Association Between Metal Exposure And Subclinical Cardiovascular Disease In A Community Population

Objective:Metal contamination is a major environmental concern in China. Metals exert multiple toxic effects on human body after entering the human body through multiple routes, especially on cardiovascular system. A large number of epidemiological studies have suggested that exposure to metals is associated with increased risk of cardiovascular disease. However, studies on the association between metal exposure and subclinical cardiovascular disease among general population were limited. Therefore, in the present study, we aimed to investigate the potential associations between urinary metals and subclinical cardiovascular disease, and further examine the associations of metals in urine with their corresponding concentrations in blood and particulate matter (PM).Methods:We recruited community residents who lived in the sampling buildings for more than5years in Wuhan city, and determined23metals in urine, blood plasma of the subjects and PM of the communities using an inductively coupled plasma mass spectrometer. Moreover, we measured the fasting blood glucose and blood lipids by a fully automated clinical chemistry analyzer. The indices of heart rate variability (HRV)(SDNN, standard deviation of normal-to-normal intervals; r-MSSD, root mean square of successive differences in adjacent normal-to-normal intervals; LF, low frequency; HF, high frequency; TP, total power) were measured by a3-channel digital Holter monitor. We then investigated the associations of23urinary metals with the levels of fasting blood glucose and blood lipids as well as altered HRV using generalized, multivariable linear and logistic regression models in the first part of the present study. We also examined the potential correlations between these metal levels in spot urine and their corresponding concentrations in blood plasma using Spearman’s rank correlations in the second part of the present study. Finally, we evaluated the association between PM metal levels and urinary metal concentrations of residents in the third part of this study. The false discovery rate (FDR) method was used to correct for multiple hypothesis tests.Results:In the first part of this study, we found that:(a) Urinary titanium, copper, zinc, selenium, rubidium, tungsten and lead were significantly associated with altered fasting plasma glucose, impaired fasting glucose or diabetes risk (all FDR-adjusted P<0.05) after adjusting for potential confounders and multiple comparisons,(b) Urinary aluminium, titanium, chromium, cobalt, selenium, rubidium, cadmium, tungsten, thallium and lead were dose-dependently associated with decreases in the concentrations of total cholesterol and triglyceride or the risk of hyperlipidemia after adjusting for potential confounders and other metals. In contrast, there were positive dose-response associations of copper, manganese, zinc, arsenic molybdenum and uranium with the levels of total cholesterol and triglyceride or the risk of hyperlipidemia (all Ptrend<0.05).(c) After adjusting for potential confounders and other metals, urinary titanium was associated with increased all HRV indices (all P<0.05); rubidium was suggestively associated with increased LF (P<0.10). Conversely, iron, copper and arsenic were associated with decreased HF, SDNN and LF respectively (all P<0.05); cadmium was associated or suggestively associated with decreased r-MSSD (P<0.10), LF (P<0.05), HF (P<0.05) and TP (P<0.10); lead was associated or suggestively associated with r-MSSD (P<0.05), HF (P<0.10) and TP (P<0.05).In the second part of this study, we found that urinary levels of molybdenum, cobalt, arsenic, thallium, strontium were positively correlated with their corresponding blood plasma concentrations, whereas urinary vanadium and titanium were adversely correlated with plasma vanadium and titanium respectively after adjusting for multiple comparisons (all FDR-adjusted P<0.05).In the third part of this study, we found that there were significant and positive associations of titanium concentrations in PM10and PM2.5with urinary excretion of titanium at lag4-7days, of arsenic levels of PM10with its urinary concentrations at lag6-7days, of PM10barium with urinary barium levels at lag1and7days while PM2.5barium with urinary barium at3-5days, of tungsten in PM10with urinary excretion of tungsten at lag1day, and of PM10lead levels with urinary lead concentrations at lag4-6days after adjusting for potential confounders and multiple comparisons (all FDR-adjusted P<0.05).Conclusions:We found that metals in urine were associated with their corresponding levels in blood plasma as well as altered blood glucose, lipids levels and HRV indices, suggesting that metal exposure is related to subclinical cardiovascular disease in the general population. At the same time, we found that metals in urine were correlated with their corresponding levels in PM, which indicate that inhalation may be an important route of human exposure to metals.