Prevalence of Hypertension in Children

In infants and young children, systemic hypertension is uncommon, with a prevalence of <1%, but when present, it is often indicative of an underlying disease process (secondary hypertension). Severe and symptomatic hypertension in children is usually due to secondary hypertension. In contrast, the prevalence of primary essential hypertension, mostly in older school age children and adolescents, has increased in prevalence in parallel with the obesity epidemic. Approximately 10% of U.S. youth overall have prehypertension and 4% have hypertension. The influence of obesity on elevated BP is evident in children as young as 2-5 yr old. Approximately 20% of American youth are obese, and up to 10% of obese youth have hypertension.

Definition of Hypertension

The definition of hypertension in adults is BP ≥140/90 mm Hg, regardless of body size, sex, or age. This is a functional definition relating level of BP elevation with the likelihood of subsequent cardiovascular events. Since hypertension-associated cardiovascular events such as myocardial infarction or stroke usually do not occur in childhood, the definition of hypertension in children is statistical rather than functional. The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents published the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents (Fourth Report) in 2004. This report established normal values based on the normative distribution of BP in healthy children and included tables with systolic and diastolic values for the 50th, 90th, 95th, and 99th percentile by age, sex, and height percentile. These normative tables can be obtained free online at www.nhlbi.nih.gov/guidelines/hypertension/child_tbl.htm. The Fourth Report defined hypertension as average systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) that is ≥95th percentile for age, sex, and height on ≥3 occasions. Prehypertension was defined as average SBP or DBP that are ≥90th percentile but <95th percentile. In adolescents beginning at age 12 yr, prehypertension is defined as BP between 120/80 mm Hg and the 95th percentile. A child with BP levels ≥95th percentile in a medical setting but normal BP outside of the office has white coat hypertension.

The Fourth Report further recommended that if BP is ≥95th percentile, then the hypertension should be staged. Children with BP between the 95th and 99th percentile plus 5 mm Hg are categorized as stage 1 hypertension, and children with BP above the 99th percentile plus 5 mm Hg have stage 2 hypertension. Stage 1 hypertension, if asymptomatic and without target organ damage, allows time for evaluation before starting treatment; whereas stage 2 hypertension calls for more prompt evaluation and pharmacologic therapy (Fig. 439-1).

Figure 439-1 Management algorithm. BMI, body mass index; BP, blood pressure; Q, every; Rx, prescription; † diet modification and physical activity; ‡ especially if younger, very high BP, little or no family history, diabetic, or other risk factors.

(From National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents, Pediatrics 114[2 Suppl 4th Report]:571, 2004.)

Measurement of BP in Children

The Fourth Report recommended that children 3 yr or older should have their BP checked during every health care episode. Selected children <3 yr old should also have their BP checked, including those with a history of prematurity, congenital heart disease, renal disease, solid organ transplant, cancer, treatment with drugs known to raise BP, other illnesses associated with hypertension, or evidence of increased intracranial pressure. The preferred method is by auscultation and a BP cuff appropriate for the size of the child’s arm should be used. Elevated readings should be confirmed on repeat visits before determining that a child is hypertensive. The BP should be measured with the child in the sitting position after a period of quiet for at least 5 min. Careful attention to cuff size is necessary to avoid overdiagnosis, as a cuff that is too short or narrow artificially increases BP readings. A wide variety of bladder sizes should be available in any medical office where children are routinely seen. An appropriate sized cuff has an inflatable bladder that is at least 40% of the arm circumference at a point midway along the upper arm. The inflatable bladder should cover at least two thirds of the upper arm length and 80-100% of its circumference.

Systolic pressure is indicated by appearance of the 1st Korotkoff sound. Diastolic pressure has been defined by consensus as the 5th Korotkoff sound. Palpation is useful for rapid assessment of SBP, although the palpated pressure is generally about 10 mm Hg less than that obtained via auscultation. Oscillometric techniques are used frequently in infants and young children, but they are susceptible to artifacts and are best for measuring mean BP.

Ambulatory blood pressure monitoring (ABPM) is a procedure where the child wears a device that records BP frequently, usually every 20-30 min, throughout a 24 hr period while the child goes about usual daily activities, including sleep. This allows calculation of the mean daytime BP, sleep BP, and mean BP over 24 hr. The physician can also determine the proportion of BP measurements that are in the hypertensive range (BP load) and whether there is an appropriate decrease in BP during sleep (nocturnal dip). ABPM is particularly useful in the evaluation for white coat hypertension and may also be useful for determining risk of hypertensive target organ damage, evaluating resistance to pharmacologic therapy, and evaluating patients with hypotensive episodes on antihypertensive medication. ABPM is also useful for certain special populations, such as children with chronic kidney disease, where it may provide important information on cardiovascular risk that cannot be determined as well by office measurements.

Etiology and Pathophysiology

BP is the product of cardiac output and peripheral vascular resistance. An increase in either cardiac output or peripheral resistance results in an increase in BP; if one of these factors increases while the other decreases, BP may not increase. When hypertension is the result of another disease process, it is referred to as secondary hypertension. When no identifiable cause can be found, it is referred to as primary (essential) hypertension. Many factors, including heredity, diet, stress, and obesity, may play a role in the development of primary hypertension. Secondary hypertension is most common in infants and younger children. In general, the younger the child, the higher the BP and the presence of symptoms related to hypertension, the more likely there will be an underlying secondary cause of hypertension. Many childhood diseases can be responsible for chronic hypertension (Table 439-1) or acute/intermittent hypertension (Table 439-2). The most likely cause varies with age. Hypertension in the premature infant is most often associated with umbilical artery catheterization and renal artery thrombosis. Hypertension during early childhood may be due to renal disease, coarctation of the aorta, endocrine disorders, or medications. In older school-aged children and adolescents, primary hypertension becomes increasingly common.

Secondary hypertension in children is most commonly due to renal abnormalities; cardiovascular disease or endocrinopathies are additional etiologies. Renal (chronic glomerulonephritis, reflux or obstructive nephropathy, hemolytic uremic syndrome, polycystic or dysplastic renal diseases), or renovascular hypertension account for approximately 90% of children with secondary hypertension. Renal parenchymal disease and renal artery stenosis lead to water and sodium retention thought to be, in part, secondary to increased renin secretion. Coarctation of the aorta should always be considered. Several endocrinopathies are associated with hypertension, usually those involving the thyroid, parathyroid, and adrenal glands. Systolic hypertension and tachycardia are common in hyperthyroidism; diastolic pressure is not usually elevated. Hypercalcemia, whether secondary to hyperparathyroidism or other causes, often results in mild elevation in BP because of an increase in vascular tone. Adrenocortical disorders (aldosterone-secreting tumors, sodium retaining congenital adrenal hyperplasia, Cushing syndrome) may produce hypertension in patients with increased mineralocorticoid secretion. Pheochromocytomas are catecholamine-secreting tumors that give rise to hypertension because of the cardiac and peripheral vascular effects of epinephrine and norepinephrine. Children with pheochromocytoma usually have sustained rather than intermittent or exercise-induced hypertension. Pheochromocytoma develops in approximately 5% of patients with neurofibromatosis. Rarely, secondary hypertension can be due to pseudohyperaldosteronism, which leads to elevated BP in the face of a suppressed renin level. Such disorders include Liddle syndrome, apparent mineralocorticoid excess, and dexamethasone suppressible aldosteronism. Altered sympathetic tone can be responsible for acute or intermittent elevation of BP in children with Guillain-Barré syndrome, poliomyelitis, burns, and Stevens-Johnson syndrome. Sympathetic outflow from the central nervous system is also affected by intracranial lesions.

A number of drugs of abuse, therapeutic agents, and toxins may cause hypertension. Cocaine may provoke a rapid increase in BP and can result in seizures or intracranial hemorrhage. Phencyclidine causes transient hypertension that may become persistent in chronic abusers. Tobacco use may also increase BP. Sympathomimetic agents used as nasal decongestants, appetite suppressants, and stimulants for attention deficit disorder produce peripheral vasoconstriction and varying degrees of cardiac stimulation. Individuals vary in their susceptibility to these effects. Oral contraceptives should be suspected as a cause of hypertension in adolescent girls, although the incidence is lower with the use of low-estrogen preparations. Immunosuppressant agents such as cyclosporine and tacrolimus cause hypertension in organ transplant recipients, and the effect is exacerbated by the co-administration of steroids. BP may be elevated in patients with poisoning by a heavy metal.

Children and adolescents with primary (essential) hypertension are commonly overweight, often have a strong family history of hypertension, and usually have BP values at or only slightly above the 95th percentile for age. Primary hypertension is the most common form of hypertension in adults, and it is recognized more often in adolescents than in young children. The cause of primary hypertension is likely to be multifactorial; obesity, genetic alterations in calcium and sodium transport, vascular smooth muscle reactivity, the renin-angiotensin system, sympathetic nervous system overactivity, and insulin resistance have been implicated in this disorder. Elevated uric acid levels may play a role in the pathophysiology of primary hypertension. Some children and adolescents demonstrate salt-sensitive hypertension, a factor that is ameliorated with weight loss and sodium restriction.

Normotensive children of hypertensive parents may show abnormal physiologic responses that are similar to those of their parents. When subjected to stress or competitive tasks, the offspring of hypertensive adults, as a group, respond with greater increases in heart rate and BP than do children of normotensive parents. Similarly, some children of hypertensive parents may excrete higher levels of urinary catecholamine metabolites or may respond to sodium loading with greater weight gain and increases in BP than do those without a family history of hypertension. The abnormal responses in children with affected parents tend to be greater in the black population than among white individuals.

Tracking of BP is the process by which individuals maintain their relative ranking of BP over time with respect to their peers. Children and young adolescents with BP greater than the 90th percentile for age have a nearly threefold greater likelihood of becoming adults with hypertension than do children with BP at the 50th percentile. Adolescents with primary hypertension may progress from high cardiac output and normal systemic vascular resistance to the adult pattern of normal cardiac output with elevated systemic vascular resistance.

Clinical Manifestations

Children and adolescents with primary hypertension are usually asymptomatic; the BP elevation is usually mild and is detected during a routine examination or evaluation before athletic participation. These children may also be obese. Children with secondary hypertension can have BP elevations ranging from mild to severe. Unless the pressure has been sustained or is rising rapidly, hypertension does not usually produce symptoms. Therefore, clinical manifestations may instead reflect the underlying disease process, such as growth failure in children with chronic kidney disease. With substantial hypertension, headache, dizziness, epistaxis, anorexia, visual changes, and seizures may occur. Hypertensive encephalopathy (generalized or posterior reversible encephalopathy syndrome [PRES]) is suggested by the presence of vomiting, temperature elevation, ataxia, stupor, CT abnormalities, and seizures. Cardiac failure, pulmonary edema, and renal dysfunction (malignant hypertension) may occur in the face of marked hypertension. Bell palsy may be seen in asymptomatic or symptomatic patients; the etiology is unknown. Hypertensive crisis may manifest with decreased vision (retinal hemorrhages of hypertensive retinopathy) and papilledema, encephalopathy (headache, seizures, depressed level of consciousness), heart failure, or accelerated deterioration of renal function.

Subclinical hypertensive target-organ injury is a common clinical manifestation in children with essential hypertension. With the use of echocardiography utilizing pediatric normative data, left ventricular hypertrophy is detected in up to 40% of hypertensive children. Other markers of target organ damage that have been demonstrated in hypertensive children include increased carotid intima-media thickness, hypertensive retinopathy, and microalbuminuria.

Diagnosis

The evaluation of the child with chronic hypertension should be directed toward uncovering potential underlying causes of the hypertension, evaluating for co-morbidities, and screening for evidence of target organ damage. The extent of the evaluation for underlying causes of hypertension depends on the type of hypertension that is suspected. When secondary hypertension is a strong consideration, as in younger children with severe and symptomatic hypertension, an extensive evaluation may be necessary (Fig. 439-2). Alternatively, overweight adolescents with a family history of hypertension who have mild elevations of BP may need only a limited number of tests.

Figure 439-2 Initial diagnostic algorithm in the evaluation of hypertension.

(From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis and therapy, ed 2, Philadelphia, 2004, Elsevier, p 222.)

In all cases, a careful history and physical examination are warranted. A family history for early cardiovascular events should be obtained. Growth parameters should be determined to detect evidence of chronic disease. BP should be obtained in all 4 extremities to detect coarctation (thoracic or abdominal) of the aorta. Other features of the physical examination that may provide evidence of an underlying cause of hypertension are noted in Table 439-3. Unless the history and physical examination suggest another cause, children with confirmed hypertension should have an evaluation to detect renal disease, including urinalysis, electrolytes, BUN, creatinine, complete blood count, urine culture, and renal ultrasound. A more complete list of tests to consider in the clinical evaluation of a child with confirmed hypertension is given in Table 439-4.

Table 439-3 FINDINGS TO LOOK FOR ON PHYSICAL EXAMINATION

HSP, Henoch-Schönlein purpura; SLE, systemic lupus erythematosus.

From Kliegman RM, Greenbaum LA, Lye PS: Practical strategies in pediatric diagnosis and therapy, ed 2, Philadelphia, 2004, Elsevier, p 200.

Table 439-4 CLINICAL EVALUATION OF CONFIRMED HYPERTENSION

BUN, blood urea nitrogen; CBC, complete blood count; R/O, rule out; U/S, ultrasound.

* Co-morbid risk factors also include diabetes mellitus and kidney disease.

From National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents, Pediatrics 114(2 Suppl 4th Report):562, 2004.

Renovascular hypertension is often associated with other diseases (Table 439-5) but may be isolated. Doppler ultrasonography as well as captopril renography and MR or spiral CT angiography are helpful screening tests, but invasive angiography is often needed especially to detect intrarenal arterial stenosis (Fig. 439-3).

Figure 439-3 Renal angiogram in 7 yr old boy with hypertension. Right renal artery is visible with a string-of-beads appearance characteristic of fibromuscular dysplasia (arrows). The aorta and left renal artery appear normal.

(From Tullus K, Brennan E, Hamilton G, et al: Renovascular hypertension in children, Lancet 371:1453–1463, 2008; p 1454, Fig 1.)

Primary hypertension often clusters with other risk factors. All hypertensive children should be screened for co-morbidities that may increase cardiovascular risk, including hyperlipidemia and glucose intolerance. A fasting lipid panel and fasting glucose level should be obtained. In addition, a sleep history should be obtained in children with confirmed hypertension to screen for disordered sleep breathing, an entity that is associated with high BP, particularly in overweight children.

Left ventricular hypertrophy (LVH) is the most common manifestation of target organ damage in hypertensive children. All children with confirmed hypertension should have echocardiography to evaluate for the presence of LVH. Left ventricular mass measurements should be indexed to height (m^2.7) to account for the effect of body size. The presence of LVH is an indication to treat the hypertension with pharmacologic therapy.

Prevention

Prevention of high BP may be viewed as part of the prevention of cardiovascular disease and stroke, the leading cause of death in adults in the USA. Other risk factors for cardiovascular disease include obesity, elevated serum cholesterol levels, high dietary sodium intake, a sedentary lifestyle, as well as alcohol and tobacco use. The increase in arterial wall rigidity and blood viscosity that is associated with exposure to the components of tobacco may exacerbate hypertension. Population approaches to prevention of primary hypertension include a reduction in obesity, reduced sodium intake, and an increase in physical activity through school and community-based programs.

Treatment

The Fourth Report recommended a management algorithm for children with confirmed hypertension according to whether the child has prehypertension, stage 1 hypertension, or stage 2 hypertension (Figs. 439-1 and 439-4). The mainstay of therapy for children with asymptomatic mild hypertension without evidence of target organ damage is therapeutic lifestyle modification with dietary changes and regular exercise. Weight loss is the primary therapy in obesity-related hypertension. It is recommended that all hypertensive children have a diet increased in fresh fruits, fresh vegetables, fiber, and nonfat dairy and reduced in sodium. In addition, regular aerobic physical activity for at least 30-60 min on most days along with a reduction of sedentary activities to less than 2 hr per day is recommended. Indications for pharmacologic therapy include symptomatic hypertension, secondary hypertension, hypertensive target organ damage, diabetes (types 1 and 2), and persistent hypertension despite nonpharmacologic measures (Table 439-6). When indicated, antihypertensive medication should be initiated as a single agent at low dose (see Fig. 439-4). The dose can then be increased until the goal BP is achieved. Once the highest recommended dose is reached or if the child develops side effects, then a second drug from a different class can be added. Acceptable drug classes for use in children include ACE inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, and diuretics. Details on recommended doses of different classes of antihypertensive medications for children can be found in the Fourth Report available free online at www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.pdf.

Figure 439-4 Stepped-care approach to antihypertensive therapy in children and adolescents. BP, blood pressure.

(From Flynn JT, Daniels SR: Pharmacologic treatment of hypertension in children and adolescents, J Pediatr 149:746–754, 2006; p 751, Fig 2.)

The goal of therapy for hypertension should be to reduce BP below the 95th percentile, except in the presence of chronic kidney disease, diabetes, or target organ damage, when the goal should be to reduce BP to less than the 90th percentile. ACE inhibitors or angiotensin receptor blockers should be used for children with diabetes and microalbuminuria or proteinuric renal disease. β-Blockers or calcium channel blockers should be considered for hypertensive children with migraine headaches.

Severe, symptomatic hypertension is a hypertensive emergency that is often accompanied by cardiac failure, retinopathy, renal failure, encephalopathy, and seizures. Intravenous administration is often preferred so that the fall in BP can be carefully titrated (Table 439-7). Drug choices include labetalol, nicardipine, and sodium nitroprusside. Because too rapid a reduction in BP may interfere with adequate organ perfusion, a stepwise reduction in pressure should be planned. In general, the pressure should be reduced by 10% in the 1st hour, and 15% more in the next 3-12 hr, but not to normal during the acute phase of treatment. Hypertensive urgencies, usually accompanied by few serious symptoms such as severe headache or vomiting, can be treated either orally or intravenously. The Fourth Report also includes detailed information on antihypertensive drugs used for the management of severe hypertension in children.

Treatment of secondary hypertension must also focus on the underlying disease such as chronic renal disease, hyperthyroidism, adrenal-genital syndrome, pheochromocytoma, coarctation of the aorta, or renovascular hypertension. The treatment of renovascular stenosis includes antihypertensive medications, angioplasty, or surgery (Fig. 439-5). If bilateral renovascular hypertension or renovascular disease in a solitary kidney is suspected, drugs acting on the renin-angiotensin axis are usually contraindicated because they may reduce glomerular filtration rates and produce renal failure. Balloon angioplasty or surgical revascularization should then be attempted.

Figure 439-5 Treatment pathway for renovascular hypertension.

(From Tullus K, Brennan E, Hamilton G, et al: Renovascular hypertension in children, Lancet 371:1453–1463, 2008; p 1458, Fig 6.)