The Mediating Effect Of Inflammatory Biomarker On The Association Between Metabolic Syndrome And Coronary Artery Disease

Background:Coronary artery disease（CAD）caused by atherosclerosis has been a worldwide public health problem.According to the Report on China Cardiovascular Health and Disease in 2019,the number of Chinese mainland residents suffering from CAD was about 11.396 million,with the increase of 1.08 million compared with the data from the National Health Service Survey in2008.Metabolic syndrome（MS）and inflammation are associated with the increased risks of CAD.Metabolic syndrome is a set of clinical syndromes including overweight/obesity,hypertension,hyperglycemia,dyslipidemia.Inflammation plays an important role in the progression of CAD.Studies have shown that inflammatory factors accelerate the development of atherosclerosis by increasing the white blood cell（WBC）count and interleukin-1β（IL-1β）levels.Few studies focus on the mediation effect of inflammation factors（WBC count,IL-1β）between metabolic syndrome and CAD risks.So,serial mediation analysis was used to explore the role of inflammatory factors（WBC count,IL-1β）in the relationship of metabolic syndrome and CAD risks.Objectives:A case-control study was designed to explore the relationship between metabolic syndrome and CAD risks.The serial mediation analysis was used to investigate the role of inflammatory factors（WBC count,IL-1β）in the pathway of metabolic syndrome leading to CAD.Methods:The subjects were selected from the cardiology department of Zhong Da Hospital Affiliated to Southeast University and the Physical Examination Center of Qixia District.The clinical characteristic and blood indicators were collected,and epidemiological questionnaires were conducted at the same time.The level of serum IL-1βwas determined by ELISA.Epi Data 3.1 was used for data entry,and SPSS 25.0 was used for statistical analysis.Multiple imputation was used to fill the missing values.Mean±standard deviation and frequency distribution were used in the descriptive analysis,t-test and chi-square test were used to in comparative analysis of basic data.Logistic regression was used to analyze the association between metabolic syndrome,inflammatory factors（WBC count,IL-1β）and CAD in Chapters1.In Chapters 2 and 3,liner regression analysis was used to explore the association between metabolic syndrome,components of metabolic syndrome（overweight/obesity,hyperglycemia,hypertension and dyslipidemia）and inflammatory factors（WBC count,IL-1β）.The PROCESS plug-in SPSS 25.0 and MPLUS 8.0 were used for the mediation analysis.Results:A total of 1267 subjects were involved in this study,including 572 patients with CAD confirmed by coronary angiography and 695 healthy controls.There were statistically significant differences in the distribution of smoking,alcohol consumption,metabolic syndrome and its components,triglyceride,total cholesterol,high-density lipoprotein cholesterol,WBC count,hemoglobin,and IL-1βlevels between the two groups（P<0.05）.There were no significant differences in education,low-density lipoprotein cholesterol,red blood cell count and platelet count between the two groups（P>0.05）.Logistic regression analysis showed that metabolic syndrome（OR=3.10,95%CI:2.42-3.99）,overweight/obesity（OR=1.33,95%CI:1.01-1.74）,hyperglycemia（OR=1.60,95%CI:1.16-2.21）,hypertension（OR=1.97,95%CI:1.49-2.59）,dyslipidemia（OR=1.39,95%CI:1.06-1.82）,high level of WBC count（OR=1.36,95%CI:1.06-1.73）and IL-1β（OR=1.54,95%CI:1.21-1.96）were associated with the increased risk of CAD.Linear regression was used to analyze the correlation between metabolic syndrome（X）,WBC count（M₁）and IL-1β（M₂）.There were pairwise correlations between the two factors(β_X→M1=0.228,β_X→M2=0.082,β_M1→M2=0.382).Serial mediation analysis showed that after adjusting the confounding factors,WBC count and IL-1βlevels were the serial mediation variables on the association between metabolic syndrome and CAD risks,with the indirect effect was 0.195（95%CI=0.117-0.286）,accounting for 15.18%of the total effect.“Metabolic syndrome-WBC count-IL-1β-CAD”pathway was 0.042（95%CI=0.017-0.074）,and the proportion of indirect effect was 3.27%.“Metabolic syndrome-WBC count-CAD”pathway was0.110（95%CI=0.043-0.193）,and the proportion of indirect effect was 8.56%.“Metabolic syndrome-IL-1β-CAD”pathway was 0.043（95%CI=0.013-0.087）,and the proportion of indirect effect was 3.35%.Linear regression was used to explore the association between overweight/obesity（X₁）,hyperglycemia（X₂）,hypertension（X₃）,dyslipidemia（X₄）,WBC count and IL-1β.The results indicated that hyperglycemia(β_X2→M1=0.082),hypertension(β_X3→M1=0.174)were associated with increased WBC count,but overweight/obesity(β_X1→M1=0.048)and dyslipidemia(β_X4→M1=-0.008)were not.Hypertension(β_X3→M2=0.060)and WBC count(β_M1→M2=0.378)were related to increased IL-1β,but overweight/obesity(β_X1→M2=0.049),hyperglycemia(β_X2→M2=0.024)and dyslipidemia(β_X4→M2=-0.036)were not associated with the increased level of IL-1β.Therefore,this study was only analyzed the role of inflammatory factors（WBC count,IL-1β）on the association between hypertension and CAD risk.Serial mediation analysis showed that WBC count and IL-1βwere the serial mediators on the association between hypertension and CAD risks,with the indirect effect was 0.130（95%CI=0.072-0.201）,accounting for 15.05%of the total effect.“Hypertension-WBC count-IL-1β-CAD”pathway was 0.031（95%CI=0.012-0.056）,and the proportion of indirect effect was 3.59%.“Hypertension-WBC count-CAD”pathway was 0.072（95%CI=0.025-0.140）,and the proportion of indirect effect was 8.33%.“Hypertension-IL-1β-CAD”pathway was 0.027（95%CI=0.003-0.075）,and the proportion of indirect effect was 3.13%.Conclusions:1.Metabolic syndrome was a risk factor for CAD.The components of metabolic syndrome including overweight/obesity,hyperglycemia,hypertension,and dyslipidemia are all the risk factors of CAD.2.Serial mediation analysis showed that WBC count and IL-1βwere serial mediation variables on the association between metabolic syndrome and CAD risks.3.Serial mediation analysis showed that WBC count and IL-1βwere serial mediation variables on the association between hypertension and CAD risks.