The Prevalence Of Carotid Atherosclerosis,Associated Risk Factors,and Its Relationship With Incident Cardiovascular Disease In Middle-aged And Older Adults

Background:Carotid atherosclerosis(CAS),a marker of systemic atherosclerosis,is relevant to cardiovascular and cerebrovascular disease(CVD).The global disease burden of CAS is high,especially in Asia.A large number of studies on the prevalence of CAS have been conducted in China,but they were mostly conducted in physical examination population or high-risk populations,and there is a lack of studies on the prevalence of CAS in general population with a large sample size.Studies of risk factors associated with carotid atherosclerosis are mostly cross-sectional studies,and prospective cohort studies with higher levels of evidence are scarce.Current studies on the relationship between CAS and its progression with incident CVD in the general population are also mostly based on European or American populations and results are controversial.There is no data on CAS and its progression in relation to incident CVD in Chinese general population.Understanding the current prevalence of CAS,associated risk factors and their relationship with incident CVD will help us to develop targeted prevention and treatment strategies to reduce the burden of CAS and its associated CVD.ObjectiveThis study was based on data from people aged 40 years and older in the Xinmi area of the National Stroke Survey Program(CNSSS).This study aimed to investigate:1)the prevalence and influencing factors of CAS;2)the progression of CAS and risk factors;and 3)the assoication between CAS and its progression with incident CVD.Methods:The data for this study were obtained from the data of the population in the rural area of Xinmi,one of the screening sites of CNSSS Base Hospital from 2018-2021.Part I:subjects of this part of the study were permanent residents aged 40 years or older in rural areas of Xinmi who participated in the 2018 or 2019 program screening and completed the direct web-based reporting;Participants with a history of malignant tumors,acute inflammatory diseases,or renal diseases and people with incomplete information collection were excluded.A total of 8811 subjects were included.The prevalence of CAS in the screening population was analyzed and standardized by the Sixth National Census;multivariate logistic regression models were used to explore the association of demographic characteristics,lifestyle,and lipid-related indicators with CAS,and the dose-response relationship between blood lipid related indexes and the risk of CAS was analyzed by restricted cubic spline(RCS).Part Ⅱ and Ⅲ:the study population was enrolled in the 2018 or 2019 screening program and followed up two years later(2020-2021)to complete follow-up data collection;and signed informed consent forms.People with a history of CVD,carotid stenosis,and incomplete information collection of follow-up data were excluded;a total of 6187 cases were included.The definition of the progression of carotid atherosclerosis in this study:the new common carotid IMT thickening of the common carotid artery or the new plaque in the common carotid artery,internal carotid artery and sinusPart Ⅱ statistical analysis:descriptive analysis of the progression of CAS distributed by gender and age was performed;multivariate logistic regression models were used to analyze the association of demographic characteristics,lifestyle,history of chronic disease,and lipid-related indicators with the progression of CAS,and RCSs were drawn.Part III statistical analysis:multivariate logistic regressions were used to analyze the association of CAS and its progression with incident CVD.Stratified analysis was used to explore the interaction of CAS and its progression with CVD risk factors.Results:1.Part Ⅰ:Analysis of the prevalence and factors of associated with CAS:a total of 8811 subjects were included,with a mean age of 60.3±10.3 years.5420(61.5%)subjects had CAS;2916(54.1%)were females;2504(73.2%)were males.The prevalence rate after standardization was 53.7%44.8%and 62.3%for the whole population,women and men,respectively;According to logistic regression analysis,the ORs(95%CI)for aged 50～years,60～years,and 70 years and above compared with those aged 40～years were 1.95(1.692.25),6.07(5.17-7.14)and 15.54(12.71～18.98),respectively.The risk for men was 1.93 times(95%CI:1.68-2.22)higher than women.Other factors such as smoking,lower vegetable and fruit intake,hypertension,diabetes,dyslipidemia,stroke history,heart disease,HHcy were associated with an increased risk of CAS.Factors associated with common carotid artery intima-media thick(IMT)and carotid plaque(CP)were similar to those associated with carotid atherosclerosis;smoking,diabetes,stroke,heart disease,HHcy were significantly associated with moderate to severe carotid stenosis.Lipid-related indicators:remnant cholesterol(RC),atherosclerosis index(AI),and fasting glucose-triglyceride(TyG)index in relation to CAS.After multivariate adjustment,RC was positively associated with CAS,common carotid IMT thickening and CP.Restricted cubic spline(RCS)showed a dose-response relationship between RC and both CAS and CP;After multivariate adjustment,AI was positively correlated with CAS,IMT thickening and CP;AI was not significantly correlated with carotid artery stenosis(P>0.05);RCS analysis showed that AI had a dose-response relationship with CAS,IMT thickening and CP.After multivariate adjustment,TyG was positively correlated with CAS,IMT thickening and CP.RCS analysis showed that TyG was doseresponsive to CAS,IMT thickening and CP.2.Part Ⅱ:Analysis of CAS progression and associated risk factors.A total of 6187 subjects were included in the two-year follow-up.2042 cases(33%)had CAS progression.the incidence of CAS progression increased with age;the incidence of progression was higher in men than that in women.842 cases(13.6%)had IMT progression in the common carotid artery;1547 cases(25.0%)had CP progression.After multi-adjustment,age,male,smoking,lower fruit intake,hypertension,diabetes,dyslipidemia,obesity,and heart rate<80 bpm were independent risk factors for CAS progression;and only with age,hypertension,and heart rate factors for progression of common carotid artery IMT thickening;age,sex,diabetes,dyslipidemia,hypertension,and obesity were independent risk factors for CP progression,similar to those for CAS progression.Association of lipid-related indicators(RC,AI,TyG)with CAS progression were further studied.After multivariate adjustment,RC was an independent risk factor for CAS progression and CP progression.RCS showed a significant dose-response relationship between RC and both CAS progression and CP progression;RC had no significant dose-response relationship with common carotid artery IMT thickening.After multivariate adjustment,AI was an independent risk factor for CAS progression,common carotid artery IMT thickening progression,and CP progression,and RCS showed that AI had a significant dose-response relationship with CAS progression,common carotid artery IMT thickening progression,and CP progression.After multivariate adjustment,TyG was an independent risk factor for CAS progression and CP progression.TyG was not associated with progression of common carotid artery IMT thickening.the RCS showed a significant dose-response relationship between TyG index and both CAS and CP.3.Part Ⅲ:Carotid atherosclerosis and its progression in relation to incident CVD.After multivariate adjustment,CAS and CP were independent risk factors for the development of diagnosed CVD;thickened IMT in the common carotid artery was not associated with incident CVD.Stratified analysis showed an interaction between CAS and dyslipidemia.In the population without dyslipidemia,CAS had a more significant effect on incident CVD.The interaction of common carotid artery IMT thickening with smoking and dyslipidemia was observed.In the non-smokers and the non-lipidemic population,the effect of common carotid artery IMT thickening on incident CVD was more pronounced.Carotid atherosclerosis progression was not significantly associated with incident CVD(P>0.05).Stratified analysis showed that the associations of progression of common carotid artery IMT with incident CVD were more pronounced in male,smokers,and the hypertensive participants.Conclusions:1.The disease burden of carotid atherosclerosis is heavy in the middle-aged and elderly population in the rural areas of Xinmi,especially in men.Older age,male,and history of chronic diseases are important influencing factors of carotid atherosclerosis.There are differences in factors associated with carotid atherosclerosis and subclinical atherosclerosis.Lipid-related indicators(RC,AI,TYG)are closely related to the increased risk of CAS.2.The incidence of CAS progression was high in two-year follow-up.Older age,male,smoking and chronic diseases are the main risk factors for the progression of CAS.Risk factors for CAS progression differed significantly from those for common carotid artery IMT progression and CP progression.Lipid-related indicators(RC,AI,TyG)are independent risk factors for CAS progression.3.Carotid atherosclerosis is an important risk factor for incident CVD.In men,smoking,and hypertensive populations,progression of common carotid artery IMT thickening is an important risk factor for incident CVD.Early attention to CAS and CAS progression in specific populations can help prevent and treat CAS-related CVD events.