Comparison of Performance in the Six-Minute Walk Test (6MWT) between Overweight/Obese and Normal-Weight Children and Association with Haemodynamic Parameters: A Cross-Sectional Study in Four Primary Schools.

Physical activity plays a pivotal role in preventing obesity and cardiovascular risks. The six-minute walk test (6MWT) is a tool to assess functional capacity and predict cardiovascular events. The aim of this cross-sectional study was to compare the performance and haemodynamic parameters before and after a 6MWT between obese/overweight vs. normal-weight children (average age 8.7 ± 0.7 years) participating in a project involving four primary schools in South Verona (Italy). Validated questionnaires for physical activity and diet, as well as blood drops, were collected. Overweight or obese children (OW&OB; n = 100) covered a shorter 6MWT distance compared to normal-weight children (NW, n = 194). At the test's conclusion, the OW&OB group exhibited a higher Rate Pulse Product (RPP = Systolic Blood Pressure × Heart Rate) as compared to the NW. Body Mass Index, waist-to-height ratio, fat mass by electrical impedance, and trans fatty acids showed direct correlations with pre and post-test haemodynamic parameters, such as RPP, and inverse correlations with oxygen saturation. OW&OB children demonstrated lower performance in this low-intensity exercise test, along with an elevated haemodynamic response. Excess fat in childhood can be considered a risk factor for haemodynamic stress, with potential deleterious consequences later in life. Efforts should be initiated early to break this cycle.

Subclinical Target Organ Damage in a Sample of Children with Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

Background and Objectives: Hypertension and vascular damage can begin in adolescents affected by Autosomal Dominant Polycystic Kidney Disease (ADPKD). This study aimed to evaluate markers of vascular damage and left ventricular geometry in a sample of children with ADPKD. Materials and Methods: Several vascular measurements were obtained: ambulatory blood pressure monitoring (ABPM), carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), pulse wave velocity (PWV), and echocardiographic measurements (relative wall thickness (RWT) and left ventricular mass index (LVMI)). Results: Eleven ADPKD children were recruited (four females and seven males, mean age 9.5 ± 3.2 years). Four children were hypertensive at the ABPM, five were normotensive, and for two ABPM was not available. RWT was tendentially high (mean 0.47 ± 0.39). Eight patients had concentric cardiac remodeling, while one patient had cardiac hypertrophy. cIMT was above the 95° percentile for sex and height in 80% of the children (0.5 ± 0.005 mm). The average PWV and cDC were between the normal range (5.5 ± 4.6 m/s and 89.6 ± 16.1 × 10-3/KPa, respectively). We observed a positive correlation between the PWV and RWT (r = 0.616; p = 0.044) and a negative correlation between cDC and RWT (r = -0.770; p = 0.015). Cardiovascular damages (cIMT > 95° percentile) were found in normotensive patients. Conclusions: Increased RWT and high cIMT, indicating subclinical organ damage, are already present in ADPKD children. RWT was significantly correlated to that of cDC and PWV, implying that vascular stiffening is associated with cardiac remodeling. None of the children had an alteration in renal function. Subclinical cardiovascular damage preceded the decline in glomerular filtration rate.

Risk factors for pre-clinical atherosclerosis in adolescents with type 1 diabetes.

AIMS: To assess whether, besides "traditional" risk factors, overall oxidative stress, oxidized lipoproteins, and glycemic variability are associated with early macro-vascular damage in type 1 diabetes (T1D). METHODS: In 267 children/adolescents with T1D (130 girls, age 9.1-23.0 years) we evaluated: derivatives of reactive oxygen metabolites [d-ROMs], serum total antioxidant capacity [TAC] and oxidized LDL-cholesterol [oxLDL]; markers of early vascular damage (Lipoprotein-associated phospholipase A2 [Lp-PLA2], z-score of carotid intima-media thickness [z-cIMT] and carotid-femoral pulse wave velocity [z-PWV]); CGM metrics of four weeks preceding the visit, central systolic/diastolic blood pressures (cSBP/cDBP), and HbA1c, z-score of BP (z-SBP/z-DBP) and circulating lipids longitudinally collected since T1D onset.. Three general linear models were built with z-cIMT, z-PWV adjusted for current cDBP, and Lp-PLA2 as independent variables. RESULTS: The z-cIMT was associated with male gender (B = 0.491, η2 = 0.029, p = 0.005), cSBP (B = 0.023, η2 = 0.026, p = 0.008) and oxLDL (B = 0.022, η2 = 0.022, p = 0.014). The z-PWV was associated with diabetes duration (B = 0.054, η2 = 0.024, p = 0.016), daily insulin dose (B = 0.52, η2 = 0.018, p = 0.045), longitudinal z-SBP (B = 0.18, η2 = 0.018, p = 0.045) and dROMs (B = 0.003, η2 = 0.037, p = 0.004). Lp-PLA2 was associated with age (B = 0.221, η2 = 0.079, p = 3*10-6), oxLDL (B = 0.081, η2 = 0.050, p = 2*10-4), longitudinal LDL-cholesterol (B = 0.031, η2 = 0.043, p = 0.001) and male gender (B = -1.62, η2 = 0.10, p = 1.3*107). CONCLUSIONS: Oxidative stress, male gender, insulin dose, diabetes duration and longitudinal lipids and blood pressure, contributed to the variance of early vascular damage in young patients with T1D.

Markers of subclinical vascular damage in young adults with type 1 diabetes mellitus: the role of central blood pressure.

INTRODUCTION: Type 1 diabetes mellitus (T1D) is a chronic disease leading to cardiovascular complications that can be diagnosed early as subclinical vascular damage. To prevent such damage, it is important to increase knowledge of the effects of the different cardiovascular risk factors in patients with T1D. The aim of our study was to assess possible associations between markers of subclinical arterial damage and traditional cardiovascular risk factors, with a special focus on peripheral blood pressure and central blood pressure (cBP), in a sample of young adults with T1D. PATIENTS AND METHODS: The study included 172 T1D patients (mean age 24.7 ±â€Š8.7 years, duration of T1D 13.5 ±â€Š9.6 years). Pulse wave velocity (PWV), pulse wave analysis and cBP were assessed by tonometry (SphygmoCor Xcel). Carotid intima-media thickness (cIMT) and carotid distensibility coefficient (cDC) were assessed by high-resolution echo-Doppler analysis and further examined with dedicated hardware. RESULTS: Seventeen patients (10.1%) were classified as hypertensive by office peripheral blood pressure, and 48 patients (27.9%) were classified as hypertensive by cBP. One hundred sixteen patients (68.8%) had cDC under the range of normality, one patient had a PWV (0.6%) above 10 m/s, and no patients had a cIMT above 0.9 mm. In multivariable analysis, central SBP, but not metabolic parameters, remained associated with all the markers of subclinical arterial damage [cIMT ( ß â€Š= 0.288 ±â€Š0.001; P  < 0.001), PWV ( ß â€Š= 0.374 ±â€Š0.007; P  < 0.001), cDC ( ß â€Š= -0.149 ±â€Š0.055; P  = 0.029)]. CONCLUSION: The independent association between cBP and markers of subclinical vascular damage underlines the importance of haemodynamic factors in the development of early signs of macrovascular disease in T1D patients. Further studies are warranted to better define the role of cBP to stratify cardiovascular risk, to individualize the need for follow-up and to tailor preventive strategies in T1D patients.

Central Systolic Blood Pressure Is Associated With Early Vascular Damage in Children and Adolescents With Type 1 Diabetes.

Objective of the study: This study aimed to test the effect of multiple cardiovascular risk factors on subclinical indices of atherosclerosis in children and adolescents with type 1 diabetes (T1D). Methods: Carotid intima-media thickness (cIMT), carotid distensibility coefficient (cDC), and carotid-femoral pulse wave velocity (PWV) were measured in children and adolescents with T1D, in a follow-up at the outpatient clinics of Verona. Blood pressure (BP; both central and peripheral), metabolic and other cardiovascular risk factors were evaluated in multivariate linear regressions to assess the association with the measured indices of subclinical vascular damage. Results: One hundred and twenty-six children and adolescents were included. cIMT was above the 95th percentile for age and height in 60.8% of the population, whereas 26% of the sample had cDC impairment (less than the 5th percentile) and 4.8% had an elevated PWV. Independent determinants of cIMT according to the regression models were only gender type of glucose monitoring and central systolic BP (cSBP). PWV was associated with age, sex, heart rate, and cSBP; cDC with age and both cSBP and, alternatively, peripheral BP (pBP). Neither pBP nor any of the tested metabolic parameters, including glycated hemoglobin, was associated with PWV and cIMT. Conclusions: A high proportion of early vascular damage, especially an increased cIMT, is present in children and adolescents with T1D in whom cSBP seems to be a common determinant. In children and adolescents with T1DM, a special focus should be on hemodynamic risk factors beyond metabolic ones.

Onset of Addison Disease appeared during the first trimester of a twin pregnancy: A case report.

Addison Disease is an uncommon, life-threatening condition affecting people at any age, including women during pregnancy. If left untreated, the disease can be rapidly fatal, but the prognosis is good if promptly recognized and hormones are replaced.

Long chain fatty acids metabolism and cardiovascular risk factors in youth with type 1 diabetes.

BACKGROUND AND AIMS: Fatty acids (FAs) and their metabolizing enzymes have been associated with several cardiometabolic outcomes. Whether they correlate with cardiovascular risk in type 1 diabetes (T1D), it is unknown. We investigated whether erythrocyte FAs correlated with cardiovascular risk factors and dietary fats in youth with T1D. METHODS AND RESULTS: We recruited 154 adolescents with T1D (aged 17.3 ± 2 years, 82 boys) and assessed blood pressure, plasma lipids, HbA1c, estimated insulin sensitivity (eIS) and dietary fats based on a 3-days weighed dietary record. Erythrocyte FAs were measured by gas chromatography and desaturase and elongase activities were estimated as product/precursor ratios. Delta-6-desaturase (D6D) activity correlated inversely with eIS (r = -0.32,p = 6.6∗10-5) and directly with triglycerides (r = 0.24, p = 0.003), adjusted for z-BMI, age and gender. No single erythrocyte FA correlated with eIS. Erythrocyte membrane stearic acid (SA) correlated with HbA1c adjusted for confounders and eIS (r = -0.26, p = 0.002). We found some weak (r ≤ 0.20) correlations between erythrocyte membrane FAs and dietary fats, which were not retained by correction for multiple testing. CONCLUSION: In youth with T1D, D6D activity might exert unfavorable effects per se, beyond its role on FAs composition. This is in accordance with previous data associating D6D activity/D6D-enhancing polymorphisms with metabolic syndrome and incident type 2 diabetes, as well as D6D activity with the regulation of cellular red-ox balance. SA was a favorable marker of glycemic control. Future research is needed to clarify the biological pathways linking D6D and SA with the cardiometabolic health of youth with T1D.

Relationship between common carotid distensibility/aortic stiffness and cardiac left ventricular morphology and function in a group of patients affected by chronic rheumatic diseases: an observational study.

OBJECTIVES: Chronic inflammatory arthritis (CIAs), including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) are characterised by high cardiovascular disease (CVD) risk, partly due to endothelial dysfunction and increased arterial stiffness of the carotid artery and aorta. The aim of the present study is to determine whether ultrasonography measures of carotid and aortic stiffness are correlated with left ventricular mass and function in patients affected by CIAs. METHODS: In this cross-sectional study, we consecutively enrolled outpatients diagnosed with CIAs with no overt CVD. For each participant we assessed disease characteristics, CVD risk factors, medications, including disease-modifying anti-rheumatic drugs (DMARDs), blood pressure, lipids and glucose levels. Carotid ultrasonography was performed in all patients using carotid distensibility (CD) and aortic stiffness index (AoSI) as measures of arterial stiffness. Participants underwent the same day a full echocardiographic study including assessment of left ventricular function and mass (LVM). RESULTS: The study population comprised 208 CIAs patients (mean age 57.4±11.4 y; females 63.9%), including 137 (65.9%) RA, 42 (20.2%) PsA and 29 (13.9%) AS patients. In multiple regression analysis, CD correlated with age (ß=-0.198, p<0.0001), mean arterial pressure (ß=-0.281, p<0.0001) and treatment with DMARDs (ß=-1.976, p=0.021), while AoSI was not associated with any anthropometric, haemodynamic or clinical covariates. CD was inversely related to LVM (r=-0.20, p=0.005), whereas AoSI was directly correlated with diastolic function of the left ventricle (E/E'; r=0.191, p=0.007). CONCLUSIONS: Our results underline the strict correlation between arterial stiffness and left ventricular mass and function in patients with CIAs.

Evaluation of circ_100219 and miR-135b in serum and exosomes of healthy pregnant women.

AIM: Circular RNAs (circRNAs) are recently discovered and highly stable noncoding RNAs acting as gene regulators. These circRNAs can function as miRNA sponges, thereby upregulating or downregulating miRNA target gene expression. MiR-135b is expressed in placenta tissue and can be found in maternal circulation, thus playing a functional role in pregnancy. This miR is a target of circ_100219. This preliminary study was aimed to evaluate circ_100219 and miR-135b expression in pregnant and nonpregnant women, and explore the relationship between circ_100219 and miR-135b in serum and exosomes. METHODS: Total RNA was isolated from serum and exosomes of 30 healthy pregnant women (32.9 ± 5.1 years) between 23-27 gestational weeks and 30 healthy nonpregnant women (31.3 ± 5.4 years). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to quantify circ_100219 and miR-135b expression. GAPDH and U6 snRNA were chosen as reference for normalizing expression levels. The differences between pregnant and nonpregnant women were assessed with Mann-Whitney test and correlation with Spearman's test. RESULTS: The circ_100219 expression levels were significantly lower both in serum and exosomes of second trimester pregnant women compared to the control group (p < .0001), whilst Mir-135b expression levels were significantly higher in pregnant than in the control group (p < .0001). A significant negative correlation was observed between circ_100219 and miR-135b expression levels in both serum and exosomes (r = -0.34 and p = .009; r = -0.31 and p = .01, respectively). The circ_100219:miR-135b ratio was significantly increased in nonpregnant women compared to the pregnant group, in both serum and exosomes (49.0 versus 1.1, p < .0001 and 2042.4 versus 28.5, p < .0001, respectively). CONCLUSIONS: Our results confirm a role for circ_100219 and miR-135b in physiological pregnancy. Further studies are needed to investigate the circ_100219:miR-135b ratio in pregnancy complications.

Influence of genetic variants in FADS2 and ELOVL2 genes on BMI and PUFAs homeostasis in children and adolescents with obesity.

BACKGROUND: Several studies identified genetic variants in FADS and ELOVL2 genes associated with obesity-related conditions, such as alterations in blood lipid parameters and insulin homeostasis. The aim of this cross-sectional study was to determine whether FADS and ELOVL2 genetic variants were associated with obesity and adiposity, besides dyslipidaemia and insulin resistance, in a large sample of obese children and adolescents. MATERIALS AND METHODS: One thousand six hundred and forty-nine obese children underwent physical examination, anthropometry, fasting blood tests measuring plasma glucose, lipid and liver profile. Two genetic variants were genotyped: rs2236212 in ELOVL2 gene and rs1535 in FADS2, for the gene cluster FADS. In a subgroup of obese children (n = 105), erythrocyte fatty acid composition was measured. Generalized linear models were used to assess association between genotypes and variables. RESULTS: A positive association between zBMI and the minor allele of rs2236212 (p = 0.028), the major allele of rs1535 (p = 0.046) and the genetic score (p = 0.008), created by summing up both risk alleles, were found. The estimation of enzymatic activity revealed that minor alleles were associated significantly with a reduction of the enzymatic activity of elongase and desaturase (p = 0.048 and p = 0.0001, respectively). DISCUSSION AND CONCLUSIONS: Common variants in the FADS2 and ELOVL2 genes were associated with BMI in a large population of obese Italian children. These SNPs were associated with alterations in LC-PUFAs homeostasis, not accompanied by modifications of plasma lipids or HOMA-IR. These findings provide additional support to the genetics accounting for BMI interindividual variability and the molecular basis of obesity.

Circulating Bile Acids Profiles in Obese Children and Adolescents: A Possible Role of Sex, Puberty and Liver Steatosis.

BACKGROUND: Childhood obesity is becoming a major health issue and contributes to increasing the risk of cardiovascular disease in adulthood. Since dysregulated metabolism of bile acids (BAs) plays a role in progression of obesity-related disorders, including steatosis and hypertension, this study aimed to investigate BAs profiles in obese children with and without steatosis and hypertension, as well as exploring the interplay between BAs profile and vascular function. METHODS: BAs concentrations were quantified with liquid chromatography-tandem mass spectrometry in 69 overweight/obese children and adolescents (mean age, 11.6 ± 2.5 years; 30 females). Liver steatosis was defined with abdomen ultrasonography, whilst hypertension was defined according to the current European guidelines. Vascular function was assessed with ultrasound technique, by measuring carotid intima media thickness (cIMT) and common carotid artery distensibility (cDC). RESULTS: Total and individual glycine-conjugated BAs concentrations were found to be significantly higher in males compared to females, as well as in pre-pubertal compared to pubertal stage (p < 0.05 for both). No difference in BAs concentration was observed between hypertensive and normotensive subjects. Total BAs and glycine conjugated BAs were significantly higher in participants with steatosis compared to those without (p = 0.004 for both). The values of total glycine-conjugate acids were positively correlated with cDC and this association remained significant in linear regression after adjusting for sex, age, pubertal stage, body mass index and aspartate aminotransferase. CONCLUSION: The results suggest a possible role of BAs in the pathogenesis of liver and/or vascular damage in children and adolescent. Further studies are hence needed to validate these preliminary findings.

Fatty Acid Profile and Desaturase Activities in 7-10-Year-Old Children Attending Primary School in Verona South District: Association between Palmitoleic Acid, SCD-16, Indices of Adiposity, and Blood Pressure.

In previous studies, dietary and circulating fatty acids (FA) and desaturases activity (delta-5 desaturase [D5D], delta-6 desaturase [D6D], and stearoyl-CoA desaturase [SCD-16]) involved in their metabolism were associated with metabolic and cardiovascular disorders. The aim of the study was to assess the association between different FAs and desaturases activity (estimated as product:precursor ratios) with individual cardiovascular risk factors (in particular, anthropometric measurements and blood pressure [BP]) in children. The FA profile was determined on a whole-blood drop in 243 children (age: 8.6 ± 0.72 years) participating in a school-based cross-sectional study. Docosahexaenoic acid (DHA) inversely correlated with indices of adiposity, glucose, and triglycerides. Palmitoleic acid and SCD-16 were directly associated with markers of adiposity and BP, even after adjustment for main confounders. D6D correlated directly with the waist/height ratio. Children with excess weight (>85th percentile; that is overweight plus obese ones) showed higher palmitic acid, palmitoleic acid, and higher SCD-16 activity as compared to normal-weight children. Most of the associations were confirmed in the excess-weight group. Omega-3 FAs, particularly DHA, but not omega-6 FA, showed a potentially beneficial association with metabolic parameters, whereas palmitoleic acid and SCD-16 showed a potentially harmful association with indices of adiposity and BP, especially in obese children.

Beneficial effects of DAAs on cardiac function and structure in hepatitis C patients with low-moderate liver fibrosis.

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.

Traditional cardiovascular risk factors and residual disease activity are associated with atherosclerosis progression in rheumatoid arthritis patients.

Patients with rheumatoid arthritis (RA) have an increased incidence of cardiovascular events. Ultrasound examination of the carotid arteries can show the presence of plaques and detect the atherosclerotic subclinical process through the evaluation of intima-media thickness (cIMT) and carotid segmental distensibility (cCD). The aim of the present study was to identify which factors could independently influence the evolution of atherosclerosis (plaques, cIMT, and cCD) after 1 year of follow-up in a sample of patients with RA. A total of 137 patients with RA without previous cardiovascular (CV) events were enrolled at baseline, and 105 (M/F: 21/84, age 59.34 ± 11.65 years) were reassessed after one year using ultrasound of carotid arteries to detect atheromatous plaques and to measure cIMT and cCD. After one year, all the indices of subclinical atherosclerosis worsened with respect to baseline (Δ-cIMT = 0.030 ± 0.10 mm, p = 0.005; Δ-cCD = -1.64 ± 4.83, 10-3/KPa, p = 0.005; Δ-plaques = 8.6%, p = 0.035). Traditional CV risk factors (age, mean arterial pressure, and diabetes) and corticosteroid therapy were independently associated with the worsening of subclinical atherosclerosis. Interestingly, when considering RA patients divided according to the degree of disease activity score 28 with C-reactive protein (DAS28 [CRP] ≥2.6), the worsening of subclinical atherosclerosis indices was detectable exclusively in the group of patients with active disease. Our longitudinal study supports the hypothesis of a key role of both traditional CV risk factors and the inflammatory activity of arthritic disease in the progression of subclinical atherosclerosis in RA patients. In addition, corticosteroids might have a deleterious effect.

Subclinical Organ Damage in Children and Adolescents with Hypertension: Current Guidelines and Beyond.

High blood pressure (BP) is becoming a growing health issue even in children and adolescents. Moreover, BP elevation in youth frequently translates into children and adult hypertension contributing to the development of cardiovascular disease. The detection of early markers of vascular damage, potentially leading to overt cardiovascular disease, is important for clinical decisions about if and how to treat hypertension and can be useful in monitoring the effectiveness of the treatment. The purpose of this review is to summarize the actual knowledge about subclinical organ damage (SOD) in hypertensive children and adolescents and its association with cardiovascular disease in children and young adults. Our focus is especially put on left ventricular mass, pulse wave velocity, carotid intima-media thickness and microalbuminuria. We also want to address the scientific evidence about possible regression of SOD and cardiovascular risk with the use of behavioural and specific anti-hypertensive therapy. Indications from current guidelines are critically discussed.

Relation between Dietary Habits, Physical Activity, and Anthropometric and Vascular Parameters in Children Attending the Primary School in the Verona South District.

The aim of this school-based study was to identify the possible association between diet and physical activity, as well as the anthropometric, vascular, and gluco-lipid parameters. We administered two validated questionnaires for diet and physical activity (Food Frequency questionnaire (FFQ), Children-Physical Activity Questionnaire (PAQ-C)) to children at four primary schools in Verona South (Verona, Italy). Specific food intake, dietary pattern, and physical activity level expressed in Metabolic Equivalent of Task (MET) and PAQ-C score were inserted in multivariate linear regression models to assess the association with anthropometric, hemodynamic, and gluco-lipid measures. Out of 309 children included in the study, 300 (age: 8.6 ± 0.7 years, male: 50%; Obese (OB): 13.6%; High blood pressure (HBP): 21.6%) compiled to the FFQ. From this, two dietary patterns were identified: "healthy" and "unhealthy". Direct associations were found between (i) "fast food" intake, Pulse Wave Velocity (PWV), and (ii) animal-derived fat and capillary cholesterol, while inverse associations were found between vegetable, fruit, and nut intake and capillary glucose. The high prevalence of OB and HBP and the significant correlations between some categories of food and metabolic and vascular parameters suggest the importance of life-style modification politics at an early age to prevent the onset of overt cardiovascular risk factors in childhood.

Author Correction: Markers of subclinical vascular damages associate with indices of adiposity and blood pressure in obese children.

Since the publication of this paper, it has been noted that the author Denise Marcon had been missed out of the author list. The correct author list is shown above.

Markers of subclinical vascular damages associate with indices of adiposity and blood pressure in obese children.

In this observational study, we aimed at investigating the influence of excess weight and traditional cardiovascular risk factors on vascular structure and function in a cohort of overweight/obese children. Sixty-six obese and 4 overweight children (age 11.5 ± 2.4 years; female n: 30) underwent office and ambulatory BP measurements (ABPM); ultrasound was used to measure carotid intima-media thickness (cIMT), endothelial function by Flow-Mediated Dilation (FMD) and carotid distensibility (cDC); and digital photopletismography was used to measure stiffness index (SIDVP). Carotid IMT directly correlated with 24-h and nighttime-systolic blood pressure (SBP); while cDC had inverse correlations with BMI, waist circumference and 24-h BP. Unexpectedly, SIDVP resulted inversely related with several indices of excess weight. Most of these correlations remained significant after adjustment for age, sex, BMI, and BP. In a replication set of 40 obese children, SIDVP but not pulse wave velocity (PWV) remained inversely associated with BMI. These data suggest that arterial structure and elasticity are negatively affected by excess weight and BP levels, even in childhood. Surprisingly, SI may not be a reliable marker of vascular stiffness in obese children, because this measurement is likely confounded by other factors, including vasodilation.

Effect of CYP4F2, VKORC1, and CYP2C9 in Influencing Coumarin Dose: A Single-Patient Data Meta-Analysis in More Than 15,000 Individuals.

The cytochrome P450 (CYP)4F2 gene is known to influence mean coumarin dose. The aim of the present study was to undertake a meta-analysis at the individual patients level to capture the possible effect of ethnicity, gene-gene interaction, or other drugs on the association and to verify if inclusion of CYP4F2*3 variant into dosing algorithms improves the prediction of mean coumarin dose. We asked the authors of our previous meta-analysis (30 articles) and of 38 new articles retrieved by a systematic review to send us individual patients' data. The final collection consists of 15,754 patients split into a derivation and validation cohort. The CYP4F2*3 polymorphism was consistently associated with an increase in mean coumarin dose (+9% (95% confidence interval (CI) 7-10%), with a higher effect in women, in patients taking acenocoumarol, and in white patients. The inclusion of the CYP4F2*3 in dosing algorithms slightly improved the prediction of stable coumarin dose. New pharmacogenetic equations potentially useful for clinical practice were derived.

Individual fatty acids in erythrocyte membranes are associated with several features of the metabolic syndrome in obese children.

PURPOSE: Obesity leads to the clustering of cardiovascular (CV) risk factors and the metabolic syndrome (MetS) also in children and is often accompanied by non-alcoholic fatty liver disease. Quality of dietary fat, beyond the quantity, can influence CV risk profile and, in particular, omega-3 fatty acids (FA) have been proposed as beneficial in this setting. The aim of the study was to evaluate the associations of individual CV risk factors, characterizing the MetS, with erythrocyte membrane FA, markers of average intake, in a group of 70 overweight/obese children. METHODS: We conducted an observational study. Erythrocyte membrane FA were measured by gas chromatography. Spearman correlation coefficients (rS) were calculated to evaluate associations between FA and features of the MetS. RESULTS: Mean content of Omega-3 FA was low (Omega-3 Index = 4.7 ± 0.8%). Not omega-3 FA but some omega-6 FA, especially arachidonic acid (AA), were inversely associated with several features of the MetS: AA resulted inversely correlated with waist circumference (rS = - 0.352), triglycerides (rS = - 0.379), fasting insulin (rS = - 0.337) and 24-h SBP (rS = - 0.313). Total amount of saturated FA (SFA) and specifically palmitic acid, correlated positively with waist circumference (rS = 0.354), triglycerides (rS = 0.400) and fasting insulin (rS = 0.287). Fatty Liver Index (FLI), a predictive score of steatosis based on GGT, triglycerides and anthropometric indexes, was positively correlated to palmitic acid (rS = 0.515) and inversely to AA (rS = - 0.472). CONCLUSIONS: Our data suggest that omega-6 FA, and especially AA, could be protective toward CV risk factors featuring the MetS and also to indexes of hepatic steatosis in obese children, whereas SFA seems to exert opposite effects.