Uric acid is linked to cardiometabolic risk factors in overweight and obese youths.

OBJECTIVE: Observational studies have indicated that high levels of serum uric acid are associated with the risk of cardiovascular disease. The aim of the present study is to investigate the association of uric acid with individual cardiometabolic risk factors, as well as their degree of clustering, in overweight and moderate obese youth. METHODS: Three hundred and thirty-three Caucasians of both sexes (149 women), from 5-18 years of age from those who underwent an assessment of overweight/obesity. Anthropometric parameters, office and 24-h blood pressure measurements and metabolic profile, including HDL-cholesterol, triglycerides, insulin, HOMA index and uric acid were assessed. RESULTS: Uric acid was significantly higher in boys than in girls. A positive significant association between uric acid, and office, daytime and night-time SBP, insulin and triglycerides was observed. When boys and girls were grouped by sex-specific uric acid tertiles, a progressive increment was observed in BMI, BMI z-score and waist circumference as well as fasting insulin and HOMA index. In boys, this was also present in office and ambulatory SBP. Likewise, the number of abnormal metabolic risk factors also increases with the uric acid values and the higher the number of metabolic components the higher the uric acid values. Moreover, in a multiple regression analysis, uric acid was significantly related with male sex, waist circumference, both office and night-time SBP and birth weight. CONCLUSION: The present study found a positive association between uric acid and blood pressure, insulin and triglycerides. As uric acid levels increase there is a relevant clustering of metabolic risk factors, whereas elevated blood pressure is the risk factor less frequently present. Further studies need to assess the mechanistic link between uric acid and the cardiometabolic risk factors.

Determinants of Cardiometabolic Risk Factors in the First Decade of Life: A Longitudinal Study Starting at Birth.

The present prospective study assessed the association of birth weight (BW) and growth pattern on cardiometabolic risk factors in a cohort followed from birth to 10 years of age. One hundred and forty-five subjects (73 girls) who fulfilled the inclusion criteria and had all their data recorded at birth and at 5 years were enrolled. Of these, 100 (52 girls) also recorded data at 10 years. Anthropometric measurements, office and 24-hour blood pressure, and metabolic parameters were obtained. At 5 years, both BW and current weight were determinants of blood pressure and metabolic parameters; however, as the subjects got older, the impact of body size increased. Higher BW and maternal obesity increased the risk of becoming obese at 5 years while this was reduced if breastfeeding. Maternal obesity was the only factor associated with becoming obese at 10 years. Twenty-two children at 10 years had insulin values ≥15 U/L, some of whom were persistent from 5 years while in others it increased afterward. Subjects with insulin values ≥15 U/L showed significant higher values of office systolic blood pressure, triglycerides, and uric acid and lower values of high-density lipoprotein than did those with normal insulin values. Highest weight gain from 5 to 10 years and lowest BW were the main determinants of high insulin levels. In conclusion, although BW was a proxy of the events during fetal life and projected its influence later, the influence of gaining weight was a key determinant in the risk to develop obesity and metabolic abnormalities.

Longitudinal study of DNA methylation during the first 5 years of life.

BACKGROUND: Early life epigenetic programming influences adult health outcomes. Moreover, DNA methylation levels have been found to change more rapidly during the first years of life. Our aim was the identification and characterization of the CpG sites that are modified with time during the first years of life. We hypothesize that these DNA methylation changes would lead to the detection of genes that might be epigenetically modulated by environmental factors during early childhood and which, if disturbed, might contribute to susceptibility to diseases later in life. METHODS: The study of the DNA methylation pattern of 485577 CpG sites was performed on 30 blood samples from 15 subjects, collected both at birth and at 5 years old, using Illumina(®) Infinium 450 k array. To identify differentially methylated CpG (dmCpG) sites, the methylation status of each probe was examined using linear models and the Empirical Bayes Moderated t test implemented in the limma package of R/Bioconductor. Surogate variable analysis was used to account for batch effects. RESULTS: DNA methylation levels significantly changed from birth to 5 years of age in 6641 CpG sites. Of these, 36.79 % were hypermethylated and were associated with genes related mainly to developmental ontology terms, while 63.21 % were hypomethylated probes and associated with genes related to immune function. CONCLUSIONS: Our results suggest that DNA methylation alterations with age during the first years of life might play a significant role in development and the regulation of leukocyte-specific functions. This supports the idea that blood leukocytes experience genome remodeling related to their interaction with environmental factors, underlining the importance of environmental exposures during the first years of life and suggesting that new strategies should be take into consideration for disease prevention.

Central blood pressure and pulse wave amplification across the spectrum of peripheral blood pressure in overweight and obese youth.

OBJECTIVE: To identify vascular phenotypes across blood pressure (BP) conditions in overweight and obese youths, by assessing office BP (oBP), and central BP (cBP), and pulse pressure (PP) amplification. Whether or not 24-h ambulatory BP monitoring (ABPM) and pulse wave velocity (PWV) add insight to the issue has also been examined. METHODS: White youths of both sexes with overweight or obesity and of European origin, ranging from 8 to 18 years of age, were included. oBP, cBP, PWV, and 24-h ABPM were measured. oBP conditions and 'white-coat' hypertension were defined as recommend by European Society Hypertension Guidelines in Children and Adolescents. Patients were divided into subgroups of 'normal' or 'high' according to cBP and PP ratio. RESULTS: A total of 593 patients (mean age, 12.2 ±â€Š2.3 years; 275 women) were included in the study. The largest differences between office SBP and central SBP correspond to the isolated systolic hypertension (ISH) group, in which only 25% of patients have high cBP, in contrast to 50% of the systo-diastolic hypertension (SDH) group. Two patterns emerged based on cBP and PP ratio - while the highest cBP was among the SDH, the highest PP amplitude was in the ISH group. Ninety percent of the SDH were confirmed with 24-h ABPM, in contrast to 75% of the ISH, who were white-coat hypertensive. PWV showed a progressive increment across the groups from normotension to SDH. Significant differences were observed only when compared with the normotensive, but not among all other groups. CONCLUSION: In overweight and obese hypertensive patients, ISH is prevalent, posing a challenge for the clinician of whether these may therefore be diagnosed and managed as hypertensive patients. Until prospective studies can give more knowledge, 24-h ABPM can offer information for making clinical decisions.

Assessment of ten trace elements in umbilical cord blood and maternal blood: association with birth weight.

BACKGROUND: Trace elements are an essential nutritional component for humans and inadequate tissue-concentrations may have a significant effect on fetal size. OBJECTIVE: To measure ten trace elements in blood samples from mothers and their newborns, and assess their association with anthropometric characteristics at birth. The effects of other factors on fetal growth, such as biologic characteristics of the infant and mother, were analysed. METHODS: A cross-sectional study was conducted in the Hospital general, University of Valencia, Spain. Healthy pregnant women, and their full-term infants were selected (n = 54 paired samples). Infants were grouped according to birth weight: small for gestational age (SGA n = 11), appropriate (AGA n = 30), and large (LGA n = 13). Anthropometric and biologic characteristics of the infant and mother were recorded. Levels of ten essential elements: arsenic (As), barium (Ba), cobalt (Co), copper (Cu), chrome (Cr), iron (Fe), magnesium (Mg), manganese (Mn), selenium (Se) and zinc (Zn), in maternal and cord plasma samples were determined. Samples were obtained from the umbilical cord immediately after delivery and the samples of their mothers were drawn at 2-4 h after delivery. RESULTS: The analysis identified that cord blood Cu (p = 0.017) and maternal blood Ba and Mg (p = 0.027 and p = 0.002, respectively) concentrations were significantly higher among SGA infants compared to AGA and LGA infants. A multiple linear regression analysis showed that increased umbilical cord Cu concentration (adjusted ß -146.4 g, 95% CI -255 to -37.7; p = 0.009), maternal smoking during pregnancy (adjusted ß -483.8 g, 95% CI -811.7 to -155.9; p = 0.005), shorter gestational age (adjusted ß 350.1 g, 95% CI 244.5 to 455.8; p = 0.000), and female sex (adjusted ß -374 g, 95% CI -648 to -100; p = 0.009) were significantly associated with decreased birth weight. Maternal anaemia was positively associated with birth weight (adjusted ß 362 g, 95% CI 20.8 to 703.1; p = 0.038). No significant associations were found between maternal trace elements and birth weight in multivariate analysis. CONCLUSIONS: We did not observe significant associations of cord blood trace elements other than Cu and maternal trace elements with birth weight in the multivariate analyses.

Cardiovascular fitness in youth: association with obesity and metabolic abnormalities.

UNLABELLED: Therapies currently implemented for obesity are focused on nutritional aspects and on physical activity. In order to make physical activity a positive therapy instead of triggering disabilities it is relevant to accurately assess cardiovascular fitness. OBJECTIVE: To assess the cardiovascular fitness by measuring the peak oxygen consumption and to asses their relationship with classical cardiometabolic parameters. METHODS: A modified Balke protocol was applied to one hundred and twenty-six Caucasians (60% males), ranging between 9 and 16 years old, who underwent an assessment of obesity. The non-obese group consisted of healthy age and sex matched subjects who were invited to participate from the general population. RESULTS: Significant differences in consumption of oxygen peak between non-obese and obese individuals were observed. In contrast, no significant differences existed between the categories of obesity. Furthermore in obese subjects consumption of oxygen peak was inversely correlated with parameters of cardiometabolic risk, particularly insulin and HOMA index. In addition, two predictive equations of consumption of oxygen peak, with an R2 of 0.74 and 0.84, respectively, have been developed. CONCLUSION: The consumption of oxygen peak is a relevant clinical parameter that should be included in the routine clinical assessment of obese subjects. Therefore, it is crucial to make exercise tests more affordable which can be achieved by employing predictive equations.

Las terapias que se implantan actualmente para la obesidad se centran en los aspectos nutricionales y sobre la actividad física. Con el fin de hacer que la actividad física sea una terapia positiva en vez de un desencadenador de discapacidades, es relevante evaluar de forma precisa el entrenamiento cardiovascular. Objetivo: evaluar el entrenamiento cardiovascular midiendo el consumo máximo de oxígeno y evaluar su relación con los parámetros cardiometabólicos clásicos. Métodos: se aplicó el protocolo modificado de Balke a 126 individuos caucásicos (60 % de varones), con edades entre 9 y 16 años, que se sometieron a una evaluación de obesidad. El grupo de no obesos consistía de individuos sanos, de la población general, emparejados por edad y sexo y a los que se les invitó a participar. Resultados: se observaron diferencias significativas en el consumo máximo de oxígeno entre los indiviudos obesos y no obesos. Por contra, no existían diferencias significativas entre las categorías de obesidad. Además, en los sujetos obesos, el consumo máximo de oxígeno se correlacionó de forma inversa con los parámetros de riesgo cardiometabólico, particularmente con la insulina y el índice HOMA. Además, se han desarrollado dos ecuaciones predictivas del consumo máximo de oxígeno con una R2 de 0,74 y de 0,84, respectivamente. Conclusión: el consumo máximo de oxígeno es un parámetro clínico relevante que debería incluirse en la evaluación clínica rutinaria de los sujetos obesos. Por lo tanto, es crucial hacer que las pruebas de esfuerzo sean más asequibles, que puedan alcanzarse empleando las ecuaciones predictivas.

Cardiovascular fitness in youth; association with obesity and metabolic abnormalities / Entrenamiento cardiovascular en la juventud; asociación con obesidad y anomalías metabólicas

Therapies currently implemented for obesity are focused on nutritional aspects and on physical activity. In order to make physical activity a positive therapy instead of triggering disabilities it is relevant to accurately assess cardiovascular fitness. Objective: To assess the cardiovascular fitness by measuring the peak oxygen consumption and to asses their relationship with classical cardiometabolic parameters. Methods: A modified Balke protocol was applied to one hundred and twenty-six Caucasians (60% males), ranging between 9 and 16 years old, who underwent an assessment of obesity. The non-obese group consisted of healthy age and sex matched subjects who were invited to participate from the general population. Results: Significant differences in consumption of oxygen peak between non-obese and obese individuals were observed. In contrast, no significant differences existed between the categories of obesity. Furthermore in obese subjects consumption of oxygen peak was inversely correlated with parameters of cardiometabolic risk, particularly insulin and HOMA index. In addition, two predictive equations of consumption of oxygen peak, with an R2 of 0.74 and 0.84, respectively, have been developed. Conclusion: The consumption of oxygen peak is a relevant clinical parameter that should be included in the routine clinical assessment of obese subjects. Therefore, it is crucial to make exercise tests more affordable which can be achieved by employing predictive equations (AU)

Las terapias que se implantan actualmente para la obesidad se centran en los aspectos nutricionales y sobre la actividad física. Con el fin de hacer que la actividad física sea una terapia positiva en vez de un desencadenador de discapacidades, es relevante evaluar de forma precisa el entrenamiento cardiovascular. Objetivo: evaluar el entrenamiento cardiovascular midiendo el consumo máximo de oxígeno y evaluar su relación con los parámetros cardiometabólicos clásicos. Métodos: se aplicó el protocolo modificado de Balke a 126 individuos caucásicos (60 % de varones), con edades entre 9 y 16 años, que se sometieron a una evaluación de obesidad. El grupo de no obesos consistía de individuos sanos, de la población general, emparejados por edad y sexo y a los que se les invitó a participar. Resultados: se observaron diferencias significativas en el consumo máximo de oxígeno entre los individuos obesos y no obesos. Por contra, no existían diferencias significativas entre las categorías de obesidad. Además, en los sujetos obesos, el consumo máximo de oxígeno se correlacionó de forma inversa con los parámetros de riesgo cardiometabólico, particularmente con la insulina y el índice HOMA. Además, se han desarrollado dos ecuaciones predictivas del consumo máximo de oxígeno con una R2 de 0,74 y de 0,84, respectivamente. Conclusión: el consumo máximo de oxígeno es un parámetro clínico relevante que debería incluirse en la evaluación clínica rutinaria de los sujetos obesos. Por lo tanto, es crucial hacer que las pruebas de esfuerzo sean más asequibles, que puedan alcanzarse empleando las ecuaciones predictivas (AU)

Associations of birth weight and postnatal weight gain with cardiometabolic risk parameters at 5 years of age.

The present prospective study assessed the impact of birth weight (BW) and postnatal weight gain on blood pressure and metabolic profile during the first 5 years of life. One hundred thirty-nine newborns (63 women) born at term after uncomplicated pregnancies and in the absence of perinatal illness were included. Subjects were divided according to size at birth in small, appropriate, and large for gestational age. After the initial evaluation on the second day of life, infants were followed up at 6 months and 2 and 5 years. Anthropometric parameters and blood pressure were measured at each visit and metabolic assessment was performed at 5 years of age. Among the BW groups, mothers did not differ in terms of age, smoking, and weight gain during pregnancy. BW was a positive determinant of systolic blood pressure at birth. Afterward, current weight was the strongest determinant, becoming significant at 2 years of age and progressively increasing in influence. At 5 years insulin, the homeostasis model assessment index and triglycerides were dependent on BW, current weight, and postnatal weight gain. In addition, BW was positively associated with high-density lipoprotein-cholesterol and inversely so to uric acid. A positive relationship among insulin, blood pressure values, and uric acid was observed even early in life. In conclusion, the acceleration of early infant weight gain may aggravate the effects of low BW. Multiple interactions between hemodynamic and metabolic parameters foreshadow the clustering of cardiometabolic risk factors later in life.

Prevalence and factors related to urinary albumin excretion in obese youths.

OBJECTIVES: The aim of the present study is to assess whether obesity is associated with urinary albumin excretion and what the main determinants are. METHODS: One hundred and thirty-four obese white children and adolescents of both sexes, ranging from 9 to 18 years of age (mean age 12.6 ±â€Š2.0), were included in the study. Obesity was defined on the basis of a threshold BMI z-score of more than 2 (Cole's LMS method) and overweight with a BMI from the 85th to 95th percentile. Office blood pressure was measured using a mercury sphygmomanometer. Urinary albumin excretion was measured in the first voiding urine of the morning and expressed in albumin/creatinine ratio in mg/g. Reproducibility of the urinary albumin excretion was studied by the Bland and Altman technique in a subgroup. Triglycerides, uric acid, fasting glucose and insulin were measured and the homeostatic model assessment (HOMA) index was calculated. RESULTS: The prevalence of microalbuminuria was 2.4%. No differences in the prevalence of microalbuminuria were observed when the different groups of obesity degree were compared (0, 2.2 and 0% in overweight, moderate and severe obese, respectively). A significant relationship emerged between the Log urinary albumin excretion and BMI z-score, waist circumference, Log triglycerides, fasting insulin and HOMA index, adjusted by age and sex. In a multiple regression analysis, the main determinants of Log urinary albumin excretion were sex, waist circumference and Log triglycerides. In 17% of the individuals who fulfil criteria for metabolic syndrome, urinary albumin excretion was significantly higher than those without. CONCLUSION: The prevalence of elevated urinary albumin excretion is not prominent in obese children, and when it is increased, it depends mainly on metabolic factors.

Sexual dimorphism in the transition from masked to sustained hypertension in healthy youths.

The risk and factors related to the development of hypertension among healthy youths with elevated ambulatory and normal conventional blood pressure, masked hypertension, have not been established. We performed a long-term follow-up study assessing how hypertension develops over time in healthy, masked hypertensive youths. The potential sex dimorphism in the incidence and timing of the development of hypertension has been analyzed. In a long-term follow-up study (median follow-up, 36 months), we enrolled 272 healthy conventional normotensive youths (aged 6-18 years; 55.8% girls) of whom 39 had masked hypertension at baseline. Development of sustained hypertension (hypertension in both conventional and ambulatory measurement) was recorded. The daytime systolic blood pressure increased from baseline to last available follow-up in boys (3.5 mm Hg; P<0.001) but not in girls (0.7 mm Hg; P=0.23), leading to a significant between-sex difference (P=0.0022). The incidence of sustained hypertension was 7.0/100 subjects/y (n=12) in masked hypertensives and 0.6/100 subjects/y (n=4) in normotensives. Masked hypertensive boys more frequently proceeded to sustained hypertension as compared with masked hypertensive girls (50.0% versus 17.4%; P=0.041). Masked hypertension at baseline (hazard ratio, 15.6; 95% confidence interval, 4.91-49.7; P<0.0001) and male sex (hazard ratio, 3.25; 95% confidence interval, 1.12-9.39; P=0.0295) were independent factors associated with the incidence of sustained hypertension during the follow-up. In youth, masked hypertension is a precursor of sustained hypertension. The risk of developing sustained hypertension is higher in boys than it is for girls. The fact that masked hypertension is not prognostically innocent increases the importance of the diagnosis at an early age.

Ambulatory blood pressure monitoring in children and adolescents: coming of age?

Over the last years, ambulatory blood pressure monitoring has been introduced into the pediatric population, contributing to a significant increase in the bulk of knowledge of crucial clinically relevant issues. Guidelines have established the currently known conditions where ambulatory blood pressure monitoring is useful and where it will provide additional information in children and adolescents. How common and important the intra-individual differences are within clinical and ambulatory blood pressure is the keystone to the use of ambulatory blood pressure monitoring as a diagnostic tool. By using not only office, but also ambulatory blood pressure, four possible situations arise. Two of these have values in agreement for normotension or hypertension. Two have values that are discrepant. The latter two are known as white coat and masked hypertension. The relationship with hypertension-induced organ damage, the prognostic value and the assessment of treatment goals are key issues of ambulatory blood pressure monitoring. In children, the accurate identification of hypertension at the earliest possible age would, therefore, give health-care providers the opportunity to initiate preventive measures, thereby reducing the chance of developing end-organ damage and its attendant morbidity and mortality.

Emotional Eating Scale for children and adolescents: psychometric characteristics in a Spanish sample.

The aims of this study were to validate the Emotional Eating Scale version for children (EES-C) in a Spanish population and study the differences in emotional eating among children with binge eating (BE), overeating (OE), and no episodes of disordered eating (NED). The questionnaire was completed by 199 children aged 9 to 16 years. Confirmatory factor analysis revealed five scales: eating in response to anger, anxiety, restlessness, helplessness, and depression. The EES-C showed good internal consistency and test-retest reliability, and it showed moderate relationships with measures of disordered-eating [Children's Eating Attitudes Test-26 (ChEAT-26), Questionnaire of Eating and Weight Patterns-Adolescent Version (QEWP-A)] and psychopathology (State-Trait Anxiety Inventory for Children, Children's Depression Inventory, Child Behavior Checklist). There were significant differences between the BE/NED groups (with the OE group in the middle position) in desire to eat when Anger (the girls in BE group, and the oldest children in OE group obtaining higher scores) or Helplessness were present. Eating due to Depression was higher in the older groups. Multiple regression analysis conducted showed that anxiety-trait was the best predictor of emotional eating. Results support the potential utility of the EES-C in the study of emotional eating in children and its validity in the Spanish population.

Early vascular phenotypes in the genesis of hypertension.

Cardiovascular complications occurring in adults find their roots in risk factors operating early in life. Among the factors influencing cardiovascular risk, blood pressure values in children represent an important measurable marker of the level of potential cardiovascular risk later in life because the levels are both the cause and the consequence of early vascular alterations. Early vascular phenotypes represent a field of great interest, and they can be studied through indirect assessment using non-invasive techniques. Estimations of blood pressure components, pulse wave velocity, and reflecting waves provide valuable information that can be easily recorded and repeated overtime. A direct assessment, carried out by examining the umbilical vessels, can add further valuable information. In this review, we discuss the potential application of surrogate markers of early vascular alterations and describe the information provided by umbilical cord vessels.

Birth weight impacts on wave reflections in children and adolescents.

The objective of the present study was to assess central aortic pressure and wave reflection in children and adolescents at different birth weights. Two hundred nineteen healthy children (126 girls), from 7 to 18 years of age (mean, 11.3 years) and born at term after a normotensive pregnancy, were included. The subjects were divided according to birth weight: <2.5 kg, from 2.5 to 2.999 kg, from 3.0 to 3.5 kg, and >3.5 kg. Pressure waveforms were recorded from the radial artery of the wrist, and the waveform data were then processed by the SphygmoCor radial/aortic transform software module to produce the estimated aortic pressure waveform. Augmentation index, an estimate of the pulse wave reflection, was significantly higher in children with the lowest birth weights compared with the other birth weight groups. In a multiple regression analysis, short stature, low heart rate, female gender, and lower birth weight had independent significant inverse correlations to the augmentation index when adjusted for diastolic blood pressure (R2=0.21). In summary, the results showed a relatively aged phenotype of large-vessel function in the children with the lowest birth weights. These early alterations may be amplified throughout life and may contribute to the increased cardiovascular risk associated with low birth weight.