Systolic Blood Pressure Z-score Research Articles

Individual Inhalation Exposure to Phthalates and Their Associations with Anthropometric and Physiological Indices in Primary School Children in Jinan, China

Phthalates are commonly found in indoor environments. Consequently, children may be exposed to phthalates through the air, potentially causing health issues. We collected 72 air samples from 60 households and 12 classrooms in Jinan, surveyed and health-examined children, assessed their phthalate inhalation exposure, and analyzed the associations between inhalation exposure levels and children’s anthropometric and physiological indicators. Eight phthalates were detected in children’s households and classrooms, with detection frequencies ranging from 91.6% to 100%. Di-iso-butyl phthalate (DiBP), di-n-butyl phthalate (DnBP), and di (2-ethylhexyl) phthalate (DEHP) were the predominant phthalates. Children’s indoor inhalation exposure to phthalates ranged from 8.90 to 147 ng/(kg·day), with DEHP being the main inhaled phthalate. The non-carcinogenic risks of indoor environments where children live are within acceptable limits. DEHP has a low carcinogenic risk. Di-n-octyl phthalate (DnOP) exposure was associated with a decrease in body mass index z-score, waist circumference, and hip circumference. Additionally, DEHP exposure was negatively associated with the waist-to-hip ratio. DiBP exposure was negatively associated with the systolic blood pressure z-score, while DnOP exposure was negatively associated with the diastolic blood pressure z-score. Furthermore, DEHP exposure was positively associated with fractional exhaled nitric oxide z-score. The findings of this study suggest that phthalate inhalation exposure may substantially affect various health metrics in children, including body mass index, waist and hip circumference, and blood pressure, and increase the risk of respiratory tract inflammation.

Gestational organophosphate pesticide exposure and childhood cardiovascular outcomes

IntroductionThe general population is chronically exposed to organophosphate pesticides through various routes including ingestion, hand-to-mouth contact, inhalation, and dermal contact. Exposure to organophosphate pesticides during pregnancy impairs fetal development, but the potential long-term effects of gestational organophosphate pesticide exposure are less well understood. MethodsWe investigated associations between gestational organophosphate pesticide exposure and cardiovascular outcomes in 643 children in the Generation R Study, a prospective pregnancy cohort based in Rotterdam, The Netherlands. Urinary organophosphate pesticide metabolites (dimethyl [∑DMAP], diethyl [∑DEAP], and total dialkyl phosphate [∑DAP] metabolites) were quantified in three urine samples collected from pregnant participants, and their children were followed until age 10 years at which time cardiac magnetic resonance imaging, ultrasonography, blood pressure, and serum biomarkers assessed cardiovascular health. Linear regression models estimated associations (β and 95 % confidence interval [CI]) between a one-interquartile range (IQR) increase in averaged gestational exposure biomarker concentrations and z-scored pediatric cardiovascular outcomes. We investigated effect modification of associations by PON1 genotype. ResultsCarotid intima-media thickness z-score was lower (β: -0.14 [95 % CI: −0.25, −0.02]) and HDL cholesterol z-score was higher (β: 0.14 [95 % CI: 0.02, 0.25]) for increases in ∑DEAP concentrations. Carotid intima-media distensibility z-score was lower (β: -0.08 [95 % CI: −0.19, 0.03]) for increases in ∑DMAP concentrations, and systolic blood pressure z-score was higher (β: 0.10 [95 % CI: −0.01, 0.21]) for increases in ∑DMAP and ∑DAP. Among those with PON1-161CC and PON1-L55MTT genotypes, higher organophosphate pesticide concentrations conferred an excess risk of adverse vascular and glycemic outcomes, respectively. ConclusionsWe observed heterogenous associations between gestational organophosphate pesticide exposure and pediatric cardiovascular health: an anti-atherogenic profile was observed for increases in ∑DEAP concentrations, and impairments in multiple aspects of cardiovascular health was observed for increases in ∑DMAP concentrations. PON1-161 and PON1-L55M single nucleotide polymorphisms modified associations for vascular and glycemic outcomes, respectively.

Altered metabolic profiles in male offspring conceived from intracytoplasmic sperm injection

BackgroundWhile most research has focused on the association between intracytoplasmic sperm injection (ICSI) and neurodevelopmental disorders in children, relatively little attention has been given to its metabolic effects. Previous studies have reported that low serum lipid levels are associated with mental health problems. Our objective was to analyze the impact of ICSI on metabolic alterations compared to their in vitro fertilization (IVF) counterparts in male offspring, as well as its interaction with paternal overweight/obesity.MethodsWe recruited families between January 2006 and December 2017 at the Center for Reproductive Medicine, Shandong University, China. Prospective data of offspring were obtained for body mass index (BMI), blood pressure, glucose, and lipid profile in their 0–11 years old. Linear mixed models were utilized to compute the mean difference and 95% confidence intervals (CI).ResultsA total of 14,196 offspring visits were identified. In offspring aged 4–11 years, ICSI-conceived offspring exhibited significantly lower fasting glucose z-scores, total cholesterol z-scores, and low-density lipoprotein cholesterol (LDL-C) z-scores compared with their IVF counterparts (fasting glucose z-score: adjusted mean difference: − 0.13, 95% CI: − 0.23 to − 0.03; total cholesterol z-score: adjusted mean difference: − 0.13, 95% CI: − 0.23 to − 0.02; LDL-C z-score: adjusted mean difference: − 0.12, 95% CI: − 0.22 to − 0.01). Paternal overweight/obesity significantly influenced the relationship between ICSI and metabolic changes in offspring. In offspring born from fathers with overweight/obesity, ICSI-conceived offspring displayed significantly lower fasting glucose and total cholesterol z-scores than their IVF controls (fasting glucose z-score: adjusted mean difference: − 0.20, 95% CI: − 0.32 to − 0.08; total cholesterol z-score: adjusted mean difference: − 0.15, 95% CI: − 0.27 to − 0.02). In offspring born to fathers with normal weight, ICSI-conceived offspring showed significantly lower systolic blood pressure z-scores compared to those conceived via the IVF procedures (adjusted mean difference: − 0.21, 95% CI: − 0.37 to − 0.05).ConclusionsThe findings of this study suggested that ICSI was associated with altered glucose and lipid profiles compared to their IVF controls, characterized by lower fasting glucose z-scores, total cholesterol z-scores, and LDL-C z-scores. Encouraging fathers to reduce their body weight could potentially improve the metabolic health of their ICSI-conceived children.

#1607 Prevalence and risk factors of aortic root dilatation in children with X-linked Alport syndrome

Abstract Background and Aims Aortic dilatation in X-linked Alport syndrome (XLAS) is considered a specific manifestation. On the other hand, all patients with CKD have been shown to have an increased risk of aortopathies. The aim was to define prevalence and risk factors for aortic dilatation in children with XLAS. Method Retrospective cross-section single center study included XLAS’ children (n = 98,64 M) and patients with CACUT (comparison group, n = 26,12 M). The aorta was measured at level of the sinus of Valsalva (SoV), aortic dilatation was determined by z-score >2 for BSA. Body mass index (BMI, kg/m2), z-scores of mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), mean blood pressure (MBP), proteinuria (Pr, mg/m2/day), eGFR (ml/min/1.73 m2), z-scores of left ventricular mass index (LVMI), left ventricular end diastolic diameter (LVEDD), relative wall thickness of the left ventricle (RWT, N < 0,42) data were obtained. Results There were no difference in age (11,12 ± 3,75 vs 10,87 ± 2,34 yrs; p = 0,78), gender (males 0,55 vs 0,46; p = 0,45), BMI (18,7 ± 3,7 vs 19,1 ± 4,7; p = 0,78), eGFR (103,1 ± 16,9 vs 90,5 ± 11,4; p = 0,50), prevalence of hypertension (0,11 vs 0,19; p = 0,21) between the groups. The prevalence of SoV dilatation did not differ between XLAS and CACUT (0,06 vs 0,08; p>0,18). SoV dilatation was associated with male gender (β1 = 0,31, p = 0,02; β2 = 0,34, p = 0,02), LVMI (β1 = 0,26, p = 0,02; β2 = 0,24, p = 0,02) in both groups, with BMI (β1 = -0,27, p = 0,03), LVEDD (β1 = 0,21, p = 0,04) in children with XLAS. No statistically significant effect of SBP, DBP, MBP, Pr, eGFR on SoV dilatation has been demonstrated. Conclusion The prevalence of SoV dilatation in children with XLAS was higher than in general population, but comparable to children with CACUT. The male gender, low BMI, LVMI and LVEDD were associated with SoV dilatation in XLAS. We did not show the relationship between blood pressure load, proteinuria, eGFR and SoV dilatation in XLAS.

THE PREVALENCE AND RISK FACTORS FOR ARTERIAL HYPERTENSION IN CHILDREN WITH IDIOPATHIC NEPHROTIC SYNDROME

Objective: Arterial hypertension (AH) is claimed to be an uncommon finding in children with idiopathic nephrotic syndrome (INS). The study aimed to analyze blood pressure, prevalence, and risk factors of AH in children with INS. Design and method: In 153 children with INS (9.32±3.84 years, 100 boys), we evaluated systolic and diastolic blood pressure (mm Hg, Z-scores), age at onset of the disease, anthropometric data, response to steroids, results of kidney biopsy, number of INS relapses, and medications. Results: The mean age at disease onset was 4.39±2.38 years; 67 patients had steroid-sensitive nephrotic syndrome (SSNS), 12 frequently relapsing nephrotic syndrome (FRNS), 58 steroid-dependent nephrotic syndrome (SDNS), and 16 steroid-resistant nephrotic syndrome (SRNS). Kidney biopsy was performed in 26: 5 – minimal change disease, 11 – mesangial proliferation, 10 – focal and segmental glomerulosclerosis. AH at disease onset was found in 10 (6.5%) patients in the following 11 (7.2%) after corticosteroid initiation. The observation period was 4.93±3.80 years, and AH was found in 31 (20.3%) – in 3 (4.5%) patients with SSNS, 2 (16.7%) with FRNS, 20 (34.5%) with SDNS, and 6 (37.5%) with SRNS. Patients with AH had lower height Z-score (-0.46±1.20 vs. 0.18±1.15, p=0.006), higher BMI Z-score (1.15±1.10 vs. 0.41±1.09, p<0.001), number of INS relapses (8.32±6.78 vs. 4.41±3.82, p<0.001), and current prednisone dose (0.49±0.67 vs. 0.18±0.29 [mg/kg/24h], p<0.001). Systolic blood pressure Z-score at the end of observation correlated with age (r=-0.192, p=0.017), BMI Z-score (r=0.368, p<0.001), and present prednisone dose [mg/kg/24h] (r=0.186, p=0.021), diastolic blood pressure Z-score with BMI Z-score (r=0.231, p=0.004), and number of INS relapses (r=0.163, p=0.044). In Cox Proportional Hazard presence of SDNS and SRNS were the only predictors of AH (SDNS: HR=4.80, 95CI(1.30-17.75), SRNS: HR=4.77, 95CI(1.06-21.53)). Conclusions: 1. Approximately one-third of patients with SDNS and SRNS develop arterial hypertension in the course of the disease. 2. Steroid dependence and steroid resistance are the strongest predictors of AH in children with INS. Other determinants of blood pressure elevation in this group of patients are high BMI and a high number of relapses.

Associations Between Paternal Obesity and Cardiometabolic Alterations in Offspring via Assisted Reproductive Technology.

Both assisted reproductive technology (ART) and obesity are associated with adverse cardiometabolic alterations in offspring. However, the combined effects of paternal obesity and ART on offspring cardiometabolic health are still unclear. To clarify cardiometabolic changes in offspring of obese fathers conceived using ART. This was a retrospective cohort study conducted between June 2014 and October 2019 at a center for reproductive medicine. A total of 2890 singleton visits aged 4-10 years were followed. Age-and sex-specific z-score of body mass index (BMI), blood pressure, insulin resistance, and lipid profile were examined. We observed a strong association between paternal BMI categories and offspring BMI, blood pressure, and insulin resistance. Compared with offspring of fathers with normal weight, multivariable-adjusted mean differences for BMI z-score were 0.53 (95% CI 0.37-0.68) for obese fathers, 0.17 (95% CI 0.05-0.30) for overweight fathers, and -0.55 (95% CI -0.95-0.15) for underweight fathers; corresponding values for systolic blood pressure z-score were 0.21(95% CI 0.07-0.35), 0.10 (95% CI -0.01-0.21), and -0.24 (95% CI -0.59-0.11), and corresponding values for homeostatic model assessment for insulin resistance z-score were 0.31 (95% CI 0.16-0.46), 0.09 (95% CI -0.02-0.21), and -0.11 (95% CI -0.48-0.28), respectively. The mediation analyses suggested that 57.48% to 94.75% of the associations among paternal obesity and offspring cardiometabolic alterations might be mediated by offspring BMI. Paternal obesity was associated with an unfavorable cardiometabolic profile in ART-conceived offspring. Mediation analyses indicated that offspring BMI was a possible mediator of the association between paternal obesity and the offspring impaired metabolic changes.

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

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. 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. 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. 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.

Vascular and Myocardial Structure and Function in Adolescents with Type 1 Diabetes: The CARDEA Study

Introduction. Despite heightened risk of cardiovascular disease (CVD) among individuals with type 1 diabetes, few studies in this population have investigated the development of CVD using early markers in adolescence. We compared risk factors (blood pressure (BP) and dyslipidemia) and early markers of CVD between adolescents with and without type 1 diabetes and explored effect modification by sex. Methods. Cross-sectional study using data from the CARdiovascular Disease risk in pEdiatric type 1 diAbetes (CARDEA) study. We recruited 100 adolescents with type 1 diabetes at the Sainte-Justine University Hospital Center and 97 adolescents without diabetes (14–18 years). We measured arterial stiffness by carotid-femoral pulse wave velocity, endothelial function by brachial artery flow-mediated dilation test, as well as left ventricular (LV) mass, papillary mass, and wall thickness by cardiac MRI. We used multivariable linear regression models to assess the impact of type 1 diabetes on each outcome adjusting for age, sex, ethnicity, adiposity, and familial income. Results. Adolescents with type 1 diabetes had 0.21 standard deviations (SD) (95% CI: 0.04; 0.38) higher diastolic blood pressure z-score (zDBP), 0.21 mmol/L (95% CI: 0.02; 0.40) higher low-density lipoprotein cholesterol (LDL-c) levels, and 17% (95% CI: 4; 29) higher triglyceride levels and lower endothelial function based on acceleration (−77.4 cm/s2, 95% CI: −133.1; −21.6) compared with adolescents without diabetes. Girls with type 1 diabetes had higher systolic blood pressure z-score (zSBP), and boys with type 1 diabetes had lower LV mass and wall thickness compared to healthy peers. Conclusions. In addition to higher BP and abnormal lipid profiles, adolescents with type 1 diabetes present endothelial dysfunction and alterations in cardiac structure (in boys) compared to adolescents without diabetes, suggesting that CVD prevention should be incorporated into type 1 diabetes management early in the disease.

Impact of the COVID-19 pandemic on body mass index in children and adolescents after kidney transplantation

BackgroundThe coronavirus SARS-CoV-2 disease (COVID-19) pandemic affected lifestyles and resulted in significant weight gain in the general population. Its impact on children after kidney transplantation (KTx) is unknown.MethodsWe retrospectively evaluated body mass index (BMI) z-scores during the COVID-19 pandemic in 132 pediatric KTx patients, followed-up at three German hospitals. Among those, serial blood pressure measurements were available for 104 patients. Lipid measurements were available from 74 patients. Patients were categorized according to gender and age group, i.e., children versus adolescents. Data were analyzed by a linear mixed model approach.ResultsBefore the COVID-19 pandemic, female adolescents presented with higher mean BMI z-scores compared to male adolescents (difference: − 1.05, 95% CI − 1.86 to − 0.24, p = 0.004). No other significant differences could be observed among the other groups. During the COVID-19 pandemic, the mean BMI z-score increased in adolescents (difference: male, 0.23, 95% CI 0.18 to 0.28; female 0.21, 95% CI 0.14 to 0.29, each p < 0.001), but not in children. The BMI z-score was associated with adolescent age, and with the combination of adolescent age, female gender, and the duration of the pandemic (each p < 0.05). During the COVID-19 pandemic, the mean systolic blood pressure z-score significantly increased in female adolescents (difference: 0.47, 95% CI 0.46 to 0.49).ConclusionsDuring the COVID-19 pandemic, adolescents in particular showed a significant increase in their BMI z-score after KTx. Additionally, an increase in systolic blood pressure was associated with female adolescents. The findings suggest additional cardiovascular risks in this cohort.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

Effect of Preoperative Weight Status and Disease Presentation on Postoperative Elevated Blood Pressure After Childhood Adenotonsillectomy.

To investigate the risk factors of postoperative elevated blood pressure (BP) in children with childhood obstructive sleep apnea syndrome (OSAS) after adenotonsillectomy (AT). Case series with planned data collection. Tertiary referral center. Two hundred forty-five consecutive children (180 boys and 65 girls, median age 6.6 years) with polysomnography-diagnosed OSAS who underwent AT between January 2010 and August 2019. Clinical, polysomnographic, and evening BP data were assessed preoperatively and postoperatively (≥3 months after AT). Changes in the variables before and after AT and between individuals with and without hypertension were compared. Postoperatively, the median (interquartile range) apnea-hypopnea index significantly decreased from 10.4 (5.3-22.6) to 2.2 (1.0-3.8) events/h. In addition, the mean (standard deviation) evening diastolic BP z-score significantly decreased from 0.7 (0.94) to 0.5 (0.81) in the overall cohort, and both systolic (2.1 [0.94]-1.0 [1.31]) and diastolic BP z-scores (1.6 [0.98]-0.7 [0.85]) significantly decreased in the preoperative elevated BP subgroup. Multivariate logistic regression analysis showed that preoperative obesity (adjusted odds ratio = 4.36, 95% confidence interval = 2.24-8.49) and mean peripheral oxygen saturation <95% during sleep (adjusted odds ratio = 2.73, 95% confidence interval = 1.29-5.79) were independently associated with postoperative elevated BP. Preoperative obesity and mean peripheral oxygen saturation <95% during sleep were significantly associated with postoperative elevated BP in the children with OSAS, further indicating the importance of careful BP monitoring in this subgroup despite AT treatment.

Benefits in Cardiac Function from a Remote Exercise Program in Children with Obesity.

Physical activity (PA) is a crucial factor in preventing and treating obesity and related complications. In this one-arm pre−post longitudinal prospective study, we evaluated the effects of a 12-week online supervised training program on cardiac morphology, function and blood pressure (BP) in children with obesity. The training program consisted of three sessions per week, each lasting 60 min. Advanced echocardiographic imaging (tissue Doppler and longitudinal strain analysis) was used to detect subclinical changes in heart function. Categorical variables were described as counts and percentages; quantitative variables as the mean and standard deviation (SD) as they were normally distributed (Shapiro−Wilks test). Pre−post comparisons were made with a paired t-test. A total of 27/38 (71%) enrolled patients (18M/9F, 11 ± 2 years) completed the training protocol and were considered in the analysis. At baseline, no hypertensive patient was noted; all echocardiographic variables were within the normal range. After training, we observed a significant reduction in BP parameters, including systolic BP values and Z-score, diastolic BP values, centiles and Z-score, and mean arterial pressure (all p < 0.05). Significant variations in echocardiographic interventricular septum (IVSd) thickness (p = 0.011), IVSd Z-score (p = 0.001), left ventricular (LV) end-diastolic diameter (p = 0.045), LV posterior wall thickness Z-score (p = 0.017), and LV global longitudinal strain (p = 0.016) were detected. No differences in LV diastolic function and right ventricular strain were noted. PA plays a decisive role in improving BP control and has benefits on left ventricle systolic function, representing a strategic approach to limit CV risk. Online exercise could be an excellent method of training in children with obesity.

Associations of maternal obesity, frozen embryos, and offspring adverse cardiometabolic alterations

To evaluate the long-term cardiometabolic health of offspring conceived by frozen embryo transfer and born to mothers with overweight/obesity. Retrospective cohort study. Center for Reproductive Medicine. A total of 2,741 offspring born to mothers who underwent invitro fertilization/intracytoplasmic sperm injection treatment were followed between June 2014 and August 2021. The offspring were singletons aged 4-11 years at follow-up. None. Age-specific z-scores of cardiometabolic parameters were examined, including adiposity, systolic/diastolic blood pressure, glucose, and lipid profiles, and the metabolic sum score of different cardiometabolic characteristics. Of 2,741 offsprings, 965 (35.21%) were born to mothers with overweight/obesity, including 396 (41.04%) offspring who were conceived by frozen embryo transfer. After adjusting for paternal and maternal age, paternal body mass index (BMI), offspring age, offspring sex, and offspring postnatal energy intake, offspring born to mothers with overweight/obesity and conceived by frozen embryo transfer showed a significantly higher BMI z-score, systolic blood pressure z-score, metabolic sum score-1, and metabolic sum score-2 compared with those conceived by fresh embryo transfer (BMI z-score: adjusted mean difference, 0.17; 95% confidence interval [CI], 0.04-0.30; systolic blood pressure z-score: adjusted mean difference, 0.16; 95% CI, 0.02-0.29; metabolic sum score-1: adjusted mean difference, 0.54; 95% CI, 0.15-0.94; metabolic sum score-2: adjusted mean difference, 0.45; 95% CI, 0.07-0.83). However, in offspring of mothers with normal weight, offspring conceived by frozen embryo transfer showed a significantly lower low-density lipoprotein-cholesterol z-score compared with those conceived by fresh embryo transfer (adjusted mean difference, -0.12; 95% CI, -0.22 to -0.02). Other cardiometabolic parameters were comparable between offspring with frozen and fresh embryo transfers after adjusting for multivariate confounder variables. This study found that among offspring from mothers who were overweight/obese, those offspring conceived by frozen embryo transfer were associated with higher systolic blood pressure z-scores and adverse metabolic changes compared with those conceived by fresh embryo transfer. The changes show that the association between frozen embryo transfer and offspring adverse cardiometabolic changes is apparent only among those born to mothers who are overweight/obese.

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.

Longitudinal Changes in Cardiac Structure and Function in Pediatric Kidney Transplant Recipients.

Cardiovascular disease results in increased morbidity and mortality in pediatric kidney transplant recipients. Longitudinal changes in cardiac structure and function and the association with blood pressure control over time in pediatric kidney transplant recipients are unknown. To determine the influence of blood pressure control on cardiac changes following pediatric kidney transplant, we conducted a retrospective cohort study of children who received their first kidney transplant at the Hospital for Sick Children from 2004 to 2015. Children were followed until transfer to adult care or censoring in July 2018. Cardiac structure and function parameters were collected from clinical echocardiograms and assessed using standardized scores. Blood pressure control was determined by systolic blood pressure Z scores (above or below the 90th percentile) in combination with antihypertensive medications. A segmented mixed-effects model assessed Z scores of interventricular septum thickness, left ventricular end-diastolic dimension, and left ventricular posterior wall dimension. Of 142 children included, 58% were men, mean age at transplant was 11 (±4.5) years, and average follow-up time was 4 (±3) years. All cardiac structural Z scores improved during follow-up. Interventricular septum thickness normalized at 4.0 years post-transplant. Left ventricular end-diastolic dimension normalized at 1.5 years post-transplant. Left ventricular posterior wall dimension normalized at 6.3 years post-transplant. Left ventricular mass index showed sustained improvement up to 12 years post-transplant. Individuals with uncontrolled blood pressure had increased left ventricular mass (β=2.97 [95% CI, 0.77-5.16]). Cardiac structural abnormalities improve following kidney transplantation and normalize within 7 years, especially with controlled blood pressure. Strict blood pressure control is critical after pediatric kidney transplantation.

MEAN PLATELET VOLUME IS A PREDICTOR OF BLOOD PRESSURE NORMALIZATION IN PEDIATRIC HYPERTENSION

Objective: Arterial hypertension in adolescents is a risk factor for elevated blood pressure and cardiovascular sequelae in adult life. The study aimed to analyze factors influencing blood pressure tracking in pediatric patients with primary hypertension (PH). Design and method: We analyzed retrospectively 77 children with primary hypertension (53 boys, 24 girls, 13.9 ± 2.7 years) and observation period at least 12 months, in whom we assessed clinical data, anthropometric parameters, office blood pressure, ABPM, and biochemical data, including markers of subclinical inflammation: mean platelet volume (MPV), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Results: At the onset of the observation, all patients had arterial hypertension – newly diagnosed (n = 51) or already treated with antihypertensive drugs (n = 26). The observation period was from 1 to 5.25, mean: 2.1 ± 1.0 years. Blood pressure (BP) normalized in 13 (16.9%) patients; seven were previously treated with antihypertensive medications. Patients in whom BP normalized compared to those with sustained hypertension were not-significantly younger (12.9 ± 3.1 vs. 14.1 ± 2.6 [years], p = 0.171), had higher birth weight (3866 ± 425 vs. 3163 ± 614 [g], p = 0.024) and lower initial MPV (9.2 ± 1.4 vs. 10.1 ± 1.3 [fL], p = 0.041) and lower BMI Z-score (0.5 ± 1.0 vs. 1.2 ± 1.2, p = 0.047) and total cholesterol (143.4 ± 26.0 vs. 167.6 ± 33.6 [mg/dL], p = 0.047) after the observation period. Z-score of systolic blood pressure (SBP) at the end of observation correlated with initial values of: BMI Z-score (R = 0.248, p = 0.032), MPV (R = 0.237, p = 0.046), PLR (R = 0.240, p = 0.044), and with nighttime diastolic BP dipping in ABPM (R = -0.309, p = 0.009). SBP Z-score at the end of the observation period also correlated with Z-scores of body weight and BMI (R = 0.327, p = 0.004; R = 0.384, p&lt;0.001) and LDL-cholesterol (R = 0.297, p = 0.031) at the end of observation and with the increase in body weight during the observation period (R = 0.384, p &lt; 0.001). At the end of the observation period, the Z-score of diastolic blood pressure correlated with MPV (R = 0.371, p = 0.003). Conclusions: 1. The chance of normalization of blood pressure in pediatric patients with primary hypertension is influenced by birth weight, body mass loss, and degree of subclinical inflammation. 2. Mean platelet volume might serve as a predictor of blood pressure change in pediatric patients with primary hypertension.

COMMON CAROTID ARTERY ELASTICITY, INTIMA-DIAMETER RATIO, AND TENSILE STRESS IN PEDIATRIC PATIENTS WITH PRIMARY HYPERTENSION

Objective: Elevated blood pressure (BP) lead to increased thickness of arterial wall and increased diameter of arteries, are risk factors of cardiovascular sequelae in adult populations. Intima-diameter ratio (IDR) and tensile stress (TS) may reflect arterial wall-remodeling to elevated BP. The aim was to evaluate common carotid artery elasticity, IDR, and TS in children with primary hypertension (PH). Design and method: 50 untreated patients with PH and we evaluated: common carotid artery(CCA) intima-media thickness (cIMT) and elasticity(E-tracking - ET), central BP and aortic elasticity (aPWV,AIx75HR), office BP and ABPM, and clinical, and biochemical data. IDR (cIMT/minimal diameter of CCA[D]) and TS (MAP∗D/cIMT) were calculated in all the subjects. Results: Patients with PH compared to CG were characterized by significantly higher peripheral, central office and ambulatory BP, BMI Z-score, uric acid, triglycerides, lower HDL-cholesterol and higher aPWV. PH patients had thicker cIMT and larger CCA D. The groups did not differ in parameters of CCA elasticity: beta stiffness index, CCA pulse wave velocity(PWVbeta) and pressure-strain elasticity modulus(Ep) and in IDR(0.08 ± 0.01vs.0.08 ± 0.02,p = 0.479) and TS(584.9 ± 135.5mmHg vs.529.7 ± 84.2,p = 0.095). We found correlations between cIMT(Z-score) and triglycerides, peripheral SBP Z-score, and ABPM MAP 24 h Z-score. CCA D correlated with BMI Z-score, uric acid and HDL-cholesterol, 24 h systolic blood pressure load(SBPL), Central systolic blood pressure(AoSBP) and peripheral diastolic BP Z-score. We found significant correlations between TS and uric acid, 24 h diastolic blood pressure load, and peripheral systolic and diastolic blood pressure Z-scores. There was no association between IDR and BP except for a weak correlation between IDR and SBPL. In PH patients, there was a strong correlation between cIMT and CCA D(r = 0.790,p &lt; 0.001). Conclusions: In children with PH, structural changes and decreased elasticity primarily affect the aorta and to a lesser extent the muscular arteries. In children with PH, both CCA wall thickness and internal diameter are associated with BP, and are significantly higher in children with PH. The changes observed in the carotid artery are probably adaptive in nature, not associated with impaired arterial function, thus intima-diameter ratio or tensile stress measurement does not appear to contribute additional information in this group of patients.

Association of exposure to organophosphate esters with increased blood pressure in children and adolescents

Organophosphate esters (OPEs) are widely added to various industrial and consumer products, and are mainly used as flame retardants and plasticizers. Existing epidemiological studies suggest that OPE exposure may be linked to increased blood pressure (BP) and hypertension risk in adults. However, it remains unclear whether OPE exposure is associated with increased BP in children and adolescents. Here, we investigated the associations between OPE exposure and BP levels in 6–18-year-old children and adolescents from a cross-sectional study in Liuzhou, China. OPE metabolites were determined in spot urine samples (n = 1194) collected between April and May 2018. Three measurements of systolic and diastolic BP for each participant were averaged as study outcomes. Associations of OPE exposure with age-, sex- and height-standardized BP were assessed using linear regression models. We found that each natural log unit increment of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) was associated with a 0.06 standard deviation unit (95% confidant interval (CI): 0.01, 0.11) increase in systolic BP z-score. When conducting stratified analysis based on sex, age, and BMI category, BDCIPP was shown to be positively associated with systolic/diastolic BP z-score in females, but not in males. The associations between bis(2-butoxyethyl) phosphate (BBOEP) and systolic/diastolic BP z-score were pronounced in adolescents, but not in children. Moreover, a significant positive association between 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) and diastolic BP z-score was observed in obese subjects. The present study provides the first evidence that OPE exposure was related to increased BP in children and adolescents. Given the scarcity of high-quality evidence supporting these results, the health effects of OPEs are warrant investigation in well-designed prospective studies.

Increased Arterial Stiffness Is Associated With Reduced Diastolic Function in Youth With Obesity and Type 2 Diabetes.

Background: Increased arterial stiffness is associated with diastolic dysfunction in adults. Data in youth are lacking, so we examined the impact of arterial stiffness on diastolic function in youth.Methods: We obtained diastolic function and augmentation index, pulse wave velocity, brachial artery distensibility, and carotid stiffness on 612 youth [10–24 years, 65% female, 38% normal weight, 36% obese, and 26% with type 2 diabetes mellitus (T2DM)]. Participants were classified as compliant (C) vs. stiff (S) arteries based on seven arterial stiffness parameters [Global Stiffness Index (GSI), S = GSI > 4). Mean differences in covariates were evaluated by Student's t-tests. A stepwise regression analysis was performed to determine if GSI was an independent predictor of diastolic function.Results: Lower diastolic function and more adverse cardiovascular disease (CVD) risk factors were present in the S group (n = 67) than the C group (n = 545) (p < 0.001). Covariates that were associated with diastolic dysfunction were higher GSI, male sex, higher body mass index (BMI), and systolic blood pressure (SBP) z-score (R2 = 0.18 to 0.25; p ≤ 0.05).Conclusion: Adverse diastolic function is seen in youth with increased arterial stiffness independent of CVD risk factors. Interventions to improve arterial stiffness prior to clinical onset of diastolic dysfunction are needed to prevent development of heart failure.

Nocturnal non-dipping on 24-h Ambulatory Blood Pressure Monitoring in children and adolescents with obesity is associated with higher total cholesterol levels

ABSTRACT Background Few studies indicate the occurrence of abnormal nocturnal dipping of blood pressure (BP) in 35–50% of children and adolescents with obesity. The relation between that phenomenon and metabolic complications of obesity remains unclear. To evaluate the association between disorders of glucose and lipid metabolism, and nocturnal non-dipping in pediatric patients with obesity. Methods In 207 children (53.14% girls, mean age 14 (range 2–17), mean BMI Z-SCORE 4.38, range 2.07–10.74) standard 24-h Ambulatory Blood Pressure Monitoring was performed. Normal dipping was defined as a ≥ 10% decline in BP during the night. Results There were 106 (51.21%) cases of non-dippers. The mean 24-h nocturnal systolic BP (SBP) reduction (%) was 9.9 ± 5.5. The mean 24-h nocturnal diastolic BP (DBP) reduction (%) was 15.8 ± 8.5. There was a significant correlation between BMI Z-SCORE and mean day-time SBP (r = 0.14 P = .042). There are positive correlations between 24-h heart rate (beats/min) and BMI Z-SCORE (r = 0.15, P = .027), between fasting glucose and systolic BP Z-SCORE (r = 0.17, P = .03) and between mean diastolic BP and LDL cholesterol (r = 0.23, P = .004). Total cholesterol level was significantly higher in non-dippers (4.34 vs. 3.99 mmol/L, P = .034). There were no significant differences between non-dippers and dippers regarding fasting glucose (4.6 vs. 4.8 mmol/L), 120ʹpost load glucose (5.7 vs. 5.9 mmol/L), insulin (19 vs. 20.2 µIU/mL), HOMA-IR (2.36 vs. 2.44), LDL cholesterol (2.64 vs. 2.51 mmol/L), HDL cholesterol (1.06 vs. 1.03 mmol/L) or triglycerides (1.36 vs. 1.34 mmol/L) levels. Conclusion Nocturnal non-dipping is frequent in pediatric patients with obesity. It is associated with higher total cholesterol levels.

Hypertension in Children with Obstructive Sleep Apnea Syndrome-Age, Weight Status, and Disease Severity.

Older age, obesity, and obstructive sleep apnea syndrome (OSAS) are known to increase the risk of hypertension in adults. However, data for children are scarce. This study aimed to investigate the relationships between hypertension, age, weight status, and disease severity in 396 children with OSAS. The prevalence rates of hypertension, obesity, and severe OSAS (apnea-hypopnea index ≥10) were 27.0%, 28.0%, and 42.9%, respectively. Weight z-score and apnea-hypopnea index were independently correlated with systolic blood pressure z-score, and minimal blood oxygen saturation (SpO2) was independently associated with diastolic blood pressure z-score. Overall, late childhood/adolescence (odds ratio (OR) = 1.72, 95% CI = 1.05–2.81), obesity (OR, 2.58, 95% CI = 1.58–4.22), and severe OSAS (OR = 2.38, 95% CI = 1.48–3.81) were independent predictors of pediatric hypertension. Furthermore, late childhood/adolescence (OR = 2.50, 95% CI = 1.10–5.71) and abnormal SpO2 (mean SpO2 < 95%; OR = 4.91, 95% CI = 1.81–13.27) independently predicted hypertension in obese children, and severe OSAS (OR = 2.28, 95% CI = 1.27–4.10) independently predicted hypertension in non-obese children. In conclusion, obesity, OSAS severity, and abnormal SpO2 are potentially modifiable targets to improve hypertension while treating children with OSAS.