The Association Between Metabolic Syndrome,Visceral Adiposity Index And Asymptomatic Intracranial Atherosclerotic Stenosis

Background:ICAS is a high-risk factor for the initial and recurrence of ischemic stroke（IS）,although many measures and risk management have been developed in the prevention of IS caused by ICAS,such as dual anti-platelet aggregation therapy,intensified management of risk factors and intravascular interventional therapy,etc.However,the risk of IS recurrence caused by ICAS is still very high,with an annual recurrence rate of approximately 12.2%,which indicates that once ICAS developed into symptomatic stage,it is difficult to prevent the recurrence of IS even if various measures have been taken.In addition,epidemiological studies have found that intracranial atherosclerotic lesions often develop years or even decades before clinical symptoms onset.Therefore,early identification of ICAS in the asymptomatic stage,that is,the stage before IS or TIA occurred,may contribute to the primary prevention and therapeutic intervention of stroke,thereby reducing the incidence of IS and vascular cognitive impairment.The prevalence of ICAS and the proportion of ICAS-related stroke vary between races,which maybe contributed by the difference in genetic and environmental factors.Therefore,it is very necessary to explore the prevalence of aICAS and its risk factors in Asian,where the prevalence of ICAS and IS were both high.There are few studies on its correlation with aICAS,and most of the existing epidemiological studies use TCD to diagnose intracranial artery stenosis,and few studies diagnose the causes of stenosis.Therefore,the etiological study of cerebral artery wall using HR-MRI is the direction in the future.ICAS is one of the main causes of IS,especially in Asia.Previous studies have confirmed that traditional cardiovascular risk factors（CRFs）,including hypertension,diabetes,dyslipidemia,and obesity,are independently associated with aICAS in asymptomatic natural populations.However,with the development of social economy,these risk factors present an aggregated incidence state.Their combination is defined as Metabolic syndrome（MetS）.MetS consists of a set of metabolic disorders,including elevated blood pressure,elevated blood glucose,dyslipidemia,and obesity.At present,three types of MetS diagnostic criteria were commonly used,including International Diabetes Federation（IDF）standard in 2005,International Multi-Society Joint Interim Statement（JIS）in 2009 and Chinese Diabetes Society（CDS）standard in 2017.In order to explore the impact of different MetS criteria on the correlation between aICAS and MetS and its components and to find the most suitable MetS diagnostic criteria for the Chinese population for aICAS risk stratification,studies in Chinese natural populations are necessary.Obesity has always been clearly regarded as a risk factor for cardiovascular disease（CVD）.Compared with subcutaneous obesity,visceral obesity is considered to be a more important risk factor for CVD.Visceral adiposity index（VAI）is a simple index calculated by a formula based on physical measurement indicators[Waist circumference（WC）,body mass index（BMI）]and metabolic related indicators[Triglycerides（TG）,high-density lipoprotein cholesterol（HDL-C）],which can quantitatively reflect the visceral fat function and insulin resistance status.The Chinese Visceral adiposity Index（CVAI）is a new index used to evaluate the visceral fat of the Chinese population,which is calculated by age,BMI,WC,TG and HDL-C.CVAI has been proven to be a reliable indicator for predicting visceral fat function,MetS and CVD in the Chinese population.At present,there are many studies exploring the relationship between VAI and coronary artery and carotid atherosclerosis in Caucasians,and there are fewer studies exploring the relationship between VAI and atherosclerosis in Asian populations.The reliability of CVAI and VAI as risk indicators of intracranial atherosclerosis in the general population is sparse.Therefore,this study aimed to compare the correlation of aICAS with VAI and CVAI in a cohort of Chinese middleaged and elderly rural communities,and to evaluate the reliability of CVAI and VAI as risk indicators of aICAS.Part 1:The prevalence of asymptomatic intracranial atherosclerotic stenosis（aICAS）in a natural population aged 40 and older in rural communities in Shandong Province,ChinaPurpose:We used TCD to screen natural population aged 40 years and above in rural communities of Shandong Province,and used MRA and HR-MRI to diagnose AICAS,then studied the prevalence of AICAS and its related risk factors in this natural population.Methods:1.The participants in this study were enrolled from the Kongcun Town Asymptomatic Intracranial Artery Stenosis study（the KT-aICAS study）.The inclusion criteria were as follows:①rural residents aged≥40 years old,and living in Kongcun Town,Pingyin County,Shandong Province;②free of clinical stroke,including cerebral infarction and transient ischemic attack（TIA）.The exclusion criteria were as follows:①The participants whose data in the questionnaire were missing;②The participants with outliers of physical examination and laboratory test results;③The participants who didn’t accept the transcranial Doppler（TCD）,magnetic resonance angiography（MRA）,and high-resolution magnetic resonance imaging（HR-MRI）examinations and those who had missing or unreliable results of above examination were excluded;④The participants whose HRMRI findings suggest non-atherosclerotic lesions.2.From October to November 2017,we conducted a structured questionnaire to get data including demographics,living habits,history of disease and current drug use.We performed physical measurements and physical examinations to get weight,height,waist and blood pressure.We collected fasting blood of the participants,and transferred them to Provincial Hospital for laboratory testing,including fasting plasma glucose（FPG）,low-density lipoprotein cholesterol（LDL-C）,HDL-C,TG and total cholesterol（TC）.3.Asymptomatic ICAS was detected through a 2-phase procedure:First,from October to November 2017,all subjects who met the inclusion criteria were screened by TCD.And then,from April to October 2018,TCD-positive subjects in the screening phase were invited to undergo MRA and HR-MRI to confirm aICAS and exclude nonatherosclerotic lesion.4.We used IBM SPSS Statistics V22.0 for Windows（IBM Corp.Released 2013,Armonk,NY:IBM Corp）for all analyses.In the statistical description,continuous variables were represented by the average（standard deviation）;discrete variables were represented by the number of participants（percentage）.The characteristics between male and female,participants with and without aICAS were compared using t-test for continuous variables and χ2 test for categorical variables.Statistical significance was defined as two-tailed P<0.05.Results:In this study,we investigated the prevalence of aICAS among middle-aged and older adults living in rural communities in China through a two-phase procedure:a screening phase with TCD,followed by a diagnostic phase with MRA and HRMRI examination.Finally,of the 1976 participants,aICAS was detected in 144 persons,of which 87 were women and 57 were men.The overall prevalence of aICAS was 7.29%.Compared with men,the most of the CRFs are more common and severe in women,including diabetes mellitus,dyslipidemia,and obesity.Conclusions:AICAS is relatively common among middle-aged and elderly residents in rural communities in China,with a prevalence of 7.29%.The prevalence of aICAS increased with the age group.Compared with men,the prevalence of aICAS and most of the CRFs are higher in women,and most of the CRFs were more severe in women.Part 2:The correlation of metabolic syndrome and its components with asymptomatic intracranial atherosclerotic stenosisPurpose:This study is to investigate whether different MetS criteria will lead to differences in results among studies,and to find the MetS diagnostic criteria most suitable for Chinese population for risk stratification of aICAS,and to study the correlation between aICAS and MetS and their components under different diagnostic criteria in Chinese natural population.Methods:1.Population selection,data collection and aICAS diagnosis were the same as the first part.2.The three types of MetS diagnostic criteria used in this study were proposed by Chinese Diabetes Society（CDS）in 2017,International Diabetes Federation（IDF）in 2005 and International Multi-Society Joint Interim Statement（JIS）in 2009.3.We used IBM SPSS Statistics V22.0 for Windows（IBM Corp.Released 2013,Armonk,NY:IBM Corp）for all analyses.In the statistical description,continuous variables were represented by the average（standard deviation）;discrete variables were represented by the number of participants（percentage）.The characteristics between participants with and without aICAS or MetS were compared using t-test for continuous variables and χ2 test for categorical variables.Multivariate logistic regressions were used to compare the correlation between aICAS and MetS diagnosed by three types of criteria,and ROC curves were used to compare the value of MetS and its components to identify aICAS.Statistical significance was defined as twotailed P<0.05.Results:1.The prevalence of MetS among 1976 people diagnosed according to three diagnostic criteria（CDS,IDF and JIS）were 31.8%,45.6%and 50.3%respectively.2.According to the prevalence of MetS and its components diagnosed according to the CDS standard,369 of 1028 female subjects had MetS,with a prevalence of 35.9%.Among 948 male subjects,260 had MetS,with a prevalence of 27.4%.The prevalence rates of MetS,abdominal obesity,high blood glucose level and high TG level in female subjects were significantly higher than those in men（P<0.05）.3.Compared with normal subjects,MetS has a higher proportion of elderly,female and low level educators.In addition,the prevalence rates of hypertension,diabetes,dyslipidemia,overweight and obesity are higher than those of the normal population,and the difference is statistically significant.4.With the increase of the number of MetS components,the prevalence of moderate and severe aICAS gradually increased（trend test p<0.001）,and the prevalence of mild aICAS did not increase significantly（P=0.098）.5.After adjusting for age,sex,smoking,drinking and LDL-C,MetS under the three diagnostic criteria（CDS,IDF and JIS）were independently related to aICAS,but there were differences in MetS components and component scores independently related to aICAS.6.By comparing the ROC curves of MetS and its components under three diagnostic criteria to identify aICAS,it is found that the model constructed by Mets components（rather than MetS diagnosis or the number of MetS components）combined with other conventional CRFs performs best in identifying aICAS.Conclusions:The prevalence of MetS among middle-aged and elderly residents in rural communities in China is high.The MetS diagnosed by three types of criterion（CDS,IDF,JIS）were all independently associated with aICAS.Part 3:Correlation between visceral adiposity index and asymptomatic intracranial atherosclerotic stenosisPurpose:This study aims to explore and compare the correlation between VAI,CVAI and aICAS in a Chinese middle-aged and elderly community cohort,and to evaluate whether these two novel indicators can be used as markers of aICAS.Methods:1.Population selection,data collection and aICAS diagnosis were the same as the first part.2.We calculated the male and female VAI and CVAI separately according to the formula,and discretized the continuous variable of VAI/CVAI into three categories according to the tertiles of VAI/CVAI separately in male and female;We determined the best thresholds of VAI/CVAI for identifying aICAS by drawing the ROC curve in men and women separately.We discretized the continuous variable of VAI/CVAI into high or low level according the best thresholds in men and women separately.3、We used IBM SPSS Statistics V22.0 for Windows（IBM Corp.Released 2013,Armonk,NY:IBM Corp）for all analyses.In the statistical description,continuous variables were represented by the average（standard deviation）;discrete variables were represented by the number of participants（percentage）.The characteristics between participants with high and low VAI level were compared using t-test for continuous variables and χ2 test for categorical variables.We calculated the AUC and 95%CI by drawing the ROC curves of VAI and CVAI for identifying aICAS in males and females,respectively.The best thresholds of VAI/CVAI were determined at the point where the Jordan index was the largest,and calculated the sensitivity and specificity at that poiint.Multivariate logistic regressions were used to compare the correlation between aICAS and VAI/CVAI.Statistical significance was defined as two-tailed P<0.05.Results:Among the middle-aged and elderly rural communities in this study,subjects with high level of CVAI had more severe CRFs than those with lower level,including high level of BMI,systolic blood pressure,diastolic blood pressure,pulse pressure,FPG,TC,TG and LDL-C and low level of HDL-C.VAI and CVAI discretized according to the best cut-offs were related to aICAS in both male and female subjects;However,when VAI and CVAI were discretized into three categorical variables according to tertile,CVAI was related to aICAS in male subjects,but not in female subjects;and VAI was related to aICAS in female subjects,but not in male subjects;And when VAI and CVAI were included into the model as continuous variables,CVAI was related to aICAS in both male and female subjects,while VAI was related to aICAS only in males.In addition,we also explored the AUC and 95%CI of the multivariate logistic regression models to identify of aICAS constructed by VAI and CVAI in different data types combined with other conventional CRFs.We found that in male subjects,the multivariate logistic regression model constructed by discretized CVAI combined with other conventional CRFs achieved the maximum of AUC to identify aICAS;and in female subjects,the multivariate logistic regression model constructed by discretized VAI combined with other conventional CRFs achieved the maximum of AUC to identify aICAS.Conclusions:VAI and CVAI were independently associated with aICAS among middle-aged and elderly residents in rural communities in China.In female participants,VAI has a greater value in identifying aICAS than CVAI.In male subjects,CVAI has a higher indictive value of aICAS than VAI.Both aICAS and MetS are common among middle-aged and elderly residents in a rural community in northern China,and MetS under different diagnostic criteria are independently related to aICAS.In clinical practice,CDS criteria can be used to stratify the risk of aICAS in the Chinese population;increased visceral fat is closely related to aICAS and may be a new target for primary prevention of aICAS.