The Association Between Overweight And Elevated Blood Pressure In Childhood And Subclinical Cardiovascular Diseases In Adulthood Based On Mixed-Effects Model

[Background]During last decades, non-communicable diseases are the leading cause of death worldwidely. According to the National Disease Surveillance, the total mortality of cardiovascular diseases (CVD) in China rose from 240.03 to 268.92 per ten thousands from 2004 to 2011. Lifestyle changed a lot among Chinese people because of rapid economic development. The prevalence of obesity, hypertension, dyslipidemia, diabetes, smoking, drinking, physical inactivity, unhealthy diet and other CVD risk factors increased year by year. It is noting that many of CVD risk factors spread gradually in children and adolescents. CVD incidence is a long slow process. With the development of CVD technology, a variety of quantitative indicators could be detected to evaluate CVD structural and functional abnormalities, such as endothelial dysfunction, arterial stiffness, atherosclerosis, left ventricular hypertrophy (LVH) and left ventricular geometry (LVG), which are all predictive CVD clinical events.Several prospective studies has explored the relationship between CVD risk factors (obesity and hypertension) at childhood and subclinical CVD at adulthood. Due to difference in sample size, baseline age, follow-up duration, race, the strength of association between CVD risk factors in children and subclinical diseases in adulthood was different but significant. CVD risk factors track from children to adults. Obese children is more likely to become obese adults, and children with evelated blood pressure is more likely to become hypertensive adults. However, weight and blood pressure druing follow-up change a lot because of physical growth, so one single measurement of weight or blood pressure can’t represent average levels of weight or blood pressure during a period of time. Thus, it is necessary to conduct a prospective study with multiple measurements of risk factors during childhood.The growth model (mixed model), one of multilevel models, was used in Bogalusa Heart study to build the growth curve of CVD risk factors through childhood to adulthood, and then calculate the area under the curves (AUC) to evaluate the effect of long term of CVD risk factors from childhood to adulthood on the development of surrogate markers of CVD. Multiple level models was developed in last two or three decades and were used in various fields, and it can deal with prospective data with multiple measurements and unfixed intervals.[Objective](1) To analyze whether multiple measurements of risk factors is better than one single measurement in predicting CVD risk factors or subclinical CVD at adulthood.(2) To analyze the relationship between overweight or elevated blood pressure at childhood and subclinical CVD at adulthood.(3) To explore the interaction between children overweight and elevated blood pressure on subclinical CVD at adulthood.(4) To analyze the association between changes of weigt status or blood pressure status from childhood to adulthood and subclinical CVD at adulthood.[Methods]Data was obtained from "Beijing children Blood pressure Study"(BBS), Excluding children with history of hypertension, or physically disabled, or suffered from chronic diseases of heart, kidney, liver, endocrine system or vascular tissue, or those with acute intercurrent febrile or diarrheal illness.3198(1700 males,53.2%) healthy children aged 6-18 years were selected from Beijing using random cluster sampling design. After excluding 756 children missing data,2442 children (70.1%) with complete childhood data at baseline were eligible in final. Since then, nine surveys had been conducted (once a year during 1988-1994, one at 2005, and one at 2011), which resulted in multiple observations of risk factors from childhood to adulthood. Markers of subclinical CVD were measured in the last 2011 survey among 1256 adults (male 695,55.2%) aged 27-42 years. Body height, weight, and blood pressure (BP) were collected at each survey round, and each individual had 2-10 measurements (total=5708, average=4.5) from initial childhood to last adulthood. The average follow-up period was 22.9±0.6 years.Using mixed model, the growth curves of body mass index (BMI) and BP during childhood and adulthood for each individual were built to calculate the area under the growth curves(AUC), which represented the average levels of BMI and BP during childhood and adulthood. The AUCs of BMI and BP were standardized to z scores specific for age and sex. The person who had baPWV, cfPWV, cIMT, LVMI, or RWT≥75th percentile by age and sex was defined as having cardiovascular structural and functional abnormality (high baPWV, high cfPWV, high cIMT, high LVMI, or high RWT). Four different patterns of LV geometry(LVG) were defined according to LVMI and RWT:1) normal LV geometry (normal RWT with normal LVMI),2) concentric remodeling (CR, high RWT but normal LVMI),3) eccentric hypertrophy (EH, normal RWT with high LVMI), and 4) concentric hypertrophy (CH; high RWT with high LVMI).The continuous variables were described as mean±standard deviation, and TG was described as median (P25-P75), and categorical variables were described as n (%). t test and chi-square test were used to compare characteristics between population between those followed up and those lost to follow-up. Pearson correlation coefficients and multiple linear regression analyses were performed to examine the association between BMI/BP during childhood and markers of subclinical CVD at adulthood after adjusting for BP and other risk factors. Logistic regression was used to examine childhood overweight or elevated blood pressure as predictors of subclinical CVD in adulthood, to analyze the interaction between childhood overweight or elevated blood pressure on subclinical CVD in adulthood, and to explore the effect of changes in weight status or blood pressure status from childhood to adulthood on subclinical CVDs in adulthood.[Results](1) The tracking coefficients based on one single measurement at initial childhood and final adulthood was 0.575 for BMI,0.35 for SBP, and 0.244 for DBP (all P<0.05). The tracking coefficients based on multiple measurements during childhood and during adulthood was 0.635 for BMI,0.439 for SBP, and 0.340 for DBP(all P<0.05).(2) After adjusting for sex, age and risk factors at adulthood (diabetes, dyslipidemia, smoking, drinking, and physical inactivity), the odds ratios (ORs) and 95% confidence intervals(CIs) of subclinical CVDs and childhood overweight were 1.89(1.33-2.69) for high cIMT,2.81(1.98-3.99) for high LVMI,1.45(1.01-2.08) for high RWT,2.30(1.47-3.60) for EH,099 and 4.07(2.38-6.95) for CH. The ORs and 95%CIs of subclinical CVD and elevated blood pressure at childhood were 2.26(1.66-3.08) for high baPWV,2.24(1.62-3.11) for high cfPWV,1.56(1.14-2.14) for high cIMT,1.39(1.00-1.92) for high LVMI,2.05(1.50-2.79) for high RWT, 2.08(1.43-3.03) for CR, and 2.19(1.32-3.66) for CH.(3) Comparing to subjects who had consistent normal weight and normal blood pressure from childhood to adulthood, subjects who were overweight and had elevated blood pressure had increased risk of high baPW, high cfPWV, high cIMT, high LVMI, high RWT, CR, and CH at adutlhood, and the ORs(95%CIs) were 4.71(2.88-7.70),2.04(1.23-3.37),2.35 (1.36-4.05),2.88 (1.76-4.72),2.64(1.61-4.32), 2.75 (1.51-4.99), and 9.30 (4.89-17.70), respectively.(4) Comparing to subjects who had consistent normal weight from childhood to adulthood, subjects who were overweight at childhood but had normal weight at adulthood has increased risk of high cIMT at adulthood, and the OR(95%CI) was 1.79 (1.13-2.84). Subjects who had normal weight at childhood but became overweight at adulthood has increased risk of high cIMT, high LVMI, high RWT, EH, and CH at adulthood, and the ORs(95%CIs) were 3.82(2.44-5.99),4.75(3.01-7.49),4.18 (2.23-7.80),2.60 (1.10-6.14), and 2.21 (1.10-4.45), respectively. Subjects who were consistently overweight had increased risk of high cIMT, high LVMI, high RWT, CR, EH, and CH, and the ORs(95%CIs) were 2.46 (1.63-3.69),7.21(4.76-10.93),1.96 (1.31-2.94),2.21(1.10-4.45),8.07(4.39-14.84), and 11.59 (5.72-23.48), respectively.(5) Comparing to subjects who had consistent normal blood pressure from childhood to adulthood, subjects who had elevated blood pressure at childhood but had normal blood pressure at adulthood has increased risk of high cfPWV, high cIMT, high LVMI, high RWT, ER, and CH at adulthood, and the ORs(95%CIs) were 1.98 (1.31-3.01),1.61(1.08-2.41),1.61(1.06-2.45),1.60(1.08-2.36),1.85(1.19-2.89), and 2.96(1.38-6.38), respectively. Subjects who had normal blood pressure at childhood but had elevated blood pressure at adulthood had increased risk of high baPWV, high cfPWV, high cIMT, high LVMI, high RWT, and CH at adulthood, and the ORs(95%CIs) were 5.46(3.65-8.17),3.46(2.27-5.27),1.94(1.30-2.91),2.06(1.36-3.13), 1.62(1.08-2.42), and 3.09(1.41-6.77). Subjects who had consistent elevated blood pressure had increased risk of high baPWV, high cfPWV, high cIMT, high LVMI, high RWT, EH, and CH, and the ORs(95%CIs) were 11.01(6.78-17.87), 5.25(3.22-8.56),1.81(1.13-2.92),2.18(1.33-3.55),2.28(1.44-3.60),2.19(1.25-3.82), 4.05(1.82-9.03), respectively.[Conclusion](1) Multiple measurements of risk factors is better than one single measurement in predicting CVD risk factors or subclinical CVDs in adulthood. Mixed-effects model can be used to deal with the data from multiple measurments, which would strength the power of the association.(2) BMI and BP track from childhood to adulthood. Overweight children are more likely to become obese adults, and children with elevated blood pressure are more likely to become hypertensive adults.(3) Overweight and elevated blood pressure are associated with subclinical CVD at adulthood, but the strengths of association are different for every subclinical CVD. There is a stronger association of high LVMI with overweight than with elevated blood pressure, however, there is a stronger association of high PWV and high RWT with elevated blood pressure than with overweight.(4) Changes in weight status and blood pressure status from childhood to adulthood are associated with subclinical CVD in adulthood. Reduction in BMI and blood pressure from childhood to adulthood will attenuate the risk of subclinical CVD in adulthood, whereas increase in BMI and blood pressure from childhood to adulthood will raise the risk of subclinical CVD.