A novel indicator of children lipid accumulation product associated with dyslipidemia in Chinese children and adolescents

The dyslipidemia contributed to more than half Cardiovascular disease (CVD) which ranked rst in all causes of death in the world. Children’s lipid accumulation product (CLAP) is signicantly related to cardiac metabolic risk factors in children and adolescents. The present study was to explore a novel indicator of children’s lipid accumulation product (CLAP) associated with dyslipidemia in Chinese children and adolescents. A total of 683 children and adolescents aged 8-15 years were recruited using the stratied cluster sampling method in this cross-sectional study, and were measured their body height, weight, waist circumference (WC), abdominal skinfold thickness (AST), triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), dietary behaviors and physical activities. A logistic regression model and receiver operating characteristic curve (ROC curve) were used to compare the effects of CLAP for predicting dyslipidemia. adolescents, and performed better than weight, WC, AST, WHtR, and BMI.


Introduction
The dyslipidemia contributed to more than half Cardiovascular disease (CVD) which ranked rst in all causes of death in the world 1 . Data from the World Health Organization (WHO) showed that ischemic heart disease and stroke were the leading killers among the 56.9 million deaths worldwide in 2016, causing a total of 15.2 million deaths 2 . Studies showed that dyslipidemia was associated with cardiovascular risk factors (such as obesity, diabetes mellitus, hypertension and smoking), and was associated with carotid artery elasticity, intima-media thickness and brachial ow-mediated dilatation from childhood to adulthood [3][4][5][6][7] . In recent decades, the prevalence of dyslipidemia has increased rapidly and shows a trend of younger age 8 . In addition, dyslipidemia in children and adolescents was closely related to chronic diseases such as adult lipid metabolism disorders and atherosclerotic CVD 9 . In china, the studies showed blood lipid levels in children aged 7-16 were signi cantly increased 10,11 . The dyslipidemia is modi able and can be prevented or controlled through the consumption of a healthy diet and adequate physical activity from early life 12 .
Previous studies revealed that obesity was one of the most important risk factors for dyslipidemia 3,13,14 .
At present, indicators of commonly using childhood obesity are body mass index (BMI), WC, abdominal skin thickness (AST), and waist height ratio (WHtR). BMI associated with dyslipidemia has been con rmed in children and adolescents 15 . As well known, BMI is the most commonly used index, which can re ect total body composition 16 . However, BMI does not distinguish between lean body mass and fat body weight 17 . WC serves as an important index to re ect central adiposity and is considered to be more strongly associated with certain risk factors of CVD compared to BMI, and WHtR has a higher ability to predict dyslipidemia than BMI 18 . However, WC and WHtR cannot re ect the state of lipid accumulation in children. Kahn et al. 19 proposed a new marker, LAP, to show total lipid accumulation in adults: LAP for men = [WC (cm)-65] × TG (mmol / L); LAP for women = [WC (cm) -58] × TG (mmol / L). Existing research showed that LAP was signi cantly related to cardiac metabolic risk factors such as high TG and low HDL. LAP could better re ect the excessive accumulation of lipids in the body, and the excessive accumulation of lipids is the main risk of cardiac metabolic diseases factor 20 . However, LAP cannot be directly applied to show lipid accumulation in children and adolescents. Zhang et al. 21 developed children's lipid accumulation product (CLAP) that was calculated using the formula of WC (cm) × TG(mmol/L) × AST (mm)/100, and reported that CLAP was signi cantly associated with metabolic syndrome (MS), and was better than BMI and WHtR for predicting MS. Wang et al. 22 showed that CLAP was signi cantly associated with hypertension in children and adolescents, and can more effectively predict childhood hypertension than WC, WHtR, BMI, AST, and TG can. Yuan et al. 23 showed that the CLAP was signi cantly associated with impaired fasting glucose (IFG) in Chinese boys, and it performed better than WC, WHtR, AST and TG. The purpose of this study was to explore power of a novel CLAP for predicting dyslipidemia among children and adolescents.

Study population
In this study, 683 students, including 366 boys (53.6%) and 317 girls (46.4%), aged 8-15 years were effectively recruited from two nine-year-system schools using a strati ed cluster sampling method. The present study was approved by the Medical Ethics Committee of Bengbu Medical College (2015 No.003).
The participants' guardians signed informed consents before medical measurements.

Outcomes and covariates
All medical staff received standard training. Participants were asked to fast, barefoot, stand upright, and wear light clothing for measurement.

Measurement of anthropometric indexes
The height is measured with a mechanical height gauge with an accuracy of 0.1 cm. Use an electronic weight scale to measure weight with an accuracy of 0.1 kg. Use nylon tape to measure the WC, that is, the circumference of the WC located 1 cm above the navel with an accuracy of 0.1 cm. AST is measured using a skinfold thickness gauge and is the thickness of the skinfold at the junction of the right midclavicular line and the horizontal line of the abdominal button, with an accuracy of 0.1 mm.

Survey of behavioral indexes
In this study, we surveyed the frequency of dietary behaviors, including the consumption of milk, nuts, carbonated drinks, outside meals, fresh vegetables, breakfast, fruits, eggs, Western fast food, fried foods, and high-energy snacks. Each dietary behavior score was assigned 0 points for never, 0.25 points for 1 time per month, 0.5 points for 2 times per month, 2 points for 1-3 times per week, 5 points for 4-6 times per week, and 7 points for 1 time per day. The total scores of healthy dietary behaviors (including fruits, eggs, milk, fresh vegetables, breakfast, and nuts) and risky dietary behaviors (including outside meals, Western fast food, carbonated drinks, fried foods, and high-energy snacks) were calculated. According to the P 75 of healthy and risky dietary behaviors total scores, the children were divided into two groups, ≥ P 75 and < P 75 , respectively. Physical activity was investigated through the Children's Leisure Activity Study Survey (CLASS) questionnaire 24 . The moderate to vigorous physical activity time was divided into ≥60 min and < 60 min grades 25 . The sedentary activity time was divided into ≥120 min and < 120 min Dyslipidemia standards: TG ≥ 1.47 mmol / L or TC ≥ 5.18 mmol / L or non-HDL-C ≥ 3.76 mmol / L or HDL-C < 1.03 mmol / L was de ned as dyslipidemia 8 .

Statistical analysis
Statistical analysis was performed using SPSS23.0. The mean ± standard deviation or proportion (%) were used to describe the measurement or enumeration data, respectively. The logarithmic CLAP (LnCLAP), weight, height, BMI, WC, WHtR, and AST were standardized for sex and age using a normal deviation method. The t-test and chi-square test were used to compare the differences of above factors between boys and girls. In addition, the receiver operating characteristic (ROC) was determined to analyze the predictive capabilities of the above standardized variables for dyslipidemia. The associations of overall obesity, abdominal obesity, SlnCLAP with dyslipidemia were analyzed using Logistic regression models. p < 0.05 was considered signi cant.

Demographics
A total of 683 children (366 boys and 317 girls) aged 8-15 years were effectively recruited in this study. The prevalence of dyslipidemia was 13.6% (13.9% in boys and 13.2% in girls). As shown in table 1, the Shieght, Sweight, SBMI, SWC, SWHtR, SAST, SLnCLAP, TC, LDL, and TG in boys with dyslipidemia were signi cantly higher than those with nondyslipidemia (P 0.05), respectively. In addition, moderate to vigorous physical activity time <60 min per day increased risk of dyslipidemia compared with moderate to vigorous physical activity time ≥60 min in boys (P 0.05). The Sweight, SBMI, SWC, SWHtR, SAST, SLnCLAP, TC, LDL, and TG among girls with dyslipidemia were signi cantly higher than those with nondyslipidemia (P 0.05). The HDL in boys and girls with dyslipidemia were signi cantly lower than those with nondyslipidemia (P 0.05), respectively.
3.2The power of predicting dyslipidemia As shown in Table 2  3.3 An optimal cutoff point of LnCLAP for predicting dyslipidemia As shown in Table 3, the results showed that OR (95% CI) of P 75 , P 80, P 85 , P 90 , and P 95 of lnCLAP for predicting dyslipidemia were 8.12 in girls, respectively. From above results, we know that the optimal cutoff point of lnCLAP should be P 75 in boys, and P 85 in girls.

Comparisons of correlations of BMI, WHtR, CLAP with dyslipidemia
As shown in Table 4

Discussion
In recent years, dyslipidemia in children and adolescents has caused widespread concern, and is one of the strongest risk factors for CVD (CVD) and often emerges during childhood 29,30 . The studies have indicated that childhood dyslipidemia also persists into adulthood due to obesity 31 . The results of this study showed that the prevalence of dyslipidemia was 13.6% (13.9% in boys and 13.2% in girls). Sapunar et al. 32 reported that the prevalence of dyslipidemia in Spanish children graded 4-6 was 11%. The study from Wang et al. 33 reported that the prevalence of dyslipidemia was 28.1% in boys and 28.9% in girls. In addition, this study found no statistically signi cant difference in the prevalence of dyslipidemia between boys and girls, which is inconsistent with the results of other studies. Kit et al. 3 reported that the prevalence of dyslipidemia among girls (21.0%) was signi cantly higher than that among boys (19.3%). The result of the present study showed moderate to vigorous physical activity time <60 min per day increased risk of dyslipidemia. The previous study also reported that leisure-time and school time physical activity were associated with dyslipidemia in children 34 .
Several studies showed that children with weight reduction had dyslipidemia clearly bene ted them with normalization of lipid pro le 35 . Therefore, more and more studies have been conducted on the correlation between dyslipidemia and indicators of re ecting obesity in children. Garcez et al. 36 found a positive correlation of body weight, WC, and BMI with the presence of dyslipidemia in adolescents. Furtado et al. 37 reported that WHtR, WC, BMI and zBMI were signi cant determinants of lipid and lipoproteins levels.
Oliosa et al. 38 reported that a positive correlation of the lipid variables LDL-c, TC, Non-HDLc with BMI and WC. Ribas et al. 39 reported that pupils with an excess of body weight (BMI ³ P 85 ) and abnormal body fat distribution (an elevated %BF) had twice the probability of developing dyslipidemia as normal-weight individuals. Zheng et al. 40 reported that the AUC of BMI z-score and WHtR for predicting dyslipidemia among Chinese boys were 0.66 and 0.72, respectively. In present study, the results showed that the SWC, SWHtR, SBMI in boys and girls with dyslipidemia were signi cantly higher than those with nondyslipidemia (AUC ( Keys et al. 41 suggested that BMI can indicate relative obesity or body fatness. However, BMI does not distinguish between fat mass and lean body mass, and can use result in large errors in the estimation of body fatness 42,43 . Studies have shown that WC and WHtR are independently associated with a higher risk for CVD and can predict other overweight related risk factors [44][45][46] . But they were limited in indicating lipid accumulation in circulating blood 47,48 . The previous studies showed the CLAP was signi cantly associated with metabolic syndrome (MS), hypertension, impaired fasting glucose among children and adolescents, and can more effectively associations than WC, WHtR, BMI can [21][22][23] . The present study showed that the AUC of CLAP for predicting dyslipidemia was higher than that of weight, WC, AST, BMI, WHtR, which indicated that CLAP had more power for predicting dyslipidemia compared with a single indicator. In addition, the optimal cutoff point of CLAP among boys and girls for predicting dyslipidemia were P 75 and P 85 , with OR (95% CI) value of 8.74(4.54-16.85) and 10.54(5.09-21.82), respectively.
There were some limitations in this study. This study was a cross-sectional study, which limits inferring causality between CLAP and dyslipidemia. In addition, dietary behaviors and physical activity might be adopted before or after suffering from dyslipidemia.
In summary, based on the results of this study, CLAP was a stronger risk factor for dyslipidemia compared with weight, AST, WC, WHtR and BMI. The optimal value of CLAP to predict dyslipidemia was P 85 among girls, P 75 among boys.

Declarations Ethics approval and consent to participate
The present study was approved by the Medical Ethics Committee of Bengbu Medical College (2015 No.003). The participants' guardians signed informed consents before medical measurements.

Consent for publication
We certify that we have participated su ciently in the work to take public responsibility for the appropriateness of the study design, and the collection, analysis, interpretation of the data. All authors have read and approved the submission of the manuscript; the manuscript has not been published and is not being considered for publication elsewhere, in whole or in part, in any language, except as an abstract.

Availability of data and materials
All the data are available for interested readers. There are no specialized materials employed in the study.

Competing interests
All authors gave nal approval of the submitted manuscript versions and declare no con icts of interest in this work.     Table 4 The association between WHtR, BMI, lnCLAP and dyslipidemia using logistic regressions  Figure 1 ROC curves of height, weight, WC, AST, lnCLAP, WHtR and BMI to predict dyslipidemia in boys and girls.