| ObjectiveCardiovascular and cerebrovascular diseases are an important cause of human death and a serious threat to human health.Due to the widespread prevalence of unhealthy lifestyle risk factors,the prevalence of cardiovascular and cerebrovascular diseases continues to rise.Risk assessment and stratification of cardiovascular and cerebrovascular diseases are necessary means to detect individuals with different risk factors,and also an important basis for formulating individualized intervention plans.The overall burden of cardiovascular and cerebrovascular diseases in Xinjiang is high.Therefore,it is urgent to predict the risk of cardiovascular and cerebrovascular diseases,evaluate healthy lifestyle,and guide individualized intervention to prevent the incidence of cardiovascular and cerebrovascular diseases in healthy population.Atherosclerosis is the pathological basis of cardiovascular and cerebrovascular diseases,which begins in early life and remains latent for a long time.Carotid plaque,as a commonly used indicator of subclinical atherosclerosis in population studies,is an important predictor of cardiovascular and cerebrovascular diseases.Unlike gender,age and other non-modifiable risk factors,traditional lifestyle 5 items,including smoking,alcohol consumption,diet,exercise and body shape,as modifiable risk factors,are independently and jointly associated with the incidence and mortality of cardiovascular and cerebrovascular diseases and the extension of life expectancy.As an emerging risk factor for cardiovascular and cerebrovascular diseases,studies have shown that sleep is related to the incidence and mortality of cardiovascular and cerebrovascular diseases.Lifestyles often interact and influence each other.However,there are few studies on the relationship between six healthy lifestyles(smoking,drinking,diet,exercise,body size,and sleep)and the risk of subclinical atherosclerosis,and the potential interaction between lifestyles is unknown.During the course of the study,we also found that a substantial proportion of our cohort participants who were predicted to be at low risk for cardiovascular disease had signs of subclinical atherosclerosis.Because the occurrence of diseases is the result of the interaction between genes and environment,the application of metabolomics technology to epidemiological research can integrate the characteristics of endogenous and exogenous risk factors and become a bridge between genes and environment.Some studies have shown that adding plasma metabolites to the classic risk prediction model of cardiovascular and cerebrovascular diseases can increase the ability of disease identification outside the original model and improve the discrimination of the model,thus further improving the risk stratification strategy of cardiovascular and cerebrovascular diseases.In summary,Part I:based on the baseline data of the natural population cohort study of cardiovascular and cerebrovascular disease in Xinjiang,we used the China-PAR model to predict the 10-year risk of cardiovascular and cerebrovascular disease in urban population of Xinjiang.To analyze the prevalence of ideal cardiovascular health(ICVH)behaviors and factors to explain the increased risk of cardiovascular and cerebrovascular diseases in this area.Part Ⅱ:based on the data from the subclinical atherosclerosis sub-cohort of the natural population cohort of cardiovascular and cerebrovascular disease,and based on the idea of moving forward the prevention and treatment,we analyzed the independent associations of traditional lifestyle 5 items including smoking,drinking,diet,exercise,and body shape and sleep quality with subclinical atherosclerosis in the healthy population in this area.To further study the potential joint effect of traditional lifestyle and sleep quality on subclinical atherosclerosis,and to construct 6 elements of healthy lifestyle including smoking,drinking,diet,exercise,body shape and sleep,so as to provide a basis for comprehensive assessment of lifestyle and guide individualized intervention.Part III:we used untargeted metabolomics techniques to identify biomarkers associated with subclinical atherosclerosis in asymptomatic subjects(i.e.,seemingly normal low-risk subjects)with comparable levels of traditional risk factors in subjects predicted to be at low risk by the China-PAR model.Thus,the risk stratification strategy for asymptomatic patients can be improved.MethodsPart Ⅰ:This was a cross-sectional study.A two-stage random sampling method was used to randomly select residents aged 30-74 years from two fixed communities in Urumqi in northern Xinjiang and Korla in southern Xinjiang from July 2019 to September 2021.A general information questionnaire survey,International Physical Activity questionnaire(IPAQ)survey,dietary survey,physical examination,and physiological and biochemical index detection were conducted.After excluding patients with previous stroke and(or)coronary heart disease,the China-PAR model was used to predict the 10-year risk of cardiovascular disease,and the prevalence of ICVH indicators was analyzed to explain the causes of the increased risk of cardiovascular disease in this area.Part Ⅱ:This was a cross-sectional study.Based on the baseline data of the subclinical atherosclerosis sub-cohort of the natural population cohort study of cardiovascular and cerebrovascular disease in Xinjiang,including general information questionnaire survey,IPAQ survey,dietary survey,Pittsburgh sleep quality Index(PSQI)survey,physical examination,physiological and biochemical indicators detection,etc.After excluding patients with previous stroke and(or)coronary heart disease and(or)diabetes,multivariate logistic regression model was used to analyze the independent effects of smoking,alcohol drinking,diet,exercise,body shape(traditional lifestyle 5 items)and sleep on subclinical atherosclerosis.Due to the interaction between traditional lifestyle 5 items and sleep on the risk of subclinical atherosclerosis,we analyzed and studied the combined effect of lifestyle factors and sleep on the risk of subclinical atherosclerosis,and further constructed the 6 elements of healthy lifestyle.Part Ⅲ:Based on the baseline data of the subclinical atherosclerosis sub-cohort of the natural population cohort study of cardiovascular and cerebrovascular disease in Xinjiang,a case-control study was conducted,including general information questionnaire survey,IPAQ survey,dietary survey,PSQI survey,physical examination,physiological and biochemical indicators detection,etc.60 patients with subclinical atherosclerosis were randomly selected,and 60 healthy controls were selected according to the principle of age,sex,chronic disease,and healthy lifestyle.Using non-targeted metabolomics technology,in the China-PAR prediction model of low-risk risk population,on the basis of the traditional risk factors,the level of risk factors was similar.To explore the metabolic biomarkers associated with subclinical atherosclerosis in asymptomatic patients(i.e.,seemingly normal low-risk population).The area under the receiver operating characteristic(ROC)curve(AUC)was used to estimate the predictive ability of the model for subclinical atherosclerosis.ResultsPart I:A total of 10520 participants were selected,with an average age of(46.58±8.92)years,including 5367 males(51.02%)and 5153 females(48.98%).Age,proportion of Han nationality,body mass index,waist circumference,proportion of ideal physical activity,proportion of current smoking,proportion of diabetes mellitus,proportion of taking antihypertensive drugs,systolic blood pressure,diastolic blood pressure,total cholesterol,triglyceride and low-density lipoprotein cholesterol were higher in men than in women(all P<0.001).The proportion of ideal diet,high density lipoprotein cholesterol and family history of cardiovascular and cerebrovascular diseases were higher in women than in men(all P<0.001).The average 10-year risk of cardio-cerebrovascular disease was 3.9%in the total population,and the average risk in men was higher than that in women(P<0.001).9.3%of the total population was at high risk of cardio-cerebrovascular disease,and the proportion of men at high risk was higher than that of women(P<0.001).The 10-year risk of cardio-cerebrovascular disease increased with age in the total population.The 10-year risk of cardio-cerebrovascular disease in men was higher than that in women in different age groups(all P<0.001).Analysis of the prevalence of ICVH indicators in the population has explained the reasons for the increased risk of cardiovascular and cerebrovascular diseases.The results showed that 78.4%(95%CI:77.6%,79.2%)of all participants had ideal fasting blood glucose,and 76.5%(95%CI:77.6%,79.2%)had ideal smoking status.65.2%(95%CI:64.3%,66.1%)of participants had ideal total cholesterol.Only 20.9%(95%CI:20.1%,21.7%)of participants achieved ideal physical activity level,31.4%(95%CI:30.5%,32.3%)achieved ideal BMI level,and 39.1%(95%CI:38.2%,40.0%)achieved ideal blood pressure level,and the ideal dietary level accounted for 43.0%(95%CI:42.0%,43.9%).Only 1.5%(95%CI:1.3%,1.7%)of the participants had seven ICVH parameters.Only 1.9%(95%CI:1.5%,2.3%)of participants in the youth group had seven ICVH indicators,ideal BMI 36.6%(95%CI:35.2%,38.0%),ideal physical activity 19.4%(95%CI:18.2%,20.5%)and ideal diet 42.6%(95%CI:41.2%,44.1%)accounted for less than 50%.Part II:A total of 1924 participants were included,with an average age of(50.12±8.66)years.There were 1014 males(52.7%)and 910 females(47.3%).After full adjustment,non-smoking,healthy alcohol consumption,healthy body type,and healthy sleep were independently associated with a 32%,40%,24%,and 40%reduction in the risk of subclinical atherosclerosis,with OR values of 0.68(95%CI:0.51,0.90)and 0.60(95%CI:0.42,0.87),0.76(95%CI:0.58,0.99),and 0.60(95%CI:0.47,0.77),respectively.There was a significant additive interaction between sleep quality and traditional lifestyle factors.Even the traditional lifestyle 5 items at low risk,the risk of subclinical atherosclerosis due to poor sleep quality was still increased(OR=1.40,95%CI:1.01,1.95).Compared with the old scoring system,13.9%(267/1924)of the subjects were underestimated for the risk of subclinical atherosclerosis.The risk of subclinical atherosclerosis decreased by 29%(OR=0.71,95%CI:0.61,0.82)with each 1-point increase in the score of the 6 elements of healthy lifestyle.Part III:A total of 15 differential metabolites were found,and 12 were up-regulated:Phthalic Acid,N-Methylalanine,N-Ethylglycine,N-Acetylglycine,LPE(O-18:1/0:0),LPE(0:0/16:0),LPA(18:0/0:0),Guanidine,Choline,Carnitine C5-OH,Betaine,and 4-hydroxyphenylglyoxylate.Three metabolites were down-regulated:3-Epideoxycholic acid,Taurolithocholic acid,and Quinic acid.Two important metabolic pathways were found to be associated with subclinical atherosclerosis,namely glycine,serine,threonine metabolism and glycerophospholipid metabolism.The addition of 15 different metabolites to traditional risk factors can increase the differentiation of subclinical atherosclerosis.Conclusions:The average 10-year risk of cardiovascular diseases in Xinjiang was higher than that in other areas of China,and the proportion of high-risk population was 9.3%.The risk of cardiovascular diseases in men was higher than that in women.The analysis of ICVH indicators showed that lack of physical activity,high blood pressure,unreasonable dietary structure,especially the low rate of ICVH level in young people were the main problems in the increased risk of cardiovascular and cerebrovascular diseases and prevention in this area.By analyzing the correlation between lifestyle and subclinical atherosclerosis in the sub-cohort of subclinical atherosclerosis,we found that in addition to smoking,drinking and body shape,poor sleep was associated with increased risk of subclinical atherosclerosis.There is a potential interaction between healthy lifestyles.Even if the traditional lifestyle 5 items are at low risk,poor sleep quality still increases the risk of subclinical atherosclerosis.Therefore,the 6 elements of healthy lifestyle were constructed to comprehensively evaluate lifestyles and provide a basis for guiding individualized intervention from the perspective of lifestyle.In the sub-cohort of subclinical atherosclerosis,we further used untargeted metabolomics technology to explore the differential markers in the low-risk population with the same level of environmental risk factors in the China-PAR prediction model.We found that adding differential metabolites on the basis of traditional risk factors could improve the discrimination of subclinical atherosclerosis.Thus,it provides a basis for improving risk stratification strategies for asymptomatic patients,that is,seemingly normal low-risk population.The above research results provide reference for the prevention and treatment of cardiovascular and cerebrovascular diseases in this region. |
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