Open Journal Systems

REVIEW ARTICLES

Received: 15/10/2015

Accepted: 23/11/2015

Systemic arterial hypertension in child and adolescent

Martín Rosas-Peralta,^a Luz Elena Medina-Concebida,^b Gabriela Borrayo-Sánchez,^c Alejandra Madrid-Miller,^d Erick Ramírez-Arias,^e Gilberto Pérez-Rodríguez^f

^aDivisión de Investigación en Salud

^bServicio de Cardiología Pediátrica

^cDirección Médica

^dServicio de Terapia Posquirúrgica

^eServicio de Urgencias

^fDirección General

Hospital de Cardiología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México

Communication with: Martín Rosas-Peralta

Email: mrosas_peralta@hotmail.com

The epidemic of childhood obesity, the risk of developing left ventricular hypertrophy, and evidence of the early development of atherosclerosis in children would make the detection of and intervention in childhood hypertension important to reduce long-term health risks; however, supporting data are lacking. Secondary hypertension is more common in preadolescent children, with most cases caused by renal disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension. Evaluation involves a through history and physical examination, laboratory tests, and specialized studies. Management is multifaceted. Nonpharmacologic treatments include weight reduction, exercise, and dietary modifications. Although the evidence of first line therapy for hypertension is still controversial, the recommendations for pharmacologic treatment are based on symptomatic hypertension, evidence of end-organ damage, stage 2 of hypertension, or stage 1 of hypertension unresponsive to lifestyle modifications, and hypertension with diabetes mellitus where is the search for microalbuminuria justified.

Key words: Hypertension; Child;Adolescent; Obesity; Treatment

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The European Society of Hypertension recently published its recommendations on the prevention, diagnosis, and treatment of hypertension in children and adolescents. Taking this contribution as a starting point, the Hypertension Study Group at the Hospital de Cardiología del Centro Médico Nacional Siglo XXI has done a reassessment of the recent literature on this topic. This review is not intended to be an exhaustive description of hypertension in the pediatric population, but is meant to provide pediatricians with practical and up-to-date indications in order to guide them in this often unappreciated problem. 

This document focuses on primary hypertension, which represents a growing problem in children and adolescents. Subjects at high risk of hypertension are those who are overweight, underweight at birth, and those with a family history of hypertension. However, children who do not have these risk factors may also have elevated blood pressure levels. The diagnosis of hypertension or normal high blood pressure in children is made with repeated blood pressure measurements in the doctor’s office, showing higher than baseline values. Blood pressure should be checked at least once a year with the appropriate methods and instruments, and the values observed ​​should be interpreted according to the latest nomograms adjusted for the gender, age, and height of the children. Currently, other available methods, such as ambulatory blood pressure measurement and home blood pressure measurement, are not properly validated for use as diagnostic tools. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child's age and directly proportional to blood pressure levels. Medical history, clinical data, and blood tests can guide the differential diagnosis of primary versus secondary forms. Prevention of hypertension is based on good lifestyle and nutrition. Treatment of primary hypertension in children is almost exclusively dietary and behavioral and includes: a) the reduction of excess weight, b) reduction of dietary sodium intake, c) increasing physical activity. Medication therapy is rarely needed and only in specific cases.

The concept of the importance of measuring blood pressure in children for pediatric health care has changed; considerable progress has been made in the detection, assessment, treatment, and prevention of hypertension (HT), and its importance as a cardiovascular risk factor in childhood.¹ The definition of HT in this group has changed. Before statistics were designed for the normal distribution of blood pressure in children, adult blood pressure was usually used. It was in 1987 when the second working group of the US National High Blood Pressure Education Program presented a report standardizing the method for measuring blood pressure in children and teens.² This served as a guide for diagnosis and treatment. In 1996, this report was updated with data collected between 1988 and 1991; new benchmarks were developed for blood pressure taking into account height and growth rate. Systolic blood pressure was determined by the onset of Korotkoff phase I. The definition of diastolic blood pressure was more controversial, since it was previously thought that it correlated best with Korotkoff phase IV; however, the American Heart Association established Korotkoff phase V as diastolic blood pressure at all ages. One of the most important developments over the past five years was the development of new blood pressure cutoffs adjusted for height, gender, and age, and published by the National Health and Nutrition Examination Survey (NHANES). These cutoffs included 50^th, 90^th, and 95^th percentiles (Table I).³ 

In recent years there has been growing interest in the subject; numerous studies have provided valuable information about its values, trends, variability, and predictive capacity for adulthood. In this regard, the World Health Organization (WHO) drew attention to the importance of regular and routine blood pressure measurement and early detection in children. Since then, several countries have established benchmarks for evaluation, and have developed diagnostic algorithms for the correct detection and characterization for each ethnic group.

Characteristics of blood pressure in children and adolescents

One of the most important features of blood pressure in childhood is that it is a variable parameter with a wide distribution of values ​​that increase progressively with growth. Under physiological conditions there is an increase in blood pressure according to age. During the first year of life, systolic blood pressure rises quickly, later to have a slower increase until age five. Between this age and the onset of puberty, systolic blood pressure increases 1.2 mm Hg and diastolic pressure increases 0.5 to 1 mm Hg per year with minimal differences between boys and girls. Between 13 and 18 years of age there is a significant increase in blood pressure values, more evident in boys than girls, because they have a later pubertal development and greater body mass. 

Definition of hypertension

Hypertension is defined as systolic or diastolic pressure equal to or greater than the 95^th percentile (measured on three or more occasions within 4 to 6 weeks) for age, gender, and height (Table II).

Normal blood pressure is defined as systolic or diastolic blood pressure < 90^th percentile for gender, age and height; ranges between 90 and 95 percentile are considered "high normal" blood pressure and the patient will have increased risk for developing hypertension.

This designation is described as prehypertension in adults. The JNC-7 defined prehypertension as values equal to or greater than 120/80 mm Hg, and recommends preventive measures related to lifestyle changes.^4,5

Epidemiology

Hypertension is not a very frequent problem in pediatrics; however, when it occurs, the consequences can be very serious. The prevalence of hypertension in school-age children in Mexico has been estimated at approximately 1%,⁶ with an increase in adolescents of up to 5.5% for boys and 6.4% for girls. In the United States this presents in 1 to 5% of the child population, and this number increases to 17% when measurement is made on obese children.⁷ Obesity has played a prominent role in the development of hypertension, and this is the most common nutritional problem in developed countries. In 1998 the WHO recognized that obesity had become one of the largest epidemics worldwide, both among children and adults^8,9 and its frequency increases with age; in children from birth to 23 months it is 10.4%, from 2 to 5 years it is 15.3%, and 6 to 11 years it is 15.5%.³ The association between obesity and hypertension in children has been demonstrated in numerous studies among different ethnic and racial groups; the Bogalusa study,9 for example, found that overweight children were between 4.5 and 2.4 times more likely to have elevated systolic and diastolic blood pressure, respectively. ENSANUT 2006¹⁰ shows that the prevalence of overweight and obesity in children aged 5 to 11 years and adolescents in Mexico amounted to 26% (4.1 million school children) and 31% (5.7 million adolescents), respectively, and it points to the urgency of implementing obesity prevention measures in schools to reduce the morbidity of hypertension. The clinical course of hypertension in obesity seems to be initially characterized by a predominance of isolated systolic hypertension, which represents an early stage of essential hypertension. In studies from Sorof et al.,¹¹ obese children with hypertension had a higher variability of daytime systolic and diastolic pressures without any of them presenting isolated diastolic hypertension.

Elevations of both blood pressures occur especially in secondary hypertension, while it has been shown that isolated systolic hypertension occurs mainly in primary hypertension. Three mechanisms acting in combination are mentioned in the pathophysiology of hypertension in obesity: alterations of autonomic function (sympathetic nervous system hyperactivity), insulin resistance, and abnormalities of vascular structure and function; however, not all is said in this association. The doctor must be familiar with the possible causes of hypertension, diagnosis, and appropriate treatment in children to improve long-term prognosis, as the impact will be reflected in adulthood. NHANES III reported an average increase of 1.4 mm Hg in systolic blood pressure and 3.3 mmHg in diastolic blood pressure from 1988 to 1994 and from 1999 to 2000, respectively.^1,3 This innocent variation in systolic blood pressure can have a significant epidemiological impact on young adults in the next decade, with a 10% increase in the adult population.¹²

Method for measuring blood pressure in children¹

Blood pressure should be measured in all children over age three when they are evaluated clinically.² The preferred method is auscultation, as aneroid gauges are very accurate when calibrated every six months.⁵ It is very important for the cuff size to be correct (Figures 1 and 2, Table III). The measurements obtained with oscillometric devices that exceed the 90^th percentile should be repeated again by auscultation.⁶

In repeated blood pressure measurements the right arm is preferred for the possibility of coarctation of the aorta, which can create false readings in the left arm.⁷ In children under three, blood pressure should be measured only in special circumstances (Table IV).

Etiology

In many cases, the presence of HT in childhood is a result of a number of underlying pathologies, whose first manifestation may be the elevation of blood pressure. In general, the younger the child and the higher the value, the more likely it is that hypertension is secondary; the most frequent causes of this could be of renal origin, parenchymal, or vascular (Table V).

Primary or essential hypertension

Today it is known that primary or essential HT is not only present in childhood, but can also be a precursor of HT in the adult. Its presentation before age 10 is rare, and the diagnosis is made by exclusion; genetic predisposition (observed in approximately 30% of the hypertensive population) and increased body mass index (BMI) are the most important factors influencing its development, although other factors are also determinants, such as race and sleep disorders. Data obtained in healthy adolescents have shown that the prevalence of hypertension increases progressively with BMI, and it is present in 30% of overweight children¹³ (BMI >95^th percentile). Both risk factors are part of metabolic syndrome, which is present in 4.2 to 8.4% of children,¹⁴ who will have a significant predisposition to coronary heart disease in adulthood. As is known, sleep disorders are associated with hypertension. Studies suggest that children who snore (13%) are more predisposed to develop obstructive sleep apnea, which occurs in 17% of the child population.¹⁵ A practical way to identify children with this problem is to get a brief medical history using an instrument called BEARS,¹⁶ which consists of measuring five major conditions that must be considered: if the child has trouble falling asleep, if they have excessive daytime sleepiness, if they wake up during the night, the regularity and duration of sleep, and if they have changes in breathing (if they snore). Essential hypertension is a common cause of mild to moderate hypertension in children and adolescents, but there are very few studies about the pathophysiological mechanisms that influence their development.

Experimental models of hypertension and effectiveness of treatment with ACE inhibitors (ACEI) indicate that the renin-angiotensin system (RAS) is probably involved in many states of hypertension.¹⁷ Classically, the RAS is considered a peptidergic hormonal system, and its precursor peptides are transformed into active products through an enzymatic process for converting angiotensinogen into angiotensin II. However, increasing evidence exists indicating that the actions of the RAS are also mediated by other angiotensin peptides.^21,22 Among these mediators, angiotensin- (1-7) is particularly interesting because it can be formed directly by angiotensin I by neutral endopeptidase (NEP) or propyl endopeptidase (PEP) or angiotensin II via PEP, carboxypeptidase propyl, or through the enzyme ACE-2, a homologue of ACE in humans and rats. Evidence suggests that angiotensin- (1-7) participates in the control of fluid and electrolyte balance and plays an important counterregulation role within the RAS. Angiotensin- (1-7) generally opposes the vascular and proliferative effects of angiotensin II,^23,24 and exerts complex actions in the kidney. Its physiological relevance is supported by the use of specific antagonists such as A-779²⁵ and D-Pro,²⁶ and more recently by the demonstration that it is an endogenous ligand of G-protein and the mas receptor binding, which is involved as a mediator of the biological actions of this peptide. Plasma levels of angiotensin- (1-7) are elevated in children with essential hypertension, and this increase persists even after having normal blood pressure figures. The explanation for these high levels in children includes dysfunction of the receptor of this heptapeptide at the renal vascular level, or changes in its formation and degradation. Simoes et al.²⁷ examined the activity of angiotensin in three different groups: normotensive children, children with essential hypertension, and renovascular hypertension in children; their results demonstrated that circulating levels of angiotensin- (1-7) were higher than those of angiotensin I and angiotensin II in children with essential hypertension than in those with renovascular disease or the control group (Figure 3).

Future studies should be aimed at establishing the enzymes involved in the determination of elevated levels of angiotensin- (1-7) in children with hypertension. The clinical consequences of elevated angiotensin- (1-7) are not entirely known, but two mechanisms are mentioned that may be involved in the pathophysiology of hypertension: 1) angiotensin dysfunction, and 2) its action as an antihypertensive agent. This angiotensin stimulates the synthesis and release of vasodilators such as prostaglandins and nitric oxide, and potentiates the biological action of bradykinin. All these physiological interactions cause vasodilation and antagonize the vasoconstriction caused by angiotensin II. Raising angiotensin- (1-7) may have the effect of lowering blood pressure, so it may be part of a compensatory mechanism secondary to increased blood pressure. The use of calcium channel blockers does not alter the expression of any peripheral component of RAS (angiotensin I, II, and 1-7) in subjects with primary hypertension. Contrary to blood pressure control, circulating levels of angiotensin- (1-7) remain high. This result contrasts with the normalization of plasma levels after surgical correction in renovascular hypertension. These findings indicate that changes in angiotensin- (1-7) in children with essential hypertension are the result of altered blood pressure depending on the renal or vascular movement of this peptide.  

Sodium, potassium, and calcium

Additional factors that have a genetic influence and have a potential effect on blood pressure in young people are sodium, potassium, and calcium. There is a correlation between sodium intake and the prevalence of hypertension, but the mechanism is not well established. Sodium restriction during the first six months of life significantly decreased systolic blood pressure in a study by Hofman et al.,⁴ but sodium restriction for 24 days had no effect on blood pressure in normotensive patients. The response of blood pressure to sodium has also been assessed in obese patients, and a correlation has been observed with high plasma insulin concentrations, high aldosterone levels, and increased sympathetic nervous system activity. Finally, it is thought that sodium sensitivity is related to race, family history, and obesity. Potassium plays an important role in regulating blood pressure by induction of natriuresis, and suppression in the production or release of renin. There is an inverse correlation of calcium intake and blood pressure in children, which is due to the increase in intracellular calcium that simultaneously increases muscle tone and peripheral vascular resistance.

Secondary hypertension

Secondary hypertension is more common in children than in adults. Medical history and physical examination are the first steps in assessing any child with persistently high blood pressure. Thus, it is important to look for signs and symptoms suggestive of renal disease (hematuria, edema, and fatigue), heart disease (chest pain, exertional dyspnea, and palpitations) and disease in other systems (endocrinology, rheumatology). We must ask the patient's relatives if there were previous hospitalizations, trauma, urinary tract infections, or sleep disorders. We must also investigate if there is a family history of diabetes mellitus, obesity, sleep apnea and kidney disease, cardiovascular disease (hyperlipidemia, stroke), or endocrine disorders. Many drugs can alter blood pressure; it is important to investigate the use of illicit drugs. It is also important to investigate the use of nutritional supplements.

Physical exam

BMI should be calculated. Poor growth indicates chronic disease. When hypertension is confirmed, it should be measured in both arms and both legs; pressure is normally 10 to 20 mm Hg higher in the legs than the arms; if the pressure is lower, the diagnosis of coarctation of the aorta should be considered. Retinal examination should be included. Table VI mentions important physical findings. The physical examination of hypertensive patients is often normal except for the elevated pressure. The extension of laboratory tests is based on the assessment of the child's age, medical history, physical examination, and the level of elevated blood pressure.

Assessing the causes of secondary HT

In secondary hypertension the search should go from the simplest to the most complex, as shown in the following order:

1. Identify the signs and symptoms that suggest a certain pathology.
2. Rule out if this pathology is secondary to medication or drug use.
3. Plasma renin levels or plasma renin activity is a test that helps assess whether there is mineralocorticoid hormone-related disease.

In the latter, renin levels are low or not measurable in the laboratory and may be associated with relative hypokalemia. High levels occur in patients with renal artery stenosis; however, one must take into account that 15% of children with clear arteriography of stenosis of this artery have normal levels of renin.^28,29

Renovascular hypertension

Renovascular hypertension is the result of one or more lesions of the renal artery that impede the flow to one or both kidneys or one more intrarenal segments.^30,31 Its presence causes a marked elevation of blood pressure and is common when there is history of neurofibromatosis. There are new techniques for assessing renovascular disease, but experience in pediatric patients is limited. Therefore it is generally recommended to use techniques such as renal angiography, digital subtraction angiography, and scintigraphy (with or without angiotensin-converting enzyme inhibition). Left ventricular hypertrophy is the most important clinical evidence of target organ damage. It has been shown that approximately 34% of children and adolescents with untreated mild hypertension have left ventricular hypertrophy, so periodic transthoracic echocardiography is suggested. The index of left ventricular mass is a standard measure; a cutoff point that determines hypertrophy is when the left ventricular mass is ≥ 51 g/m². This cutoff is > 99^th percentile for children and adolescents and is associated with increased morbidity and mortality.³² The presence of hypertrophy is of great importance because it indicates the initiation or intensification of antihypertensive treatment. Children and adolescents with severe elevation in pressure are at increased risk of adverse effects, including hypertensive encephalopathy, seizures, stroke, and heart failure.^33,34 When hypertension is less severe and chronically established, it contributes to target organ damage (the most affected organs are usually the kidney and heart). Two studies in adolescents and young adults who died from trauma demonstrated a significant relationship between blood pressure levels or hypertension and the presence of atherosclerosis in the aorta and coronary arteries, but neither the degree of hypertension nor the time required for such damage to be established have been determined. There is difficulty in assessing the damage of hypertension on the cardiovascular system due to the small number of non-invasive studies. The structural and functional vascular level changes can be assessed by measuring the intima-media thickness of the carotid.³⁵

Medical treatment

Lifestyle modification

Reducing weight is part of the primary treatment for obesity-related hypertension. Preventing excessive and abnormal weight gain can help reduce blood pressure increase.

Regular physical activity and restriction of sedentary lifestyles can help maintain ideal weight and decrease hypertension.

Dietary modification should be strongly encouraged in children and adolescents, especially those in the range of prehypertension.

Hypertensive patients benefit from an increase in vegetables, fruit, and fiber in the diet, and reduced sodium. Although some studies suggest calcium supplements, clinical evidence is too limited to support this recommendation. Sodium reduction has been associated with a small reduction in blood pressure ranges from 1 to 3 mm Hg.

Medication treatment

Medication treatment¹ is indicated in children with secondary or primary hypertension who have not adequately controlled it with lifestyle changes.² The drugs most commonly used to control pressure in this age group are ACE inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, and diuretics.³ The goal is for antihypertensive treatment to reduce blood pressure <95^th percentile.

In case of severe hypertension, treatment should be intravenous.

Table VII lists some indications for the use of antihypertensive drugs in children. These indications include the presence of secondary symptoms, secondary hypertension, established target organ damage, and failure to control pressure with nonpharmacological measures.

Currently there are many drugs used to control blood pressure in children, but the use of diuretics and beta-adrenergic blockers as first-line drugs is preferred, but there are special situations in which other drugs are preferred, for example, ACE inhibitors or angiotensin receptor blockers in children with diabetes mellitus and microalbuminuria, as well as beta-adrenergic blockers or calcium channel blockers in hypertensive children with migraines. There is no experience in the combined use of drugs, except bisoprolol/hydrochlorothiazide,³⁶ so their routine use in children is not recommended (Table VIII).

Hypertensive emergency

Hypertensive emergency is considered when blood pressure is above the 99^th percentile and there are signs of target organ damage, such as hypertensive encephalopathy, which most often manifests in the child as seizures. It is recommended to reduce blood pressure by 25% in the first eight hours to bring it to normal in the next 26-48 hours. Table IX shows the recommended doses of drugs for its treatment.

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