Pediatric,body,mass,index,trajectories,and,the,risk,of,hypertension,among,adolescents,in,China:,a,retrospective,cohort,study

Wen-Xin Ge · Di Han · Zi-Yao Ding · Li-Ping Yi · Zhuo-Qiao Yang · Xin-Nan Wang · Yue Xiao · Fei Liang ·Bo Hai · Hui-Ling Lv · Hui Shen,,6 · Hai-Bing Yang,,6 · Jie-Yun Yin · Jia Hu,,6

Abstract Background The impact of pediatric body mass index (BMI) trajectories on the risk of adolescent hypertension (HTN)determined by three separate visits remains unclear.This longitudinal study aims to identify potential pediatric sex-specific BMI trajectories and to assess their associations with HTN and HTN subtypes.Methods Based on the Health Promotion Program for Children and Adolescents (HPPCA) in Suzhou,China,a total of 24,426 participants who had initial normal blood pressure (BP) and had at least four BMI measurements during 2012–2020 were included.HTN was defined as simultaneously having three separate visits of elevated BP in 2020.Latent class growth models were used to explore sex-specific BMI trajectories,whose associations with HTN and HTN subtypes were further examined by logistic regression.Results The incidence of HTN determined through three separate visits was 3.34%.Four trajectories were identified for both sexes: low BMI increasing,medium BMI increasing,high BMI increasing,and highest BMI increasing.Compared to the medium BMI increasing group,the odds ratio (95% confidential interval) for developing adolescent HTN of the low,high,and highest BMI increasing groups among boys were 0.54 (0.39,0.75),1.90 (1.44,2.51),and 2.89 (1.90,4.39),respectively;and the corresponding values for girls were 0.66 (0.48,0.90),2.30 (1.72,3.09),and 4.71 (3.06,7.26).Similar gradually elevated associations between different trajectories with isolated systolic hypertension,systolic and diastolic hypertension were observed.Conclusion Current results emphasized the adverse effects of stable high BMI on HTN and the benefits of maintaining normal weight throughout childhood.

Keywords Body mass index · Children · Hypertension · Pediatric · Trajectories

Hypertension (HTN),an important risk factor for cardiovascular disease (CVD),has become a severe global health concern [1,2].Blood pressure (BP) levels and the prevalence of HTN among children and adolescents have increased rapidly in recent decades,especially in adolescents [3,4].Based on three separate BP visits,two recent multicenter studies in China [5,6] reported that the prevalence of HTN among adolescents aged 12–17 years was 8.8% and 5.0%,respectively.A large amount of evidence suggests that adolescent HTN is strongly associated with future target organ damage (i.e.,carotid intima-media thickness and left ventricular hypertrophy) [7] and increases the risks of adult HTN [8] and premature death [9],which further aggravates the pediatric burden of CVD.Notably,the earlier the onset of HTN is,the longer the treatment period and the worse the prognosis will be [10].Therefore,early identification and intervention of adolescent HTN may be an effective strategy to protect pediatric health and to prevent HTN in adults.

Pediatric BP measurements are susceptible to “white coat effects”,mood,and environmental factors [11–13].Moreover,the prevalence of elevated BP in children gradually decreased as the number of separate BP visits increased [14].For this reason,the diagnosis of pediatric HTN should be based on at least three separate occasions of elevated BP [15,16].However,a large proportion of previous studies [17–19]in China focused only on elevated BP at a single visit,which greatly overestimates the true prevalence of pediatric HTN[14].

A rising prevalence of adolescent HTN often accompanies the epidemic of childhood obesity [20].Obesity,of which body mass index (BMI) is the most widely used indicator [21],has been identified as the most common risk factor for HTN [5,18,22].Different changing patterns of BMI from childhood to adolescence have been demonstrated,as BMI usually fluctuates in early life and has sex differences[23–25].Hence,a single cross-sectional BMI measurement,which ignores the dynamics of BMI over time,may be insufficient to assess pediatric obesity-related disease risks.Fortunately,BMI trajectory,based on the latent class growth model (LCGM) of utilizing multiple repeated measures in a longitudinal cohort,may provide additional information about BMI and BP-related outcomes [18,23].

Although the association of childhood BMI trajectories with single-occasion elevated BP during adolescence was assessed in China [18,19],there are few studies of BMI trajectories and HTN determined by three visits.To fill this knowledge gap,the present study aims to identify potential pediatric sex-specific BMI trajectories and to assess their associations with HTN and HTN subtypes in adolescence using longitudinal data from the Health Promotion Program for Children and Adolescents (HPPCA) in Suzhou,China.

Study design and population

The current study was a retrospective cohort study based on a large-scale,ongoing,school-based monitoring program (HPPCA) conducted from 2012 to 2020 in Suzhou,China.Detailed information about HPPCA has previously been published [26–28].Briefly,HPPCA provided free annual health check-ups for all school-based students aged 6–17 years in Suzhou to assess the growth and development of children and adolescents.Physical examinations were conducted at general hospitals,centers for disease prevention and control,or community healthcare facilities.Notably,students in the third year of junior high school and third year of senior high school who would take other special physical examinations for school entrance were not included.

In 2020,we randomly selected 66 junior/senior high schools attending HPPCA to conduct specific BP surveillance to determine the epidemic status of HTN among adolescents in Suzhou.As a result,a total of 46,788 schoolbased adolescents aged 12–17 years were enrolled.To give an accurate picture of the incidence of adolescent HTN,we used the 2020 surveillance data as an endpoint and excluded 9838 children who had elevated BP at their initial HPPCA visit.Subsequently,12,524 participants with less than four BMI measurements during 2012–2020 were further excluded.Finally,24,426 participants were included in the current analysis.Figure 1 displays the details of our study population selection.Differences between the included and overall populations (excluding those with elevated BP at the initial HPPCA visit) in 2020 were examined.

All HPPCA work was carried out with the consent of participants and their parents.This study was approved by the Ethics Committee of Suzhou Center for Disease Prevention and Control (No.SZJK2020-XW001).

BMI measurements and definitions

All physical examinations were carried out by professionally trained health workers using the same type of age-appropriate equipment and following the same procedures.Participants were asked to wear light clothes and without shoes before measuring their height and weight with accuracies of 0.1 cm and 0.1 kg,respectively.BMI was calculated as weight (kg) divided by the square of the height (m).Underweight,normal weight,overweight,and obesity were defined according to the latest Chinese pediatric standards of ageand sex-specific BMI cut-offs for children and adolescents,respectively [29,30].

BP measurements and definitions

At the annual HPPCA visit,a clinically validated Electronic Blood Pressure Monitor (i.e.,Omron HBP1300,HBP1320)of appropriate size was used to measure BP in children and adolescents.After sitting and resting in a quiet environment for at least 15 minutes,the BP device was placed at the same level as the participant"s heart and right arm cuff.

Three consecutive BP values were measured at two-minute intervals each time,and the average of the two closest BP readings was recorded.

Participants enrolled at the specific BP surveillance in 2020 were remeasured at least two weeks later if their first BP recorded by HPPCA was defined as elevated BP.If elevated BP was again diagnosed at the second visit,a third BP measurement was made following the same process.The second and third BP measurements were conducted by acquainted school nurses on the campus of the specific student.Almost all students with elevated BP at first (97.16%of cooperation rate) or second (98.18% of cooperation rate)visit participated in subsequent BP measurements except children who transferred to other cities or were on long-term sick leave.Supplementary Fig.1 shows a detailed detection process of HTN,which was consistent with other surveys in China [6,13].

Fig.1 Details of the study population selection. HPPCA Health Promotion Program for Children and Adolescents,BMI body mass index

Elevated BP was defined as systolic blood pressure (SBP)and/or diastolic blood pressure (DBP) equal to or above the age-,sex-and height-specific 95th percentile (P95) according to the Chinese standard “Reference of screening for elevated blood pressure among children and adolescents aged 7–18 years” (WS/T 610–2018) [16].HTN was defined as simultaneously having three separate visits of elevated BP[16].Isolated systolic hypertension (ISH),isolated diastolic hypertension (IDH),and systolic and diastolic hypertension(SDH) was defined as SBP ≥ P95and DBP < P95,DBP ≥ P95and SBP < P95,and SBP ≥ P95and DBP ≥ P95,respectively.

Statistical analysis

LCGM was a semiparametric model designed to identify clusters of boys or girls with similar BMI growth trajectories across the longitudinal cohort by SAS procedure trajectory (Proc Traj) [31,32].The BMI trajectory model with a censored normal distribution was fitted using maximum likelihood estimation.First,considering that a systematic review summarized that most child BMI trajectory studies reported three to four latent classes [23],we sequentially explored two to six classes of trajectory models.Next,we assumed that all trajectory shapes were cubic and compared their statistical significance from higher to lower degrees(i.e.,cubic,quadratic,and linear).If the higher degrees were not significant,then lower degrees would be selected in turn.

As recommended in studies [31,32],the detailed selection criteria for the best-fit model were as follows: (1) Bayesian information criteria (BIC).The closer the BIC values are to 0,the better the model is fitted;(2) BIC log Bayes factor.This value is approximately equal to two times the difference in BIC between the compared models.When comparing two models,if the BIC log Bayes factor is greater than 6,it is recommended to choose the complex model;(3) average posterior probability is required to be greater than 0.7,and (4) each trajectory contains at least 5% of participants of the included populations.Supplementary Table 1 shows the results of trajectory parameter estimation by LCGM in both sexes.Finally,four trajectory groups with cubic polynomials were selected as the optimum models for boys and girls.

Continuous and categorical variables were represented as [mean (standard deviation,SD)] andn(%),respectively.Analysis of variance and chi-square tests were adopted to assess group differences across BMI trajectories.Multiple linear regression analysis and Cochran-Armitage trend analysis were used to examine the trends of SBP,DBP,and different HTN subtypes in adolescents.Binary logistic regression was used to assess the associations of different BMI trajectories with multiple BP-related outcomes (i.e.,first elevated BP,HTN,ISH,IDH,and SDH),after adjusting for the district,the number of measurements,age in 2020,as well as BMI,SBP,DBP at the initial HPPCA visit.Simultaneously,the odds ratio (OR) and 95% confidence interval (CI) were calculated.All analyses were conducted using SAS statistical (version 9.4,SAS Institute) software.A value ofP<0.05 was considered statistically significant.

The basic characteristics of the overall populations (without individuals who had elevated BP at their initial HPPCA visit) in 2020 and included participants are shown in Supplementary Table 2.The included participants consisted of 24,426 adolescents aged 12–17 years,12,446 (50.95%)of whom were boys.The average age of the included participants was 14.07 ± 1.66 years.The vast majority of the variable characteristics were comparable between the overall and included participants.

Boys and girls had similar BMI trajectories in the current study.The four trajectories were identified as “low BMI increasing” [4565 boys (36.68%) vs.4493 girls (37.50%)],“medium BMI increasing” [4311 boys (34.64%) vs.4844 girls (40.43%)],“high BMI increasing” [2615 boys (21.01%)vs.2024 girls (16.89%)],and “highest BMI increasing” [955 boys (7.67%) vs.619 girls (5.17%)],respectively.The identified four BMI trajectories are compared with the growth curves recommended by Chinese standards in both sexes[29,30] (Fig. 2).More than half of the overweight subsets in 2020 (54.72% for boys and 69.48% for girls) were classified into the high BMI increasing group,and a large proportion of obese individuals in 2020 (48.80% for boys and 60.84%for girls) were placed in the highest BMI increasing group(Fig. 3).Interestingly,for both sexes the low and highest BMI increasing trajectories were very close to the growth curves of underweight and obesity thresholds,respectively.During the nine-year visits,the medium BMI increasing group was always intermediate between the underweight and overweight cutoffvalues,so we chose this trajectory as a reference.

Fig.2 Four different BMI trajectories among children by sex. a Boys;b girls.Underweight,overweight,and obesity were defined according to the Chinese pediatric standards of age-and sex-specific BMI cutoffs for children and adolescents,respectively [29,30]. BMI body mass index

Fig.3 Proportions of different BMI trajectories for both sexes by district and weight status in 2020. a Boys by district group;b girls by district group; c boys by weight status; d girls by weight status. BMI body mass index

Table 1 presents the basic characteristics across BMI trajectory groups in both sexes.The average age at initial HPPCA was 8.88 years for boys and 8.91 years for girls.In 2020,the prevalence of overweight and obesity in boys was nearly twice as high as in girls (36.64% vs.20.20%,P<0.01).Incidences of HTN and HTN phenotypes at separate third BP visits for boys and girls are shown in Table 2.The incidence of ISH,IDH,SDH,and HTN differedsignificantly between the four trajectories in both sexes (allP<0.05).The incidence of elevated BP at the first,second,and third visits was 20.27%,6.21%,and 3.34% in boys,whereas the corresponding values were 18.31%,6.01%,and 3.34% in girls (Pfor trend <0.001).The incidence of HTN in adolescents was 3.34% in the included populations.However,boys had a higher incidence of ISH but a lower incidence of IDH than girls (P<0.05).Furthermore,the incidence of ISH,IDH,and SDH significantly decreased at three separate visits (allPfor trend <0.001).The same trends were found in the different trajectories in both sexes(allPfor trend <0.001).

Table 1 Basic characteristics of different BMI trajectory groups in boys and girls

Table 2 Incidences of HTN and HTN phenotypes at separate third BP visits for boys and girls

Table 2 (continued)

Tables 3 and 4 summarize the OR (95% CI) for the associations of different BMI trajectory groups with elevated BP at the first visit,HTN,and different HTN subtypes.Compared to the medium BMI increasing group,the high and highest BMI increasing groups had gradually increased risks of elevated BP at first visit and HTN in the included populations,whereas the low BMI increasing group had a decreased risk of HTN.The OR (95% CI) for developing adolescent HTN of the low,high,and highest BMI increasing groups vs.the medium BMI increasing group among boys were 0.54 (0.39,0.75),1.90 (1.44,2.51),and 2.89 (1.90,4.39),respectively;the corresponding values for girls were 0.66 (0.48,0.90),2.30 (1.72,3.09),and 4.71 (3.06,7.26).In the included participants,the highest BMI increasing group was significantly associated with ISH and SDH compared to the medium BMI increasing group,with OR (95% CI) of 3.08 (2.11,4.51) and 7.16 (4.06,12.65),respectively.However,the association of the highest increasing BMI group with IDH was neutral[1.36 (95% CI 0.56,3.30)].

Table 3 Association between different BMI trajectory groups and HTN

Table 4 Association between different BMI trajectory groups and HTN subtypes at the third visit

In this retrospective cohort study,we found that the incidence of elevated BP gradually decreased as the number of separate BP visits increased,approaching the accurate level of pediatric HTN.In addition,we identified four pediatric BMI growth trajectories of both sexes in 24,426 participants.Children who were grouped into the high and highest BMI increasing (mainly defined as overweight and obese in 2020) trajectories had higher risks of developing adolescent HTN than children with medium BMI increasing trajectory(mainly defined as normal weight in 2020);in contrast,the low BMI increasing trajectory may be a protective factor.

In both clinical and epidemiological practice,three separate BP visits are required to assess BP levels and the incidence of HTN in adolescents [14].For example,a meta-analysis showed that the global prevalence of pediatric elevated BP at the first,second,and third visits was 12.10%,5.60%,and 2.70%,respectively [14].Another study in China reported that the prevalence of elevated BP in adolescents aged 12–17 years decreased from 16.50%at the first visit to 5.00% at the third visit [6].These findings are similar to the results of our study.Three separate BP visits can significantly reduce the impact of the“white coat effect” or other confounding factors,and thus may contribute to accurate screening ofindividuals who require further clinical diagnosis and treatment [11,12].In addition,the prevalence of HTN in the total population(including those with elevated BP at the initial HPPCA visit) was 4.09% in 2020 in this study (results not shown),which was slightly lower than in other surveys in China [5,6].Differences in cities and HTN definition criteria may explain this phenomenon.

Pediatric weight gain is positively associated with BP levels,and persistent obesity has a long-term and cumulative effect on the risk of developing elevated BP or HTN in adolescence or adulthood [6,33,34].Similar pediatric studies conducted in Iran [35],South Africa [36],Germany[37],and other Chinese studies [18,19],consistently showed that the higher BMI increasing trajectory was,the higher prevalence or incidence of elevated BP assessed by a single BP visit would be.Notably,in a cross-sectional study conducting three separate BP visits in China,the risk of elevated BP and HTN in obese children was 8.6 and 14.0 times higher than in normal-weight individuals,respectively[13].In this nine-year cohort,we also found that the risk of adolescent HTN in the highest BMI increasing group was significantly higher than that of elevated BP,using the medium BMI increasing group as a reference.Studies on the risk of elevated BP at a single measurement in children might be inaccurate [14],which also implied that the current disease burden of true HTN in obese adolescents might have been underestimated in previous studies [17–19].In addition,Wang et al.[18] emphasized that the peak age of childhood obesity onset was approximately three years earlier than that of elevated BP.Therefore,early scientific interventions for obese children to bring their weight down to the standard range may effectively reduce their risk of HTN in adolescence.

This study provided insight into the associations between different HTN subtypes and BMI trajectories.We found a significantly increased risk of the highest BMI increasing group for ISH and SDH,but not for IDH.Studies have shown that with increasing age in children,the incidence of ISH increases,while the incidence of IDH decreases [38].Besides,obesity mainly affects central pulsatile hemodynamics changes (i.e.,aortic stiffness),resulting in a greater elevation of SBP than DBP [39].Interestingly,boys had higher ISH incidence but lower IDH incidence compared togirls,possibly due to different hormone levels between sexes during puberty [40].Therefore,it is significant to classify children who have different types of HTN and to adopt sexspecific interventions.

There were some strengths in the current study.To our knowledge,this was one of the first studies to explore the association of pediatric BMI growth trajectories with HTN and different subtypes on three separate occasions.The large sample size recruited from the general population and standardly measured data enhanced the robustness of the results,in contrast to other self-reported or hospital-based studies.The second and third BP measurements in this study were conducted by acquainted school nurses on the campus of the specific student,which could be beneficial in reducing the white coat effect.In addition,the 2020 specific BP surveillance had a high cooperation level (97.16% for the second visit vs.98.18% for the third visit).Finally,after excluding participants who had elevated BP at their initial HPPCA visit,we used incidence rather than prevalence to get a clearer picture of the rate of new-onset and risk estimates for pediatric HTN over nine years.

Admittedly,there remained some limitations in our current study.First,only children and adolescents in Suzhou(a developed region in eastern China),were recruited in the current study,which might not be generalized to other populations;second,consistent with other large-scale screening studies [6,13] in China,the second or third BP visits were conducted only for children diagnosed with elevated BP at the previous visit.Children with normal BP at the first or the second visit were not assessed for the second or third visit,which may underestimate the risk of masked HTN;third,limited confounders were included in the statistical analysis without access to dietary habits,physical activity,and genetic family history of HTN.Finally,it is challenging to distinguish fat distribution in the body with BMI,and subsequent studies should explore growth trajectories that better reflect the degree of obesity.

In conclusion,the current results emphasized the adverse effects of high BMI on adolescent HTN and the benefits of maintaining a normal weight throughout childhood.Authorities should consider guiding obese children to reduce their weight actively and strengthen the routine monitoring of three separate BP measurements.

Supplementary InformationThe online version contains supplementary material available at https:// doi.org/ 10.1007/ s12519-022-00626-1.

AcknowledgementsWe sincerely appreciate all the children,parents,and workers who were involved in the study.

Author contributionsGWX: writing–original draft.HD,DZY,HB,LHL,SH,and YHB: data curation,formal analyses.YLP,YZQ,WXN,XY,and LF: writing–review and editing.YJY,HJ: conceptualization.GWX and HD contributed equally to this study.All authors had final approval of the submitted and published versions.

FundingThis work was supported by Gusu Health Talents Program Training Project in Suzhou,China (GSWS2020100),the National Natural Science Foundation of China (81602911,82204070,and 82273635),and Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Data availabilityData are only available on an approved request to the corresponding author.

Declarations

Conflict of interestNo financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article.

Ethical approvalAll work was carried out with the consent of participants and their parents.This study was approved by the Ethics Committee of Suzhou Center for Disease Prevention and Control (No.SZJK2020-XW001).

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