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.

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.

Pregnancy-Related Complications in Patients With Fibromuscular Dysplasia: A Report From the European/International Fibromuscular Dysplasia Registry.

Current literature suggests a higher risk of pregnancy-related complications in patients with renal fibromuscular dysplasia (FMD). The aim of our study was to assess the nature and prevalence of pregnancy-related complications in patients subsequently diagnosed with FMD. A call for participation was sent to centers contributing to the European/International FMD Registry. Patients with at least 1 pregnancy were included. Data on pregnancy were collected through medical files and FMD characteristics through the European/International FMD Registry. Data from 534 pregnancies were obtained in 237 patients. Despite the fact that, in 96% of cases, FMD was not diagnosed before pregnancy, 40% of women (n=93) experienced pregnancy-related complications, mostly gestational hypertension (25%) and preterm birth (20%), while preeclampsia was reported in only 7.5%. Only 1 patient experienced arterial dissection and another patient an aneurysm rupture. When compared with patients without pregnancy-related complications, patients with complicated pregnancies were younger at FMD diagnosis (43 versus 51 years old; P<0.001) and had a lower prevalence of cerebrovascular FMD (30% versus 52%; P=0.003) but underwent more often renal revascularization (63% versus 40%, P<0.001). In conclusion, the prevalence of pregnancy-related complications such as gestational hypertension and preterm birth was high in patients with FMD, probably related to the severity of renal FMD. However, the prevalence of preeclampsia and arterial complications was low/moderate. These findings emphasize the need to screen hypertensive women for FMD to ensure revascularization before pregnancy if indicated and appropriate follow-up during pregnancy, without discouraging patients with FMD from considering pregnancy.

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.

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.

Possible Role of CYP450 Generated Omega-3/Omega-6 PUFA Metabolites in the Modulation of Blood Pressure and Vascular Function in Obese Children.

Obesity is often accompanied by metabolic and haemodynamic disorders such as hypertension, even during childhood. Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP450) enzymes to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), vasoactive and natriuretic metabolites that contribute to blood pressure (BP) regulation. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 polyunsaturated fatty acids may compete with AA for CYP450-dependent bioactive lipid mediator formation. We aimed at investigating the role of AA, EPA and DHA and their CYP450-dependent metabolites in BP control and vascular function in 66 overweight/obese children. Fatty acid profile moderately correlated with the corresponding CYP450-derived metabolites but their levels did not differ between children with normal BP (NBP) and high BP (HBP), except for higher EPA-derived epoxyeicosatetraenoic acids (EEQs) and their diols in HBP group, in which also the estimated CYP450-epoxygenase activity was higher. In the HBP group, EPA inversely correlated with BP, EEQs inversely correlated both with systolic BP and carotid Intima-Media Thickness (cIMT). The DHA-derived epoxydocosapentaenoic acids (EDPs) were inversely correlated with diastolic BP. Omega-3 derived epoxymetabolites appeared beneficially associated with BP and vascular structure/function only in obese children with HBP. Further investigations are needed to clarify the role of omega-3/omega-6 epoxymetabolites in children's hemodynamics.