| The harmful effects caused by heavy metals have been widely concerned.Previous studies revealed that exposure to heavy metals was not only associated with elevated risks for neurological diseases,but also resulted in damage to blood composition and cardiovascular system.Recently published evidences have shown that exposure to some heavy metals was positively related with the prevalence of hypertension,diabetes and cardiovascular diseases.However,studies on the associations between heavy metals exposure and 10-year atherosclerotic cardiovascular disease(ASCVD)risk are limited,and the mechanisms of adverse effects induced by heavy metals on cardiovascular system remain unclear.Mean platelet volume(MPV),the parameter of platelet size and activity,has been regarded as an inflammatory biomarker of system inflammation response.More and more clinical researches and epidemiological studies shown that elevated MPV was significantly associated with the increased prevalence and severity of ASCVD.Moreover,enhanced inflammation response was reported to be involved in heavy metals exposure,which play a crucial role in the pathogenesis of ASCVD.But few studies focused on the associations between heavy metals and MPV.And whether MPV plays a potential role in ASCVD caused by heavy metals exposures has not been studied.In the current study,urinary heavy metals were measured as biomarkers of internal levels for heavy metals exposure,and MPV was assayed as the parameter of platelet function.The China-PAR models were performed to calculate the scores for 10-year ASCVD risk.The associations of heavy metals exposure with MPV and 10-year ASCVD risk were analyzed among Wuhan-Zhuhai cohort in China.This study was divided into the following two parts.Part 1 Associations of urinary heavy metals with MPV in the community populationsObjective: To analysis the associations of urinary heavy metals with MPV.Method: A total of 3641 participants from Wuhan-Zhuhai cohort were included for this part of the study.Detail information of demographic characteristics,medical history,family history,life habits,as well as height,weight and blood pressure,were collected through questionnaire survey and physical examination,respectively.Urinary heavy metals and blood MPV were measured by inductively coupled plasma mass spectrometry and the fully automatic biochemical analyses,respectively.The associations of urinary heavy metals with MPV were analyzed through generalized linear models and restricted cubic spline function(RCS).Besides,stratified analysis was further used to explore the effects of individual characteristics and lifestyle on the associations.Results: 1.In the community populations,the geometric mean values(interquartile range)of urinary concentrations of manganese,iron,copper,zinc,cadmium,antimony,barium,lead and arsenic was 1.028(0.531-3.147)?50.76(26.060-107.500)?8.190(5.490-12.776)?304.56(26.010-506.680)?1.140(0.629-2.159)?0.131(0.011-0.205)?2.281(1.556-5.100)?2.756(1.888-4.357)and 32.257(19.580-55.660)?g/L.Except for cadmium,the urinary concentrations of other heavy metals were higher in men than in women(P <0.05).2.The associations were analyzed by regarding urinary heavy metals as continuous variables and classification variables respectively.In the continuous variable analysis,each 1-U increase in log-transformed urinary levels of iron,zinc,antimony and arsenic was associated with a 1.30%,1.42%,1.61% and 2.18% increases of MPV(All P value <0.05),while each 1-U increase in log-transformed urinary levels of cadmium and lead was associated with a 0.95% and 1.16% decrease of MPV(All P value <0.05).Moreover,the similar trends were observed in the categorical variable analysis.In addition,a stronger association between urinary iron and MPV in women than men was observed through the stratified analysis.3.The associations of urinary heavy metals with 10-year ACVD risk were also analyzed by RCS with the 10 th percentile as reference(Knots: 10 th,50th and 90th).The results showed that nonlinear correlations were observed of urinary iron and copper with MPV(P for non-linearity <0.05).With the increase of urinary iron and copper,MPV decreased first and then increased.However,there were no non-linear correlations of urinary zinc,cadmium,antimony,lead and arsenic with MPV(all P for non-linearity >0.05).Conclusions: Urinary zinc,antimony and arsenic were positively and linearly correlated with MPV,while urinary cadmium and lead were negatively and linearly correlated with MPV.Meanwhile,the non-linear correlations were observed between urinary iron,copper and MPV.Part 2 The role of MPV in the associations between urinary heavy metals and 10-year ASCVD risk in the community populationsObjective: To assess the associations of urinary heavy metals and MPV with 10-year ASCVD risk,and to explore the mediating role of MPV in the associations of urinary heavy metals with 10-year ASCVD risk.Method: On the basis of part 1 of this study,participants not aged 35 to 74 years old and those with ASCVD were further excluded,a total of 3081 participants from WuhanZhuhai cohort were eventually included in this part.Ten-year ASCVD risk was calculated through the risk assessment equation,which was developed and validated in China-PAR project.According to the calculated score,the ASCVD risk was divided into two group: low risk(<0.05)and high risk(?0.05).Logistic regression analysis was used to assess the associations of urinary heavy metals,arsenic and MPV with 10-year ASCVD risk.Meanwhile,the associations of heavy metals with 10-year ASCVD risk were further analyzed by subgroup of individual characteristics and lifestyle.Furthermore,the mediated analysis was conducted to explore the potential effect of MPV on urinary heavy metals and 10-year ASCVD risk.Results: 1.In the continuous variable analysis,each 1-U increase in log-transformed urinary iron,copper,zinc,cadmium,antimony and arsenic was associated with a 14.00%,40.00%,55.00%,21.00%,46.00% and 16.00% increase in OR of 10-year ASCVD risk;while each 1-U increase in log-transformed urinary barium was associated with a 10% decrease in OR of 10-year ASCVD risk.The similar trends of dose-response relationships were also observed in the categorical variable analysis(All P for trend <0.05).2.The results of subgroup analysis based on individual factors and lifestyle showed that the associations between urinary iron,copper,zinc,cadmium,antimony,arsenic and 10-year ASCVD risk were stronger in obese people,smokers,drinkers and those without regular exercise.3.In the continuous variable model,MPV was positively associated with the increased 10-year ASCVD risk(OR=5.03,95%CI: 2.71 ~ 9.33).In the categorical variable model,the adjusted ORs(95% CI)of 10-year ASCVD risk for the second,third and fourth quartiles of MPV were 1.23(0.87 ~ 1.74),1.69(1.11 ~ 2.59)and 2.53(1.60 ~ 3.99),respectively,with the first quartile as reference(P for trend <0.05).4.Mediated analysis indicated that MPV mediated 18.60%,6.63%,7.77% and 22.89% of the associations between urinary iron,zinc,antimony,arsenic and 10-year ASCVD risk,respectively(all P value < 0.05).Conclusions: We found the positive associations of urinary iron,copper,zinc,cadmium,antimony,arsenic with 10-year ASCVD risk,which might be enhanced by obesity,smoking,alcohol consumption and irregular exercise;and a negative association of urinary barium with 10-year ASCVD risk.Furthermore,MPV partially mediated the associations of urinary iron,zinc,antimony and arsenic with ten-year ASCVD risk. |
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