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Background and Aim: Obesity and hyperuricemia (HUA) often coexist and have been widely accepted as risk factors for hypertension, but the role of uric acid (UA) in the relationship between obesity and hypertension remains unknown in children and adolescents., Methods and Results: A total of 7525 subjects aged 6-16 years were from the School-based Cardiovascular and Bone Health Promotion Program (SCVBH) at baseline (2017) and followed up in 2019. Multivariable logistic regression with interaction terms, cross-lagged panel analysis, and causal mediation model were applied to delineate the joint impact of obesity and HUA on hypertension, including the interaction effect, the temporal association, and the mediating effect of UA in the relationship between obesity and hypertension. There were 10.8 % of the participants with normotension at baseline developed hypertension after two years of follow-up. Cross-lagged panel analysis showed that the two-time point association was significant only from baseline BMI to follow-up UA (β1 = 0.302, P < 0.001), but not from baseline UA to follow-up BMI (β2 = 0.002, P = 0.745). Multivariable logistic regression showed that both obesity and HUA increased the risk of hypertension, but no interaction effect between HUA and obesity. The causal mediation analysis found that UA partially mediated the association between BMI and SBP (mediate proportion: 20.3 %, 95 % CI: 17.4-22.9 %) or DBP (mediate proportion: 11.9 %, 95 % CI: 3.9-18.2 %). The results were consistent in the analysis of systolic hypertension rather than diastolic hypertension., Conclusions: It is mediating effect that UA played in the progress from obesity to hypertension, particularly systolic hypertension in children and adolescents., Competing Interests: Declaration of competing interest None., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: This study aims to examine the temporal relationship between uric acid (UA) and insulin and their joint impact on T2DM in middle-aged adults., Methods and Results: The cohort consisted of 1351 non-diabetic adults who had serum UA and insulin measured twice at baseline and follow-up over 7.7 years on average, and incidence of T2DM in the outcome survey12.2 years later. After adjusting for covariates, the path coefficient from baseline UA to follow-up insulin was 0.082 (p < 0.001); the path from baseline insulin to follow-up UA was 0.060 (p = 0.030). In the mediation model with baseline UA as the predictor, total effect of baseline UA on incident T2DM was 0.089 (p = 0.016). The mediation effect through follow-up insulin on the UA-T2DM association was 28.1%. The direct effect of baseline UA on T2DM (0.064) became nonsignificant (p = 0.078). In the mediation model with baseline insulin as the predictor, total effect of baseline insulin on T2DM was 0.218 (p < 0.001). The mediation effect through follow-up UA on the insulin-T2DM association was 5.5%. The direct effect of baseline insulin on T2DM (0.206) remained significant (p < 0.001). The baseline hyperinsulinemia-follow-up hyperuricemia group showed the highest incidence rate of T2DM (27.9%)., Conclusions: The bidirectional temporal relationship suggests that UA and insulin influence each other in non-diabetic individuals, and the directionality plays pathogenic roles in the development of T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Data are limited regarding differential and common effects of cardiovascular risk factors on subclinical changes in vascular structure and function. We aimed to examine the relationships of life-course cumulative burdens of cardiovascular risk factors with adult arterial pulse wave velocity (PWV) and carotid intima-media thickness (CIMT) in a longitudinal cohort of the Bogalusa Heart Study., Methods: The cohort consisted of 900 subjects who had aortic-femoral PWV and CIMT measurements. These participants were examined 5-16 times for body mass index (BMI), blood pressure, atherogenic index of plasma (AIP), and low-density lipoprotein cholesterol (LDLC) from childhood to adulthood. The area under the curve (AUC) was calculated as a measure of long-term burden of the risk factors., Results: Adjusting for covariates, adult PWV was associated with AUCs of BMI, systolic blood pressure (SBP) and AIP (standardized regression coefficient [β] = 0.191, 0.321, 0.153, respectively; P < 0.001 for all). Adult CIMT was associated with AUCs of BMI, SBP, AIP and LDLC (β = 0.115, 0.202, 0.141, 0.152, respectively; P < 0.001 for all). Moreover, childhood BMI was associated with adult PWV and CIMT (β = 0.088 and 0.075, respectively; false discovery rate q values < 0.05 for both), and childhood LDLC with adult CIMT (β = 0.079; false discovery rate q value < 0.05). These associations did not differ significantly among race and sex groups., Conclusions: The life-course cumulative burden of BMI, SBP, and AIP has common effects on arterial wall stiffening and thickening, whereas LDLC is specifically associated with arterial wall thickness, and this effect starts in early life., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Despite an increasing number of studies investigating the links between increased BMI and a better prognosis of cardiovascular disease, which has been termed the "obesity paradox," few of them take the lean mass into consideration., Objectives: This study aimed to explore the associations of body composition compartments, especially the lean mass, with cardiometabolic abnormalities in children and adolescents., Methods: In a nationwide cross-sectional study of 6- to 18-y-old children (n = 8967, 50.1% boys), we measured body composition using DXA scan, and calculated BMI, fat mass index (FMI), and lean mass index (LMI). The exploratory outcomes were cardiometabolic abnormalities, including hypertension, dyslipidemia, hyperglycemia, and insulin resistance. Adjusted linear regression coefficients and ORs were calculated to assess the associations between body composition indicators and cardiometabolic abnormalities., Results: Unlike BMI and FMI, LMI was inversely associated with homeostasis model assessment of insulin resistance (β: -0.06; 95% CI: -0.09, -0.03; P < 0.001), fasting plasma glucose (β: -0.08; 95% CI: -0.11, -0.05; P < 0.001), non-HDL cholesterol (β: -0.10; 95% CI: -0.13, -0.08; P < 0.001), LDL cholesterol (β: -0.12; 95% CI: -0.14, -0.09; P < 0.001), and total cholesterol (TC) (β: -0.16; 95% CI: -0.19, -0.14; P < 0.001). After multivariable adjustment, all the odds of cardiometabolic abnormalities were increased from the lowest quartile to the highest quartile of BMI and FMI (P-trend < 0.05); however, the odds of high TC, high LDL cholesterol, hyperglycemia, and insulin resistance were decreased with LMI (P-trend < 0.05). Obese children with high LMI did not have significantly increased odds of high TC, high LDL cholesterol, and high non-HDL cholesterol compared with normal-weight children without high LMI., Conclusions: Greater lean mass may have a protective impact on high TC, high LDL cholesterol, hyperglycemia, and insulin resistance in children and adolescents. This finding suggests that the "obesity paradox" may be partly explained by high lean mass., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background & Aims: The rise in the prevalence of childhood obesity has increased the demand for accurately evaluating body fatness in pediatric population. The aim of this study was to provide a series of sex- and age-specific body fat reference centiles for evaluating total body fat development and fat distribution in Chinese children and adolescents using dual-energy x-ray absorptiometry (DXA)., Methods: A nationwide sample of Chinese children and adolescents aged 3-18 years (n = 12,790) was drawn from a cross-sectional survey of the China Child and Adolescent Cardiovascular Health study (2013-2019). Fat measurements, including total fat mass index (FMI), total body fat percentage (BF%), regional FMI, trunk to leg (T/L) fat ratio and android to gynoid (A/G) fat ratio, were derived from whole body DXA scans. Sex- and age-specific centiles were estimated using the lambda-mu-sigma method and then compared with values derived from the US National Health and Nutrition Examination Survey (1999-2004) and Korean National Health and Nutrition Examination Survey (2008-2011)., Results: During early childhood, almost all body fat parameters decreased with age, except an increase in A/G ratio. After 7 years onward, drastic upward trends of total FMI and BF% were exhibited in boys till 10 years, followed by opposite downward trends during 11-14 years; while sustained increase of FMI was shown in girls across ages accompanied by relatively constant BF% levels. Meanwhile, steady increases were noticed for A/G ratio and T/L ratio, which were more pronounced in boys. In addition, the proposed body fat references were much lower than the US but similar to Koreans despite of subtle differences., Conclusions: This is the first study to present a set of DXA-based body fat reference for Chinese children and adolescents aged 3-18 years. The new reference provides clinicians and researchers a useful tool for assessing body fat development and distribution patterns throughout early childhood and adolescence., Competing Interests: Conflict of Interest The authors have no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

Background: Observational studies have reported inconsistent results on the association between circulating fatty acids and obesity., Objective: The objective of this study was to investigate the relationship between erythrocyte phospholipid fatty acid composition and obesity in children and adolescents., Methods: We conducted a case-control study including 1442 obese and 1442 normal-weight children and adolescents. Circulating fatty acid composition between cases and controls were compared both in the present study and literature-based meta-analysis. Individual fatty acids contributing most to discriminating cases and controls were identified by orthogonal partial least squares-discriminant analysis and their associations with obesity were explored by a conditional logistic regression model., Results: Five saturated fatty acids (14:0, 16:0, 17:0, 18:0, 20:0) were higher, 9 polyunsaturated fatty acids (18:3n-3, 20:3n-3, 20:5n-3, 22:5n-3, 22:6n-3, 18:2n-6, 20:2n-6, 20:3n-6, 20:4n-6) were lower in cases than in controls, while pooled results from the comparative meta-analysis were only consistent in 22:5n-3, 22:6n-3 and 18:2n-6. The orthogonal partial least squares-discriminant analysis model indicated that 16:0, 18:0, 20:4n-6, and 22:6n-3 were the fatty acids contributing most to discriminating cases and controls. In the conditional logistic regression model, significant positive associations were found for 16:0 (per 1 SD OR = 1.43, 95% CI, 1.35-1.52) and 18:0 (per 1 SD OR = 1.12, 95% CI, 1.09-1.16), while significant inverse associations were found for 20:4n-6 (per 1 SD OR = 0.63, 95% CI, 0.58-0.69) and 22:6n-3 (per 1 SD OR = 0.56, 95% CI, 0.52-0.61)., Conclusions: Erythrocyte phospholipid 16:0 and 18:0 were positively and 20:4n-6 and 22:6n-3 were inversely associated with obesity in children and adolescents., (Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Considerable attention is given nowadays to the presence of cardiovascular diseases risk factors in children. The current blood lipid classification system for Chinese children was based on the United States National Cholesterol Education Program (NCEP) cutpoints, which did not take the age, gender and race differences into consideration. This study aimed to develop gender- and age-specific lipid cutpoints for dyslipidemia screening in Chinese children and compare the ability of new cutpoints and NCEP pediatric cutpoints to predict obesity and unfavorable blood pressure (BP) levels., Methods: Data were obtained from a nationwide multicenter cross-sectional study: The China Child and Adolescent Cardiovascular Health Study, comprising 12,875 Chinese children aged 6-18 years. We calculated cutpoints for abnormal levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) that were linked to Chinese adult abnormal lipid thresholds using the General Additive Model for Location Scale and Shape method., Results: Borderline-high and high cutpoints (TC, LDL-C and TG) as well as low cutpoints (HDL-C) were developed to classify the abnormal blood lipid levels in Chinese children. Better performance for prediction of obesity, elevated BP, and hypertension were found with the proposed cutpoints in comparison with the NCEP pediatric cutpoints (AUC for obesity: 0.612 vs. 0.597, p = 0.017; AUC for elevated BP: 0.529 vs. 0.521, p = 0.017; AUC for hypertension: 0.536 vs. 0.527, p = 0.016)., Conclusions: The gender- and age-specific cutpoints should improve the accuracy of dyslipidemia screening in China and be more reasonable in practice., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Studies have shown that peak circulatory power (peak CircP; peak oxygen uptake × peak systolic blood pressure) is a variable predictor of prognosis in patients with left heart failure. It remains unknown whether peak CircP also predicts outcome in patients with idiopathic pulmonary arterial hypertension (IPAH)., Methods: Patients with newly diagnosed IPAH who underwent symptom-limited cardiopulmonary exercise testing (CPET) from 1 January 2011 to 1 January 2014 in Fuwai Hospital were prospectively enrolled and followed for up to 66 months for cardiac events (mortality and lung transplantation)., Results: One hundred forty patients with IPAH (104 female, mean age: 33 ± 11 years) were studied. During follow-up (mean: 42 ± 14 months), 24 patients died and 1 patient underwent lung transplantation. In the univariate analysis, peak oxygen uptake(VO 2 ), oxygen uptake at anaerobic threshold, ventilation (VE)/carbon dioxide output (VCO 2 ) slope, end-tidal partial pressure of carbon dioxide at anaerobic threshold, peak systolic blood pressure (SBP), the change of SBP, the change of heart rate, peak work rate, peak CircP, pulmonary vascular resistance, cardiac index and World Health Organization functional class were predictive of cardiac events (all P < .05).In the multivariate analysis, Peak CircP in the fourth model had the highest significance compared with peak VO 2 and VE/VCO 2 slope in the second and third model (chi-square = 5.26, P < .02, HR: 0.99, 95% CI: 0.99 to 1.00)., Conclusions: Peak CircP, better than peak VO 2 and VE/VCO 2 slope, was a strong predictor of cardiac events among exercise parameters in patients with IPAH., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: Obesity and hypertension are two risk factors of left ventricular hypertrophy (LVH) in adults. We aimed to examine the impacts of body weight and blood pressure (BP) from childhood on adult LV geometric remodeling., Methods: The study cohort consisted of 1256 adults aged 27-42years who had 2-10 measurements of body mass index (BMI) and BP from childhood in 1987 to adulthood in 2010. We calculated the cumulative and incremental values of BMI and BP from childhood to adulthood. In adulthood, four LV geometric patterns were defined based on the values of left ventricular mass index (g/m 2.7 ) and relative wall thickness: normal geometry, concentric remodeling (CR), eccentric hypertrophy (EH) and concentric hypertrophy (CH)., Results: The prevalence of abnormal LV geometric patterns in adults was 26.4% for CR, 2.0% for EH and 2.5% for CH. For childhood values, systolic BP (Odds Ratio [OR]=1.26, 95% confidence interval [CI]=1.08-1.47) but not BMI (OR=1.06, 95%CI=0.93-1.18) was associated with adult CR, whereas BMI (OR=3.53, 95%CI=2.09-5.98) but not systolic BP (OR=1.04, 95%CI=0.65-1.66) was associated with adult EH. Both childhood BMI (OR=2.69, 95%CI=1.77-4.09) and systolic BP (OR=1.64, 95%CI=1.07-2.51) were independently associated with adult CH. For adulthood, cumulative and incremental values, BMI and systolic BP were independently associated with adult CR, EH and CH., Conclusion: Excessive body weight and elevated BP from childhood have independent influences on the development of adult LV geometric remodeling., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: The American Heart Association's 2020 Strategic Goals have defined a new concept of cardiovascular health for adults and children, emphasizing the importance of primordial prevention of cardiovascular diseases. However, detailed data on the trends of ideal cardiovascular health in Chinese children and adolescents are sparse., Methods: A total of 5596 children and adolescents (aged 6-18years) were selected from two cross-sectional surveys conducted in 2004 and 2014, respectively. Cardiovascular health behaviors (smoking, body mass index, physical activity, and diet) and factors (total cholesterol, blood pressure, and glucose) were evaluated, and only participants with information on all 7 metrics (n=4309) were included for the cardiovascular score analysis., Results: During 2004-2014, ideal levels of almost all the seven metrics decreased, except for a marked increase in physical activity (boys: 23.0% vs 52.8%; girls: 16.2% vs 41.0%). Overall, only 19.5% of boys and 22.0% of girls had ideal cardiovascular health (score≥6) in 2004, which worsened in 2014 (boys: 9.8%; girls: 16.0%). The prevalence of ideal cardiovascular health factors also declined, but the prevalence of ideal cardiovascular health behaviors increased. Being a girl and having a younger age (aged 6-11years) were associated with higher prevalence of ideal cardiovascular health. Higher family income and parental education were associated with a higher prevalence of ideal cardiovascular health behaviors., Conclusion: Adverse trends in ideal cardiovascular health were observed among Chinese children and adolescents during 2004-2014. Effective intervention programs, in particular targeting children and adolescents, need to be developed to promote cardiovascular health in China., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background/objectives: There are few studies investigating the long-term association between childhood blood pressure (BP) and adult cardiovascular remodeling. We seek to examine the effect of elevated childhood BP on cardiovascular remodeling in early or middle adulthood., Methods: We used the "Beijing BP Cohort Study", where 1259 subjects aged 6-18 years old were followed over 24 years from childhood (1987) to early or middle adulthood (2011). Anthropometric measures and BP were obtained at baseline and follow-up examinations. Carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (cIMT), and left ventricular mass index (LVMI) were measured to assess cardiovascular remodeling in early or middle adulthood. Multiple logistic regression models were used to assess the odds ratio (OR) and 95% confidence interval (CI) for cardiovascular remodeling., Results: 82 out of 384 children with elevated BP (21.4%) had adult hypertension. Compared to those with normal BP, children with elevated BP were at 2.1 times (95% CI: 1.4-3.1) likely to develop hypertension in early or middle adulthood. Compared to those with normal BP, children with elevated BP were at higher OR of developing high cfPWV (OR=1.8, 95% CI=1.3-2.4), high cIMT (1.4, 1.0-1.9), or high LVMI (1.4, 1.0-1.9) in early or middle adulthood. The ORs for remodeling (for any measures) were 1.4 (0.9-2.0) in early adulthood for children age 6-11 years, and 1.6 (1.1-2.4) in middle adulthood for those aged 12-18 years., Conclusions: Children with elevated BP from 6 years old have accelerated remodeling on both cardiac and arterial system in early or middle adulthood., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)