Clinical Practice Guideline for Screening and Management of High Blood Pressure in Children and Adolescents

2.1 Prevalence of HTN in Children

Information on the prevalence of high blood pressure (BP) in children is largely derived from data from the NHANES and typically is based on a single BP measurement session. These surveys, conducted since 1988, indicate that there has been an increase in the prevalence of childhood high BP, including both HTN and elevated BP.^4,5 High BP is consistently greater in boys (15%–19%) than in girls (7%–12%). The prevalence of high BP is higher among Hispanic and non-Hispanic African American children compared with non-Hispanic white children, with higher rates among adolescents than among younger children.⁶

However, in a clinical setting and with repeated BP measurements, the prevalence of confirmed HTN is lower in part because of inherent BP variability as well as an adjustment to the experience of having BP measured (also known as the accommodation effect). Therefore, the actual prevalence of clinical HTN in children and adolescents is ∼3.5%.^7,8 The prevalence of persistently elevated BP (formerly termed “prehypertension,” including BP values from the 90th to 94th percentiles or between 120/80 and 130/80 mm Hg in adolescents) is also ∼2.2% to 3.5%, with higher rates among children and adolescents who have overweight and obesity.^7,9

Data on BP tracking from childhood to adulthood demonstrate that higher BP in childhood correlates with higher BP in adulthood and the onset of HTN in young adulthood. The strength of the tracking relationship is stronger in older children and adolescents.¹⁰ Trajectory data on BP (including repeat measurements from early childhood into midadulthood) confirm the association of elevated BP in adolescence with HTN in early adulthood¹¹ and that normal BP in childhood is associated with a lack of HTN in midadulthood.¹¹

2.2 Awareness, Treatment, and Control of HTN in Children

Of the 32.6% of US adults who have HTN, almost half (17.2%) are not aware they have HTN; even among those who are aware of their condition, only approximately half (54.1%) have controlled BP.¹² Unfortunately, there are no large studies in which researchers have systematically studied BP awareness or control in youth, although an analysis of prescribing patterns from a nationwide prescription drug provider found an increase in the number of prescriptions written for high BP in youth from 2004 to 2007.¹³

The SEARCH for Diabetes in Youth study found that only 7.4% of youth with type 1 diabetes mellitus (T1DM) and 31.9% of youth with type 2 diabetes mellitus (T2DM) demonstrated knowledge of their BP status.¹⁴ Even after becoming aware of the diagnosis, only 57.1% of patients with T1DM and 40.6% of patients with T2DM achieved good BP control.¹⁴ The HEALTHY Primary Prevention Trial of Risk Factors for Type 2 Diabetes in Middle-School Youth, which examined a school-based intervention designed to reduce cardiovascular (CV) risk among middle school students, found the prevalence of stage 1 or 2 HTN to be ∼9.5%.¹⁵ There was no significant reduction in HTN in the control group after the intervention; the intervention group saw a reduction in the prevalence of HTN of ∼1%, leaving 8.5% with BP still above the ideal range.

Researchers in a number of small, single-center studies have evaluated BP control in children and adolescents with HTN. One study found that lifestyle change and medications produced adequate BP control in 46 of 65 youth (70%) with HTN.¹⁶ Another study in which researchers used ambulatory blood pressure monitoring (ABPM) to assess BP control among a group of 38 children (of whom 84% had chronic kidney disease [CKD]) found that only 13 children (34%) achieved adequate BP control even among those who received more than 1 drug.¹⁷ A similar study found that additional drugs did increase rates of BP control in children with CKD, however.¹⁸

2.3 Prevalence of HTN Among Children With Various Chronic Conditions

It is well recognized that HTN rates are higher in children with certain chronic conditions, including children with obesity, sleep-disordered breathing (SDB), CKD, and those born preterm. These are described below.

2.4 Importance of Diagnosing HTN in Children and Adolescents

Numerous studies have shown that elevated BP in childhood increases the risk for adult HTN and metabolic syndrome.^10,60–62 Youth with higher BP levels in childhood are also more likely to have persistent HTN as adults.^60,63 One recent study found that adolescents with elevated BP progressed to HTN at a rate of 7% per year, and elevated BMI predicted sustained BP elevations.⁶⁴ In addition, young patients with HTN are likely to experience accelerated vascular aging. Both autopsy⁶⁵ and imaging studies⁶⁶ have demonstrated BP-related CV damage in youth. These intermediate markers of CVD (eg, increased LV mass,⁶⁷ cIMT,⁶⁸ and pulse wave velocity [PWV]⁶⁹) are known to predict CV events in adults, making it crucial to diagnose and treat HTN early.

Eighty million US adults (1 in 3) have HTN, which is a major contributor to CVD.¹² Key contributors to CV health have been identified by the American Heart Association (AHA) as “Life’s Simple 7,” including 4 ideal health behaviors (not smoking, normal BMI, physical activity at goal levels, and a healthy diet) and 3 ideal health factors (untreated, normal total cholesterol; normal fasting blood glucose; and normal untreated BP, defined in childhood as ≤90th percentile or <120/80 mm Hg). Notably, elevated BP is the least common abnormal health factor in children and adolescents⁷⁰; 89% of youth (ages 12–19 years) are in the ideal BP category.⁶

Given the prevalence of known key contributors in youth (ie, tobacco exposure, obesity, inactivity, and nonideal diet^12,71), adult CVD likely has its origins in childhood. One-third of US adolescents report having tried a cigarette in the past 30 days.⁷² Almost half (40%–48%) of teenagers have elevated BMI, and the rates of severe obesity (BMI >99th percentile) continue to climb, particularly in girls and adolescents.^73–75 Physical activity measured by accelerometry shows less than half of school-aged boys and only one-third of school-aged girls meet the goal for ideal physical activity levels.⁷² More than 80% of youth 12 to 19 years of age have a poor diet (as defined by AHA metrics for ideal CV health); only ∼10% eat adequate fruits and vegetables, and only ∼15% consume <1500 mg per day of sodium, both of which are key dietary determinants of HTN.⁷⁶

Finally, measuring BP at routine well-child visits enables the early detection of primary HTN as well as the detection of asymptomatic HTN secondary to another underlying disorder. Early detection of HTN is vital given the greater relative prevalence of secondary causes of HTN in children compared with adults.

3.1 Definition of HTN (1–18 Years of Age)

Given the lack of outcome data, the current definition of HTN in children and adolescents is based on the normative distribution of BP in healthy children.¹ Because it is a major determinant of BP in growing children, height has been incorporated into the normative data since the publication of the 1996 Working Group Report.¹ BP levels should be interpreted on the basis of sex, age, and height to avoid misclassification of children who are either extremely tall or extremely short. It should be noted that the normative data were collected by using an auscultatory technique,¹ which may provide different values than measurement obtained by using oscillometric devices or from ABPM.

In the Fourth Report, “normal blood pressure” was defined as SBP and DBP values <90th percentile (on the basis of age, sex, and height percentiles). For the preadolescent, “prehypertension” was defined as SBP and/or DBP ≥90th percentile and <95th percentile (on the basis of age, sex, and height tables). For adolescents, “prehypertension” was defined as BP ≥120/80 mm Hg to <95th percentile, or ≥90th and <95th percentile, whichever was lower. HTN was defined as average clinic measured SBP and/or DBP ≥95th percentile (on the basis of age, sex, and height percentiles) and was further classified as stage 1 or stage 2 HTN.

There are still no data to identify a specific level of BP in childhood that leads to adverse CV outcomes in adulthood. Therefore, the subcommittee decided to maintain a statistical definition for childhood HTN. The staging criteria have been revised for stage 1 and stage 2 HTN for ease of implementation compared with the Fourth Report. For children ≥13 years of age, this staging scheme will seamlessly interface with the 2017 AHA and American College of Cardiology (ACC) adult HTN guideline.* Additionally, the term “prehypertension” has been replaced by the term “elevated blood pressure,” to be consistent with the AHA and ACC guideline and convey the importance of lifestyle measures to prevent the development of HTN (see Table 3).

3.2 New BP Tables

New normative BP tables based on normal-weight children are included with these guidelines (see Tables 4 and 5). Similar to the tables in the Fourth Report,¹ they include SBP and DBP values arranged by age, sex, and height (and height percentile). These values are based on auscultatory measurements obtained from ∼50 000 children and adolescents. A new feature in these tables is that the BP values are categorized according to the scheme presented in Table 3 as normal (50th percentile), elevated BP (>90th percentile), stage 1 HTN (≥95th percentile), and stage 2 HTN (≥95th percentile + 12 mm Hg). Additionally, actual heights in centimeters and inches are provided.

Unlike the tables in the Fourth Report,¹ the BP values in these tables do not include children and adolescents with overweight and obesity (ie, those with a BMI ≥85th percentile); therefore, they represent normative BP values for normal-weight youth. The decision to create these new tables was based on evidence of the strong association of both overweight and obesity with elevated BP and HTN. Including patients with overweight and obesity in normative BP tables was thought to create bias. The practical effect of this change is that the BP values in Tables 4 and 5 are several millimeters of mercury lower than in the similar tables in the Fourth Report.¹ These tables are based on the same population data excluding participants with overweight and obesity, and the same methods used in the Fourth Report.¹ The methods and results have been published elsewhere.⁷⁷ For researchers and others interested in the equations used to calculate the tables’ BP values, detailed methodology and the Statistical Analysis System (SAS) code can be found at: http://sites.google.com/a/channing.harvard.edu/bernardrosner/pediatric-blood-press/childhood-blood-pressure.

There are slight differences between the actual percentile-based values in these tables and the cut-points in Table 3, particularly for teenagers ≥13 years of age. Clinicians should understand that the scheme in Table 3 was chosen to align with the new adult guideline and facilitate the management of older adolescents with high BP. The percentile-based values in Tables 4 and 5 are provided to aid researchers and others interested in a more precise classification of BP.

3.3 Definition of HTN in the Neonate and Infant (0–1 Year of Age)

Although a reasonably strict definition of HTN has been developed for older children, it is more difficult to define HTN in neonates given the well-known changes in BP that occur during the first few weeks of life.⁷⁹ These BP changes can be significant in preterm infants, in whom BP depends on a variety of factors, including postmenstrual age, birth weight, and maternal conditions.⁸⁰

In an attempt to develop a more standardized approach to the HTN definition in preterm and term neonates, Dionne et al⁷⁹ compiled available data on neonatal BP and generated a summary table of BP values, including values for the 95th and 99th percentiles for infants from 26 to 44 weeks’ postmenstrual age. The authors proposed that by using these values, a similar approach to that used to identify older children with elevated BP can be followed in neonates, even in those who are born preterm.

At present, no alternative data have been developed, and no outcome data are available on the consequences of high BP in this population; thus, it is reasonable to use these compiled BP values in the assessment of elevated BP in newborn infants. Of note, the 1987 “Report of the Second Task Force on Blood Pressure Control in Children” published curves of normative BP values in older infants up to 1 year of age.⁸¹ These normative values should continue to be used given the lack of more contemporary data for this age group.

4.1 BP Measurement Technique

BP in childhood may vary considerably between visits and even during the same visit. There are many potential etiologies for isolated elevated BP in children and adolescents, including such factors as anxiety and recent caffeine intake.⁸² BP generally decreases with repeated measurements during a single visit,⁸³ although the variability may not be large enough to affect BP classification.⁸⁴ BP measurements can also vary across visits^64,85; one study in adolescents found that only 56% of the sample had the same HTN stage on 3 different occasions.⁸ Therefore, it is important to obtain multiple measurements over time before diagnosing HTN.

The initial BP measurement may be oscillometric (on a calibrated machine that has been validated for use in the pediatric population) or auscultatory (by using a mercury or aneroid sphygmomanometer^86,87). (Validation status for oscillometric BP devices, including whether they are validated in the pediatric age group, can be checked at www.dableducational.org.) BP should be measured in the right arm by using standard measurement practices unless the child has atypical aortic arch anatomy, such as right aortic arch and aortic coarctation or left aortic arch with aberrant right subclavian artery (see Table 7). Other important aspects of proper BP measurement are illustrated in an AAP video available at http://youtu.be/JLzkNBpqwi0. Care should be taken that providers follow an accurate and consistent measurement technique.^88,89

An appropriately sized cuff should be used for accurate BP measurement.⁸³ Researchers in 3 studies in the United Kingdom and 1 in Brazil documented the lack of availability of an appropriately sized cuff in both the inpatient and outpatient settings.^91–94 Pediatric offices should have access to a wide range of cuff sizes, including a thigh cuff for use in children and adolescents with severe obesity. For children in whom the appropriate cuff size is difficult to determine, the midarm circumference (measured as the midpoint between the acromion of the scapula and olecranon of the elbow, with the shoulder in a neutral position and the elbow flexed to 90°^86,95,96) should be obtained for an accurate determination of the correct cuff size (see Fig 2 and Table 7).⁹⁵

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FIGURE 2

Determination of proper BP cuff size.⁹⁵ A, Marking spine extending from acromion process. B, Correct tape placement for upper arm length. C, Incorrect tape placement for upper arm length. D, Marking upper arm length midpoint.

If the initial BP is elevated (≥90th percentile), providers should perform 2 additional oscillometric or auscultatory BP measurements at the same visit and average them. If using auscultation, this averaged measurement is used to determine the child’s BP category (ie, normal, elevated BP, stage 1 HTN, or stage 2 HTN). If the averaged oscillometric reading is ≥90th percentile, 2 auscultatory measurements should be taken and averaged to define the BP category (see Fig 3).

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FIGURE 3

Modified BP measurement algorithm.

4.2 BP Measurement Frequency

It remains unclear what age is optimal to begin routine BP measurement in children, although available data suggest that prevention and intervention efforts should begin at a young age.^{10,60,101–106} The subcommittee believes that the recommendation to measure BP in the ambulatory setting beginning at 3 years of age should remain unchanged.¹ For otherwise healthy children, however, BP need only be measured annually rather than during every health care encounter.

Some children should have BP measured at every health encounter, specifically those with obesity (BMI ≥95 percentile),^{5,27,107–109} renal disease,⁴⁶ diabetes,^110,111 aortic arch obstruction or coarctation, or those who are taking medications known to increase BP (see Table 8 and the “Secondary Causes: Medication-related” section of this guideline).^112,113

Children younger than 3 years should have BP measurements taken at well-child care visits if they are at increased risk for developing HTN (see Table 9).¹

4.3 Patient Management on the Basis of Office BP

4.4 Use of Electronic Health Records

Studies have demonstrated that primary care providers frequently fail to measure BP and often underdiagnose HTN.^85,115,116 One analysis using nationally representative survey data found that providers measured BP at only 67% of preventive visits for children 3 to 18 years of age. Older children and children with overweight or obesity were more likely to be screened.¹¹⁷ In a large cohort study of 14 187 children, 507 patients met the criteria for HTN, but only 131 (26%) had the diagnosis documented in their electronic health records (EHRs). Elevated BP was only recognized in 11% of cases.⁷

It is likely that the low rates of screening and diagnosis of pediatric HTN are related, at least in part, to the need to use detailed reference tables incorporating age, sex, and height to classify BP levels.¹¹⁸ Studies have shown that using health information technology can increase adherence to clinical guidelines and improve practitioner performance.^119–121 In fact, applying decision support in conjunction with an EHR in adult populations has also been associated with improved BP screening, recognition, medication prescribing, and control; pediatric data are limited, however.^122–125 Some studies failed to show improvement in BP screening or control,^122,126 but given the inherent complexity in the interpretation of pediatric BP measurements, EHRs should be designed to flag abnormal values both at the time of measurement and on entry into the EHR.

4.5 Oscillometric Versus Auscultatory (Manual) BP Measurement

Although pediatric normative BP data are based on auscultatory measurements, oscillometric BP devices have become commonplace in health care settings.¹²⁷ Ease of use, a lack of digit preference, and automation are all perceived benefits of using oscillometric devices. Unlike auscultatory measurement, however, oscillometric devices measure the oscillations transmitted from disrupted arterial flow by using the cuff as a transducer to determine mean arterial pressure (MAP). Rather than directly measuring any pressure that correlates to SBP or DBP, the device uses a proprietary algorithm to calculate these values from the directly measured MAP.¹²⁷ Because the algorithms vary for different brands of oscillometric devices, there is no standard oscillometric BP.¹²⁸

Researchers in several studies have evaluated the accuracy of oscillometric devices^{127,129–134} and compared auscultatory and oscillometric readings’ ability to predict target organ damage.¹³⁵ These studies demonstrated that oscillometric devices systematically overestimate SBP and DBP compared with values obtained by auscultation.^129,133 BP status potentially can be misclassified because of the different values obtained by these 2 methods, which may be magnified in the office setting.^86,88,129 Target organ damage (such as increased LV mass and elevated PWV) was best predicted by BPs obtained by auscultation.¹³⁵

A major issue with oscillometric devices is that there appears to be great within-visit variation with inaccurately high readings obtained on initial measurement.¹³⁶ An elevated initial oscillometric reading should be ignored and repeat measures averaged to approximate values obtained by auscultation.

4.6 Forearm and/or Wrist BP Measurement

Wrist monitors have several potential advantages when compared with arm devices. They are smaller; they can be placed more easily; and, because wrist diameter is less affected by BMI, they do not need to be modified for patients with obesity.^83,137 Several studies in adults have found excellent reproducibility of wrist BP measurements, equivalence to readings obtained by mercury sphygmomanometers or ABPM, and better correlation with left ventricular mass index (LVMI) than systolic office BP.^138,139

Although many wrist devices have been validated in adults,^140–142 some studies have shown greater variation and decreased accuracy in the resulting measurements.^143–146 These negative outcomes may possibly result from differences in the number of measurements taken,¹³⁹ the position of the wrist in relation to the heart,¹⁴⁷ flexion or extension of the wrist during measurement,¹⁴⁸ or differences in pulse pressure.¹⁴⁹ Technologies are being developed to help standardize wrist position.^150,151

Few studies using wrist monitors have been conducted in children. One study in adolescents compared a wrist digital monitor with a mercury sphygmomanometer and found high agreement between systolic measurements but lower agreement for diastolic measurements, which was clinically relevant.¹⁵² Researchers in 2 small studies conducted in PICUs compared wrist monitors with indwelling arterial lines and found good agreement between the 2 measurement modalities.^153,154 No large comparative studies or formal validation studies of wrist monitors have been conducted in children, however. Because of limited data, the use of wrist and forearm monitors is not recommended in the diagnosis or management of HTN in children and adolescents at this time.

4.7 ABPM

An ambulatory BP monitor consists of a BP cuff attached to a box slightly larger than a cell phone, which records BP periodically (usually every 20–30 minutes) throughout the day and night; these data are later downloaded to a computer for analysis.¹⁵⁵

ABPM has been recommended by the US Preventive Services Task Force for the confirmation of HTN in adults before starting treatment.¹⁵⁶ Although a growing number of pediatric providers have access to ABPM, there are still gaps in access and knowledge regarding the optimal application of ABPM to the evaluation of children’s BP.^155,157 For example, there are currently no reference data for children whose height is <120 cm. Because no outcome data exist linking ABPM data from childhood to hard CV events in adulthood, recommendations either rely largely on surrogate outcome markers or are extrapolated from adult studies.

However, sufficient data exist to demonstrate that ABPM is more accurate for the diagnosis of HTN than clinic-measured BP,^158,159 is more predictive of future BP,¹⁶⁰ and can assist in the detection of secondary HTN.¹⁶¹ Furthermore, increased LVMI and LVH correlate more strongly with ABPM parameters than casual BP.^162–166 In addition, ABPM is more reproducible than casual or home BP measurements.¹⁵⁹ For these reasons, the routine application of ABPM is recommended, when available, as indicated below (see also Tables 12 and 13). Obtaining ABPM may require referral to a specialist.

4.8 Measurement in Children With Obesity

Accurate BP measurement can be challenging in individuals with obesity.^23,211,212 Elevated BMI in children and adolescents is associated with an increase in the midarm circumference,⁹⁶ requiring the use of a larger cuff to obtain accurate BP measurements.⁸³ During NHANES 2007–2010, among children 9 to 11 years of age with obesity, one-third of boys and one-quarter of girls required an adult BP cuff, and a fraction required a large adult cuff or an adult thigh cuff for an accurate measurement of BP.²¹³ Researchers in studies of adults have also noted the influence of the conical upper arm shape on BP measurements in people with obesity.^214,215 ABPM is a valuable tool in the diagnosis of HTN in children with obesity because of the discrepancies between casual and ambulatory BP^23,33 and the higher prevalence of MH.^{26,29,155,216,217}

4.9. At-Home Measurement

Home measurement (or self-monitoring) of BP has advantages over both office and ambulatory monitoring, including convenience and the ability to obtain repeated measurements over time.^83,218 Furthermore, automated devices with memory capacity are straightforward to use and avoid potential problems, such as observer bias, inaccurate reporting, and terminal digit preference (ie, overreporting of certain digits, like 0, as the terminal digit in recording BP).^219,220

Numerous studies have shown that it is feasible for families to conduct repeated measurements at home.^221–223 Home BP measurements appear to be more reproducible than those conducted in the office, likely because of the familiarity of the home environment and greater comfort with repeated measurements.^159,223,224 Inaccuracies occur when measurements obtained at home are either excluded or inappropriately recorded.²¹⁹ Inconsistencies in home, office, and ambulatory BP measurements seem to be influenced by both age and HTN status, with ABPM tending to be higher than home BP measurements in children.^{222,225–227} Home BP measurements show no consistent pattern when compared with office measurements.^228–230

There are several practical concerns with the use of home BP measurement, however. The only normative data available are from the relatively small Arsakeion School study.²³¹ In addition, only a few automated devices have been validated for use in the pediatric population, and available cuff sizes for them are limited. Furthermore, there is no consensus regarding how many home measurements across what period of time are needed to evaluate BP.

4.10 School Measurement and the Role of School-Based Health Professionals

There is limited evidence to support school-based measurement of children’s BP.^8,232 Observational studies demonstrate that school measurements can be reliable²³³ and that longitudinal follow-up is feasible.^8,232,234 Available data do not distinguish between the efficacy of school-based screening programs in which measurements are obtained by trained clinical personnel (not a school nurse) versus measurements obtained by the school nurse. Because of insufficient evidence and a lack of established protocols, the routine use of school-based measurements to diagnose HTN cannot be recommended. However, school-based BP measurement can be a useful tool to identify children who require formal evaluation as well as a helpful adjunct in the monitoring of diagnosed HTN. Note: School-based health clinics are considered part of systems of pediatric primary care, and these comments would not apply to them.

5.1 Primary HTN

Primary HTN is now the predominant diagnosis for hypertensive children and adolescents seen in referral centers in the United States,^235,236 although single-center studies from outside the United States still find primary HTN to be uncommon.²³⁷ Although prospective, multicenter studies are generally lacking, at least one large study in which researchers used insurance claims data confirmed that primary HTN is significantly more common than secondary HTN among American youth.²³⁸

General characteristics of children with primary HTN include older age (≥6 years),^239,240 positive family history (in a parent and/or grandparent) of HTN,^236,237,240 and overweight and/or obesity.^{16,236,237,239} Severity of BP elevation has not differed significantly between children with primary and secondary HTN in some studies,^235,237 but DBP elevation appears to be more predictive of secondary HTN,^239,240 whereas systolic HTN appears to be more predictive of primary HTN.^236,239

5.2 Secondary Causes: Renal and/or Renovascular

Renal disease and renovascular disease are among the most common secondary causes of HTN in children. Renal parenchymal disease and renal structural abnormalities accounted for 34% to 79% of patients with secondary HTN in 3 retrospective, single-center case series, and renovascular disease was present in 12% to 13%.^101,240,241 The literature suggests that renal disease is a more common cause of HTN in younger children.²³⁹ Renal disorders (including vascular problems) accounted for 63% to 74% of children <6 years of age who were enrolled in 3 recent clinical trials of angiotensin receptor blockers (ARBs).^{239,242–244} No increased frequency was seen in younger patients in a recent single-center case series, however.¹⁰¹ It is appropriate to have a high index of suspicion for renal and renovascular disease in hypertensive pediatric patients, particularly in those <6 years of age.

5.3 Secondary Causes: Cardiac, Including Aortic Coarctation

Coarctation of the aorta is a congenital abnormality of the aortic arch characterized by discrete narrowing of the aortic arch, generally at the level of the aortic isthmus. It is usually associated with HTN and right arm BP that is 20 mm Hg (or more) greater than the lower extremity BP. Repair in infants is often surgical; adolescents may be treated with angioplasty or stenting. Long-segment narrowing of the abdominal aorta can also cause HTN and should be considered in children with refractory HTN and a gradient between the upper and lower extremities in which the upper extremity SBP exceeds the lower extremity SBP by 20 mm Hg.²⁴⁵ Of note, children with abdominal aortic obstruction may have neurofibromatosis, Williams syndrome, Alagille syndrome, or Takayasu arteritis.

Patients with coarctation can remain hypertensive or develop HTN even after early and successful repair, with reported prevalence varying from 17% to 77%.¹¹² HTN can be a manifestation of recoarctation. Recoarctation in repaired patients should be assessed for by using 4 extremity BP measurements and echocardiography. HTN can also occur without recoarctation.²⁴⁶ The prevalence of HTN increases over time after successful coarctation repair.¹¹²

Routine office BP measurement alone is often insufficient for diagnosing HTN after coarctation repair.^113,246 Children who have undergone coarctation repair may have normal in-office BP but high BP out of the office, which is consistent with MH.^58,112 Of children with a history of aortic coarctation, ∼45% have MH at ∼1 to 14 years after coarctation repair.^58,113 Children with a history of repaired aortic coarctation and normal in-office BP are at risk for LVH,⁵⁸ HTN, and MH.^58,112

ABPM has emerged as the gold standard for diagnosing HTN among individuals who have undergone coarctation repair, and it is likely more useful than casual BP.^58,245–247 Screening is recommended as a part of usual care on an annual basis beginning, at most, 12 years after coarctation repair. Earlier screening may be considered on the basis of risk factors and clinician discretion.

5.4 Secondary Causes: Endocrine HTN

HTN resulting from hormonal excess accounts for a relatively small proportion of children with secondary HTN. Although rare (with a prevalence ranging from 0.05% to 6% in children^{101,237,239,240}), an accurate diagnosis of endocrine HTN provides the clinician with a unique treatment opportunity to render a surgical cure or achieve a dramatic response with pharmacologic therapy.²⁴⁸ Known endocrine causes with associated molecular defects (when known) are summarized in Table 15.

5.5 Secondary Causes: Environmental Exposures

Several environmental exposures have been associated with higher childhood BP, although most studies are limited to small case series. Among the most prominent are lead, cadmium, mercury, and phthalates.

• Lead: Long-term exposure to lead in adults has been associated with higher BP in population studies^295,296 and in studies of industrial workers with high lead exposure,²⁹⁷ although findings have not been consistent.²⁹⁸ At least 1 cross-sectional study of 122 children demonstrated that children with higher blood lead concentrations had higher BP; lower socioeconomic status was also seen in this group, which may have confounded the BP results.²⁹⁹ Furthermore, in a randomized study of lead-exposed children, those who received chelation with succimer did not have lower BP than in those who received a placebo.³⁰⁰

• Cadmium: Environmental cadmium exposure has been linked to higher BP levels and the development of HTN in adults, particularly among women.^{296,301–303} Although cross-sectional studies have confirmed potential nephrotoxicity of cadmium in children,³⁰⁴ no definite effect on BP has been demonstrated.^304,305

• Mercury: Mercury is a known nephrotoxin, particularly in its elemental form.^306,307 Severe mercury intoxication has been linked to acute HTN in children in several case reports; patients’ symptoms may resemble those seen in patients with pheochromocytoma (PCC).^308–310

• Phthalates: Antenatal and childhood exposure to phthalates has recently been associated with higher childhood BP^311–313 but not with the development of overt HTN. Specific metabolites of these ubiquitous chemicals may have differential effects on BP,³¹³ indicating that much more detailed study is needed to completely understand the effect of such exposure.

5.6 Secondary Causes: Neurofibromatosis

Neurofibromatosis type 1 (NF-1) (also known as Von Recklinghausen disease) is a rare autosomal dominant disorder characterized by distinct clinical examination findings. These include the following: cafe-au-lait macules, neurofibromas, Lisch nodules of the iris, axillary freckling, optic nerve gliomas, and distinctive bone lesions. Patients with NF-1 have several unique and potential secondary causes of HTN, most commonly renal artery stenosis (RAS); coarctation of the aorta, middle aortic syndrome, and PCC are also well described.^314–319

Additionally, an increased incidence of idiopathic HTN has been documented in patients with NF-1, as high as 6.1% in a recent pediatric case series, which is a much greater incidence than in the general population.³²⁰ PCC has also been well described in patients with NF-1, although exact incidences are difficult to determine, and patients may not have classic symptoms of PCC.^321,322

Vascular causes of HTN and PCC all require specific treatment and follow-up, so maintaining a high index of suspicion for these disorders is important in evaluating hypertensive children and adolescents with NF-1.

5.7 Secondary Causes: Medication Related

Many over-the-counter drugs, prescription medications, alternative therapies (ie, herbal and nutritional supplements), dietary products, and recreational drugs can increase BP. Common prescription medications associated with a rise in BP include oral contraceptives,^323–325 central nervous system stimulants,³²⁶ and corticosteroids.^1,327 When a child has elevated BP measurements, the practitioner should inquire about the intake of pharmacologic agents (see Table 8).

Usually, the BP elevation is mild and reversible on discontinuation of the medication, but a significant increase in BP can occasionally occur with higher doses or as an idiosyncratic response. Over-the-counter cold medications that contain decongestants (eg, pseudoephedrine and phenylpropanolamine) may cause a mild increase in BP with the recommended dosing, but severe HTN has been observed as an idiosyncratic response with appropriate dosing as well as with excessive doses.

Nonsteroidal anti-inflammatory drugs may antagonize the BP-lowering effect of antihypertensive medications (specifically, angiotensin-converting enzyme [ACE] inhibitors) but do not appear to have an impact on BP in those without HTN. The commonly used supplement ephedra (ma haung) likely contains some amount of ephedrine and caffeine that can cause an unpredictable rise in BP. Recreational drugs associated with HTN include stimulants (eg, cocaine and amphetamine derivatives) and anabolic steroids.

5.8 Monogenic HTN

Monogenic forms of HTN are uncommon, although the exact incidence is unknown. In a study of select hypertensive children without a known etiology, genetic testing for familial hyperaldosteronism type I (FH-I), or glucocorticoid-remediable aldosteronism, confirmed responsible genetic mutations in 3% of the population.²⁶³

Other monogenic forms of HTN in children include Liddle syndrome, pseudohypoaldosteronism type II (Gordon syndrome), apparent mineralocorticoid excess, familial glucocorticoid resistance, mineralocorticoid receptor activating mutation, and congenital adrenal hyperplasia (see “Secondary Causes: Endocrine Causes of Hypertension”).³²⁸ All manifest as HTN with suppressed plasma renin activity (PRA) and increased sodium absorption in the distal tubule. Other features may include serum potassium abnormalities, metabolic acid-base disturbances, and abnormal plasma aldosterone concentrations, although the clinical presentations can be highly variable.^263,328,329 In the study of FH-I, all affected children had suppressed PRA and an aldosterone to renin ratio (ARR) (ng/dL and ng/M1 per hour, respectively) of >10; the authors suggest that an ARR >10 is an indication to perform genetic testing in a hypertensive child.²⁶³ Monogenic forms of HTN should be suspected in hypertensive children with a suppressed PRA or elevated ARR, especially if there is a family history of early-onset HTN.

6.1 Patient Evaluation

As with any medical condition, appropriate diagnostic evaluation is a critical component in the evaluation of a patient with suspected HTN. Evaluation focuses on determining possible causes of and/or comorbidities associated with HTN. Evaluation, as is detailed in the following sections, should include appropriate patient history, family history, physical examination, laboratory evaluation, and imaging.

6.2 History

The first step in the evaluation of the child or adolescent with elevated BP is to obtain a history. The various components of the history include the perinatal history, past medical history, nutritional history, activity history, and psychosocial history. Each is discussed in the following sections.

6.3 Physical Examination

A complete physical examination may provide clues to potential secondary causes of HTN and assess possible hypertensive end organ damage. The child’s height, weight, calculated BMI, and percentiles for age should be determined at the start of the physical examination. Poor growth may indicate an underlying chronic illness.

At the second visit with confirmed elevated BP or stage 1 HTN or the first visit with confirmed stage 2 HTN, 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 in the history and should focus on body systems and findings that may indicate secondary HTN and/or end organ damage related to HTN. Table 14 lists important physical examination findings in hypertensive children.³⁵³ These are examples of history and physical findings and do not represent all possible history and physical examination findings. The physical examination in hypertensive children is frequently normal except for the BP elevation.

6.4 Laboratory Evaluation

The purpose of the laboratory evaluation is to identify underlying secondary causes of HTN (eg, renal or endocrine disease) that would require specific treatment guided by a subspecialist. In general, such testing includes a basic set of screening tests and additional, specific tests; the latter are selected on the basis of clues obtained from the history and physical examination and/or the results of the initial screening tests.³⁵⁴ Table 10 provides a list of screening tests and the populations in which they should be performed.

6.5 Electrocardiography

Approximately one-half of adolescents with HTN have undergone electrocardiography at least once as an assessment for LVH.³⁵⁵ Unlike echocardiography, electrocardiography takes little time and is a relatively low-cost test. Electrocardiography has high specificity but poor sensitivity for identifying children and adolescents with LVH.^356–358 The positive predictive value of electrocardiography to identify LVH is extremely low.³⁵⁹

6.6 Imaging Evaluation, Echocardiography: Detection of Target Organ Damage

Echocardiography was identified in the Fourth Report as a tool to measure left ventricular (LV) target organ injury related to HTN in children.¹ The basis for this assessment is as follows: (1) the relationship of LV mass to BP,³⁶¹ (2) the independent and strong relationship of LVH to adverse CVD outcomes in adults,^362–364 and (3) that a significant percentage of children and adolescents with HTN demonstrate the degree of LVH associated with adverse outcomes in adults.^365–367 Antihypertensive treatment reduces LVH. Observational data suggest that the regression of LVH independently predicts outcomes in adults.³⁶⁸

The best-studied measures of LV target organ injury are measures of LV structure (LV mass and the relationship of LV wall thickness or mass to LV cavity volume) and systolic function (LV ejection fraction). LV structure is usually stratified into 4 groups on the basis of LV mass (normal or hypertrophied) and relative LV wall thickness (normal or increased). These 4 are as follows: (1) normal geometry with normal LV mass and wall thickness, (2) concentric geometry with normal LV mass and increased LV wall thickness, (3) eccentric LVH with increased LV mass and normal LV wall thickness, and (4) concentric LVH with both increased LV mass and increased relative wall thickness.^369,370

The American Society of Echocardiography recommendations should be followed with regard to image acquisition and LV measurement for calculating LV ejection fraction, mass, and relative wall thickness.^369,371 LV ejection fraction may be significantly decreased in severe or acute onset HTN with associated congestive heart failure.¹ Rarely, LV ejection fraction may be mildly depressed in chronic HTN.

Because the heart increases in size in relation to body size, indexing LV mass is required.³⁶¹ Indexing LV mass is particularly important in infants and younger children because of their rapid growth.^372,373 Physical training increases LV mass in a healthful manner. Lean body mass is more strongly associated with LV mass than fat mass.³⁷⁰ Because body composition is not routinely measured clinically, surrogate formulae for indexing are required. It is unclear whether expected values for LV mass should be derived from reference populations of normal weight and normotensive children or should include normotensive children who have overweight or obesity. The best method for indexing LV mass in children is an area of active investigation.

For this document, the following definitions for LV target organ injury have been chosen regarding hypertrophy, relative wall thickness, and ejection fraction. These definitions are based on published guidelines from the American Society of Echocardiography and associations of thresholds for indexed LV mass with adverse outcomes in adults^362,363,369:

• LVH is defined as LV mass >51 g/m^2.7 or LV mass >115 g per body surface area (BSA) for boys and LV mass >95 g/BSA for girls. (Note that the values for LVH are well above the 95th percentile for distributions of LV mass in children and adolescents.³⁶⁹ The clinical significance of values between the 95th percentile of a population-based distribution and these thresholds is uncertain³⁷²);

• An LV relative wall thickness >0.42 cm indicates concentric geometry. LV wall thickness >1.4 cm is abnormal³⁷³; and

• Decreased LV ejection fraction is a value <53%.

There are a number of additional evidence gaps related to the echocardiographic assessment of LV target organ injury. The value of LV mass assessment in risk reclassification independent of conventional risk assessment has not been established in adults.³⁶⁴ The costs and benefits of incorporation of echocardiography into HTN care has not been assessed. Quality control regarding reproducibility of measurements across laboratories may be suboptimal.³⁷⁴ The most accurate method to measure LV mass (M-mode; two-dimensional; or, in the near future, three-dimensional techniques) requires further research.

6.7 Vascular Structure and Function

Emerging data demonstrate an association of higher levels of BP in youth with adverse changes in measures of vascular structure and function, including ultrasonography of the cIMT, PWV, a robust measure of central arterial stiffness⁶⁶ that is related to hard CV events in adults (eg, stroke, myocardial infarction, etc),⁶⁹ and FMD, which assesses endothelial function and describes the ability of the endothelium to release nitric oxide in response to stress.³⁷⁵

Although there are multiple large studies of PWV in youth,^376–381 they all suffer from notable limitations, primarily the lack of racial and ethnic diversity and differences in measurement devices and protocols. Researchers in the largest study of PWV in youth to date (N = 6576) only evaluated 10 and 11 year olds and measured only carotid-radial PWV across the arm; this measure has not been linked to CV events in adults.³⁸² Researchers in one large study of FMD performed in youth (N = 5809) only included 10- to 11-year-old children in England.³⁸² The largest set of data for cIMT included 1155 European youth who were 6 to 18 years of age.³⁸³ No racial and ethnic breakdown was provided for this study. The wide heterogeneity in the methods for cIMT measurement hinders the pooling of data. For instance, researchers in the aforementioned article only measured common carotid,³⁸³ although the bulb and internal carotid are the sites of earliest atherosclerotic disease.³⁸⁴

Many studies have had significant issues related to methodology. For example, carotid-femoral PWV is not measured identically with different devices and is not equivalent to other measures of PWV, such as brachial-femoral PWV.^385,386 No direct comparisons have been made between carotid-femoral and brachial-ankle PWV, methods in which brachial-ankle PWV provide values considerably higher than carotid-femoral PWV.³⁷⁸ The brachial-ankle PWV measures stiffness along both a central elastic artery (aorta) and the medium muscular arteries of the leg.

Therefore, insufficient normative data are available to define clinically actionable cut-points between normal and abnormal for these vascular parameters. The routine measurement of vascular structure and function to stratify risk in hypertensive youth cannot be recommended at this time.

6.8 Imaging for Renovascular Disease

6.9 Uric Acid

Cross-sectional data have suggested a relationship between elevated serum uric acid (UA) levels and HTN. Two recent studies of adolescents included in NHANES 1999–2000 and a small study conducted in Italy found that elevated UA levels were associated with higher BP.^395–397 In the Italian study and in another US study of youth with obesity and HTN,^397,398 elevated UA was also associated with other markers of CV risk. These findings suggest that the measurement of UA levels may best be viewed as 1 component of CV risk assessment, especially in those with obesity.

A causative role for elevated UA in the development of childhood HTN has not been definitively established, although recent studies suggest that it may be on the causal pathway. A longitudinal study in which researchers followed a group of children for an average of 12 years demonstrated that childhood UA levels were associated with adult BP levels even after controlling for baseline BP.³⁹⁹ A few small, single-center clinical trials have also shown that lowering UA can decrease BP levels, and increased UA levels blunt the efficacy of lifestyle modifications on BP control.^400–404 No large-scale, multicenter study has yet been conducted to confirm these preliminary findings. Hence, there is currently not sufficient evidence to support the routine measurement of serum UA in the evaluation and management of children with elevated BP.

6.10 Microalbuminuria

Microalbuminuria (MA), which should be differentiated from proteinuria in CKD, has been shown to be a marker of HTN-related kidney injury and a predictor of CVD in adults.^405–408 MA has been shown to be effectively reduced via the use of ARBs and ACE inhibitors in adults. Lowering the degree of MA in adults has been associated with decreased CVD risk.

In contrast, data to support a clear relationship between HTN and MA in pediatric patients with primary HTN are limited.^408–410 A single, retrospective study of children with primary HTN and WCH found that 20% of the former had MA versus 0% of the latter.⁴¹¹ MA appears to be a nonspecific finding in children that can occur in the absence of HTN; it can occur in children who have obesity, insulin resistance, diabetes, dyslipidemia, and even in those who have recently participated in vigorous physical activity.⁴¹² The previously mentioned study by Seeman et al⁴¹¹ did not control for these potential confounders.

Limited, single-center data suggest that a reduction in the degree of MA, more than a reduction in BMI or SBP, is associated with a decrease in LVMI. In particular, researchers in this single-center, nonrandomized, prospective study of 64 hypertensive children without kidney disease who were 11 to 19 years of age evaluated the children at baseline and after 12 months of combination ACE and hydrochlorothiazide (N = 59) or ACE, hydrochlorothiazide, and ARB therapy (N = 5). Results found that lowering MA in children is associated with a regression of LVH.⁴¹³ Given the single-center design and lack of a control group, however, the applicability of these findings to the general population of children with primary HTN is unknown.

7.1 Overall Goals

The overall goals for the treatment of HTN in children and adolescents, including both primary and secondary HTN, include achieving a BP level that not only reduces the risk for target organ damage in childhood but also reduces the risk for HTN and related CVD in adulthood. Several studies have shown that currently available treatment options can even reverse target organ damage in hypertensive youth.^105,414,415

The previous recommendations for HTN treatment target in children without CKD or diabetes were SBP and DBP <95th percentile. Since that recommendation was made, evidence has emerged that markers of target organ damage, such as increased LVMI, can be detected among some children with BP >90th percentile (or >120/80 mm Hg) but <95th percentile.^66,416,417 Longitudinal studies on BP from childhood to adulthood that include indirect measures of CV injury indicate that the risk for subsequent CVD in early adulthood increases as the BP level in adolescence exceeds 120/80 mm Hg.^11,103,418 In addition, there is some evidence that targeting a BP <90th percentile results in reductions in LVMI and prevalence of LVH.¹⁰⁴ Therefore, an optimal BP level to be achieved with treatment of childhood HTN is <90th percentile or <130/80 mm Hg, whichever is lower.

Treatment and management options are discussed below, including lifestyle modifications and pharmacologic therapy to achieve optimal BP levels in children and adolescents with HTN.

7.2 Lifestyle and Nonpharmacologic Interventions

Lifestyle interventions are recommended to lower BP. There is good evidence from studies in adults showing that nutritional interventions lower BP,⁴¹⁹ including clinical trials demonstrating that reducing dietary sodium results in lower BP and CV mortality,³³⁸ and a diet high in olive oil polyphenols lowers BP.⁴²⁰ Studies of hypertensive youth suggest that the relationship between diet, physical activity, and BP in childhood is similar to that observed in adults.

7.3 Pharmacologic Treatment

Children who remain hypertensive despite a trial of lifestyle modifications or who have symptomatic HTN, stage 2 HTN without a clearly modifiable factor (eg, obesity), or any stage of HTN associated with CKD or diabetes mellitus therapy should be initiated with a single medication at the low end of the dosing range (see Table 17). Depending on repeated BP measurements, the dose of the initial medication can be increased every 2 to 4 weeks until BP is controlled (eg, <90th percentile), the maximal dose is reached, or adverse effects occur. Although the dose can be titrated every 2 to 4 weeks using home BP measurements, the patient should be seen every 4 to 6 weeks until BP has normalized. If BP is not controlled with a single agent, a second agent can be added to the regimen and titrated as with the initial drug. Because of the salt and water retention that occurs with many antihypertensive medications, a thiazide diuretic is often the preferred second agent.

Lifestyle modifications should be continued in children requiring pharmacologic therapy. An ongoing emphasis on a healthy, plant-strong diet rich in fruits and vegetables; reduced sodium intake; and increased exercise can improve the effectiveness of antihypertensive medications. The use of a combination product as initial treatment has been studied only for bisoprolol and hydrochlorothiazide,⁴⁴⁹ so the routine use of combination products to initiate treatment in children cannot be recommended. Once BP control has been achieved, a combination product can be considered as a means to improve adherence and reduce cost if the dose and formulation are appropriate.

7.4 Treatment-Resistant HTN

Resistant HTN in adults is defined as persistently elevated BP despite treatment with 3 or more antihypertensive agents of different classes. All of these drugs should be prescribed at maximally effective doses, and at least 1 should be a diuretic. Key to the identification of patients with true resistant HTN is correct office BP measurement, confirmation of adherence to current therapy, and confirmation of treatment resistance by ABPM.

The treatment of patients with resistant HTN includes dietary sodium restriction, the elimination of substances known to elevate BP, the identification of previously undiagnosed secondary causes of HTN, the optimization of current therapy, and the addition of additional agents as needed.⁴⁷⁵ Recent clinical trial data suggest that an aldosterone receptor antagonist (such as spironolactone) is the optimal additional agent in adults with resistant HTN; it helps address volume excess as well as untreated hyperaldosteronism, which is common in adult patients with true resistant HTN.^476,477

At present, there are no data on whether true treatment-resistant HTN exists in pediatric patients. Evaluation and management strategies similar to those proven effective in adults with resistant HTN would be reasonable in children and adolescents who present with apparent treatment resistance.

8.1 Treatment in Patients With CKD and Proteinuria

8.2. Treatment in Patients With Diabetes

Based on the Fourth Report criteria for the diagnosis of HTN,¹ between 4% and 16% of children and adolescents with T1DM are found to have HTN.^14,489–491 In the SEARCH study of 3691 youth between the ages of 3 and 17 years, elevated BP was documented in 6% of children with T1DM, with the highest prevalence in Asian Pacific Islander and American Indian children followed by African American and Hispanic children and those with higher glycosylated hemoglobin A1c levels.¹⁴ An office-based study in Australia found much higher rates (16%) and a positive correlation with BMI.⁴⁹⁰ BP >130/90 mm Hg has been associated with a more-than-fourfold increase in the relative risk of coronary artery disease and mortality at 10-year follow-up of individuals with T1DM.⁴⁹²

The prevalence of HTN is higher in youth with T2DM compared with T1DM, ranging from 12% at baseline (N = 699) in the Treatment Options for Type 2 Diabetes in Adolescents and Youth study⁴⁹³ to 31% (N = 598) in the Pediatric Diabetes Consortium Type 2 Diabetes Clinic Registry.⁴⁹⁴ BP and arterial stiffness in cohort studies have correlated with BMI, male sex, African American race, and age of onset of diabetes.^14,494,495 Unlike T1DM, HTN in T2DM is not correlated with glycosylated hemoglobin A1c levels or glycemic failure, and it develops early in the course of the disease.⁴⁹⁶ It is also associated with rapid onset of adverse cardiac changes^111,497 and may not respond to diet changes.⁴²⁵ The concurrence of obesity and T2DM compounds the risks for target end organ damage.^111,498

Empirical evidence shows a poor awareness of HTN in youth with T1DM and T2DM.¹⁴ Additionally, only a fraction of children with HTN and diabetes were found to be on pharmacologic therapy^{14,490,498,499} despite treatment recommendations from the American Diabetes Association,⁴⁹⁹ the International Society for Pediatric and Adolescent Diabetes,⁵⁰⁰ AHA,¹¹⁰ and the National Heart, Lung, and Blood Institute.⁵⁰¹

9.1 Comorbidities: Dyslipidemia

Children and adolescents with HTN are at increased risk for lipid disorders attributable to the “common soil” phenomenon,⁵⁰² in which poor diet, inactivity, and obesity contribute to both disorders. Some observational pediatric data confirm this association.^503–506 Furthermore, both HTN and dyslipidemias are associated with subclinical atherosclerosis²⁰⁶ and are risk factors for future CVD.⁵⁰³ Screening is recommended to identify those at increased risk for early atherosclerosis.⁵⁰³ Treatment of lipid disorders identified in the setting of HTN should follow existing pediatric lipid guidelines with lifestyle advice, including weight loss and pharmacotherapy, as necessary.⁵⁰³

9.2 Comorbidities: OSAS

Children with snoring, daytime sleepiness (in adolescents), or hyperactivity (in younger children) may have OSAS and consequent HTN.⁵⁰⁷ The more severe the OSAS, the more likely a child is to have elevated BP^44,45 (see Table 18). Children with moderate to severe OSAS are at increased risk for HTN. However, it is not known whether OSAS treatment with continuous positive airway pressure results in improved BP in all children.⁴⁴ Furthermore, adenotonsillectomy may not result in BP improvement in all children with OSAS. In particular, children who have obesity and OSAS may be less likely to experience a lowering of BP after an adenotonsillectomy.⁵⁰⁸

Therefore, children with signs of OSAS (eg, daytime fatigue, snoring, hyperactivity, etc) should undergo evaluation for elevated BP regardless of treatment status. Given that both nighttime and daytime BP is affected by OSAS, the use of ABPM is the recommended method for assessing the BP of children with suspected OSAS.

9.3 Comorbidities: Cognitive Impairment

Data from studies conducted in adults suggest that the central nervous system is a target organ that can be affected by HTN.⁴¹⁹ Preliminary studies suggest that this is true in children as well. Hypertensive children score lower on tests of neurocognition and on parental reports of executive function compared with normotensive controls.^509,510 Adams et al⁵¹¹ found an increased prevalence of learning disabilities in children with primary HTN compared with normotensive controls. The postulated mechanism for these findings is impaired cerebrovascular reactivity.^512–515 At the present time, these findings do not have specific clinical implications with respect to the diagnostic evaluation of childhood HTN, although they underscore the importance of early detection and treatment.

11.1 Acute Severe HTN

There is a lack of robust evidence to guide the evaluation and management of children and adolescents with acute presentations of severe HTN. Thus, much of what is known is derived from studies conducted in adults, including medication choice.⁵²² The evidence base has been enhanced somewhat over the past decade by the publication of several pediatric clinical trials and case series of antihypertensive agents that can be used to treat such patients.^{465,523–530}

Although children and adolescents can become symptomatic from HTN at lesser degrees of BP elevation, in general, patients who present with acute severe HTN will have BP elevation well above the stage 2 HTN threshold. In a study of 55 children presenting to a pediatric ED in Taiwan with hypertensive crisis, 96% had SBP greater than that of stage 2 HTN, and 76% had DBP greater than that of stage 2 HTN.⁵³¹ The major clinical issue in such children is that this level of BP elevation may produce acute target organ effects, including encephalopathy, acute kidney injury, and congestive heart failure. Clinicians should be concerned about the development of these complications when a child’s BP increases 30 mm Hg or more above the 95th percentile.

Although a few children with primary HTN may present with features of acute severe HTN,⁵³² the vast majority will have an underlying secondary cause of HTN.^532,533 Thus, for patients who present with acute severe HTN, an evaluation for secondary causes is appropriate and should be conducted expediently. Additionally, target organ effects should be assessed with renal function, echocardiography, and central nervous system imaging, among others.

Given the potential for the development of potentially life-threatening complications, expert opinion holds that children and adolescents who present with acute severe HTN require immediate treatment with short-acting antihypertensive medications that may abort such sequelae.^533,534 Treatment may be initiated with oral agents if the patient is able to tolerate oral therapy and if life-threatening complications have not yet developed. Intravenous agents are indicated when oral therapy is not possible because of the patient’s clinical status or when a severe complication has developed (such as congestive heart failure) that warrants a more controlled BP reduction. In such situations, the BP should be reduced by no more than 25% of the planned reduction over the first 8 hours, with the remainder of the planned reduction over the next 12 to 24 hours.^533,534 The ultimate short-term BP goal in such patients should generally be around the 95th percentile. Table 19 lists suggested doses for oral and intravenous antihypertensive medications that may be used to treat patients with acute severe HTN.

11.2 HTN and the Athlete

Sports participation and increased physical activity should be encouraged in children with HTN. In adults, physical fitness is associated with lower all-cause mortality.⁵³⁶ Although meta-analyses and randomized controlled trials consistently show lower BP after exercise training in adults,⁵³⁵ the results are less robust in children.³⁴⁰ On the basis of this evidence, sports participation should improve BP over time. Additionally, there is evidence that exercise itself has a beneficial effect on cardiac structure in adolescents.⁵³⁷

The athlete interested in participating in competitive sports and/or intense training presents a special circumstance. Existing guidelines present conflicting recommendations.^1,538 Although increased LV wall dimension may be a consequence of athletic training,³⁶⁰ recommendations from AHA and ACC include the following: (1) limiting competitive athletic participation among athletes with LVH beyond that seen with athlete’s heart until BP is normalized by appropriate antihypertensive drug therapy, and (2) restricting athletes with stage 2 HTN (even among those without evidence of target organ injury) from participating in high-static sports (eg, weight lifting, boxing, and wrestling) until HTN is controlled with either lifestyle modification or drug therapy.⁵³⁹

The AAP policy statement “Athletic Participation by Children and Adolescents Who Have Systemic Hypertension” recommends that children with stage 2 HTN be restricted from high-static sports (classes IIIA to IIIC) in the absence of end organ damage, including LVH or concomitant heart disease, until their BP is in the normal range after lifestyle modification and/or drug therapy.⁵³⁸ It is further recommended that athletes be promptly referred and evaluated by a qualified pediatric medical subspecialist within 1 week if they are asymptomatic or immediately if they are symptomatic. The subcommittee agrees with these recommendations.

It should be acknowledged that there are no data linking the presence of HTN to sudden death related to sports participation in children, although many cases of sudden death are of unknown etiology. That said, athletes identified as hypertensive (eg, during preparticipation sports screening) should undergo appropriate evaluation as outlined above. For athletes with more severe HTN (stage 2 or greater), treatment should be initiated before sports participation.

11.3 HTN and the Posttransplant Patient

HTN is common in children after solid-organ transplants, with prevalence rates ranging from 50% to 90%.^{179,180,540,541} Contributing factors include the use of steroids, calcineurin inhibitors, and mTOR (mammalian target of rapamycin) inhibitors. In patients with renal transplants, the presence of native kidneys, CKD, and transplant glomerulopathy are additional risk factors for HTN. HTN rates are higher by 24-hour ABPM compared with clinic BP measurements because these populations commonly have MH and nocturnal HTN.^{179–183,542} Control of HTN in renal-transplant patients has been improved with the use of annual ABPM.^184,185 Therefore, ABPM should be used to identify and monitor nocturnal BP abnormalities and MH in pediatric kidney and heart-transplant recipients. The use of home BP assessment may provide a comparable alternative to ABPM for BP assessment after transplant as well.¹⁸⁶

The management of identified HTN in the pediatric transplant patient can be challenging. Rates of control of HTN in renal-transplant patients generally range from 33% to 55%.^180,187 In studies by Seeman et al,¹⁸⁸ intensified antihypertensive treatment in pediatric renal-transplant recipients improved nocturnal SBP and significantly reduced proteinuria.⁵⁴³ Children in these studies who achieved normotension had stable graft function, whereas those who remained hypertensive at 2 years had a progression of renal disease.⁵⁴⁴

Antihypertensive medications have rarely been systematically studied in this population. There is limited evidence that ACE inhibitors and ARBs may be superior to other agents in achieving BP control and improving long-term graft survival in renal-transplant patients.^185,543,544 However, the combination of ACE inhibitors and ARBs in renal-transplant patients has been associated with acidosis and hyperkalemia and is not recommended.⁵⁴⁵

13.1 Importance of Preventing HTN

BP levels tend to increase with time even after adult height is reached. The rate of progression to frank HTN in a study of more than 12 000 Japanese adults (20–35 years of age at baseline, followed for 9 years) was 36.5% and was greater with higher baseline BP category.⁵⁴⁸ The rate of progression may also be accelerated in African American individuals. Similarly, both the Bogalusa Heart⁶³ and Fels Longitudinal⁶⁰ studies have clearly demonstrated that the risk of HTN in early adulthood is dependent on childhood BP, with greater numbers of elevated BP measurements in childhood conferring an increased risk of adult HTN.

Because the tracking of BP levels in children has also been well documented,¹⁰ it is not surprising that analyses of the National Childhood BP database found 7% of adolescents with elevated BP per year progressed to true hypertensive BP levels. Of note, initial BMI and change in BMI were major determinants of the development of HTN.²² Therefore, in both children and adults, efforts (discussed below) should be made to prevent progression to sustained HTN and to avoid the development of hypertensive CV diseases.

13.2 Strategies for Prevention

One of the largest trials of preventing progression to HTN in adults, the Trial of Preventing Hypertension study, proved that 2 years of treatment with candesartan reduced the number of subjects with elevated BP from developing stage 1 HTN even after the drug was withdrawn.⁵⁴⁷ However, no similar study has been conducted in youth; for this reason, prevention efforts to date have focused on lifestyle modification, especially dietary intervention,⁴²⁶ exercise,⁵⁴⁹ and treatment of obesity.⁵⁵⁰ The best evidence for the potential of such prevention strategies comes from epidemiologic evidence for risk factors for the development of HTN or from studies focused on the treatment of established HTN. These risk factors include positive family history, obesity, a high-sodium diet, the absence of a DASH-type diet, larger amounts of sedentary time, and possibly other dietary factors.^551–553

Because family history is immutable, it is difficult to build a preventive strategy around it. However, a positive family history of HTN should suggest the need for closer BP monitoring to detect HTN if it occurs.

Appropriate energy balance with calories eaten balanced by calories expended in physical activity is important. This is the best strategy to maintain an appropriate BMI percentile for age and sex and to avoid the development of obesity.⁵⁵⁴ From a broader dietary perspective, a DASH-type diet (ie, high in fruits, vegetables, whole grains, and low-fat dairy, with decreased intake of foods high in saturated fat or sugar) may be beneficial (see Table 16).^423,427 Avoiding high-sodium foods may prove helpful in preventing HTN, particularly for individuals who are more sensitive to dietary sodium intake.⁵⁵⁵

Adhering to recommendations for 60 minutes a day of moderate to vigorous physical activity can be important to maintaining an appropriate weight and may be independently helpful to maintaining a lower BP.³⁴⁴ The achievement of normal sleep habits and avoidance of tobacco products are also reasonable strategies to reduce CV risk.

These preventive strategies can be implemented as part of routine primary health care for children and adolescents.

15.1 Economic Impact of BP Management

Researchers in a small number of studies have examined the potential economic impacts related to pediatric BP management.^208,558,559 Wang et al⁵⁵⁸ estimated both the effectiveness and cost-effectiveness of 3 screening strategies and interventions to normalize pediatric BP based on the literature and through a simulation of children (n = 4 017 821). The 3 screening strategies included the following: (1) no screening; (2) selected screening and treatment, as well as “treating everyone” (ie, with population-wide interventions, such as targeted programs for overweight adolescents [eg, weight-loss programs, exercise programs, and salt-reduction programs]); and (3) nontargeted programs for exercise and salt reduction.

The simulation suggested that these various strategies could reduce mortality, with a modest expected survival benefit of 0.5 to 8.6 days. The researchers also examined quality-adjusted life-years (QALYs) and the cost per QALY. Only 1 intervention, a nontargeted salt-reduction campaign, had a negative cost per QALY. This intervention and the other 2 described in that article support the concept that population-wide interventions may be the most cost-effective way to improve CV health. The article has serious limitations, however, including the fact that population-wide interventions for exercise and the reduction of sodium intake have not, thus far, been effective.

The accurate determination of those who actually have HTN (as opposed to WCH) is fundamental to providing sound care to patients. Researchers in two studies examined the effects of using ABPM in the diagnosis of HTN.^208,559 Davis et al⁵⁵⁹ compared 3 HTN screening strategies; these options are summarized in the following value-analysis framework (see Table 20).⁵⁶⁰ It appears that the implementation of ABPM for all patients is not ensured. The next best option, screening clinic BP with ABPM, is most likely to be implementable and has significant clinical benefit given the high prevalence of WCH.

Swartz et al²⁰⁸ conducted a retrospective review of 267 children with elevated clinic BP measurements referred for ABPM. Of the 126 patients who received ABPM, 46% had WCH, 49% had stage 1 HTN, and 5% had stage 2 HTN. This is consistent with the concept that screening with clinic BP alone results in high numbers of false-positive results for HTN. The diagnosis of HTN in this study resulted in an additional $3420 for evaluation (includes clinic visit, facility fee, laboratory testing, renal ultrasound, and echocardiography) vs $1265 (includes clinic visit, facility fee, and ABPM). This suggests that ABPM is cost-effective because of the reduction of unnecessary testing in patients with WCH.

When examining these costs, the availability of ABPM, and the availability of practitioners who are skilled in pediatric interpretation, the most cost-effective and implementable screening solution is to measure clinic BP and confirm elevated readings by ABPM.

15.2 Patient Perspective and Pediatric HTN

Children and adolescents are not just patients; they are active participants in their health management. If children and adolescents lack a clear understanding of what is happening inside their bodies, they will not be able to make informed choices in their daily activities. Better choices lead to better decisions executed in self-care. For clear judgments to be made, there needs to be open communication between physicians and families, a provision of appropriate education on optimal HTN management, and a strong partnership assembled within a multidisciplinary health care team including physicians, advanced practice providers, dietitians, nurses, and medical and clinical assistants.

It is important for physicians to be mindful that children and adolescents want, and need, to be involved in their medical care. Pediatric HTN patients are likely to feel excluded when clinicians or other providers speak to their parents instead of including them in the conversation. When patients are neither included in the discussion nor encouraged to ask questions, their anxiety can increase, thus worsening their HTN. Keeping an open line of communication is important and is best done by using a team approach consisting of the patient, the family, health care support staff, and physicians. With practical education on HTN management provided in easily understandable terms, the patients will be more likely to apply the concepts presented to them. Education is important and should be given in a way that is appropriate for young children and their families to understand. Education should consist of suitable medication dosing, a proper diet and level of activity, the identification of symptoms, and appropriate BP monitoring (including cuff size).

15.3 Parental Perspective and Pediatric HTN

Parents play a key role in the management and care of their children’s health. Parents and physicians should act as a cohesive unit to foster the best results. It is vital for physicians to provide concise information in plain language and do so using a team approach. This will facilitate parents having a clear understanding of the required tests, medications, follow-ups, and outcomes.

Parents of children with hypertensive issues can encounter 1 or more specialists in addition to their pediatric clinician. This can prove to be overwhelming, frightening, and may fill the parent with anxiety. Taking these things into account and creating unified partners, built with the physician and family, will encourage the family to be more involved in the patient’s health management. Plain language in a team approach will yield the most positive outcomes for the patient.

Understanding the family and patient’s perception of HTN and any underlying disease that may be contributing to it is important to resolve any misconceptions and encourage adherence to the physician’s recommendations. To attain therapeutic goals, proper education must be provided to the family as a whole. This education should include proper medication dosages, recommended sodium intake, any dietary changes, exercise expectations, and any other behavioral changes. It is equally important to stress to the family the short- and long-term effects of HTN if it is not properly managed. Parents with younger children will carry the ultimate burden of daily decisions as it applies to medications, food choices, and activity. Parents of older adolescents will partner with the children to encourage the right choices. Education as a family unit is important for everyone involved to understand the consequences.

A family-based approach is important for all pediatric diseases but plays a particular role in conditions that are substantially influenced by lifestyle behaviors. This has been shown in several pediatric populations, including those with T2DM and obesity.^561–565