Performance Of Different Metabolic Syndrome Definitions In Identifying Left Ventricular Hypertrophy And Geometric Remodeling In Children

BackgroundObesity has become an important health issue in children.Metabolic risk factors such as elevated blood pressure,dyslipidemia,and hyperglycemia have become common in children with the epidemic of obesity.Metabolic syndrome(MetS)is diagnosed when an individual has over 3 metabolic risk factors.Pediatric MetS is an important risk factor for cardiovascular diseases in adulthood,and timely detection and intervention of pediatric MetS could reduce the burden of cardiovascular diseases.However,there are many pediatric MetS references at present with large variations across different criteria.In general,these criteria are mainly divided into 2 categories:dichotomous MetS references(5 types of commonly used domestic and foreign references)and continuous MetS(cMetS)score.Pediatric left ventricular hypertrophy(LVH)and left ventricular geometric remodeling(LVG)are ones of the most commonly used indicators for evaluating subclinical left ventricular structure damage in children.The relationship between LVH or LVG and MetS diagnosed by different references was established,and the accuracy evaluated by screening tests can further test the applicability of MetS definitions.Most previous studies were conducted based on cross-sectional data of foreign populations and only explored the association between LVH or LVG and MetS in children.Few studies rely on the Chinese children population to compare the accuracy of different dichotomous references and cMetS scores for screening pediatric LVH and LVG.Objectives1.To describe the detection rate of MetS defined based on 5 dichotomous references in children;2.To analyze the association of MetS with LVH and LVG diagnosed by different definitions in children;3.To compare the accuracy of MetS diagnosed by different definitions for screening LVH and LVG in children.Subjects and methods1.SubjectsThe study was based on the baseline and the follow-up survey of the "Huantai Childhood Cardiovascular Health Cohort Study",using the convenient cluster sampling method.Participants were from a primary school in Huantai County,Shandong Province.The baseline survey of 1 515 children aged 6-11 years was conducted in 2017,and the follow-up survey of 1 243 children was conducted in 2 years later with the follow-up rate of 82.0%.After excluding those with missing study variables and lost to follow-up,1 111 children were included at baseline and follow-up period to analyze the detection rate of MetS,to test the consistency of the dichotomous MetS references,to explore the association of children with different definitions of MetS with LVH and LVG and to further evaluate the applicability of MetS definitions for screening pediatric LVH and LVG.2.MethodsInformation such as height,weight,waist circumstance and blood pressure of children was acquired through physical examinations.Children’s left ventricular mass index(LVMI)and relative wall thickness(RWT)values were got through the ultrasound diagnostic equipment,and children’s basic demographic information was obtained through questionnaires.Blood biochemical analyzer was used to detect children’s serum lipids,fasting plasma glucose and other serum biochemical indexes.3.DefinitionsThe definition and prevention recommendations of metabolic syndrome in children and adolescents in China(hereinafter referred to as the China reference),the International Diabetes Federation(IDF)reference(hereinafter referred to as the IDF reference),the reference revised by Cook et al.according to the third report of the American Cholesterol Education Program Adult Treatment Group(hereinafter referred to as the Cook reference),the American Heart Association(AHA)reference(hereinafter referred to as the AHA reference)and World Health Organization(WHO)reference(hereinafter referred to as the WHO reference)were used to diagnosed MetS in children.The age-and sex-specific 90th percentiles(P90)of LVMI and RWT based on the present population were used to define the LVH and high RWT.According to LVH and high RWT,pediatric LVG could be categorized three types:children with normal LVMI but elevated RWT were diagnosed as concentric remodeling(CR);children with LVH but normal RWT were diagnosed as eccentric hypertrophy(EH);and children with LVH and elevated RWT were diagnosed as concentric hypertrophy(CH).4.Statistical analysesStatistical analyses were performed using SAS 9.4 software.The consistency tests were used to analyze the consistency of children’s MetS and its components with different dichotomous references.Generalized estimating equation(GEE)model was used to analyze the association between MetS diagnosed by dichotomous references and cMetS scores with LVH and LVG in children.The receiver operating characteristic curve(ROC)based on the GEE model was used to explore the accuracy of screening children LVH and LVG with different MetS references,and net reclassification improvement(NRI)was used to assess the the improvement in the accuracy of cMetS scores compared with dichotomous MetS for screening children’s LVH and LVG.Results1.Detection rate of MetS and its components in children based on 5 dichotomous referencesBased on China,IDF,Cook,AHA,and WHO references,the MetS detectable rates in children aged 6-11 years old at baseline were 4.1%,1.0%,3.7%,7.0%and 1.5%,respectively.The detection rates of MetS in children aged 8-13 years old at follow-up were respectively 9.1%,3.2%,8.2%,12.0%and 3.4%.Obesity had the highest detection rates among components of MetS.2.Consistency comparison of 5 dichotomous MetS referencesAmong the 5 dichotomous references for diagnosing pediatric MetS,there was relatively high consistency between Cook and AHA references[kw=0.67,95%confidence interval(C1):0.58～0.77]for children aged 6-11 years old in the baseline period.However,the consistencies of the remaining dichotomous references were general or poor,whose kws were ranged from 0.18 to 0.56.The consistencies between the China reference,the AHA reference and the Cook reference were acceptable[China reference vs.Cook reference:kw=0.61,95%CI:0.53-0.70,China reference vs.AHA reference:kw-0.66,95%CI:0.58-0.73,Cook reference vs.AHA reference:kw=0.79,95%CI:0.73-0.85]for children aged 8 to 13 years old during the follow-up period,while the consistency of other dichotomous MetS references was general or poor,ranging from 0.40 to 0.55.3.GEE analysis of the relationship between MetS based on different references with children’s LVH and LVGThe baseline and follow-up data were combined and results of the GEE models showed that,except for the IDF reference,the MetS diagnosed by other dichotomous reference was associated with children’s LVH[e.g.China reference:the odds ratio(OR)was 4.02,95%CI was 2.59-6.24]after adjusted for gender,age group,screening time,sleep time and intake of vegetables/fruits.There was no significant association between MetS diagnosed by the dichotomous reference and children’s CR(all P>0.05).With the exception of the IDF reference,the MetS children diagnosed by the dichotomous references(the remaining 4 references)showed a higher risk of EH compared with normal children[e.g.China reference:OR(95%CI)=3.96(2.41-6.49)].With the exception of IDF and WHO references,the MetS diagnosed by the dichotomous references(the remaining 3 references)[e.g.China reference:OR(95%CI)=6.43(2.99-12.85)].Moreover,the elevated cMetS score was associated with pediatric LVH,CR,EH and CH,with ORs(95%CIs)of 1.30(1.23-1.37),1.14(1.07-1.20),1.30(1.23-1.38)and 1.37(1.24-1.50)respectively.4.Evaluation of the accuracy of MetS based on different definitions of screening for children with LVH and LVGThe data of the baseline period and the follow-up period were combined,and the GEE model was used to calculate the predicted value to obtain the combined ROC.The area under curves(AUCs)of the dichotomous references for screening children’s LVH were low,ranging from 0.53 to 0.60,and the AUC(95%CI)value of the cMetS score for screening children’s LVH was 0.72(0.67-0.75);the AUCs of screening for pediatric CR,EH and CH were 0.55-0.56,0.56-0.61 and 0.57-0.64,respectively.The AUCs(95%CIs)of cMetS score screening children’s LVG were 0.61(0.57-0.66),0.72(0.67-0.76)and 0.75(0.67-0.83),respectively.5.Difference analyses comparing the accuracy of cMetS and dichotomous references for screening children with LVH and LVGThe accuracy of the 5 dichotomous references was poor in screening LVH and LVG In contrast,the China reference was acceptable,so this part used the China standard as a reference.The AUC differences,continuous NRI and categorical NRI all showed that the accuracy of the cMetS score was better than the China reference in screening children’s LVH and LVG Taking LVH as an example,the estimated values of AUC difference(95%CI),continuous NRI(95%CI)and categorical NRI(95%CI)were 0.141(0.093-0.189),0.517(0.381-0.653)and 0.311(0.228-0.394),respectively,all P<0.001.The cMetS score showed a similar improvement in accuracy of screening for each type of LVG compared with the China reference.Conclusions1.The detection rates of pediatric MetS based on different dichotomous criteria were quite different.Except for the AHA and Cook references,the consistency of the other dichotomous MetS references is weak.2.It was similar that the accuracy of screening pediatric LVH and LVG based on 5 dichotomous MetS references,while none of them was strong.3.The cMetS score was better than the dichotomous MetS references in screening pediatric LVH and LVG.