Associations Of Multiple Metals Exposure With The Risk Of Coronary Atherosclerotic Heart Disease And Related Organ Function

Coronary heart disease(CHD)is a major public health problem with high morbidity,mortality and disability.The report of the 2017 Global Burden of Diseases showed that the prevalence and mortality of CHD were still rising.CHD is the leading cause of death in men and the second cause in women,and causes the highest loss of life.CHD is a complex disease with multiple causes.More and more studies have shown that metals exposure was associated with the occurrence and development of CHD patients.leading serious impact to the treatment and prognosis of CHD.Meanwhile,CHD patients are much more susceptible to metals exposure than healthy people,and their liver,kidney and thyroid may be more prone to be damaged.Therefore,it is certainly worth investigating the associations of multiple metals exposure with the risk of CHD and related organs function,which is of great significance for formulating prevention and treatment strategies of CHD and improving residents' quality of life.This study was divided into two parts:Prat I Associatins of multiple metals exposure with the risk of coronary atherosclerotic heart disease(CHD)Objective:Human multiple metals' exposure levels were assessed by urinary metal concentration,and the correlations between metals exposure and risk of coronary heart disease were analyzed.Methods:Based on a 1:1 case-control study design,urinary concentration of 20 metals in 512 paried subjects was detected by ICP-MS.The effect of metal exposure on the risk of coronary heart disease(CHD)was assessed by multiple logistic regression model.False discovery rate(FDR)was utilized to control false positive hypotheses,and the combined effect of metals was analyzed by multi-metal model.Results:Data analysis showed that there was a positive dose-response relationship between the concentrations of aluminum,manganese,cobalt,nickel,strontium,barium and mercury in urine and the risk of CHD,while the concentrations of urinary vanadium and rubidium had a negative dose-response relationship.In the multi-metal model,compared with those in the lowest quartiles,participants in the highestquartiles of aluminum,manganese,nickel,strontium and mercury had 6.78 times(95%CI:2.29,20.06),3.56 times(95%CI:1.15,11.05),2.80 times(95%CI:1.11,7.06),3.02 times(95%CI:1.11,8.16)and 6.11 times(95%CI:2.72,13.74)increased risk of CHD,respectively.Conclusions:Increased environmental exposure levels of metals such as aluminum,manganese,cobalt,nickel and mercury was positively asociated the risk of CHD,while vanadium and strontium was negatively associated with it.Part ? Effects of multiple metals exposure on organ function in patients with coronary heart diseaseSection ? Effects of multiple metals exposure on liver function in patients with coronary heart diseaseObjective:To study the associations of multiple metals exposure with liver function in CHD patients.Methods:Based on a cross-sectional study design,urinary metal concentrations in 457patients with CHD was measured.Total bilirubin(TBil),direct bilirubin(DBil),alanine aminotransferase(ALT),albumin protein(AP),pre-albumin(PA)and total bile acid(TBA)were used to evaluate liver function.Multivariate linear regression model and multi-metal model were applied to explore the relationship between metal exposure and liver function.Results:The concentration of zinc and strontium in urine were positively correlated with the level of TBil,but the two associations were not significant after FDR correction;the concentration of zinc and uranium in urine were positively correlated with the level of DBil,and the correlation between urinary zinc concentration and DBil was still significant even after FDR adjustment;urinary selenium,rubidium,cesium,thallium,lead had a positive dose response relationship with ALT.Copper concentration in urine was inversely with PA.In the multi-metal model,a two-fold increase in the concentration of thallium in urine increased ALT levels by 24.61%(95%Cl:10.21%,40.89%).At the same time,a two-fold increase in urinary aluminum concentration increased ALT levels by 12.08%(95%Cl:2.43%,22.63%).Conclusions:Increased exposure levels of aluminum,copper,thallium and lead were associated with hepatic dysfunction in CHD patients.Section ? Effects of multiple metals exposure on renal function in patients with coronary heart diseaseObjective:To study the associations of multiple metals exposure with the renal function in CHD patients.Methods:Based on a cross-sectional study design,urinary metal concentrations in 451 patients with CHD was measured.Estimated glomerular filtration rate(eGFR)was used to evaluate renal function.Multivariate linear regression model and multi-metal model were applied to explore the relationship between metal exposure and eGFR level.Results:Data analysis showed that the concentrations of arsenic and strontium in urine were positively correlated with the levels of eGFR in male and total coronary heart disease patients,and the concentrations of selenium in urine were positively correlated with the levels of eGFR in total population.Compared with low arsenic and low strontium exposure group,high arsenic and high strontium exposure increased the eGFR by 9.44(95%CI:2.00,16.88)mL/min/1.73m2.In the multi-metal model,a two-fold increase of urinary vanadium and zinc decrease eGFR by 5.37(95%Cl:1.82,8.92)and 5.04(95%Cl:1.18,8.90)mL/min/1.73m2,respectively,while doubling of urinary strontium increase eGFR by 8.56(95%Cl:4.84,12.28)mL/min/1.73m2.Conclusions:Increased arsenic was associated with renal dysfunction in CHD patients,while increased selenium and strontium levels was associated with improved renal function in CHD patients.Section ? Effects of multiple metals exposure on thyroid function in patients with coronary heart diseaseObjective:To study the associations of multiple metals exposure with thyroid function in CHD patients.Methods:Based on a cross-sectional study design,urinary metal concentrations in 453 patients with CHD was measured.Free triiodothyronine(FT3)and free thyroxine(FT4)and thyroid stimulating hormone(TSH)were used to evaluate thyroid function.Multivariate linear regression model and multi-metal model were applied to explore the relationship between metal exposure and thyroid function.Results:Urinary thallium concentrations were positively associated with FT3 levels,and the association was statistically significant even after FDR adjustment(PFDR<0.05).Urinary rubidium was positively associated with FT3(P=0.042)and FT4(P=0.049)levels,but these associations were not significant after FDR adjustment(PFDR>0.05).Multi-metal model results showed that doubling the concentration of thallium increased the FT3 by 0.075(95%CI:0.008,0.141).Conclusions:The exposure levels of thallium were associated with throid dysfunction in CHD patients.