Hypertension in children and adolescents: Nonemergency treatment

INTRODUCTION — 

Hypertension (HTN) contributes to the early development of cardiovascular disease (CVD). In hypertensive adults, multiple randomized trials have shown that reduction of blood pressure (BP) by antihypertensive therapy reduces cardiovascular morbidity and mortality. This indirect evidence, as well as data from long-term cohort studies, suggests that identifying children with HTN and successfully treating their HTN should have an important impact on long-term outcomes of CVD.

Issues related to the ambulatory (outpatient) treatment of persistent HTN in children and adolescents will be reviewed here. Other aspects of HTN in children are discussed separately:

●(See "Hypertension in children and adolescents: Epidemiology, risk factors, and etiology".)

●(See "Hypertension in children and adolescents: Definition and diagnosis".)

●(See "Hypertension in children and adolescents: Evaluation".)

●(See "Initial management of hypertensive emergencies and urgencies in children".)

DEFINITIONS

●Blood pressure (BP) categories – Categories for classifying normal BP, elevated BP, and hypertension (HTN) in children are outlined in the table (table 1) [1].

•For children <13 years, the definitions for normal and increased BP are based on BP percentiles, which can be derived from a calculator (calculator 1) or normative tables (table 2A-B).

•For those ≥13 years, the normal BP is <120/80 mmHg (the same value used in adults). The definitions used for increased BP are shown in the table.

Slightly different definitions and age categories are used outside of the United States. (See "Hypertension in children and adolescents: Definition and diagnosis", section on 'Definitions'.)

●Primary versus secondary HTN – HTN is called "primary" if no identifiable cause is found and "secondary" if it has an underlying cause, such as renovascular disease. Clinical features that help to distinguish primary from secondary HTN are summarized in the table (table 3) and discussed in more detail in a separate topic review. (See "Hypertension in children and adolescents: Epidemiology, risk factors, and etiology".)

RATIONALE FOR INTERVENTION — 

Pediatric HTN is associated with short-term as well as long-term complications such as cardiovascular disease (CVD) and chronic kidney disease (CKD).

Prevention of cardiovascular disease — Because of a limited number of years during the pediatric age group, there is no direct evidence that initiating therapy to lower blood pressure (BP) in children and adolescents with persistent HTN lowers the risk of subsequent CVD. However, there is strong indirect evidence that HTN in childhood and adolescence contributes to premature atherosclerosis and increases the risk of CVD later in life [1-3]. These data suggest that lowering the BP in hypertensive children would reduce the risk of accelerated atherosclerosis and, subsequently, premature CVD in adults.

●Tracking of HTN – Children and adolescents who have prehypertension or HTN are more likely to have HTN as adults. (See "Hypertension in children and adolescents: Definition and diagnosis", section on 'Tracking'.)

●HTN and markers of atherosclerosis – Increased BP in children causes early vascular aging and biologic maturation, as demonstrated by structural and functional changes in the vascular system. These include significantly increased carotid intima-media thickness, increased stiffness of large arteries, lower area of microcirculation, and decreased endothelial function [4,5]. (See "Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)", section on 'Hypertension' and "Overview of pediatric risk factors for premature atherosclerotic cardiovascular disease (ASCVD)", section on 'Association between pediatric risk factors and adult ASCVD'.)

●HTN and left ventricular hypertrophy (LVH) – LVH has been reported in approximately 15 percent of children >8 years with HTN [6-9]. Longitudinal data from the Bogalusa Heart study have shown that elevated childhood BP and body mass index were associated with an increased risk of LVH in adulthood [10-12]. In a meta-analysis, ambulatory HTN substantially increased the risk of LVH [13]. In adults, LVH is a risk factor for CVD. (See "Overview of possible risk factors for cardiovascular disease", section on 'Left ventricular hypertrophy'.)

Limited pediatric data also show that antihypertensive therapy is associated with LVH regression [14-18]. In one study in children with primary and secondary HTN, the prevalence of LVH decreased from 42 to 11 percent after six months of treatment with ramipril, an angiotensin-converting enzyme (ACE) antihypertensive agent [15].

●HTN and CVD – HTN is a well-established risk factor for CVD in adults, and accumulating data suggest that this is also true for persistent childhood HTN [3,19-22]. In a longitudinal study of more than 1 million young men in Sweden who were followed for a median of 36 years, the adjusted hazard ratios for major cardiovascular events were 1.15 to 1.3 for stage 1 HTN and 1.3 to 1.71 for stage 2 HTN [19]. Similarly, a study of 16- to 19-year-old adolescents with persistent HTN reported an increased risk of cardiovascular death in midlife after adjusting for confounding factors [20]. In a multinational observational study with more than 20,000 participants and mean follow-up of 35 years, HTN was an important risk factor for having fatal or nonfatal cardiovascular events in adulthood (hazard ratio 2.31, 95% CI 1.7-3.1) [22]. Other contributors to risk for cardiovascular included youth smoking, obesity, and lipid abnormalities. Another study also reported a higher risk of stroke and cardiac complications after a median follow-up of approximately 13 years in patients diagnosed with HTN in childhood [21].

Prevention of chronic kidney disease — Untreated HTN is associated with CKD and progression of preexisting CKD. (See "Chronic kidney disease in children: Complications", section on 'Hypertension'.)

Primary HTN during late adolescence increases the risk of kidney failure in adulthood. This was illustrated in a large retrospective study of almost 2.7 million healthy adolescents recruited to the Israeli army (age 16 to 19 years of age) that reported that 2189 individuals (0.1 percent) developed kidney failure (defined as requiring hemodialysis, peritoneal dialysis, or undergoing kidney transplantation) at a median follow-up of 19.6 years (range 10.4 to 31.2) [23]. Among 7997 individuals diagnosed with HTN (defined as BP >140/90) at the time of conscription, 42 (0.5 percent) subsequently developed kidney failure. In a multivariable regression analysis, HTN at the time of conscription doubled the risk of kidney failure (hazard ratio 1.98, 95% CI 1.42-2.77). Although the incidence of kidney failure was low in this cohort, these results highlight the long-term, potentially avoidable adverse effects of pediatric HTN on the development of kidney failure.

TARGET BLOOD PRESSURE — 

Our target is to reduce blood pressure (BP) to the normal range for age, ie, below the 90^th percentile (for age <13 years) or <120/80 mmHg (for age ≥13 years). Other expert groups use different age cutoffs or suggest slightly less stringent targets (eg, BP <130/80 for adolescents), but there is no clinical evidence to support the less stringent targets [1,24,25]. Our target of normal BP is supported by evidence for an association between BP in the prehypertensive range and hypertensive target organ damage [26].

LIFESTYLE INTERVENTIONS AND MANAGEMENT OF COMORBID CONDITIONS

Overview — Lifestyle intervention is provided for all children with high blood pressure (BP). We suggest implementing the following measures for children with any BP elevation (elevated BP, stage 1 or stage 2 HTN), consistent with several society guidelines [1,4,24]:

●Weight reduction for children who are overweight with elevated BP or HTN.

●Regular vigorous exercise and restriction of sedentary activity.

●Dietary modification, including sodium restriction and following the Dietary Approaches to Stop Hypertension (DASH) diet.

●Measures to reduce other cardiovascular disease (CVD) risk factors, such as preventing or treating dyslipidemia and avoiding smoking and alcohol. (See "Pediatric prevention of adult cardiovascular disease: Promoting a healthy lifestyle and identifying at-risk children" and "Dyslipidemia in children and adolescents: Management".)

The long-term beneficial effects of these measures were shown in a prospective study of 798 participants that measured BP in children at 9, 12, or 15 years and at follow-up 20 years later [27]. Resolution of elevated BP as adults was observed in approximately 44 percent of participants with elevated childhood BP measurements. Factors associated with resolution of pediatric elevated BP included significant decrease in body mass index, decrease in alcohol consumption, increase in vegetable consumption, and improved socioeconomic status.

Weight reduction — For children with excess body weight, the initial intervention is health behavior and lifestyle counseling. This includes customized guidance to reduce caloric intake and improve dietary quality, increase physical activity, and reduce sedentary activities. This counseling can be done in the primary care setting, ideally supported by an allied health care provider, such as a dietitian, nurse, or health coach. In some cases, referral to a comprehensive obesity treatment program for appropriate dietary, pharmacologic, and/or surgical therapy may be warranted. (See "Prevention and management of childhood obesity in the primary care setting".)

Excessive weight is an independent risk factor for HTN [28]. Although data in children are not as robust as in adults, several studies and a systemic review of the literature have reported that weight reduction was associated with lower BP values in hypertensive children [1,29]. A 2014 systematic review showed that obesity intervention regimens modestly reduced BP, with a mean decrease of 1.64 mmHg (95% CI -2.56 to -0.71) in systolic BP and 1.44 mmHg (95% CI -2.28 to -0.60) in diastolic BP, which is similar to results seen in adults [29]. In this review, interventions that combined diet and physical activity were more effective in lowering BP than diet or physical activity alone. (See "Overweight, obesity, and weight reduction in hypertension".)

Exercise — Regular physical activity should be encouraged for all children with HTN, regardless of their weight status. Children should be instructed to participate in moderate to vigorous aerobic activity in 30- to 60-minute sessions for at least three to five days per week. Age-based recommendations for daily physical activity for children have been developed by an expert panel sponsored by the United States National Heart, Lung, and Blood Institute (table 4) [30]. Children with stage 2 HTN should initially be restricted from participating in high-static sports. (See 'Sports participation' below.)

Exercise lowers BP, decreases the risk of atherosclerosis and CVD, and prevents and treats metabolic syndrome [29,31-34]. Sustained regular physical activity appears to be effective in lowering BP and, the more vigorous the activity, the greater the impact on reducing BP [35,36]. In a small randomized trial, four 90-minute exercise sessions per week for one year decreased the proportion of children with excessive weight with HTN from 86 to 16 percent [34].

The antihypertensive effect of physical activity combined with weight loss is greater than that with weight loss or exercise alone [29]. However, the combination of weight loss and physical training may not have beneficial effects on left ventricular function or size in adolescents with obesity [37].

Diet — Dietary counseling for children and adolescents with HTN focuses on reducing salt intake and increasing intake of fresh fruits, vegetables, and low-fat dairy products (eg, the DASH diet) [1,4].

Key steps in counseling about the DASH diet include (table 5):

●Salt restriction – We begin dietary salt modification with a no-added-salt diet. This also includes a reduction in or elimination of foods containing large amounts of salt (eg, potato chips, pretzels, and many processed foods in fast food restaurants or cooked at home). Parents and caregivers are encouraged to read food package labels to determine the sodium content of prepared foods and avoid those with high salt content. In addition, menus for meals provided at school should be reviewed to help the child avoid foods with high salt content. The 2017 American Academy of Pediatrics guidelines recommend that dietary sodium be restricted to <2300 mg/day [1]. In younger children, the normal requirement of sodium is between 2 to 3 mEq/kg per day [38]. (See "Salt intake and hypertension" and "Patient education: Low-sodium diet (Beyond the Basics)".)

The benefit of salt restriction for children with HTN is based on indirect data from well-controlled trials in adults and observational pediatric data [39].

●Limit added sugar – We also limit added sugars, starting with avoiding sugar-sweetened beverages (sodas, juice, and flavored milks) and sweets. Added sugars contribute excess calories and are typically found in food with low nutritional value. Limiting sugar-sweetened beverages and sweets is a clinically practical way to reduce added sugars and calories.

●Other – In addition to the above steps, the DASH diet emphasizes (table 5) [1]:

•Fresh vegetables and fruits – Providing increased potassium intake

•Whole grains

•Lean proteins, such as low-fat milk products, fish, and poultry – To reduce fat

Evidence supporting the DASH diet includes observational studies and clinical trials in adolescents [40-44] and extensive clinical evidence in adults. (See "Diet in the treatment and prevention of hypertension", section on 'Our approach: Comprehensive dietary modification'.)

Other interventions — Other lifestyle changes that may contribute to management of HTN or related cardiovascular risk include:  

●Avoid excessive alcohol – Multiple studies in adults have shown a clear association between excessive alcohol intake and the development of HTN. The applicability of these findings to children has not been well studied. Nevertheless, excess alcohol intake should be avoided to improve weight loss, BP control, and other health concerns. (See "Cardiovascular benefits and risks of moderate alcohol consumption".)

●Avoid smoking and smoke exposure – Avoidance of smoking and exposure to tobacco smoke ("secondhand smoke") is particularly important for individuals with HTN because these exposures increase the risk of CVD, as well as lung cancer. (See "Smoking and hypertension" and "Secondhand smoke exposure: Effects in children", section on 'Cardiovascular disease'.)

●Manage dyslipidemia – Dyslipidemia and HTN have additive effects on the risk for CVD. If dyslipidemia is present, it should be managed promptly with dietary and/or pharmacologic measures, as indicated. (See "Dyslipidemia in children and adolescents: Management", section on 'Dietary modification'.)

●Healthy sleep – Longer sleep duration is associated with lower BP in children [45], and healthy sleep lowers CVD risk in adults with HTN. Although no specific data in children are available, interventions to improve sleep habits might be helpful, including addressing sleep disruption due to video games and social media. (See "Overview of the management of the child or adolescent at risk for premature atherosclerotic cardiovascular disease (ASCVD)", section on 'Healthy sleep habits'.)

●Avoid caffeine and energy drinks – Caffeine and so-called "energy drinks" should be avoided in children with elevated BP. Energy drinks typically contain a high amount of sugar, caffeine, and other stimulants. They can cause excessive weight gain and increase in BP or worsening of BP in those with elevated BP or HTN [46,47].

Other lifestyle interventions that are being actively investigated include stress reduction by various means including yoga, combining exercise modalities, and technology-based interventions [48].

ANTIHYPERTENSIVE MEDICATION

Indications — The decision to initiate antihypertensive medication is based on the blood pressure (BP) category (table 1) and the presence of end-organ damage, symptoms, or other cardiovascular disease (CVD) risk factors [1].

Patients with primary hypertension — For patients with primary hypertension (and without diabetes mellitus or CKD), the timing of initiating antihypertensive therapy depends on severity:

●Stage 1 HTN

•For those without evidence of end-organ damage, lifestyle intervention is the initial intervention. If BP target goals are not met within four to six months after initial therapy (ie, BP below the 90^th percentile), we initiate antihypertensive medication.

•For those who are symptomatic or have evidence of end-organ damage (eg, if left ventricular hypertrophy [LVH] is detected), we initiate antihypertensive medication in addition to lifestyle intervention. (See "Ocular effects of hypertension" and "Hypertension in children and adolescents: Evaluation", section on 'Detection of end-organ damage'.)

●Stage 2 HTN – For children with stage 2 HTN, we initiate treatment with both antihypertensive medications and lifestyle intervention.

●Acute severe HTN – Patients with severe acute HTN should have emergency evaluation and treatment. This includes children with stage 2 HTN and symptoms of target organ involvement (headache, altered mental status, papilledema), or more asymptomatic patients with more severe HTN (eg, >180/120 in an adolescent). (See "Approach to hypertensive emergencies and urgencies in children" and "Initial management of hypertensive emergencies and urgencies in children".)

Other populations

●Patients with diabetes mellitus – Patients with diabetes mellitus are at risk for nephropathy and may benefit from early initiation of antihypertensive therapy, especially if albuminuria is present. (See "Chronic complications and screening in children and adolescents with type 2 diabetes mellitus", section on 'Hypertension' and "Type 1 diabetes mellitus in children and adolescents: Screening and management of complications and comorbidities", section on 'Elevated blood pressure and hypertension'.)

●Patients with chronic kidney disease (CKD) – Strict BP control has been shown to slow the progression of CKD. Management of HTN in CKD is discussed separately. (See "Chronic kidney disease in children: Complications", section on 'Hypertension'.)

●Patients with secondary HTN – For children with secondary HTN, management should also be directed to correcting the underlying cause, if possible. Depending on severity, antihypertensive medication may need to be initiated. If the underlying cause cannot be corrected so that HTN is abolished, the patient may require ongoing antihypertensive medication, in addition to lifestyle intervention and management of comorbid conditions such as dyslipidemia. The causes of secondary HTN are discussed separately. (See "Hypertension in children and adolescents: Epidemiology, risk factors, and etiology", section on 'Secondary hypertension'.)

Renovascular HTN (renal artery stenosis) is usually more severe (stage 2) and warrants immediate initiation of antihypertensive medication. In some cases, endovascular or surgical intervention is warranted. (See 'Choice of drug' below and "Hypertension in children and adolescents: Epidemiology, risk factors, and etiology", section on 'Kidney disease'.)

General principles — Based on strong indirect evidence of the association between pediatric HTN and CVD, antihypertensive drug therapy is used for children with persistently high BP, especially those with evidence of end-organ damage or other CVD risk factors and those with symptomatic HTN. (See 'Rationale for intervention' above and 'Indications' above.)

The step-wise approach to antihypertensive drug therapy is based on the following principles [1]:

●First-line drug therapy should combine efficacy with minimum side effects. Starting doses should be the lower end of the known effective dose. Depending on the patient's response, the dose may gradually be increased (table 6).

●If the target BP is still not achieved, the medication may be changed or a second drug from a different class is added.

●Long-acting agents should be used whenever possible to reduce treatment burden and improve adherence. Once-daily medications can be taken in either the morning or evening, as long as they are taken consistently at approximately the same time.

●Lifestyle intervention is continued even if antihypertensive medication is initiated.

●Ambulatory BP monitoring is useful to assess response to therapy, especially when clinic or home BP monitoring is insufficient to determine treatment effectiveness. (See "Ambulatory blood pressure monitoring in children".)

Choice of drug — Recommendations on the choice of agent for initial therapy are based on the underlying cause of HTN, concurrent disorders, and preference and experience of the responsible clinician [24,49]. Information about the relative efficacy and safety of different antihypertensive drugs is based mostly on indirect evidence from studies in adults and limited evidence in children, including observational studies and indirect comparisons between separate placebo-controlled trials [50,51]. (See "Hypertension in adults: Initial drug therapy".)

Initial therapy

●First-line choices – We suggest initial therapy with an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or calcium channel blocker (CCB) rather than other agents. Specific antihypertensive drugs, doses, and other considerations are outlined in the table (table 6) [1].

For most patients, the choice among these drug classes (ACE inhibitor, ARB, or CCB) depends on clinician and patient familiarity/preference, cost considerations, and need for laboratory monitoring.

Additional considerations about the choice of drug include:

•Adolescent females – ACE inhibitors and ARBs should be used with caution because of adverse effects on the fetus. If these classes of drug are used in a patient capable of getting pregnant, provide counseling about contraception and consider monitoring with periodic point-of-care pregnancy tests. A CCB is a reasonable alternative.

•Laboratory monitoring – Patients on an ACE inhibitor or ARB require periodic monitoring for changes in serum creatinine and potassium, particularly after medication initiation or significant dose increases or during an acute illness that may cause electrolyte imbalance. This is particularly important for those with impaired kidney function. Some of these agents may also cause leukopenia or elevations in transaminases. Treatment with thiazides also requires periodic monitoring of electrolytes, glycemia, and lipids. Treatment with CCBs does not require specific laboratory monitoring. (See 'Details on specific antihypertensive drugs' below.)

•Concerns about kidney disease – If there are concerns about kidney disease (eg, proteinuria, established CKD), we typically choose an ACE inhibitor or ARB for initial therapy because of their established renoprotective effects and evidence for benefits in patients with CKD. (See "Chronic kidney disease in children: Complications", section on 'Pharmacologic therapy'.)

•Renovascular disease – For patients with renovascular disease (eg, renal artery stenosis), we generally use CCBs rather than an ACE inhibitor or ARB because of the concern that ACE inhibitors and ARBs reduce glomerular filtration rate and may contribute to kidney function impairment and hyperkalemia. However, the use of an ACE inhibitor or ARB is not contraindicated if there is appropriate monitoring of kidney function and serum potassium, as well as follow-up for adjustment of medication if there is evidence of kidney impairment or an increase in potassium level.

In some cases of renovascular disease, endovascular or surgical intervention is warranted [52]. Causes and diagnosis of renovascular disease are discussed separately. (See "Hypertension in children and adolescents: Epidemiology, risk factors, and etiology", section on 'Kidney disease' and "Etiology, clinical features, and diagnosis of neonatal hypertension", section on 'Vascular disease'.)

●Alternatives – Thiazides are generally considered a second-line option for initial treatment due to moderate risks for metabolic complications (hypokalemia, glucose intolerance, weight gain, dyslipidemia) and because the efficacy depends on dietary sodium restriction. However, this drug class is a reasonable choice for initial treatment in patients who are adherent with medication and dietary sodium restriction and have no evidence of hyperglycemia, hyperlipidemia, or hyperuricemia. Thiazides are also useful options for add-on therapy, if needed. (See 'Thiazide diuretics' below and 'Adding a second agent' below.)

More details on these antihypertensive drugs and evidence supporting their use in children are summarized below. (See 'Details on specific antihypertensive drugs' below and 'Evidence supporting antihypertensive agents in children' below.)

Adding a second agent — If the target BP goal is not met with the maximum allowable dose of the initial medication (ACE inhibitor, ARB, or CCB), we typically add a thiazide diuretic as a second agent [1]. Alternative approaches include switching agents between drug classes or adding a CCB in combination with either an ACE inhibitor or ARB. Concomitant use of an ACE inhibitor and ARB is not recommended, based on multiple studies in adult patients that demonstrated an increased risk of adverse effects (eg, hypotension, syncope, worsening of kidney function, hyperkalemia). (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Combination of ACE inhibitors and ARBs'.)

Follow-up care

●Monitoring and dose adjustments – For children and adolescents treated with pharmacotherapy, regular follow-up is required to monitor the response and to detect any drug-related adverse effects. After initiation of antihypertensive medication, we generally reassess the BP every four to six weeks for dose adjustments and to evaluate the possible need for a second or third agent [1]. If there is a good response, the target BP is met, and no additional changes are needed, we gradually reduce the frequency of follow-up to every three to six months.

Children and adolescents who are treated with lifestyle intervention alone can be monitored less frequently: approximately every three to six months [1]. The goals of these visits are to assess the efficacy of the intervention, reinforce adherence, and determine whether antihypertensive medication should be initiated.

Home monitoring of BP is a useful adjunct to office BP measurements because it provides additional BP data and eliminates the "white-coat effect" [1]. For home monitoring, we ask the parents/caregivers to record BP readings taken during the first two weeks after medication initiation or adjustments. If clinic and home BP monitoring are insufficient to determine treatment effectiveness, we perform ambulatory BP monitoring. (See "Ambulatory blood pressure monitoring in children".)

●Discontinuation of therapy – A trial of gradually discontinuing pharmacotherapy is appropriate for:

•Patients with mild initial HTN who are well controlled on a single drug and who have made progress with lifestyle intervention, such as weight loss and sodium restriction. These patients will require ongoing lifestyle intervention and BP monitoring after drug therapy is discontinued.

•Patients with secondary HTN if the cause has been identified and corrected. However, patients with prolonged secondary HTN (eg, those with coarctation of the aorta or renal artery stenosis) may have persistent HTN even after successful repair and may require continued antihypertensive medication. (See "Management of coarctation of the aorta", section on 'Systemic hypertension'.)

Sports participation — Recommendations about sports participation depend on the degree of BP elevation [1]:

●Patients with stage 1 HTN should complete a full evaluation for causes and end-organ damage (primarily LVH). If there is no evidence of end-organ damage, they may participate in competitive sports without restrictions. (See "Hypertension in children and adolescents: Evaluation", section on 'Initial evaluation'.)

●Patients with stage 2 HTN should initially be restricted from high-static sports even if there is no evidence of end-organ injury. High-static sports are defined as classes IIIA to IIIC in a system that classifies sports based on their cardiovascular demands (figure 1). If stage 2 HTN is effectively treated and the child is documented to be normotensive, they may be allowed to participate in these sports with ongoing monitoring.

DETAILS ON SPECIFIC ANTIHYPERTENSIVE DRUGS — 

Dosing recommendations for antihypertensive drugs are outlined in the table (table 6), based on the 2017 American Academy of Pediatrics guideline [1].

The following sections describe the antihypertensive drugs used in the treatment of pediatric HTN. The initial choice of antihypertensive agent is discussed above. (See 'Choice of drug' above.)

Angiotensin-converting enzyme inhibitors — Angiotensin-converting enzyme (ACE) inhibitors (eg, enalapril, lisinopril, fosinopril) are appropriate first-line choices for treatment of HTN in most children.

ACE inhibitors reduce blood pressure (BP) by inhibiting the production of angiotensin II. Studies in adults suggest that the antihypertensive effect of ACE inhibitors is increased by concurrent sodium restriction [53]. This is because sodium restriction increases renin release, making the BP more angiotensin II-dependent and, therefore, more responsive to therapy with an ACE inhibitor. Evidence for their efficacy for treating HTN in children is summarized below (see 'Evidence supporting antihypertensive agents in children' below). Indirect evidence from adult populations including cardioprotective and renoprotective effects is discussed in a separate topic review. (See "Renin-angiotensin system inhibition in the treatment of hypertension".)

ACE inhibitors are generally safe and well tolerated. The most common adverse effect is dry cough, which may be seen in up to 3 percent of pediatric patients [54]. Patients who develop this problem are typically switched to an angiotensin receptor blocker (ARB). ACE inhibitors also reduce glomerular filtration rate and may cause kidney function impairment and hyperkalemia in patients with impaired kidney function. ACE inhibitors are contraindicated in pregnancy and should be used with caution in patients capable of getting pregnant unless effective contraception can be assured.

In children, the most commonly used ACE inhibitors are enalapril, lisinopril, benazepril, and fosinopril. These drugs are relatively long acting, usually allowing for once-daily dosing (except for enalapril), and have adequate data on pharmacokinetics, safety, and efficacy from clinical trials [50,55-60]. Dosing and age limitations are outlined in the table (table 6).

Angiotensin receptor blockers — ARBs are also first-line agents for treatment of HTN in children. They are a good alternative for children who have significant side effects (eg, angioedema, cough) associated with the use of an ACE inhibitor. ARBs block the binding of angiotensin II to the AT1 receptor.

Similar to ACE inhibitors, ARBs are contraindicated in pregnancy and should be used with caution in patients capable of getting pregnant unless effective contraception can be assured. Both ARBs and ACE inhibitors reduce glomerular filtration rate and may cause kidney function impairment and hyperkalemia in patients with impaired kidney function.

ARBs used in children include candesartan, losartan, olmesartan, and valsartan (table 6). (See 'Evidence supporting antihypertensive agents in children' below.)

Concomitant use of an ACE inhibitor and ARB is not recommended, due to an increased risk of adverse effects. (See 'Adding a second agent' above and "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Combination of ACE inhibitors and ARBs'.)

Calcium channel blockers — Calcium channel blockers (CCBs) are an appropriate first-line antihypertensive agent for most children, including those with impaired kidney function. They are the preferred choice for patients with:

●Barriers to routine laboratory monitoring

●Patients who may become pregnant

●Hyperkalemia with renin-angiotensin-aldosterone system blockade (ACE inhibitors or ARBs) that does not respond to medical management

Increasing experience with long-acting CCBs (especially extended-release nifedipine and amlodipine) demonstrates their efficacy and safety in children with HTN, particularly primary HTN [61-65]. Extended-release felodipine has also been used but has not been well studied. (See 'Evidence supporting antihypertensive agents in children' below.)

A limitation of long-acting CCBs is that they are not available in small-dose formulations, resulting in a wide range of mean daily dose from 0.06 to 0.23 mg/kg per day [61,63]. Because of these dosing constraints, smaller children may be treated with relatively high doses of medication per body weight and, consequently, might experience dose-related adverse effects. Short-acting (rather than extended-release) nifedipine is not recommended in hypertensive children, given concerns about its safety and the inability to accurately administer small doses [66]. CCBs may cause pedal edema and are contraindicated in patients with sinus node dysfunction. (See "Major side effects and safety of calcium channel blockers".)

Thiazide diuretics — A thiazide diuretic may be used as an initial agent or as a second agent, when needed. These drugs enhance the effect of many other antihypertensive drugs (eg, ACE inhibitors, ARBs, beta blockers) when given as combination therapy [67,68]. There is an extensive clinical experience but limited published efficacy data regarding the use of these agents in children [69]. Concurrent sodium restriction is required for optimal efficacy of thiazides, given alone or in combination with other antihypertensive medications [70,71].

Thiazide diuretics are associated with several adverse effects including hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, hyperlipidemia, hypomagnesemia, and an increased incidence of type 2 diabetes mellitus, so ongoing monitoring of laboratory tests is needed. (See "Salt intake and hypertension" and "Use of thiazide diuretics in patients with primary (essential) hypertension", section on 'Side effects'.)

Beta blockers — Beta blockers are not recommended as initial therapy in children. However, they may be added as second or third agents for patients who fail to respond to initial monotherapy or dual therapy with a thiazide diuretic. Other agents are preferred because of the adverse effects associated with beta blockers, which include impaired glucose tolerance, interference in lipid metabolism, weight gain, and increased bronchial obstruction and airway reactivity in children with asthma. Moreover, beta blockers are less effective than other antihypertensive agents in preventing stroke in adults with primary HTN. (See "Major side effects of beta blockers" and "Treatment of hypertension in asthma and COPD", section on 'Beta blockers' and "Hypertension in adults: Initial drug therapy".)

When beta blockers are used, the preferred options are the more selective drugs such as atenolol, metoprolol, and bisoprolol, which are better tolerated and longer acting than propranolol. Bisoprolol, metoprolol, and atenolol have all been shown to be effective in reducing BP in children [51]. These agents are available in combination with hydrochlorothiazide. Labetalol is another beta blocker agent, which also has alpha blocking activity [67,72,73].

EVIDENCE SUPPORTING ANTIHYPERTENSIVE AGENTS IN CHILDREN — 

The evidence supporting antihypertensive drugs in children comes largely from placebo-controlled trials and trials comparing different doses of the same drug [50,51]. There are very few data directly comparing different agents. A 2018 network meta-analysis identified 13 placebo-controlled trials evaluating various antihypertensive drugs, including angiotensin-converting enzyme (ACE) inhibitors (enalapril, lisinopril, fosinopril), angiotensin receptor blockers (ARBs; candesartan, losartan, olmesartan, telmisartan), calcium channel blockers (CCBs; amlodipine, felodipine), beta blockers (metoprolol, combination bisoprolol/hydrochlorothiazide), and mineralocorticoid receptor antagonists (eplerenone), in 2378 children with HTN (most had primary HTN) [50]. In most trials, follow-up was limited to two to four weeks. ACE inhibitors and ARBs were found to be among the most effective drugs for reducing blood pressure (BP). For ACE inhibitors, the pooled mean reduction in systolic BP compared with placebo was 7 mmHg (95% CI 4-10 mmHg). ARBs reduced systolic BP by a mean of 3 mmHg (95% CI 1-6 mmHg) compared with placebo.

Additional indirect evidence supporting ACE inhibitors and ARBs comes from studies involving children with chronic kidney disease (CKD) and proteinuria, for whom these agents have an antiproteinuric effect independent of their effect on BP. These data are discussed separately. (See "Chronic kidney disease in children: Complications", section on 'Hypertension'.)

For CCBs, evidence for efficacy comes from randomized trial of amlodipine in 268 children, in which those treated with a 5 mg dose had mean BP reduction of -5.1 mmHg (95% CI 1.3-8.9 mmHg; p = 0.009) compared with placebo [63]. Adverse events included edema (<5 percent) and headache. In a separate smaller trial, extended-release felodipine had minimal effect on systolic BP, although it did reduce diastolic BP by approximately 5 mmHg [74]. The use of CCBs in children is also supported by clinical experience in children and indirect evidence from studies in adults.

Limitations of these studies are that the main measure of efficacy is lowering BP rather than long-term outcomes or end-organ damage. In addition, most of the efficacy and safety data are for antihypertensive medications that were introduced after 2000, after the passage of legislation that required systematic studies of drugs and especially for pediatric populations. Data are more sparse on the effects of older classes of antihypertensive medications in children (thiazides and beta blockers) [51].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in children".)

INFORMATION FOR PATIENTS — 

UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: High blood pressure in children (The Basics)")

●Beyond the Basics topics (see "Patient education: High blood pressure in children (Beyond the Basics)" and "Patient education: High blood pressure treatment in children (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Lifestyle intervention and management of comorbid conditions – All children with elevated blood pressure (BP) or any stage of hypertension (HTN) should be counseled on healthy lifestyle changes, including regular exercise (table 4), restriction of sedentary activity, healthy diet including avoidance of added salt (table 5), healthy sleep habits, and avoidance or cessation of smoking or nicotine exposure. In addition, other cardiovascular disease (CVD) risk factors (eg, dyslipidemia, obesity, diabetes mellitus) should be managed appropriately. (See 'Lifestyle interventions and management of comorbid conditions' above and "Overview of the management of the child or adolescent at risk for premature atherosclerotic cardiovascular disease (ASCVD)".)

●Target BP goal – For children with HTN treated with lifestyle intervention and/or antihypertensive medication, our goal is to reduce BP to normal range for age (ie, below the 90^th percentile [for age <13 years] or <120/80 [for age ≥13 years]). For children ≥13 years with primary HTN, some expert groups use a less stringent target of <130/80. (See 'Target blood pressure' above.)

●Antihypertensive medication: Patients with primary HTN

•Patient selection – We suggest initiation of antihypertensive medications for patients with stage 2 HTN (table 1), or stage 1 HTN that persists despite six months of lifestyle intervention or with evidence of end-organ damage (Grade 2C). (See 'Indications' above.)

Children with neurologic symptoms require emergency evaluation and treatment. (See "Approach to hypertensive emergencies and urgencies in children" and "Initial management of hypertensive emergencies and urgencies in children".)

•Choice of initial drug therapy – For most children with HTN, we suggest an angiotensin-converting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or calcium channel blocker (CCB) rather than other antihypertensive drug classes (Grade 2C). Dosing is summarized in the table (table 6). Each of these drug classes has been shown to be safe and effective for reducing BP in placebo-controlled trials in children, though head-to-head trials comparing these antihypertensive agents in children are lacking. For most patients, the choice among these drug classes depends on clinician and patient familiarity/preference, cost considerations, and need for laboratory monitoring. (See 'Initial therapy' above and 'Evidence supporting antihypertensive agents in children' above.)

These agents are generally well tolerated. Children who develop significant side effects (eg, cough) on an ACE inhibitor should be switched to an ARB. ACE inhibitors and ARBs are contraindicated in pregnancy. Thus, patients capable of getting pregnant should be counseled.

•Add-on therapy – In general, we initiate therapy with a single agent (ACE inhibitor, ARB, or CCB). If this intervention does not achieve the BP target at maximal tolerated doses, options include adding a thiazide diuretic or switching drug classes. An ACE inhibitor should not be used in combination with an ARB, due to increased risk of adverse effects. (See 'Adding a second agent' above.)

•Follow-up – Continued follow-up is required to monitor the response to therapy, detect any drug-related adverse effect, and make dosing changes or introduce additional agents to achieve target BP goal. (See 'Follow-up care' above.)

•Sports participation – Patients with stage 2 HTN should initially be restricted from high-static sports (figure 1). Once the stage 2 HTN is effectively treated and the child is normotensive, they may be allowed to participate in these sports with ongoing monitoring. (See 'Sports participation' above.)

●Antihypertensive medication: Other populations

•Chronic kidney disease (CKD) and diabetes mellitus – Antihypertensive therapy for these patients is discussed in separate topic reviews. (See "Chronic kidney disease in children: Complications", section on 'Hypertension' and "Type 1 diabetes mellitus in children and adolescents: Screening and management of complications and comorbidities", section on 'Elevated blood pressure and hypertension' and "Chronic complications and screening in children and adolescents with type 2 diabetes mellitus", section on 'Hypertension'.)

•Renovascular disease (renal artery stenosis) – For children with HTN due to renal artery stenosis, we suggest using a CCB as initial treatment rather than an ACE inhibitor or ARB (Grade 2C). ACE inhibitors and ARBs reduce glomerular filtration rate and may contribute to kidney function impairment and hyperkalemia. (See 'Choice of drug' above.)