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Background: Elevated lipoprotein (Lp(a)) levels are associated with increased risk of atherosclerotic processes and cardiovascular events in adults. The amount of Lp(a) is mainly genetically determined. Therefore, it is important to identify individuals with elevated Lp(a) as early as possible, particularly if other cardiovascular risk factors are present. The purpose of the study was to investigate whether, in a population of children and adolescents already followed for the presence of one or more cardiovascular risk factors (elevated blood pressure (BP), and/or excess body weight, and/or dyslipidemia), the measurement of Lp(a) can be useful for better stratifying their risk profile., Methods: In a sample of 195 children and adolescents, height, body weight, waist circumference and systolic (SBP) and diastolic (DBP) BP were measured. Body Mass Index (BMI) and SBP and DBP z-scores were calculated. Plasma Lp(a), total cholesterol, high-density lipoprotein (HDL), triglycerides, glucose, insulin, uric acid and creatinine were assessed. Low-density lipoprotein (LDL) cholesterol was calculated with the Friedewald formula. High Lp(a) was defined as ≥ 75 nmol/L and high LDL cholesterol as ≥ 3.37 mmol/L., Results: Our sample of children and adolescents (54.4% males, mean age 11.5 years) had median LDL cholesterol and Lp(a) values equal to 2.54 (interquartile range, IQR: 2.07-3.06) mmol/L and 22 (IQR: 7.8-68.6) nmol/L respectively. 13.8% of children had LDL cholesterol ≥ 3.37 mmol/L and 22.6 Lp(a) values ≥ 75 nmol/L. Lp(a) values were higher in children of normal weight than in those with excess weight (p = 0.007), but the difference disappeared if normal weight children referred for dyslipidemia only were excluded from the analysis (p = 0.210). 69.4% of children had normal Lp(a) and LDL cholesterol values and only 6.2% showed both elevated Lp(a) and LDL cholesterol levels. However, 16.6% of the sample, despite having normal LDL cholesterol, had elevated Lp(a) values. Multivariable analyses showed a significant association of LDL cholesterol both with Lp(a) values, and with the presence of elevated Lp(a) levels. For each mmol/L increase in LDL cholesterol the risk of having an elevated Lp(a) value increased by 73%. There was an inverse correlation between BMI z-score and Lp(a). Neither BP z-scores, nor other biochemical parameters were associated with Lp(a)., Conclusions: In our population more than one out of five children had elevated Lp(a) values, and in about 17% of children elevated Lp(a) values were present in the absence of increased LDL cholesterol. Our results suggest that Lp(a) measurement can be useful to better define the cardiovascular risk profile in children and adolescents already followed for the presence of other cardiovascular risk factors such as elevated BP, excess body weight and high LDL cholesterol., (© 2024. The Author(s).)

In younger generations, excess weight has reached very alarming levels. Excess weight in adults is associated with increased mortality and morbidity from cardiovascular disease. However, it is not easy to distinguish to what extent these effects are the result of obesity itself or how much is due to the various cardiovascular risk factors that often accompany excess weight. Several risk factors, such as hypertension, dyslipidemia, hyperuricemia, glucose intolerance, and type 2 diabetes mellitus, are already present in pediatric age. Therefore, early intervention with the goal of correcting and/or eliminating them is particularly important. In the child and adolescent with obesity, the first approach to achieve weight reduction and correct the risk factors associated with severe excess weight should always be non-pharmacologic and based on changing poor eating habits and unhealthy lifestyles. The purpose of this review is to give an update on non-pharmacological interventions to be implemented for cardiovascular prevention in children and adolescents with obesity, and their effectiveness. In particular, interventions targeting each individual cardiovascular risk factor will be discussed.

Background: It is not known whether, in children and adolescents with alterations in weight and/or blood pressure (BP), lifestyle modifications are associated with an improvement of early cardiac damage., Methods: In a pediatric population referred for excess weight, high BP, or both (n = 278, 10.6 (2.3) years), echocardiography was performed at enrollment and after 15 months of follow-up, during which participants received nonpharmacological treatment, based on correcting unhealthy lifestyles and improving dietary habits. Left ventricular mass was indexed for height (g/m 2.7 , LVMI), and an LVMI value higher than or equal to age- and gender-specific 95 th percentile was the criterion for defining left ventricular hypertrophy (LVH). Multiple linear and logistic regression analyses were carried out to determine associations between changes in BMI and BP z-scores and changes of LVMI values and LVH prevalence, from baseline to follow-up., Results: At baseline, 33.1% of study participants were hypertensive, 52.9% obese, and 36.3% had LVH. At follow-up, the prevalence of hypertension, obesity, and LVH was 18.7%, 30.2%, and 22.3%, respectively (p < 0.001 for all). A decrease in LVMI from 37.1 to 35.2 g/m 2.7 (p < 0.001) was observed. Only delta BMI z-score positively related to an improvement of LVMI. Reductions of BMI (OR = 0.22, 95% CI 0.07-0.64) and diastolic BP (OR = 0.64, 95% CI 0.42-0.93) z-scores from baseline to follow-up and family history of hypertension (OR = 0.36, 95% CI 0.16-0.78) were associated with a lower prevalence of LVH., Conclusions: In a pediatric population at cardiovascular risk, changing incorrect lifestyle and dietary habits is associated with both reduction of BMI and BP values and regression of early cardiac damage. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2023. The Author(s).)

Background: Pulse wave velocity (PWV) assessment represents a simple method to estimate arterial distensibility. At present, carotid-femoral PWV (cf-PWV) is considered the gold standard method in the non-invasive evaluation of the elastic properties of the aorta. On the other hand, the mechanical properties of muscular arteries can be evaluated on the axillo-brachial-radia axis by estimating the carotid-radial PWV (cr-PWV). While a number of studies have addressed these issues in adults, limited information is available on the respective features of cf-PWV and cr-PWV and on their modulating factors in children and adolescents at increased cardiovascular risk., Methods: The mechanical properties of the predominantly elastic (aorta) and muscular (axillo-brachial-radial axis) arteries were evaluated in a pediatric population characterized by either elevated blood pressure (BP) or excess body weight, and the main factors affecting cf-PWV and cr-PWV values in these individuals were investigated., Results: 443 children and adolescents (median age 11.5 years, 43.3% females) were enrolled; 25% had BP values >90th percentile and 81% were excess weight. The cf-PWV values were significantly lower than the cr-PWV values: median (Q1-Q3) = 4.8 m/s (4.3-5.5) and 5.8 m/s (5.0-6.5), respectively ( p < 0.001). The pubertal development ( p < 0.03), systolic BP and diastolic BP z-scores ( p = 0.002), heart rate ( p < 0.001), and waist-to-height ratio ( p < 0.005) were significantly associated with cf-PWV values. No significant association was found between BMI z-score and cf-PWV. Predictors of high cf-PWV (>95th percentile) were the heart rate (OR 1.07, 95%CI 1.04-1.10, p < 0.001) and waist-to-height ratio (OR 1.06, 95%CI 1.0-1.13, p = 0.04). The variables significantly related with cr-PWV values were diastolic BP z-score ( p = 0.001), heart rate ( p < 0.01), and HOMA index ( p < 0.02). No significant association was found between the cr-PWV and BMI z-score or waist-to-height ratio., Conclusions: Systolic and diastolic BP values and central obesity are associated with aortic stiffness in a population of children and adolescents at increased cardiovascular risk. In contrast, diastolic BP, heart rate, and levels of insulin resistance appear to be related to distensibility of the upper limb vascular district.

Lipoprotein(a) (Lp(a)) is made up of apoprotein(a) (apo(a)) and an LDL-like particle. The LPA gene encodes apo(a) and thus determines the characteristics and amount of apo(a) and Lp(a). The proportion of Lp(a) in each individual is genetically determined and is only minimally modifiable by the environment or diet. Lp(a) has important pro-atherosclerotic and pro-inflammatory effects. It has been hypothesized that Lp(a) also has pro-coagulant and antifibrinolytic actions. For these reasons, high Lp(a) values are an important independent risk factor for cardiovascular disease and calcific aortic valve stenosis. Numerous studies have been performed in adults about the pathophysiology and epidemiology of Lp(a) and research is under way for the development of drugs capable of reducing Lp(a) plasma values. Much less information is available regarding Lp(a) in children and adolescents. The present article reviews the evidence on this topic. The review addresses the issues of Lp(a) changes during growth, the correlation between Lp(a) values in children and those in their parents, and between Lp(a) levels in children, and the presence of cardiovascular disease in the family. Gaining information on these points is particularly important for deciding whether Lp(a) assay may be useful for defining the cardiovascular risk in children, in order to plan a prevention program early.

Excess weight and high waist circumference (WC) are associated with increased blood pressure (BP), starting from the pediatric age. Insulin resistance is associated with elevated BP in childhood. The aim of the study was to assess the role of insulin resistance in mediating the relationship between body mass index (BMI), WC, and BP values in a pediatric population referred to a cardio-pediatric center for the presence of one or more cardiovascular risk factors. In 419 children (mean age 10.7 [standard deviation, SD 2.5] years), the following parameters were collected both in basal conditions and after 18.6 (SD 9.3) months of follow-up during which a treatment based on lifestyle and dietary modifications was given: systolic and diastolic BP (SBP and DBP), WC, plasma glucose, and insulin values. The HOMA (Homeostasis Model Assessment)-index was considered as an expression of insulin resistance. At baseline there was a significant correlation between HOMA-index and SBP z-score (β = 0.081, p = 0.003), and insulin resistance was a mediator of the relationship between BMI and SBP z-score ( p = 0.015), and between waist circumference to height (WtHr) and SBP z-score ( p = 0.008). The effect of BMI z-score modifications on SBP z-score changes from baseline to follow-up was totally mediated by HOMA-index changes ( p = 0.008), while HOMA-index only partially mediated the effect of WtHr modifications on SBP z-score changes ( p = 0.060). Our study strongly suggests that, in a pediatric population at cardiovascular risk, the HOMA-index is an important mediator of the relationship between BMI, WC and SBP.

It has been argued that metabolically healthy obesity (MHO) does not increase the risk of cardiovascular disease. The aim of this study is to evaluate whether, in a population of obese children/adolescents, the metabolically unhealthy obesity (MUO) phenotype is associated with higher left ventricular mass index and/or higher prevalence of left ventricular hypertrophy than the MHO phenotype. We also tested whether the addition of an insulin resistance index (HOMA-index >90th percentile by sex and age) and the presence of hyperuricemia (serum uric acid >90th percentile by sex and age) to the definition of MUO better identified obese children with early cardiac damage. Left ventricular hypertrophy was defined as the presence of left ventricular mass index greater than or equal to the age- and sex-specific 95th percentile. The study population included 459 obese children (males 53.2%, mean age 10.6 [standard deviation, 2.6] years), of whom 268 (58.4%) were MUO. The left ventricular mass index was higher in MUO children than in MHO children (37.8 vs 36.3 g/m 2.7 , p=0.015), whereas the percentage of MUO children presenting left ventricular hypertrophy was only slightly higher in MUO children (31.1 vs 40%, p=0.06). Multiple linear regression analyses showed that the variables significantly associated with higher left ventricular mass index were male gender (p<0.01), Body Mass Index z-score (p<0.001) and Waist-to-Height-ratio (p<0.001). Multiple logistic regression analyses showed that the presence of left ventricular hypertrophy was only significantly associated with higher Body Mass Index z-score (p<0.05) and Waist-to-Height-ratio (p<0.05). In spite of the higher left ventricular mass index of MUO as compared to MHO children, the MUO phenotype was not a significant predictor of either higher left ventricular mass index or higher left ventricular hypertrophy prevalence. The MUO phenotype had a low predictive ability on the presence of left ventricular hypertrophy. The area under the receiver operating characteristic curve was 0.57 (sensitivity 0.64, 1-specificity 0.55). The addition of insulin resistance and hyperuricemia to the definition of MUO did not change the results observed with the standard definition of MUO at multivariable analysis. The MUO phenotype appears to be of little usefulness in identifying the early presence of cardiac damage in a large population of obese children and adolescents. Excess weight and abdominal obesity are confirmed as an important determinant of early organ damage in obese children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Genovesi, Tassistro, Giussani, Lieti, Patti, Orlando, Montemerlo, Antolini and Parati.)

Several studies describe the association between serum uric acid (SUA) and arterial stiffness in adults. Uric acid contributes through several mechanisms to the increase in blood pressure (BP) and adversely affects the insulin signaling pathway. Moreover, SUA predict the development of hypertension and insulin resistance up to type 2 diabetes. Early arterial stiffening, estimated by carotid-femoral pulse wave velocity (PWV), may already be present in pediatric age. Aim of our study was to investigate the relationship between SUA and PWV in a pediatric population and its interaction with insulin resistance and BP. In 322 children and adolescents (56.2% male, mean age 11.3 [SD 2.8] years), we measured weight, height, waist circumference, BP and PWV. We also assayed SUA and estimated glomerular filtration rate (eGFR) and calculated HOMA-index as a marker of insulin resistance. Simple and multiple regression analyses were performed to assess variables associated with PWV. Mediation models were applied to identify the direct and indirect effects of individual variables on PWV. On univariate analysis, age ( p < 0.001), waist circumference-to-height ratio ( p = 0.036), systolic and diastolic BP (SBP and DBP) z- score ( p < 0.001), heart rate ( p = 0.028), SUA ( p = 0.002), HOMA-index ( p < 0.001), and eGFR ( p = 0.014) were significantly associated with PWV. The multiple regression model showed that only age ( p = 0.028), SBP z- score ( p = 0.006), and heart rate ( p = 0.001) were significantly associated with PWV. The results were superimposable when the DBP z- score replaced the SBP z- score in the model. Mediation models showed that the effect of eGFR on PWV was fully mediated by SUA ( p = 0.015) and that the effect of SUA on PWV was totally mediated by HOMA-index ( p < 0.001). Both SUA ( p < 0.01) and HOMA-index ( p < 0.01) had a significant association with higher SBP (DBP) z- scores. The double mediation model including both BP and HOMA-index showed that the SUA effect on PWV was totally mediated by both variables ( p = 0.005, for HOMA-index, p = 0.004, for SBP z- score and p = 0.007, for combined effect). The results were superimposable when the DBP z- score replaced the SBP z- score in the model. In conclusion, insulin resistance and BP are both important mediators of the association between SUA and vascular stiffness in pediatric age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Genovesi, Montelisciani, Viazzi, Giussani, Lieti, Patti, Orlando, Antolini, Salvi and Parati.)

Arterial hypertension, dyslipidemia, alterations in glucose metabolism and fatty liver, either alone or in association, are frequently observed in obese children and may seriously jeopardize their health. For obesity to develop, an excessive intake of energy-bearing macronutrients is required; however, ample evidence suggests that fructose may promote the development of obesity and/or metabolic alterations, independently of its energy intake. Fructose consumption is particularly high among children, because they do not have the perception, and more importantly, neither do their parents, that high fructose intake is potentially dangerous. In fact, while this sugar is erroneously viewed favorably as a natural nutrient, its excessive intake can actually cause adverse cardio-metabolic alterations. Fructose induces the release of pro-inflammatory cytokines, and reduces the production of anti-atherosclerotic cytokines, such as adiponectin. Furthermore, by interacting with hunger and satiety control systems, particularly by inducing leptin resistance, it leads to increased caloric intake. Fructose, directly or through its metabolites, promotes the development of obesity, arterial hypertension, dyslipidemia, glucose intolerance and fatty liver. This review aims to highlight the mechanisms by which the early and excessive consumption of fructose may contribute to the development of a variety of cardiometabolic risk factors in children, thus representing a potential danger to their health. It will also describe the main clinical trials performed in children and adolescents that have evaluated the clinical effects of excessive intake of fructose-containing drinks and food, with particular attention to the effects on blood pressure. Finally, we will discuss the effectiveness of measures that can be taken to reduce the intake of this sugar., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Giussani, Lieti, Orlando, Parati and Genovesi.)

The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric oxide in hypertensive adolescents. The purpose of this review is to address the main biochemical and pathophysiological aspects of endothelin and nitric oxide involvement in hypertension and to summarize the available scientific evidence on their role in the onset and maintenance of high blood pressure in children and adolescents., (© 2021. The Author(s).)

Cardiometabolic risk factors are frequent in children and adolescents with excess weight. The aim of this study was to evaluate the effects of lifestyle modifications on alterations in lipid and glycemic profiles and uric acid values in a pediatric population at increased cardiovascular risk. The study involved 276 subjects with a mean age of 10.6 (2.3) years. Body mass index (BMI) z-score and biochemical parameters (serum low-density lipoprotein (LDL) cholesterol, triglycerides and uric acid and homeostasis model assessment to quantify insulin resistance (HOMA index)) were assessed at baseline and at the end of a median follow-up of 14.7 (12.4, 19.3) months. Throughout follow-up, all children received a non-pharmacological treatment based on increased physical activity, reduced sedentary activity and administration of a personalized, healthy and balanced diet. All children attended periodic quarterly control visits during follow-up. Multivariable statistical analyses showed that each BMI z-score point reduction at follow-up was associated with an 8.9 (95% CI −14.2; −3.6) mg/dL decrease in LDL cholesterol (p = 0.001), 20.4 (95% CI −30.0; −10.7) mg/dL in triglycerides (p < 0.001), 1.6 (95% CI −2.2; −1.0) in HOMA index (p < 0.001), and 0.42 (95% CI −0.66; −0.18) mg/dL in uric acid (p = 0.001) values. At each reduction of the BMI z-score by one point, the odds of presenting with insulin resistance and hyperuricemia at follow-up significantly decreased (OR 0.23, 95% CI 0.10−0.50, and OR 0.32, 95% CI 0.10−0.95, p < 0.001 and p < 0.05, respectively). Improvement of dietary habits and lifestyles may improve lipid and glycemic profiles and serum uric acid values in a pediatric population.

Adequate and balanced nutrition is essential to promote optimal child growth and a long and healthy life. After breastfeeding, the second step is the introduction of complementary feeding (CF), a process that typically covers the period from 6 to 24 months of age. This process is, however, still highly controversial, as it is heavily influenced by socio-cultural choices, as well as by the availability of specific local foods, by family traditions, and pediatrician beliefs. The Società Italiana di Pediatria Preventiva e Sociale (SIPPS) together with the Federazione Italiana Medici Pediatri (FIMP), the Società Italiana per lo Sviluppo e le Origine della Salute e delle Malattie (SIDOHaD), and the Società Italiana di Nutrizione Pediatrica (SINUPE) have developed evidence-based recommendations for CF, given the importance of nutrition in the first 1000 days of life in influencing even long-term health outcomes. This paper includes 38 recommendations, all of them strictly evidence-based and overall addressed to developed countries. The recommendations in question cover several topics such as the appropriate age for the introduction of CF, the most appropriate quantitative and qualitative modalities to be chosen, and the relationship between CF and the development of Non-Communicable Diseases (NCDs) later in life.

The prevalence of essential arterial hypertension in children and adolescents has grown considerably in the last few decades, making this disease a major clinical problem in the pediatric age. The pathogenesis of arterial hypertension is multifactorial, with one of the components being represented by incorrect eating habits. In particular, excessive salt and sugar intake can contribute to the onset of hypertension in children, particularly in subjects with excess weight. Babies have an innate predisposition for sweet taste, while that for salty taste manifests after a few weeks. The recent modification of dietary styles and the current very wide availability of salt and sugar has led to an exponential increase in the consumption of these two nutrients. The dietary intake of salt and sugar in children is in fact much higher than that recommended by health agencies. The purpose of this review is to explore the mechanisms via which an excessive dietary intake of salt and sugar can contribute to the onset of arterial hypertension in children and to show the most important clinical studies that demonstrate the association between these two nutrients and arterial hypertension in pediatric age. Correct eating habits are essential for the prevention and nondrug treatment of essential hypertension in children and adolescents.

There is limited information on the prevalence of dyslipidemia in the Italian pediatric population. Aim of the study was to evaluate total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglyceride levels, and associated factors in a large sample of Italian children, applying a micro-sampling procedure in the family pediatrician's office. In a population of 1910 children (50.2% males, age 7-11 years), 27.6% was overweight or obese and 28.3% had at least one parent with referred hypercholesterolemia. Total cholesterol and triglyceride levels were elevated in 4.5% and 23.5% of the subjects, respectively, while HDL cholesterol was below 40 mg/dl in 3.3%. Male gender (OR 1.58, 95% CI 1.01-2.49) and positive family history (OR 2.13, 95% CI 1.36-3.32) were independent predictors of hypercholesterolemia, while BMI z-score was associated with low HDL cholesterol (OR 1.46, 95% CI 1.13-1.88) and high levels of triglycerides (OR 1.39, 95% CI 1.26-1.55).Conclusion: The prevalence of dyslipidemia in our sample is worthy of attention. The study suggests the opportunity and feasibility to check for the presence of dyslipidemia at the family pediatrician's office. Familiarity is associated with high cholesterol levels, regardless of the children's weight class, while weight excess identifies subjects with the typical lipid profile of metabolic syndrome. What is Known: • Few data are available on the lipid profile in Italian children. • Early treatment of hypercholesterolemia is effective in reducing cardiovascular events later in life; there is no agreement on how to screen for dyslipidemia in childhood, however. What is New: • In a large sample of Italian children, familiarity doubles the risk of hypercholesterolemia, while increased BMI is associated with low HDL cholesterol levels and hypertriglyceridemia. • The pediatrician may perform an assessment of plasma lipids in his office as a first step to diagnose familial hypercholesterolemia.

Background: High blood pressure (BP) and excess weight can lead to early cardiovascular organ damage already in children. Carotid-femoral pulse wave velocity (cf-PWV) is the non-invasive gold standard method for assessing aortic stiffness, while carotid-radial PWV (cr-PWV) provides information on the distensibility of the upper limb arteries. The aim of this study was to evaluate the relationship of BP and BMI z-scores with arterial stiffness and left ventricular mass index (LVMI) in a pediatric population., Methods: In 343 children (57.7% males; age ± SD 11.7 ± 2.9 years), systolic (SBP) and diastolic (DBP) BP, BMI, cf-PWV, cr-PWV and LVMI were measured. A multiple linear regression model was used to assess the impact of BMI and SBP (or DBP) z-scores on cf-PWV, cr-PWV and LVMI., Results: About 21% of children were normal weight, 34% were overweight and 45% obese. Adjusted for possible confounders, SBP and DBP z-scores were significantly associated with cf-PWV ( p < 0.001), while only DBP z-scores were related to cr-PWV ( p < 0.01). BMI was neither associated with cf-PWV nor with cr-PWV values but was a strong predictor of LVMI (<0.001), whereas cardiac mass and BP z-scores were not related., Conclusions: Our study suggests that, in children, elevated BP values and excess weight may have different effects on the heart and the vessels in causing early cardiovascular alterations.

Children are defined as hypertensive when their blood pressure values equal or exceed the 95th percentile of the blood pressure value distribution in a pediatric population, according to gender, age and height. The population on which reference tables are based is of fundamental importance to establish the threshold values for the diagnosis of hypertension in pediatric age. Before 2017, both American and European guidelines used nomograms created in the same reference population which included children of all weight classes. Given the close and well-known association between hypertension and excess weight in childhood, the 2017 American guidelines proposed new reference nomograms excluding subjects with overweight and obesity from the "historical" reference population. Furthermore, the new American guidelines suggested a fixed cut-off of 130/80 mmHg, starting from 13 years and regardless of gender and height, to make the diagnosis of hypertension. In this document, the Italian Hypertension Society (SIIA) and the Italian Pediatric Society (SIP) jointly discuss a number of issues raised by the new American guidelines that involve the entire medical community, and also address the definition of arterial hypertension in the transition phase between childhood and adulthood.

Complementary feeding practices are debated among pediatricians, primarily regarding whether nutritional needs or developmental readiness should be prioritized in recommendations for starting complementary feeding. The aim of the present study was to analyze the timing of the start of complementary feeding and the related motivations with an 8-item online survey administered to active members of the Italian Society of Primary Care Pediatricians. The participation rate was 43.3% (350 of 808), and 213 (60.9%) and 137 (39.1%) of the participants chose items related to developmental readiness and nutritional needs, respectively, as the criteria for starting complementary feeding. Approximately 74% of the participants reported that they recommended starting complementary feeding between 5 and 6 months of age, 17% recommended starting before 5 months, and 8% recommended starting after 6 months. Predefined schemes were proposed by 38% of the participants, and a responsive feeding modality was proposed by 13%, while the majority (49%) recommended both modalities depending on family characteristics. Regarding recommendations based on nutritional needs, 89% of pediatricians reported providing indications concerning the quantity of meat consumed during the first year of life, and 91% reported recommending introducing added salt only after 12 months of age. Compared with pediatricians who emphasized developmental readiness, those who prioritized nutritional needs suggested earlier complementary feeding start and a higher use of predefined schemes and were more likely to make recommendations regarding meat quantity and added salt (p < 0.0001).Conclusions: Pediatricians who used a developmental readiness criterion for starting complementary feeding may less frequently provide nutritional advice to parents, even if a trend to harmonize the different positions regarding complementary feeding start time is emerging.What is Known:• Pediatricians make suggestions for introducing complementary feeding based on scientific evidence, local traditions, and personal beliefs.• Either infants' nutritional needs or their developmental readiness currently is used as determinant for the timing of complementary feeding.What is New:• More than 60% of Italian pediatricians consider developmental readiness a priority for introducing complementary feeding.• Pediatricians following the criterion of developmental readiness may less frequently give detailed nutritional advice.

Background: In pediatric age the prevalence of obesity is high. Obese children who do not have other risk factors than excess weight have been defined as "metabolically healthy obese" (MHO). Aim: The aim of this study is to evaluate, in a population of obese children, the prevalence of the MHO and "metabolically unhealthy obese" (MUO) phenotype. Furthermore, we evaluated the distribution of Uric Acid, HOMA index and Waist-Height ratio (W-Hr) in the MHO and MUO sub-groups and the impact of these non-traditional risk factors on the probability to be MUO. Methods: In 1201 obese children and adolescents [54% males, age (±SD) 11.9 (±3.0) years] weight, height, waist circumference, systolic (SBP) and diastolic (DBP) blood pressure, pubertal status, glucose, insulin, HDL cholesterol, triglycerides and Uric Acid serum values were assessed. MUO phenotype was defined as the presence of at least one of the following risk factors: SBP or DBP ≥ 90th percentile, glycaemia ≥ 100 mg/dl, HDL cholesterol <40 mg/dl, triglycerides ≥100 mg/dl (children <10 years) or ≥130 mg/dl (children ≥10 years). A multivariate logistic regression analysis was used to estimate the association between MUO phenotype and non-traditional cardiovascular risk factors. Results: The prevalence of the MUO status was high (61%). MUO subjects were more often male, older and pubertal ( p < 0.001). The levels of the three non-traditional risk factors were significantly higher in MUO children compared to MHO children ( p < 0.001) and all of them were independent predictors of the fact of being MUO [OR 1.41 (95% CI 1.24-1.69); 1.15 (95% CI 1.06-1.23) and 1.03 (95% CI1.01-1.05) for Uric Acid, HOMA index and W-Hr, respectively]. About 15% of MHO subjects had serum Uric Acid, HOMA index and W-Hr values within the highest quartile of the study population. Conclusion: The prevalence of MUO subjects in a large pediatric population is high and serum Uric Acid, HOMA index and W-Hr values are independent predictors of the probability of being MUO. A non-negligible percentage of subjects MHO has high values of all three non-traditional risk factors., (Copyright © 2020 Genovesi, Antolini, Orlando, Gilardini, Bertoli, Giussani, Invitti, Nava, Battaglino, Leone, Valsecchi and Parati.)

The aim of this study was to investigate the relationship between endothelin-1, nitric oxide, insulin resistance, and blood pressure in young subjects with a high prevalence of excess weight and/or elevated blood pressure. In a cohort of 238 children (mean age = 11.1 years), height, weight, waist circumference, and blood pressure were assessed. Body mass index, waist-to-height ratio, and blood pressure percentiles were calculated, and the children were classified as having excess weight and elevated blood pressure according to the International Obesity Task Force and the US blood pressure nomograms specific for gender, age and height, respectively. Endothelin-1 and nitric oxide production were assessed, and the homeostatic model assessment index was calculated. Forty-three percent of children were male, 71% had excess weight, and 37% had systolic and/or diastolic values above the ninetieth percentile. Plasma endothelin-1 and nitric oxide production were independently correlated (p < 0.05). In multivariate analyses, the HOMA index was associated with systolic and diastolic blood pressure (p = 0.01), and nitric oxide was independently related to diastolic blood pressure (p = 0.04), even after adjustment for measures of body composition. By using the waist-to-height ratio instead of BMI in the statistical model, the association between the homeostatic model assessment index and blood pressure was attenuated, while the results remained similar for nitric oxide. No correlation was found between endothelin-1 and blood pressure. In our study population, the correlation between nitric oxide and blood pressure and the lack of a relationship between endothelin-1 and blood pressure could be explained by an increase in the vasodilator effect of local and systemic nitric oxide, which counteracts the possible hypertensive effect of endothelin-1.

Adiponectin (Ad) is a cytokine produced by adipocytes that acts on specific receptors of several tissues through autocrine, paracrine, and endocrine signaling mechanisms. Ad is involved in the regulation of cell survival, cell growth, and apoptosis. Furthermore, Ad plays an important pathophysiological role in metabolic activities by acting on peripheral tissues involved in glucose and lipid metabolism such as skeletal muscle, and the liver. Adiponectin has anti-inflammatory, anti-atherogenic, and insulin-sensitizing effects. For this reason, low levels of Ad are associated with the development of cardiovascular complications of obesity in adulthood. Numerous studies have shown that, even in children and adolescents, Ad is associated with risk factors for cardiovascular diseases. In obese children, reduced levels of Ad have been reported and Ad plasma levels are inversely related with abdominal obesity. Moreover, lower Ad concentrations are associated with the development of metabolic syndrome, insulin resistance and hypertension in pediatric subjects. In addition to a higher prevalence of cardiovascular risk factors, plasma values of Ad are also inversely associated with early organ damage, such as an increase in carotid intima-media thickness. It has been suggested that low Ad levels in childhood might predict the development of atherosclerosis in adulthood, suggesting the possibility of using Ad to stratify cardiovascular risk in obese children. Some evidence suggests that lifestyle modification may increase Ad plasma levels. The aim of this review is to summarize the evidence on the relationship between Ad, obesity, metabolic alterations and hypertension in children and adolescents, and to address the possibility that Ad represents an early marker of cardiovascular risk in pediatric subjects. Furthermore, the effects of non-pharmacological treatment (weight loss and physical activity) on Ad levels are considered.

Objective and Methods: The study aimed at evaluating, in a large sample of Italian children, the reclassification of blood pressure categories with the new U.S. nomograms, obtained in a population of normal-weight children (American Academy of Pediatrics Clinical Practice Guidelines, AAP-CPG), compared with the Fourth Report/European Society of Hypertension (ESH) nomograms. The performance of the two classifications in identifying the presence of left ventricular hypertrophy was also assessed., Results: In 951 individuals referred to a Pediatric Center for Cardiovascular Risk Prevention, a 12% increase in the prevalence of children with blood pressure at least 90th percentile was observed by using the new nomograms. In the subsample of children aged at least 13 years, the application of the blood pressure fixed cutoff values of 120/<80 mmHg (for 'elevated' blood pressure) and of 130/80 mmHg (for hypertension) led to a change in the blood pressure category (worse or better) in about 30% of cases as compared with the AAP-CPG classification based on percentiles. Regarding the identification of individuals with left ventricular hypertrophy, the AAP-CPG classification led to an increase in the true positive fraction (sensitivity) of 5.5%, and to an increment of the false-positive fraction (1 - specificity) of 5.8%. The logistic regression model, adjusted for possible confounding factors, and the ROC curves obtained from the linear predictor of the model showed an identical performance of the Fourth Report/ESH and the AAP-CPG classifications., Conclusion: In our paediatric population, the AAP-CPG classification slightly increased the prevalence of elevated blood pressure values compared with the Fourth Report/ESH classification. Moreover, the application of more 'physiological' nomograms, based on a population of normal-weight children, did not yield any advantage in identifying individuals with early cardiac organ damage.

The atherosclerotic alterations that are the basis of cardiovascular diseases can start already in childhood. For this reason the prevention of cardiovascular diseases should be undertaken very early both in the general population and, in a targeted manner, in subjects at cardiovascular risk. Preventive strategies should include measures to encourage physical activity and correct eating habits and to reduce exposure to pollutants. The main actors responsible for carrying out these preventive interventions are the local and national political authorities. Moreover, particular attention should be paid to the first thousand days of life starting from conception, to prevent unfavorable epigenetic modifications. In addition to initiatives aimed at the general population, interventions should be planned by the medical community to assess the individual risk profile. The current obesity epidemic has in fact made it relatively frequent even among children and adolescents to find some cardiovascular risk factors known in adults such as arterial hypertension, dyslipidemia, glucose metabolism disorders and increased of uric acid values. The purpose of this review is to indicate lines of intervention for cardiovascular prevention in children and adolescents.

Background: Children's excess weight is a common problem due to low-quality diet and poor physical activity and is a risk factor associated with hypertension. Aim of this study was to assess the effect of a nonpharmacological multidisciplinary intervention on blood pressure (BP) and body weight in a population of children with excess weight and/or elevated BP., Methods: Children consecutively referred to a Prevention of Cardiovascular Risk Clinic by the primary care pediatrician from 2009 to 2015 were assessed at baseline and followed up over time., Results: Out of 273 children (median age 11.4 years, 55% male), 61% were excess weight only, 7% had elevated BP only, and 32% showed both conditions. The probability of reaching the clinical target (normal weight and BP values) at 1 year of follow-up was 19% (confidence interval [CI]: 14%; 24%) and increased up to 38% (CI: 28%; 47%) at 3 years. At 1 year of follow-up, in the overall population both body mass index (BMI) and systolic BP z-scores decreased significantly from 1.77 to 1.47 and from 0.99 to 0.52, respectively (P < 0.0001). BP was significantly reduced in both children with elevated BP only (reduction = 0.91, P = 0.0157) and subjects with excess weight and elevated BP (reduction = 0.89, P < 0.0001). Variables significantly related with systolic BP z-score at 1 year of follow-up were baseline systolic BP z-score and BMI z-score reduction during follow-up (P < 0.001 and P = 0.0003, respectively)., Conclusion: Our data demonstrate the efficacy of lifestyles modification on weight and BP in children, both when elevated BP and excess weight were present as distinct clinical problems and in the case of their association.

The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.

Over the past 60 years there has been a dramatic increase in the prevalence of overweight in children and adolescents, ranging from 4% in 1975 to 18% in 2016. Recent estimates indicate that overweight or obese children and adolescents are more than 340 million. Obesity is often associated with hypertension, which is an important cardiovascular risk factor. Recent studies show that the presence of hypertension is a frequent finding in the pediatric age. Hypertensive children easily become hypertensive adults. This phenomenon contributes to increasing cardiovascular risk in adulthood. Primary hypertension is a growing problem especially in children and adolescents of western countries, largely because of its association with the ongoing obesity epidemic. Recently, it has been hypothesized that a dietary link between obesity and elevated blood pressure (BP) values could be simple carbohydrate consumption, particularly fructose, both in adults and in children. Excessive intake of fructose leads to increased serum uric acid (SUA) and high SUA values are independently associated with the presence of hypertension and weaken the efficacy of lifestyle modifications in children. The present review intends to provide an update of existing data regarding the relationship between BP, simple carbohydrates (particularly fructose), and uric acid in pediatric age. In addition, we analyze the national policies that have been carried out over the last few years, in order to identify the best practices to limit the socio-economic impact of the effects of excessive sugar consumption in children.

Objective: To determine plasma aldosterone concentration (PAC) and plasma renin concentration (PRC) and aldosterone-to-renin ratio (ARR) values in a population attending a Clinic for Cardiovascular Risk Assessment in Children., Methods: We assessed ARR and associated factors in a cohort of 287 children (137 female, 4-18 years). Weight and blood pressure (BP) were recorded. PAC (ng/dl) and PRC (mU/l) were measured using direct immunochemiluminescent assays. Data were examined by sex and according to four age classes., Results: Median PAC was similar from the youngest to the oldest age class ranging from 7.5 to 9.9 ng/dl in males and from 11.0 to 12.6 ng/dl in females. Median PRC was also similar across age classes in males ranging from 58.2 to 55.5 mU/l, whereas it progressively decreased from 61.5 to 36.6 mU/l in females (P < 0.01). Median PRC was higher in prepubertal than in pubertal females only (53.6 vs. 40.2 mU/l, P < 0.03). As a result ARR was unchanged with increasing age in males (from 0.18 to 0.19), whereas in females it increased from 0.19 to 0.36 (P < 0.03). After adjusting for body weight, BP and other possible confounders, age was inversely related with PRC and directly with PAC and ARR (P < 0.001 for all), in females only. No relationship was found in both sexes between ARR values, BP, weight and family history of hypertension., Conclusion: In our children population, ARR is lower than in adults and diverges with increasing age between sexes, due to the age and puberty driven fall in PRC observed only in females. BP and weight are not associated with ARR distribution.

The influence of feeding patterns on the growth of infants and how salt is included in the diet are unknown in the area of West Bengal, India. A cross-sectional study was carried on 517 infants (median age 6.5 months). Negative Z-scores were observed for all anthropometric parameters. About 72.7% of infants aged 0-6 months received exclusive breastfeeding. In the 6-12-month-old group (n = 235), 91.5% had salt added to foods. In a regression model adjusted for age, a low salt diet resulted a significant factor in increasing weight-for-length and BMI for age z-scores, with increments equal to 0.637 SD (p = 0.037) and 0.650 SD (p = 0.036), respectively. In West Bengal infants showing poor growth, breastfeeding was associated with better anthropometric indexes, but early in life salt is added to their diet. Early life low weight coupled with high salt intake may be a risk factor for arterial hypertension in Indian children.

Background: Sleep in childhood and adolescence is crucial for mental and physical health; however several researches reported an increasing trend towards a sleep deprivation in this age. Due to the lack of recent epidemiological studies in Italy, the aim of our study was to depict sleep habits and patterns in Italian children aged 1-14 years and to evaluate their relationships with video devices use (TV, tablet, smartphone, PC) and evening/night child activities., Methods: A structured interview was conducted during 2015 by 72 Family Pediatricians in 2030 healthy children aged 1-14 years by a cross-sectional survey named "Ci piace sognare". Total sleep duration was calculated, 2015 National Sleep Foundation Recommendations were used as reference. Optimal sleepers were defined children sleeping in own bed all night without awakenings. Multivariable median regression was performed to identify predictors of sleep duration and multivariable logistic regression for predictors of optimal sleep., Results: Total sleep duration and numbers of awakenings decreased with age. Only 66.9% of children had sleep duration in agreement with Recommendations (50% in 10-14 years group). Before sleeping 63.5% of children used video devices (39.6% at 1-3 years), 39.1% read, 27.5% drank and 19.5% ate. Bottle users at bedtime were 30.8% at 1-3 years, 16.6% at 3-5 years and 4.9% at 5-7 years. Overall, 23.4% of children changed sleeping place during the night, 22.4% referred sleeping problems in the first year of life. Video devices use was negative predictor of sleep duration (-0.25 h [95%CI:-0.35,-0.14], p < 0.001). Optimal sleep was inversely related with bedroom TV (OR 0.63 [0.50,0.79], p < 0.001), with sleeping disorders in the first year (OR 0.62 [0.48,0.80], p < 0.001)), with bottle use (OR 0.64 [0.44,0.94], p < 0.05) and posivively related with high mother's education level (OR 1.44 [1.11,1.88], p < 0.01)., Conclusions: About one third of 1 to 14 year Italian children sleep less than recommended, one half in teenage. Modifiable risk factors for sleep abnormalities such as video devices use, bedroom TV and bottle use should be target of preventive strategies for a correct sleep. Pediatricians should give priority to the identification of sleep disorders early in life.

The present article intends to provide an update of the article "Focus on prevention, diagnosis and treatment of hypertension in children and adolescents" published in 2013 (Spagnolo et al., Ital J Pediatr 39:20, 2013) in this journal. This revision is justified by the fact that during the last years there have been several new scientific contributions to the problem of hypertension in pediatric age and during adolescence. Nevertheless, for what regards some aspects of the previous article, the newly acquired information did not require substantial changes to what was already published, both from a cultural and from a clinical point of view. We felt, however, the necessity to rewrite and/or to extend other parts in the light of the most recent scientific publications. More specifically, we updated and extended the chapters on the diagnosis and management of hypertension in newborns and unweaned babies, on the use and interpretation of ambulatory blood pressure monitoring, and on the usefulness of and indications for physical activity. Furthermore, we added an entirely new section on the role that simple carbohydrates (fructose in particular) and uric acid may play in the pathogenesis of hypertension in pediatric age.

Primary hypertension is a growing concern in children because of the obesity epidemic largely attributable to western lifestyles. Serum uric acid is known to be influenced by dietary habits, correlates with obesity, and could represent a risk factor for hypertension. Preliminary studies in children highlighted uric acid as a potentially modifiable risk factor for the prevention and treatment of hypertension. The effect of lifestyle changes (increase of physical activity and dietary modifications) on blood pressure values, weight status, and serum uric acid levels in a cohort of 248 children referred for cardiovascular risk assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of children were obese and 50% showed blood pressure values >90th percentile. At follow-up, a significant improvement in weight class (24% obese;P<0.0001) and blood pressure category (22% >90th percentile;P<0.0001) was found. Systolic blood pressure z-score (P<0.0001), uric acid value (P=0.0056), and puberty at baseline (P=0.0048) were independently associated with higher systolic blood pressure z-score at follow-up, whereas a negative association was observed with body mass index z-score decrease during follow-up (P=0.0033). The risk of hypertension at follow-up was associated with body mass index (P=0.0025) and systolic blood pressure (P<0.0001) z-score at baseline and inversely related to delta body mass index (P=0.0002), whereas the risk of showing hypertension ≥99th percentile was more than doubled for each baseline 1 mg/dL increase of serum uric acid (P=0.0130). Uric acid is a powerful determinant of blood pressure over time, independent of lifestyle modifications., (© 2016 American Heart Association, Inc.)

Background: Hypertension and obesity in childhood are related to early cardiac damage, as left ventricular hypertrophy. Few studies have analyzed the independent effects of hypertension and weight excess on diastolic function and left ventricular geometry., Objective: We studied the effects of weight, waist circumference (as an index of fat distribution) and blood pressure on left ventricular mass index, the risk of left ventricular hypertrophy, diastolic function and left ventricular geometry in 526 children (237 girls, age range 6-15 years)., Methods: Children were divided into normotensive, prehypertensive and hypertensive (US Nomograms) groups, and into normal-weight, overweight, and obese (International Obesity Task Force classification) groups. Left ventricular mass index, diastolic function and left ventricular geometry were assessed., Results: SBP z-scores and blood pressure categories significantly influenced cardiac mass (P < 0.001 and P = 0.02, respectively) and the prevalence of left ventricular hypertrophy (P < 0.001 and P < 0.05, respectively). Obesity, BMI, and waist circumference z-scores were significantly associated with an increment in E/Em ratio (P < 0.001, P < 0.01, and P < 0.01, respectively). Increasing blood pressure values and the presence of prehypertension (P < 0.05) and hypertension (P < 0.003), but not weight excess, were associated with concentric cardiac remodeling. In contrast, concentric hypertrophy was associated with hypertension (P < 0.01), obesity (P < 0.001), and increasing waist circumference (P < 001)., Conclusions: Blood pressure values and hypertension are independently associated with an increase of cardiac mass and the presence of cardiac hypertrophy. Obesity and waist circumference, but not hypertension, are associated with a worsening of diastolic function, whereas only hypertensive children show high prevalence of concentric remodeling. Blood pressure and body weight and fat distribution have an independent and different impact on left ventricular structure and function in children.

Objectives: Hyperuricemia has been shown to be a strong correlate of hypertension in children. However, the complex interaction between serum uric acid (UA), systemic blood pressure (BP), and possibly confounding factors has been elucidated only in part., Methods: We evaluated office BP as well as clinical and biohumoral parameters in a cross-sectional cohort of 501 children (280 boys and 221 girls) aged between 6 and 18 years (mean = 10.8 years) consecutively referred for cardiovascular risk assessment., Results: Overall, 156 (31.1%) were normotensive, 122 (24.4%) showed transient hypertension, 87 (17.4%) had prehypertension, and 136 (27.1%) had hypertension. Altogether 33.3% and 40.5% of the study group were overweight or obese, respectively. There was a trend toward greater weight and waist circumference and higher BMI, Homeostasis Model Assessment index, and UA levels as the BP categories rose. Moreover, the prevalence of pubertal children, obesity, and waist-to-height ratio above 0.50 progressively increased from lower to upper BP categories. After adjusting for puberty, gender, BMI (z-score), Homeostasis Model Assessment index, and renal function, UA was found to be directly related to systolic and diastolic BP values (P = .03). Using normotensive children for comparison, the risk of showing prehypertension or hypertension increased by at least 50% for each 1 mg/dL UA increase (P < .01), whereas it doubled for children in the top gender-specific UA quartile (P < .03)., Conclusions: Increased UA levels showed an independent predictive power for the presence of higher BP levels among a cohort of children at relatively high cardiovascular risk.

Objective: Aim of the study was to assess the role of family history, physical activity and parental smoking in the prediction of BMI, SBP and hypertension risk in children., Participants and Methods: In a paediatric primary care setting, a sample of 1310 children aged 5-14 years was systematically selected by 48 family paediatricians in northern Italy. BMI, waist circumference-to-height ratio (WtHr), SBP and DBP were measured and the information on the presence of small birth weight for gestational age (SGA) and early adiposity rebound (EAR) was collected. Data concerning exercise, video time, family history for cardiovascular diseases and parental smoking were derived from parental interview. Data were collected using an 'ad hoc designed' electronic sheet available online., Results: Multiple linear regression showed that the presence of EAR, low exercise (<2 h/week), high video time (>2  h/day TV/videogames/computer) and parental smoking were associated to higher BMI (z-score; P < 0.005). Age, BMI (z-score), WtHr, presence of SGA, low exercise, high video time and family history of cardiovascular diseases were associated to SBP values (P < 0.03). Logistic regression analysis showed that factors related to risk of hypertension and prehypertension were BMI (z-score; odds ratio, OR 2.63; 95% confidence interval, CI 2.12-3.28), WtHr (OR 1.13; 95% CI 1.10-3.28) and low exercise (OR 1.58; 95% CI 1.12-2.24; P <0.01)., Conclusion: Our study demonstrates that a simple tool like a cardiovascular multi-item sheet can provide useful information to paediatricians for child health. Physical exercise plays a pivotal role in obesity prevention and protection from hypertension risk.

The European Society of Hypertension has recently published its recommendations on prevention, diagnosis and treatment of high blood pressure in children and adolescents. Taking this contribution as a starting point the Study Group of Hypertension of the Italian Society of Pediatrics together with the Italian Society of Hypertension has conducted a reappraisal of the most recent literature on this subject. The present review does not claim to be an exhaustive description of hypertension in the pediatric population but intends to provide Pediatricians with practical and updated indications in order to guide them in this often unappreciated problem. This document pays particular attention to the primary hypertension which represents a growing problem in children and adolescents. Subjects at elevated risk of hypertension are those overweight, with low birth weight and presenting a family history of hypertension. However, also children who do not present these risk factors may have elevated blood pressure levels. In pediatric age diagnosis of hypertension or high normal blood pressure is made with repeated office blood pressure measurements that show values exceeding the reference values. Blood pressure should be monitored at least once a year with adequate methods and instrumentation and the observed values have to be interpreted according to the most updated nomograms that are adjusted for children's gender, age and height. Currently other available methods such as ambulatory blood pressure monitoring and home blood pressure measurement are not yet adequately validated for use as diagnostic instruments. To diagnose primary hypertension it is necessary to exclude secondary forms. The probability of facing a secondary form of hypertension is inversely proportional to the child's age and directly proportional to blood pressure levels. Medical history, clinical data and blood tests may guide the differential diagnosis of primary versus secondary forms. The prevention of high blood pressure is based on correct lifestyle and nutrition, starting from childhood age. The treatment of primary hypertension in children is almost exclusively dietary/behavioral and includes: a) reduction of overweight whenever present b) reduction of dietary sodium intake c) increase in physical activity. Pharmacological therapy will be needed rarely and only in specific cases.

Background: Adiponectin (AD) reduces the risk of hypertension because of its anti-inflammatory, antiatherogenic, and insulin-sensitizing properties. The study described here was done to evaluate the interrelationships of AD, blood pressure (BP), obesity, body-fat distribution, puberty, and insulin resistance in a selected group of children., Methods: The study was a cross-sectional, observational study of 186 children ranging in age from 5-18 years and grouped according to weight class (obese (OB), n = 100; normal weight (NW), n = 86) and BP category (hypertensive (HT) n = 79; normotensive (NT); n = 107). The children were also classified on the basis of fat distribution (waist circumference/height ratio). Their blood glucose, insulin, and AD concentrations were assayed, and their homeostatic model assessment (HOMA) index was calculated as an estimate of insulin resistance., Results: Serum AD was lower in OB-HT (7,111±4,163ng/ml) than in NW-NT (12,622±6,276ng/ml) children (P < 0.0001). Intermediate values of AD were found in OB-NT (9,099±3,988ng/ml) and NW-HT (9,808±4,211ng/ml) children. Weight and waist circumference-to-height ratio, BP category, and pubertal stage were all independently and inversely associated with serum levels of AD (P < 0.02). In a logistic regression model, after adjustment for body mass index (BMI) and waist circumference/height ratio, serum levels of AD maintained an independent association with hypertension (P < 0.05), as did also the HOMA index (P < 0.05). A reduction of 10 times (i.e., one unit on the log(10) scale) in AD serum levels was associated with a 50% increased probability of having hypertension., Conclusions: In childhood, serum levels of AD are inversely related to hypertension. This relationship is partly independent of obesity, fat distribution, and insulin resistance. Low values of AD in both OB and NW children are associated with a higher probability of hypertension.

Objective: The aim of the present study was to evaluate whether insulin resistance [as measured by Homeostasis Model Assessment (HOMA) index] has an effect on prehypertension and hypertension risk in children after acknowledging the role of BMI and waist-to-height ratio., Methods: We studied a sample of 377 children 10.5 ± 2.3 years old who had a first diagnosis of hypertension or family history of cardiovascular disease. In this sample all weight classes were represented. The HOMA index was standardized by a linear regression model including BMI, waist-to-height ratio and pubertal status., Results: The role of BMI and waist-to-height ratio on the risk of prehypertension and hypertension was confirmed by univariate logistic regression models, odds ratio of 1.59 [95% confidence interval (CI) = 1.27-2.00] for BMI, and 1.56 (95% CI = 1.06-2.31) for waist-to-height ratio (>50 vs. ≤50%). When standardized HOMA index was added to BMI or waist-to-height ratio in a multivariate model, it gave a significant independent contribution to explain the risk of prehypertension and hypertension. Odds ratio was 1.23 (95% CI = 1.01-1.51) in the model with BMI, and 1.23 (95% CI = 1.01-1.50) in the model with waist-to-height ratio. The role of HOMA index was confirmed when continuous values of systolic and diastolic blood pressure (standardized by age, sex and height) were analysed, instead of hypertension category., Conclusions: These results strongly support the hypothesis that in children, insulin resistance plays a role on hypertension independently from obesity, fat distribution and puberty across weight classes.

Background: Childhood hypertension is an established predictor of adult hypertension and organ damage, an underestimated problem in developing countries. The aim of the study was to assess the prevalence of arterial hypertension, as well as the relationship of blood pressure values and weight class and urinary abnormalities in 1176 children (aged 5-12 years) from a suburban area south of Kolkata, India., Method: Arterial blood pressure, height, weight and waist circumference were measured. Weight class was defined according to the tables of the International Obesity Task Force. Urinalysis was performed with reagent strips to detect glucosuria, microhematuria and proteinuria., Results: The majority of children (74.7%) were underweight and 5.2% had systolic and/or diastolic blood pressure values higher or equal to the 95th percentile, according to the National High Blood Pressure Education Program normograms. Hypertension had a high prevalence both in underweight children (4.3%) and in normal-weight children (6.9%) and significantly increased in the rare overweight children (4/20, 20%). A fraction of 8.5% of hypertensive children had urinary abnormalities (microhematuria only) vs. 12.5% in nonhypertensive children (P value 0.36)., Conclusion: Prevalence of hypertension in North-Eastern Indian children is higher than in Western countries and only partly associated to weight class. Causes of hypertension do not seem to be related to overt kidney disease and remain to be elucidated.

Background: To assess the prevalence of hypertension (H), prehypertension (PH), and transient elevated blood pressure (TH) and their relationship with weight class and waist circumference (WC) in an unselected population of Northern Italian children., Methods: A cross-sectional study was conducted in 5,131 children (5-11 years). Weight class was defined according to the International Obesity Task Force references, H and PH according to the National High Blood Pressure Education Program. A child was classified as having PH or H when systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) at first screening were > or =90th percentile and the mean of three subsequent measures was between the 90th and 95th or > or =95th percentile, respectively. When BP values at the first screening were > or =90th percentile but the mean of three subsequent measures was <90th percentile the child was classified as having TH., Results: A proportion of 3.4% presented H, 2.7% PH, and 10.4% TH, 20% overweight, and 6% obesity. Weight class and WC were significantly associated to an increased risk of falling into any of the hypertensive categories. In children with TH BP z-scores of the mean of the three subsequent measurements following the first screening were significantly higher than BP z-scores observed in normotensive children (P value <0.001)., Conclusions: Weight class and WC are associated with BP. This is observed not only for H but also for PH, and for nonsustained forms of H. Prospective studies are needed to assess whether children with PH and TH will develop sustained H.

Objective: To investigate the ability of BMI and waist circumference, single and combined, in identifying children who are at risk of hypertension and in influencing absolute blood pressure values., Methods: The body weight, height, waist circumference and blood pressure of 4177 5-11-year-old school children [2005 (48%) girls] were collected. Elevated blood pressure was defined if either systolic or diastolic blood pressure values or both were more than the 95th percentile according to sex, age and height (US normative blood pressure tables). Overweight and obese children were defined according to International Obesity Task Force BMI cut-offs., Results: The prevalence of hypertension was 4.1% and increased together with weight class: 1.4% (n = 42/3076) in normal weight, 7.1% (n = 59/827) in overweight and 25% (n = 69/274) in obese (P < 0.001). Only BMI and waist circumference showed a remarkable ability to discriminate hypertensive children (areas under receiver operating characteristic curves, 0.84 and 0.76, respectively). The multivariate analysis showed that z-scores for both BMI and waist circumference were significantly related to the risk of hypertension with odds ratios of 3.59 (95% confidence interval, 2.55, 5.06) and 1.20 (95% confidence interval, 1.04, 1.39), respectively, after adjusting for sex and age. When the weight class was included in the multivariate analysis, waist circumference retained its ability to identify hypertensive children only in the obese class (odds ratio, 1.44; 95% confidence interval, 1.21, 1.72; P < 0.01). When considering blood pressure as a continuous variable, both weight class and waist circumference showed a significant effect on systolic and diastolic blood pressure absolute values (P < 0.01). The effect of waist circumference on blood pressure values was maintained even when corrected for BMI., Conclusion: High blood pressure is strongly associated with excess weight. Waist circumference improves the ability of BMI to identify hypertension in obese children. Waist circumference is related to absolute blood pressure values in all weight classes.

In adults, initial stages of hypertension are associated with elevated sympathetic drive and significant alterations in indirect autonomic markers. There is growing evidence that children in the highest-pressure percentiles will be more likely to develop hypertension in adulthood, although mechanisms are not understood. We assessed whether computer analysis of RR interval and arterial blood pressure variability could detect early autonomic alterations in childhood hypertension, as assessed by noninvasive time and frequency domain measures of baroreflex regulation. We studied 75 children, subdivided in 3 subgroups of similar age (9.7+/-0.2 years): control subjects, prehypertensive children (ie, children with arterial pressure values >90th and <95th percentile for age, gender, and height), and children in the hypertensive range (ie, >95th percentile; systolic arterial pressure: 97+/-3/57+/-2, 121+/-5/70+/-1, and 128+/-2/80+/-2 mm Hg, respectively). We observed that hypertensive children demonstrate a significant impairment of the baroreflex as compared with control subjects (index alpha: 20+/-2 and 40+/-4 ms/mm Hg; spontaneous baroreflex slope: 20+/-2 and 37+/-5; ms/mm Hg; P<0.05 in both cases) and reduced RR variance. A similar baroreflex impairment is also observed in children whose arterial pressure falls short of this limit, ie, in the prehypertensive range. In conclusion, hypertensive children display a marked baroreflex impairment. A similar baroreflex impairment is also observed in the prehypertensive state. Baroreflex assessment could furnish additional information in the clinical assessment of pediatric hypertension.

Objective: To verify the possibility to use the Anthropometric Health Report (AHR), containing the BMI value, for overweight/obesity evaluation in 5-6-years-old children., Design: Between January 2001 and December 2004, 4619 AHR had been examined. BMI values were compared with age and sex-specific BMI cutoffs, according to Cole, as well as with a single BMI value, calculated as the mean between boys and girls cutoff at 5.5 yrs of age., Setting: 4619 children of ASL Provincia di Milano 2, aged 5-6 years were examined. PARTECIPANTS: 81 Family Pediatricians working in the area of Provincia di Milano 2., Main Outcome Measures: An easily available and low cost method for epidemiological studies on overweight and obesity in childhood., Results: During the study period the number of examined children increased constantly (from 8% to 30% of the overall resident population). Also the correct compilation of the AHR raised (from 47% to 95%). The elevated percentage of overweight children (range 17-23%) and obese children (range 5-7%) in the study group confirms other published data in this age group. The use of a single BMI cutoff did not affect significantly (p > 0.05) the results with regard to the use ofage and sex-specific cut offs. Required time for carrying out the study was limited. Efficiency increased during the study: the number ofAHRs analyzed per hour increased from 37.5 in 2001 to 103.5 in 2004. Some critical points about current uses of AHR are discussed, Conclusions: AHR could be used for epidemiological purposes. It could be considered an useful method in monitoring overweight/obesity in 5-6 years old children as well as in checking the efficacy of prevention and therapeutic strategies.

Objectives: To study the prevalence of high blood pressure (BP) in an Italian paediatric population, and to verify whether in this population elevated BP values are associated with overweight (OW)., Study Design: Children (1206 males, 1210 females) from the lower-grade public schools (ages 6-11 years) were studied. Body weight, height and BP were measured in each child. Elevated BP was defined if resting systolic and/or diastolic BP values equalled or exceeded the 95th percentile according to gender, age and height, based on the US normative BP tables. Overweight children were identified using four different methods: (1) the classification based on the relative body weight; (2) the French references by Rolland-Cachera et al. (Am J Clin Nutr 1982; 36:178-184); (3) the International Obesity Task Force charts; and (4) the Italian charts defined by Cacciari et al. (Eur J Clin Nutr 2002; 56:171-180)., Results: The prevalence of high BP in our population was 4.2% and was significantly higher in females (65/1210 = 5.4%) than in males (37/1206 = 3.1%), P = 0.005. The different methods used to define OW provide different estimates of OW prevalence (from 17.0 to 38.6%). The percentage of high BP subjects was significantly higher in OW than in normal-weight children regardless of the method used for the definition of the weight class (P < 0.0001), in both genders. In addition, for each age range, absolute systolic and diastolic BP values were higher in OW as compared to normal-weight children both in males and in females (P < 0.0001)., Conclusions: Our study indicates the importance of performing BP screenings in the paediatric population, and to promote interventions that may reduce the prevalence of OW in children.