Associations Of Long-term Exposure To PM_2.5 Constituents With Cardiovascular Diseases And All-cause Mortality In Chinese Adults

Objective:Limited evidence exists for chronic effects of ambient PM_2.5constituents in China.To date,there has been no large-scale cohort studies investigating the associations of long-term exposure to PM_2.5 constituents with CVD incidence and all-cause mortality.Hence,we aimed to a)systematically assess associations between long-term exposure to PM_2.5 constituents and cardiovascular diseases（CVD）incidence as well as all-cause mortality in Chinese adults;b)estiblish a local exposure-response relationship for the association of long-term exposure to PM_2.5 constituents with CVD incidence and all-cause mortality at Chinese regional coverage and exposure concentration range;c)explore population susceptibility factors for chronic health effects caused by PM_2.5and its components.Methods:We conceived a nationwide perspective cohort of adults aged 16–110years from 25 provincial regions in mainland China,in which a total of 23,171 people were included in the cohort with the outcome of CVD,and 30,524 people were included with the outcome of all-cause mortality.The cohort was followed from years 2010 to2016 or 2017.Annual county-level exposures of PM_2.5and its constituents(i.e.,BC,OM,NO₃^-,NH₄⁺and SO₄^2-)for each participant were assessed by aggregating satellite-derived estimates at a monthly time-scale and 1 km-resolution.Cox proportional hazards models with time-varying exposures were employed to quantify associations of long-term exposure to PM_2.5and constituents with CVD incidence and all-cause mortality.A restricted cubic spline function was employed to smooth the concentration-response（CR）relationship with the appropriate number of knots according to the model performance.Results:1.During 114,039.1 person-years’follow-up,a total of 1575 CVD incidents occurred.No evidently nonlinear trends were observed for all CR curves,with all p values of likelihood ratio（LR）tests being>0.05.A multiadjusted Cox model estimated an hazard ratio（HR）of 1.237（95%confidence interval:1.100-1.391）for CVD incidence,associated with an interquartile range（IQR=27.5μg/m³）rise in exposure to PM_2.5.Elevated CVD risks were also significantly related to several PM_2.5constituents,with the largest HRs observed in SO₄^2-（1.533[1.346–1.747],IQR=5.6μg/m³）,followed by NH⁴+（1.383 [1.205–1.586],IQR=4.4 μg/m³）,BC（1.221 [1.095–1.360],IQR=2.3 μg/m³）and NO₃^-（1.195[1.032–1.385],IQR=4.4μg/m³）.BC was more strongly associated with total CVD incidence among southern residents,while SO₄^2-was the opposite.2.A total of 1210 deaths occurred during 172297.7 person-years.A multi-adjusted Cox model estimated an HR of 1.125（1.058-1.197）for all-cause mortality,associated with an interquartile range（IQR=26.7μg/m³）rise in exposure to PM_2.5.Comparable or stronger associations were found among PM_2.5constituents with the mortality risk increased by 11.3-14.1%per IQR increase in exposure concentrations.Longitudinal associations of PM_2.5,BC,NO₃^-,and SO₄^2-exposure with all-cause mortality were nearly linear over the whole exposure range,with all p values of LR tests being>0.05.Meanwhile,we detected evident nonlinear relationships between all-cause mortality and OM（p for nonlinear=0.009）as well as NH₄⁺（0.013）.The HR values of death due to exposure to PM_2.5components were significantly higher in men than in women.Smoking and alcohol consumption may exacerbate mortality risks from exposure to PM_2.5components.Meanwhile,more significant and larger risk effect estimates were observed only in urban residents and northern residents,with the effect estimates of partial component significantly different between groups.Conclusions:1.Long-term exposures to PM_2.5and specific constituents(i.e.,BC,NO₃^-,NH₄⁺and SO₄^2-)were associated with increased risks of CVD incidence in Chinese adults,and its associations have potiential regional heterogeneity.2.The CR curves between the risk of CVD incidence and PM_2.5,BC,NH₄⁺,NO₃^-as well as SO₄^2-were approximately linear over the entire exposure range,with a steeper slope in the low concentrations except for SO₄^2-.3.Long-term exposures to PM_2.5compositions(i.e.,BC,OM,NO₃^-,NH₄⁺and SO₄^2-)were associated with all-cause mortality in Chinese adults.The CR curves between the mortality risk and PM_2.5,BC,NH₄⁺,NO₃^-as well as SO₄^2-were approximately linear over the entire exposure range,with evidently nonlinear relationships between all-cause mortality and OM as well as NH₄⁺.With the exception of OM,all CR curves were more slower at the low concentrations.4.Alcohol drinkers,smokers,and men were more susceptible to life loss caused by ambient PM_2.5constituents.Potiential regional heterogeneity also exists in PM_2.5 constituents-mortality associations.