Primary Hypertension In Children Research Articles

Therapeutic Options for the Treatment of Hypertension in Children and Adolescents

Primary hypertension in children is increasing in prevalence with many cases likely going undiagnosed. The prevalence is currently estimated at between 3%–5% in the United States and may be higher in certain ethnic groups. Primary hypertension, once felt to be rare in children, is now considered to be about five times more common than secondary hypertension. This review provides information to guide physicians through an organized approach to: 1) screening children and adolescents for hypertension during routine visits; 2) using normative percentile data for diagnosis and classification; 3) performing a clinical evaluation to identify the presence of co-morbidities; 4) initiating a plan of care including subsequent follow-up blood pressure measurements, therapeutic lifestyle changes and pharmacologic therapies.

The role of obesity, salt and exercise on blood pressure in children and adolescents

The increasing trends of blood pressure (BP) in children and adolescents pose great concern for the burden of hypertension-related cardiovascular disease. Although primary hypertension in childhood is commonly associated with obesity, it seems that other factors, such as dietary sodium and exercise, also influence BP levels in children and adolescents. Several studies support that sympathetic nervous system imbalance, impairment of the physiological mechanism of pressure natriuresis, hyperinsulinemia and early vascular changes are involved in the mechanisms causing elevated BP in obese children and adolescents. Under the current evidence on the association of salt intake and BP, dietary sodium restriction appears to be a rational step in the prevention of hypertension in genetically predisposed children and adolescents. Finally, interventional studies show that regular aerobic exercise can significantly reduce BP and restore vascular changes in obese with hypertensive pediatric patients. This article aims to summarize previous studies on the role of obesity, salt intake and exercise on BP in children and adolescents.

Primary versus secondary hypertension in children followed up at an outpatient tertiary unit

Childhood hypertension has classically been recognized as a secondary disease. However, primary hypertension also occurs in children. The aim of this study was to compare clinical features of pediatric patients with elevated blood pressure, which were referred to an outpatient tertiary unit, and to detect variables associated with the identification of primary hypertension. The records of 220 patients with hypertension followed between 1996 and 2006 were analyzed. The variable of interest was primary hypertension. Logistic regression analysis was applied to identify clinical variables that were independently associated with primary hypertension. Of 220 patients, 33 (15%) had primary hypertension, and 187 (85%) exhibited secondary hypertension. No statistically significant differences were detected in gender, race, age at diagnosis, and systolic/diastolic blood pressure levels between both groups. After adjustment, four variables at baseline remained independently associated with primary hypertension: absence of signs/symptoms (OR 18.87, 95% CI 6.32-56.29), normal serum creatinine (OR 0.02, 95% CI 0.00-0.27), family history of hypertension (OR 3.03, 95% CI 1.04-8.79), and elevated body weight (OR 1.06, 95% CI 1.02-1.10). The absence of signs/symptoms, normal serum creatinine, family history of hypertension, and overweight/obesity at admission are clues to diagnose primary hypertension in childhood.

Hypertension, Growth, and Skeletal Maturation in the Young

Traditionally, most cases of hypertension in children and adolescents have been attributed to secondary causes, with renal and cardiac disorders being the most common, at least in preadolescent children. However, most hypertensive adolescents have no identifiable underlying cause for their hypertension, perhaps with the exception of obese adolescents, in whom the hypertension is likely attributable to the same renal, central, and hormonal mechanisms present in hypertensive obese adults. 1 But what causes hypertension in youth with no underlying renal or other systemic disease and who are not obese? The answer to this question would likely provide significant insight into the pathophysiology of “essential” hypertension in adults as well. In this issue of Hypertension, Pludowski et al2 present intriguing data supporting the hypothesis that hypertension in the young is a disorder of maturation. Using dual x-ray absorptiometry to assess bone age, they demonstrate that hypertensive children and adolescents manifest advanced skeletal maturation compared with matched, normotensive control subjects. Advanced bone age was an independent predictor of blood pressure (BP) status in children with normal BP, prehypertension, and stages 1 and 2 hypertension. Significantly, the investigators matched not only for sex and age, but also for body mass index, thereby avoiding the confounding effects of obesity, which is known to be associated with accelerated skeletal growth in children.3 These data reinvigorate a line of investigation from several decades ago, when the phenomenon of pediatric hypertension was first being recognized, and mechanisms of hypertension in the young were first being examined. As summarized by Ingelfinger, 4 early investigators interested in childhood primary hypertension focused on multiple possible underlying factors, including altered hemodynamic regulation, abnormalities of the renin-angiotensin system, and other hormonal perturbations that had already been demonstrated in adults with hypertension. At the same time, epidemiologists interested in childhood hypertension were recognizing that normative values for childhood BP based on age only might result in misclassification of BP because of differences in maturation among children of comparable ages.5 It was, therefore, suggested that height as an index of maturation should be considered when classifying a child’s or an adolescent’s BP as normal or elevated, an approach that was adopted by the Working Group on High Blood Pressure in Children and Adolescents in 1996 and that remains a cornerstone of current consensus recommendations for evaluating childhood BP. At approximately the same time, investigators associated with the Philadelphia Blood Pressure Project analyzed data including bone age on a sample of children (all black) followed longitudinally into adolescence and found those children who had the highest levels of BP at 7 years of age achieved adult levels of BP earlier than those who had the lowest levels of BP at age 7 and had advanced bone age in adolescence compared with those with the lowest levels of BP at 7 years of age. 6 In other words, advanced skeletal maturation in children with high BP was demonstrated to be associated with higher BP in early adolescence. Although drawn from different data, these findings reinforced the conclusions drawn by epidemiologists5 that growth and maturational status should be considered when assessing BP in the young. It was Lever and Harrap 7 who eventually summarized multiple lines of evidence, including the bone age data from the Philadelphia Blood Pressure Project, to advance the hypothesis that, in childhood, the development of primary hypertension is likely tied to other growth-promoting processes and suggested 3 possible endocrinologic mechanisms,

Baroreflex sensitivity and essential hypertension in adolescents

It has been known for many years that baroreflex sensitivity is lowered in hypertensive patients. There are several known factors implicating this association, e.g. high blood pressure leads to remodeling of the carotid arterial wall, to its stiffness and to a diminished activation of baroreceptors; leptin released from a fatty tissue activates the sympathetic nervous system etc. On the other hand, low baroreflex sensitivity (BRS, usually quantified in ms/mmHg) can be inborn. Studies on primary hypertension in children and adolescents have brought new information about the role of baroreflex in the development of an early stage of primary hypertension. BRS lower than 3.9 ms/mmHg was found in 5 % of healthy subjects. This value approaches the critical value for the risk of sudden cardiac death in patients after myocardial infarction and corresponds to the value present in hypertensive patients. A decreased BRS and BRSf (baroreflex sensitivity expressed in mHz/mmHg, index independent of the mean cardiac interval), was found not only in children with hypertension, but also in those with white-coat hypertension. This is in accordance with a single interpretation. The decrease of BRS/BRSf precedes a pathological blood pressure increase. The contribution of obesity and BRS/BRSf to the development of hypertension in adolescents was also compared. Both factors reach a sensitivity and a specificity between 60 % and 65 %, but there is no correlation between the values of the body mass index and BRS either in the group of hypertensive patients or in healthy controls. If a receiver operating curve (sensitivity versus specificity) is plotted for both values together using logistic regression analysis, a sensitivity higher than 70 % and a specificity over 80 % are reached. This means that low baroreflex sensitivity is an independent risk factor for the development of primary hypertension. Studies demonstrate that adolescents with increased blood pressure and with BRS under 7 ms/mmHg should be given care and intensively motivated to change their lifestyle including a change in diet and increase in physical activity.

Obesity-Associated Hypertension in Childhood: A New Epidemic Problem

In recent years, opinions on hypertension in the paediatric age range have been changing. Although secondary forms of childhood hypertension maintain important clinical relevance, lately much more attention has been paid to primary forms of high blood pressure in children. At present, the prevalence of primary hypertension in children is not easily defined, also because of an unsatisfactory knowledge of this phenomenon. A child with elevated blood pressure values shows a high probability of developing hypertension in adulthood. Many factors that contribute to the development and maintenance of hypertension in the adult population are already present and operating in childhood. Overweight is one of the most important of these factors. In the industrialised countries, prevalence of childhood overweight has increased markedly during the last five decades and as in adults, overweight is related to several cardiovascular risk factors in children too. For these reasons, it may be important to precisely identify the children with high blood pressure values and body weight excess that might develop cardiovascular diseases in adulthood, and thus allow activation of preventive measures and therapeutic interventions that may reduce morbidity and mortality related to cardiovascular diseases. Keywords: Overweight, obesity, waist circumference, nsulin resistance, blood pressure, children

Effects of Childhood Primary Hypertension on Carotid Intima Media Thickness

To determine whether carotid intima media thickness is increased in children with primary hypertension, the current study compared carotid intima media thickness in hypertensive children with that of normotensive control subjects matched closely for body mass index and determined the relationship between carotid intima media thickness and hypertension severity determined by ambulatory blood pressure monitoring. Children with newly diagnosed office hypertension (n=28) had carotid intima media thickness, left ventricular mass index, and ambulatory blood pressure monitoring performed. Carotid intima media thickness was performed in normotensive control subjects (n=28) matched pairwise to hypertensive subjects for age (+/-1 year), gender, and body mass index (+/-10%). Eighty-two percent of subjects were overweight or obese (body mass index > or =85th percentile). The median carotid intima media thickness of hypertensive subjects was greater than that of matched controls (0.67 versus 0.63 mm; P=0.045). In the hypertensive subjects, carotid intima media thickness correlated strongly with several ambulatory blood pressure monitoring parameters, with the strongest correlation for daytime systolic blood pressure index (r=0.57; P=0.003). In the hypertensive group, the prevalence of left ventricular hypertrophy was 32%, but unlike carotid intima media thickness, left ventricular mass index did not correlate with ambulatory blood pressure monitoring. Together, the findings that hypertensive subjects had increased carotid intima media thickness compared with matched controls and that higher carotid intima media thickness correlated with more severe hypertension by ambulatory blood pressure monitoring provide strong evidence that carotid intima media thickness is increased in childhood primary hypertension, independent of the effects of obesity.

Utility of Renal Imaging in the Diagnostic Evaluation of Obese Childhood Primary Hypertension

Although childhood primary hypertension (CP-HTN) associated with obesity is considered an earlier manifestation of typical adult-onset primary hypertension (adult-HTN), the recommendations for diagnostic evaluation are not identical in the two conditions. In particular, renal imaging is not recommended in adult-HTN, but is still currently recommended in CP-HTN. In this study, the clinical value of renal imaging in the initial diagnostic evaluation of CP-HTN was determined. A retrospective chart review was conducted of older and overweight children (> 7 years of age) evaluated in the pediatric nephrology clinic at the University of Florida from 1999 to 2004 for hypertension. The final highly selected study group was composed of obese or overweight children (body mass index > 85th percentile for age and gender) with otherwise unremarkable history, physical examination, and urinalysis. Renal imaging was performed (ultrasound in 49, computed tomography in one) in 50 patients (M:F = 28:22; age range, 7-20 years) with clinical features compatible with CP-HTN, and was normal in all patients. In this study, renal imaging did not add any clinical value to the initial evaluation of CP-HTN associated with obesity. Larger studies may confirm that the evaluation of CP-HTN in older obese children could be similar to guidelines for evaluation of adult-HTN.

Significance of Heritability in Primary and Secondary Pediatric Hypertension

Patient weight and family history are significant risk factors for the development of hypertension in children. Multiple genetic factors have been identified in primary (essential) hypertension in adults; however, the delineation of genetic factors in the separate populations of children with primary or secondary hypertension are not well understood. Heritability is the proportion of observed variation in a particular trait that can be attributed to an inherited genetic factor in contrast to environmental factors. In the consideration of hypertension, heritability can be assessed in terms of an underlying continuous gradient of the liability for developing hypertension. With this assumption it is possible to compute heritability using hypertension incidence among relatives and described by Falconer. Heritability values range from 0 (no genetic contribution) to 1 (complete genetic contribution). The aim of this study was to determine the genetic contribution to primary and secondary hypertension in a pediatric population through heritability analysis. This was a retrospective case-control analysis of medical records of children (n=276) followed in the Pediatric Nephrology Clinic over a 4-year period from 1999 to 2002. There were 192 children and adolescents with primary hypertension (124 male, 68 female, age 0 to 21 years) and 84 children and adolescents with secondary hypertension (46 male, 38 female, age 0 to 21 years). Each hypertensive group served as the control for the other. Estimates of heritability were made using Falconer's method 2. The model assumes independence between the environment and genetic factors and that the joint distribution of liabilities between parent and child are normally distributed. Problems can arise from computing heritability due to dominance within loci, correlations between nongenetic familial effects, or the presence of a major gene. Of the children and adolescents with primary hypertension, 49% had parents with primary hypertension; and of the children and adolescents with secondary hypertension, 24% had parents with primary hypertension. Of the children and adolescents with primary hypertension, 10% had parents with secondary hypertension; and of the children and adolescents with secondary hypertension, 46% had parents with secondary hypertension. The estimated heritability for primary hypertension was 0.84 (SE=0.21). The estimated heritability for secondary hypertension was 1.14 (SE=0.21). As the value was >1, this indicates that the fit of the liability model is poor and that a few genes, or even one major gene, were significantly involved in the causes of secondary hypertension in the children and adolescents studied. The results suggest that primary and secondary hypertension do not share the same type of genetic profile. Primary hypertension in children and adolescents is likely due to a large number of additive contributions of genes, although a highly correlated environmental component can not be excluded. The continuous liability model is inappropriate for secondary hypertension because the estimate was substantially greater than one. This study supports the model that secondary hypertension in children and adolescents may be related to just a few genes.

Extended-release metoprolol is effective in the treatment of primary hypertension in children,

Extended-release metoprolol is effective in the treatment of primary hypertension in children,

Characteristics of primary hypertension in children of different racial groups

Characteristics of primary hypertension in children of different racial groups

Characteristics of children with primary hypertension seen at a referral center

Primary hypertension is well known to occur in children, but the characteristics of such children are changing due to the influence of the obesity epidemic. In view of this, we conducted a cross-sectional study of 70 children [age 13.3+/-4 years (mean +/- SD)] with primary hypertension referred to a specialized pediatric hypertension clinic. Secondary hypertension had been excluded after a standardized diagnostic evaluation. Isolated systolic hypertension was present in 62.9% of subjects. Family history of hypertension was present in 86.2%, and 52.9% were obese (BMI > or =95th percentile). BMI was weakly correlated with systolic BP (r =0.28,P =0.10) and was significantly correlated with total cholesterol (r =0.36,P =0.005) and triglycerides (r =0.42,P =0.01). Mean plasma renin activity (PRA) was 3.1+/-2.7 ng/ml/h. PRA was correlated with diastolic but not systolic BP. Patients with high PRA had higher diastolic BP and lower BMI compared to those with low PRA. Left ventricular hypertrophy was present in 24%. Mean 24-h systolic BP load by ambulatory BP monitoring was 52+/-24%; mean 24-h diastolic BP load was 18+/-16%; BP loads were greater in patients with high PRA. These data suggest that primary hypertension in children is characterized by systolic BP elevation, positive family history and obesity. Hyperlipidemia accompanies primary hypertension in obese children, and left ventricular hypertrophy is common. Patients with high PRA have more severe BP elevation. Future studies should focus on further defining the pathophysiology of primary hypertension in children, including the roles of renin and insulin resistance, so that improved methods of prevention and treatment can be developed.

Body mass index in primary and secondary pediatric hypertension

The objectives of this study were (1) to determine the relationship of body mass index (BMI) to primary or secondary hypertension in children and adolescents and (2) to assess BMI at the age of onset of hypertension in children and adolescents. Patient demographics, BMI, family history, presentation of disease, etiology of hypertension, medication, laboratory data, and findings from other procedures were recorded for all patients with hypertension followed in the Pediatric Nephrology Clinic at Children's Hospital, Columbus, Ohio, over a 4-year period. In total, 314 patients were studied: 218 with primary hypertension and 96 with secondary hypertension. Our patient population (166 males, 148 females) was diverse in age (13+/-6.3 years) and ethnicity (237 Caucasians, 54 African-Americans, 23 other). BMI was greater in patients with primary (27.5+/-9.2 kg/m2) versus secondary (23.9+/-9.3 kg/m2) hypertension (P=0.002). Children with primary hypertension with an increased BMI presented at an earlier age than children with secondary hypertension and an increased BMI. The age of onset (10.5+/-2.6 years) in primary hypertension was related to increased BMI (r=0.12, P=0.001); however, there was no relationship between BMI and age of onset of secondary hypertension (P=0.21). Children whose family members had essential hypertension had increased BMI compared with children without a family history of essential hypertension. Based on the logistic regression model constructed from our data, the likelihood of primary versus secondary hypertension was influenced by the presence of family history of hypertension independent of presence of obesity in the child. In conclusion, increased BMI is more common in children with primary than secondary hypertension; earlier onset of primary hypertension in the pediatric population was associated with increased BMI; the assessment of BMI is important in the evaluation of secondary as well as primary hypertension; the role of obesity in the development of secondary as well as primary hypertension in children merits further study.

The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents

The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents

Hyperuricemia in childhood primary hypertension.

Experimental animal models suggest that uric acid might have a pathogenic role in the early development of primary hypertension. We hypothesized that serum uric acid is correlated with blood pressure in children with new-onset, untreated, primary hypertension. We evaluated 125 consecutive children referred to the Baylor Pediatric Renal Program for evaluation of hypertension. None of the subjects had previously been evaluated or treated for hypertension. The children ranged in age from 6 to 18 years (mean, 13.4+/-3.3) and had normal renal function (creatinine clearance >80 mL x min(-1) x 1.73 m(-2)). Sixty-three children had primary hypertension, 40 had secondary hypertension, and 22 had white-coat hypertension. Forty controls with normal blood pressure were recruited from the renal clinic. Uric acid levels were directly correlated with systolic (r=0.80, P=0.0002) and diastolic (r=0.66, P=0.0006) blood pressure in controls and in subjects with primary hypertension and were independent of renal function. Serum uric acid concentrations >5.5 mg/dL were found in 89% of subjects with primary hypertension, in 30% with secondary hypertension, in 0% with white-coat hypertension, and in 0% of controls. We conclude that serum uric acid is directly correlated with blood pressure in untreated children and that a serum uric acid value >5.5 mg/dL in an adolescent being evaluated for hypertension strongly suggests primary hypertension as opposed to white-coat or secondary hypertension. These results are consistent with the hypothesis that uric acid might have a role in the early pathogenesis of primary hypertension.

Obesity hypertension in children: a problem of epidemic proportions.

Obesity has become an increasingly important medical problem in children and adolescents. In national surveys from the 1960s to the 1990s, the prevalence of overweight in children grew from 5% to 11%. Outcomes related to childhood obesity include hypertension, type 2 diabetes mellitus, dyslipidemia, left ventricular hypertrophy, nonalcoholic steatohepatitis, obstructive sleep apnea, orthopedic problems, and psychosocial problems. Once considered rare, primary hypertension in children has become increasingly common in association with obesity and other risk factors, including a family history of hypertension and an ethnic predisposition to hypertensive disease. Obese children are at approximately a 3-fold higher risk for hypertension than nonobese children. In addition, the risk of hypertension in children increases across the entire range of body mass index (BMI) values and is not defined by a simple threshold effect. As in adults, a combination of factors including overactivity of the sympathetic nervous system (SNS), insulin resistance, and abnormalities in vascular structure and function may contribute to obesity-related hypertension in children. The benefits of weight loss for blood pressure reduction in children have been demonstrated in both observational and interventional studies. Obesity in childhood should be considered a chronic medical condition that is likely to require long-term management. Ultimately, prevention of obesity and its complications, including hypertension, is the goal.

Primary hypertension in childhood and adolescence.

Hypertension is a major public health problem in the adult population. The focus in children should be on identifying those children in the highest percentiles of systolic and diastolic blood pressure. In order to do this, blood pressure must be measured routinely in children aged 3 years and older during well-child examinations. Blood pressure must be measured accurately and interpreted correctly. Once such children with elevated blood pressures are identified, appropriate nonpharmacologic measures should be instituted. For those children with marked elevation of blood pressure or who are at risk for target-organ damage, it is reasonable to consider antihypertensive medication after weighing the potential risks and benefits. The hope is that this strategy will ultimately lead to decreased morbidity and mortality from hypertension in the adult population.

Blood pressure and primary hypertension in childhood and adolescence

Blood pressure and primary hypertension in childhood and adolescence