifiable cause) or secondary (underlying cause present).
Risk factors for essential hypertension
A parental family history of hypertension is linked to a twofold-increased risk of developing essential hypertension in children and young adults. This association led to extensive research to elucidate the underlying genetic cause of PH. Family studies have shown that 20% to 40% of cases seen are genetically determined. Different monogenic causes of PH have been established, including mutations in the corticosteroidogenic genes, CYP11B1 and HSD11B2 ; mutations in the epithelial sodium channel (SCNN1B, SCNN1G); in the WNK serine-threonine kinase ; and polymorphisms in the renin-angiotensin-aldosterone system. However, pure monogenic causes of PH are still rare.
In a 10-year longitudinal study, African American children were shown to have a significantly greater elevation in systolic BP compared with white children from childhood to adulthood, even after adjusting for height, body mass index (BMI), and socioeconomic status. Recently, mutations in the apolipoprotein-L1 gene in chromosome 22 were discovered that seem to explain the increased prevalence of hypertension-associated nephropathy in the African American population. These mutations are thought to have an autosomal recessive pattern of inheritance and patients who are homozygous for the mutations have a higher likelihood for developing hypertension-associated nephropathy, focal segmental glomerulosclerosis, and HIV-associated nephropathy.
Increasing age and BMI have also been significantly associated with the development of hypertension with a higher prevalence in African Americans and Asians. There is a growing body of evidence on the inverse relationship between birth weight and hypertension in children and adolescents. A strong association has been observed among patients with a history of low birth weight and intrauterine growth retardation. A more significant relationship is seen when adjustments are made for current body weight.
In a recent study by Yang and colleagues, children were found to consume between 1300 mg and 8100 mg of sodium a day (mean of 3387 mg). Children with the highest sodium intake were twice as likely to have elevated BP compared with those with lower sodium intake. This effect was more pronounced in the overweight and obese children. Overweight or obese children in the highest quartile of sodium consumption had more than three times the risk of elevated or high BP compared with overweight children in the lowest quartile of sodium consumption.
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Risk factors for developing PH
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Family history has been linked to increased risk
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Racial predilection has been seen; the African American population is at higher risk
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Increasing age and BMI
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Low birth weight and intrauterine growth retardation
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Increased sodium consumption.
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Diagnosis of hypertension
Clinical Evaluation of a Hypertensive Teen
History
A thorough history is essential in guiding the evaluation and management of a hypertensive adolescent. Detailed information regarding the timing when elevated BP was first noted and the presence of comorbid conditions are crucial for establishing the diagnosis. For this age group, the clinical history should include questions about the use of anabolic steroids, stimulants, and caffeine-containing energy drinks, which can elevate the BP. A history of snoring in an obese individual should prompt the evaluation for obstructive sleep apnea. History suggestive of renal disease or an endocrine tumor should be elicited.
Physical examination
A comprehensive physical examination could suggest the underlying cause of hypertension in children and the presence of target organ damage. Attention to the BMI is essential to identify overweight and obese patients. Table 2 summarizes the physical findings and laboratory investigations used to look for common causes of SH in the adolescent.
| Physical Examination | Causes | Investigation |
|---|---|---|
| General: overweight, obese, acanthosis nigricans | PH or metabolic syndrome | Urinalysis, fasting blood sugar, lipid panel. Obtain ambulatory BP monitoring to rule out white coat hypertension |
| Edema, pallor, palpable kidneys on abdominal examination (polycystic kidney disease), rash, arthralgia, growth retardation | Renal parenchymal disease | Urinalysis, serum creatinine, electrolytes, complete blood count, urine protein to creatinine ratio, antinuclear antibodies, dsDNAse, complements C3 or C4, renal ultrasound |
| Tachycardia, widened pulse pressure, enlarged thyroid, weight loss, tremor | Hyperthyroidism | Thyroid function test: free T4 and thyroid-stimulating hormone |
| Moon facies, acne, hirsutism, truncal obesity, striae | Cushing’s syndrome, steroid therapy, Liddle syndrome | Serum electrolytes, cortisol level, serum renin and aldosterone |
| Weak lower extremity pulses, BP in upper limbs more than 10 mm Hg greater than lower extremity BP | Coarctation of the aorta | Echocardiography |
| Abdominal bruit | Renal artery stenosis | Renal artery angiography, captopril scintigraphy |
| Tachycardia, flushing, visual disturbances, episodic hypertension | Pheochromocytoma | 24-h urine metanephrine I 131 or I 123 metaiodobenzylguanidine scan |
| Café au lait spots, axillary or inguinal freckling | Neurofibromatosis | CT scan or MRI |
| Bradycardia, widened pulse pressure | Central nervous system lesion: tumor, bleed | CT scan or MRI |
BP measurement
To obtain an accurate resting BP, patients should be allowed to sit for at least 5 minutes with the back supported and both feet on the ground. A study of 390 children evaluated at 580 visits by Podoll and colleagues revealed that 74% of BP readings were predominantly higher at the vital sign station using oscillometric devices compared with readings taken by auscultation in the examination room by personnel trained according to the Fourth Task Force recommendations. Mean differences of 13.2 plus or minus 8.9 mm Hg for systolic and 9.6 plus or minus 7.6 mm Hg for diastolic BP were seen. This highlights the importance of proper technique and the need to reevaluate initial elevated BP readings carefully.
BP should be measured with an appropriate-sized cuff in an upper extremity. The preferred method of measurement is by auscultation, especially because the normative BP tables for children are based on similar measurements. An appropriate-sized cuff should have an inflatable bladder width that spans at least 40% of the patient’s arm circumference measured at the midpoint between the olecranon (elbow) and the acromion (shoulder). The bladder length should cover 80% to 100% of the arm circumference. Although previous recommendations to determine cuff adequacy included cuff length, current recommendations are based on the cuff width only. Previous recommendations from the Task Force on High Blood Pressure in Children and Adolescents were that the width of the BP cuff should cover at least three-quarters of the length of the arm measured from the acromion to the olecranon. However, this was found to result in an exaggeration in pediatric cuff choice. A review by Arafat and Mattoo evaluated the appropriateness of this recommendation and reported that if three-quarters of the arm length is used to determine cuff size, there would be an overestimation in pediatric cuff selection. An update on the Task Force recommendations in 1996 included recommendations for a cuff width of 40% of the mid-upper arm circumference; there was no reference to cuff length or the reason for the change in recommendations. It is thought that the updated recommendation is based on the idea that the bladder width should be 40% to 50% of the mid-upper arm circumference, supported by evidence that the correct ratio of bladder width to arm circumference is 0.4.
BP readings are overestimated when the cuff size is too small, which increases the possibility of a wrong diagnosis of hypertension. Elevated BP readings obtained by oscillometric devices that exceed the 90th percentile should be confirmed by auscultation.
In the outpatient setting, documented elevations in BP on three separate occasions at least 1 week apart are essential to confirm the diagnosis. Alternatively, ambulatory BP monitoring (ABPM) could be performed to arrive at the diagnosis of hypertension.
ABPM
ABPM forms the basis for the diagnosis when there is discordance in BP readings between daytime ambulatory BP measurements and office BP readings. It is particularly useful in patients with white coat or isolated clinic hypertension and masked hypertension. White coat hypertension is defined as office hypertension and ambulatory normotension, whereas masked hypertension, the opposite, refers to ambulatory hypertension and office normotension.
ABPM uses oscillometric measures to obtain BP measurements. BP is measured every 20 to 30 minutes in the patient’s home environment over a 24-hour period. Patients are advised to continue their routine activities but avoid rigorous activities during this monitoring period. A record of the actual sleep and wake times is maintained by the patients to enable evaluation of nocturnal dipping patterns and nocturnal hypertension. In the authors’ practice, we measure BP every 30 minutes during the day and every hour at night. An adequate ABPM report should have at least 40 to 50 BP readings with at least one reading every hour including at nighttime. BP load is the percent of BP above the 95th percentile for age, gender, and height in the 24-hour period. Based on the ABPM, hypertension is defined as elevated mean systolic BP above the 95th percentile and/or an elevated BP load above 25%. Normative standards have been established and are available for ambulatory BP measurements.
Twenty-four hour ABPM has become commonplace in pediatric nephrology clinics for diagnosing white coat hypertension and masked hypertension. There is growing evidence supporting its use in the pediatric population. Nephrology groups own and perform ABPM; it is less commonly performed by the cardiologist and rarely by the endocrinologist. Recently, Davis and Davis recommended incorporating ABPM in the primary care setting to increase diagnostic accuracy of hypertension and avoid unnecessary treatment. This makes it important that primary care providers be familiar with the role of ABPM for their patients with discordant BP readings or other diagnostic challenges.
The prevalence of white coat hypertension and masked hypertension in the general population are reported at 1% and 10%, respectively. Patients with white coat hypertension have a lower risk for cardiovascular mortality than those with masked or sustained hypertension, although they have a greater risk for developing sustained hypertension later. White coat hypertension in children is not associated with the development of LVH or hypertension-related kidney damage, unlike PH, which has been linked to microalbuminuria. However, it has been related to a slight increase in left ventricular mass index, intermediate in range between normotensive and hypertensive subjects. This finding was highlighted in a study by Lande and colleagues in which 81 subjects were divided in three groups matched for age and BMI. They were studied and found to have mean left ventricular mass indices of 29.2, 32.3, and 25.1 g/m 2 in the normotensive, white coat hypertensive, and sustained hypertensive groups, respectively. White coat hypertension has been associated with increased pulse wave velocity, which is a marker of increased arterial stiffness and it might signify a greater cardiovascular risk than previously thought.
Masked hypertension has also been associated with increased cardiovascular mortality and other target organ damage in adults. In a study of 592 children aged between 5 and 18 years, Lurbe and colleagues showed that subjects with masked hypertension were likely to be obese and to have a family history of hypertension and were at an increased risk of developing sustained hypertension. Masked hypertension is a precursor of sustained hypertension and LVH in young children and adolescents. The risk for LVH is similar between participants with stage I hypertension and masked hypertension.
ABPM has been closely associated with target organ damage and increased left ventricular mass index, leading to increased cerebrovascular events and a concomitant increase in cardiovascular mortality risk. White coat hypertension is linked to a low risk for stroke, a finding by Verdecchia and colleagues who reported a hazard ratio for stroke of 1.15 and 2.01 in patients with white coat hypertension and sustained hypertension, respectively. Researchers from the Dublin outcome study proposed ambulatory arterial stiffness index as a novel marker of cardiovascular mortality.
Investigations in a Hypertensive Adolescent
Initial investigations
Initial evaluation should include a urinalysis, serum creatinine, and echocardiography to evaluate for LVH. Renal sonography need not be routinely performed in the obese adolescent with a normal physical examination and normal urinalysis results. This was confirmed in a retrospective study by Tuli and Dharnidharka in which routine renal imaging in 50 children did not provide any additional diagnostic information to the initial evaluation. These recommendations are similar to the evaluation of an adult hypertensive patient.
Subsequent investigations
Subsequent investigations include fasting blood sugar and lipid profile in the obese teenager to rule out comorbid conditions.
Selected tests in unusual cases
Further investigations should be guided by the history, risk factors, and symptoms identified as outlined in Table 2 .
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Detailed history and comprehensive physical examination are important for indentifying an underlying cause of hypertension and other comorbid conditions.
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BP estimation by proper technique is crucial.
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Elevated BP readings above the 90th percentile obtained by oscillometric devices should be confirmed by auscultation.
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BP readings are overestimated when the cuff size is small.
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Elevated BP on three separate occasions at least 1 week apart is essential to confirm the diagnosis.
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ABPM may be performed to diagnose hypertension in cases of discordance between ambulatory BP and office BP readings.
Management of a hypertensive teen
After the diagnosis of hypertension is reached, management should be tailored to the individual patient. Fig. 1 shows an algorithm for the management of teenage hypertension according to the severity.
Therapeutic Lifestyle Modification
Therapeutic lifestyle modification is the first line of management of pediatric hypertension and can be the sole modality of therapy in patients diagnosed with prehypertension and stage I hypertension. It focuses on dietary management, increased physical activity, stress reduction, and avoidance of illicit drug and tobacco use. Dietary management should include an age-appropriate, salt-restricted diet with emphasis on weight loss in overweight or obese children. To have a better chance of success, the entire family should adopt these lifestyle modifications; a primary provider can be instrumental in this endeavor.
Pharmacologic Therapy
The available evidence on the therapeutic management of pediatric hypertension is based on available evidence and consensus expert opinion when such evidence is lacking. The Fourth Task Force report on High Blood Pressure in Children and Adolescents include the following indications for pharmacologic therapy :
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Symptomatic hypertension
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Persistent hypertension despite lifestyle modification
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SH
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Presence of hypertensive target organ damage, such as LVH, hypertensive retinopathy, and microalbuminuria
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Presence of comorbid conditions that increase cardiovascular risk, such as diabetes mellitus.
For patients with uncomplicated PH, the target BP is less than the 95th percentile for age, gender, and height; whereas it is less than the 90th percentile for patients with comorbid conditions such as diabetes, chronic kidney disease, or evidence of target organ damage.
Choice of antihypertensive medications
There are no specific recommendations on the optimal first-line agent for the treatment of pediatric hypertension. The classes of antihypertensive medications that can be used in the pediatric hypertensive patient include:
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Calcium channel blockers (CCBs)
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Angiotensin-converting enzyme inhibitors (ACEI)
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Angiotensin receptor blockers (ARBs)
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Diuretics, beta-blockers (BBs)
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Alpha-blockers
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Centrally acting agents, vasodilators
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Combined alpha-adrenergic and beta-adrenergic antagonists
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Renin inhibitors
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Aldosterone receptor blockers.
Commonly used formulations from the different classes are shown in Table 3 .
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