| Objective:The high prevalence and lethality of coronary heart disease（CHD）has been increasing as the standard of living has become more damaging to people’s health,but the complex etiological mechanisms have prevented more effective means of prevention and control.To analyse the effects of hyperuricemia,dyslipidaemia and their combination on the incidence and risk of coronary heart disease（CHD）in the Jinchang cohort,and analyse the effects of different uric acid levels and lipid parameters levels on the risk of CHD,and to further explore the causal relationship between hyperuricemia,dyslipidaemia and CHD.To provide a theoretical basis for scientific prevention and control of CHD.Methods:This study used the epidemiological approach of a prospective cohort study to investigate the effect of baseline uric acid and lipids on the risk of CHD in the Jinchang cohort.The COX proportional risk regression model was used to analyse the effect of hyperuricemia and dyslipidaemia on the risk of CHD development,and further explore the relationship between serum uric acid（SUA）,total cholesterol（TC）,triglyceride（TG）,high density lipoprotein cholesterol（HDL-C）,low density lipoprotein cholesterol（LDL-C）and CHD development using continuous variables to calculate the incidence,relative risk and their 95%confidence intervals（HR,95%CI）.SUA,TC,TG,HDL-C and LDL-C levels were grouped at interquartile spacing to evaluate the effect of different dose levels on CHD risk,and dose-response relationships between SUA,TC,TG,HDL-C and LDL-C levels and CHD risk were analysed using restricted cubic spline.Combining hyperuricemia and dyslipidaemic states to explore the effect of different combined states on the development of CHD.The mediating effect model was used to explore the mediating role of uric acid in the risk of CHD development by lipids and the mediating role of lipids in the development of CHD by uric acid to analyse whether there is a mediating role of uric acid in the development of CHD by lipids and the mediating role of lipids in the development of CHD by uric acid,respectively,by including uric acid and blood lipids as mediating variables.Results:1.The total population of the Jinchang cohort had a total of 1,338 new CHD cases between 2014-2019,with a cumulative incidence of 3.97%,of which the incidence of CHD was 4.60%in men and 3.01%in women.The incidence of CHD showed an increasing trend with increasing age（P<0.05）.2.During the follow-up of the Jinchang cohort,the prevalence of CHD was5.42%and 3.70%in hyperuricemic and normal uric acid patients,respectively,and5.39%and 4.40%and 5.55%and 2.77%in men and women,respectively,and the prevalence of CHD in hyperuricemic patients was significantly higher than that in normal uric acid patients（P<0.05）.The risk of CHD was 1.49 times higher in those with normal uric acid（RR=1.49,95%CI:1.31,1.71）and 1.28 times higher in the hyperuricemic group（HR=1.28,95%CI:1.12,1.46）after adjusting for lifestyle,physiological and other factors.Further stratification of SUA concentrations according to interquartile spacing and stratification analysis showed that the incidence of CHD in the total cohort,male and female populations showed an increasing trend with increasing SUA levels（P<0.05）,and after further adjustment for confounding factors using the COX risk proportion model,the risk of CHD in the highest SUA concentration group in the total population was 1.60 times higher than in the lowest SUA concentration group（HR=1.60,95%CI:1.33,1.92）.SUA was analyzed as a continuous variable for its dose-response relationship on the risk of CHD development,and a linear dose-response relationship between SUA levels and CHD development was found in the total cohort population and in the male population(P overall<0.05,P non-linear>0.05),and a nonlinear dose-response relationship between uric acid levels and the risk of CHD development in the female population(P overall<0.05,P non-linear<0.05).3.Dyslipidaemia significantly increased the risk of CHD,with the prevalence of CHD in dyslipidaemic and normal individuals being 5.50%and 3.06%,respectively,and the risk of CHD in hyperlipidaemic individuals being 1.84 times higher than in normal individuals（RR=1.84,95%CI:1.65,2.06）.Statistically significant differences in CHD prevalence between hyperlipidemic and normolipidemic groups in the total population and in male and female populations after adjusting for confounding factors such as important lifestyle and physiological indicators by COX risk proportional models（total population:HR=1.38,95%CI:1.24,1.54,male:HR=1.24,95%CI:1.09,1.41,female:HR=1.64,95%CI:1.34,2.00）.4.The differences in the incidence of CHD were statistically significant in the presence or absence of abnormal TC,TG,HDL-C and LDL-C indicators（P<0.05）.In the total population,elevated LDL-C and TC had a greater impact on the development of CHD,with abnormal indicators increasing the risk of developing CHD by 55%（HR=1.55,95%CI:1.31,1.84）and 46%（HR=1.46,95%CI:1.21,1.77）respectively.Stratified analysis of the concentrations of each lipid index according to interquartile spacing showed that the risk of developing CHD gradually increased with increasing levels of TC,TG and LDL-C（P<0.05）and decreased with increasing levels of HDL-C（P<0.05）.The results of the restricted cubic spline analysis showed a linear dose-response relationship between TC levels and HDL-C levels and the risk of developing CHD(P overall<0.05,P non-linear>0.05),and a non-linear dose-response relationship between TG levels and LDL-C levels and the risk of developing CHD(P overall>0.05,P non-linear>0.05).5.In the Jinchang cohort,the risk of CHD increased with the number of dyslipidemia（P<0.05）.After adjustment by a multifactorial COX proportional risk model,the risk of CHD was highest when the number of dyslipidemia was three or more,1.83 times higher than that in the group without abnormalities（HR=1.83,95%CI:1.37,2.43）.6.When SUA levels and lipid levels were combined in different combinations,the prevalence of CHD differed for different combinations of SUA levels and lipid levels（P<0.05）.In the total population and in the male and female populations,the risk of CHD was highest in the hyperuricemia+dyslipidaemia group,being 1.61times（HR=1.61,95%CI:1.36,1.91）,1.48 times（HR=1.48,95%CI:1.22,1.80）and1.76 times（HR=1.76,95%CI:1.24,2.28）.7.Analysing the causal chain of disease between uric acid,lipids and CHD in the Jinchang cohort,there was a mediating effect of 0.08（95%CI:0.06,0.10）between dyslipidaemia and the development of CHD,with a mediating effect of 29.87%.The percentage of mediating effect of hyperuricemia on dyslipidemia was 5.52%.Further analysis of lipid indicators showed that TG had the largest mediating effect between hyperuricemia and CHD development with an indirect effect of 0.08（95%CI:0.05,0.10）and a mediating effect of 29.05%.Conclusions:1.Hyperuricemia and hyperlipidemia are risk factors for the development of CHD,and there is a synergistic effect of hyperuricemia and dyslipidemia on the risk of developing CHD.2.Dyslipidemia is an intermediate variable in the pathogenesis of CHD by hyperuricemia,and the etiological chain is hyperuricemia-dyslipidemia-CHD. |
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