A Ambispective Cohort And Metabolomics Study On The Relationship Between Occupational Stress And Hypertension In Xinjiang Coal Miners

Objective:This study aimed to explore the psychological and physical health status and the influencing factors of coal miners in Xinjiang,and analyze the relationship between occupational stress and physical and mental health.The purpose was to validate the causal association between occupational stress and hypertension,establish the optimal prediction model for the risk of hypertension development in coal miners in Xinjiang,and visually present it through the nomogram model.From the perspective of molecular biology,the potential biomarkers of hypertension and the possible metabolic pathways were preliminarily screened to provide a scientific basis for improving the health and occupational quality of life of coal miners,and to lay a foundation for the study of the mechanism of hypertension.Methods:（1）A random cluster sampling method was used to select 4,537 front-line workers from state-owned coal mines in Xinjiang as the research subjects,questionnaire surveys were conducted on the occupational stress,job burnout,psychological symptoms,sleep quality and their related factors of coal miners by using the Job Demand-Control（JDC）and Effort-Reward Imbalance（ERI）Scale,Chinese Maslach Burnout Inventory（CMBI）,Chinese Version Symptom Checklist-90（SCL-90）and Pittsburgh Sleep Quality Index（PSQI）,respectively,and blood pressure（BP）information was collected.（2）Based on the database established by the research team in 2019,a ambispective cohort study was conducted among 1396 front-line workers from 5 coal mines through the cluster sampling method to analyze the effect of occupational stress on hypertension,the dose-response relationship between occupational stress and the risk of hypertension was analyzed using the restricted cubic spline model（RCS）,and multiple machine learning models such as LASSO regression,random forest,and nomogram were used to screen and visually present the optimal prediction model for the development of hypertension among coal miners in Xinjiang.（3）Based on liquid chromatography-mass spectrometry（LC-MS）technology,a non-targeted metabolomics study of hypertension was conducted on 36 randomly selected cases in the hypertension group and 36 controls,screening for potential biomarkers and related metabolic pathways of hypertension.Results:（1）A total of 4072 valid questionnaires were finally collected in this study,with a valid rate of 91.82%.（2）The occupational stress detection rates in JDC and ERI models for coal miners were 26.7%and 26.4%,respectively,which varied by age,education level,length of service,shift work,type of work,smoking and alcohol consumption groups（P<0.05）.（3）The detection rates of job burnout was 53.6%,which varied among groups with different educational levels,monthly income,length of service,shift work,working environment,type of work,smoking,occupational stress in the JDC and ERI models（P<0.05）.（4）The detection rates of sleep quality problems was 19.7%,which varied among groups with different educational levels,monthly income,marital status,length of service,shifts,working environment,smoking,drinking,occupational stress in the JDC and ERI models,and job burnout（P<0.05）.（5）The positive detection rate of psychological symptoms among coal miners was 24.5%,age between 31-45 years old,two-shift work,higher monthly income and married were protective factors for positive psychological symptoms（P<0.05）.The results of multiple-factor logistic regression show that higher education level,seniority of11-20 years,underground work,the type of work was coal mining,smoking,drinking,occupational stress in the JDC and ERI models,higher degree of job burnout and sleep quality problems were risk factors（P<0.05）.Occupational stress also had positive multiplicative interaction with different degrees of job burnout and sleep quality problems on psychological symptoms（P<0.05）.（6）The prevalence of hypertension among coal miners was 27.7%,age≥31 years old,overweight or obesity,smoking,underground work,occupations such as coal mining,electrical and mechanical maintenance,electrical and mechanical transportation,and tunneling,occupational stress in the ERI model,mild and medium job burnout were risk factors for hypertension（P<0.05）,and monthly income≥8000 yuan（P<0.05）.Moreover,the results of the structural equation model（SEM）showed that occupational stress had both direct and indirect effects on hypertension,and job burnout plays a mediating role.（7）Among 1286baseline coal miners,129 were lost to follow-up,and 1157 completed the follow-up,of which 270 developed hypertension（the incidence rate was approximately 23.4%）.The BP levels of coal miners were associated with age,length of service,marriage,education level,BMI,alcohol consumption,occupational stress,and the imbalance of job control demands（P<0.05）,older age,alcohol consumption,shift work,overweight or obesity,occupational stress,and imbalance between job demands and control were risk factors for the incidence of hypertension（P<0.05）.RCS results showed a linear dose-response relationship between the ERI/JDC ratio and the risk of hypertension(P_overall<0.05,P_{non-linearity}>0.05).（8）Upon comprehensive analysis of the results of multi-factor Logistic regression,LASSO regression,and random forest prediction model,ultimately,age,drinking,BMI,occupational stress and job demand-control imbalance were screened out as the key predictive factors of hypertension,and a nomogram for the prediction of the occurrence risk of hypertension was constructed（AUC=0.742,95%CL:0.709-0.777）.（9）Predictive performance was better for the nomogram model in the training cohort（AUC=0.739,95%CL:0.697-0.780）and the internal validation cohort（AUC=0.740,95%CL:0.676-0.804）.（10）In this study,63 differentially expressed metabolites associated with hypertension were identified（23 up-regulated and 40 down-regulated）.Hierarchical clustering and correlation analysis showed that the differential metabolites were significantly different and correlated with each other in the hypertensive and control groups.（11）10-Hydroxydecanoic acid,bilirubin,Lauric acid,15（R）,19（R）-hydroxy prostaglandin F1α,cysteinylglycine,delta-tridecalactone and o-arachidonoyl ethanolamine may be potential biomarkers of hypertension.（12）A total of 63 metabolites were involved in five metabolic pathways,among which the biosynthesis of fatty acids（pathway impact coefficients=0.022）and arachidonic acid metabolism（pathway impact coefficients=0.015）were the most predominant metabolic pathways（P<0.05）.Conclusion:（1）The psychological and physical health problems of coal miners were prominent,and poor mental health was related to factors such as education level,income,and shift work.（2）The occupational stress of coal miners was related to occupational burnout,sleep quality problems,positive psychological symptoms,and the prevalence of hypertension,and there were positive multiplicative interaction between occupational burnout,sleep quality problems and occupational stress on psychological symptoms.（3）Occupational stress had direct and indirect effects on hypertension,and occupational burnout played a mediating role.（4）Occupational stress and the imbalance of job demands and control would increase the risk of hypertension,and there were linear dose-response relationships between ERI and JDC ratios and the incidence of hypertension.（5）The established nomogram prediction model for the risk of hypertension had a good effect.（6）10-Hydroxydecanoic acid,bilirubin,Lauric acid,15（R）,19（R）-hydroxy prostaglandin F1α,cysteinylglycine,delta-tridecalactone and o-arachidonoyl ethanolamine may be potential biomarkers of hypertension of coal miners in Xinjiang.（7）The biosynthesis of fatty acids and the arachidonic acid metabolic pathway may be the main metabolic pathways of hypertension.Paying attention to the psychological and physiological health of coal miners,improving the working environment,reducing the degree of occupational stress,and monitoring of biomarkers early will help to identify coal miners with poor health conditions,laying the foundation for safe production.