Characteristics Of Individual-level Exposure To PAHs And Factors Affecting The Association Of Individual PAHs Exposure With Blood Pressure Or The Risk Of Atherosclerotic Cardiovascular Disease

Cardiovascular disease?CVD?a chronic non-infectious disease that impose serious threat to human health.At present,the number of CVD patients approximated to 290million,and CVD has become the first leading causes of death in China.It is estimated that the number of CVD deaths will increase additional 39 million individuals in China during the period from 2016 to 2030.Therefore,it is very important for us to investigate risk factors for the development of CVD and the mechanisms involved in the pathogenesis of CVD in order to prevent and control CVD.Polycyclic aromatic hydrocarbons?PAHs?are widely exist in the environment,including air,water and soil.Human beings are environmentally and occupationally exposed to PAHs through inhalation,ingestion,or direct dermal contact.PAHs and their metabolites have been detected in a variety of biological specimens such as blood,urine and hair samples.Urinary monohydroxylated polycyclic aromatic hydrocarbons?OH-PAHs?are considered as biomarkers to assess individual internal PAHs exposure,especially urinary 1-hydroxypyrene?1-OHP?often is used as an indicator for assessing occupational exposure to PAHs.Accumulated evidence show that exposure to PAHs is associated with increased risk of CVD,alonging with PAHs-induced stematic oxidative stress and inflammatory response as well as total cumulative exposure to atherogenic risk factors such as hypertension.Several studies also suggest that PAHs exposure may affect the lipid metabolism,and lead to increasing CVD risk.However,limited data are available on the impact of obesity on the association between PAHs exposure and CVD risk in general population.Therefore,we conducted a repeated-measures panel study.We measured ambient fixed-sites,household or individual-level fine particulate matter?PM2.5?concentrations in different seasons,estimated personal exposure dose of PAHs via inhalation and dietary intake,and further estimated the mediating effect of obesity on the association between exposure to PAHs and increased risk for developing hypertension or atherosclerotic cardiovascular diseases?ASCVD?.Part One Associations of estimated personal PM_2.5 deposition doses in the respiratory tracts based on environmental and individual-level concentrations of PM_2.5 and PM_2.5-bound PAHs with and blood pressureObjectives:The first part of this study aimed to investigate short-term effects of ambient PM2.5 and PM2.5-bound PAHs on changes of systemic inflammatory indicators?including fractional exhaled nitric oxide?FeNO?,C-reactive protein,white blood count,platelets,platelet distribution width and mean platelet volume?and blood pressure?BP?.Methods:A total of 1240 participants from different age groups?<18 years,18^years and?60 years?were recruited from two communities in Wuhan city,China using stratified random cluster sampling method.A panel study of 106 individuals was conducted based on the 1240 participants.There were no apparent differences between two groups in age,gender,education,monthly per capita income,smoking status,drinking alcohol and physical activity,body mass index?BMI?,FeNO and BP?P>0.05?.During the period between the winter of 2014 and summer of 2015,we measured mass concentration of PM2.5 in each community in which the participants lived for 15consecutive days in each season.Meanwhile,we did their household and individual-level PM2.5 concentrations for 3 consecutive days.Subsequently,we assessed personal PM2.5exposure?including deposited doses of PM2.5 in the human respiratory tracts?by using multiple path particle dosimetry?MPPD?model.In addition,benzo?a?pyrene toxic equivalents?TEQBaP?doses in the human respiratory tracts?extrathoracic or head region,tracheobronchial region and pulmonary or alveolar region?were estimated based on the outdoor PM2.5-bound PAHs concentrations,indoor/outdoor PM2.5 ratios and personal/outdoor PM2.5 ratios using MPPD model.Data were collected form all participants in each season by the questionaire survey and physical examination,including demographic characteristics,weight,height,BP,lung function and the inflammatory indicators.Subsequently,we assessed adverse effects of exposure to PM2.5and PM2.5-bound parent PAHs using generalized additive models.Results:We observed increased in BP at lag 1 with an interquartile range increase in PM2.5 mass concentrations of the ambient fixed-sites,household or individual-level PM2.5exposure,and the corresponding estimated deposited doses in the respiratory tract based on data on the ambient fixed-sites,household or individual-level PM2.5 concentrations?all P<0.05?,however,decreased in BP at lag 2 with an interquartile range increase in PM2.5mass concentrations of the ambient fixed-sites,households and the corresponding estimated deposited doses in the respiratory tract based on data on the ambient fixed-sites,household PM2.5 concentrations?all P<0.05?.The estimated deposited doses of PM2.5 by the obtained deposition fractions in this study and by the reported deposition fractions were equivalently associated with alternation in BP.TEQBaP values in the respiratory tract were associated with the values of BP and inflammatory indicators?including FeNO,platelets,platelet distribution width and mean platelet volume??all P<0.05?.Conclusions:The estimated deposited doses of PM2.5 or PAHs?TEQBaP?in the respiratory tract by MPPD model may be a quantitative indicator to assess adverse cardiovascular events triggered by short-term exposure to PM2.5 or PM2.5-bound parent PAHs.However,we need more caution to assess acute adverse cardiovascular events after short-term exposure to PM2.5 using ambient fixed-site PM2.5.Part Two Associations of urinary OH-PAHs levels and daily dietary intakes of PAHs with the risk of ASCVDObjectives:The second part of this study aimed to investigate the associations between environmental PAHs exposure and prehypertension,BP or the risk of ASCVD using based on repeated measurements of urinary OH-PAHs.Methods:In the repeated-measures panel study,106 community-dwelling residents were from the participants?n=1240?who lived at the two communities and finished the physical examination and provided a 3-consecutive-day spot urine samples in each season?see the first part of this study?.Eight urinary OH-PAHs were measured using high performance liquid chromatography.Associations of urinary OH-PAHs with BP and prehypertension with the risk for ASCVD were assessed using either linear mixed-effect models or generalized estimating equations models.In addition,daily dietary intakes of PAHs were estimated based on data on the concentrations of urinary OH-PAHs,and the TEQBaP values were calculated using different sets of toxic equivalency factors.Results:We observed the positive association between urinary OH-PAHs levels and BP values or the odds ratios for prehypertension?all P<0.05?.Additionally,each one-unit increase in ln-transformed urinary levels of 4-hydroxyphenanthrene or the sum of OH-PAH was associated with a 12.63%or 11.91%increase in estimated 10-year risk of ASCVD?both P<0.05?.Moreover,we found the lag-effect pattern in the relationship between urinary OH-PAHs and BP or prehypertension,especially at lag 1?24⁴7 h??all P<0.05?.No association was found between the TEQBaP and BP,prehypertension or estimated 10-year risks of ASCVD?all P>0.05?.Conclusions:The findings indicated that exposure to PAHs may be associated with elevated BP and an increased risk of prehypertension or ASCVD.Inhalation may be a main pathway of exposure to PM2.5-bound parent PAHs for the 106 participants rather than dietary exposure to PAHs.Part three The mediated effect of obesity on the association of exposure to PAHs with blood pressure or the risk of ASCVDObjectives:The thirth part of this study aimed to investigate potential mediation effect of obesity on the association of exposure to PAHs with BP or increased risk of ASCVD.Methods:Among 106 participants from the repeated-measures panel study,the 3-day moving average concentrations of 8 urinary OH-PAHs were determined.Based on obtained data(including 8 urinary OH-PAHs levels for 3 consecutive days and 8 adiposity indicators?including BMI,waist circumferences?WC?,waist-to-hip ratio and waist-to-height ratio?WHtR?,visceral adiposity index,triglyceride glucose index?TyG?,TyG-BMI and TyG-WC?from the second part of this study,mediation analysis?two linear mixed-effect regression model with random intercepts?was performed to evaluate the mediating effect of obesity on the association of urinary OH-PAHs with BP or the risk of ASCVD.Results:We only found a significant pathway?4-hydroxyphenanthrene?4-OHPh??WHtR?ASCVD Risk?in the mediation analysis.The results showed that the WHtR mediated 29.0%of the association of urinary 4-OHPh with increased risk of ASCVD?P<0.05?.The mediation proportions were 18.5%,19.6%and 26.6%for intermediate variables?WC,TyG-BMI and TyG-WC?,respectively,which partially explained the effect of urinary 4-OHPh on systolic BP?all P<0.05?.Additionally,the mediation proportion of WC was 15.8%,which partially explained the effect of urinary 4-OHPh on diastolic BP?P<0.05?.Conclusions:Obesity may partially mediate the association between PAHs exposure and BP or increased risk of ASCVD.