Relationship Between Low-level Inorganic Arsenic Exposure And Vascular Endothelial Dysfunction

Objective:Epidemiological studies have shown that low-level inorganic arsenic(iAs)exposure can increase the incidence and mortality of cardiovascular diseases.However,the relationship between low-level iAs exposure and vascular endothelial dysfunction remains unclear.Vascular endothelial dysfunction is an early pathological alteration of the cardiovascular system.Therefore,we analyzed the distribution of iAs exposure and vascular endothelial function in the population,as well as its influencing factors.This study also explores the relationship between low-level iAs exposure and vascular endothelial dysfunction.Methods:We conducted a cross-sectional analysis and recruited 899 residents in a subordinate administrative village of an abandoned lead-zinc mine and the non-polluted area in an adjacent township in Guangxi.Cadmium is the main heavy metal pollutant in a lead-zinc mine,while arsenic is a light-to-moderate pollutant.The concentration of total urine arsenic(TAs)and urine cadmium(UCd)were used to reflect the degree of arsenic exposure and cadmium exposure,respectively.Vascular endothelial function was assessed by flow-mediated dilatation(FMD).Firstly,geographic information system(GIS)was used to describe the spatial distribution characteristics and the correlation between TAs concentrations and UCd concentrations.Secondly,simple logistic regression and stepwise multiple logistic regression were used to investigate the influencing factors of elevated TAs concentrations and vascular endothelial dysfunction.Thirdly,multiple linear regression and logistic regression were used to analyze the linear dose-response relationship between TAs concentrations and vascular endothelial function.The nonlinear dose-response relationship between TAs concentrations and vascular endothelial function was estimated using the restricted quadratic spline.Finally,Pearson product moment correlation analysis was used to investigate the correlation between dimethylarsinate(DMA),DMA%(DMA/TAs)and FMD levels,and asymmetric dimethylarginine(ADMA).Results:1.A total of 697 subjects who met the analytical requirements had a mean age of 54.38 ± 0.45 years old.Median levels of TAs,UCd,and FMD were 2.34 μg/g creatinine [interquartile range(IQR): 16.20 μg/g creatinine],1.26 μg/g creatinine(IQR: 3.54 μg/g creatinine),and 8.5%(IQR: 5.1%),respectively.Subjects with TAs concentrations less than 100 μg/L,and those with vascular endothelial dysfunction accounted for 98.1% and 33.0% of the total number of subjects respectively.2.The results of GIS showed that the concentration of UCd in the population around the abandoned lead-zinc mine had a high value aggregate,while the distribution of TAs has no such characteristics.The geographically weighted regression coefficient of TAs concentrations and UCd concentrations ranged from-0.067 to-0.096,the difference was not of statistical significance(P>0.05).There was no correlation between TAs concentrations and UCd concentrations.3.The stepwise multiple logistic regression showed that elevated TAs concentrations was related to an increase in age,farming,and lower body mass index(BMI)(P<0.05).The risk of vascular endothelial dysfunction increases with age,being of a female gender,Han race/ethnicity,having an education level of high school and higher,lower BMI and total cholesterol,and larger baseline brachial artery diameter(P<0.05).4.After multivariable adjustments,subjects in the highest quartile of TAs concentrations had 11% lower FMD levels than the subjects in the lowest quartile(ratio=0.89,95% CI: 0.81,0.98);and TAs concentrations and FMD levels showed a linear trend(P for trend value<0.05).Multiple logistic regression analysis of iAs exposure and vascular endothelial dysfunction showed that the fully adjusted odds ratio for vascular endothelial dysfunction,by comparing the highest quartile to the lowest quartile,was 1.94(95% CI: 1.94,3.30);there was a linear trend for the TAs concentrations and vascular endothelial dysfunction(P for trend value<0.05).The restricted quadratic spline showed that FMD levels have an overall downward trend within the TAs concentrations range,and the risk of vascular endothelial dysfunction increased with the increase in TAs concentrations.5.The correlation coefficient between DMA,DMA% and FMD were 0.25 and 0.16,respectively.The difference was not statistically significant(P>0.05).The correlation coefficient between DMA,DMA% and ADMA were-0.25 and-0.12,respectively.The difference was not statistically significant(P>0.05).Conclusions:1.The iAs exposure of the study population was generally low,and there is no correlation between TAs concentrations and UCd concentrations in the population around the abandoned lead-zinc mine.There were 33% of the subjects had vascular endothelial dysfunction.2.An increase in TAs concentrations in the low-level range increases the risk of vascular endothelial dysfunction,suggesting that even low-level iAs exposure may be a risk factor for vascular endothelial dysfunction.