| ObjectiveWith the rapid development of economy and the acceleration of industrialization,metal pollution has become a widespread concern.A variety of metals in the environment are mainly absorbed by human through respiratory tract,digestive tract and skin contact.People are often exposed to multiple metals in daily life,the level of metals of those susceptible to the effect of industrial progression and agricultural pollution may be higher.Therefore,based on the Wanjiang community-based cohort,this study was conducted to explore the levels and changes of urinary metals,as well as the relationship between metal exposure with obesity and hypertension.MethodsFrom September 2014 to June 2015,the baseline survey of Wanjiang Cohort was conducted,and a total of 2,625 residents were surveyed.The follow-up survey was conducted from May 2019 to December 2019,341 were lost to follow-up and the follow-up rate of 86.97%.In this study,residents were surveyed by questionnaire,physical measurement,and the first-morning urine was collected at baseline and at follow-up.The urinary concentrations of 21 metals(Al,As,B,Ba,Bi,Co,Cr,Cu,Fe,Hg,Li,Mg,Mn,Mo,Ni,Pb,Rb,Se,Sr,Ti)were measured using inductively coupled plasma optical emission spectrometry.The level of urine Cd was tested by atomic absorption spectrophotometry(TAS-900).The levels of urinary metals were corrected by urinary creatinine,which was measured using the ultraviolet spectrophotometer.In the first part of our study,multiple linear regression was used to explore the influencing factors of the level of urinary metals,and comparing the changes of metal concentrations in different time periods.In the second and third parts of our study,multivariate regression models were used to investigate the association between multiple metals exposure with obesity and hypertension.The effects of metal mixtures exposure on obesity and hypertension were investigated by using quantile g-computation and Bayesian kernel machine regression(BKMR).ResultsPart I: The distribution and changes of urinary metal of participants in the Wanjiang communityA total of 2089 residents in the Wanjiang cohort were included in this study,with935 males and 1154 females.The mean ages of study population for males and females were 49.26 ± 16.67 years and 49.30 ± 16.81 years,respectively.The median concentrations of As,B,Ba,Bi,Cd,Co,Cr,Cu,Fe,Li,Mg,Mn,Mo,Rb,Se,Sr and Zn in urine were 74.06μg/g creatinine,382.29μg/g creatinine,5.55μg/g creatinine,17.59μg/g creatinine,2.50μg/g creatinine,2.39μg/g creatinine,19.01μg/g creatinine,14.69μg/g creatinine,15.84μg/g creatinine,13.66μg/g creatinine,33.60mg/g creatinine,0.45μg/g creatinine,76.09μg/g creatinine,308.34μg/g creatinine,33.70μg/g creatinine,114.87μg/g creatinine and 479.21μg/g creatinine,respectively.The results of multiple linear regression model showed that the concentrations of Ba,Cd,Co,Cr,Cu,Fe,Li,Mn,Sr and Zn were higher in females(P < 0.05).Age was positively correlated with the concentrations of As,B,Cd,Fe,Li,Mg,Mn and Zn(P<0.05).Smoking was positively correlated with the level of Cd,and negatively correlated with Mg and Mo(P<0.05).The concentrations of As,Cd and Mo were lower in population who drank alcohol(P<0.05).A total of 871 subjects were included in the metal variability analysis,when compared with the concentrations of urinary metals at baseline,As,Ba,Cd,Co,Cu,and Zn were lower(P<0.001),Cr,Fe,Li,Mg,Mn,Mo,Se and Sr were higher at follow-up(P<0.001).Part II: Association of multiple metals exposure with obesity in the Wanjiang community-based cohortA total of 982 participants were followed up in 2019.The average follow-up time was 4.5 years(range = 4.0-5.3),and 351(35.7%)were diagnosed with incident obesity.The results of single metal model showed that eight metals were negatively correlated with obesity(As,Ba,Cd,Co,Cr,Fe,Mn and Se),while Mo was positively correlated with obesity(P-trend <0.05).In the multi-metal models,compared with the participants in the lowest quartile of As and Fe,the HR for obesity of participants in the highest quartile was 0.44(95%CI: 0.29,0.65;P-trend <0.001)and 0.53(95%CI:0.32,0.85;P-trend =0.019).Urinary Mo concentrations in the highest quartile were associated with an increased risk of obesity 1.70(95%CI: 1.18,2.43;P-trend =0.002).After FDR-adjustments were made,the p-trend for urinary As and Mo was still statistically significant.RCS analyses shows significant nonlinear associations for As and Mo(with P-values for nonlinearity of 0.03 and 0.001,respectively).Quantile g-computation showed the HR when increasing all seventeen metals by one quartile for obesity was 0.27(95%CI:0.15,0.47,P < 0.05).As and Fe contributed the largest negative weights;Mo,Zn and Li were assigned the largest positive weights.Exposure to metal mixtures was primarily associated with abdominal obesity,with the HR for obesity of 0.26(95%CI: 0.14,0.47,P < 0.05).Part III: Association of multiple metals exposure with hypertension in the Wanjiang community-based cohortIn total of 1303 participants living along the Yangtze River were included in this study,and 385(29.6%)were diagnosed with incident hypertension.The results of single-metal models showed that five metals were significantly associated with hypertension(Cd,Cu,Mg,Mo and Zn,P-trend <0.05).In the multi-metal models that simultaneously included five metals,trends for Cd and Zn remained significant.Compared with the participants in the lowest quartile of Cd and Zn,the OR for the risk of hypertension in the highest quartile was 1.49(95%CI: 1.01,2.21;P-trend=0.05)and 1.60(95%CI: 1.08,2.38;P-trend =0.023),respectively.RCS analysis shows significant linear associations for Cd and Zn(with p-values for nonlinearity of0.50 and 0.19,respectively).Quantile g-computation mixtures showed OR when increasing all seventeen metals by one quartile for hypertension was 1.62(95%CI:0.85,3.09,P = 0.141).Ba and Rb contributed the largest negative weights;Cu,Cd and Li were assigned the largest positive weights.The results of BKMR model showed that there was a positive linear correlation between exposure to metal mixtures and the risk of hypertension.In the joint association analysis for Cd and Zn,it was found that the two metals had interaction effects on the risk of hypertension(P-interaction =0.022).Compared with the lower levels of Cd and Zn,exposure to higher level of Cd and Zn would further increase the risk of hypertension(ORint =1.41,95%CI: 1.05,1.89;AP=0.67,95%CI: 0.27,1.06;S = 4.01,95%CI: 1.41,11.40).ConclusionThe concentrations of urinary Ba,Cd,Co,Cr,Cu,Fe,Li,Mn,Sr and Zn are related to gender or age.And the education level,obesity,smoking and other factors are also related to some metal levels.In the follow-up,the levels of heavy metals(As,Cd),Ba,Co and Cu were decreased,while the levels of other essential metals were increased.Our study evaluate the association between exposure to metal mixtures with obesity and hypertension by using quantile g-computation and BKMR.It was found that when all metals were increased by one quartile,exposure to the metal mixtures had a negative effect on obesity and a positive effect on hypertension.In addition,the interaction of Cd and Zn on the risk of hypertension was also found.Considering the high concentration of metals and the impact on human health for residents living along the Yangtze River,further large-sample cohort studies are needed to explore the biological mechanism of the association between metal mixture exposure with obesity and hypertension. |
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