Wall Properties of Elastic and Muscular Arteries in Children and Adolescents at Increased Cardiovascular Risk.

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.

Evidence and Uncertainties on Lipoprotein(a) as a Marker of Cardiovascular Health Risk in Children and Adolescents.

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.

Association between lifestyle modifications and improvement of early cardiac damage in children and adolescents with excess weight and/or high blood pressure.

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/m2.7, LVMI), and an LVMI value higher than or equal to age- and gender-specific 95th 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/m2.7 (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.

Role of Insulin Resistance as a Mediator of the Relationship between Body Weight, Waist Circumference, and Systolic Blood Pressure in a Pediatric Population.

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 (ß = 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.

Association of obesity phenotypes with left ventricular mass index and left ventricular hypertrophy in children and adolescents.

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/m2.7, 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.

Uric acid and arterial stiffness in children and adolescents: Role of insulin resistance and blood pressure.

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.

Fructose Intake, Hypertension and Cardiometabolic Risk Factors in Children and Adolescents: From Pathophysiology to Clinical Aspects. A Narrative Review.

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.

Impact of Lifestyle Modifications on Alterations in Lipid and Glycemic Profiles and Uric Acid Values in a Pediatric Population.

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.

Recommendations on Complementary Feeding as a Tool for Prevention of Non-Communicable Diseases (NCDs)-Paper Co-Drafted by the SIPPS, FIMP, SIDOHaD, and SINUPE Joint Working Group.

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.

Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents.

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.

Salt and Sugar: Two Enemies of Healthy Blood Pressure in Children.

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.

Lipid profile assessed in the family pediatrician's office: the COLIBRI'- SIMPeF study.

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.

Blood Pressure and Body Weight Have Different Effects on Pulse Wave Velocity and Cardiac Mass in Children.

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.

How to Apply European and American Guidelines on High Blood Pressure in Children and Adolescents. A Position Paper Endorsed by the Italian Society of Hypertension and the Italian Society of Pediatrics.

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.

Cardiovascular Risk Factors Associated With the Metabolically Healthy Obese (MHO) Phenotype Compared to the Metabolically Unhealthy Obese (MUO) Phenotype in Children.

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.

Do the opinions of pediatricians influence their recommendations on complementary feeding? Preliminary results.

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.

Adiponectin and Cardiovascular Risk. From Pathophysiology to Clinic: Focus on Children and Adolescents.

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.

Prevention of Cardiovascular Diseases in Children and Adolescents.

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.

Nomograms to identify elevated blood pressure values and left ventricular hypertrophy in a paediatric population: American Academy of Pediatrics Clinical Practice vs. Fourth Report/European Society of Hypertension Guidelines.

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.

Endothelin-1/nitric oxide balance and HOMA index in children with excess weight and hypertension: a pathophysiological model of hypertension.

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.