Introduction

The importance of abnormal blood pressure among pediatric patients is becoming clearer, with numerous recent studies adding to our understanding of its prevalence and possible consequences [1]. In a study of data from national health surveys examining high blood pressure trends in children and adolescents in the United States (US), the authors found the prevalence of pre-hypertension and hypertension among children and adolescents to be increasing among all ethnic groups in parallel with the increase in obesity, especially among African American and Mexican American youth. They found a prevalence of hypertension of 3.7 % overall, but up to 9 % in some groups [2]. Other studies have found prevalence rates of hypertension as high as 15 %, especially among American racial minorities and in overweight or obese children [1, 3]. The variation in exact prevalence rates reported in these studies is due to differences in study design as well as how blood pressure was measured and whether repeated or average measurements were reported. Further discussion and recommendations regarding these issues can be found below.

The epidemiologic data not only demonstrate an increase in overall blood pressure values and prevalence of hypertension and pre-hypertension, but also show an alarming rate of progression and tracking of elevated blood pressure into adulthood [4]. Falkner and colleagues reported the rate of progression from prehypertension to hypertension at 7 % per year. In that study, initial body mass index (BMI) and changes in BMI had significant effect on blood pressure changes over time [5]. In a more recent study, Redwine and colleagues also reported that elevated blood pressure increases the risk for the development of hypertension during adolescence. In their study, students with pre-hypertension by the 2004 Task Force definition developed hypertension at a rate of 1.1 %/year (hazard ratio 2.98; 0.77–11.56) [6]. Among those with hypertension, it will persist in many children after 2 y of follow-up [7]. This was also the conclusion of the systematic review and meta-regression analysis by Chen and Wang; they showed that the evidence of blood pressure tracking from childhood to adulthood is strong, that elevated childhood blood pressure is associated with elevated blood pressure later in life, and that early intervention is important to reduce future cardiovascular risk [8]. The take-home message from these data is that blood pressure elevation in children or adolescents will progress over time, so youth with blood pressure even in the pre-hypertensive range merit intervention and long-term follow-up.

Relationship Between Obesity and Hypertension

The increasing burden of pediatric hypertension is undoubtedly related to the worldwide childhood obesity epidemic, which shows no signs of slowing. Defining obesity as a BMI ≥95th percentile for age and gender, the prevalence of obesity among US children and adolescents is 17 % [7]. A recent meta-analysis in India of studies performed over the last decade found the prevalence rate of overweight (BMI ≥85th and <95th percentile) to be over 12 % and that of obesity to be over 3 %. Some suggest that this may even be an underestimation since charts used to define percentiles are based on normative data from the US and United Kingdom [9]. Among Indian children from higher socioeconomic classes, the rates are even higher, with overweight rates of 16–19 % and obesity rates of 5–6 % [10].

Higher socioeconomic status is associated with obesity in several developing African countries as well, in contrast to developed nations, where higher socioeconomic status appears to be protective [11]. A quickly increasing rate of overweight and obesity among children has been found in many other countries, including Thailand, China, Brazil and South Africa [12, 13]. Worldwide, the overall prevalence of overweight and obesity in children increased by 2.5 % between 1990 and 2010. That year, the estimated prevalence among the world’s children was 6.7 %. At the current rate of increase, it is expected to exceed 9 % by 2020 [14]. Other estimates already exceed 10 % [11]. In addition to the alarming rate of rise in overweight and obesity, the rates of co-morbities such as type 2 diabetes mellitus (with India demonstrating one of the highest rates in the world) and the metabolic syndrome are also increasing [15].

While the presence of obesity or hypertension does not necessarily predict the other, there is a clear correlation between the two. For example, Robinson et al. found a positive correlation between increased BMI and primary hypertension as well as presentation of hypertension at a younger age among those with increased BMI [16]. Flynn et al. also found a correlation between higher BMI and higher systolic blood pressure [17]. In the study by Muntner et al. [18], blood pressure levels correlated with BMI and waist circumference. Among obese adolescents in the US, the prevalence of hypertension has been estimated to be at least 10 % and strong associations have been found in younger children as well [3, 18]. Data from European and Indian cohorts show higher rates of hypertension, with up to 35 % of overweight or obese children having hypertension in each population [14].

Clearly, obesity-associated hypertension has become an important pediatric health problem and predicts an expected increase in adult cardiovascular disease in the future. Hypertension in adolescents has been shown to significantly increase the risk of adult hypertension [19]. Based on current data, some extrapolated estimates show an increase in coronary artery disease among adults to increase by 5–15 % over the next 25 y. In the US, for example, this corresponds to >100,000 extra cases that will be attributable solely to childhood obesity [7]. Data from Egypt not only demonstrate the relationship between obesity and hypertension, but also development of the metabolic syndrome, including hypertriglyceridemia and insulin resistance [20]. In summary, the significant rise in the prevalence of obesity over this last decade has been accompanied by a corresponding increase in the prevalence of hypertension.

Pathophysiology

There are several pathophysiological mechanisms that probably contribute to the development of hypertension in obesity (Fig. 1). Insulin resistance and hyperinsulinemia are independent activators of the renal sympathetic nervous system. This causes vasoconstriction and reduced renal blood flow, which is a trigger for renin release. The end result of this activation of the renin-angiotensin-aldosterone system is sodium and water retention, which raises blood pressure. Also contributing to the reduced renal blood flow is direct compression of the parenchyma by perinephric fat, which encourages sodium reabsorption and higher blood pressure. This phenomenon occurs even in the absence of signs of sclerosis or chronic kidney disease.

Fig. 1
figure 1

Mechanisms of obesity-related hypertension

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Higher levels of leptin, a hormone produced by adipose tissue, are associated with elevated blood pressure, a relationship that is mediated by BMI and effects on sympathetic nervous system [21]. Conversely, obese individuals produce less adiponectin, an anti-atherogenic, cardioprotective hormone made in adipose tissue, which inversely correlates with blood pressure in obese children and adolescents [22]. The proinflammatory cytokines and oxidative stress produced in obesity probably contribute to vascular endothelial dysfunction, impairing the local vasodilatory response, thereby increasing peripheral resistance.

Obese children with sleep-disordered breathing (apnea, hypopnea) are at even higher risk of developing hypertension, especially at night. Furthermore, sympathetic activation via multiple other mechanisms and morbidities may contribute to a higher blood pressure in obese children; these include but are not limited to the proinflammatory state created by cytokines such as increased IL-6 production, which in turn results in an acute phase response. In addition, the sympathetic nervous system plays a role in energy balance and metabolic syndrome as fasting suppresses, and meal ingestion induces sympathetic activity [23]. Weight loss reduces sympathetic overactivity in obesity, which may partly explain the lower blood pressure in response to dieting [24]. Central fat distribution is associated with disturbances in the hypothalamic-pituitary-adrenal axis, suggesting that a disturbed axis may be implicated in the development of the metabolic syndrome [25].

Finally, there is often a history of poor nutrition in overweight and obese patients. Calorie dense foods are often also high in sodium and obese patients with hypertension are more likely to have salt-sensitive blood pressure than their normal weight counterparts. Related to this may be the impact of stress on blood pressure and the phenomenon of stress-eating, which may compound an individual’s risk of both obesity and hypertension [14].

Patient Evaluation

Evaluation of a patient with hypertension should first confirm the diagnosis of hypertension, then seek an underlying cause and finally screen for any end-organ effects [26]. A complete history is obtained, including diet and exercise habits and family history of hypertension, cardiovascular disease or heritable diseases. Family history should be updated periodically as it may change over time. Past medical history should be taken, beginning with perinatal history, including birth weight and umbilical artery catheterization, and a history of symptoms of other medical conditions associated with increased risk of hypertension. This includes a history of renal malformations, urinary tract infections, acute kidney injury, cardiac, endocrine or neurologic diseases or a history of solid organ or bone marrow transplant.

Symptoms of the disorders listed above may suggest an underlying cause of hypertension that has not yet been diagnosed. These include virilization, polydipsia and polyuria, hematuria, weight loss, palpitations or temperature intolerance. A careful sleep history as well as other parts of the social history may also suggest a secondary cause, including life stressors, smoking, alcohol and the intake of any medications, including those that are prescribed, over-the-counter or illicit substances. Finally, any clinical symptoms of end-organ damage are important to identify as this may change the subsequent evaluation, including headaches, dizziness or vertigo, visual changes, nausea or vomiting, epistaxis, nerve palsies and dyspnea.

The physical examination should include vital signs, height, weight and BMI, all reported as percentiles using accepted population curves. Skin manifestations of underlying diseases, such as neurofibromatosis and insulin resistance should be looked for. Cardiovascular exam includes pulses and blood pressure measurement in all extremities and the auscultation for bruits and murmurs. Palpation of the abdomen may reveal hepatosplenomegaly or other masses related to renal or oncologic disease. Neurologic examination should be completed, including fundoscopy, cranial nerve testing and evaluation for any focal defect suggesting stroke.

Blood pressure should be measured with an appropriately sized cuff and repeated on several occasions to confirm the diagnosis of hypertension. The cuff size is considered appropriate if the width of the inflatable bladder covers at least 40 % of the arm circumference at about midway between the olecranon and acromion. The length of the bladder should cover 80–100 % of the arm circumference. Similarly, if the original measurement was taken using an oscillometric device, it should be confirmed by auscultation [27–29]. Normative data tables published by the US National High Blood Pressure Education Program [27] have been endorsed for wide use by the European Hypertension Association Guidelines [28].

Recent research has highlighted the importance of using ambulatory blood pressure monitoring (ABPM) in the diagnosis and management of childhood hypertension [29]. ABPM uses a portable device worn by the patient that measures and records blood pressure during the patient’s daily activities and therefore has the ability to diagnose masked hypertension, including nocturnal hypertension. Obese children and adolescents have been shown to have more blood pressure variability, and those with sleep-disordered breathing often have reduced normal nocturnal dipping. Both masked and white-coat hypertension are shown to contribute to development of hypertensive target organ damage. In adult studies, ABPM has been shown to better predict cardiovascular outcomes than clinic blood pressures, since it more accurately records blood pressure during normal daily activities. The accurate use of ABPM requires some expertise in the reading and interpretation of data. This may not be a practical option in some areas without easily accessible specialists [27–30].

Recommendations for routine laboratory investigation vary only slightly among authors and most recommend the following for all hypertensive children and adolescents: blood counts, serum electrolytes, urea, creatinine, fasting glucose and lipid panel, and urinalysis with culture. All patients with confirmed hypertension should have a renal ultrasound to rule out underlying renal disease and echocardiography to assess for hypertensive target organ damage. There is no role for routine chest x-rays or electrocardiograms in pediatric patients with hypertension unless there is a suspicion for underlying cardiac disease. Because of the correlation between obesity, hypertension and the metabolic syndrome, patients with obesity and abnormal blood pressure should be screened for additional components of the metabolic syndrome as recommended.

Depending on the history and the results of screening studies, additional evaluation may be required, including drug screen, polysomnography, plasma renin activity and aldosterone levels, urine and plasma catecholamines and steroid measurements, ultrasonography with Doppler, radionuclide (DMSA) scan, CT or MRI, angiography and genetic studies to evaluate for monogenic sodium transport abnormalities causing hypertension (e.g., Liddle syndrome) [31]. The interested reader should consult detailed references for guidance regarding further evaluation [26].

Treatment

Therapy for obesity related hypertension should begin by addressing the child’s weight and implementing non-pharmacologic lifestyle modifications. Dietary recommendations include avoiding excess sugar, soft drinks, saturated fat and salt, while increasing the intake of dietary fiber in the form of fruits, vegetables and whole grains. Implementation of the DASH-style diet has been shown to be associated with lower blood pressure [32]. Increased physical activity and limitation of time spent in sedentary activities is also an important part of the treatment of obesity. The clinician should recognize that lifestyle changes are difficult and should involve the whole family to be successful [7, 27]. Ongoing support in the form of nutritional counseling as well as frequent follow-up with the primary care provider may be very useful to continue to encourage efforts to lose weight.

Pharmacological antihypertensive treatment should be started when these efforts fail, though the lifestyle changes should continue even after beginning a medication. Children who are able to lose weight may later be able to stop their medication and control their hypertension solely with lifestyle measures. Other indications for starting a medication are symptomatic hypertension, secondary causes as well as specific underlying diseases such as diabetes mellitus that are independent cardiovascular risk factors, or evidence of target organ damage, such as elevated left ventricular mass by echocardiogram [27].

Pediatric studies on specific antihypertensive drugs and drug classes have increased and there is a growing base of experience with many agents. In general, therapy should be started with a single drug at the lowest recommended dose and increased until the blood pressure goal is achieved or the highest dose is reached. The choice of antihypertensive medication will depend on any underlying co-morbid conditions, e.g., angiotensin-converting enzyme inhibitors are the initial choice for a child with diabetes and hypertension. Detailed discussion of the indications for antihypertensive medications in children and adolescents, as well as guidelines for how to prescribe antihypertensive medications in the young can be found elsewhere [33].

Close follow-up after making a diagnosis of hypertension is necessary. Home and repeat ambulatory monitoring of blood pressure is recommended to ensure adequate control. Home blood pressure monitoring enables the patient and their families to be involved in their care and ensures adherence. Follow-up visits every 3–6 mo are recommended for overweight and obese patients to monitor weight and blood pressure.

Conclusions

Multiple obesity related pathophysiological factors and co-morbidities contribute to high blood pressure. The workup of the obese child with high blood pressure should include screening for complications and abnormal biochemical characteristics known to be associated with both obesity and hypertension. The first line in managing an obese, hypertensive child or adolescent should target weight loss and family centered lifestyle modifications. Pharmacological therapy with one or more antihypertensive medications is frequently needed.