Pediatrics

Hypertension

OVERVIEW: What every practitioner needs to know

Are you sure your patient has hypertension? What are the typical findings for this disease?

Pediatric hypertension (HTN) affects up to 5% of all children. All children 3 years of age and older, and children with co-morbid conditions associated with HTN, should therefore have a blood pressure (BP) measured at each physician encounter (sick, well, emergency department visit) at least once yearly. Any systolic or diastolic BP above the 90th percentile is elevated and should be confirmed via manual auscultation. A child with an average BP greater than or equal to the 95th percentile measured on three separate occasions is hypertensive and should undergo a work-up to investigate for secondary causes of HTN.

Typical findings for HTN

Children with sustained elevation of BP, defined as an average systolic and/or diastolic BP greater than or equal to the 95th percentile for the child's age, sex and height, from measurements obtained multiple times on three separate occasions, have HTN.

HTN can be further staged based on degree of elevation:

For children up to 17 years of age:

1. Stage I HTN: Systolic and/or diastolic BP between the 95th percentile and the 99th percentile PLUS 5 mmHg (ie, if the reported 99th percentile for the child's age, sex and height percentile is 75 mmHg, the upper limit of this stage of HTN would be 80 mmHg).

2. Stage II HTN: Systolic and/or diastolic BP above the 99th percentile + 5 mmHg.

For individuals18 years of age and older:

1. Stage I HTN: Systolic BP 140 mmHg or greater and less than 160 mmHg or diastolic BP 90 mmHg or greater and less than 100 mmHg

2. Stage II HTN: Systolic BP 160 mmHg or greater or diastolic BP 100 mmHg or greater.

It is important to recognize that HTN is defined by an elevated systolic OR diastolic BP; both systolic and diastolic BPs do not need to be elevated to diagnose a child with hypertension. The sex-, age- and height percentile-specific 50th, 90th, 95th and 99th percentile systolic and diastolic BPs can be found in the August 2004 edition of Pediatrics (PUBMED:15286277).

Additionally, it should be emphasized that HTN is defined as the sustained elevation of BP, which in children requires documentation of elevated BP values on three separate occasions. Any BP above the 90th percentile during an office visit should be confirmed with a measurement conducted via manual auscultation. If that measurement confirms the BP to be greater than the 90th percentile, the BP should be repeated twice and the average SBP and DBP should be used to determine staging of BP.

Asymptomatic children with a BP in the range of stage I HTN should have their BP repeated on two additional occasions, 1-2 weeks apart, in the same manner. If stage I HTN is confirmed, they should undergo evaluation within 1 month. Referral to care and initiation of work-up should occur sooner in the presence of symptoms.

Children with a BP in the range of stage II HTN should undergo evaluation and treatment within 1 week, or immediately if symptomatic.

Pediatric HTN is largely asymptomatic, however, children may initially present in hypertensive crisis with severely elevated BP and symptoms ranging from nausea and vomiting to seizures and coma (see chapter on Hypertensive Crises for more information) or with symptoms related to the underlying etiology of their HTN (see What causes this disease and how frequent is it?).

How do I measure BP? How do I know if I have the right cuff size?

Any BP above the 90th percentile should be confirmed with a measurement conducted via manual auscultation. Automated devices, while useful as screening tools, can be inaccurate and are not uniform across devices. These devices do not directly measure BP, but estimate the systolic and diastolic BP based on the point of maximal oscillation (the mean intra-arterial pressure) during cuff deflation.

The algorithms utilized to make this calculation vary from device to device and are proprietary, so are not available from the individual manufacturers. Lastly, the devices will automatically inflate to 30 mmHg above the previous reading, which may influence the reading obtained for each new patient. These limitations, and the fact that the normative values that make up the reference tables were obtained via auscultation, emphasize the need for BP elevations be confirmed using manual auscultatory techniques.

In addition, proper BP measurement requires that the patient's:

1. Arm is supported.

2. Feet are supported.

3. Back is supported.

4. Cubital fossa is at heart level.

It is also imperative that the measurement be taken after FIVE minutes of rest, the cuff is applied to the child's bare arm and that the correct cuff size is used. An inappropriately small cuff will give a reading that is higher than the actual BP. When in doubt, because the cuff bladder (easily felt inside of the cuff) is often much smaller than the cuff itself, choose a larger cuff.

The BP cuff that is chosen should be measured against the child's arm. The following conditions should be met:

1. The bladder width should encircle at least 40% of the child's mid-arm circumference.

2. The bladder length should encircle 80% to 100% of the mid-arm circumference.

The correct way to measure BP by manual auscultation:

1. Locate radial pulse, inflate sphygmomanometer quickly to 60 mmHg and then slowly inflate in increments of 10 mmHg until the pulse disappears.

2. The value at which the pulse disappears + 30 mmHg = peak inflation level.

3. Deflate, wait 30 seconds, inflate to peak inflation level.

4. Deflate at 2-3 mmHg/second to a level 10 mmHg lower than the level of last Korotfoff sound (K5).

a. SBP = Onset of tapping (K1)

b. DBP = Disappearance of Korotkoff sounds (K5)

There are additional factors that can lead to inaccurate blood pressure estimation. These are summarized in Table I.

Table I.

Additional factors that can lead to inaccurate blood pressure estimation.

What other disease/condition shares some of these symptoms?

HTN is often a symptom of another condition or systemic illness. In fact, because most pediatric HTN is secondary to an underlying condition, all children with HTN should undergo an evaluation for underlying etiology. These conditions and diseases are listed and discussed in more detail in the following sections.

What caused this disease to develop at this time?

Past medical history

Prior history of HTN or treatment of hypertension?

Is the measured BP consistent with prior BP measurements in children with longstanding HTN, or is this an increase in BP from baseline?

Did the child abruptly stop a prescribed beta-blocker or alpha-adrenergic agonist (ie, clonidine)?

Rebound HTN

Did the child recently stop another prescribed anti-hypertensive medication?

Poor adherence to anti-HTN meds is the #1 cause of accelerated HTN in adults

History of UTIs or unexplained fever(s)?

Chronic pyelonephritis, reflux nephropathy

Prior hospitalization(s)

Prior renal injury, exposure to nephrotoxic medications

Underlying systemic illness associated with HTN

Prior streptococcal infection of pharynx or skin, or exposure to enterohemorrhagic Escherichia .coli

Resolving or resolved post-infectious glomerulonephritis, hemolytic uremic syndrome

Prior trauma

Renal or neurologic

Pain assessment

Endocrine disease

Diabetes

Thyroid disease (hyper- or hypothyroidism)

Cushings syndrome

Systemic lupus erythematosus, other rheumatologic disorder

Obstructive sleep apnea

Known syndromes

Williams syndrome: Associated with: supravalvular aortic stenosis, mid-aortic syndrome, renal artery stenosis, renal anomalies

Turner syndrome: Associated with coarctation of the aorta, renal anomalies, idiopathic HTN

Tuberous sclerosis: Associated with: coarctation of the aorta, renal artery stenosis, brain tumors

Neurofibromatosis: Associated with essential and renovascular HTN

Polycystic kidney disease

Oncologic history: Wilms tumor, neuroblastoma, pheochromocytoma

Birth history

Estimated gestational age, birth weight

Prematurity and low birth weight are associated with decreased nephron endowment and HTN

Neonatal course, including a history of umbilical catheter placement

Renal artery stenosis, renal vein thrombosis

Medications

Steroids

Decongestants/cold preparations

Oral contraceptive pills

Anti-hypertensive medications

Recent discontinuation of these medications

Beta-adrenergic agonists/theophylline

Erythropoietin

Cyclosporine/tacrolimus

Attention deficit hyperactivity disorder (ADHD) medications

Family history

HTN, early cardiovascular or cerebrovascular events, chronic or end-stage kidney disease, polycystic kidney disease

Associated with primary HTN, monogenic forms of HTN, renal disease

Social history:

Sexual activity

Pregnancy, preeclampsia

Diet

Caffeine

Licorice

Excessive salt intake

Salt craving

May suggest monogenic forms of HTN, underlying urologic disease

Nutritional supplements

Smoking/drinking/illicit drug history

Nicotine, cocaine, amphetamines, anabolic steroids, phencyclidine (PCP), MDMA (ecstasy)

Physical activity

Obesity

Sleep history

Snoring, daytime somnolence, difficulty awakening, which may suggest obstructive sleep apnea

Psychosocial history

Stress, anxiety

Important physical examination elements and possible etiologies

Obtain a full set of vital signs, including:

Four-limb BP

Lower BPs in lower extremities compared to upper extremities: coarctation of the aorta

Heart rate.

Tachycardia: hyperthyroidism, pheochromocytoma, neuroblastoma, primary HTN

Obtain an accurate weight and height, and appropriate percentiles

Growth failure: chronic renal disease, endocrine disease, other chronic disease

Obesity: primary HTN

General

Assess volume status: Fluid overload or edema; renal or heart failure

Assess overall appearance: moon facies (Cushing's syndrome, steroid use); elfin facies (Williams syndrome); webbed neck (Turner's syndrome)

Fundoscopic examination

Evaluate for papilledema, retinal hemorrhage, exudates, cotton wool spots, AV nicking

Papilledema, retinal hemorrhage, or exudates may be the only sign of a hypertensive emergency

The presence of papilledema should prompt investigation and treatment of increased intracranial pressure; lowering the BP in individuals with increased intracranial pressure is contraindicated.

Head, eyes, ears, nose and throat (HEENT)

Evaluate for signs of head trauma: contusions, lacerations, palpable skull defect, hemotympanum

Evaluate for hyperthyroidism: exophthalmos, thyromegaly

Evaluate for adenotonsillar hypertrophy: obstructive sleep apnea

Cardiovascular examination

Evaluate for heart murmur: coarctation of the aorta, patent ductus arteriosus

Evaluate for friction rub: systemic lupus erythematosus, collagen vascular disease

Pulmonary examination

Evaluate for accessory muscle use, crackles, wheeze: heart failure, asthma, bronchopulmonary dysplasia

Abdominal examination

Assess for hepatomegaly: heart failure

Evaluate for bruits: renal artery stenosis, arteriovenous fistula

Assess for abdominal mass: Wilms tumor, neuroblastoma, pheochromocytoma

Assess for palpable kidneys: polycystic kidney disease, urologic disease

Extremity examination

Assess for joint swelling: systemic lupus erythematosus

Neurologic examination:

Assess mental status: hypertensive encephalopathy, anxiety

Assess for weakness: monogenic forms of HTN, hyperaldosteronism

Skin examination

Cafe au lait spots, axillary freckling, neurofibromas: neurofilbromatosis

Ash leaf patches, angiofibromas: tuberous sclerosis

Malar rash: systemic lupus erythematosus

Palpable purpura: Henoch-Schonlein purpura, vasculitis

What laboratory studies should you request to help confirm the diagnosis? How should you interpret the results?

The following labs should be obtained on all children with confirmed HTN in the initial evaluation:

Urinalysis with microscopy, urine culture: Rule out occult renal disease, urinary tract infection

BUN and creatinine: Rule out acute kidney injury, chronic kidney disease

Serum electrolytes, calcium: Evaluate for endocrine or genetic forms of HTN

Complete blood count: Rule out anemia, which may indicate kidney disease, rheumatologic disease, chronic disease

Fasting lipids

-Evaluate for comorbidity

Fasting glucose: Evaluate for hyperglycemia, diabetes

Plasma renin activity and serum aldosterone: Evaluate for endocrine and genetic forms of hypertension

Urine pregnancy test in all postmenarchal females: Rule out pregnancy, preeclampsia

Depending on the clinical scenario, the following may be useful in your initial lab assessment:

Urine toxicology screen

Plasma and urine steroid levels: Rule out steroid-mediated hypertension

Plasma metanephrines: Rule out pheochromocytoma

Draw after 20 minutes of rest, when fasting and no acetaminophen intake in the previous 5 days (can interfere with assay).

Would imaging studies be helpful? If so, which ones?

All children with confirmed HTN should undergo the following imaging studies:

Renal ultrasound

Evaluate for the presence of two structurally normal kidneys -

Mass may be secondary to Wilm’s tumor, neuroblastoma, pheochromocytoma, Arteriovenous malformation

Evaluate kidney size -

Bilaterally small kidneys may indicate chronic kidney disease

Discrepant kidney sizes may suggest past perfusional insults, renal scar, renal artery stenosis, renal hypoplasia, renal vein thrombosis

Bilaterally large kidneys +/- cysts may suggest cystic kidney disease

Evaluate for hydronephrosis -

May indicate vesicoureteral reflux, reflux nephropathy, obstructive kidney stone

May indicate underlying urologic disease which can lead to chronic kidney disease

Evaluate for congenital anomaly -

Renal tubers: tuberous sclerosis

Horseshoe kidney, pelvic kidney

Echocardiogram

Evaluate for left ventricular hypertrophy: This form of end-organ damage may suggest more long-standing HTN, and its presence signifies the need for pharmacologic therapy aiming for BPs at or below the 90th percentile (see section on treatment).

Evaluate for cardiac abnormalities: Coarctation of the aorta, heart dysfunction, congenital anomalies

When the etiology remains unclear among very young children with stage I HTN and older children with stage II HTN, angiography may be indicated to rule out renal artery stenosis.

If you are able to confirm that the patient has hypertension, what treatment should be initiated?

Any child in hypertensive crisis should be treated promptly after ruling out conditions in which it would be contraindicated to decrease the BP (increased intracranial pressure, coarctation of the aorta). Please refer to the chapter on Hypertensive Crisis for guidance on appropriate treatment in this scenario.

Among asymptomatic children, once HTN is confirmed and the work-up is completed, treatment should focus on the underlying etiology and the institution of a heart healthy lifestyle. Children and their families should be counseled and encouraged to adopt the following lifestyle modifications:

Weight reduction if overweight

Moderate to vigorous aerobic exercise: 60 minutes daily, with activity vigorous on at least 3 days of the week

Limit sedentary activities to less than 2 hours per day

Increased intake of fresh vegetables, fruits, and low-fat dairy (the Dietary Approaches to Stop Hypertension [DASH] Study eating plan)

Avoid sugar-sweetened beverages

Salt restriction: Can start with recommending “no added salt” with ultimate goal of achieving the current recommendation of 1.2 grams per day total for 4- to 8-year-olds and 1.5 grams per day total for children 9 years of age and older

Adequate intake of potassium and calcium

Cessation of smoking

Children who remain hypertensive after 6 months of lifestyle modifications should be started on pharmacologic therapy. In addition, any child with symptomatic HTN, secondary HTN, hypertensive target-organ damage (left ventricular hypertrophy, hypertensive retinopathy), or diabetes (types 1 and 2) should be started on anti-hypertensive therapy at the time of diagnosis while also implementing the above lifestyle modifications.

The particular agent chosen should be aimed at treating the underlying etiology, with particular attention being paid to co-morbid conditions. Ease of administration and side effect profile should also be initial considerations.

In general, initial anti-hypertensive therapy should include either a calcium channel blocker or an angiotensin converting enzyme (ACE) inhibitor, unless there is a compelling reason to use an agent from another class. These medications are well tolerated, have a minimal side-effect profile, and can be dosed once daily.

ACE inhibitors can be teratogenic in first trimester, so contraception should be discussed with females of childbearing age; consider alternate medication if you cannot ensure adequate contraception.

Because ACE inhibitors can lead to hyperkalemia and renal failure in some individuals, these agents should only be initiated after the initial laboratory assessment and a renal ultrasound is completed. In addition, laboratory monitoring should be undertaken 1-2 weeks after starting and increasing the dose of an ACE inhibitor.

(See Table II and Table III for a listing of Oral medications for the treatment of hypertension in children).

Table II.

Oral medications for the treatment of HTN in children

Table III.

Oral Medications for the Treatment of Pediatric Hypertension

Therapeutic Goals

The goal of anti-hypertensive therapy is achievement of normotension, defined as BP less than 95%.

BP less than 90% in children with chronic kidney disease, diabetes or end-organ damage.

This should be achieved with the least amount of drug necessary to effectively reduce BP. As a general rule, you should start with a single agent at the lowest recommended dose, and titrate up as needed. Once the maximum dose is reached or side effects occur, initiate an additional medication from a different class in the same manner.

What are the possible outcomes of HTN?

The possible outcomes of hypertension in children are intricately related to the underlying etiology. Children with secondary HTN may experience complete resolution of HTN as the underlying disease process resolves. However, in instances where a chronic condition is the cause of HTN, resolution of HTN is unlikely and may require long-term therapy and monitoring.

Children with primary, or essential, HTN may be most able to lower their BP with successful implementation of lifestyle modifications, obviating the need for pharmacologic therapy. This is particularly true for obesity-related HTN, as salt reduction can lead to more substantial reductions in BP among children who are obese, and weight reduction can be particularly effective.

All children with HTN are at risk for cardiac, ocular and renal end-organ damage in the form of left ventricular hypertrophy, hypertensive retinopathy and microalbuminuria. While often clinically silent in childhood, these entities are associated with significant morbidity and mortality in adulthood. The presence of any one of these entities signifies increased cardiovascular risk and the need for prompt anti-hypertensive treatment to reverse these findings and prevent worsening cardiovascular disease.

What causes this disease and how frequent is it?

Over the last 35 years, the prevalence of pediatric HTN has increased from 0.3-1.2% to now 3.2-4.5%. One possible explanation for this increase in prevalence is the obesity epidemic. 30% of obese children are hypertensive, and the prevalence of HTN in children increases with increasing BMI percentile.

While primary HTN is on the rise in children, it should be a diagnosis of exclusion, as the majority of pediatric HTN is related to an underlying etiology.

There are several monogenic causes of pediatric HTN, almost all of which present very early in childhood with characteristically severely elevated BP (See Table IV and Table V).

Table IV.

Monogenic forms of HTN

Table V.

Monogenic forms of HTN and Treatment

What complications might you expect from the disease or treatment of the disease?

Inadequately treated chronic HTN can lead to end-organ damage as described above (left ventricular hypertrophy, hypertensive retinopathy, microalbuminuria) which can lead to progressive organ injury in adulthood. Children with unrecognized hypertensive emergencies, or those who experience a delay in treatment for these emergencies, may suffer from irreversible end-organ damage such as cerebrovascular accidents, visual impairment or defects, myocardial infarction, and kidney injury.

Are additional laboratory studies available; even some that are not widely available?

There are laboratory tests available to test for monogenic forms of HTN. See Table VI.

Table VI.

Laboratory Tests Available for Monogenic Forms of HTN

How can hypertension be prevented?

As pediatric HTN is often secondary to an underlying disease or condition, HTN can often only be prevented in as much as the underlying condition can be prevented. In many other cases, HTN can be prevented by adhering to a heart healthy lifestyle that includes a low-fat, low-salt diet rich in fruits and vegetables, with regular physical activity, avoidance of smoking and maintenance of a healthy body weight.

Early recognition of HTN is of paramount importance, as early diagnosis and treatment can lead to a reduction in cardiovascular disease risk. Provider adherence to recommended guidelines of measuring BP at each physician visit may help to improve recognition, which may lead to earlier diagnosis and treatment.

What is the evidence?

"Expert panel on integrated guidelines for cardiovascular health and risk reduction in children and adolescents: summary report". Pediatrics. vol. 128. 2011. pp. S213-56.

(This comprehensive report detailing current evidence-based guidelines for cardiovascular disease prevention and management in childhood was initiated by the former director of the National Heart, Lung, and Blood Institute, Dr Elizabeth Nabel. The recommendations from the expert panel focuses on the promotion of cardiovascular health and risk reduction in children and adolescents.)

"The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents". Pediatrics. vol. 114. 2004. pp. 555-76.

(This comprehensive report developed by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents details the recent evidence leading to the current recommendations regarding hypertension in children. These recommendations for diagnosis, evaluation, and treatment of pediatric hypertension are also provided in this important report.)

Couch, SC, Saelens, BE, Levin, L, Dart, K, Falciglia, G, Daniels, SR. "The efficacy of a clinic-based behavioral nutrition intervention emphasizing a DASH-type diet for adolescents with elevated blood pressure". J Pediatr. vol. 152. 2008. pp. 494-501.

(This pediatric study demonstrated the efficacy of a DASH-type diet on improving systolic blood pressure in adolescents with elevated blood pressure.)

"Harriet Lane Handbook: A Manual for Pediatric House Officers". Mosby. 2009.

(This important pediatric resource provides additional information regarding dosing, side effects and monitoring of anti-hypertensive therapy.)

Flynn, JT, Ingelfinger, J, Portman, R. Pediatric Hypertension. Humana Press Inc.. 2013.

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