Insulin resistance parameters in children born very preterm and adequate for gestational age.

BACKGROUND: Preterm neonates are at risk for metabolic syndrome later in life. Whether prematurity constitutes an independent risk factor for the development of cardiovascular disease and metabolic syndrome remains controversial. OBJECTIVE: To compare anthropometric measures, cardiometabolic risk factors and insulin resistance variables between children who were born very preterm (VPT, <32 gestational weeks) and at term (Term, >37 gestational weeks) and adequate for gestational age (AGA). METHODS: We designed a cross-sectional cohort study, recruiting 120 children (5.0-8.5 years old) from the preterm clinic at Red de Salud UC-Christus and Complejo Asistencial Dr. Sótero del Río, and term children from the community. We excluded children born small for gestational age, based on INTERGROWTH21. Anthropometrics data were classified using WHO reference standards. The homeostasis model assessment insulin resistance (HOMA-IR) index, quantitative insulin sensitivity check index (QUICKI), triglyceride-to-HDL-C ratio (TG/HDL-C) and Pediatric Score Index for Metabolic Syndrome (PsiMS) were calculated. RESULTS: VPT children born AGA had lower HDL cholesterol levels (p = .019) and a higher PsiMS score than those born at term (p = .043). We observed a higher percentage of children with HDL cholesterol ≤40 mg/dl (13.0% vs. 2.3%, p = .026) and BP ≥90th percentile among the VPT children than among the Term children (26.0% vs. 11.6%, p = .031). CONCLUSIONS: At school age, blood pressure was higher, and HDL-C was lower among VPT children born AGA, suggesting a potential metabolic risk; therefore, it is essential to follow this group throughout their lives.

La presión arterial es un importante marcador de ateroesclerosis subclínica en niños / Association of carotid intima media thickness with blood pressure and HDL cholesterol in children

Background: Cardiovascular risk factors must be controlled since childhood. Aim: To assess the association of carotid intima media thickness (CIMT) with the components of the metabolic syndrome in Children. Material and Methods: Cross sectional assessment of 299 children aged 11.5 ± 0.9years (58% women) with and without metabolic syndrome components. Anthropometric parameters and blood pressure were measured and a blood sample was obtained to measure blood glucose and lipids. CIMT was measured using high resolution ultrasound. Results: Ninety three percent of children were post puberal, 64% were overweight and 25% had metabolic syndrome. Mean and maximum CIMT correlated with systolic blood pressure (r = 0.21 and 0.21 respectively p < 0.01). Children with a CIMTover the 75th percentile had higher blood pressure and lower HDL cholesterol. A stepwise logistic regression accepted both variables as predictors of CIMT with odds ratios for mean CIMT of 1.46 (1.19-1-79) and 0.81 (0.7-0.94) perfive units of change, respectively. Conclusions: In this group of children systolic blood pressure and HDL cholesterol are associated to CIMT.

[Association of carotid intima media thickness with blood pressure and HDL cholesterol in children]. / La presión arterial es un importante marcador de ateroesclerosis subclínica en niños.

BACKGROUND: Cardiovascular risk factors must be controlled since childhood. AIM: To assess the association of carotid intima media thickness (CIMT) with the components of the metabolic syndrome in Children. MATERIAL AND METHODS: Cross sectional assessment of 299 children aged 11.5 ± 0.9 years (58% women) with and without metabolic syndrome components. Anthropometric parameters and blood pressure were measured and a blood sample was obtained to measure blood glucose and lipids. CIMT was measured using high resolution ultrasound. RESULTS: Ninety three percent of children were post puberal, 64% were overweight and 25% had metabolic syndrome. Mean and maximum CIMT correlated with systolic blood pressure (r = 0.21 and 0.21 respectively p < 0.01). Children with a CIMT over the 75th percentile had higher blood pressure and lower HDL cholesterol. A stepwise logistic regression accepted both variables as predictors of CIMT with odds ratios for mean CIMT of 1.46 (1.19-1-79) and 0.81 (0.7-0.94) per five units of change, respectively. CONCLUSIONS: In this group of children systolic blood pressure and HDL cholesterol are associated to CIMT.

Adiponectin levels, cardiometabolic risk factors and markers of subclinical atherosclerosis in children.

BACKGROUND: Low levels of adiponectin have been associated with metabolic risk factors (RF) and cardiac disease. Minimal data is available about the relationship between adiponectin and subclinical atherosclerosis. OBJECTIVES: To determine the relationship of adiponectin to cardiometabolic RF, C-reactive protein (CRP), anthropometric parameters of obesity, and subclinical atherosclerosis in children. METHODS: Cross-sectional study in 103 children. We determined body mass index (BMI), waist circumference, percent fat mass, systolic and diastolic blood pressures, fasting lipid profile, glycemia and insulinemia, and CRP. Subclinical atherosclerosis was determined by carotid intima-media thickness (IMT) and flow-mediated dilation of the brachial artery (FMD). RESULTS: Mean age of the group was 12.4+/-1.9 years (47% girls; 20.4% prepubertal; 45 eutrophic, 23 overweight and 35 obese). Adiponectin levels were not statistically significantly different in eutrophic children versus obese+overweight: 17.7+/-5.6 and 15.9+/-5.3 microg/mL, respectively. Adiponectin levels in boys were no different from those in girls. Adiponectin correlated significantly with age, BMI, zBMI, waist circumference, systolic and diastolic blood pressures, HDL, insulinemia, and HOMA index. No statistically significant association with adiponectin was found for CRP, FMD or IMT. After adjusting by sex, pubertal status, and degree of obesity, the adiponectin levels associated significantly with HDL cholesterol and the HOMA index (r(2)=0.34, p<0.0001). CONCLUSIONS: Adiponectin levels were inversely correlated with anthropometric parameters of obesity and insulin resistance and directly correlated with HDL levels. However, no relationship with subclinical atherosclerosis was demonstrated in this study.

[Early markers for atherosclerosis and metabolic syndrome in children]. / Marcadores de aterosclerosis temprana y síndrome metabólico en niños.

BACKGROUND: The high prevalence of obesity in children favors the appearance of metabolic syndrome (MS), increasing their cardiovascular risk. AIM: To evaluate components of MS in children and to correlate them with surrogate markers of atherosclerosis and subclinical inflammation. MATERIAL AND METHODS: We studied 209 children aged 11.5 +/- 2 years (50% girls, 30% prepuberal). Fifty percent had normal weight, 18% were overweight, 29% were obese and 3% were undernourished. A fasting blood sample was obtained to measure lipid levels, glucose, insulin, adiponectin and ultrasensitive C-reactive protein (usCRP). Subclinical atherosclerosis was evaluated using flow mediated dilatation of brachial artery (FMD) and carotid intima-media thickness (IMT). For diagnosis of MS we adapted Cook's criteria. RESULTS: Five percent of all children and 18% of those with overweight had MS. Children with more components had significantly higher fasting insulin and Homeostasis Model Assessment (HOMA) values. Clustering of MS components was also associated to higher values of usCRP and non significantly to lower adiponectin levels. We did not find differences in FMD. In obese children there was a tendency towards a higher IMT with clustering of MS components, although not significant. CONCLUSIONS: Children with overweight presented a higher risk of a clustering of MS components, which was also associated with insulin resistance and increase in ultrasensitive C reactive protein.

Marcadores de aterosclerosis temprana y síndrome metabólico en niños / Early markers for atherosclerosis and metabolic syndrome in children

Background: The high prevalence of obesity in children favors the appearance of metabolic syndrome (MS), increasing their cardiovascular risk. Aim: To evaluate components of MS in children and to correlate them with surrogate markers of atherosclerosis andsubclinical inflammation. Material and methods: We studied 209 children aged 11.5 ± 2 years (50% girls, 30% prepuberal). Fifty percent had normal weight, 18% were overweight, 29% were obese and 3% were undernourished. A fasting blood sample was obtained to measure lipid levels,glucose, insulin, adiponectin and ultrasensitive C-reactive protein (usCRP). Subclinical atherosclerosis was evaluated using flow mediated dilatation of brachial artery (FMD) andcarotid intima-media thicknes (IMT). For diagnosis of MS we adapted Cook’s criteria. Results: Five percent of all children and 18% of those with overweight had MS. Children with more components had significantly higher fasting insulin and Homeostasis Model Assessment (HOMA) values. Clustering of MS components was also associated to higher values of usCRP and non significantly to lower adiponectin levels. We did not find differences in FMD. In obese children there was a tendency towards a higher IMT with clustering of MS components, although not significant. Conclusions: Children with overweight presented a higher risk of a clustering ofMS components, which was also associated with insulin resistance and increase in ultrasensitive C reactive protein.

[Relationship of C-reactive protein to adiposity, cardiovascular risk factors and subclinical atherosclerosis in healthy children]. / Proteína C reactiva y su relación con adiposidad, factores de riesgo cardiovascular y aterosclerosis subclínica en niños sanos.

INTRODUCTION AND OBJECTIVES: In adults, C-reactive protein is a marker of cardiovascular risk. It is associated with both classical and metabolic risk factors and is a predictor of cardiovascular events. The aim was to investigate the relationship of the C-reactive protein concentration to classical cardiovascular risk factors, measures of adiposity subclinical atherosclerosis in children. METHODS: The values of traditional risk factors, anthropometric parameters, fasting lipids, glucose and C-reactive protein levels were recorded. In addition, the carotid artery intima-media thickness was measured, and brachial artery endothelial function was assessed using flow-mediated dilation. RESULTS: The study included 112 children (58 male) with a mean age of 11.3+/-1.9 years. The mean C-reactive protein concentration was 0.9+/-1.5 mg/L. In males, there were significant direct correlations between the C-reactive protein concentration and body mass index, total fat mass, central adiposity, waist circumference, and low-density lipoprotein (LDL) cholesterol level. In females, C-reactive protein was associated with only body mass index. Boys in the highest C-reactive protein tertile had a significantly higher body mass index, total fat mass, LDL cholesterol level, and waist circumference. In the whole group, the best predictor of an elevated ultrasensitive C-reactive protein concentration was the body mass index (odds ratio=2.04 [1.30-3.21]). No relationship was found between the C-reactive protein concentration and the percentage flow-mediated dilation of the brachial artery or the carotid intima-media thickness. CONCLUSIONS: The results indicate that, in children, there is a significant direct relationship between the ultrasensitive C-reactive protein concentration and measures of adiposity, particularly body mass index. However, no relationship between C-reactive protein and subclinical atherosclerosis was observed.

Proteína C reactiva y su relación con adiposidad, factores de riesgo cardiovascular y aterosclerosis subclínica en niños sanos / Relationship of C-reactive protein to adiposity, cardiovascular risk factors and subclinical atherosclerosis in healthy children

Introducción y objetivos. En adultos, la proteína C reactiva es un marcador de riesgo cardiovascular que se asocia a los factores de riesgo tradicionales y metabólicos y predice eventos cardiovasculares. Métodos. Estudiamos la concentración de proteína C reactiva ultrasensible para establecer su relación con medidas de adiposidad, factores de riesgo tradicionales y aterosclerosis subclínica en niños. El objetivo ha sido la evaluación de factores de riesgo clásicos, antropometría, lípidos, glucemia y proteína C reactiva en ayunas, junto con evaluación de la función endotelial mediada por flujo en la arteria braquial y el grosor intimomedial de la arteria carótida. Resultados. Se estudió a 112 niños (58 varones) con una media ± desviación estándar de edad de 11,3 ± 1,9 años. La media de proteína C reactiva del grupo fue 0,9 ± 1,5 mg/l. En los varones, la proteína C reactiva se correlacionó en forma directa y significativa con el índice de masa corporal, la masa grasa total, la grasa troncal y la cintura y el colesterol de las lipoproteínas de baja densidad (cLDL). En las mujeres, se asoció sólo al índice de masa corporal. Los varones en el tercil superior de proteína C reactiva presentaron mayor índice de masa corporal, grasa total, cintura y cLDL. El factor que mejor determinó una proteína C reactiva ultrasensible elevada en el grupo total fue el índice de masa corporal (odds ratio [OR] = 2,04 [1,30-3,21]). No se demostró asociación entre proteína C reactiva y porcentaje de dilatación de la arteria braquial mediada por flujo o grosor de la carótida. Conclusiones. Este estudio indica que la proteína C reactiva ultrasensible se asocia en forma directa y significativa al grado de adiposidad, especialmente el índice de masa corporal, pero no a marcadores de aterosclerosis subclínica en niños (AU)

Introduction and objectives. In adults, C-reactive protein is a marker of cardiovascular risk. It is associated with both classical and metabolic risk factors and is a predictor of cardiovascular events. The aim was to investigate the relationship of the C-reactive protein concentration to classical cardiovascular risk factors, measures of adiposity subclinical atherosclerosis in children. Methods. The values of traditional risk factors, anthropometric parameters, fasting lipids, glucose and C-reactive protein levels were recorded. In addition, the carotid artery intima-media thickness was measured, and brachial artery endothelial function was assessed using flow-mediated dilation. Results. The study included 112 children (58 male) with a mean age of 11.3±1.9 years. The mean C-reactive protein concentration was 0.9±1.5 mg/L. In males, there were significant direct correlations between the C-reactive protein concentration and body mass index, total fat mass, central adiposity, waist circumference, and low-density lipoprotein (LDL) cholesterol level. In females, C-reactive protein was associated with only body mass index. Boys in the highest C-reactive protein tertile had a significantly higher body mass index, total fat mass, LDL cholesterol level, and waist circumference. In the whole group, the best predictor of an elevated ultrasensitive C-reactive protein concentration was the body mass index (odds ratio=2.04 [1.30­3.21]). No relationship was found between the C-reactive protein concentration and the percentage flow-mediated dilation of the brachial artery or the carotid intima-media thickness. Conclusions. The results indicate that, in children, there is a significant direct relationship between the ultrasensitive C-reactive protein concentration and measures of adiposity, particularly body mass index. However, no relationship between C-reactive protein and subclinical atherosclerosis was observed (AU)

Proteína C-reactiva y su relación con adiposidad, factores de riesgo cardiovascular y aterosclerosis subclínica en niños sanos de la Región Metropolitana / C-reactive protein in relation to adiposity, cardiovascular risk factor and subclinical atherosclerosis in healthy children from Santiago, Chile

Introducción: La proteína C-reactiva ultrasensible (PCRus) es un marcador de riesgo (FR) emergente. En adultos, se asocia a la mayoría de los FR metabólicos, al desarrollo de diabetes y predice eventos cardiovasculares futuros. Dado que la aterosclerosis puede comenzar en la niñez, es importante conocer los niveles de este marcador y sus relaciones con los FR clásicos en la población pediátrica. Objetivo: Determinar los niveles de PCRus y establecer su relación con medidas antropométricas de adiposidad, FR tradicionales y medidas de aterosclerosis subclínica en niños de Santiago. Método: Estudio prospectivo en hijos de sujetos sanos de la zona urbana de Santiago. En todos los niños se realizó una encuesta sobre FR clásicos, se evaluó antropometría, maduración puberal y perfil lipídico, glicemia y PCR ultrasensible (Dade Behring) en muestra de sangre en ayunas. En todos se realizó además estudio de función endotelial por dilatación mediada por flujo en arteria braquial (DMF) y del grosor íntima-media carotídeo (IMT). Resultados: Se incluyeron en este análisis 88 niños (51 por ciento hombres), edad 10 +/- 2 (promedio DS) años. La PCRus del grupo fue 0.88 +/- 1.47 mg/L (mediana = 0.38 mg/L). En ambos sexos, la PCRus se correlacionó en forma directa a índice de masa corporal (IMC, expresado en puntaje z), a estimación clínica de grasa corporal: masa grasa total (MGT), grasa troncal, perímetro de cintura (PC) y a colesterol LDL (p<0.04). Los niños en el tercil superior de PCR presentaron mayor: zIMC, MGT, PC y LDL que los niños en los terciles inferiores (ver tabla). Los factores de riesgo para determinar una PCR elevada, en forma aislada, fueron: zIMC (OR=2.25 {1.25-4.04}), MGT (OR=1.09 {1.03-1.15}) y PC (OR=1.06 {1.01-1.11}). No se demostró asociación entre PCRus y DMF o IMT. Conclusión: La PCRus se asocia en forma directa a índices de adiposidad y a colesterol LDL en niños...

Background: Ultrasensitive C-reactive protein (USCRP) is an emergent cardiovascular risk factor (RF). In adults, USCRP is associated to most metabolic RF, to diabetes and future cardiovascular events. Since atherosclerosis may develop in childhood, the relation of USCRP to classic RF in children deserves attention. Aim: To correlate USCRP levels with adiposity, traditional RF and subclinical atherosclerosis in children from Santiago Methods: Children from healthy parents living in urban areas of Santiago were prospectively studied. A survey of traditional RF, anthropometric measurements, pubertal maturation, serum lipid profile, serum blood sugar level and USCRP (Dade Behring) were determined in all children in a fasting sample. Endothelial function was assessed by flow mediated vasodilation of the brachial artery (FMD) and intimal media thickness (IMT) Results: 88 children (51 percent males) aged 10 +/-2 years were studied. Mean USCRP was 0.88 mg/L(SD 1.47, median 0.38). In both gender groups USCRP was directly correlated to body mass index (BMI, z score), total body fat (TBF) , central adiposity measured by skin folds, waist circumference (WC) and LDL cholesterol (p<0.04). Children at top tercile USCRP level exhibited greater BMI, total body fat, central adiposity, WC and LDL level as compared to those in the lower USCRP tercile (Table). Independent predictors of high CRP levels were BMI (OR 2.55, 95 percent CI1.25-4.04), MGT (OR 1.09 (1.03-1.15)) and WC (OR 1.06 (1.01-1.11)). There was no association between USPCR and FMV or IMT. Conclusion: USCRP is directly associated to adiposity indices and serum LDL level in children. This study showed no association of USCRP and indices of subclinical atherosclerosis. Follow up of these children will help determine whether subclinical inflammation will predict the appearance of atherosclerosis when they reach adult age.

Efecto de la inhibición de enzima convertidora de antagonista de angiotensina con perindopril sobre la hipertrofia ventricular izquierda en pacientes hipertensos / Effect of ACE inhibition using perindopril upon left ventricular hypertrophy in hypertensive patients

La regresión de hipertrofia ventricular izquierda (HVI) en pacientes hipertensos podría tener beneficios clínicos en la historia natural de estos pacientes. En el presente estudio hemos evaluado prospectivamente y en forma abierta el efecto del inhibidor de la enzima convertidora de angiotensina perindopril (Per) (adicionando hidrocloratiazida cuando no se pudo controlar la presión arterial) sobre la masa ventricular izquierda (MVI) medida ecográficamente (fórmula de Devereux). Se estudiaron 19 pacientes hipertensos esenciales (PA promedio 165 ñ 4/99 ñ 3 mmHg, promedio ñ ES) con HVI (10 hombres, 9 mujeres, edad promedio 57,7 ñ 8.9 años, índice de masa corporal 29,3 ñ 3,6 m/kg²) antes y después de 3, 6 y 12 meses de tratamiento. Dieciocho pacientes (95 por ciento) recibieron 8 mg/día de Per y 17 pacientes requirieron la adición de Hctz (dosis promedio 26 ñ 2 mg/día). Con el tratamiento se obtuvo un descenso significativo de las presiones arteriales aisladas (140 ñ 2/86 ñ 2 mmHg) y en la monitoría ambulatoria de 24 horas. No se observaron variaciones significativas en el peso corporal y tampoco en ninguno de los parámetros evaluados a lo largo del estudio (potasio plasmático, creatinina, glicemia, hematocrito, colesterol). Con el tratamiento se observó disminución significativa de la dimensión diastólica (F = 3,5 p < 0,03) y del grosor de la pared posterior del VI (F = 7,69, p < 0,001) a contar de los 6 meses de tratamiento y de la aurícula izquierda a partir de los 3 meses (F 5,62, p < 0,03). No se observaron cambios en la dimensión sistólica, grosor del septum interventricular, fracción de acortamiento, velocidades de las ondas E y A ni en la relación E/A de llenado diastólico transmitral. La masa ventricular y el índice de masa ventricular izquierda se redujeron significativamente (F = 7,04,p < 0,001 y F = 6,2, p < 0,01, respectivamente) alcanzando al final del estudio un 82 por ciento de la masa ventricular inicial. El descenso de la MVI y del IMVI se correlacionó significativamente con disminución de la PA sistólica y diastólica, de la PA media y diastólica nocturna. En conclusión: el control de la presión arterial con perindopril, asociado en la mayoría de los casos a hidroclorotiazida en dosis bajas logró inducir regresión de la HVI a partir de los 6 meses de tratamiento con disminución tanto del volumen diastólico como del grosor de la pared libre del VI