| Background:Coronary artery disease(CAD)caused by atherosclerosis is a common heart disease and has the highest incidence and mortality in the world.In recent years,the burden of CAD-related diseases has significantly increased around the globe and has become a major public health problem.The traditional epidemiological researches show that hypertension,diabetes,dyslipidemia,inflammation and heredity are the risk factors of CAD.Among them,lipid metabolism disorder plays an important role in the occurrence and development of CAD and has been identified as one of the major risk factors for CAD.At the same time,vascular inflammation is a key factor in the progression of atherosclerosis and plaque instability.Animal researches have shown that inflammation is involved in all stages of the atherosclerotic process.Cardiovascular injury was caused by inflammatory factors(IL-6,hs-CRP)through a variety of ways,which can promote the development of coronary atherosclerosis,plaque rupture,thrombosis and coronary artery occlusion by accelerating the rupture of lipid pool and upregulation of coagulant substances.Inflammatory factors(IL-6,hs-CRP)are considered to be a necessary condition for the development CAD,and a potential target for the prevention and treatment of CAD.However,it is not clear how inflammatory factors affect the pathogenesis of CAD.And there is no report whether inflammatory factors are involved in lipid metabolism and then affect the CAD.In order to elaborate whether the relationship between dyslipidemia and CAD is partly mediated by inflammatory factors,mediation analysis was used to evaluate whether inflammatory factors(IL-6,hs-CRP)act as potential mediators of the relationship between dyslipidemia and CAD risk.Objectives:A case-control study was designed to explore the association between risk factors and CAD in the population of Jiangsu province.The mediation analysis was used to investigate the causal relationship among dyslipidemia,inflammatory factors(IL-6,hs-CRP)and CAD risk.Methods:The subjects were selected from the cardiology department of Zhongda Hospital Affiliated to Southeast University and the Physical Examination Center of Qixia District.The clinical characteristic,biochemical indicators and blood samples of each subject were collected,and serological separation was conducted.The levels of inflammatory factors(IL-6,hs-CRP)were detected by ELISA.Data analysis: Epi Data3.1 was used to establish the database,and SPSS 23.0 was used for statistical analysis.Mean ± standard deviation and frequency distribution were used in the descriptive analysis,t-test and chi-square test were used in comparative analysis of basic data.The univariate Logistic regression and multivariate Logistic regression were used to analyze the risk factors of CAD for epidemiological survey data and biochemical indicators in Chapters1.Logistic regression analysis were performed to determine the association between dyslipidemia(X)and CAD(Y)as well as inflammatory factor(M)and CAD(Y)in which linear regression analysis was used to determine the association between dyslipidemia(X)and inflammatory factor(M)in Chapters 2 and 3.The Process 3.3 plug-in SPSS 23.0 was used for the mediation analysis.Results:A total of 1305 subjects were involved in the study,including 532 in the case group and 773 in the control group.Compared with the control group,the distribution differences in BMI,education,diabetes,hypertension,dyslipidemia,smoking,alcohol drinking,and family history of hypertension were statistically significant(P<0.05).The levels of TC,HDL-C,TG,white blood cells,platelets,hemoglobin,creatinine,fasting blood glucose,IL-6 and hs-CRP were statistically different between the case group and the control group(P<0.05).The results of univariate Logistic regression analysis showed that there were diabetes,hypertension,dyslipidemia,alcohol drinking,family history of hypertension,family history of diabetes,the levels of BMI,LDL-C,TG,white blood cells,platelets,creatinine,fasting blood glucose,IL-6and hs-CRP were associated with the 12% to 113% increased risk of CAD,and patients with dyslipidemia had a 91% increased risk of CAD(Adjusted OR = 1.91,95% CI: 1.52-2.40),and IL-6 and hs-CRP were associated with 12% increased risk of CAD by each standard deviation increased(Adjusted OR = 1.12,95% CI: 1.00-1.25;Adjusted OR = 1.12,95% CI: 1.01-1.25).Multivariate Logistic regression analysis found that diabetes,hypertension,dyslipidemia,smoking,family history of hypertension,high levels of BMI,white blood cells,platelets and IL-6 were associated with the increased risk of CAD.Logistic regression and linear regression were used to analyze the association of dyslipidemia,inflammatory factors(IL-6,hs-CRP)and CAD,and there was pairwise correlations between the three factors(βX→Y ungroup =0.430,βX→Y not taken statins group =0.460;IL-6 βM→Y ungroup =0.156,βM→Y not taken statins group =0.284,βX→M ungroup =0.123,βX→M not taken statins group =0.191;hs-CRP βM→Y ungroup =0.132,βM→Y not taken statins group =0.233,βX→M ungroup =0.144,βX→M not taken statins group =0.170;P<0.05).The mediation analysis found that after adjusting the confounding factors,IL-6 played a partial mediator in dyslipidemia and CAD,the indirect effect was 0.021(95% CI: 0.001-0.051),after the antilogarithmic conversion,the OR of mediating effect of dyslipidemia on the risk of CAD through IL-6 levels was 1.02(95% CI: 1.01-1.05),suggesting that in the risk of CAD caused by dyslipidemia,with the increase of IL-6 levels by 1 standard deviation,the risk of CAD was increased by 2%,and the proportion of indirect effect was 4.79% among the whole subjects.And subgroup analysis showed that in the group not taking statins,the indirect effect was 0.058(95% CI: 0.012-0.120),the OR of mediating effect of dyslipidemia on the risk of CAD through IL-6 levels was 1.06(95% CI: 1.01-1.13),suggesting that in the risk of CAD caused by dyslipidemia,with the increase of IL-6 levels by 1 standard deviation,the risk of CAD was increased by 6%,and the proportion of indirect effect was 9.43%.Also,hs-CRP played a partial mediator in dyslipidemia and CAD,the indirect effect was 0.022(95% CI:0.001-0.051),after the antilogarithmic conversion,the OR of mediating effect of dyslipidemia on the risk of CAD through hs-CRP levels was 1.02(95% CI: 1.01-1.05),suggesting that in the risk of CAD caused by dyslipidemia,with the increase of hs-CRP levels by 1 standard deviation,the risk of CAD was increased by 2%,and the proportion of indirect effect was 4.91% among the whole subjects.And subgroup analysis showed that in the group not taking statins,the indirect effect was 0.048(95% CI: 0.007-0.104),the OR of mediating effect of dyslipidemia on the risk of CAD through hs-CRP levels was 1.05(95% CI: 1.01-1.11),suggesting that in the risk of CAD caused by dyslipidemia,with the increase of hs-CRP levels by 1 standard deviation,the risk of CAD was increased by 5%,and the proportion of indirect effect was 7.83%.Conclusions:The independent risk factors of CAD included diabetes,hypertension,dyslipidemia,smoking,family history of hypertension,increased BMI,white blood cells,platelets,and IL-6.Higher education and increased hemoglobin might be protective factors for CAD.Mediation analysis found that inflammatory factors(IL-6,hs-CRP)played a partial mediation role in the association between dyslipidemia and CAD risk. |
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