Carolina Loureiro

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.

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.

Aldosterone, Plasma Renin Activity, and Aldosterone/Renin Ratio in a Normotensive Healthy Pediatric Population

Primary aldosteronism is an important cause of secondary hypertension and is suspected in adults with an aldosterone/renin ratio ≥25. The normal aldosterone/renin ratio is unknown in children. The aim was to establish serum aldosterone, plasma renin activity, and aldosterone/renin ratio values in a healthy pediatric population. A cross-sectional study was performed in 211 healthy normotensive children (4 to 16 years old). Two subgroups of normotensive children were obtained: with hypertensive parents (NH) (n=113) and normotensive parents (n=98). Blood samples for measuring serum aldosterone, plasma renin activity, aldosterone/renin ratio, and DNA were collected. In subjects with aldosterone/renin ratio ≥25, the chimeric CYP11B1/CYP11B2 gene was investigated by long-extension PCR. Results are expressed as median [Q1–Q3]. NH and normotensive parents groups were similar in serum aldosterone (6.5 [3.6 to 9.0] ng/dL versus 6.5 [2.9 to 9.7] ng/dL; P=0.968) and plasma renin activity (2.3 [1.6 to 3.1] versus 2.4 [1.7 to 3.7] ng/mL per hour; P=0.129). The aldosterone/renin ratio was higher in the NH group, but this difference did not reach statistical significance (2.8 [1.9 to 4.1] versus 2.5 [1.4 to 4.0], P=0.104). In one subject of the NH group, the chimeric CYP11B1/CYP11B2 gene was detected. We demonstrated that normal aldosterone/renin ratio values in a healthy pediatric population without NH were lower than those reported for an adult normotensive population.

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

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.

Esteatosis Hepática: ¿preludio de diabetes tipo 2 en población pediátrica?

UNLABELLED Non alcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance (IR) and increased type 2 diabetes (T2D). Alanine aminotransferase (ALT) is recognized as biochemical marker of NAFLD, currently used as screening for this disease. OBJECTIVE To estimate the associations between (ALT) with anthropometric variables, insulin resistance and inflammatory markers in pediatric population. PATIENTS AND METHOD we studied 348 subjects (52.7% females), aged between 4.9 and 15.6 years. Blood samples for measuring: AST, ALT, glycaemia, insulin, lipid profile, hsCRP TNF-α, IL-6 and adiponectin. We calculate HOMA-IR, QUICKI y el HOMA-β. The results are expressed are expressed as median interquartile range. Variables were log10 transformed before Pearson correlations analyze. RESULTS Serum ALT levels were positively associated with BMI-SDS (r = 0.335), waist/ height ratio (r = 0.358), insulin (r = 0.33), HOMA-IR (r = 0.33), HOMA-β (r = 0.26), TG/HDL-c (r = 0.2), hsCRP (r = 0.3); and a negative association with QUICKI (r = -0.25) and adiponectin (r = -0.113). Non-association with ALT, glycaemia, TNF-α and IL-6 was found. CONCLUSION Our study demonstrated that ALT, but not AST, was significantly correlated with of insulin resistance and inflammatory markers, all of them recognized as risk parameters of pre diabetes stage. ALT should be part of the evaluation of all obesity children, mainly those with other cardiometabolic risk factors, since it could predict later development of T2DM. Further imaging studies are necessary to confirm fatty liver disease in this population.

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.

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.

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.