Association Of Exposure To Polycyclic Aromatic Hydrocarbons And Sleep With Major Cardiometabolic Diseases

Cardiometabolic disease is the general term of cardiovascular diseases and metabolic diseases.It mainly includes metabolic syndrome(MetS),diabetes and coronary heart disease(CHD).The real causes of cardiometabolic diseases are poorly understood,and air pollution is one of the major risk factors for cardiometabolic diseases.Polycyclic aromatic hydrocarbons(PAHs)are a wide class of air pollutants.One recent study established an association of PAHs and MetS in general US adults,but little is known about the risk of MetS due to high pollution levels of PAHs exposure.Elevated PAHs metabolites were associated,in a dose-dependent manner,with increased risk of diabetes in general US adults.However,evidence on such relations among Chinese population was scarce.As a more generalized environmental factor,sleep is also an important health-related lifestyle.A growing body of epidemiological evidence showed shorter or longer sleep and midday napping are independently related to increased risk of MetS and/or its components.However,most of the previous studies are cross-sectional and several prospective studies on such relations have produced heterogeneous findings.Futhermore,no study has examined the relationship of sleep duration or midday napping on the reversion of MetS and its components.Most of the prospective studies in white population have showed that shorter sleep duration is associated with an increased risk of CHD incidence.However,it remains unclear whether sleep duration or midday napping is an independent risk factor of CHD incidence,especially in Chinese.In addition,it remains unestablished whether the association of sleep duration with CHD incidence would be modified by genetic effects.Therefore,we aimed to explore the associations of exposure to PAHs and sleep with risk of major cardiometabolic diseases,respectively.The main contents are as follows:Part 1.Association of polycyclic aromatic hydrocarbon exposure with risk of major cardiometabolic diseases-the cross-sectional study1.1 Association between occupational exposure to polycyclic aromatic hydrocarbons and metabolic syndrome in coke oven workersObjective:We aimed to examine whether occupational exposure to PAHs would be one of the important risk factors for MetS in the coke oven workers.Methods:A total of 1157 male coke oven workers were qualified for the present study.Information on demographic characteristics,lifestyle factors,history of disease,and occupational history were collected using standard questionaires by trained interviewers.We measured 12 urinary PAHs metabolites and plasma BPDE-Alb adducts by gas chromatography-mass spectrometry and enzyme-linked immunosorbent assay,respectively.Mutiple logistic regression models were used to evaluate the associations between PAHs internal biomarkers and risk of MetS and its individual components,with adjustments for the potential covariates.Results:The prevalence of MetS in coke oven workers was 26.5%.Urinary 4-hydroxyphenanthrene(4-OHPh)was associated,in a dose-dependent manner,with elevated risk of MetS and elevated levels of fasting blood glucose(FBG).Compared with the lowest quartile,the adjusted odds ratio(OR)and 95%confidence interval(CI)of having MetS in the highest quartile was 1.97(1.29-3.00)(Ptrend<0.001).In stratified analysis,the association between urinary 4-OHPh and risk of MetS and elevated levels of FBG was more evident in subjects who worked longer than 20 years,smokers,and overweight individuals.Joint effects of urinary 4-OHPh with working years and overweight,respectively,on the risk of MetS were also observed.Conclusions:Elevated urinary 4-OHPh was associated with a dose-response increased risk of MetS in coke oven workers.High levels of 4-OHPh combined with longer working years and overweight had a joint effect on the risk of MetS.1.2 Association between polycyclic aromatic hydrocarbon metabolites and risk of diabetes in the general populationObjective:We aimed to examine the association between PAHs metabolites and risk of diabetes in the general population.Methods:Volunteers who resided in the Hankou and Hanyang community of Wuhan at least 5 years were recruited in the survey.After excluding those with missing information on PAHs metabolites.FBG.or other covariates,a total of 2824 subjects were included in the final analysis.Twelve urinary PAHs metabolites were measured by gas chromatography-mass spectrometry.Multiple logistic regression models were conducted to evaluate the association between PAHs metabolites and risk of diabetes.Results:After adjustment for potential covariates,we found that increasing levels of 2-hydroxyfluorene(2-OHFlu),1-hydroxyphenanthrene(1-OHPh),2-OHPh,and 4-OHPh were associated,in a dose-dependent manner,with elevated risk of diabetes(Ptrend=0.021,0.001,0.005,and<0.001.respectively)and a marginally significant association between 9-OHPh and risk of diabetes(Ptrendd=0.050).Compared with the lowest quartile,the adjusted OR of having diabetes in the highest quartile were 1.6 for 2-OHFlu,2.1 for 1-OHPh,1.7 for 2-OHPh,2.1 for 4-OHPh.and 1.7 for 9-OHPh.respectively.In addition,the association was more evident in subjects who were younger than 55 years old,females,nonsmokers,and normal weight.Moreover,the receiver operating curve(ROC)was 0.9570 for the conventional diabetes risk factor model and slightly but significantly increased to 0.9600 when the sum of PAHs metabolites was added.In terms of net reclassification index(NRI),and intergrated discrimination index(IDI),the addition of sum of PAHs metabolites to the basic model resulted in significantly improved risk reclassification with both methods(NRI=0.0512.SE=0.0143.P<0.001;IDI=0.0093,SE=0.042,P=0.025).Conclusions:Elevated PAHs metabolites were dose-responsive related to increased risk of diabetes in the general population.The association was stronger in subjects who were younger than 55 years old,females,nonsmokers,and normal weight.Discrimination of diabetes was modestly but significantly improved when some PAHs metabolites were added to model incorporating conventional diabetes risk factors.Part 2.The association of sleep with major cardiometabolic diseases-the prospective study2.1 Association of sleep duration and midday napping with the incidence and reversion of metabolic syndromeObjective:We aimed to examine the associations of sleep duration and midday napping with risk of incidence and reversion of MetS and its components among a middle-aged and older Chinese population.Methods:We included 14399 subjects from the Dongfeng-Tongji cohort study who were free of CHD,stroke,and cancer at baseline,and without missing information on sleep duration or components of MetS at baseline and during the follow up.Baseline data were obtained by questionnaires and health examinations.ORs and 95%CI were derived from multivariate logistic regression models.Results:After controlling for potential covariates,longer sleep duration(?9 h)was associated with a higher risk of MetS incidence(OR,1.29;95%CI,1.08-1.55)and lower reversion of MetS(OR,0.80;95%CI,0.66-0.96)compared with sleep duration of 7-<8 h;whereas shorter sleep duration(<6 h)was not related to incidence or reversion of MetS.For midday napping,subjects with longer napping(>90 min)was also associated with a higher risk of MetS incidence and a lower risk of MetS reversion compared with those with napping of 1-<30 min(OR,1.48;95%CI,1.05-2.10 and OR,0.70;95%CI,0.52-0.94,respectively).Significance for incidence or reversion of certain MetS components remained in shorter and longer sleepers but disappeared across napping categories.In addition,compared with subjects reporting 7.5-<8.5 h of total sleep per day,those with longer total sleep time(9.5-<10.5 h and ?10.5 h)showed a higher incidence and a lower reversion of MetS,whereas those with longer total sleep time(>10.5 h)exhibited a higher incidence and a lower reversion of central obesity.Conclusions:Both longer sleep duration and longer midday napping were potential risk factors for MetS incidence,and concurrently exert adverse effects on MetS reversion.2.2 Association of sleep duration and midday napping with coronary heart disease incidence and changes in cardiometabolic traitsObjective:To analyze the independent and combined relations of sleep duration and midday napping with CHD incidence along with the underlying changes of cardiometabolic traits among Chinese adults.Methods:We included 19370 subjects who were free of CHD,stroke,or cancer at baseline,and with completed data on sleep duration,midday napping,or other covariates from the Dongfeng-Tongji cohort.Cox proportional hazards models and general linear models were used for multivariate longitudinal analyses.Results:Compared with sleeping 7-<8 h/night,the hazard ratio(HR)of CHD incidence was 1.33(95%CI=1.10-1.62)for sleeping ?10 h/night.The association was particularly evident among individuals who were normal weight and without diabetes.Similarly,the HR of incident CHD was 1.25(95%CI=1.05-1.49)for midday napping>90 min compared with 1-30 min.When sleep duration and midday napping were combined,individuals having sleep duration>10 h and midday napping>90 min were at a greater risk of CHD than those with sleeping 7-<8 h and napping 1-30 min:the HR was 1.67(95%CI=1.04-2.66).In addition,longer sleep duration>10 h was significantly associated with increases in triglycerides(TG)and waist circumference,and a reduction in high-density lipoprotein cholesterol(HDL-c);while longer midday napping>90 min was related to increased waist circumference.Conclusions:Both longer sleep duration and midday napping were independently and jointly associated with a higher risk of CHD incidence,and altered lipid profile and waist circumference may partially explain the relationships.2.3 Interaction of lipid-related genes and sleep duration on the longitudinal changes of blood lipids and incident coronary heart disease-the prospective studyObjective:We aimed to examine whether the polymorphisms of lipid-related genes(the APOA4-APOA5-ZNF259-BUD13 gene cluster)may interact with sleep duration on 5-year changes in lipid profiles and CHD incidence among a middle-aged and older Chinese population.Methods:Four single nucleotide polymorphisms(SNPs)---rs 17119975,rs651821,rs7396835,and rs964184 in the APOA4-APOA5-ZNF259-BUD13 gene cluster were selected and genotyped among 6804 healthy subjects from the Dongfeng-Tongji cohort study at baseline.General linear models were fitted to examine the associations of genetic variants in the APOA4-APOA5-ZNF259-BUD13 gene cluster and genetic risk score(GRS)with 5-year changes in lipid levels[total cholesterol(TC),TG,HDL-c,and low-density lipoprotein cholesterol(LDL-c)].Multiple logistic models were used to evaluate the effects of SNPs and the gene-sleep interaction on CHD incidence.Results:After adjusting for other covariates,we found that rs17119975,rs651821,and GRS were significantly associated with increased TG.In addition,all of the 4 SNPs in the APOA4-APOA5-ZNF259-BUD13 gene cluster and GRS were inversely associated with HDL-c changes.Moreover,the genetic association with TG change consistently strengthened across the sleep duration categories.For rs651821,no significant genetic effect on TG change was observed in individuals with sleep duration<7 h,whereas the differences in TG change per increment of risk allele for rs651821 were 0.033(SE 0.011,P=0.003),and 0.049(SE 0.020,P=0.008)in individuals with sleep duration 7-<9 h,and>9 h,respectively(P interaction=0.039).A weighted GRS derived from the 4 SNPs also showed a significant interaction with longer sleep duration(>9 h)on TG change(P interaction=0.032).No significant associations were observed between the 4 SNPs and incident CHD.Conclusions:Longer sleep duration(>9 h)may exacerbate the genetic effects of variants in APOA4-APOA5-ZNF259-BUD13 gene cluster on 5-year TG changes...