Prospective Cohort Study On The Association Of Hyperuricemia,common Metabolic Diseases With Coronary Heart Disease

Objective:To investigate the incidence of coronary heart disease?CHD?,reveal the association of hyperuricemia,common metabolic diseases and CHD,and provide basic data for prevention of CHD in Jinchang cohort.Methods:Subjects were all from the fully matched population between baseline and first-round follow-up of Jinchang cohort,except for those with missing data on important indicators,such as CHD diagnosis,uric acid,blood pressure,fasting blood-glucose,lipid-related index,including total cholesterol?TC?,triglyceride?TG?,high density lipoprotein cholesterol?HDL?and low density lipoprotein cholesterol?LDL?,and body mass index?BMI?.Prospective cohort study,as epidemiological method and Cox proportional hazard regression model were used to analyze the relationship between hyperuricemia,levels of uric acid and the incidence as well as corresponding risk ratio?HR?of CHD,the relationship between common metabolic diseases and incidence as well as corresponding HR of CHD,and the relationship between hyperuricemia,levels of uric acid and incidence as well as corresponding HR of common metabolic diseases.95%confidence interval of HRs were also calculated?HRs,95%CI?.The spline method was used to figure out the dose-response relationship between uric acid,as well as metabolic indicators of common metabolic diseases and the risk of CHD.Mediating effect model was applied to reveal mediation effect of common metabolic diseases on causal relationship between hyperuricemia and CHD.Results:1.The overall incidence of CHD in Jinchang cohort was 2.37%.This figure was 2.42%for the male and 2.29%for the female respectively,with no statistical difference between genders.The incidence of CHD grew up apparently with raising age.After 60 years of age,the incidence of CHD in female increased faster than that of male.2.The incidence rate of CHD was significantly higher in subjects with hyperuricemia than those without hyperuricemia.Figures for hyperuricemia and non-hyperuricemia were 3.42%and 2.19%,3.01%and 2.27%,5.17%and 2.08%in general population,male and female,respectively.After adjustment for age,occupation,marriage status,education status,smoking,and drinking,the risk of CHD for hyperuricemia increased by 31%?HR=1.31,95%CI:1.08-1.58?and 26%?HR=1.26,95%CI:1.01-1.59?compared to non-hyperuricemia in general population and male,respectively.However,statistical association wasn't observed between hyperuricemia and risk of CHD in female.When uric acid was stratified by interquartile range(P₂₅,P₅₀,P₇₅),the incidence rate of coronary heart disease raised apparently with increasing levels of uric acid in general population and male(P _trend<0.05).After adjusting confounding factors,such as age,occupation,marriage status,education status,smoking,and drinking,the Cox proportional hazard regression model showed no statistical association between levels of uric acid and risk of CHD.According to criticality value of definition for hyperuricemia?420?mol/L for male,360?mol/L for female?,different levels of uric acid were also stratified.It was showed that the incidence rate of CHD grew up significantly with raising levels of uric acid in both male and female.After adjustment for same confounding factors,significant association between raising risk of CHD and increasing levels of uric acid was observed in male but not female.The risk of CHD with uric acid?460?mol/L was 1.37 times?HR=1.37,95%CI:1.02-1.84?compared to normal uric acid.There was a linear dose-response relationship(P _overall<0.05,P _nonlinearity>0.05)between levels of uric acid and risk of CHD in male,while a non-linear dose-response relationship in female(P _overall<0.05,P nonlinearity<0.05).3.Both incidence rate and risk of CHD were higher for subjects with hypertension,diabetes,dyslipidemia,and obesity respectively than those without common metabolic diseases.After adjusting age,occupation,marriage status,education status,smoking,and drinking,HRs of CHD were 1.86?1.57-2.19?,1.58?1.30-1.92?,1.31?1.09-1.57?and 1.83?1.48-2.26?for four types of common metabolic disease respectively.Both systolic blood pressure?SBP?and BMI had positive dose-response relationship with risk of CHD.TC and LDL showed positive dose-response relationship with the risk of CHD in general population and male,while a negative dose-response relationship in female.Positive dose-response relationship between TG and the risk of CHD were showed in general population and female,while negative for HDL.4.The incidence rate and risk of hypertension,diabetes,and obesity among subjects with hyperuricemia were higher than those without hyperuricemia.Hazard ratios for hypertension,diabetes,and obesity were 1.20?1.08-1.33?,1.32?1.13-1.54?and 1.99?1.73-2.29?respectively in general population.Compared to first-quartile uric acid,Hazard ratios?HR:Q4/Q1?for hypertension,diabetes,and obesity with fourth-quartile uric acid were 1.33?1.78-1.51?,1.54?1.22-1.94?,and 3.44?2.77-4.26?,respectively.5.Hypertension,dyslipidemia,and obesity have mediating effects on causal relationship between hyperuricemia and CHD.Figures for indirect effect of hypertension,dyslipidemia and obesity were 0.0022?0.0015-0.0010?,0.0010?0.0004-0.0020?and 0.0017?0.0008-0.0020?,corresponding proportion mediated were 25.33%,10.84%and 21.79%.6.With increasing of hyperuricemia plus numbers of common metabolic diseases,both incidence rate and risk of CHD grew up significantly.The incidence rate of CHD among subjects only with hyperuricemia,hyperuricemia plus any one of common metabolic diseases,hyperuricemia plus any two of common metabolic diseases,hyperuricemia plus any three or all kinds of common metabolic diseases were 1.64%,1.87%,3.99%and 7.92%,respectively.Compared to subjects with hyperuricemia alone,hazard ratio for CHD of those with hyperuricemia plus three or all kinds of common metabolic diseases was 2.36 times?HR=2.36,95%CI:1.10-5.07?.Conclusions:1.Hyperuricemia can significantly increase the risk of CHD.Positive dose-response relationship between uric acid and the risk of CHD among both male and female were observed.2.Common metabolic diseases,including hypertension,diabetes,dyslipidemia and obesity were independent risk factors of CHD.3.Hyperuricemia was the cause of common metabolic diseases,such as hypertension,diabetes,and obesity.4.Common metabolic diseases were intermediate variables between hyperuricemia and CHD.A chain of causation,hyperuricemia-common metabolic disease-CHD,may exist.5.Combination of hyperuricemia and common metabolic diseases can raise risk of CHD significantly.