US Pharm. 2010;35(3):HS-8-HS-15.
Hypertension has become a significant pediatric health problem owing to the increased number of overweight children. Over the past two decades, a steep rise in the prevalence of childhood obesity has been seen.1 As the prevalence of hypertension has increased, a direct relationship between weight and systolic blood pressure (SBP) has been reported.2,3 In 2004, almost 20% of children aged 6 to 11 years were obese (body-mass index [BMI] ≥95th percentile) and slightly more than 30% were overweight or at risk of overweight (BMI ≥85th percentile).4 A recent study estimated the incidence of obesity in 35-year-olds in 2020 based on the prevalence of overweight adolescents in 2000. The investigators projected that there would be a considerable increase in obesity, which could lead to a significant increase in adult coronary heart disease.5 In addition to hypertension, obesity in children and adolescents may lead to other comorbidities, such as type 2 diabetes, obstructive sleep apnea, dyslipidemia, and metabolic syndrome.6 According to recent epidemiologic studies, hypertension is currently diagnosed in approximately 5% of adolescents.7,8
Hypertension can be secondary to another disease process, or it can be primary (also known as essential). Secondary hypertension, which is more common in pediatric patients, is most often caused by renal disease, coarctation of the aorta, or endocrine disease.9 Primary hypertension usually is associated with a positive family history of hypertension or cardiovascular disease. It has been observed that patients with primary hypertension frequently are overweight and that the prevalence of hypertension increases with increasing BMI.10
Diagnosis and Monitoring
The current guidelines of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents recommend that BP monitoring begin in children over the age of 3 years.11 BP should be measured at each health care visit via auscultation. When measuring BP in children, it is important that the appropriate cuff size be used, based on the size of the child’s upper arm. A cuff that is too large will cause BP to be underestimated, whereas a cuff that is too small will cause it to be overestimated. In addition, it is recommended that the child avoid stimulants (e.g., caffeine, medications), be in a nonthreatening environment when measured, and sit quietly for 5 minutes with the back supported and the arm supported at the level of the heart. Based on certain conditions, some children should have their BP measured before age 3 years.11 Conditions that warrant BP measurement in children younger than 3 years are listed in TABLE 1.11
Classification and Staging
In children and adolescents, normal BP is based on gender, age, and height. The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents provides tables including the 50th, 90th, 95th, and 99th percentiles by gender, age, and height (see TABLE 2 for an example).11 The height percentile is determined by using the Centers for Disease Control and Prevention growth charts. Once the height percentile and BP are obtained, the SBP and DBP percentiles can be determined by finding the child’s age on the left side of the table and following the age row horizontally across the table to the intersection of the column for the height percentile.11
Prehypertension is defined as average SBP or diastolic BP (DBP) between the 90th and 95th percentiles, or BP ≥120/80 mmHg in an adolescent. Guidelines state that if a patient’s BP is >90th percentile, BP should be remeasured during the same visit and an average of the two readings should be used.11 Hypertension is defined as SBP and/or DBP ≥95th percentile for gender, age, and height on at least three occasions. Once it is recognized that a patient has hypertension, the disease should be staged. Stage 1 hypertension is defined as between the 95th and 99th percentiles plus 5 mmHg; stage 2 hypertension is defined as >99th percentile plus 5 mmHg (TABLE 3).11
As with adults, initial therapy for hypertension in children and adolescents includes diet and exercise.11,12 Weight loss, particularly for the obese child, often will prevent the addition of pharmacologic therapy.12 Nonpharmacologic dietary interventions recommended for adults (including increased intake of fruits and vegetables, consumption of low-fat dairy products, and sodium restriction) may also be beneficial for children and adolescents. Current recommendations for sodium intake are 1.2 g/day for children aged 4 to 8 years and 1.5 g/day for those older than 8 years. Reducing dietary sodium is expected to provide a decrease in BP of 1 mmHg to 3 mmHg.11 Additional interventions include the cessation of alcohol and tobacco products, along with increased exercise.11 Patients should be encouraged to engage in 30 to 60 minutes of physical activity daily and to minimize (i.e., <2 hours) time spent in sedentary activities, including watching television and playing video or computer games.11 There are limitations on the types of activities children with uncontrolled or severe hypertension should participate in. Currently, it is recommended that patients with severe hypertension (>99th percentile) avoid competitive and high static sports, including, but not limited to, activities such as gymnastics, water skiing, weight lifting, and wrestling.11,13
Pharmacotherapy is indicated for patients with secondary hypertension and for those who are unable to control BP through diet and exercise.11 Currently recommended agents for the treatment of hypertension in pediatric patients include angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics.11 Patients should be treated to a goal BP of <95th percentile; in patients with comorbid conditions, however, treatment should aim for a goal of <90th percentile. The choice of initial agent is based largely upon clinician preference or compelling indications, as evidence of the impact on clinical outcomes is lacking.11 For example, a BB or alpha antagonist would be most beneficial in a patient with high catecholamine levels.12 For a diabetic patient, an ACE inhibitor would be ideal.11 Additional conditions to take into consideration when selecting an agent are the presence of symptomatic hypertension, secondary causes of hypertension, target-organ damage, and persistent hypertension despite nonpharmacologic interventions.11
Several ACE inhibitors have been studied in children, with captopril having the most evidence. Enalapril, lisinopril, and ramipril have been assessed in small trials and pharmacokinetic studies.14 In the treatment of adult hypertension, it is well established that this class of medications has disparities in efficacy according to race. A recently published meta-analysis evaluated results from six trials submitted to the FDA to determine whether these differences were present among children as well. Agents studied included benazepril, enalapril, fosinopril, lisinopril, quinapril, and ramipril. This analysis found that, even with high-dose therapy, African American children did not respond to ACE inhibitor therapy as well as children of other races did.15
CCBs are also commonly prescribed for pediatric patients. Nifedipine, isradipine, amlodipine, and nicardipine have the most evidence for use. Short-acting nifedipine is typically used for hypertensive crisis. Data regarding the use of extended-release nifedipine are limited; however, anecdotal reports show that it has been well tolerated when given at doses less than 120 mg/day.16 Retrospective data for isradipine are available. These trials utilized a much higher dose than that recommended for adults and administered the drug multiple times per day, which may limit the usefulness of the drug.16 Amlodipine may be a more desirable alternative owing to its longer half-life and capacity for once-daily dosing. Additionally, an amlodipine suspension may be prepared that has extended stability. Nicardipine is largely used intravenously for treatment of severe hypertension.16
Outside of hypertension associated with renal disease, data are extremely limited regarding the use of ARBs for the treatment of pediatric hypertension. Since the publication of recent guidelines, two studies have been published that examined the use of valsartan and candesartan.17,18 In an open-label, uncontrolled trial, candesartan 8 mg was shown to effectively lower BP in 11 children aged 6 to 18 years.17 A study of 90 patients aged 1 year to 5 years found valsartan 20 mg, 40 mg, and 80 mg to be effective. This study also evaluated valsartan’s effects on growth and development. No significant changes between valsartan and placebo were seen for length per height for age or BMI throughout the study. Developmental skills such as language and motor ability and social development all progressed normally.18
Beta-blockers are used less often owing to complications with disease states such as diabetes and asthma and the development of lipid abnormalities after long-term use.11,12 Consideration should be given to BBs in the presence of severe hypertension or when combination therapy is needed. Additionally, the use of diuretics is often reserved for patients with renal disease or when combination therapy is needed.14
TABLE 4 describes commonly used medications for the treatment of pediatric hypertension, along with dose recommendations and side effects.11,15,16
When treatment for hypertension is initiated, a 6-month trial of nonpharmacologic interventions should be attempted. If BP goals are not met after this time, pharmacologic therapy should be started. The patient should be seen every 2 weeks and medications adjusted until the goal BP is achieved. Once the patient has sustained a normal BP for 6 months, the physician may elect to begin discontinuing pharmacotherapy. If pharmacotherapy is discontinued entirely, the patient should be seen again in 6 months; if normal BP is maintained, yearly visits are appropriate.13 As the long-term effects of antihypertensive therapy, both beneficial and detrimental, are currently not known, discontinuation of therapy may be warranted in patients who have successfully incorporated lifestyle modifications into their treatment regimen.11
The prevalence of hypertension among children has increased in response to the increased prevalence of childhood obesity. Despite this increase, secondary causes remain the most common reason for hypertension in this patient population. Monitoring of BP using appropriate techniques should begin when the child reaches the age of 3 years. Percentiles are used to determine whether a child’s BP is appropriate and take into consideration gender, age, and height. Nonpharmacologic measures such as diet and exercise can be very successful, particularly for the obese child; however, pharmacotherapy will likely be needed in patients with secondary causes of hypertension. ACE inhibitors and CCBs are commonly prescribed, owing to a better adverse-effect profile. Additional agents such as ARBs, BBs, and diuretics may be included as part of a multidrug regimen.
Pharmacists can play a key role in the treatment of children with hypertension. Encouraging lifestyle modifications, ensuring that the pharmacotherapy plan is appropriate, providing adequate counseling, and assisting in the monitoring of the patient’s BP are a few examples of how the pharmacist can assist in the treatment of pediatric hypertension.
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