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SUPPLEMENT ARTICLE |
Abbreviations: BP, blood pressure • NHBPEP, National High Blood Pressure Education Program • SBP, systolic blood pressure • DBP, diastolic blood pressure • NHANES, National Health and Nutrition Examination Survey • JNC 7, Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure • NHLBI, National Heart, Lung, and Blood Institute • ABPM, ambulatory blood pressure monitoring • CVD, cardiovascular disease • BMI, body mass index • PRA, plasma renin activity • DSA, digital-subtraction angiography • ACE, angiotensin-converting enzyme • MRA, magnetic resonance angiography • CT, computed tomography • LVH, left ventricular hypertrophy
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INTRODUCTION |
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 TOP INTRODUCTION METHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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The purpose of this report is to update clinicians on the latest scientific evidence regarding BP in children and to provide recommendations for diagnosis, evaluation, and treatment of hypertension based on available evidence and consensus expert opinion of the working group when evidence was lacking. This publication is the fourth report from the National High Blood Pressure Education Program (NHBPEP) Working Group on Children and Adolescents and updates the previous 1996 publication, "Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents."1
This report includes the following information:
95th percentile. BP between the 90th and 95th percentile in childhood had been designated "high normal." To be consistent with the Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7), this level of BP will now be termed "prehypertensive" and is an indication for lifestyle modifications.2 |
METHODS |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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The background papers served as focal points for review of the scientific evidence at the first meeting. The members of the working group were assembled into teams, and each team prepared specific sections of the report. In developing the focus of each section, the working group was asked to consider the peer-reviewed scientific literature published in English since 1997. The scientific evidence was classified by the system used in the JNC 7.2 The chair assembled the sections submitted by each team into the first draft of the report. The draft report was distributed to the working group for review and comment. These comments were assembled and used to create the second draft. A subsequent on-site meeting of the working group was conducted to discuss additional revisions and the development of the third-draft document. Amended sections were reviewed, critiqued, and incorporated into the third draft. After editing by the chair for internal consistency, the fourth draft was created. The working group reviewed this draft, and conference calls were conducted to resolve any remaining issues that were identified. When the working group approved the final document, it was distributed to the Coordinating Committee for review.
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DEFINITION OF HYPERTENSION |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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95th percentile for gender, age, and height on 3 occasions. 90th percentile but <95th percentile. 120/80 mm Hg should be considered prehypertensive.
The definition of hypertension in children and adolescents is based on the normative distribution of BP in healthy children. Normal BP is defined as SBP and DBP that are <90th percentile for gender, age, and height. Hypertension is defined as average SBP or DBP that is 95th percentile for gender, age, and height on at least 3 separate occasions. Average SBP or DBP levels that are 90th percentile but <95th percentile had been designated as "high normal" and were considered to be an indication of heightened risk for developing hypertension. This designation is consistent with the description of prehypertension in adults. The JNC 7 committee now defines prehypertension as a BP level that is 120/80 mm Hg and recommends the application of preventive health-related behaviors, or therapeutic lifestyle changes, for individuals having SBP levels that exceed 120 mm Hg.2 It is now recommended that, as with adults, children and adolescents with BP levels 120/80 mm Hg but <95th percentile should be considered prehypertensive.
The term white-coat hypertension defines a clinical condition in which the patient has BP levels that are >95th percentile when measured in a physician's office or clinic, whereas the patient's average BP is <90th percentile outside of a clinical setting.
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MEASUREMENT OF BP IN CHILDREN |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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Children >3 years old who are seen in medical care settings should have their BP measured at least once during every health care episode. Children <3 years old should have their BP measured in special circumstances (see Table 1).
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2 cm above the cubital fossa). The use of the bell of the stethoscope may allow softer Korotkoff sounds to be heard better.3,4 The use of an appropriately sized cuff may preclude the placement of the stethoscope in this precise location, but there is little evidence that significant inaccuracy is introduced, either if the head of the stethoscope is slightly out of position or if there is contact between the cuff and the stethoscope. Preparation of the child for standard measurement can affect the BP level just as much as technique.5 Ideally, the child whose BP is to be measured should have avoided stimulant drugs or foods, have been sitting quietly for 5 minutes, and seated with his or her back supported, feet on the floor and right arm supported, cubital fossa at heart level.6,7 The right arm is preferred in repeated measures of BP for consistency and comparison with standard tables and because of the possibility of coarctation of the aorta, which might lead to false (low) readings in the left arm.8 Correct measurement of BP in children requires use of a cuff that is appropriate to the size of the child's upper right arm. The equipment necessary to measure BP in children, ages 3 through adolescence, includes child cuffs of different sizes and must also include a standard adult cuff, a large adult cuff, and a thigh cuff. The latter 2 cuffs may be needed for use in adolescents.
By convention, an appropriate cuff size is a cuff with an inflatable bladder width that is at least 40% of the arm circumference at a point midway between the olecranon and the acromion (see www.americanheart.org/presenter.jhtml?identifier=576).9,10 For such a cuff to be optimal for an arm, the cuff bladder length should cover 80% to 100% of the circumference of the arm.1,11 Such a requirement demands that the bladder width-to-length ratio be at least 1:2. Not all commercially available cuffs are manufactured with this ratio. Additionally, cuffs labeled for certain age populations (eg, infant or child cuffs) are constructed with widely disparate dimensions. Accordingly, the working group recommends that standard cuff dimensions for children be adopted (see Table 2). BP measurements are overestimated to a greater degree with a cuff that is too small than they are underestimated by a cuff that is too large. If a cuff is too small, the next largest cuff should be used, even if it appears large. If the appropriate cuffs are used, the cuff-size effect is obviated.12
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The standard device for BP measurements has been the mercury manometer.14 Because of its environmental toxicity, mercury has been increasingly removed from health care settings. Aneroid manometers are quite accurate when calibrated on a semiannual basis15 and are recommended when mercury-column devices cannot be obtained.
Auscultation remains the recommended method of BP measurement in children under most circumstances. Oscillometric devices measure mean arterial BP and then calculate systolic and diastolic values.16 The algorithms used by companies are proprietary and differ from company to company and device to device. These devices can yield results that vary widely when one is compared with another,17 and they do not always closely match BP values obtained by auscultation.18 Oscillometric devices must be validated on a regular basis. Protocols for validation have been developed,19,20 but the validation process is very difficult.
Two advantages of automatic devices are their ease of use and the minimization of observer bias or digit preference.16 Use of the automated devices is preferred for BP measurement in newborns and young infants, in whom auscultation is difficult, and in the intensive care setting, in which frequent BP measurement is needed. An elevated BP reading obtained with an oscillometric device should be repeated by using auscultation.
Elevated BP must be confirmed on repeated visits before characterizing a child as having hypertension. Confirming an elevated BP measurement is important, because BP at high levels tends to fall on subsequent measurement as the result of 1) an accommodation effect (ie, reduction of anxiety by the patient from one visit to the next) and 2) regression to the mean. BP level is not static but varies even under standard resting conditions. Therefore, except in the presence of severe hypertension, a more precise characterization of a person's BP level is an average of multiple BP measurements taken over weeks to months.
ABPM
ABPM refers to a procedure in which a portable BP device, worn by the patient, records BP over a specified period, usually 24 hours. ABPM is very useful in the evaluation of hypertension in children.21–23 By frequent measurement and recording of BP, ABPM enables computation of the mean BP during the day, night, and over 24 hours as well as various measures to determine the degree to which BP exceeds the upper limit of normal over a given time period, ie, the BP load. ABPM is especially helpful in the evaluation of white-coat hypertension as well as the risk for hypertensive organ injury, apparent drug resistance, and hypotensive symptoms with antihypertensive drugs. ABPM is also useful for evaluating patients for whom more information on BP patterns is needed, such as those with episodic hypertension, chronic kidney disease, diabetes, and autonomic dysfunction. Conducting ABPM requires specific equipment and trained staff. Therefore, ABPM in children and adolescents should be used by experts in the field of pediatric hypertension who are experienced in its use and interpretation.
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BP TABLES |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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In children and adolescents, the normal range of BP is determined by body size and age. BP standards that are based on gender, age, and height provide a more precise classification of BP according to body size. This approach avoids misclassifying children who are very tall or very short.
The BP tables are revised to include the new height percentile data (www.cdc.gov/growthcharts)24 as well as the addition of BP data from the NHANES 1999–2000. Demographic information on the source of the BP data is provided in Appendix A. The 50th, 90th, 95th, and 99th percentiles of SBP and DBP (using K5) for height by gender and age are given for boys and girls in Tables 3 and 4. Although new data have been added, the gender, age, and height BP levels for the 90th and 95th percentiles have changed minimally from the last report. The 50th percentile has been added to the tables to provide the clinician with the BP level at the midpoint of the normal range. Although the 95th percentile provides a BP level that defines hypertension, management decisions about children with hypertension should be determined by the degree or severity of hypertension. Therefore, the 99th percentile has been added to facilitate clinical decision-making in the plan for evaluation. Standards for SBP and DBP for infants <1 year old are available.25 In children <1 year old, SBP has been used to define hypertension.
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90th percentile, the BP measurement should be repeated at that visit to verify an elevated BP. BP measurements between the 90th and 95th percentiles indicate prehypertension and warrant reassessment and consideration of other risk factors (see Table 5.) In addition, if an adolescent's BP is >120/80 mm Hg, the patient should be considered to be prehypertensive even if this value is <90th percentile. This BP level typically occurs for SBP at 12 years old and for DBP at 16 years old.
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95th percentile, the child may be hypertensive, and the measurement must be repeated on at least 2 additional occasions to confirm the diagnosis. Staging of BP, according to the extent to which a child's BP exceeds the 95th percentile, is helpful in developing a management plan for evaluation and treatment that is most appropriate for an individual patient. On repeated measurement, hypertensive children may have BP levels that are only a few mm Hg >95th percentile; these children would be managed differently from hypertensive children who have BP levels that are 15 to 20 mm Hg above the 95th percentile. An important clinical decision is to determine which hypertensive children require more immediate attention for elevated BP. The difference between the 95th and 99th percentiles is only 7 to 10 mm Hg and is not large enough, particularly in view of the variability in BP measurements, to adequately distinguish mild hypertension (where limited evaluation is most appropriate) from more severe hypertension (where more immediate and extensive intervention is indicated). Therefore, stage 1 hypertension is the designation for BP levels that range from the 95th percentile to 5 mm Hg above the 99th percentile. Stage 2 hypertension is the designation for BP levels that are >5 mm Hg above the 99th percentile. Once confirmed on repeated measures, stage 1 hypertension allows time for evaluation before initiating treatment unless the patient is symptomatic. Patients with stage 2 hypertension may need more prompt evaluation and pharmacologic therapy. Symptomatic patients with stage 2 hypertension require immediate treatment and consultation with experts in pediatric hypertension. These categories are parallel to the staging of hypertension in adults, as noted in the JNC 7.2
Using the BP Tables
120/80 mm Hg is prehypertension, even if this figure is <90th percentile.
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PRIMARY HYPERTENSION AND EVALUATION FOR COMORBIDITIES |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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High BP in childhood had been considered a risk factor for hypertension in early adulthood. However, primary (essential) hypertension is now identifiable in children and adolescents. Primary hypertension in childhood is usually characterized by mild or stage 1 hypertension and is often associated with a positive family history of hypertension or cardiovascular disease (CVD). Children and adolescents with primary hypertension are frequently overweight. Data on healthy adolescents obtained in school health-screening programs demonstrate that the prevalence of hypertension increases progressively with increasing body mass index (BMI), and hypertension is detectable in 30% of overweight children (BMI >95th percentile).26 The strong association of high BP with obesity and the marked increase in the prevalence of childhood obesity27 indicate that both hypertension and prehypertension are becoming a significant health issue in the young. Overweight children frequently have some degree of insulin resistance (a prediabetic condition). Overweight and high BP are also components of the insulin-resistance syndrome, or metabolic syndrome, a condition of multiple metabolic risk factors for CVD as well as for type 2 diabetes.28,29 The clustering of other CVD risk factors that are included in the insulin-resistance syndrome (high triglycerides, low high-density lipoprotein cholesterol, truncal obesity, hyperinsulinemia) is significantly greater among children with high BP than in children with normal BP.30 Recent reports from studies that examined childhood data estimate that the insulin-resistance syndrome is present in 30% of overweight children with BMI >95th percentile.31 Historically, hypertension in childhood was considered a simple independent risk factor for CVD, but its link to the other risk factors in the insulin-resistance syndrome indicates that a broader approach is more appropriate in affected children.
Primary hypertension often clusters with other risk factors.31,32 Therefore, the medical history, physical examination, and laboratory evaluation of hypertensive children and adolescents should include a comprehensive assessment for additional cardiovascular risk. These risk factors, in addition to high BP and overweight, include low plasma high-density lipoprotein cholesterol, elevated plasma triglyceride, and abnormal glucose tolerance. Fasting plasma insulin concentration is generally elevated, but an elevated insulin concentration may be reflective only of obesity and is not diagnostic of the insulin-resistance syndrome. To identify other cardiovascular risk factors, a fasting lipid panel and fasting glucose level should be obtained in children who are overweight and have BP between the 90th and 94th percentile and in all children with BP >95th percentile. If there is a strong family history of type 2 diabetes, a hemoglobin A1c or glucose tolerance test may also be considered. These metabolic risk factors should be repeated periodically to detect changes in the level of cardiovascular risk over time. Fewer data are available on the utility of other tests in children (eg, plasma uric acid or homocysteine and Lp[a] levels), and the use of these measures should depend on family history.
Sleep disorders including sleep apnea are associated with hypertension, coronary artery disease, heart failure, and stroke in adults.33,34 Although limited data are available, they suggest an association of sleep-disordered breathing and higher BP in children.35,36
Approximately 15% of children snore, and at least 1% to 3% have sleep-disordered breathing.35 Because of the associations with hypertension and the frequency of occurrence of sleep disorders, particularly among overweight children, a history of sleeping patterns should be obtained in a child with hypertension. One practical strategy for identifying children with a sleep problem or sleep disorder is to obtain a brief sleep history, using an instrument called BEARS.37(table 1.1). BEARS addresses 5 major sleep domains that provide a simple but comprehensive screen for the major sleep disorders affecting children 2 to 18 years old. The components of BEARS include: bedtime problems, excessive daytime sleepiness, awakenings during the night, regularity and duration of sleep, and sleep-disordered breathing (snoring). Each of these domains has an age-appropriate trigger question and includes responses of both parent and child as appropriate. This brief screening for sleep history can be completed in 5 minutes.
In a child with primary hypertension, the presence of any comorbidity that is associated with hypertension carries the potential to increase the risk for CVD and can have an adverse effect on health outcome. Consideration of these associated risk factors and appropriate evaluation in those children in whom the hypertension is verified are important in planning and implementing therapies that reduce the comorbidity risk as well as control BP.
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EVALUATION FOR SECONDARY HYPERTENSION |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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Secondary hypertension is more common in children than in adults. The possibility that some underlying disorder may be the cause of the hypertension should be considered in every child or adolescent who has elevated BP. However, the extent of an evaluation for detection of a possible underlying cause should be individualized for each child. Very young children, children with stage 2 hypertension, and children or adolescents with clinical signs that suggest the presence of systemic conditions associated with hypertension should be evaluated more extensively, as compared with those with stage 1 hypertension.38 Present technologies may facilitate less invasive evaluation than in the past, although experience in using newer modalities with children is still limited.
A thorough history and physical examination are the first steps in the evaluation of any child with persistently elevated BP. Elicited information should aim to identify not only signs and symptoms due to high BP but also clinical findings that might uncover an underlying systemic disorder. Thus, it is important to seek signs and symptoms suggesting renal disease (gross hematuria, edema, fatigue), heart disease (chest pain, exertional dyspnea, palpitations), and diseases of other organ systems (eg, endocrinologic, rheumatologic).
Past medical history should elicit information to focus the subsequent evaluation and to uncover definable causes of hypertension. Questions should be asked about prior hospitalizations, trauma, urinary tract infections, snoring and other sleep problems. Questions should address family history of hypertension, diabetes, obesity, sleep apnea, renal disease, other CVD (hyperlipidemia, stroke), and familial endocrinopathies. Many drugs can increase BP, so it is important to inquire directly about use of over-the-counter, prescription, and illicit drugs. Equally important are specific questions aimed at identifying the use of nutritional supplements, especially preparations aimed at enhancing athletic performance.
Physical Examination
The child's height, weight, and percentiles for age should be determined at the start of the physical examination. Because obesity is strongly linked to hypertension, BMI should be calculated from the height and weight, and the BMI percentile should be calculated. Poor growth may indicate an underlying chronic illness. When hypertension is confirmed, BP should be measured in both arms and in a leg. Normally, BP is 10 to 20 mm Hg higher in the legs than the arms. If the leg BP is lower than the arm BP or if femoral pulses are weak or absent, coarctation of the aorta may be present. Obesity alone is an insufficient explanation for diminished femoral pulses in the presence of high BP. The remainder of the physical examination should pursue clues found on history and should focus on findings that may indicate the cause and severity of hypertension. Table 8 lists important physical examination findings in hypertensive children.39
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Additional Diagnostic Studies for Hypertension
Additional diagnostic studies may be appropriate in the evaluation of hypertension in a child or adolescent, particularly if there is a high degree of suspicion that an underlying disorder is present. Such procedures are listed in Table 7. ABPM, discussed previously, has application in evaluating both primary and secondary hypertension. ABPM is also used to detect white-coat hypertension.
Renin Profiling
Plasma renin level or plasma renin activity (PRA) is a useful screening test for mineralocorticoid-related diseases. With these disorders, the PRA is very low or unmeasurable by the laboratory and may be associated with relative hypokalemia. PRA levels are higher in patients who have renal artery stenosis. However, 15% of children with arteriographically evident renal artery stenosis have normal PRA values.40–42 Assays for direct measurement of renin, a different technique than PRA, are commonly used, although extensive normative data in children and adolescents are unavailable.
Evaluation for Possible Renovascular Hypertension
Renovascular hypertension is a consequence of an arterial lesion or lesions impeding blood flow to 1 or both kidneys or to 1 intrarenal segments.43,44 Affected children usually, but not invariably, have markedly elevated BP.40,44 Evaluation for renovascular disease also should be considered in infants or children with other known predisposing factors such as prior umbilical artery catheter placements or neurofibromatosis.44,45 A number of newer diagnostic techniques are presently available for evaluation of renovascular disease, but experience in their use in pediatric patients is limited. Consequently, the recommended approaches generally use older techniques such as standard intraarterial angiography, digital-subtraction angiography (DSA), and scintigraphy (with or without angiotensin-converting enzyme [ACE] inhibition).44 As technologies evolve, children should be referred for imaging studies to centers that have expertise in the radiologic evaluation of childhood hypertension.
Invasive Studies
Intraarterial DSA with contrast is used more frequently than standard angiography, but because of intraarterial injection, this method remains invasive. DSA can be accomplished also by using a rapid injection of contrast into a peripheral vein, but quality of views and the size of pediatric veins make this technique useful only for older children. DSA and formal arteriography are still considered the "gold standard," but these studies should be undertaken only when surgical or invasive interventional radiologic techniques are being contemplated for anatomic correction.46
Newer imaging techniques may be used in children with vascular lesions. Magnetic resonance angiography (MRA) is increasingly feasible for the evaluation of pediatric renovascular disease, but it is still best for detecting abnormalities in the main renal artery and its primary branches.47–49 Imaging with magnetic resonance requires that the patient be relatively immobile for extended periods, which is a significant difficulty for small children. At present, studies are needed to assess the effectiveness of MRA in the diagnosis of children with renovascular disease. Newer methods, including 3-dimensional reconstructions of computed tomography (CT) images, or spiral CT with contrast, seem promising in evaluating children who may have renovascular disease.50
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TARGET-ORGAN ABNORMALITIES IN CHILDHOOD HYPERTENSION |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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Hypertension is associated with increased risk of myocardial infarction, stroke, and cardiovascular mortality in adults,2,51 and treatment of elevated BP results in a reduction in the risk for cardiovascular events.
Children and adolescents with severe elevation of BP are also at increased risk of adverse outcomes, including hypertensive encephalopathy, seizures, and even cerebrovascular accidents and congestive heart failure.52,53 Even hypertension that is less severe contributes to target-organ damage when it occurs with other chronic conditions such as chronic kidney disease.54–56 Two autopsy studies57,58 that evaluated tissue from adolescents and young adults who had sudden deaths due to trauma demonstrated significant relationships between the level of BP, or hypertension, and the presence of atherosclerotic lesions in the aorta and coronary arteries. The exact level and duration of BP elevation that causes target-organ damage in the young has not been established.
One difficulty in the assessment of these relationships is that, until recently, few noninvasive methods could evaluate the effect of hypertension on the cardiovascular system. Noninvasive techniques that use ultrasound can demonstrate structural and functional changes in the vasculature related to BP. Recent clinical studies using these techniques demonstrate that childhood levels of BP are associated with carotid intimal-medial thickness59 and large artery compliance60 in young adults. Even healthy adolescents with clustering of cardiovascular risk factors demonstrate elevated carotid thickness,61,62 and those with BP levels at the higher end of the normal distribution show decreased brachial artery flow-mediated vasodilatation. Overall, evidence is increasing that even mild BP elevation can have an adverse effect on vascular structure and function63 in asymptomatic young persons.
LVH is the most prominent clinical evidence of target-organ damage caused by hypertension in children and adolescents. With the use of echocardiography to measure left ventricular mass, LVH has been reported in 34% to 38% of children and adolescents with mild, untreated BP elevation.64–66 Daniels et al67 evaluated 130 children and adolescents with persistent BP elevation. They reported that 55% of patients had a left ventricular mass index >90th percentile, and 14% had left ventricular mass index >51 g/m2.7, a value in adults with hypertension that has been associated with a fourfold greater risk of adverse cardiovascular outcomes. When left ventricular geometry was examined in hypertensive children, 17% had concentric hypertrophy, a pattern that is associated with higher risk for cardiovascular outcomes in adults, and 30% had eccentric hypertrophy, which is associated with intermediate risk for cardiovascular outcomes.67
In addition, abnormalities of the retinal vasculature have been reported in adults with hypertension.68 Few studies of retinal abnormalities have been conducted in children with hypertension. Skalina et al69 evaluated newborns with hypertension and reported the presence of hypertensive retinal abnormalities in 50% of their patients. On repeat examination, after the resolution of hypertension, these abnormalities had disappeared.
Clinical Recommendation
Echocardiography is recommended as a primary tool for evaluating patients for target-organ abnormalities by assessing the presence or absence of LVH. Left ventricular mass is determined from standard echocardiographic measurements of the left ventricular end-diastolic dimension, the intraventricular septal thickness, and the thickness of the left ventricular posterior wall and can be calculated as: left ventricle mass (g) = 0.80 [1.04(intraventricular septal thickness + left ventricular end-diastolic dimension + left ventricular posterior wall thickness)3 – (left ventricular end-diastolic dimension)3] + 0.6 (with echocardiographic measurements in centimeters). From these measures, the left ventricular mass can be calculated by using the equation of Devereux et al70 when measurements are made according to the criteria of the American Society of Echocardiography.71
Heart size is closely associated with body size.72 Left ventricular mass index is calculated to standardize measurements of left ventricular mass. Several methods for indexing left ventricular mass have been reported, but it is recommended that height (m2.7) be used to index left ventricular mass as described by de Simone et al.73 This method accounts for close to the equivalent of the effect of lean body mass and excludes the effect of obesity and BP elevation on left ventricular mass. Some echo laboratories use height as the indexing variable. This calculation is also acceptable and is somewhat easier to use, because fewer calculations are needed.
Children and adolescents with established hypertension should have an echocardiogram to determine if LVH is present. A conservative cutpoint that determines the presence of LVH is 51 g/m2.7. This cutpoint is >99th percentile for children and adolescents and is associated with increased morbidity in adults with hypertension.73 Other references exist for normal children,74 but unlike adults, outcome-based standards for left ventricular mass index are not available for children. In interpreting the left ventricular mass index, it should be remembered that some factors such as obesity and hypertension have pathologic effects on the heart, whereas others (such as physical activity, particularly in highly conditioned athletes) may be adaptive.
Ascertainment of left ventricular mass index is very helpful in clinical decision-making. The presence of LVH can be an indication for initiating or intensifying pharmacologic therapy to lower BP. For patients who have LVH, the echocardiographic determination of left ventricular mass index should be repeated periodically.
At the present time, additional testing for other target-organ abnormalities (such as determination of carotid intimal-medial thickness and evaluation of urine for microalbuminuria) is not recommended for routine clinical use. Additional research will be needed to evaluate the clinical utility of these tests.
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THERAPEUTIC LIFESTYLE CHANGES |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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Evidence that supports the efficacy of nonpharmacologic interventions for BP reduction in the treatment of hypertension in children and adolescents is limited. Data that demonstrate a relationship of lifestyle with BP can be used as the basis for recommendations. On the basis of large, randomized, controlled trials, the following lifestyle modifications are recommended in adults2: weight reduction in overweight or obese individuals75; increased intake of fresh vegetables, fruits, and low-fat dairy (the Dietary Approaches to Stop Hypertension Study eating plan)76; dietary sodium reduction76,77; increased physical activity78; and moderation of alcohol consumption.79 Smoking cessation has significant cardiovascular benefits.32 As information on chronic sleep problems evolves, interventions to improve sleep quality also may have a beneficial effect on BP.80
The potential for control of BP in children through weight reduction is supported by BP tracking and weight-reduction studies. BP levels track from childhood through adolescence and into adulthood81–83 in association with weight.84,85 Because of the strong correlation between weight and BP, excessive weight gain is likely to be associated with elevated BP over time. Therefore, maintenance of normal weight gain in childhood should lead to less hypertension in adulthood.
Weight loss in overweight adolescents is associated with a decrease in BP.30,86–90 Weight control not only decreases BP, it also decreases BP sensitivity to salt88 and decreases other cardiovascular risk factors such as dyslipidemia and insulin resistance.32 In studies that achieve a reduction in BMI of 10%, short-term reductions in BP were in the range of 8 to 12 mm Hg. Although difficult, weight loss, if successful, is extremely effective.32,91–93 Identifying a complication of overweight such as hypertension can be a helpful motivator for patients and families to make changes. Weight control can render pharmacologic treatment unnecessary but should not delay drug use when indicated.
Emphasis on the management of complications rather than on overweight shifts the aim of weight management from an aesthetic to a health goal. In motivated families, education or simple behavior modification can be successful in achieving moderate weight loss or preventing additional weight gain. Steps can be implemented in the primary care setting even with limited staff and time resources.32,91 The patient should be encouraged to self-monitor time spent in sedentary activities, including watching television and playing video or computer games, and set goals to progressively decrease these activities to <2 hours per day.94 The family and patient should identify physical activities that the child enjoys, engage in them regularly, and self-monitor time spent in physical activities (30–60 minutes per day should be achieved).94–96 Dietary changes can involve portion-size control, decrease in consumption of sugar-containing beverages and energy-dense snacks, increase in consumption of fresh fruits and vegetables, and regular meals including a healthy breakfast.32,91,93,97,98 Consultation with a nutritionist can be useful and provide customized recommendations. During regular office visits, the primary care provider can supervise the child's progress in self-monitoring and accomplishing goals and provide support and positive feedback to the family. Some patients will benefit from a more intense and comprehensive approach to weight management from a multidisciplinary and specialized team if available.91–93
Despite the lack of firm evidence about dietary intervention in children, it is generally accepted that hypertensive individuals can benefit from a dietary increase in fresh vegetables, fresh fruits, fiber, and nonfat dairy as well as a reduction of sodium. Despite some suggestion that calcium supplements may decrease BP in children,99,100 thus far the evidence is too limited to support a clinical recommendation.101 Lower BP has been associated in children and adolescents with an increased intake of potassium,100–103 magnesium,100,101 folic acid,101,104 unsaturated fat,100,105,106 and fiber100,101,104 and lower dietary intake of total fat.100,101 However, these associations are small and insufficient to support dietary recommendations for specific, individual nutrients.
Sodium reduction in children and adolescents has been associated with small reductions in BP in the range of 1 to 3 mm Hg.100,103,107–110 Data from 1 randomized trial suggest that sodium intake in infancy may affect BP in adolescence.111 Similarly, some evidence indicates that breastfeeding may be associated with lower BP in childhood.112,113 The current recommendation for adequate daily sodium intake is only 1.2 g/day for 4- to 8-year-olds and 1.5 g/day for older children.114 Because this amount of sodium is substantially lower than current dietary intakes, lowering dietary sodium from the current usual intake may have future benefit. Reduced sodium intake, with calorie restriction, may account for some of the BP improvement associated with weight loss.
Regular physical activity has cardiovascular benefits. A recent meta-analysis that combined 12 randomized trials, for a total of 1266 children and adolescents, concluded that physical activity leads to a small but not statistically significant decrease in BP.115 However, both regular physical activity and decreasing sedentary activities (such as watching television and playing video or electronic games) are important components of pediatric obesity treatment and prevention.32,91–93 Weight-reduction trials consistently report better results when physical activity and/or prevention of sedentary activity are included in the treatment protocol. Therefore, regular aerobic physical activity (30–60 minutes of moderate physical activity on most days) and limitation of sedentary activities to <2 hours per day are recommended for the prevention of obesity, hypertension, and other cardiovascular risk factors.94–96 With the exception of power lifting, resistance training is also helpful. Competitive sports participation should be limited only in the presence of uncontrolled stage 2 hypertension.116
The scope of hypertension as a public health problem in adults is substantial. Poor health-related behaviors such as physical inactivity, unfavorable dietary patterns, and excessive weight gain raise the risk for future hypertension. The therapeutic lifestyle changes discussed above may have benefit for all children in prevention of future disease, including primary hypertension. Accordingly, appropriate health recommendations for all children and adolescents are regular physical activity; a diet with limited sodium but rich in fresh fruits, fresh vegetables, fiber, and low-fat dairy; and avoiding excess weight gain.
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PHARMACOLOGIC THERAPY OF CHILDHOOD HYPERTENSION |
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TOPINTRODUCTIONMETHODSDEFINITION OF HYPERTENSIONMEASUREMENT OF BP IN...BP TABLESPRIMARY HYPERTENSION AND...EVALUATION FOR SECONDARY...TARGET-ORGAN ABNORMALITIES IN...THERAPEUTIC LIFESTYLE CHANGESPHARMACOLOGIC THERAPY OF...APPENDIX A. DEMOGRAPHIC DATAAPPENDIX B. COMPUTATION OF...REFERENCESREFERENCES |
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In adults, hypertension is typically a life-long condition. Most hypertensive patients will need to remain on medications for the rest of their lives. Usually, adults readily accept this fact, given the known long-term adverse consequences of untreated or undertreated hypertension.117 In children, however, the long-term consequences of untreated hypertension are unknown. Additionally, no data are available on the long-term effects of antihypertensive drugs on growth and development. Therefore, a definite indication for initiating pharmacologic therapy should be ascertained before a drug is prescribed.
Table 6 summarizes the indications for use of antihypertensive drugs in children. These indications include symptomatic hypertension, secondary hypertension, established hypertensive target-organ damage, and failure of nonpharmacologic measures. Other indications for use of antihypertensive drugs can be considered depending on the clinical situation. For example, because the presence of multiple cardiovascular risk factors (elevated BP, dyslipidemia, tobacco use, etc) increases cardiovascular risk in an exponential rather than additive fashion,118,119 antihypertensive therapy could be considered if the child or adolescent is known to have dyslipidemia.
The number of antihypertensive drugs has increased since the publication of the first task force report on BP control in children.120 The number of drugs that have been studied systematically in children has increased also, largely because of incentives provided to the pharmaceutical industry under the auspices of the 1997 Food and Drug Administration Modernization Act (FDAMA) and the 2002 Best Pharmaceuticals for Children Act.121–123 These developments have had both negative and positive consequences. Chief among the negative consequences is the lack of reliable pediatric data for older, commonly used compounds with expired patent protection. Currently, no incentives exist for industry-sponsored trials of such drugs, and alternative methods of stimulating pediatric studies such as those contained in the Best Pharmaceuticals for Children Act123–125 have yet to come to fruition. On the other hand, publication of the results of industry-sponsored clinical trials and single-center case series will provide additional data that can be combined with prior recommendations based on expert opinion and collective clinical experience to guide the use of antihypertensive drugs in children and adolescents who require pharmacologic treatment.
Table 9 contains dosing recommendations for antihypertensive drugs in children 1–17 years old. It should be noted that many other drugs are available in addition to those listed in Table 9. Those drugs are not included in the table, however, because few or no pediatric data were available at the time this report was prepared.
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Specific classes of antihypertensive drugs should be used preferentially in certain hypertensive children with specific underlying or concurrent medical conditions. Examples include the use of ACE inhibitors or angiotensin-receptor blockers in children with diabetes and microalbuminuria or proteinuric renal diseases, and the use of ß-adrenergic blockers or calcium channel blockers in hypertensive children with migraine headaches. This approach is similar to that outlined in the recent JNC 7 report, which recommends specific classes of antihypertensive drugs for use in adults in certain high-risk categories.2
All antihypertensive drugs should be prescribed in a similar fashion: The child is initially started on the lowest recommended dose listed in Table 9. The dose can be increased until the desired BP goal is achieved. Once the highest recommended dose is reached, or if the child experiences side effects from the drug, a second drug from a different class should be added. Consideration should be given to combining drugs with complementary mechanisms of action such as an ACE inhibitor with a diuretic or a vasodilator with a diuretic or ß-adrenergic blocker. Because little pediatric experience is available in using fixed-dose combination products, except for bisoprolol/hydrochlorothiazide,131 routine use of these products in children cannot be recommended at this time.
For children with uncomplicated primary hypertension and no hypertensive target-organ damage, the goal BP should be <95th percentile for gender, age, and height, whereas for children with chronic renal disease, diabetes, or hypertensive target-organ damage, the goal BP should be <90th percentile for gender, age, and height. Again, this approach is similar to the recommended treatment of hypertension in adults with additional cardiovascular risk factors or comorbid conditions.2
Important adjunctive aspects to the drug therapy of childhood hypertension include ongoing monitoring of target-organ damage as well as BP monitoring, surveillance for drug side effects, periodic monitoring of electrolytes in children treated with ACE inhibitors or diuretics, counseling regarding other cardiovascular risk factors, and continued emphasis on nonpharmacologic measures. It also may be appropriate to consider "step-down" therapy in selected patients. This approach attempts a gradual reduction in the drug after an extended course of good BP control, with the eventual goal of completely discontinuing drug therapy. Children with uncomplicated primary hypertension, especially overweight children who successfully lose weight, are the best candidates for the step-down approach. Such patients require ongoing BP monitoring after the cessation of drug therapy as well as continued nonpharmacologic treatment, because hypertension may recur.
Severe, symptomatic hypertension with BP well above the 99th percentile occurs in some children, usually those with underlying renal disease, and requires prompt treatment. Hypertensive emergencies in children are usually accompanied by signs of hypertensive encephalopathy, typically causing seizures. Hypertensive emergencies should be treated by an intravenous antihypertensive that can produce a controlled reduction in BP, aiming to decrease the pressure by 
25% over the first 8 hours after presentation and then gradually normalizing the BP over 26 to 48 hours.132,133 Hypertensive urgencies are accompanied by less serious symptoms such as severe headache or vomiting. Hypertensive urgencies can be treated by either intravenous or oral antihypertensives depending on the child's symptomatology. Table 10 provides dosing recommendations for treatment of severe hypertension in children when prompt reduction in BP is indicated.
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, diet modification and physical activity; 
, especially if younger, very high BP, little or no family history, diabetic, or other risk f