Hypertension is a global problem, affecting both developed and developing nations. In addition to being a major cause of morbidity and mortality, hypertension places a heavy burden on health care systems, families, and society as a whole. Despite evidence of an increasing prevalence of hypertension among youth, the consequences of early onset are poorly established and often overlooked. Childhood hypertension is often asymptomatic and easily missed, even by health professionals. Target organ damage is detectable in children and adolescents, however, and hypertension continues into adulthood. Additional strategies to improve cardiovascular health among children and adolescents are needed, including methods to achieve healthy lifestyles at home and in school, improved systems for diagnosis, and research on mechanisms and timing of interventions. The burden of hypertension in the young will continue to grow unless it is given the attention it deserves by policy makers, health care providers, schools, parents, and society. This report aims to increase awareness of the problem of hypertension in childhood. Recent reports on prevalence and target organ injury are discussed and health policy initiatives to improve blood pressure control are proposed.
High blood pressure (BP) is a clearly established, but modifiable, risk factor for early disability and death.1 While few would dispute the importance of taking effective steps to identify and manage this condition in middle-aged and elderly people, relatively little attention has been paid to the problem of high BP in children. It is now established, however, that high BP is detectable in children and adolescents, is surprisingly common, and is increasing in prevalence.2,3
Importantly, the negative and potentially severe consequences of high BP are not limited to adulthood. Evidence of target organ damage, such as left ventricular hypertrophy (LVH), and pathological vascular changes have been found even in young children and in children with newly diagnosed high BP.4,5 Even subtle neurological changes, which manifest as reduced cognitive function, have also been detected among children with high BP.6
While there are no long-term cohort studies that directly link high BP in childhood to cardiovascular (CV) events in adults, hypertension and prehypertension in childhood commonly lead to hypertension in young adulthood.2 Intermediate markers of CV disease are also identifiable in such patients.7,8 There is little doubt, therefore, that without intervention, high BP in childhood will increase the risk of premature CV disease. It is reasonable to think that effective preventive interventions that are applied early in life could modify disease progression. Despite the body of emerging evidence, pediatric hypertension has received less recognition than diseases with fewer potential consequences.
Against this background, it is a serious concern that even when high BP is recorded, action is not regularly taken. For example, one study that examined electronic medical records found that three quarters of the pediatric patients with high BP, documented in electronic medical records, were not diagnosed as hypertension or prehypertension.9 The limited attention to high BP in children and adolescents is of further concern because it is frequently associated with modifiable risk factors such as poor nutrition, poor sleep habits, lack of physical activity, and obesity.10–12 If the diagnosis of high BP is not made, these associated risk factors are likely to remain unmodified.13
Prevention and management of obesity, hypertension, and other CV risk factors, such as dyslipidemia and insulin resistance, are critical for ensuring the health of young people today and the adults of tomorrow. Lifestyle modifications, such as better nutritional choices, improved sleep quality, and increased physical activity, are obvious first-line approaches to the management of such risk factors. There is ample evidence that greater public awareness and concerted public health initiatives are needed. While position statements and recommendations for childhood CV health14 and nutrition13 have been published, best practice approaches have not been widely implemented to date.
Scope of the Report
This report aims to increase awareness of the problem of high BP in childhood, discuss the most recent evidence on risks associated with high BP in children, and consider health policy changes that are needed to reduce the long-term health burden of high BP beginning in the young.
Burden of High BP in Adults
High BP is a global problem, affecting both developed and developing countries. Recently reported prevalence figures in adults range from 11% in China and 26% in Singapore and approach 40% in Europe and America.15
It is well established that high BP in adults is a major risk factor for CV and cerebrovascular disease as well as a leading cause of premature death worldwide. According to the World Health Organization,16 62% of cases of cerebrovascular disease and 49% of ischemic heart disease cases can be attributed to suboptimal BP. Further, data from the US Framingham Heart Study indicate that patients with prehypertension (BP 130–139/85–89 mm Hg) have a more than 2-fold increase in the risk of CV disease compared with those whose BP is “normal” (<120/80 mm Hg).17
Significant end-organ damage results from CV risk factors such as hypertension. This damage includes LVH, heart failure, myocardial infarction, kidney disease, retinopathy, stroke, and dementia, significantly increasing the risk of premature death.18 Left untreated, such risk factors place a substantial burden on health care systems, families, caregivers, and society as a whole.
Reduction of systolic BP by as little as 10 mm Hg decreases the risk of stroke by about one third among adults aged 60 to 79 years in North America, Western Europe, and the Asia Pacific region.19 Smaller but highly significant reductions have also been shown in the incidence of myocardial infarction. However, the awareness, treatment, and control of high BP remain inadequate in both developed and developing countries. Rates of BP control around the world are typically in the range of 30% to 50% and are often much lower.15 These issues and the actions needed to address them are discussed in more detail in High Blood Pressure and Health Policy: Where We Are and Where We Need To Go Next.20
Burden of High BP in Children and Adolescents
BP is Rising in Children and Adolescents
In the United States, mean BP values in children have increased in recent years. Data from the National Health and Nutrition Examination Surveys (NHANES) show that mean systolic BP (SBP) and diastolic BP (DBP) increased by 1.4/3.3 mm Hg from 1988–1994 to 1999–2000 (P<.001 for both SBP and DBP increases).3 Increases in SBP were most pronounced for non-Hispanic blacks, Mexican Americans, and those in the 8- to 12-year-old age group (Figure). Increases in DBP were large and observed in all subgroups. There was a strong association between body mass index (BMI) and SBP, thus obesity was considered to be a significant determinant of the population increase in BP.
Prevalence of High BP
Estimates for the prevalence of high BP among children are in the range of 3% to 5%, with higher rates in certain subgroups.9,21 A school BP screening program conducted in Houston, Texas, in 2003 to 2005 found that among 6790 adolescents (aged 11–17 years), 15.7% had prehypertension and 3.2% had hypertension (based on 3 separate BP readings).21 The frequency of high BP was much higher among obese adolescents, with rates of hypertension and prehypertension in excess of 30% in obese boys (42% among Hispanics) and 23% to 30% in obese girls (rates varied depending on ethnicity). In a regression model, classification as being overweight—but not by sex or ethnicity—was independently associated with high BP, with an odds ratio of 4.2 (95% confidence interval, 3.07–5.75).21
Another cohort study in the United States evaluated the electronic medical records of 14,187 children (aged 3–18 years) from a large academic urban medical system who had received at least 3 well-child care visits between 1999 and 2006.9 On the basis of documented BP records, 3.6% of children had high BP and 3.4% had prehypertension. However, only 26% of children with high BP had a diagnosis of hypertension entered in their medical record. Thus, 74% of cases of hypertension were undiagnosed and untreated over an extended period, despite having sufficient BP measurements to make the diagnosis.
The worldwide prevalence of hypertension among children and adolescents is not known. Estimates derived on data from a number of more recent regional epidemiologic studies are summarized in Table I. Despite variations in age, sample size, and definition across the different studies, the reported prevalence of high BP among children and adolescents describes a significant health issue.
Table I. Prevalence of Hypertension Around the World
Systolic prehypertension (≥90th and ≤95th percentile for age and sex): 27% of boys/21.5% of girls Systolic hypertension (>95 percentile for age and sex): 12.3% of boys and 15.1% of girls Diastolic prehypertension (≥90th and ≤95th percentile for age and sex): 19% of boys and 21.5% of girls Diastolic hypertension (>95 percentile for age and sex): 13.3% of boys and 15.1% of girls
Why Is High BP Underdiagnosed in Children and Adolescents?
The definitions of hypertension and prehypertension are less clear in children than in adults. Normal BP values in children vary according to sex, age, and height. High BP in children is defined as BP values that are at or above the top 5% of the normal BP range (≥95th percentile).2 High BP may be underdiagnosed in children and adolescents for several reasons, including an overall lack of routine testing and technical issues. Compared with adults, there are more technical issues in accurate BP measurement such as the appropriate BP cuff size and difficulty with auscultation in small children. Cuffs of different sizes are needed for children of different ages and for the obese patient. Use of an inappropriately sized cuff may give false readings. Auscultation is the preferred method for BP measurement, but this can be difficult, particularly in small children. Automated oscillometric instruments are not recommended in routine care because they calculate BP values from proprietary algorithms that differ between manufacturers and devices; thus, results can vary widely.2 However, these devices are commonly used in large pediatric clinics due to convenience. When an automated instrument is used, it should be one that has been validated in the pediatric population (http://www.eshonline.org). It is recommended that BP measurements obtained by oscillometric devices that exceed the 90th percentile should be repeated by auscultation.2
Evaluation of a BP measurement in a child first requires determination of the child’s height percentile, and then a comparison of the child’s BP level with the childhood BP tables according to sex, age, and height percentile of the child. Because the normal range of BP shifts with normal growth and development, the BP levels that denote high BP will change accordingly (for BP tables see http://www.nhlbi.nih.gov/guidelines/hypertension/child_tbl.pdf). Although the tables were developed to achieve more precision and avoid overdiagnosis of high BP, they are complex and cumbersome to use. The National Heart, Lung, and Blood Institute (NHLBI) has recently created simplified BP classification charts for children that can be downloaded from the Internet. While pediatricians are probably the clinicians most likely to routinely measure BP at well-child visits, other health professionals who evaluate children may not have an appropriately sized cuff, and normative BP tables may not be readily available.
Ambulatory BP monitoring (ABPM; usually over a period of 24 hours) is an additional tool that is useful for evaluating patterns of BP in children but, because it requires special instrumentation and trained staff, ABPM is used mostly by pediatric hypertension experts.2,22 ABPM is very useful in the diagnosis of white coat hypertension and in identifying less obvious BP patterns that are associated with end-organ damage in children23 or predisposing factors such as low birth weight. Although some height-adjusted pediatric ABPM reference tables have been published,24 more reference data are needed both in children with normal BP as well as children with high BP. Recommendations on implementation of ABPM in clinical practice and interpretation of results have been recently published in a scientific statement from the American Heart Association (AHA)22 as well as in a recent document about the management of high BP in children and adolescents released by the European Society of Hypertension.25
Home BP monitoring is an alternative method to obtain multiple casual BP readings away from the clinic setting. Home BP monitoring may also have positive educational effects on the families’ awareness, commitment to BP management, and long-term adherence to medication.26 Limitations to home BP monitoring in children include the effort of training relatives and the persistent need for the families’ willingness and abilities to cooperate. Significant misreporting can occur, which may be overcome in part by the use of oscillometric devices with internal memory. In the foreseeable future, telemonitoring may become a useful tool to achieve effective and objective home BP monitoring. The most significant obstacle to use of home BP monitoring is the paucity of normative data.27 An initial set of reference values obtained in 778 schoolchildren and adolescents has recently been published.28
Classification of High BP in Children and Adolescents
Classification of high BP in children and adolescents varies from country to country. In the United States, high BP in children and adolescents is defined as SBP and/or DBP that is ≥95th percentile for sex, age, and height on at least 3 separate occasions.2 Prehypertension is defined as SBP and/or DBP that is ≥90th percentile but <95th percentile on at least 3 separate occasions. The child BP reference tables can be viewed at http://www.nhlbi.nih.gov/guidelines/hypertension/child_tbl.pdf. In ado-lescents (13–18 years), the 90th percentiles are higher than 120 mm Hg for SBP and 80 mm Hg for DBP. Thus, for adolescents, a BP level 120/80 mm Hg (and <95th percentile) is used to define prehypertension. Overall, the BP values of 120/80 mm Hg can be used as an easily remembered number regarding evaluation of BP in adolescents. A value <120/80 mm Hg can be regarded as normal BP. Repeat BP measurements should be obtained for BP values >120/80 mm Hg and the BP charts should be checked for interpretation.
In the United Kingdom, high BP in children is defined as BP >98th percentile for age, measured on repeated occasions.29 High-normal BP is defined as BP between the 91st and 98th percentiles for age. Other countries may have local definitions for normal and abnormal BP readings among children, or they may adapt US or UK standards to their own populations.
Causes of High BP in Children and Adolescents
In very young children and children with severe BP elevations, there is commonly an underlying disorder that is causing the hypertension. In older children and adolescents, high BP can be due to primary (essential) hypertension. As in adults, primary hypertension in children often coexists with other CV risk factors.
Obesity among children and adolescents has increased around the world over the past 4 decades, reaching epidemic proportions in many countries, particularly industrialized nations.30–33 According to the 3 most recent NHANES reports, the prevalence of obesity increased dramatically among children aged 2 to 19 years in the United States from 1988 to 2004: from 10.5% to 17.4% among boys and from 10.5% to 17.8% among girls.34 Similarly, from the 1970s to the end of the 1990s, the prevalence of obesity in children has doubled or tripled in many countries, including Canada, Brazil, Australia, Japan, Germany, Greece, Finland, and Spain.30
It is projected that by 2010 the prevalence of obesity or overweight among children and adolescents will exceed 45% in the Americas, 40% in the Eastern Mediterranean, 38% in Europe, and 25% in Asia and the Western Pacific regions.32
As in adults, there is a strong association between high BP and BMI in children and adolescents.5 Data from 8 large epidemiologic studies in the United States involving 47,196 children demonstrated an increased risk of hypertension on the basis of BMI.35 For children with BMI ≥90th percentile, odds ratios for having BP >95th percentile for height and weight were 1.7 to 2.9 for elevated DBP and 2.4 to 3.7 for elevated SBP, depending on age, sex, and race.35
Metabolic Syndrome and Insulin Resistance
High BP and obesity are components of the metabolic syndrome, a term used to define the clustering within individuals of the CV risk factors of abdominal obesity, dyslipidemia, impaired glucose tolerance, and high BP. Adults with the metabolic syndrome are at increased risk for developing diabetes and CV events. Therefore, it should be of concern that the prevalence of the metabolic syndrome among children and adolescents has risen in the past 2 decades in line with increases in the prevalence of obesity and hypertension.36,37 Insulin resistance itself may contribute to the development of high BP in children with other CV risk factors. In an evaluation of 87 overweight or obese children aged 6 to 18 years, insulin resistance was associated with high SBP during the sleep phase of ABPM.38 The investigators postulated that the early elevation of BP at rest may be a harbinger of hypertension-related insulin resistance.38
The increasing prevalence of pediatric type 2 diabetes coincides with increasing obesity in children. In a recent report, 60% of obese children had insulin resistance, 5% had impaired glucose tolerance, 1% had impaired fasting glucose, and 0.2% had type 2 diabetes.39 Reducing overweight and impaired glucose tolerance may help prevent or delay the development of type 2 diabetes in high-risk youths.
High Cholesterol and Dyslipidemia
The Working Group guidelines published in 2004 recommended measuring plasma lipids in children and adolescents with high BP in order to assess for additional risk factors. However, little information is available on treatments for lipid abnormalities beyond diet and weight control in overweight children. Recently, the AAP revised recommendations regarding the management of hypercholesterolemia in the pediatric population.40 The preferred approach for hypercholesterolemia is lifestyle modifications in diet. However, some children do have marked hyperlipidemia. The recommended lipid thresholds for pharmacologic treatment are consistent with severe hyperlipidemia, on the order of levels present in children with genetic hyperlipidemia. These recommendations have been prompted by evidence showing that atherosclerosis begins at an early age and treatment of hypercholesterolemia may reduce the lifetime risk of CV disease. Much debate has emerged over these recommendations, especially with respect to the inclusion of statins as first-line treatment. While short-term data demonstrate that statins are safe in children, long-term follow-up is lacking.41 Due to the important functions of cholesterol in various roles during the development of the brain, as well as other key biological functions during development, the long-term safety of this approach has not been resolved. Preventing hypercholesterolemia by modifying lifestyle risk factors is a preferable treatment option in most children with modest dyslipidemia. Further research is needed to evaluate the long-term effects and benefits of these and many other drugs in the pediatric population.
Other Lifestyle Factors
Other factors that are likely to contribute to high BP in children and adolescents include a sedentary lifestyle, dietary factors, and poor sleep quality. Dietary patterns have shifted among children and adolescents as a result of changes in the world food supply and food economy. As a result there has been increasing consumption of highly processed foods, including energy-rich foods, foods that are dense in sodium and fat, and sweetened soft drinks. Concurrently, there has been a reduction in consumption of fruits, vegetables, and milk.32 Despite the lack of direct evidence for links between high BP, nutrition, and exercise, trends in dietary patterns and physical activity patterns clearly favor the rising prevalence of obesity and are at least indirectly related to hypertension.32 Thus, improving diet quality and increasing physical activity and weight loss are cornerstones for both the prevention and the nonpharmacologic treatment of hypertension in children2 as well as adults.
Poor sleep quality has also been connected with hypertension in adults, and a recent study by Javaheri and colleagues found that poor-quality sleep is linked to prehypertension and hypertension in otherwise healthy adolescents. Even after adjustment for other potential contributing factors such as obesity, poor sleeping patterns led to SBP levels that were an average of 4 mm Hg higher compared with children with healthy sleeping patterns (P<.01).12 The sleep apnea syndrome is also frequently associated with hypertension, particularly among overweight children. Recommended treatments focus on measures to reduce obesity. In extreme cases with severe obstructive sleep apnea, treatments with positive pressure breathing equipment or surgery could provide benefit in select individuals.42
Low Birth Weight
Low birth weight is also a possible etiology of high BP in some children.2,25,43 CV risk is determined not only by conventional risk factors important in adult life, but there may also be a contribution from early life programming in response to the intrauterine fetal environment. Several epidemiologic studies have documented that low birth weight or reduced fetal growth are conditions associated with increased risk of hypertension, coronary heart disease, stroke, and CV disease in later life.44
Secondary causes of hypertension are much more common in children than in adults. The proportion of secondary hypertension observed in pediatric tertiary care centers vary considerably, depending on region and age distribution.45 Secondary forms of hypertension commonly cause severe hypertension and should always be considered when hypertension is diagnosed in children, especially in those without risk factors such as obesity or a family history of hypertension. Secondary hypertension is particularly prevalent in young children and the degree of hypertension is often more severe. Renal parenchymal disease accounts for at least 75% and renovascular disease for another 10% of cases. Less common causes of secondary hypertension include endocrine disorders, CV disease (eg, coarctation of the aorta), and monogenetic inherited forms of hypertension such as Liddle syndrome and glucocorticoid remedial hypertension.46,47 The latter should be considered when parents have a history of early-onset (adolescence or young adulthood) and severe hypertension.
Consequences of High BP in Children and Adolescents
As in adults, mild to moderate hypertension in children and adolescents can be asymptomatic or may involve subtle symptoms such as headache, epistaxis, shortness of breath, and changes in behavior or school performance, although relationships between these observations and hypertension could easily be overlooked.
Hypertensive Children Become Hypertensive Adults
Elevated BP in children continues into adulthood.2 SBP that meets the definition of high BP at any age increases the odds of developing high BP in adulthood (≥30 years) by 3- to 4-fold compared with children whose SBP is normal.2 What is not known is whether interventions to reduce high BP during childhood will dampen progression to hypertension in adulthood. While it is well established that hypertension in adulthood is a major risk factor for CV, cerebrovascular, and renal disease, there are few long-term prospective studies that have observed BP levels from childhood into mid-adulthood. Therefore, the level of BP in childhood that predicts CV or renal disease in adulthood is not known. These are issues that are in need of further research.
Recent data from the Fels Longitudinal Study, in which serial BP readings were recorded from 2 years of age to adulthood in 493 participants (240 men, 253 women), found that adults who developed the metabolic syndrome had significantly higher childhood SBP than those without the metabolic syndrome (P<.05).7 The odds ratios for developing the metabolic syndrome, if BP exceeded criterion values at a single examination, ranged from 1.1 to 1.8 for girls and 1.2 to 5.6 for boys. Among adults with vs without the metabolic syndrome, the earliest significant difference in SBP values occurred at 5 years of age for men and 8 years of age for women.7
Although BP levels in childhood cannot be directly linked with risk for CV or renal disease in adulthood, a number of studies have reported that intermediate markers of target organ damage are detectable in children and adolescents with elevated BP.
Left Ventricular Hypertrophy
In adults, LVH is an independent risk factor for CV morbidity and mortality and is considered to be the most prominent clinical evidence of target organ damage resulting from hypertension during childhood and adolescence.2 In a cross-sectional study of 130 patients aged 6 to 23 years with persistent BP elevation >90% percentile for a mean of 2 years, only 58 patients (45%) had a left ventricular mass index (LVMI) <90th percentile (which is considered normal).48 Nineteen patients (14%) had an LVMI >99th percentile (ie, severe hypertrophy), with 11 (8%) of these above the adult cut-off of 51 g/m2,7 which is associated with a 4-fold increased risk of CV morbidity in hypertensive adults.49 Among patients with an LVMI >95th percentile, 22 (17%) had concentric hypertrophy and 39 (30%) had eccentric hypertrophy. A logistic regression analysis determined that high BMI, low heart rate at maximum exercise, and male sex were independent predictors of LVH.48 BMI and male sex were also found to independently predict LVMI in a recent study in 137 children with mild to moderate chronic kidney disease.50
The Strong Heart Study evaluated CV risk factors among Native American communities from 1989 to 2003.5 Of the 1940 participants who were younger than 40 years, 15% had hypertension and another 35% had prehypertension. The prevalence of LVH was increased more than 3-fold in those with hypertension and was 2-fold higher in those with prehypertension compared with participants with normal BP.5 The finding that even a prehypertensive state is associated with an adverse effect on left ventricular structure in adolescents and young adults is a significant finding.
Obesity may further contribute to the development of hypertensive LVH. The Bogalusa Heart Study was a compilation of serial observations from childhood to young adulthood based on 7 cross-sectional surveys of children aged 4 to 17 years and 5 surveys of young adults aged 18 to 38 years who participated as children (and were still available to participate as adults), conducted from 1973 to 1996.51 In an early subanalysis of this study, left ventricular mass (LVM) was tracked from 1973 to 1982 among a cohort of 160 healthy children/young adults initially aged 9 to 22 years. In both sexes, higher LVM was predicted by higher SBP and DBP, as well as age, height, weight, and adiposity at first examination. After adjusting for linear growth in a univariate analysis, initial weight and obesity remained significantly correlated with the presence of LVH in both sexes (male: r=0.28, female r=0.32; P<.01), and SBP remained correlated in women (r=0.23; P<0.05).52
Carotid intima–media thickness (CIMT) is often used as a surrogate marker of CV health (preclinical atherosclerosis). Lande and colleagues4 found that CIMT was significantly higher in 28 children with newly diagnosed hypertension confirmed by ABPM than in age- and weight-matched controls, with a particularly strong correlation for elevated daytime SBP (r=0.57; P=.003) that was independent of effects of obesity. Higher CIMT correlated with more severe hypertension.
In the Bogalusa Heart Study, carotid artery ultrasonography was performed in the 1996 survey to examine the relationships between CV risk factors in childhood and carotid intima–media artery thickness in young adults.51 Childhood SBP, low-density lipoprotein cholesterol (LDL-C) levels, and BMI correlated with CIMT in young adults, as did SBP in adulthood.
Similarly, in the Young Finns Study, a population-based cohort study that included 2229 white adults aged 24 to 39 years from 5 centers in Finland who were examined in childhood, adolescence, and 21 years later, childhood SBP was a risk variable associated with increased adult CIMT in both men and women.8 Other risk variables included BMI in both men and women and LDL-C, total cholesterol, triglyceride levels, and DBP in men. In a multivariate analysis, childhood SBP, LDL-C levels, smoking, and BMI were significantly associated with adult intima-media thickness in an age- and sex-adjusted model.8 When adjusted for other risk variables, SBP and LDL-C levels remained independently associated with CIMT (P=.006 and P=.02, respectively).
Postmortem findings from participants in the Bogalusa Heart Study who died between 2 and 39 years of age from various causes (primarily trauma) provide direct evidence for a relationship between atherosclerosis in children and young adults and CV risk factors, based on the extensive data on risk factors that had been collected for these participants during the study. There were significant correlations of BMI, BP, and lipoproteins with lesions in either the aorta or coronary arteries. Specifically, SBP was strongly and significantly correlated with fatty streaks in both the aorta and coronary arteries, and with fibrous plaques in the coronary arteries. DBP also correlated with fibrous plaques in the coronary arteries.53 These observations confirm the notion that CV risk factors that contribute to atherosclerosis have origins in childhood.
Retinal arteriolar narrowing is a known consequence of high BP and can predict CV morbidity and mortality.54 Recent data from 2 parallel population-based studies among 1952 children in Australia and Singapore shows that significant and consistent retinal artery narrowing is evident among children as young as 6 to 8 years of age with high BP. For each 10-mm Hg increase in SBP, retinal arterioles were reduced in diameter by 2.08 μm in Australian children and 1.43 μm in children from Singapore, according to a multivariate regression analysis adjusted for age, sex, race, BMI, ocular factors, and birth weight.55
In adults, high BP and dyslipidemia are risk factors for developing mild cognitive impairment, leading to poorer attention, reaction time, verbal fluency, and executive function.18 Cognitive impairment may be a result of narrowing and sclerosis of smaller arteries in the brain, which contributes to hypoperfusion, loss of autoregulation, and demyelination of subcortical white matter. Using NHANES III data (1988–1994) from children aged 6 to 16 years, Lande and colleagues demonstrated a relationship between elevated SBP (≥90th percentile) and significantly lower scores for digit span, block design, and mathematics tests (measurements of intellectual function, constructional skills, and academic performance, respectively), when compared with children whose SBP was <90th percentile.56 In a subsequent case-control study, these investigators reported that children with hypertension, independent of obesity, demonstrated lower parental ratings of executive function compared with normotensive control children,6 indicating that even in childhood, subtle changes in cognitive function associated with hypertension are detectable.
Urinary Albumin Excretion
Renal excretion of small amounts of protein, or microalbuminuria, is an early marker of kidney injury. Proteinuria (even microalbuminuria) is associated with an increased risk for CV and renal disease in adults with and without diabetes.57
A few studies in children have demonstrated a relationship between microalbuminuria and CV risk factors such as high BP.58–60 A small study of 55 children aged 11 to 19 years with essential hypertension found that microalbuminuria is a predictor of LVH in this age group.58 In the Bogalusa Heart Study, high BP in childhood predicted microalbuminuria in adulthood among African Americans but not among whites.59 Racial differences in urinary albumin excretion were also observed in a recent study of 317 adolescents with normal BP.60 In this study, the albumin excretion rate was significantly higher (by approximately 10%) in black adolescents compared with their white peers (P=.006). Albumin excretion rate was positively related to SBP in black men but not in any other subgroup. The authors postulated that this may be evidence of end-organ damage preceding the clinical finding of sustained high BP in this at-risk group.60
The impact of high BP on microalbuminuria appears to be compounded when it exists with other CV risk factors. A cross-sectional analysis of NHANES 1999 to 2004 data found that the only CV risk factor associated with microalbuminuria among normal-weight adolescents was diabetes mellitus, whereas among overweight adolescents, microalbuminuria was associated with a number of CV risk factors, including hypertension, impaired fasting glucose levels, insulin resistance, diabetes, and smoking.61 Data from the prospective German Diabetes Documentation System identified high BP, LDL-C level, and duration of diabetes as risk factors for developing microalbuminuria among children with type 1 diabetes.62 Although the role of microalbuminuria assessment in pediatric essential hypertension has yet to be fully established, assessment of microalbuminuria emerges as a marker of early end-organ damage.25
Management of Pediatric High BP
In 2004, the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents published guidelines based on the available evidence for the management of high BP in children and adolescents.2 Nonpharmacologic treatments involving therapeutic lifestyle changes and health-related behaviors were recommended for all children and adolescents with high BP (Table II). Indications for pharmacologic therapy and pediatric dosing information are also included in the report. Since the 2004 working group report, additional findings have been published that are relevant to treatment of high BP in pediatric patients.25
Table II. Lifestyle Changes for the Treatment of Hypertension in Children and Adolescents2,13
Primary therapy for obesity-related hypertension
Regular physical activity
Restriction of sedentary activity (ie, watching television or playing video games) to <2 h/d Participation in 30–60 min of physical activity 4 or 5 times per week, generating energy expenditures above the resting level and ideally at least 50%–60% of maximal exertion
Better sleep practices
Identification and treatment of sleep disorders including trouble falling asleep or waking early Ensure a minimum of 7 h of sleep a night
Reduce sodium intake
Limit sodium intake based on recommended guidelines by age (<1500 mg/d for 1- to 3-year-olds; <2300 mg/d for 14- to 18-year-olds)
Other dietary modifications
Calorie restriction and portion control Reduce consumption of sugar-containing beverages and energy-dense snacks and processed foods Increase consumption of fruit, vegetables, and fiber; change to low-fat dairy foods Eat regular meals, including a healthy breakfast Consultation with a nutritionist; possible multidisciplinary approach
Improves success rates
Weight Loss. Given the strong association between hypertension and childhood obesity, loss of excess weight is particularly important in overweight children and adolescents, but instituting preventive or weight-loss measures for childhood obesity is challenging.63 Adequate nutrition must be maintained for healthy growth and development, while avoiding risks such as smoking for weight control and the development of eating disorders. Weight control and weight-loss programs therefore require careful supervision and involve a variety of interventions and outcomes. Counseling for children and families is an integral part of obesity prevention. Recent publications detail current recommendations for treatment of obesity in children and adolescents.63,64
Diet Modification. Dietary sodium intake in children and adults in more developed countries is far in excess of nutritional requirement. Based on a large body of epidemiologic and clinical evidence, dietary modification to lower sodium intake has been recommended in the management of adults with hypertension. The association of sodium intake with BP in children has been more difficult to define. Recently, He and colleagues65 performed a meta-analysis on reported studies that examined the effect of dietary sodium reduction on BP in children and adolescents. In combining the results of 10 separate studies conducted between 1981 and 2004, the investigators found that a 54% reduction in sodium intake was associated with modest (2.47 mm Hg) reduction in systolic BP. While the absolute change in BP with sodium reduction appears small, the population effect is likely to be greater and the lifelong burden of modest increases in BP due to dietary sodium could be important. Another concern regarding excess dietary sodium intake is the effect on thirst. Another study was conducted by the same investigators66 to compare sodium intake with the volume and type of beverage consumption in children in Great Britain. A statistically significant correlation (P<.001) of sodium intake with beverage consumption was demonstrated, plus a high consumption of sugary beverages. These findings indicate that excess dietary sodium intake may not only raise BP but, through effecting thirst that was satisfied by increased consumption of sugary beverages, also contribute to childhood obesity.
Reducing dietary sodium intake from usual levels that are in excess of 2500 mg are recommended.2 However, lowering dietary sodium is difficult for both adults and children because of hidden salt in the processed foods of westernized diets. Because >75% of dietary sodium is derived from processed foods, a decrease in salt intake is difficult to achieve without avoidance, to a large degree, of these foods. An alternative approach would be a progressive reduction in the quantity of salt added in the processing of food products by the food industry.
Other dietary nutrients confer health benefits. The classic Dietary Approaches to Stop Hypertension (DASH) study demonstrated the BP-lowering benefits in adults with high BP of a diet that was high in fresh fruits, vegetables, whole grains, and low-fat dairy products.67 Although comparable clinical trials have not been conducted in children, it is generally accepted that children with high BP may benefit from diets that emphasize fruits, vegetables, fiber, and dairy, plus a reduction in sodium.2 A recent report by Couch and colleagues68 provides some data to support this recommendation. The investigators compared, in an outpatient setting, a DASH diet for children vs standard nutrition counseling in 57 children with hypertension or prehypertension. There was a significantly greater reduction in SBP in children assigned to the DASH diet compared with standard diet counseling, and BP was normalized in 50% of children in the DASH group compared with 36% in the routine-care group, despite no reductions in BMI. Although this report is described as a pilot study, the results support both the need for further investigation and also current recommendations on the emphasis of fruits, vegetables, fiber, and dairy in children’s diets.
Pharmacologic Therapy. Hypertension in children is undertreated, likely a reflection not only of underdiagnosis, but also of the lack of clearly established consequences of undertreatment in this population, lack of parental understanding of the need for treatment, lack of clear-cut guidelines for treatment, and lack of prioritization and reimbursement by third-party payers.
Pharmacologic therapy is recommended for patients with symptomatic hypertension, secondary hypertension, hypertensive end-organ damage (in particular LVH), diabetes, and hypertension that persists despite nonpharmacologic therapeutic interventions.2
Limited pediatric data are available on many antihypertensive drugs. The clinical trial studies that are required for regulatory approval are normally conducted on adults. In recent years, a series of legislative policies in the United States, including the Food and Drug Administration Modernization Act, The Best Pharmaceuticals for Children Act, and the Pediatric Research Equity Act, encouraged and then required pharmaceutical companies to obtain pediatric data on their more recently developed drugs. In a similar legislative move, European authorities created the Regulation of Medicinal Products for Pediatric Use regulation, which also requires development of pediatric data on new pharmaceutical products. Subsequently, a number of drugs have been or are being investigated for safety and tolerability as well as efficacy in the pediatric population. Recent clinical trial data have become available to guide drug treatment on several medications within several drug classes (eg, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], calcium channel blockers [CCBs], and β-blockers).2,25
On the basis of evidence from clinical trials and available dosing information for children, when lifestyle changes have failed, first-line therapy should be with a single agent: an ACE inhibitor, ARB, β-blocker, CCB, or diuretic.2 At this stage of knowledge there is insufficient information to determine whether one antihypertensive drug class is preferable to another for treatment of primary hypertension in childhood. The goal should be to reduce BP to <95th percentile value for uncomplicated hypertension or to <90th percentile for children with concurrent conditions such as chronic renal disease, diabetes, dyslipidemia, or end-organ damage.69 These recommendations are derived from expert opinion and best available evidence, as there are few data relating to long-term outcomes beyond BP-lowering in the pediatric hypertensive population.2
Further research is needed on the long-term outcomes and benefits of antihypertensive medication beyond only BP reduction, including reversal of markers of target organ damage such as LVH and albuminuria. Moreover, more data are needed to determine the optimal timing of pharmacologic interventions to optimize long-term effect. Until such data become available, specific classes of antihypertensive agents should be used depending on comorbidities and individual factors specific to each patient. Pediatric clinical trial data are beginning to emerge to support clinical decisions, such as a clinical trial report that ACE inhibitors and ARBs are more effective than CCBs in reducing proteinuria in children with high BP.70
Life-long follow-up is indicated in the majority of children. Home monitoring of BP can greatly facilitate this management. In children with renal hypertension, regular ABPM measurements at 6- to 12-month intervals are indispensible to rule out selective nocturnal hypertension.25
Impact of Pediatric High BP on Health Care Systems
The economic impact of the increasing prevalence of high BP in children and adolescents worldwide has yet to be evaluated. Given that children with high BP are likely to become adults with high BP, with all the attendant hypertension-related sequelae, the impact will be substantial. Alternatively, if appropriate attention could be applied to identification, evaluation, and management of children with high BP, the long-term benefit could also be substantial.
From a clinical perspective, the evaluation and monitoring of high BP require ongoing assessments above and beyond those needed for children and adolescents with normal BP, which adds to health care costs. For example, the Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents recommends a number of diagnostic studies for children with confirmed hypertension including standard blood and urine laboratory tests and renal ultrasonography. In addition, screening for associated risk factors and target organ damage is recommended, which adds plasma lipid and glucose measurements and an echocardiogram. Additional studies are to be considered when an underlying cause of secondary hypertension is suspected.2 These tests have obvious economic implications in terms of both direct and indirect costs (eg, lost productivity because parents take time off work to take children to clinic visits). Although the economic impact has not been quantified, at least one small study has demonstrated echocardiographic evidence for regression of LVH after drug therapy for hypertension in children.71 Similarly, the pharmacologic treatment of pediatric hypertension has implications in terms of drug costs and continued monitoring for efficacy and safety. The costs of treating high BP in children and adolescents have not been compared with costs associated with its prevention in the first place.
What Should We Do Next?
High BP is clearly a major chronic health problem worldwide. Although long considered a disease of aging, its prevalence is increasing in children and adolescents, adding to the global problem of high BP. Most alarming is that evidence of end-organ damage caused by high BP, such as LVH and vascular changes, are identifiable even in young children. Given the trends observed so far, as well as additional predictive data discussed in this report, the situation can only worsen without concerted efforts to modify high-risk behaviors that adversely affect CV health among children and also efforts to develop comprehensive, population-based approaches to this problem.
At a local level, families, schools, and communities should be encouraged to foster healthy lifestyles among children and adolescents through efforts to improve diets and physical activity. As a step in this direction, the Valencian Community, an autonomous region of Spain, has initiated a public program aimed at reducing CV risk in this target population. The program has established objectives and recommendations both for identifying early markers of CV risk as well as for assessing and treating them. Actions to be carried out at the individual, family, school, and community levels are specifically addressed. An electronic network records the data of the entire pediatric population and permits close tracking, which, in turn, facilitates the implementation and follow-up processes.
Healthy Lifestyle Choices
A major contributor to the increases in BP among children and adolescents around the world is the soaring prevalence of obesity, resulting from the increase in consumption of calorie-dense foods and the decline in physical activity (creating an “obesogenic” environment).32 Programs that effectively reduce childhood obesity will, no doubt, also reduce the incidence of childhood hypertension. Scientific position statements have been developed on CV health promotion by physicians and in schools. However, more efforts are needed. Kosti and colleagues32 highlighted the imbalance between exposure to nutrition education relative to advertising for nonnutritive foods such as biscuits/cookies, sweets/candy, gum, and snacks.
Although parents are theoretically in a position to influence proper nutrition for younger children, this is not happening in reality. According to a review of what children eat conducted by the AHA, consumption of deep-yellow vegetables and fruit declines substantially at as early as 19 months of age, to the point where toddlers consume more fried potatoes, baked desserts, and sweetened beverages than fruits.13 Thus, the stage is set for poor nutrition at a young age. The problem continues into adolescence. Adolescents are often free to make their own food choices and, as Kosti notes, this age group is heavily targeted by the food industry and are big spenders.32
Encouraging parents to establish good eating habits at home, instead of supplying fast foods and nonnutritive snacks, is a vital component of any CV health promotion program. Both the AHA and the AAP recommend limiting sedentary activities such as watching television and playing computer games by children to <2 hours a day. In addition to limiting their children’s sedentary activity and encouraging greater physical activity, parents should also set an example by avoiding smoking and excessive alcohol consumption.
Role of Policy Makers and Schools
It is unrealistic to believe that great improvements in CV health among children can be accomplished at home alone. Concerted efforts are needed by policy makers and society globally to promote healthy lifestyle choices for and by children. Aggressive strategies are needed to promote the health benefits and fun of engaging in physical activity, to promote healthy food and beverage choices (highlighting the nutrition deficits of processed foods), and ideally to limit direct marketing of nonnutritional foods such as candy/sweets, soft drinks, and heavily salted snacks to children.
Schools should be provided with—and carry out—opportunities for promoting CV health, such as more time for classroom health education and physical education. Schools should also provide food choices that are conducive to good CV health, while limiting availability of food with poor nutritive value and excessive sugar and salt.72
Improve Diagnosis of High BP in Childhood
The problem of pediatric hypertension is among us right now. Currently, the majority of cases appear to be undiagnosed,9 which restricts abilities to provide preventive lifestyle interventions. Thus, greater efforts are needed to identify and treat children and adolescents with high BP. Children are now commonly having their BP measured but clinicians need to develop greater awareness and have better tools to recognize and diagnose prehypertension and hypertension. Children at high risk require evaluation and monitoring. Insurers and payers must act to reimburse for the evaluation and treatment costs, including lifestyle counseling, associated with high BP in children and adolescents.
Professional education programs, public health campaigns, and school-based educational programs should be implemented to raise awareness of pediatric hypertension and its consequences among health care professionals and the general public.
Professional education programs should be developed to increase awareness of the importance of routine BP screening among children and adolescents and discuss ways to overcome current diagnostic barriers. Further, professional groups should collaborate on the development of standardized user-friendly diagnostic guidelines for this population.
Optimize Management and Control
Health care professionals should also collaborate in developing treatment guidelines for the pediatric population. Professional education programs regarding the management and control of pediatric hypertension should be developed to increase awareness of the importance of treatment as well as provide guidance with regard to specific management strategies. Public health campaigns should be developed to inform on the importance of normal BP among adolescents and children and to reduce the parental resistance to treatment.
It is clear that pediatric high BP will further contribute to the current epidemic of CV disease unless it is given the attention it deserves by policy makers, health care providers, schools, parents, caregivers, and society as a whole. Action is required to address this problem in one of the most vulnerable and precious sectors of our society: the children who should be able to rely on us to provide the care they deserve.
Call to Action
• Policy action as global health priorities is required in both developed and developing countries to establish awareness, identification, management, and control of high BP in children and adolescents.
• Public awareness is needed for recognition of the increasing prevalence of high BP among children and adolescents. The situation is likely to worsen without definitive efforts by society and public policy makers, as well as clinicians, to modify risks.
• Public commitment and action must be taken to discourage and modify high-risk health behaviors that both contribute to obesity and are associated with high BP in children and adolescents.
− Public policy must more strongly advocate and encourage healthy nutrition, reduced salt intake, good sleep practices, physical activity, and prevention of obesity from birth.
− There is a need for programs that encourage parents to set the stage for a healthy lifestyle, encouraging home-cooked meals, limiting prepackaged “fast food,” and nonnutritive snacks and beverages; reducing sodium intake; avoiding smoking and alcohol; and limiting sedentary activities.
− Policy is needed to limit direct marketing of nonnutritional foods such as sweets, soft drinks, and heavily salted snacks to children.
− Schools in both developed and developing countries should actively promote CV health programs, including health education and increased physical activities, as well as provide meals with limited amounts of foods with excess sugar and salt and poor nutritive value.
• Public health programs and health care payers need to support methods to improve identification and management of high BP among children and adolescents in both developed and developing countries.
− Pediatric health care programs should include the assessment of BP as part of standard health assessment throughout childhood.
− Clinicians should develop a better understanding of the normal values for BP in childhood and a more consistent approach to BP measurement as part of our everyday management of young patients.
− Insurers and other payers must acknowledge the magnitude of the problem of pediatric high BP and increase their reimbursement of associated costs to ensure appropriate investigation, treatment, and improved long-term outcomes.
− In developing countries, the charitable community, intergovernmental organizations, nongovernmental organizations, civil society groups, philanthropic foundations, the private for-profit sector, health professionals, and the research community must unite against the threat of high BP in children and adolescents, as well as in adults.
• A global effort is needed to promote research that will fill gaps in knowledge on initiating mechanisms, biomarkers for vascular and organ injury, noninvasive tools to detect and quantify progression and reversal of vascular and organ injury, and interventions. Research is critical to achieve the following objectives:
− To clarify the risk factors for development of pediatric hypertension.
− To identify the adverse sequelae associated with high BP in children and adolescents.
− To define at-risk BP levels.
− To measure the global impact on health care costs, societal burden, and human lives.
− To compare the various treatments and establish the best options to reduce morbidity and mortality for children and adolescents with high BP.
The problem of high BP in children and adolescents will continue to grow, further contributing to the current epidemic of CV disease and its burden on society, unless it is given the attention it deserves by policy makers, health care providers, schools, parents, caregivers, and society as a whole.
Acknowledgments and disclosures: The authors wish to acknowledge Oxford PharmaGenesis, Inc for their editorial support with the development of this manuscript. This support was funded by Novartis Pharma AG. Dr Falkner received research support from the National Institutes of Health and the Pennsylvania Department of Public Health. Dr Falkner is also a consultant on a pediatric clinical trial for Pfizer and serves on a Data Safety Monitoring Board for Merck. Dr Lurbe is a consultant/advisory board participant for Novartis. Dr Schaefer is a consultant for Novartis, AstraZeneca, Boehringer Ingelheim, and Bristol-Myers Squibb.