Hypertension

CHAPTER 106


Hypertension


Gangadarshni Chandramohan, MD, MSc, FASN, FAAP, and Michael Nguyen, DO



CASE STUDY


A 16-year-old girl is seen in the emergency department with a history of persistent headaches of 2 weeks’ duration. She has been having occasional headaches for the past 2 years, which have been treated primarily with acetaminophen. She denies any recent weight loss, hair loss, joint pain, sweating, or palpitations. She has no history of swelling of her eyes or legs or blood noticed in the urine. She was born preterm at 30 weeks’ gestational age and was kept in the hospital for 2 weeks. She has no history of urinary tract infection. Her 34-year-old mother and 58-year-old maternal grandmother have been on antihypertensive agents for the past several years; however, she has no family history of renal or heart disease. She is an average student. Her diet includes mostly meat and refined carbohydrates, such as bread and pasta. Additionally, she regularly eats salty snacks but drinks soda only occasionally. She has never been involved in any physical activity on a regular basis. She has never been sexually active and denies the use of illicit drugs, alcohol, or tobacco. She denies taking any medication prior to this visit, including oral contraceptives.


The physical examination is remarkable for a girl with weight, height, and body mass index above the 95th percentile for age. Her pulse is 85 beats per minute, and her blood pressure is 158/78 mm Hg in the right arm in the supine position. Equal pulses are palpable in all 4 extremities. Blood pressure is 164/92 mm Hg in the right lower extremity. Funduscopic examination reveals evidence of arteriovenous nicking but no papilledema. Normal breath sounds are noted on chest examination, along with an active precordium with the apical impulse shifted to the left. No murmurs are heard. The liver is palpable 1 cm below the right costal margin. The neurologic examination is unremarkable; no focal neurologic deficit is present. Urinalysis is normal. Hemoglobin is 11.2 g/dL, and hematocrit is 33%. Sodium is 139 mEq/L, potassium is 3.8 mEq/L, chloride is 102 mEq/L, and bicarbonate is 22 mEq/L. Blood urea nitrogen is 15 mg/dL, and serum creatinine is 0.9 mg/dL. Electrocardiography shows left ventricular enlargement. Computed tomography of the head is normal.


Questions


1. What is the definition of hypertension in children and adolescents?


2. What are the causes of hypertension in children and adolescents?


3. What is the appropriate evaluation of hypertension in children and adolescents?


4. What are the comorbid conditions and long-term complications associated with essential (ie, primary) hypertension?


5. What is the appropriate emergency treatment of symptomatic hypertension?


6. What is the long-term management of children and adolescents with essential hypertension?


Hypertension (HTN) has become a highly concerning chronic non-communicable medical condition among children and adolescents in the past few decades because of a multitude of factors including, but not limited to, increasing prevalence of childhood obesity, survival of children with renal anomalies, and children born preterm who often sustain hypoxic injuries to the kidneys. Hypertension is blood pressure (BP) that is elevated above the normative BP data based on age, sex, and height.


Hypertension takes primary and secondary forms. Primary HTN is the most predominant cause among pediatric patients in the United States. General characteristics of patients with primary HTN include age of 13 years or older, family history of HTN, and overweight or obesity. Primary HTN in pediatrics has become a major public health concern. Secondary HTN is proportionally more prevalent among younger children and has an underlying cause that, if identified, may be curable, thereby eliminating the need for lifelong medical treatment. Renal and renovascular disease are the most common causes of secondary HTN. With early diagnosis and intervention, however, the long-term adverse consequences of HTN can be prevented. Children who are expected to be at increased risk for end-organ (ie, heart, central nervous system, kidneys, eyes) damage are those with persistently elevated BP, high body mass index (BMI), excessive weight gain, comorbid conditions (eg, type 2 diabetes), and a family history of HTN.


Normal Blood Pressure and Definition of Hypertension


Systolic and diastolic BP gradually increase from the newborn period through adolescence; therefore, age-appropriate norms should be used to classify a BP reading as normal or hypertensive. The stages and age-appropriate values of HTN are defined by the American Academy of Pediatrics (AAP) “Clinical Practice Guideline (CPG) for Screening and Management of High Blood Pressure in Children and Adolescents,” published in August 2017. The newer version of the previous BP chart published by AAP CPG compared with the previous guidelines The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents excluded children with obesity in the analysis and included height values rather than height percentiles for easier reference.


The classification of BP consists of normal BP, elevated BP, stage 1 HTN, and stage 2 HTN. In the most recent AAP CPG, the term “prehypertension” was replaced with “elevated BP.” Currently, the stages of HTN are defined differently for children younger than 13 years than for adolescents age 13 years or older (Table 106.1, Table 106.2, and Table 106.3). For neonates and for infants age 1 through 12 months, similar guidelines for diagnosing HTN apply (Table 106.4, Table 106.5A, and Table 106.5B). For a diagnosis of HTN, measurement in any of the ranges provided must be noted on 3 or more occasions.


Definition of White Coat Hypertension and Masked Hypertension


It is well known that BP measurements are dynamic and can be misleading in a single clinic visit. Recent knowledge from ambulatory BP monitoring (ABPM) has contributed substantially to the understanding of HTN in children by revealing different BP responses under different circumstances. Ambulatory BP monitoring is continuous and assesses changes in BP over a 24-hour period, noting changes in BP at various intervals throughout the day and night. Ambulatory BP monitoring has helped identify 2 situations in which the BP measured during the clinical visit may significantly differ from home: white coat HTN and masked HTN (Table 106.6).































Table 106.1. Definition of Hypertension in Children and Adolescents

Term


Definition


<13 years


≥13 years


Normal BP


Systolic and diastolic BP <90th percentile for age, sex, and height


<120/<80 mm Hg


Elevated BP


Average systolic or average diastolic BP of 90th–94th percentiles for age, sex, and height


120/<80 mm Hg to
129/<80 mm Hg


Stage 1 hypertension


Average systolic and/or diastolic BP ≥95th percentile through the 94th percentile + 12 mm Hg for age, sex, and height with measurements obtained on ≥3 occasions


130/80 mm Hg to
139/89 mm Hg


Stage 2 hypertension


Average systolic and/or diastolic BP >5 mm Hg above the 95th percentile for age, sex, and height


≥140/90 mm Hg


Abbreviation: BP, blood pressure.


With white coat HTN, isolated elevated BP measurements in the hypertensive range are noted in the clinic, but the patient has otherwise normal values outside the medical setting. White coat HTN can account for a significant number of elevated BP readings in clinics, possibly in up to 50% of patients. These isolated elevated values may result in a misinterpretation of a child’s actual BP values.


With masked HTN, however, the child or adolescent at risk for HTN has normal BP measurements in the office but has hypertensive BP measurements outside the office. The child with masked HTN is twice as likely as a child who is not hypertensive to have a family history of HTN. If the child also has a high pulse rate and elevated BMI, the child is at increased risk for developing a cardiovascular disorder. It is important to promptly identify and diagnose masked HTN because left untreated, it can put the patient at significant risk for end-organ damage, resulting in stroke, left ventricular hypertrophy (LVH), visual impairment, and/or renal failure. Studies have shown a significant direct association between not only elevated BP and left ventricular mass index but also between white coat and masked HTN and left ventricular mass index. The prevalence and long-term implications of the latter 2 types of HTN remain unclear.


Accurate Method of Measuring Blood Pressure


It is essential to obtain an accurate BP measurement in children. Several factors can influence BP measurement, and proper planning is important to optimize the likelihood of obtaining an accurate measurement. Prior to measurement, the child should be seated for 3 to 5 minutes with the back supported and with the feet uncrossed and resting on a firm surface to ensure an accurate reading. An appropriately sized BP cuff should be used based on the child’s arm circumference and length; the inner cuff width should be approximately 40% of the arm circumference midway between the olecranon and the acromion, and the length should be greater than 80% around the arm circumference at the same point to avoid an inaccurately high reading (Figure 106.1). The right arm should be used for con-sistency in comparison with standard tables. In addition to using a variety of cuff sizes, it is recommended to use a thigh cuff in children and adolescents whose BMI is greater than the 95th percentile and in cases in which all standard arm cuffs are too small. For the child with suspected coarctation of aorta, the child should be in a prone position, lying on a flat surface, and the thigh cuff should be placed at the mid-thigh level. Of note, the BP in the lower extremities is usually 10% to 20% higher than the brachial artery pressures (Table 106.7).


Various other factors to consider to minimize errors while measuring BP include the patient’s posture (ie, sitting versus lying down) and level of the arm in relation to level of the heart (ie, the elbow should be at the level of the heart). It is also important that the child remain calm and not be anxious or agitated while the measurement is taken. Additionally, the person taking the measurement must ensure that the child has not ingested any stimulants (eg, caffeinated beverages, dietary supplements) that could artificially increase BP measurement within 30 to 60 minutes before testing.


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Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure.


Adapted with permission from Flynn JT, Kaelber DC, Baker-Smith CM, et al; American Academy of Pediatrics Subcommittee on Screening and Management of High Blood Pressure in Children. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904.


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Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure.


Adapted with permission from Flynn JT, Kaelber DC, Baker-Smith CM, et al; American Academy of Pediatrics Subcommittee on Screening and Management of High Blood Pressure in Children. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904.


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Abbreviations: DBP, diastolic blood pressure; MAP, mean arterial pressure; SBP, systolic blood pressure.


Reprinted with permission from Dionne JM, Abitbol CL, Flynn JT. Hypertension in infancy: diagnosis, management and outcome. Pediatr Nephrol. 2012;27(1):17–32.


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Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure.


Reprinted with permission from Mistry K, Gupta C. Neonatal hypertension. NeoReviews. 2017;18(6)e357–e371.


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Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; SBP, systolic blood pressure.


a Derived from Flynn JT, Daniels SR, Hayman LL, et al. Update: ambulatory blood pressure monitoring in children and adolescents. Hypertension. 2014;63(5):1116–1135.


b SBP load % is defined as number of SBP readings above the normal value divided by the total number of blood pressure readings × 100.


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Figure 106.1. Determining the proper cuff size in the pediatric patient. A, Marking the scapula extending from the acromion process. B, Correct tape placement for upper arm length. C, Incorrect tape placement for upper arm length. D, Marking upper arm length at the midpoint.


Reprinted with permission from Flynn JT, Kaelber DC, Baker-Smith CM, et al; American Academy of Pediatrics Subcommittee on Screening and Management of High Blood Pressure in Children. Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics. 2017;140(3):e20171904.


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a Calculated so that the largest arm would still allow bladder to encircle arm by at least 80 percent. Reprinted with permission from National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Washington, DC: National Heart, Lung, and Blood Institute; May 2005. NIH publication 05–5267.


Various methods of monitoring BP are used in pediatric practice, including manual auscultatory aneroid sphygmomanom-eters and oscillometric automated devices, the latter of which use mean arterial pressure to calculate systolic and diastolic BP. The pediatrician should ensure that all devices are validated for pediatric ages using a resource such as www.dableducational.org. Oscillometric devices are known to correlate significantly with arterial BP, although a tendency exists for higher systolic and slightly higher diastolic pressures with portable devices. Therefore, according to the 2017 AAP CPG, after obtaining a BP reading with elevated BP using an automated oscillometric device, BP measurements must be repeated twice more and an average of the measurements calculated. If the BP remains elevated, the BP should be confirmed using a manual auscultatory aneroid device.


Epidemiology


Based on the current definition of persistent HTN in children, the prevalence of HTN in the pediatric population is approximately 4% to 5%; however, the prevalence of HTN is 10% in children with elevated BP who are at risk for HTN. Hypertension can vary depending on patient factors such as age, ethnicity, and geographic distribution as well as type of HTN. Recent data suggest that the overall prevalence of HTN has decreased among children of normal weight in the past decade. Among children with obesity, however, recent studies indicate that the prevalence of HTN is between 2- and 5-fold, compared with children of normal weight. Prevalence of HTN varies by the study population and the age group studied. Hypertension in pediatrics remains a major health issue because of increasing prevalence of obesity, survival of preterm infants, and cultural and lifestyle changes, including increases in stress and sedentary behavior. As in adults, HTN is more common among black and Hispanic children compared with white children. Furthermore, adolescents and those from urban areas tend to have higher prevalence of HTN compared with younger children and those from rural areas. Recent evidence has also shown that parental socioeconomic status is a risk factor for development of HTN in childhood, with low income populations disproportionately affected. Primary care providers should recognize at-risk patient populations to identify HTN promptly and treat it appropriately to avoid long-term cardiovascular complications.


Secondary HTN is more common among infants and young children and is associated with other conditions, including most commonly renal and/or renovascular disease. Secondary HTN also can be caused by cardiovascular disease, such as coarctation of aorta or prior surgical repair of cardiovascular lesions, endocrine disorders, or environmental exposures. Children who require hospital admission for HTN usually have secondary HTN, which may have been triggered by an acute event—often volume overload.


Occasionally, the cause of HTN is uncertain. In many such children, the acutely increased BP resolves with appropriate medical intervention, and most children do not require long-term treatment. What is certain, however, is that essential HTN in childhood increases the risk for adult HTN and metabolic syndrome.


Etiology and Pathophysiology


An increase in BP results from an increase in peripheral resistance or cardiac output or a combination of these. In 90% to 95% of adults, the precise cause of HTN is uncertain; hence, the term essential, primary, or idiopathic HTN. Historically, HTN was considered secondary to an underlying disorder in more than 80% of children, and fewer than 20% of cases were idiopathic; however, this was true only in children with very severe HTN. Adolescents with obesity and mildly elevated BP in whom no etiology of HTN is identified often have a family history of HTN and are classified as having essential HTN.


Many factors play a role in the development of essential HTN. Research reveals variable degrees of alteration in cardiac output, extracellular fluid volume, peripheral resistance, renin-angiotensin system, aldosterone, electrolyte balance, catecholamines, sympathetic nervous system, natriuretic hormones, prostaglandins, kinins, antidiuretic hormone, insulin response, endothelin, nitric oxide (ie, endothelium-derived relaxing factor), and others. Whether these abnormalities are primary or secondary and what their exact role is in the pathogenesis of essential HTN remains uncertain.


Additionally, several maternal factors, such as smoking, alcohol consumption, diet, obesity, diabetes, and hypothyroidism/hyperthyroidism may influence epigenetic pathways. Epigenetic changes occur as a result of methylation or acetylation of the noncoding gene segment (ie, histones) that can change the chromosomal configuration and result in activation or inhibition of a specific gene transcription (ie, turning the gene on or off), which may result in abnormal developmental. This hypothesis has been further supported by data demonstrating an association between fewer neph-rons (resulting from underexpression of genes responsible for branching) in children who were born small for gestational age and later developed HTN. Thus, it is quite important to optimize maternal health to prevent potentially long-term adverse effects on the fetus.


Other important factors in the development of HTN include ethnicity, heredity, stress response, sleep apnea, obesity, hyperlipidemia, and increased salt intake. Studies showing that weight reduction in patients with obesity results in reduced BP strengthen the argument that obesity contributes to HTN.


Secondary HTN is more likely to exist in very young children with HTN, those who meet the criteria for stage 2 HTN, and those with systemic symptoms of HTN. The etiology of secondary HTN varies based on patient age and the nature of the HTN, that is, whether the condition is acute or chronic. Renal abnormalities account for 70% to 80% of secondary HTN in children. The pathogenesis of the HTN may be related to an increase in extracellular fluid volume (eg, acute glomerulonephritis, chronic renal failure), an increase in renin-angiotensin II activity (eg, renal artery stenosis, renin-producing tumor, pheochromocytoma, reflux nephropathy), or a combination of both mechanisms (eg, a patient with chronic renal failure caused by reflux nephropathy). Additionally, in young children, HTN may rarely be caused by a disorder with a single gene mutation that affects different pathways related to renal sodium handling.


Clinical Presentation


In most children, elevated BP, white coat HTN, masked HTN, and stage 1 HTN usually are asymptomatic. With stage 2 HTN, however, a child can develop headache or blurring of vision and, less commonly, nosebleed, changes in mental status, vomiting, and cardiac complaints (eg, chest pain, palpitations). Acute presentations of HTN are divided into 2 categories: hypertensive urgency and hypertensive emergency. Hypertensive urgency is defined by the sudden development of elevated BP without evidence of severe end-organ damage or life-threatening symptoms but may present with more mild symptoms, such as headache and vomiting. A hypertensive emergency, often called hypertensive crisis, in comparison, is defined by obvious signs of significant end-organ damage and life-threatening symptoms, such as encephalopathy, seizure, papilledema, retinal hemorrhage, and kidney injury. In children, these conditions usually are caused by secondary HTN rather than primary HTN. Cases of hypertensive urgency and hypertensive emergency both warrant immediate evaluation and referral to an emergency department for treatment.


Differential Diagnosis


An effort should be made to identify the cause of HTN in all young children because only 30% of them are likely to have essential HTN. In older children and adolescents with mildly elevated BP, essential HTN is the most likely diagnosis. In the setting of stage 1 or 2 HTN, however, a detailed history, complete physical examination, and simple laboratory tests to identify etiology should be completed (Boxes 106.1 and 106.2).


Evaluation


Blood pressure measurement should be part of the annual routine physical examination for all children older than 3 years and for all hospitalized children. If BP is normal in the annual examination, routine BP measurements between that examination and the next annual examination are not required. Regardless of age, however, all children with risk factors such as history of prematurity, congenital heart disease, recurrent urinary tract infections, renal disease, or chronic systemic illnesses, should undergo BP measurement as a routine part of every visit.


The physician also should verify that an appropriately sized cuff is being used for BP measurement and that efforts have been made to put the child at ease. Many children develop mild increases of BP (which can extend into the hypertensive range) when they visit a doctor’s office because of anxiety or apprehension (ie, white coat HTN). In the patient with a BP measurement in the elevated, stage 1, or stage 2 HTN ranges, BP should be reassessed with at least 2 additional measurements in the same clinic visit by oscillometric or auscultatory BP and the values averaged. If the averaged BP remains elevated based on oscillometric technique alone, BP should be remeasured twice by auscultation with stethoscope and appropriate sphygmomanometer by a trained professional to confirm the reading.



Box 106.1. Causes of Acute or Intermittent Increases in Blood Pressure in Children


Renal


Acute glomerulonephritis


Hemolytic uremic syndrome


Henoch-Schönlein purpura nephritis


Renal trauma


Renal artery or vein thrombosis


After renal biopsy


Acute obstructive uropathy


After genitourinary surgery


Blood transfusion in the patient with renal failure


After kidney transplant or with transplant rejection


Drug-induced


Corticosteroids


Amphetamine overdose


Phencyclidine hydrochloride overdose


Cocaine overdose


Anabolic steroids


Oral contraceptives


Excessive erythropoietin use in the patient with end-stage renal disease


Cyclosporine A and tacrolimus


Central Nervous System


Increased intracranial pressure (eg, subdural hematoma, meningitis, tumors)


Encephalitis


Poliomyelitis


Guillain-Barré syndrome


Porphyria


Familial dysautonomia


Miscellaneous


Wrong blood pressure cuff size


Anxiety, apprehension (ie, white coat hypertension)


Pain


Fracture


Immobilization


Orthopedic procedures, especially leg lengthening and those requiring traction


Abdominal wall defect


Burns


Leukemia


Stevens-Johnson syndrome


Bacterial endocarditis


Hypernatremia


Hypercalcemia


Heavy metal poisoning

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