[Blood hypertension in children. Guideliness for diagnosis and treatment. Part 2 Pediatric Nephrology Branch, Chilean Pediatric Society]. / Hipertensión arterial en la infancia. Recomendaciones para su diagnóstico y tratamiento. Parte 2 Rama de Nefrología Infantil, Sociedad Chilena de Pediatría.

Hypertension (HTN) in children and adolescents is an important pathology, of, guarded prognosis, associated with modifiable and non-modifiable factors. The estimated prevalence is around 3.5% which increases progressively with age. The ideal method for its diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. According to the American Academy of Pedia trics (AAP), BP should be measured in children older than three years of age once a year, and in children younger than three years of age if they present risk factors. Once the HTN is confirmed, the evaluation should be directed towards the detection of a causative disease and/or the search for risk factors associated with a primary HTN. The objective of treating primary and secondary HTN in pediatrics is to achieve a BP level that decreases the risk of target organ damage. Therapeutic op tions include treatment according to specific etiology, non-pharmacological and pharmacological one. This paper presents the position of the Chilean Society of Pediatrics Nephrology Branch with the aim of guiding pediatricians and pediatric nephrologists in the correct management of HTN in childhood. In this second part, recommendations on antihypertensive treatment are presented with an emphasis on lifestyle changes.

Hipertensión arterial en la infancia: recomendaciones para su diagnóstico y tratamiento. Parte 2 Rama de Nefrología Infantil, Sociedad Chilena de Pediatría / Blood hypertension in children: guideliness for diagnosis and treatment. Part 2 Pediatric Nephrology Branch, Chilean Pediatric Society

Resumen: La hipertensión arterial (HTA) en niños y adolescentes es una importante patología, de reservado pronóstico, asociada a factores modificables y no modificables. La prevalencia estimada es de apro ximadamente un 3,5%, la cual va aumentando progresivamente con la edad. El método ideal para su diagnóstico es la medición de la presión arterial (PA) con instrumentos auscultatorios. De acuerdo a la Academia Americana de Pediatría (AAP) la PA debe ser medida en niños mayores de 3 años una vez al año, y en niños menores de 3 años, si presentan factores de riesgo. Una vez confirmada la HTA, la evaluación debe dirigirse hacia la detección de una enfermedad causal y/o a la búsqueda de factores de riesgo asociados a una HTA primaria. El objetivo del tratamiento de la HTA primaria y secundaria en pediatría es lograr un nivel de PA que disminuya el riesgo de daño de los órganos blanco. Las opciones terapéuticas incluyen: tratamiento según etiología específica, no farmacológico y farmacológico. En esta Guia se presenta la posición de la Rama de Nefrología de la Sociedad Chile na de Pediatría con el objetivo de orientar a pediatras y nefrólogos infantiles en correcto manejo de la HTA en la infancia. En esta segunda parte se presentan las recomendaciones sobre el tratamiento antihipertensivo, haciendo énfasis en los cambios de estilo de vida.

Abstract: Hypertension (HTN) in children and adolescents is an important pathology, of, guarded prognosis, associated with modifiable and non-modifiable factors. The estimated prevalence is around 3.5% which increases progressively with age. The ideal method for its diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. According to the American Academy of Pedia trics (AAP), BP should be measured in children older than three years of age once a year, and in children younger than three years of age if they present risk factors. Once the HTN is confirmed, the evaluation should be directed towards the detection of a causative disease and/or the search for risk factors associated with a primary HTN. The objective of treating primary and secondary HTN in pediatrics is to achieve a BP level that decreases the risk of target organ damage. Therapeutic op tions include treatment according to specific etiology, non-pharmacological and pharmacological one. This paper presents the position of the Chilean Society of Pediatrics Nephrology Branch with the aim of guiding pediatricians and pediatric nephrologists in the correct management of HTN in childhood. In this second part, recommendations on antihypertensive treatment are presented with an emphasis on lifestyle changes.

[Blood hypertension in childrens. Guideliness for diagnosis and treatment. Part 1. Pediatric Nephrology Branch, Chilean Pediatric Society]. / Hipertensión arterial en la infancia. Recomendaciones para su diagnóstico y tratamiento. Parte 1. Rama de Nefrología Infantil, Sociedad Chilena de Pediatría.

Hypertension (HT) in children and adolescents is an important pathology, associated with modi fiable and non-modifiable factors. In the pediatric, the prevalence of HT is around 3.5%, and it in creases progressively with age. The ideal method for diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. As published by the American Academy of Pediatrics (AAP), BP should be measured in children over 3 years of age once a year, and in children under 3 years of age, if it presents risk factors. Once HT has been confirmed, the evaluation should be directed towards the detection of a causative disease and the search for risk factors associated with primary HTN. The goal of treating primary and secondary HTN in pediatrics is to achieve a level of BP that decreases the risk of target organ damage. The therapeutic options include: treatment according to specific etiology, non-pharmacological and pharmacological. This document is the product of a collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with the aim of helping pediatricians and pediatric nephrologists in the diagnosis and treatment of hypertension in childhood. In this first part, the recommendations of the diagnosis and study are presented.

Hipertensión arterial en la infancia: recomendaciones para su diagnóstico y tratamiento. Parte 1. Rama de Nefrología Infantil, Sociedad Chilena de Pediatría / Blood hypertension in childrens: guideliness for diagnosis and treatment. Part 1. Pediatric Nephrology Branch, Chilean Pediatric Society

Resumen: La hipertensión arterial (HTA) en niños y adolescentes es una patología importante, asociada a fac tores modificables y no modificables. En la edad pediátrica, la prevalencia de la HTA es de alrededor de un 3,5%, y va aumentando progresivamente con la edad. El método ideal para su diagnóstico es la medición de la presión arterial (PA) con instrumentos auscultatorios. Según lo publicado por la Academia Americana de Pediatría (AAP) la PA debe ser medida en niños mayores de 3 años una vez al año, y en niños menores de 3 años, si presenta factores de riesgo. Una vez confirmada la HTA, la evaluación debe dirigirse hacia la detección de una enfermedad causal y a la búsqueda de factores de riesgo asociados a una HTA primaria. El objetivo del tratamiento de la HTA primaria y secundaria en pediatría es lograr un nivel de PA que disminuya el riesgo de daño de órgano blanco. Las opcio nes terapéuticas incluyen: tratamiento según etiología específica, no farmacológico y farmacológico. Este documento es producto de un esfuerzo colaborativo de la Rama de Nefrología de la Sociedad Chilena de Pediatría con el objetivo de ayudar a los pediatras y nefrólogos infantiles en el diagnóstico y tratamiento de la HTA en la infancia. En esta primera parte, se presentan las recomendaciones del diagnóstico y estudio.

Abstract: Hypertension (HT) in children and adolescents is an important pathology, associated with modi fiable and non-modifiable factors. In the pediatric, the prevalence of HT is around 3.5%, and it in creases progressively with age. The ideal method for diagnosis is the measurement of blood pressure (BP) with auscultatory instruments. As published by the American Academy of Pediatrics (AAP), BP should be measured in children over 3 years of age once a year, and in children under 3 years of age, if it presents risk factors. Once HT has been confirmed, the evaluation should be directed towards the detection of a causative disease and the search for risk factors associated with primary HTN. The goal of treating primary and secondary HTN in pediatrics is to achieve a level of BP that decreases the risk of target organ damage. The therapeutic options include: treatment according to specific etiology, non-pharmacological and pharmacological. This document is the product of a collaborative effort of the Nephrology Branch of the Chilean Society of Pediatrics with the aim of helping pediatricians and pediatric nephrologists in the diagnosis and treatment of hypertension in childhood. In this first part, the recommendations of the diagnosis and study are presented.

Cortisol/cortisone ratio and matrix metalloproteinase-9 activity are associated with pediatric primary hypertension.

OBJECTIVE: To identify novel biomarkers associated with pediatric primary hypertension. METHODS: We recruited 350 participants (4-16 years). Anthropometric parameters and aldosterone, plasma renin activity, cortisol, cortisone, Homeostasis Model Assessment Insulin Resistance (HOMA-IR), high-sensitivity C-reactive protein, adiponectin, IL-6, plasminogen activator inhibitor type 1 levels and matrix metalloproteinase-9 and matrix metalloproteinase-2 (MMP-9 and MMP-2) activities were measured. Genomic DNA was isolated. Patients with altered glucose metabolism, severe obesity [BMI-SD score (BMI-SDS) > 2.5], renovascular disease, primary aldosteronism and apparent mineralocorticoid excess syndrome were excluded. RESULTS: In selected participants (n = 320), SBP was positively correlated with BMI-SDS (r = 0.382, P < 0.001), HOMA-IR (r = 0.211, P < 0.001), MMP-9 activity (r = 0.215, P < 0.001) and the cortisol/cortisone ratio (r = 0.231, P < 0.001). DBP showed similar correlations with these variables. No correlation was observed with aldosterone or plasma renin activity. Participants were categorized as hypertensive (n = 59) or nonhypertensive (n = 261). In the univariate analysis, hypertensive patients had higher BMI-SDS (P < 0.001), HOMA-IR (P < 0.001), high-sensitivity C-reactive protein (P < 0.001), MMP-9 activity (P < 0.001), plasminogen activator inhibitor type 1 (P < 0.001) and cortisol/cortisone ratio (P < 0.001) than nonhypertensive patients. Multiple regression analysis showed that the variables that remained associated with hypertension were higher BMI-SDS [odds ratio (OR) = 3.74; 95% confidence interval (CI) = 1.84-7.58], a higher cortisol/cortisone ratio (OR = 3.92; 95% CI = 1.98-7.71) and increased MMP-9 activity (OR = 4.23; 95% CI = 2.15-8.32). CONCLUSION: We report that MMP-9 activity and the cortisol/cortisone ratio were higher in pediatric primary hypertensive patients, and these associations were independent of the effect of obesity. The potential role of these novel biomarkers in predicting hypertension risk and blood pressure regulation warrants further investigation.

Usefulness and Pitfalls in Sodium Intake Estimation: Comparison of Dietary Assessment and Urinary Excretion in Chilean Children and Adults.

BACKGROUND: High sodium intake has been associated with various noncommunicable disease like hypertension, cardiovascular disease, or stroke. To estimate accurately sodium intake is challenging in clinical practice. We investigate the usefulness and limitations of assessing sodium intake simultaneously by dietary assessment and urinary samples in both children and adults. METHODS: We used a cross-sectional study design inviting 298 Chilean subjects (74 children and 222 adults) aged between 9 and 66 years of both genders. Sodium intake by dietary assessment was obtained from Chilean food composition data, based on FAO tables. Sodium and creatinine excretion were measured in 24-hour urine samples, in all participants. RESULTS: Adequate urinary collection was obtained in 81% of children (59/74) and 61% of adults (135/222). The mean sodium intake by dietary assessment was similar to the sodium excretion in 24 hours (3,121±1,153mg/d vs. 3,114±1,353mg/24h, P = nonsignificant) in children but was significantly lower (3,208±1,284mg/d vs. 4,160±1,651mg/24h, P < 0.001) in adults. In both children and adults, sodium intake correlated with urinary sodium excretion (r = 0.456, P < 0.003 and r = 0.390, P < 0.001, respectively). Secondary analyses also suggested that the dietary assessment was more inaccurate in overweight adult subjects. CONCLUSIONS: Our results showed that average sodium intake was higher than recommended in both children and adults (WHO ≤2,000mg/d). The sodium intake estimated by dietary assessment correlated with urinary excretion in all subjects, but in obese adults was more inaccurate than in children. Future studies to validate the appropriate test to assess sodium intake by age and nutritional status are warranted.

Citosine-Adenine-Repeat Microsatellite of 11ß-hydroxysteroid dehydrogenase 2 Gene in Hypertensive Children.

BACKGROUND: The impairment of 11ß-hydroxysteroid dehydrogenase type 2 enzyme (11ßHSD2) results in an inefficient conversion of cortisol to cortisone, which triggers hypertension. Cytosine-adenine repeat (CA repeat) microsatellite has been associated with low HSD11B2 gene expression. AIM: To determine whether the CA-repeat length in intron 1 affect the serum cortisol to cortisone (F/E) ratio and/or blood pressure (BP) levels in pediatric subjects. SUBJECTS AND METHODS: Eighty-one hypertensive (HT) and 117 normotensive (NT) subjects participated in this study. We measured BP levels, as well as the F and E and F/E ratio in morning sera and 12-hour urine samples. The length of CA repeats was determined through fragment analysis. We compared the allele distribution between the HT and NT groups, and the patients were dichotomized into groups with short alleles (S) (<21 CA repeats) or long alleles (L), and also in groups according genotype (allele combination: S/S and S/L + L/L). RESULTS: We found no differences in the distribution of CA-repeat allelic length between the NT and HT groups (P = 0.7807), and there was no correlation between the CA-repeat allelic length and BP (P = 0.1151) levels or the serum F/E ratio (P = 0.6778). However, the serum F/E ratio was higher in the HT group than in the NT group (P = 0.0251). The serum F/E ratio was associated with systolic BP index independent of body mass index only in HT group. CONCLUSIONS: The CA-repeat length did not influence BP levels or serum F/E ratios in pediatric subjects. However, the serum F/E ratio was associated with BP, suggesting a role of 11ßHSD2 in mineralocorticoid hypertension.

Metabolic syndrome and its components are strongly associated with an inflammatory state and insulin resistance in the pediatric population / Síndrome metabólico y sus componentes se asocian con insulino resistencia y marcadores de inflamación en poblacion pediátrica

Introduction: Endothelial inflammation and insulin resistance (IR) begin in childhood and constitute the pathophysiological basis of Metabolic Syndrome (MS). The increase levels in plasma of inflammatory markers such as high sensitive PCR (hsPCR), plasminogen activator inhibitor 1 (PAI-1) and tests suggestive of IR such as Insulin (Ins) and alanine aminotransferase (ALT) have been associated with MS in adults, but have not been studied in children. Objectives: Correlate the presence of MS and its components with the inflammatory and IR markers seen in the pediatric population. Methods: Cross-sectional study of 337 children (10,9±9,7 years) whose levels of hsPCR, PAI-1, Ins and ALT were determined, along with their association with MS and its individual components. Results: 37 children had MS (10,4%). The frequency of MS components was: abdominal obesity 38,5%, hypertension (HTN) 21,3%, hypertriglyceridemia 17,8%, HDL 21,3% and hyperglycemia 1,4%. hsPCR, PAI-1, ALT and Ins were higher in the presence of MS and increased progressively when components were came together. Conclusions: The pediatric population segment with MS had a higher concentration of hsPCR, PAI-1, Ins and ALT.These levels increase proportionally MS components add up, suggesting that even before diagnosis criteria are fulfilled there is a inflammatory state (AU)

Introducción: La insulino resistencia (IR) y la inflamación endotelial constituyen la base fisiopatológica del Síndrome metabólico (SM) . El aumento de los niveles plasmáticos de mascadores de inflamación como PCRus, Inhibidor del activador de plasminógeni tipo 1 (PAI-1) y parámetros sugerentes de insulino resistencia (IR) como insulina, triglicéridos y Alanino aminotransferasa (ALT) se han asociado a síndrome metabólico en adultos pero han sido menos estudiados en pediatría. . Objetivo: Correlacionar los componentes del SM con marcadores de inflamación e IR en población pediátrica. Métodos: Estudio transversal de 337 niños (10,9±9,7 años). Se determinó niveles plasmáticos de PCRus, PAI- 1, ALT e Insulina y se evaluó su asociación con Síndrome metabólico y sus criterios de forma individual. Resultados: 37 sujetos tuvieron diagnóstico de SM (10.4%). 38.5% presentó obesidad abdominal, 21.3% Hipertensión arterial, 17.8% Hipertrigliceridemia, 21.3% niveles bajos de HDL y un 1.4% Hiperglicemia. Encontramos que PCRus, PAI-1 y ALT fueron más altas en presencia de SM y aumentaban progresivamente a medida que se agregaban criterios diagnósticos. Conclusión: Este estudio demuestra que en población pediátrica con diagnóstico de SM existen niveles más altos de PCRus, PAI-1, ALT e insulina y que a mayor nú- mero de criterios presentes la inflamación pareciera ser mayor lo que sugiere que incluso antes de tener el diagnóstico de SM ya existe un estado pro inflamatorio (AU)

Metabolic syndrome and its components are strongly associated with an inflammatory state and insulin resistance in the pediatric population.

INTRODUCTION: Endothelial inflammation and insulin resistance (IR) begin in childhood and constitute the pathophysiological basis of Metabolic Syndrome (MS). The increase levels in plasma of inflammatory markers such as high sensitive PCR (hsPCR), plasminogen activator inhibitor 1 (PAI-1) and tests suggestive of IR such as Insulin (Ins) and alanine aminotransferase (ALT) have been associated with MS in adults, but have not been studied in children. OBJECTIVES: Correlate the presence of MS and its components with the inflammatory and IR markers seen in the pediatric population. METHODS: Cross-sectional study of 337 children (10,9±9,7 years) whose levels of hsPCR, PAI-1, Ins and ALT were determined, along with their association with MS and its individual components. RESULTS: 37 children had MS (10,4%). The frequency of MS components was: abdominal obesity 38,5%, hypertension (HTN) 21,3%, hypertriglyceridemia 17,8%, HDL 21,3% and hyperglycemia 1,4%. hsPCR, PAI-1, ALT and Ins were higher in the presence of MS and increased progressively when components were came together. CONCLUSIONS: The pediatric population segment with MS had a higher concentration of hsPCR, PAI-1, Ins and ALT.These levels increase proportionally MS components add up, suggesting that even before diagnosis criteria are fulfilled there is a inflammatory state.

La insulino resistencia (IR) y la inflamación endotelial constituyen la base fisiopatológica del Síndrome metabólico (SM) . El aumento de los niveles plasmáticos de mascadores de inflamación como PCRus, Inhibidor del activador de plasminógeni tipo 1 (PAI-1) y parámetros sugerentes de insulino resistencia (IR) como insulina, triglicéridos y Alanino aminotransferasa (ALT) se han asociado a síndrome metabólico en adultos pero han sido menos estudiados en pediatría. Objetivo: Correlacionar los componentes del SM con marcadores de inflamación e IR en población pediátrica. Métodos: Estudio transversal de 337 niños (10,9±9,7 años). Se determinó niveles plasmáticos de PCRus, PAI-1, ALT e Insulina y se evaluó su asociación con Síndrome metabólico y sus criterios de forma individual. Resultados: 37 sujetos tuvieron diagnóstico de SM (10.4%). 38.5% presentó obesidad abdominal, 21.3% Hipertensión arterial, 17.8% Hipertrigliceridemia, 21.3% niveles bajos de HDL y un 1.4% Hiperglicemia. Encontramos que PCRus, PAI-1 y ALT fueron más altas en presencia de SM y aumentaban progresivamente a medida que se agregaban criterios diagnósticos. Conclusión: Este estudio demuestra que en población pediátrica con diagnóstico de SM existen niveles más altos de PCRus, PAI-1, ALT e insulina y que a mayor número de criterios presentes la inflamación pareciera ser mayor lo que sugiere que incluso antes de tener el diagnóstico de SM ya existe un estado pro inflamatorio.

The Expression of RAC1 and Mineralocorticoid Pathway-Dependent Genes are Associated With Different Responses to Salt Intake.

BACKGROUND: Rac1 upregulation has been implicated in salt-sensitive hypertension as a modulator of mineralocorticoid receptor (MR) activity. Rac1 could affect the expression of oxidative stress markers, such as hemoxigenase-1 (HO-1) or nuclear factor-B (NF-κB), and the expression of neutrophil gelatinase-associated lipocalin (NGAL), a cytokine upregulated upon MR activation. AIM: We evaluated RAC1 expression in relation of high salt intake and association with MR, NGAL, HO-1, and NF-κB expression, mineralo- and glucocorticoids levels, and inflammatory parameters. SUBJECTS AND METHODS: We studied 147 adult subjects. A food survey identified the dietary sodium (Na) intake. RAC1 expression was considered high or low according to the value found in normotensive subjects with low salt intake. We determined the gene expression of RAC1, MR, NGAL, HO-1, NF-κB, and 18S, isolated from peripheral leukocytes. We measured aldosterone, cortisol, sodium, potassium excretion, metalloproteinase (MMP9 y MMP2), and C-reactive protein. RESULTS: We identified 126 subjects with high Na-intake, 18 subjects had high, and 108 low-RAC1 expression. The subjects with high-RAC1 expression showed a significant increase in MR (P = 0.0002), NGAL (P < 0.0001) HO-1 (P = 0.0004), and NF-κB (P < 0.0001) gene expression. We demonstrated an association between RAC1 expression and MR (R sp 0.64; P < 0.0001), NGAL (R sp 0.48; P < 0.0001), HO-1 (R sp 0.53; P < 0.0001), and NF-κB (R sp0.52; P < 0.0001). We did not identify any association between RAC1 and clinical or biochemical variables. CONCLUSIONS: RAC1 expression was associated with an increase in MR, NGAL, NF-κB, and HO-1 expression, suggesting that RAC1 could be a mediator of cardiovascular damage induced by sodium, and may also useful to identify subjects with different responses to salt intake.

Polymorphisms in the RAC1 gene are associated with hypertension risk factors in a Chilean pediatric population.

BACKGROUND: The GTPase Rac1 has been implicated in hypertension as a modulator of mineralocorticoid receptor activity. Our aim is to investigate the frequency of polymorphisms rs10951982 (intron 1, G>A) and rs836478 (intron 3, T>C) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort. METHODS: Two hundred two normotensive (NT) subjects (aged 4-16 years) were divided into 2 groups: NT subjects with hypertensive parents (NH; n = 103) and NT subjects with NT parents (NN; n = 99). We measured markers of inflammation (high-sensitivity C-reactive protein, interleukin 6 (IL-6), interleukin 8, and tumor necrosis factor α), endothelial damage (Plasminogen activator inhibitor-1 metalloproteinase-9, and metalloproteinase-2), and oxidative stress (malondialdehyde). Data were expressed as median and interquartile range (IQR). RESULTS: We found differences in polymorphism rs836478 (intron 3, C>T) in both genotypic (χ(2) = 15.2, 2 df; P = 0.0005) and allelic (X(2)=5.5, 1 df; P = 0.01) frequencies in NH vs. NN subjects. NH subjects with a TT genotype showed increase MMP9 expression (median = 2.3, IQR - 1.6-3.2; vs. median = 1.6, IQR = 1.6-2.3 AU; P = 0.01) and lower IL-6 expression (median = 8.8, IQR = 7.0-11.8; vs. median = 12.1, IQR = 8.2-14.7 pg/ml; P = 0.02) compared with subjects with TC/CC genotype. No difference in the allelic frequency distribution was seen in the polymorphism rs10951982 (NH vs. NN: χ(2)=0.2, 1 df; P = 0.6). For this SNP, NN subjects with GA/AA genotype showed decreased diastolic BP indexes compared with subjects with native GG genotype (median = 1.08, IQR = 1.0-1.2; vs. median = 0.99, IQR = 0.94-1.1; P = 0.02). CONCLUSIONS: We report the frequency of polymorphisms rs836478 and rs10951982 of the RAC1 gene in a Spanish-Amerindian cohort. The polymorphism rs836478 was associated with an increased expression in markers of inflammation and endothelial damage (MMP9 and IL-6) in pediatric subjects with a hypertensive genetic background.

Age-related changes in 11ß-hydroxysteroid dehydrogenase type 2 activity in normotensive subjects.

BACKGROUND: Impairment in 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) activity results in inefficient inactivation of cortisol to cortisone, and it can trigger hypertension through activation of the mineralocorticoid receptor. Information about age-related changes in 11ß-HSD2 activity and its physiological consequences is scarce. Our aim was to investigate whether 11ß-HSD2 activity is age dependent in normotensive subjects. METHODS: We recruited 196 healthy, normotensive subjects. Of these, 93 were children (Group 1: aged 5-15 years), and 103 were adults who were divided according to their ages: Group 2: aged 30-41 years (n = 10); Group 3: aged 42-53 years (n = 72); and Group 4: aged 54-65 years (n = 21). Fasting serum cortisol, cortisone, aldosterone, and plasma renin activity (PRA) were measured. The 11ß-HSD2 activity was estimated by the cortisol/cortisone ratio. The results were expressed as median (interquartile range (IQR)) values and compared using Kruskal-Wallis and Dunn's multiple-comparison tests. RESULTS: As subject age increased, cortisol concentrations increased (Group 1 median = 8.6, IQR = 6.3-10.8 µg/dl; Group 4 median = 12.4, IQR = 10.7-14.7 µg/dl; P < 0.001), and cortisone concentrations showed a gradual decrease (Group 2 median = 4.0, IQR = 3.3-4.2 µg/dl; Group 4 median =2.8, IQR = 2.6-3.3 µg/dl; P < 0.01). As a consequence, the cortisol/cortisone ratio was higher in the oldest subjects (Group 4) than in the subjects from the other 3 groups; the ratios from Group 4 to Group 1 were 4.4 (IQR = 3.7-5.1) µg/dl, 3.3 (IQR = 2.7-3.8) µg/dl, 2.5 (IQR = 2.3-3.8) µg/dl, and 2.7 (IQR = 2.1-3.4) µg/dl, respectively (P < 0.01). The PRA decreased with age. Blood pressure levels increased with age but stayed within the normal range. CONCLUSIONS: Cortisol and the cortisol/cortisone ratio increased with age, but cortisone decreased, suggesting a decrease in 11ß-HSD2 activity. These results suggest that the cortisol-mediated activation of the mineralocorticoid receptor may explain the blood pressure increase in elderly subjects.

Positive association between aldosterone-renin ratio and carotid intima-media thickness in hypertensive children.

INTRODUCTION: From an early age, hypertension can damage blood vessels through multiple mechanisms. The aim of this study was to evaluate the presence of vascular damage and whether it is associated with the mineralo- and glucocorticoid profiles of hypertensive children. SUBJECTS AND METHODS: We studied 64 hypertensive children. Anthropometric parameters and serum aldosterone (SA), plasma renin activity (PRA), aldosterone/renin ratio (ARR), cortisol (F) and cortisone (E) were measured. The serum F/E ratio was calculated to estimate the activity of the enzyme 11ß-HSD2. Vascular damage was determined by carotid intima-media thickness (cIMT) and flow-mediated dilation of the brachial artery (FMD) on ultrasound. RESULTS: (median; Q1-Q3) Of the patients observed, 39% were females, and the median value for age (years) was 11.2 (9.1-13.3), for BMI (SDS) was 1.36 (0.84-1.80), for body fat mass (%) was 28.3 (17.8-36.0), for SBP index was 1.17 (1.12-1.25) and for the DBP index was 1.27 (1.16-1.36). Measurements revealed an SA level higher than 491 pmol/l in 4/64 patients, a PRA value lower than 0.5 ng/ml/h in 2/64, an ARR higher than 10 in 3/64 and serum F/E ratio higher than 4.3 in 10/64. The median brachial FMD (%) was 8.41 (5.61-10.91), and the median cIMT (mm) was 0.40 (0.37-0.43). The ARR was the only variable that explained changes in cIMT (ß = 0.571, R(2 ) = 0.315, P < 0.0001). CONCLUSION: Our results showed a positive association between cIMT and the ARR, suggesting an important role of the renin-aldosterone axis in the regulation of early vascular damage in hypertensive children.

A new presentation of the chimeric CYP11B1/CYP11B2 gene with low prevalence of primary aldosteronism and atypical gene segregation pattern.

Familial hyperaldosteronism type I is caused by an unequal crossover of 11ß-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, giving rise to a chimeric CYP11B1/CYP11B2 gene (CG). We describe a family carrying a CG with high levels of free 18-hydroxycortisol but low prevalence of primary aldosteronism (PA) and an atypical CG inheritance pattern in a family of 4 generations with 16 adults and 13 children, we measured the arterial blood pressure, serum aldosterone, and plasma renin activity and then calculated the serum aldosterone:plasma renin activity ratio and urinary free 18-hydroxycortisol. We identified the CG by long-extension PCR and predicted its inheritance pattern. The CG was found in 24 of 29 subjects (10 children and 14 adults). In CG+ patients, hypertension and high 18-hydroxycortisol were prevalent (83% and 100%, respectively). High serum aldosterone:plasma renin activity ratio was more frequent in pediatric than adult patients (80% versus 36%; P<0.001). An inverse association between serum aldosterone:plasma renin activity ratio and age was observed (r=-0.48; P=0.018). Sequence analysis identified the CYP11B1/CYP11B2 crossover in a 50-bp region spanning intron 3 of CYP11B1 and exon 4 of CYP11B2. The CG segregation differs from an autosomal disease, showing 100% of CG penetrance in generations II and III. Statistical analysis suggests that inheritance pattern was not attributed to random segregation (P<0.001). In conclusion, we describe a family with an atypical CYP11B1/CYP11B2 gene inheritance pattern and variable phenotypic expression, where the majority of pediatric patients have primary aldosteronism. Most adults have normal aldosterone and renin levels, which could mask them as essential hypertensives.

Birth weight is inversely associated with blood pressure and serum aldosterone and cortisol levels in children.

CONTEXT: Low birth weight has been independently associated with adult hypertension, and renin-angiotensin system (RAS) plays a role in this connection. OBJECTIVE: To characterize the associations between birth weight (BW) and serum aldosterone (SA), serum cortisol, plasma renin activity (PRA) and blood pressure (BP). DESIGN: Cross-sectional study. SUBJECTS: Children from the community born at a gestational age >32 weeks. METHODS: Systolic and diastolic BP indices (SBPi and DBPi) were calculated using the observed BP/50th percentile BP for gender, age and stature. BW was transformed to a standard deviation score (SDS) for gestational age, whereas SA, serum cortisol and PRA were transformed using the natural log. RESULTS: We selected 288 subjects between the ages of 4·9 and 15·5 years (Females, 50%). After adjusting for body mass index (BMI) SDS and Tanner, multiple regression analysis revealed that BW (SDS) was both independently and inversely associated with the natural log of SA (ß = -0·065; P = 0·039), the natural log of serum cortisol (ß = -0·064; P = 0·009), SBPi (ß = -0·012; P = 0·020) and DBPi (ß = -0·023; P = 0·002). An association was not observed with PRA (P = 0·178) and aldosterone renin ratio (ARR) (P = 0·452). Serum cortisol levels were positively associated with SA (r = 0·125; P = 0·034), while an association with PRA (P = 0·251) and ARR (P = 0·052) was not observed. CONCLUSIONS: The results of this study demonstrate an inverse association between birth weight and blood pressure and serum aldosterone and cortisol levels. This association is independent of BMI and Tanner, suggesting foetal programming of the hypothalamic-pituitary-adrenal axis.

[Prevalence of hypertension in school age children and its association with obesity]. / Prevalencia de hipertensión arterial y su asociación con la obesidad en edad pediátrica.

BACKGROUND: Hypertension in children is a frequently overlooked problem that is an important cardiovascular risk factor. AIM: To determine the prevalence of hypertension among school age children. MATERIAL AND METHODS: Cross-sectional study of 2980 children aged 10 ± 2 years (48% females) from 10 schools of middle and lower class in Metropolitan Santiago. Blood pressure (BP) was measured in the sitting position on three occasions after a rest period, using a mercury sphygmomanometer with appropriate cuff arm diameter, averaging the results of the measurements. Systolic and diastolic hypertension were defined as blood pressure values over 95 percentile for age, sex and height. RESULTS: The overall prevalence of hypertension was 12.2% in women and 15% in men (p < 0.05). According to nutritional status, the prevalence was 6.7, 8.9,13.6 and 26% in underweight, eutrophic, overweight and obese children, respectively (p < 0.01). Compared with normal weight children, the risk of being hypertensive for overweight children was 1.6 (95% confidence intervals (CI) 1.2-2.3) and for obese children was 3.6 (95% CI 2.8-4.7). CONCLUSIONS: The studied children had a high prevalence of hypertension, that was directly related to a higher body mass index.

Prevalencia de hipertensión arterial y su asociación con la obesidad en edad pediátrica / Prevalence of hypertension in school age children and its association with obesity

Background: Hypertension in children is a frequently overlooked problem that is an important cardiovascular risk factor. Aim: To determine the prevalence of hypertension among school age children. Material and Methods: Cross-sectional study of 2980 children aged 10 ± 2years (48 percent females) from 10 schools of middle and lower class in Metropolitan Santiago. Blood pressure (BP) was measured in the sitting position on three occasions after a rest period, using a mercury sphygmomanometer with appropriate cuff arm diameter, averaging the results of the measurements. Systolic and diastolic hypertension were defined as blood pressure values over 95percentilefor age, sex and height. Results: The overall prevalence of hypertension was 12.2 percent in women and 15 percent in men (p < 0.05). According to nutritional status, the prevalence was 6.7, 8.9,13.6 and 26 percent in underweight, eutrophic, overweight and obese children, respectively (p < 0.01). Compared with normal weight children, the risk of being hypertensive for overweight children was 1.6 (95 percent confidence intervals (CI) 1.2-2.3) and for obese children was 3.6 (95 percent CI 2.8-4.7). Conclusions: The studied children had a high prevalence of hypertension, that was directly related to a higher body mass index.

Frequency of familial hyperaldosteronism type 1 in a hypertensive pediatric population: clinical and biochemical presentation.

Familial hyperaldosteronism type 1 is an autosomal dominant disorder attributed to a chimeric CYP11B1/CYP11B2 gene (CG). Its prevalence and manifestation in the pediatric population has not been established. We aimed to investigate the prevalence of familial hyperaldosteronism type 1 in Chilean hypertensive children and to describe their clinical and biochemical characteristics. We studied 130 untreated hypertensive children (4 to 16 years old). Blood samples for measuring plasma potassium, serum aldosterone, plasma renin activity, aldosterone/renin ratio, and DNA were collected. The detection of CG was performed using long-extension PCR. We found 4 (3.08%) of 130 children with CG who belonged to 4 unrelated families. The 4 patients with CG had very high aldosterone/renin ratio (49 to 242). In addition, we found 4 children and 5 adults who were affected among 21 first-degree relatives. Of the 8 affected children, 6 presented severe hypertension, 1 presented prehypertension, and 1 presented normotension. High serum aldosterone levels (>17.7 ng/dL) were detected in 6 of 8 subjects (range: 18.6 to 48.4 ng/dL) and suppressed plasma renin activity (≤0.5 ng/mL per hour) and high aldosterone/renin ratio (>10) in 8 of 8 children (range: 49 to 242). Hypokalemia was observed in only 1 of 8 children. We demonstrated that the prevalence of familial hyperaldosteronism type 1 in a pediatric hypertensive pediatric population was surprisingly high. We found a high variability in the clinical and biochemical characteristics of the affected patients, which suggests that familial hyperaldosteronism type 1 is a heterogeneous disease with a wide spectrum of presentations even within the same family group.

Índice cintura estatura y agregación de componentes cardiometabólicos en niños y adolescentes de Santiago / Waist height ratio, ultrasensitive c reactive protein and metabolic syndrome in children

Background: Waist to height ratio and ultrasensitive C-reactive protein are predictors of the presence of the metabolic syndrome in children. Aim: To determine the proportional risk of metabolic syndrome component clustering in children, using waist to height ratio and ultrasensitive C-reactive protein. Material and Methods: Anthropometric measures, blood pressure, fasting serum lipid profle, blood glucose and ultrasensitive C-reactive protein were determined in 209 children aged 11.5 ± 2 years (50 percent females). The presence of the metabolic syndrome as a function of waist to height ratio and C-reactive protein was modeled using logistic regression equations. The risk of clustering one, two or more components of the metabolic syndrome was calculated. Results: Metabolic syndrome was present in 5 percent of all children and 18 percent of those that were obese. The cut off points for waist to hip ratio and ultrasensitive C-reactive protein were 0.55 and 0.61 mg/L, respectively. For each 0.01 increment in waist to height ratio, the odds ratio of increasing one component of the metabolic syndrome was 1.2 (1.15-1.25) or 15 to 25 percent. The odds ratio for log-transformed ultrasensitive C-reactive protein was 1.62 (1.26-2.09). Excluding waist circumference, the odds ratio of adding one or more components of the metabolic syndrome was 1.05 (1.01-1.09) per 0.01 increment in waist to height ratio, but the odds ratio for C-reactive protein was no longer significant. Conclusions: Waist to height ratio and ultrasensitive C-reactive protein predict the risk of clustering components of the metabolic syndrome in these children.