Adolescent Health Care: A Practical Guide

Chapter 13

Systemic Hypertension

Joseph T. Flynn

Although more than 58 million American adults, or approximately 29% of the population, have systemic hypertension, screening studies in children and adolescents have demonstrated a prevalence of persistent hypertension of between 1% and 2%. Given the impact of the obesity epidemic on the prevalence of hypertension in adolescents, more recent studies, however, have demonstrated a higher prevalence of approximately 5% in obese minority adolescents (Sorof et al., 2004). Most adolescents and adults with hypertension have primary hypertension—that is, no identifiable underlying cause can be found for their blood pressure (BP) elevation. Most hypertensive adolescents, particularly those with primary hypertension, are asymptomatic. Therefore, it is imperative that BP is measured whenever an adolescent is seen for health care. Detection and treatment of hypertension in the adolescent years may prevent later cardiovascular diseases, with their catastrophic consequences (Kavey et al., 2003).

Definition of Hypertension in Adolescence

Definition

The cardiovascular endpoints used to define hypertension in adults (myocardial infarction, stroke, etc.) do not occur in children and adolescents. Therefore, the definition of hypertension in the young is a statistical one derived from analysis of a large database of BPs obtained from healthy children (National High Blood Pressure Education Program Working Group, 2004). The most recent classification of BP in the young is summarized in Table 13.1.

Normative BP values for adolescents ≤17 years of age are listed in Tables 13.2 and 13.3. For these children, height should first be obtained and plotted on a standard growth curve to determine the child's height percentile. Then the gender-appropriate chart should be used to determine the BP percentile. For adolescents ≥18 years of age, the adult BP classification scheme issued by the Joint National Commission (Chobanian et al., 2003) should be followed (Table 13.4).

Prehypertension

Common to both the pediatric and adult BP classification schemes is the recent concept of “prehypertension”. This refers to BPs that would have been classified as “high-normal” in prior consensus recommendations. Although the term prehypertension has proved to be controversial, it is meant to serve as a means of alerting patients and physicians alike of the potential for later development of hypertension, and of the need to make lifestyle changes that might prevent this from occurring. The same BP value of >120/80 mm Hg is used in both adolescents and adults to designate prehypertension.

TABLE 13.1 Classification of Blood Pressure in Adolescents 17 years and Younger

Blood Pressure Classification Systolic or Diastolic Blood Pressure Percentilea a See Tables 13.2 and 13.3. taken from National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National Heart, Lung, and Blood Institute, Bethesda, Maryland. NIH Publication 05-5267, 2005. Normal <90th Prehypertension 90th–95th; or if BP is >120/80 mm Hg even if <90th Stage 1 hypertension 95th to 99th plus 5 mm Hg Stage 2 hypertension >99th plus 5 mm Hg

Staging

Also common to both the pediatric and adult BP classification schemes is the concept of “staging” the degree of hypertension. For children and adolescents, this replaces the older terms of denoting higher levels of hypertension, such as “significant” and “severe”. As will be discussed later, the staging system also plays a role in determining how rapidly a hypertensive adolescent should be

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evaluated, and when antihypertensive drug therapy should be instituted.

TABLE 13.2 Blood Pressure Values for Adolescent Boys 17 Years or Younger

Systolic BP (mm Hg) Diastolic BP (mm Hg) ← Percentile of Height → ← Percentile of Height → Age (yr) BP Percentile 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th BP, blood pressure. To use the table, first plot the child's height on a standard growth curve (www.cdc.gov/growthcharts). The child's measured systolic blood pressure and diastolic blood pressure are compared with the numbers provided in the table according to the child's age and height percentile. National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National Heart, Lung, and Blood Institute, Bethesda, Maryland. NIH Publication 05-5267, 2005. 10 50th 97 98 100 102 103 105 106 58 59 60 61 61 62 63 90th 111 112 114 115 117 119 119 73 73 74 75 76 77 78 95th 115 116 117 119 121 122 123 77 78 79 80 81 81 82 99th 122 123 125 127 128 130 130 85 86 86 88 88 89 90 11 50th 99 100 102 104 105 107 107 59 59 60 61 62 63 63 90th 113 114 115 117 119 120 121 74 74 75 76 77 78 78 95th 117 118 119 121 123 124 125 78 78 79 80 81 82 82 99th 124 125 127 129 130 132 132 86 86 87 88 89 90 90 12 50th 101 102 104 106 108 109 110 59 60 61 62 63 63 64 90th 115 116 118 120 121 123 123 74 75 75 76 77 78 79 95th 119 120 122 123 125 127 127 78 79 80 81 82 82 83 99th 126 127 129 131 133 134 135 86 87 88 89 90 90 91 13 50th 104 105 106 108 110 111 112 60 60 61 62 63 64 64 90th 117 118 120 122 124 125 126 75 75 76 77 78 79 79 95th 121 122 124 126 128 129 130 79 79 80 81 82 83 83 99th 128 130 131 133 135 136 137 87 87 88 89 90 91 91 14 50th 106 107 109 111 113 114 115 60 61 62 63 64 65 65 90th 120 121 123 125 126 128 128 75 76 77 78 79 79 80 95th 124 125 127 128 130 132 132 80 80 81 82 83 84 84 99th 131 132 134 136 138 139 140 87 88 89 90 91 92 92 15 50th 109 110 112 113 115 117 117 61 62 63 64 65 66 66 90th 122 124 125 127 129 130 131 76 77 78 79 80 80 81 95th 126 127 129 131 133 134 135 81 81 82 83 84 85 85 99th 134 135 136 138 140 142 142 88 89 90 91 92 93 93 16 50th 111 112 114 116 118 119 120 63 63 64 65 66 67 67 90th 125 126 128 130 131 133 134 78 78 79 80 81 82 82 95th 129 130 132 134 135 137 137 82 83 83 84 85 86 87 99th 136 137 139 141 143 144 145 90 90 91 92 93 94 94 17 50th 114 115 116 118 120 121 122 65 66 66 67 68 69 70 90th 127 128 130 132 134 135 136 80 80 81 82 83 84 84 95th 131 132 134 136 138 139 140 84 85 86 87 87 88 89 99th 139 140 141 143 145 146 147 92 93 93 94 95 96 97

There are several important considerations in evaluating BP in children and adolescents of any age. They are as follows:

1. Although various methods are available to measure BP, auscultation is the most accurate and is the method of choice. Because of the removal of mercury sphygmomanometers from most health care settings, aneroid devices should be made available and utilized. The stethoscope bell should be used for auscultation, as it is better suited to detect soft, low-pitched Korotkoff sounds than the diaphragm.
2. BP in the young is labile; therefore, hypertension should not be diagnosed on the basis of a single measurement. At least three elevated readings on separate occasions are necessary to diagnose hypertension. Using one isolated measurement may lead to mislabeling of an individual, with adverse consequences.
3. Proper cuff bladder size is critical. The length of the cuff bladder should be at least 80% of the mid-arm circumference. For practical purposes, use the largest cuff that fits the arm while leaving the antecubital fossa free for auscultation. It is better to choose a cuff slightly too big than one too small, as a cuff that is too small will give a falsely elevated BP, but one that is slightly large will not give a falsely low reading.
4. BP measurements should be taken with the adolescent in the sitting position, with the sphygmomanometer at heart level. The arm (preferably the right) used for the measurement should be recorded in the chart. Ideally,

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the adolescent should have rested for several minutes and should not have smoked or ingested caffeine within 30 minutes before measurement.

5. For apprehensive patients, BP measurements obtained outside of the office setting, such as by a school nurse or at home using a calibrated over-the-counter device may provide insight as to the existence of “white coat” hypertension. However, ambulatory monitoring, in which BP measurements are obtained over a 24-hour period with an automated device, is the preferred technique for diagnosing white coat hypertension. Given the high prevalence of white coat hypertension in recent studies (Sorof and Portman, 2000), ambulatory BP monitoring should be considered as part of the initial evaluation of an adolescent or young adult with elevated BPs in the office setting.

TABLE 13.3 Blood Pressure Values for Adolescent Girls 17 Years or Younger

Systolic BP (mm Hg) Diastolic BP (mm Hg) ← Percentile of Height → ← Percentile of Height → Age (yr) BP Percentile 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th BP, blood pressure. To use the table, first plot the child's height on a standard growth curve (www.cdc.gov/growthcharts). The child's measured systolic blood pressure and diastolic blood pressure are compared with the numbers provided in the table according to the child's age and height percentile. From National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National Heart, Lung, and Blood Institute, Bethesda, Maryland. NIH Publication 05-5267, 2005. 10 50th 98 99 100 102 103 104 105 59 59 59 60 61 62 62 90th 112 112 114 115 116 118 118 73 73 73 74 75 76 76 95th 116 116 117 119 120 121 122 77 77 77 78 79 80 80 99th 123 123 125 126 127 129 129 84 84 85 86 86 87 88 11 50th 100 101 102 103 105 106 107 60 60 60 61 62 63 63 90th 114 114 116 117 118 119 120 74 74 74 75 76 77 77 95th 118 118 119 121 122 123 124 78 78 78 79 80 81 81 99th 125 125 126 128 129 130 131 85 85 86 87 87 88 89 12 50th 102 103 104 105 107 108 109 61 61 61 62 63 64 64 90th 116 116 117 119 120 121 122 75 75 75 76 77 78 78 95th 119 120 121 123 124 125 126 79 79 79 80 81 82 82 99th 127 127 128 130 131 132 133 86 86 87 88 88 89 90 13 50th 104 105 106 107 109 110 110 62 62 62 63 64 65 65 90th 117 118 119 121 122 123 124 76 76 76 77 78 79 79 95th 121 122 123 124 126 127 128 80 80 80 81 82 83 83 99th 128 129 130 132 133 134 135 87 87 88 89 89 90 91 14 50th 106 106 107 109 110 111 112 63 63 63 64 65 66 66 90th 119 120 121 122 124 125 125 77 77 77 78 79 80 80 95th 123 123 125 126 127 129 129 81 81 81 82 83 84 84 99th 130 131 132 133 135 136 136 88 88 89 90 90 91 92 15 50th 107 108 109 110 111 113 113 64 64 64 65 66 67 67 90th 120 121 122 123 125 126 127 78 78 78 79 80 81 81 95th 124 125 126 127 129 130 131 82 82 82 83 84 85 85 99th 131 132 133 134 136 137 138 89 89 90 91 91 92 93 16 50th 108 108 110 111 112 114 114 64 64 65 66 66 67 68 90th 121 122 123 124 126 127 128 78 78 79 80 81 81 82 95th 125 126 127 128 130 131 132 82 82 83 84 85 85 86 99th 132 133 134 135 137 138 139 90 90 90 91 92 93 93 17 50th 108 109 110 111 113 114 115 64 65 65 66 67 67 68 90th 122 122 123 125 126 127 128 78 79 79 80 81 81 82 95th 125 126 127 129 130 131 132 82 83 83 84 85 85 86 99th 133 133 134 136 137 138 139 90 90 91 91 92 93 93

Epidemiology

As noted in the introduction, the prevalence of hypertension in children and adolescents in screening studies is generally between 0.5% and 2%. The importance of repeated measurements is demonstrated in a study of

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3,537 adolescents in New York (Kilcoyne et al., 1974). In this study, 5.4% of adolescents had systolic hypertension and 7.8% had diastolic BPs of >140/90 mm Hg on the first screening. The prevalence dropped to 1.2% and 2.4%, respectively, after a second screening. More recently, screenings conducted in Houston, Texas, public schools have also demonstrated a decreased prevalence of hypertension after repeated measurements (Sorof et al., 2004). Table 13.5 lists various prevalence studies of hypertension in children and adolescents.

TABLE 13.4 Classification of Blood Pressure in Adolescents 18 Years or Older

Blood Pressure classification Systolic Blood Pressure (mm Hg) Diastolic Blood Pressure (mm Hg) From Chobanian AV, Bakris GL, Black HR, et al. The seventh report of the joint national committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 2003;289:2560. Normal <120 and <80 Prehypertension 120–139 or 80–89 Hypertension: Stage 1 140–159 or 90–99 Stage 2 ≥160 or ≥100

TABLE 13.5 Prevalence of Hypertension in Children and Adolescents

Study Location Number Screened Age (yr) Number of Screenings Threshold BP Value Prevalence Reference BP, blood pressure; dHTN, diastolic hypertension; sHTN, systolic hypertension; TF, Second Task Force Report (1987); WG, Working Group Report (1996). Muscatine, IA, United States 1,301 14–18 1 140/90 8.9% sHTN 12.2% dHTN Lauer et al., 1975 Edmonton, Canada 15,594 15–20 1 150/95 2.2% Silverberg et al., 1975 Dallas, TX, United States 10,641 14 3 95th percentile 1.2% sHTN 0.4% dHTN Fixler et al., 1979 Minneapolis, MN, United States 14,686 10–15 1 1987 TF 4.2% Sinaiko et al., 1989 Tulsa, OK, United States 5,537 14–19 1 1987 TF 6.0% O'Quin et al., 1992 Buraidah, Saudi Arabia 3,299 3–18 1 1996 WG 10.6% Soyannwo et al., 1997 Minneapolis, MN, United States 14,686 10–15 2 1996 WG 0.8% sHTN 0.4% dHTN Androgue and Sinaiko, 2001 Houston, TX, United States 5,102 12–16 3 1996 WG 4.5% Sorof et al., 2004

Factors that Influence Blood Pressure

Height and Weight

Height has already been mentioned as part of the definition of normative BP in childhood and adolescence (Rosner et al., 1993; National High Blood Pressure Education Program Working Groups, 1996, 2004); this conclusion was based on statistical analysis of the childhood BP database. Others hold that weight is the most important factor in determining BP. Weight has long been held to have a positive relationship with BP, as demonstrated in a study of Minneapolis school children (Luepker et al., 1999). More than half of hypertensive young people are obese. Higgins et al. (1984) suggested that if weight could be reduced in young people to below-obesity levels the prevalence of hypertension would decrease by one third.

Age

BP increases with age in a nonlinear manner through adolescence; this is likely related to growth. Beyond adolescence, BP continues to increase in a significant percentage of individuals as the result of genetic and environmental factors.

Sodium and Other Dietary Constituents

Controversy prevails over the numerous studies concerning the relationship of sodium intake to BP. For most individuals, little correlation exists. However, in certain

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salt-sensitive individuals, sodium restriction appears beneficial. For example, it has been suggested (Hohn et al., 1983) that African-American children from hypertensive families may be salt sensitive. Obese adolescents also have heightened responsiveness to sodium intake (Rocchini et al., 1989).

Other studies have found a link between potassium intake and both elevated and low BP. However, efforts to correlate calcium and other divalent cations with BP have been equivocal. Similarly, correlations between BP and vitamins A, C, and E, although suggestive, remain to be proved. Falkner et al. (2000) noted that dietary modification of certain nutrients when instituted at an early age could contribute to the prevention of hypertension in urban minority adolescents at risk for hypertension.

Stress

Both physical stress and mental stress evoke changes in BP. Indeed, the degree of change has been thought by some to be useful in predicting later-life hypertension. Early studies by Falkner demonstrated that hypertensive adolescents had significantly greater increases in heart rate, systolic BP, and diastolic BP during mental stress (performance of difficult arithmetic problems) than normotensive adolescents (Falkner et al., 1981). Increased cardiovascular reactivity to the cold pressor test has also been shown to predict the subsequent development of hypertension (Menkes et al., 1989).

Race

Although a significant determinant in adult BP, race is not a factor in teens. Hohn et al. (1983) suggested that certain subgroups of African-American youths have higher BPs than their white counterparts, and Rabinowitz et al. (1993) found a higher prevalence of hypertension among African-American females than among non-Hispanic females. However, Baron et al. (1986) found no significant differences in BP among white, black, and Mexican-American youths. Ethnicity and socioeconomic status have also been related to BP and cardiovascular reactivity (Barnes et al., 2000).

Genetics

Both familial aggregation BP studies, such as those of Lascaux-Lefebvre et al. (1999), and twin studies, such as those of Schieken (1993), indicate a strong positive correlation between hereditary influences and BP measurements. Colhoun (1999) estimated that approximately one third of variations in BP among individuals are due to genetic factors most likely from several genes. Additionally, several single-gene defects have also been recently described (Lifton et al., 2001), which account for hypertension in a small number of children and adolescents, especially those with a family history of severe hypertension of early onset.

Birth Weight and Other Perinatal Factors

The so-called “fetal origins” hypothesis maintains that low birth weight is a risk factor for the subsequent development of primary hypertension in adulthood. This hypothesis is based on the findings of large population studies that demonstrate an inverse correlation between birth weight and adult BP (Barker et al., 1993; Zureik et al., 1996). Proposed explanations for this effect include deficient maternal nutrition, possibly leading to acquisition of a reduced number of nephrons in utero. Other investigators have demonstrated that maternal smoking during pregnancy and bottle-feeding of newborns also may lead to hypertension later in life (Beratis et al., 1996; Singhal et al., 2001), thereby widening the spectrum of possible influences on later BP to include postnatal factors as well. On the other hand, other epidemiological studies have found that adult BP is more closely related to early childhood growth (Falkner et al., 1998) than to birth weight. While more research is clearly needed, it is apparent that at least in some individuals, perinatal and early childhood factors may play an important role in the later development of hypertension.

Etiology

The causes of hypertension vary among different age-groups. In adolescents, the prevalence of primary hypertension is increased in comparison with younger children. This is particularly true for mild hypertension. Table 13.6 shows an estimation of the causes of hypertension in adolescents from data gathered from a number of population studies. This information shows that primary hypertension is by far the most common cause of hypertension in the adolescent. As in younger children, renal parenchymal diseases are the most common secondary cause in the adolescent age-group.

TABLE 13.6 Estimated Causes of Hypertension in Children and Adolescents

School-aged Children Adolescents a Breakdown of causes is generally similar to that for school-aged children. Primary/essential 15%–30% 80%–90% Secondary 70%–85% 10%–20%a Renal parenchymal disease 60%–70% Renovascular 5%–10% Endocrine 3%–5% Aortic coarctation 10%–20% Reflux nephropathy 5%–10% Neoplastic 1%–5% Miscellaneous 1%–5%

At least 80% of hypertensive adolescents have no known cause for their disorder and are labeled as having primary or essential hypertension. Primary hypertension in adolescents is frequently characterized by isolated systolic BP elevation (Flynn and Alderman, 2005), whereas diastolic

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BP elevation is more likely to be present in secondary hypertension. Obesity and a positive family history of hypertension are also common in adolescents with primary hypertension.

Diagnosis

Confirmation of Hypertension

Adolescents make fewer visits per year to health care practitioners than other age-groups. However, each visit presents an opportunity to assess the BP. Approximately 10% of these young people will have a high initial BP (at or above the 95th percentile). They should be labeled as having an elevated BP, and not given a diagnosis of hypertension. Before a diagnosis of hypertension can be made, two subsequent BP determinations on different days must also show a high systolic or diastolic pressure or both (National High Blood Pressure Education Program Working Group, 2004). Only 1% to 2% of adolescents will fulfill these criteria and, by definition, have hypertension.

Additionally, determination of “out-of-office BP” to assess possible “white coat hypertension” is increasingly advocated. Recently, however, Vaindirlis et al. (2000) presented data supporting the hypothesis that such “white coat” hypertension may actually be a prelude to permanent hypertension.

Once the diagnosis of hypertension has been confirmed, a diagnostic evaluation and management plan can be initiated. The algorithm in Figure 13.1, although originally designed for children ≤17 years of age, is appropriate for all adolescents and should be followed.

FIGURE 13.1 Algorithm for the identification, diagnosis, and management of hypertension in adolescents. BMI, body mass index; BP, blood pressure; Rx, Treatment. *See tables 13.2, 13.3 and 13.4. †Diet modification and physical activity. ‡Especially if younger, very high BP, little or no family history, diabetic, or other risk factors. Reprinted from National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. National Heart, Lung, and Blood Institute, Bethesda, Maryland. NIH Publication 05-5267, 2005.

Diagnostic Evaluation

The diagnostic evaluation must be tailored to the individual patient, taking into account the age, sex, race, family history, and level of hypertension. For example, a 12-year-old white female with a past medical history of recurrent urinary tract infections, no family history of hypertension, and a BP of 150/115 mm Hg would be a candidate for an aggressive evaluation for secondary causes, particularly renal parenchymal disease, specifically reflux nephropathy.

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In contrast, invasive studies to look for a secondary cause are unlikely to be helpful in a 17-year-old obese African-American boy with a family history of hypertension and a BP of 150/78 mm Hg. Consultation with someone knowledgeable about hypertension in young people can often be helpful to pursue the most cost-effective and safest diagnostic evaluation.

TABLE 13.7 Substances That May Elevate Blood Pressure in Adolescents

Prescription Medications Nonprescription Medications Others a These cause elevated blood pressure relatively infrequently compared with the other agents in the table. Calcineurin inhibitors (cyclosporine, tacrolimus) Caffeine Cocaine Ephedrine Ethanol Dexedrinea Nonsteroidal anti-inflammatory drugsa Heavy metals (lead, mercury) Erythropoietin MDMA (“Ecstasy”) Glucocorticoids Pseudoephedrine Tobacco Methylphenidatea Herbal preparations (Ephedra, Glycyrrhiza) Oral contraceptives Phenylpropanolamine Pseudoephedrine Tricyclic antidepressantsa

1. History: Investigating a young person for hypertension requires that a detailed history be elicited. The history should aim at eliciting clues of possible secondary causes, target-organ damage, and other cardiovascular risk factors. Look for symptoms of urinary tract infections or renal disease and for a family history of hypertension or other cardiovascular disease. Activity, dietary, and other habits should be sought. The adolescent with an elevated BP should also be questioned about alcohol, tobacco, and substance use, as many substances may elevate BP (Table 13.7). Also ask about ergogenic aids such as anabolic steroids as well as any complementary or alternative medicine products that they might be using. Clues from the history suggestive of secondary hypertension are listed in Table 13.8.
2. Physical examination: A thorough examination is also an essential part of the diagnostic study. The adolescent in question will often be obese. The examination should include an exploration for evidence of a secondary cause or end-organ damage and an evaluation of the following:
3. Height, weight, and body mass index (BMI) (calculated)
4. BP in both arms and a lower extremity
5. Femoral pulses
6. Neck: Carotid bruits or an enlarged thyroid gland
7. Fundi: Arteriolar narrowing, arteriovenous nicking, hemorrhages, exudates
8. Abdomen: Bruits, hepatosplenomegaly, flank masses
9. Heart: Rate, precordial heave, clicks, murmurs, arrhythmias
10. Extremities: Pulses, edema
11. Nervous system
12. Skin: Striae, acanthosis nigricans, café au lait spots, neurofibromas

Physical examination findings suggestive of secondary causes of hypertension are listed in Table 13.8. In addition, the clinician should remember that severe hypertension in an adolescent suggests a secondary cause, particularly renal disease. Acute onset may also suggest acute renal disease.

3. Laboratory testing: Some basic/screening studies should be performed in all adolescents with confirmed BP elevation, whereas others should be reserved for those in whom secondary hypertension is suspected or in those with stage 2 hypertension.
4. Screening tests—should be done in all patients and these include:

• Electrolytes
• Blood urea nitrogen (BUN) and creatinine
• Urinalysis
• Fasting lipid profile
• Complete blood cell (CBC) count
• Urine cultures should be done as appropriate based on the history and urinalysis findings. Add a fasting glucose with or without a fasting insulin in obese adolescents to screen for impaired glucose tolerance/hyperinsulinemia.

1. Specific laboratory testsshould be done as appropriate to follow up on clues from the history and physical examination, or from the screening test results. These might include an antinuclear antibody (ANA) test and sedimentation rate in a hypertensive female adolescent with a malar rash, thyroid studies if there is a history of thyroid dysfunction for example, heat/cold intolerance, menstrual dysfunction, and so on.
2. Echocardiogramsare now recommended to be obtained in all adolescents with confirmed hypertension (National High Blood Pressure Education Program Working Group, 2004). This is to detect left ventricular hypertrophy (LVH), which is a risk factor for sudden cardiac death and an indication to initiate or intensify antihypertensive drug therapy. Recent studies have shown that LVH occurs commonly in hypertensive adolescents (Hanevold et al., 2004; Flynn, 2005).
3. Advanced testingshould only be done to confirm suspected secondary causes of hypertension, for

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example, plasma normetanephrine to norepinephrine ratio if pheochromocytoma is suspected, or a 24-hour urine collection for proteinuria if there is persistent proteinuria on the urinalysis.

1. Imaging studiesshould only be obtained in specific circumstances. Renal ultrasonography should be obtained in all adolescents with stage 2 hypertension, or in those with stage 1 hypertension and an abnormal urinalysis. Chest x-rays should only be obtained if the cardiac examination is abnormal. More advanced studies such as renal scans or angiography are useful in a very small percentage of hypertensive adolescents and should only be obtained under the direction of the appropriate subspecialist.

TABLE 13.8 History and Physical Examination Findings Suggestive of Secondary Causes of Hypertension

UTI, urinary tract infection; BP, blood pressure; SLE, systemic lupus erythematosus; RAS, renal artery stenosis; HTN, hypertension. Present in History Suggests Known UTI/UTI symptoms Reflux nephropathy Joint pains, rash, fever Vasculitis, SLE Acute onset of gross hematuria Glomerulonephritis, renal thrombosis Renal trauma Renal infarct, RAS Abdominal radiation Radiation nephritis, RAS Renal transplant Transplant RAS Precocious puberty Adrenal disorder Muscle cramping, constipation Hyperaldosteronism Excessive sweating, headache, pallor and/or flushing Pheochromocytoma Known illicit drug use Drug-induced hypertension Present on Examination Suggests BP >140/100 mm Hg at any age Secondary hypertension Leg BP < arm BP Aortic coarctation Poor growth, pallor Chronic renal disease Turner syndrome Aortic coarctation Café au lait spots Renal artery stenosis Delayed leg pulses Aortic coarctation Precocious puberty Adrenal disorder Bruits over upper abdomen Renal artery stenosis Edema Renal disease Excessive sweating Pheochromocytoma Excessive pigmentation Adrenal disorder Striae in a male Drug-induced HTN

Therapy

Prevention

Optimally, measures to prevent or minimize the effects of hypertension should be applied to those adolescents at risk of developing hypertension later in life. The difficulty lies in finding those at risk and deciding what measures to apply. Data from young people for this purpose are lacking, and long-term follow-up information is unavailable. Nevertheless, a starting point for such a strategy is to consider those with the findings listed in the subsequent text as being at risk. They should be counseled about nonpharmacologic approaches to maintain lower BP and should be periodically monitored:

1. Those with prehypertension (>120/80 mm Hg)
2. Those with BMI >85th percentile, particularly if parents are obese
3. Those with hyperlipidemia or a family history of the disorder, particularly if there is a known family history of coronary artery disease or stroke
4. Those with type 1 or type 2 diabetes mellitus
5. Those with two or more family members with treated hypertension, particularly African-Americans and Hispanics

Nonpharmacologic Interventions

Although the magnitude of change in BP may be modest, weight loss, aerobic exercise, and dietary modifications have all been shown to successfully reduce BP in children and adolescents, at least in research settings. Such “therapeutic lifestyle changes” should therefore be incorporated into the treatment plan for any hypertensive adolescent, whether a secondary cause has been identified, and whether there is an indication to initiate antihypertensive drug therapy (Fig. 13.1).

1. Weight reduction: Excess body weight is correlated closely with increased BP. Weight reduction reduces BP in a large proportion of hypertensive individuals who are >10% above ideal weight.

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2. Dietary changes: Moderate sodium restriction in hypertensive individuals has been shown, on average, to reduce systolic BP by 4.9 mm Hg and diastolic BP by 2.6 mm Hg. The benefits of sodium restriction are probably greatest in those with renal disease, those with long-standing hypertension, and possibly also African-Americans. Although there has been some evidence to suggest that potassium, calcium, or magnesium supplementation might theoretically be of benefit, studies have not always confirmed a beneficial effect of supplementing the diet with these minerals. On the other hand, the so-called “DASH diet,” which is lower in sodium content and enhanced in potassium and calcium intake, has been demonstrated to be of benefit in hypertensive adults (Appel et al., 1997) and should probably be recommended for hypertensive adolescents.
3. Regular physical exercise: Regular aerobic physical activity, adequate to achieve at least a moderate level of physical fitness, may be beneficial for both prevention and treatment of hypertension. Regular aerobic physical activity (≥30 minutes/session, 4–5 days/week) can reduce systolic BP in hypertensive patients by approximately 10 mm Hg.
4. Other Lifestyle changes: Discontinuance of smoking and avoidance of alcohol excess, medications (except as directed by health care providers), and drugs (e.g., cocaine, amphetamines). In addition to elevating BP, cigarette smoking is a major risk factor for cardiovascular disease and therefore should be avoided by hypertensive individuals. Excessive alcohol intake can raise BP and cause resistance to antihypertensive therapy.

Pharmacologic Treatment

1. Antihypertensive medications are definitely indicated for those who have the following:
2. Symptoms of hypertension
3. Stage 2 hypertension
4. Evidence of hypertensive end-organ damage
5. Type 1 or type 2 diabetes
6. Secondary hypertension
7. Persistent hypertension despite lifestyle changes
8. If none of the above indications are present, drug treatment can be withheld. Lifestyle modifications as discussed in the preceding text should be recommended. If these measures fail to lower BP after a reasonable period of time, then medication should be prescribed.
9. Drug therapy should be simple so that compliance will be increased in what may be a lifelong but asymptomatic problem.
10. Explicit education should be given regarding hypertension and the reasons for therapy.
11. The adolescent should generally be responsible for taking his or her own medication.
12. Antihypertensive agents should be chosen to obtain the maximum benefit with the fewest and least-severe side effects. The ideal hypertensive agent would
13. Lower BP in almost all hypertensive individuals
14. Address specific pathogenic mechanisms
15. Improve hemodynamics
16. Be associated with few biochemical changes
17. Be associated with few or no adverse reactions
18. Be dosed once or, at most, twice daily
19. Be inexpensive
20. Unfortunately, the ideal antihypertensive agent does not exist. Initial therapeutic regimens have been debated. In adults, diuretics have been advocated as first-line therapy based on the results of the ALLHAT trial (ALLHAT Collaborative Research Group, 2002). However, the findings of this study are not directly applicable to otherwise healthy adolescents with hypertension. Instead, individualized stepped-care approach, as suggested by the National High Blood Pressure Education Program Working Group (2004) and as illustrated in Figure 13.1, should be followed. In this approach, a monotherapy drug regimen is superimposed on nonpharmacologic therapy as initial treatment. Advocates of this approach recommend the following:
21. Begin with a low dose of the chosen initial drug. Because all classes of antihypertensive agents have now been studied in adolescents, either a diuretic, β-blocker, angiotensin-converting enzyme (ACE) inhibitor, or calcium channel blocker may be chosen as the initial agent. Preparations with once- or twice-daily dosing are available for members of all drug classes and can improve compliance. Increases in the dose of the initial medication may be used to achieve BP control if necessary. If BP control is still not achieved, proceed to combination treatment.
22. Add a low dose of another drug with a complementary mechanism of action. In many cases, the second agent will be a diuretic. Combination antihypertensive drug treatment with one of the medications being a diuretic is being advocated increasingly in adolescents (Wells and Stowe, 2001). Proceed to a full dose if necessary.
23. If BP control is still not achieved, one may choose to add a third antihypertensive drug, usually a vasodilator or renin-angiotensin inhibitor, or preferably obtain consultation from an expert on hypertension in adolescents.
24. Suggested initial and maximum doses of various antihypertensive agents are given in Table 13.9. Many of these now have pediatric-specific Food and Drug Administration (FDA)-approved labeling as a result of recent trials in children and adolescents. More comprehensive references, specifically published clinical trial results, should be consulted for detailed discussion of the specific adverse effects of these medications.
25. For adolescents younger than 18 years with uncomplicated primary hypertension, target BP should be the 95th percentile for age, gender, and height; for those with secondary hypertension, diabetes, or chronic kidney disease, target BP should be the 90th percentile. In those 18 years or older, BP targets should be <140/90 mm Hg for those with uncomplicated primary hypertension, and <130/80 mm Hg for those with secondary hypertension, diabetes, or chronic kidney disease.
26. Step-down therapy, or drug withdrawal, should not be forgotten. After an extended course of drug therapy and sustained BP control, a gradual reduction in or withdrawal of medication can be attempted. This requires close observation and continuation of nonpharmacologic therapy, and will probably be successful only in the adolescent who has been successful with lifestyle modification.

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TABLE 13.9 Antihypertensive Agents for Use in Chronic Treatment of Hypertension in Adolescents

Class Drug Starting Dose Interval Maximum Dosea q.d., once-daily; b.i.d., twice-daily; t.i.d., three times daily; q.i.d., four times daily; HCTZ, hydrochlorothiazide. a The maximum recommended adult dose should never be exceeded. Angiotensin-converting enzyme (ACE) inhibitors Benazepril 0.2 mg/kg/d up to 10 mg/d q.d. 0.6 mg/kg/d up to 40 mg q.d. Captopril 0.3–0.5 mg/kg/dose b.i.d.–t.i.d. 6 mg/kg/d up to 450 mg/d Enalapril 0.08 mg/kg/d q.d. 0.6 mg/kg/d up to 40 mg/d Fosinopril 0.1 mg/kg/d up to 10 mg/d q.d. 0.6 mg/kg/d up to 40 mg/d Lisinopril 0.07 mg/kg/d up to 5 mg/d q.d. 0.61 mg/kg/d up to 40 mg/d Quinapril 5–10 mg/d q.d. 80 mg/d Ramipril 2.5 mg/d q.d. 20 mg/d Angiotensin-receptor blockers α-and β-Antagonists Candesartan 4 mg/d q.d. 32 mg q.d. Irbesartan 75–150 mg/d q.d. 300 mg/d Losartan 0.75 mg/kg/d up to 50 mg/d q.d.–b.i.d. 1.44 mg/kg/d up to 100 mg/d Labetalol 2–3 mg/kg/d b.i.d. 10–12 mg/kg/d up to 2.4 g/d Carvedilol 0.1 mg/kg/dose up to 12.5 mg b.i.d. b.i.d. 0.5 mg/kg/dose up to 25 mg b.i.d. β-Antagonists Atenolol 0.5–1 mg/kg/d q.d.–b.i.d. 2 mg/kg/d up to 100 mg/d Bisoprolol/HCTZ 0.04 mg/kg/d up to 2.5/6.25 mg/d q.d. 10/6.25 mg q.d. Metoprolol 1–2 mg/kg/d b.i.d. 6 mg/kg/d up to 200 mg/d Propranolol 1 mg/kg/d b.i.d.–t.i.d. 16 mg/kg/d Calcium channel blockers Amlodipine 0.06 mg/kg/d q.d. 0.6 mg/kg/d up to 10 mg/d Felodipine 2.5 mg/d q.d. 10 mg/d Isradipine 0.05–0.15 mg/kg/dose t.i.d.–q.i.d. 0.8 mg/kg/d up to 20 mg/d Extended-release nifedipine 0.25–0.5 mg/kg/d q.d.–b.i.d. 3 mg/kg/d up to 120 mg/d Central α-agonists Clonidine 5–10 µg/kg/d b.i.d.–t.i.d. 25 µg/kg/d up to 0.9 mg/d Methyldopa 5 mg/kg/d b.i.d.-q.i.d. 40 mg/kg/d up to 3 g/d Diuretics Amiloride 5–10 mg/d q.d. 20 mg/d Chlorthalidone 0.3 mg/kg/d q.d. 2 mg/kg/d up to 50 mg/d Furosemide 0.5–2.0 mg/kg/dose q.d.–b.i.d. 6 mg/kg/d HCTZ 1 mg/kg/d b.i.d. 3 mg/kg/d up to 50 mg/d Spironolactone 1 mg/kg/d q.d.–b.i.d. 3.3 mg/kg/d up to 100 mg/d Triamterene 1–2 mg/kg/d b.i.d. 3–4 mg/kg/d up to 300 mg/d Peripheral α-antagonists Doxazosin 1 mg/d q.d. 4 mg/d Prazosin 0.05–0.1 mg/kg/d t.i.d. 0.5 mg/kg/d Terazosin 1 mg/d q.d. 20 mg/d Vasodilators Hydralazine 0.25 mg/kg/dose t.i.d.–q.i.d. 7.5 mg/kg/d up to 200 mg/d Minoxidil 0.1–0.2 mg/kg/d b.i.d.–t.i.d. 1 mg/kg/d up to 50 mg/d

Special Populations

1. African-Americans: The frequency of hypertension in African-Americans is among the highest in the world. Hypertension develops at an earlier age and is more severe in African-Americans than in whites. In African-Americans, diuretics have been proved to reduce hypertensive morbidity and mortality rates, so diuretics should be seriously considered for use in the absence of other conditions that prohibit their use. ACE inhibitors used to be considered less effective in African-Americans than in whites, although recent research indicates otherwise (Bakris et al., 2005). Calcium channel blockers and α-receptor blockers are as effective in African-Americans as in whites.
2. Females who take oral contraceptives: Most females who take oral contraceptives have a small increase in systolic and diastolic BPs but usually within the reference range. Hormonal contraceptives, mainly those that contain estrogen, can increase angiotensinogen, leading to an increase in angiotensin II and an increase in BP in some individuals. The risk of overt hypertension appears to increase with age, duration of use, and body mass. Many of the studies of BP and oral contraceptive agents involved higher doses of both estrogen and progesterone than are used currently. If concurrent treatment with an oral contraceptive and antihypertensive medication is needed, consideration should be given to using a low-estrogen or progestin-only contraceptive.
3. Adolescents with asthma: In teens with asthma and hypertension, β-blocking drugs can worsen bronchoconstriction and are therefore relatively contraindicated. Some of the newer, β₁receptor selective agents such as metoprolol or bisoprolol may be tried, especially in adolescents with mild asthma.

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4. Diabetes: As noted in the preceding text, the diagnosis of hypertension or even prehypertension in an adolescent with either type 1 or type 2 diabetes is an indication to initiate antihypertensive drug therapy. ACE inhibitors or angiotensin-receptor blockers should be used as the initial agent in hypertensive diabetic patients because of their potential benefit in slowing the progression of or even preventing diabetic nephropathy.

Hypertensive Emergencies

Rarely an adolescent will have signs of encephalopathy or heart failure at presentation and be found to have extraordinarily high BP, at levels well above stage 2 hypertension. This constitutes a true emergency and may have disastrous consequences unless efforts to lower the BP are begun at once. Assistance from an expert in hypertension should be sought. Meanwhile, the patient should be hospitalized and an intravenous line placed. Usually, a continuous infusion of either nicardipine or labetalol should be started at a low dose and then titrated up as needed to slowly reduce the BP. The initial reduction should be no more than 25% over the first 8 hours in order to prevent cerebral, cardiac, or renal ischemia from overly rapid BP reduction (Adelman et al., 2000). BP can be further lowered to the 95th percentile over the next 24 hours. When adequate pressure control has been achieved, oral antihypertensive agents can be gradually introduced and the intravenous agents discontinued. A vigorous search for the cause of the hypertension, if not known, must be made once the patient's condition has been stabilized.

Summary

As adolescents mature toward full adulthood, an increasing number will be found to have hypertension. Perhaps this progression can be delayed or avoided through the applications of the principles outlined in this chapter. At the very least, BP should be taken when adolescents are seen for health care, regardless of the complaint.

When pressures are found to be repeatedly elevated, nonpharmacologic antihypertensive measures should be started. They are good general health rules. Initially, in the absence of severe hypertension, a set of basic diagnostic studies should be obtained. Depending on the history, physical examination, and results of the initial studies, other tests may or may not be necessary.

For selected adolescents, drug therapy is indicated. The individualized stepped-care approach displayed in Figure 13.2 is recommended. When hypertension is resistant to initial drug therapies, consultation with an expert on hypertension in adolescents should be sought.

FIGURE 13.2 Stepped-care approach to antihypertensive therapy. BP, blood pressure.

Web Sites

For Teenagers and Parents

http://www.americanheart.org/presenter.jhtml?identifier=4609. American Heart Association site on childhood hypertension. Free.

http://pediatrichypertension.org. Home of the International Pediatric Hypertension Association. Includes links to additional patient education Web sites about hypertension. Free.

http://www.nhlbi.nih.gov/hbp/index.html. NIH patient education site on hypertension. Free.

http://www.medscape.com/pages/editorial/patiented/index/index-hypertension. WebMD/Medscape patient education site on hypertension. Requires free registration.

http://www.nlm.nih.gov/medlineplus/highbloodpressure.html. “Medline Plus” site on hypertension. Free.

http://www.mayoclinic.com/health/high-blood-pressure/DS00100. Mayo Clinic patient education site on hypertension. Free.

http://monitorbloodpressure.com/. Commercial site to buy home BP monitors.

For Health Care Professionals

http://www.nhlbi.nih.gov/health/prof/heart/hbp/hbp_ped.htm. Home of The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Includes link to downloadable PDA application. Free.

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http://pediatrichypertension.org. Home of the International Pediatric Hypertension Association. Includes links to additional Web sites about hypertension for health care professionals. Free; membership available for health care professionals.

http://www.who.int/topics/cardiovascular_diseases/en/. World Health Organization site containing links to various cardiovascular disease-related WHO initiatives and resources. Free.

http://www.hdcn.com/fhh.htm. Nephrology-oriented site on hypertension. Contains links to educational lectures and other materials. Requires paid annual subscription to access all content.

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