The prevalence of pediatric obesity has greatly increased worldwide, particularly in low- and middle-income countries (1, 2). In China, the prevalence of general obesity (3) and abdominal obesity (4) among children and adolescents has markedly increased over the past three decades. Obesity is related to cardiovascular (CV) risk (including hyperglycemia, elevated blood pressure, dyslipidemia, metabolic syndrome, and insulin resistance) (5) and short-term target organ damage (6, 7) in childhood. For example, obesity increases the risk of left ventricular hypertrophy (LVH) and left ventricular geometric (LVG) remodeling (8–11) (markers of cardiac structural damage), which are independent predictors of cardiovascular disease (CVD) (12, 13).

LVH was independently associated with the long term adverse CV events, such as coronary heart disease, other CVD related death, and heart failure (14). Specific abnormal LVG remodeling also provided distinct prognostic information. For example, hypertensive patients with concentric hypertrophy (CH) had the highest CV events and all-cause mortality, followed by those with eccentric hypertrophy (EH) and concentric remodeling (CR), compared with those with normal geometry (15). Importantly, participants converting from CR to normal geometry had decreased risk of all-cause mortality (16). LVH has been the most common target organ damage in children and adolescents with hypertension (17), and obesity is strongly associated with abnormal LVG modeling (8–11). Therefore, assessing the presence of LVH and LVG in the early life using a simple and effective obesity-related indicator could be helpful to prevent target organ damage such as LVG remodeling in the short term and the CVD outcomes in the long term.

Although BMI is universally used to determine obesity-related comorbidity and mortality, as an index of obesity it has several limitations. For example, sex- and age-specific cut-offs (18, 19) complicate the use of BMI to define obesity in practice, and BMI does not accurately discriminate body fat distribution (20). In contrast, WC and WHtR are markers of abdominal adiposity that are more closely linked with metabolic disturbances (21), and more strongly associated with CVD outcomes (22) and all-cause mortality (23). Sex- and age-specific cut-offs of WC are also required to define central obesity, whereas WHtR is standardized for height and indirectly adjusts for the effect of age, which is a simple and pragmatic index to correctly assess central obesity (24).

Although recent studies have reported that BMI, WC and WHtR performed similarly to predict common CV risk factors in children and adolescents (25–30), how these adiposity indices comparison when identifying LVH and LVG remodeling in children is largely unknown. A simplified and effective method to identify preclinical cardiac remodeling in the pediatric population is important. Therefore, we aimed to assess the utility of BMI, WC and WHtR for identifying LVH and LVG remodeling (including CR, EH and CH) and to determine the optimal cut-off of WHtR in Chinese children aged 6-11 years.

In this population-based study of Chinese children aged 6-11 years, we found that the magnitude of association of central obesity defined by WHtR with LVH and LVG remodeling was similar with obesity defined by BMI, and both were stronger than central obesity defined by WC; WHtR performed similarly or better than BMI or WC for discriminating LVH and LVG remodeling; and WHtR cut-offs of ~0.5 for boys and <0.5 for girls provided the best discrimination of those with LVH and LVG remodeling. Our findings contribute to the evidence base that support the use of WHtR to identify children at risk of cardio-metabolic outcomes by extending them to include subclinical cardiac structural damage.

Consistent with previous studies (10, 49–51), we found obesity was associated with LVH, and the magnitude of the association was stronger for central obesity defined by WHtR and general obesity defined by BMI than central obesity defined by WC. A cross-sectional study including 281 outpatient children aged 6-16 years found that WHtR was significantly associated with LVH, while BMI or WC was not (51). However, another cross-sectional study among 96 children and adolescents aged 7-15 years showed that WHtR was less strongly correlated with LVMI among these three adiposity indices (52). Differences in demographic characteristics (e.g., different distributions of sex and age) and various methods for measurements of anthropometric and cardiac structural indices (e.g., different positions and devices during measurements) might explain these inconsistent results.

In our study, obesity was also associated with LVG remodeling, and the magnitude of the association of obesity with CH was the strongest, followed by EH and CR. A study including 62 normotensive children aged 8-11 years showed that elevated WHtR increased the odds of any phenotype of LVG remodeling (8). A study among 526 children aged 6-15 years found that neither obesity (defined by BMI) nor WC Z-score was associated with CR, whereas obesity and WC Z-score was independently associated with EH and CH (11). Another study including 343 African American youths with a mean age of 13.8 years reported that obesity (defined by BMI) was associated with CR independent of BP, but not with CH (53). The heterogeneity of ethnicity, the definition of LVG remodeling patterns and the consideration of potential covariates might partially explain these inconsistent findings.

Previous studies have compared the predictive utility of BMI, WC and WHtR for common CV risk factors in children and adolescents (25–30, 54–56) with most reporting similar performance among these three adiposity indices (25–30). However, few studies have assessed the performance for identifying LVH and LVG remodeling among children. A cross-sectional study of 10,907 adults from China reported no discrimination utility of BMI, WC or WHtR for CR (all AUCs <0.5), and similarly fair performance for EH and CH (AUCs ranging from 0.63 to 0.72) (57). Another study including 281 white children aged 6-16 years reported that WHtR performed best for identifying LVH compared with BMI or WC, with AUCs (95% CI) of 0.711 (0.650-0.733), 0.680 (0.616-0.743) and 0.657 (0.593-0.722), respectively (51). Likewise, our study reported that WHtR performed similarly or better than BMI or WC for identifying LVH and LVG remodeling; suggesting the use of WHtR to screen CV risk factors in practice could improve the ability to identify youth at high risk of cardiac remodeling. It has been shown that WHtR could outperform BMI and WC to predict total and trunk adiposity in children and adolescents (58). And increased adiposity may contribute to cardiac remodeling by hemodynamic and metabolic pathways, including increase in stroke volume and cardiac output, disorder of cardiac metabolism, activation of sympathetic nervous system, and secretion of adipokines by the adipose tissue (10, 59).

However, we found that all three adiposity indices had low predictive utility of CR with the AUCs of around 0.6, suggesting that a single index alone might have limited value to predict this remodeling phenotype in children. In addition, generally low PPVs but high NPVs suggest the better utility for identifying those without abnormal cardiac structures, which might be explained by the low prevalence of LVH/LVG remodeling among children.

It has been generally accepted that a WHtR cut-off of 0.5 might be useful in predicting CV risk in youth, independent of sex, age or ethnicity (44, 60), whereas a study including children and adolescents aged 7-19 years from Europe (13,172; boys: 49.7%) and southern China (14,566; boys: 50.3%) reported that a WHtR cut-off of 0.5 was not suitable for diverse ethnic groups, with a lower threshold of WHtR proposed, especially for girls from southern China (61). Another multicenter study involving 8,130 children and adolescents aged 7-18 years (boys: 53.2%) from China suggested that the optimal WHtR cut-off of 0.467 would be more accurate to identify the clustering of CV risk factors in the pediatric population, and that the optimal cut-offs varied across sex and age with lower cut-offs for girls and those aged 12 years or older (62). In our study, the optimal cut-offs of WHtR were ~0.5 for boys and <0.5 for girls, which may support the sex dependent cut-offs of WHtR. Besides, there were some differences in basic characteristics between boys and girls in our study ( Supplementary Table 5 ). For example, boys had higher BMI, WC, WHtR, and SBP than girls, and boys tended to have unhealthy eating habits (such as insufficient intake of vegetable/fruit and more frequent intake of soft drink) compared with girls. Sex hormones (e.g., estrogens and androgens) and genetic mechanisms could regulate glucose and lipid homeostasis, energy metabolism and gene expression in a sexually dimorphic manner resulting in sex-specific cardio-metabolic disorders (63). Therefore, sex dependent cut-offs for identifying LVH/LVG are necessary according to these different sex-specific features in cardio-metabolic disorders. Importantly, a simple and effective index for screening obesity in youth could be useful to identify obesity-related CV risk factors and to prevent the target organ damage in the early stage, and further cohort studies with a large sample size are needed to confirm our findings.

The strengths of our study were that we compared the discriminatory capability of BMI, WC and WHtR and determined the optimal cut-off of WHtR based on more clinically relevant markers of target organ damage, LVH and LVG remodeling, among children in a relatively large sample. However, our study has several limitations. First, the design of this study was cross-sectional and the interpretation of predictive utility of these three adiposity indices should be made with caution as we are unable to discount reverse causation. Second, the present study only included children aged 6-11 years from one primary school, which limits the generalizability of our findings. Third, despite a standard questionnaire being used to collect lifestyle variables, only diet frequency was assessed without more details about food quality and quantity, and puberty status was not evaluated in the present study. Therefore, it is possible that our estimates might be biased due to unmeasured or residual confounding.

In summary, WHtR performed similarly well or better than BMI or WC for identifying LVH and LVG remodeling, with a WHtR cut-off of ~0.5 for boys and <0.50 for girls shown to have the best discriminatory utility. Our data suggest that WHtR could be used to identify children at risk of having subclinical cardiac structural damage.

The original contributions presented in the study are included in the article/ Supplementary Material . Further inquiries can be directed to the corresponding author.

The studies involving human participants were reviewed and approved by Ethics Committees of the School of Public Health, Shandong University (Approval number: 20160308). Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.

BX conceptualized and designed the study, supervised the data collation, statistical analyses, and reviewed and revised the manuscript. HW did the statistical analyses, drafted the initial manuscript, and reviewed and revised the manuscript. CM, MZ, and BX reviewed and revised the manuscript. All authors contributed to the article and approved the submitted version.

This work was supported by the National Natural Science Foundation of China (81722039, 81673195).

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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