| [Background]Hypertension is a major public challenge in China.China faces high prevalence and low control rate of adult hypertension,and the consequent serious disease burden.Hypertensive risk factors are prevalent gradually in children and adolescents.The childhood blood pressure(BP)levels increase alarmedly.Target organ damage is present in the hypertensive children.Hypertensive children are likely to be hypertension as adults.Childhood hypertension is associated with risk of early onset of adult subclinical cardiovascular diseases(CVD).The prevention and treatment of childhood hypertension is crucial to control the rising trend of hypertension and reduce the future burden of disease.Establishing child BP reference should be the fundamental aspect in the prevention of childhood hypertension.The child BP reference is based on BP distribution in the reference population and comprised of BP percentiles for sex,age and height.The BP distribution varies across ethnic groups.Consequently,it is necessary to establish country-specific child BP reference.In 2010,national sex-and age-specific BP standards were developed in China.The standards did not include height,which caused misdiagnosis and missed diagnosis of childhood hypertension.Consequently,the use of the standards is limited.This study aimed to develop national BP references for sex,age and height(the new proposed Chinese references)for identifying accurately Chinese hypertensive children.The child BP reference for sex,age and height can be used to identify accurately hypertensive children but it has two main limitations.On the one hand,it is unknown whether children identified as hypertension using this definition have higher CVD risk in adulthood.On the other hand,the definition provides so many cutoff values that the process of diagnose is complex and time-consuming.To provide evidence for improving the use of the new proposed Chinese references,we used the prospective cohort study to compare the ability of 4 definition(the new proposed Chinese,updated US in 2017 and international references,and the definition presented by US fourth report)to predict adult hypertension and subclinical CVD.This study also simplified the new proposed Chinese references.The cross-sectional and cohort studies were used to validate the screening efficiency of the simplified Chinese definition and its ability to predict adult hypertension and subclinical CVD,respectively.[Objective](1)To establish Chinese child BP references for sex,age and height(the new proposed Chinese references)(2)To compare the ability of the new proposed Chinese,and three other references to identify Chinese children with elevated BP(including prehypertension and hypertension),and predict adult hypertension and subclinical CVD(3)To develop the simplified Chinese child BP reference,and assess its screening efficiency and ability to predict adult hypertension and subclinical CVD[Methods]The reference population from the new proposed Chinese references was composed of 106123 children(males:50.6%;mean age:11.0 years)from 11 cross-sectional studies.The generalized additive model for location,scale and shape(GAMLSS)is used to develop the new proposed Chinese references.BP levels of the 95th percentiles of the new proposed Chinese references at the height of 5th or 95th percentiles in each age group are compared with the corresponding BP levels of Chinese child BP references in 2010.Data which was obtained from a separate cross-sectional study(China child and adolescent cardiovascular health,CCACH;n=43476;males:51.2%;mean age:11.5 years)is used to compare the diagnostic consistency and differences between two aforementioned Chinese child BP standards.Beijing children and adolescents blood pressure cohort study(BBS)was conducted in 1987(n=2296;males:54.1%;mean age:10.6 years).In 2011,the follow-up study was conducted including 1177 subjects.At follow-up,the measurements of carotid-femoral pulse wave velocity(cfPWV),carotid artery intima media thickness(CIMT)and left ventricular mass index(LVMI)were to evaluate cardiovascular function and structure.The differences in the prevalence of pediatric elevated BP at baseline(n=2296)among four different definitions are tested using ?2 test.At follow-up(n=1177),the ability of the four standards to predict adult hypertension and subclinical CVD is assessed by the logistic regression model and area under the receiver operating characteristic curve(AUC).Based on 95th BP percentiles of the new proposed Chinese references,we developed a simplified table and a formula for BP references.According to the CCACH study,sensitivity,specificity,positive predictive value(PPV),negative predictive value(NPV),agreement rate and Kappa correlation coefficient are calculated.Based on the BBS study,the ability of two simplified standards to predict adult hypertension and subclinical CVD is assessed by the logistic regression model and AUC.[Results](1)The BP percentiles of the new proposed Chinese references increase with age and height.Compared with corresponding BP levels of child BP references in 2010,the 95th percentiles systolic BP(SBP)levels of the new proposed Chinese references at the height of 5th percentiles in each age group are lower(males:3-7 mm Hg,females:0-6 mm Hg),the 95th percentiles SBP levels of the new proposed Chinese references at the height of 95th percentiles are higher(males:2-6 mm Hg,females:0-4 mm Hg),the 95th percentiles diastolic BP(DBP)levels of the new proposed Chinese references at the height of 5th percentiles from 3 to 13 years are lower,and the 95th percentiles DBP levels of the new proposed Chinese references at the height of 95th percentiles are similar.Based on the CCACH study,9.9%of hypertensive and 2.7%of normotensive children,diagnosed by child BP references in 2010,are identified as normotension and hypertension by the new proposed Chinese references,respectively.(2)The prevalence of pediatric elevated BP is significantly higher according to the new proposed Chinese versus the Fourth Report,the updated US in 2017,and international references(18.7%vs 14.2%,17.5%,and 18.0%,respectively,all Ps<0.001)according to baseline data of the BBS.According to follow-up data of the BBS,the children identified as elevated BP using any of the the new proposed Chinese,Fourth Report,international and the updated US standards are more likely to have adult hypertension(odds ratio and 95%confidence interval:2.33,1.53-3.57;2.19,1.39-3.46;1.99,1.30-3.06;2,05,1.34-3.15,respectively),high cfPWV(odds ratio and 95%confidence interval:1.78,1.24-2.55;1.62,1.08-2.41;1.71,1.18-2.46;1.83,1.27-2.65,respectively),high LVMI(odds ratio and 95%confidence interval:1.70,1.20-2.40;1.75,1.19-2,58;1.83,1.29-2.60;1.99,1.39-2.83,respectively)and the presence of at least one of high cfPWV,high CIMT,or high LVMI(odds ratio and 95%confidence interval:2.09,1.51-2.91;1.89,1.31-2.73;2.06,1.47-2.88;2.08,1.48-2.92,respectively).Only the new proposed Chinese or updated US standards still have a significant association with adult high CIMT(odds ratio and 95%confidence interval:1.49,1.05-2.10;1.46,1.02-2.08,respectively).The new proposed Chinese reference performs equally compared with three other references in predicting adult outcomes,except that it shows a significantly larger AUC for at least one of adult high cfPWV,high CIMT,or high LVMI prediction in comparison with the Fourth Report standards(P= 0.002 for AUC comparison).(3)Based on CCACH study,the formula for BP references has higher sensitivities(90.0%vs 87.6%),specificity(95.7%vs 93.6%),PPV(81.7%vs 74.5%),NPV(97.8%vs 97.3%),agreement rate(94.7%vs 92.6%)and Kappa correlation coefficient(0.824 vs 0.760)than the simplified BP table.Based on BBS study,childhood elevated BP defined by two simplifed references has the significant associations with adult hypertension and at least one of high cfPWV,high CIMT,or high LVMI(Ps<0.05).Only childhood elevated BP defined by the formula for BP references has the significant association with adult high CIMT(odds ratio and 95%confidence interval:1.65,1.05-2.57).The simplified BP table performs equally compared with the formula for BP references in predicting adult outcomes,except that the simplified BP table shows a significantly larger AUC for adult hypertension prediction(P<0.001 for AUC comparison).[Conclusion](1)The new proposed Chinese references were established,and can be used to accurately identify hypertensive children aged 3-17 years in the clinical practice.(2)The prevalence of pediatric elevated BP is significantly higher for the new proposed Chinese references versus three other standards.The new proposed Chinese references perform equally or better compared with three other standards in predicting adult hypertension and subclinical CVD.Our results indicate that the new proposed Chinese references seem to be more appropriate to monitor the prevalence of childhood elevated BP,and identify Chinese children with elevated BP who has the consequent long-term risk of CVD.(3)The formula for BP references has higher sensitivities,specificity,PPV,NPV,agreement rate,and Kappa correlation coefficient than the simplified BP table.Generally,predictions of adult hypertension and subclinical CVD are equivalent for the simplified BP table and the formula for BP references.The formula for BP references is simple and accurate for screening hypertensive Chinese children. |
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