| IntroductionResearches of epidemiology have shown that,the morbidity and mortality of cardiovascular diseases in developing countries gradually grows up to be the same with that in developed countries.In China,approximately three million people die each year with cardiovascular diseases.Furthermore,ischaemic cardiovascular disease(ICVD)prevails significantly being associated with age,gender,blood pressure,serum cholesterol,body mass index,smoking and diabetes mellitus.In addition to these factors,hypercholesterolaemia,hyperlipidaemia and hypertension elicit a synergistic effect to increase the death rate of cardiovascular diseases.Referred to the Whitehall Ⅱ study,coronary artery disease is correlated with working category.As different kind of working pressure may cause different kind of health problem,regular physiological health assessment is necessary for the civil servants.However,the Chinese,they rarely do the physiological health assessment.In this study,size of the sample was 2,400 subjects,of which the statuses of risk factors of cardiovascular diseases were investigated in Henan province civil servants.The risk of morbidity related with 10 years follow-up of ICVD was also evaluated to examine the major factors affecting the cardiovascular health of the Civil servants lived in Henan province.Furthermore,we proposed a method to improve assessment strategies.From epidemiology point of view,if some of the levels of physiological chemicals(markers)in blood should reveal the possibility of cardiac disorder,the death rate of Ischemic Cardiovascular Disease(ICVD)could be reduced.Laboratory blood test is a tool helpful in evaluating the health status for the patient.Based on 17 years follow-up observation and using of Cox proportional hazard model,we also evaluated the risk of morbidity and mortality of cardiac disorder with risk score(RS),in which the calculation procedure was reported by Wu et al.in 2003.However,we are wondering about if the ICVD can be found in a head of time via the precursors in blood.Through the RS in terms of the markers in blood,we can assess and alert the clinicians the risk of ICVD for the patients.In this study,collecting enough sample size of 2,400 subjects,we calculated the RS for the subjects.Meanwhile,we assumed that the RS is correlated with the selected predictors in blood,so that we may find the significance of the markers in blood to assess the risk of ICVD statistically.Object1.Understanding the cardiovascular disease risk factors and how to use it to assess the risk of ischemic cardiovascular diseases(ICVD)for the civil servants in Henan Province.2.By using of blood biochemical indicators,to establish a prediction model to evaluate the risk of ischemic cardiovascular disease.Method1.Adopted stratified random sampling method,we did collect a sample size of 2.400 subjects from the age of 35 to 59 and carried out the supplementary investigation but excluding the civil servants diagnosed as coronary heart disease and cerebral apoplexy already.2.We investigated the risk factors of cardiovascular disease from the subjects,including blood lipid,blood pressure,blood glucose,weight,smoking,etc.3.We assessed the risk through the model of "Chinese ICVD risk assessment table in decade" for our target group,civil servants in Henan Province in China..4.We compared the exposure differences of risk factors among different risk groups in our target group.5.We selected BMI,LDL,HDL,GOT,GGT,ALT,ALP,TG,CK and Uric Acid(UA)as the predictor variables to assess the risk of ICVD,and used multiple regression procedures to create a regression model.6.We used principal component analysis(PCA)to find the significance of the predictor variables and then calculate the impact weighting coefficients of principal components analysis.7.By using four integrated factors,we proposed a multiple-variable regression model.Result1.The 2,400subjects were randomly selected from the civil servants in Henan province aged from 35 years to 59 years.Among2,400 subjects,the valid sample subjects 1,468 were males(66.40%)and 743 were females(33.60%).The average age was 48.09±6.99 years.2.Their general exposure rates related to overweight,hyperlipidaemia,hypertension,diabetes mellitus and smoking were 62.96%,76.07%,34.87%,8.10%and 21.30%,respectively.In the 5 risk factors,there are significant differences between genders,age groups and worse health status found in male group.Dyslipidemia and diabetes incidence increases with age.3.Gender ICVD absolute average risk increases with age,and there exist significant differences between the male and female of all age groups(p<0.05).Male absolute risk less than 10%accounted for 94.1%,greater or equal to 10%occupied 5.9%.Female absolute risk less than 10%accounted for 96.8%,greater than or equal to 10%occupied 3.2%.Risk distribution between different genders,age groups was statistically significant difference(p<0.05).4.The comparison of the principal risk factor between the two group of ICVD absolute risk greater than or equal to 10%and less than 10%,there existed statistic significant differences.5.Calculate β coefficients correlated to the predictor variables for the response of RS are presented.We constructed a multiple regression model with the linear combination of those predictor variables and here we named it RM1 that is presented as equation(1).RS =-12.714 + 0.409 ×BMI + 0.585×HDL + 0.801 × LDL + 0.227×TG + 0.020 ×CR+0.248×UA+0.011×ALP-0.014×ALT + 0.013×GOT+0.011×GGT(1)None of the physiological chemicals be an independent affecting factor for assessing the risk of cardiac disorder.6.By using of principal component analysis,we obtained four principal components comprising of H(Hepatic),N(Nephritic),M(Metabolic)and B(BMI).The hepatic(H)related markers comprise of ALT,GOT and GGT.The metabolic(M)related markers include ALP,LDL and HDL,and TG.The nephritic(N)related markers include CR and UA.The RS was stratified into three levels as no risk(RS=1),low risk(RS=2)and high risk(RS=3).From Equation(2)to Equation(5),it shows the impact weighting coefficients of principal components analysis and which were preceded.H = H11×GOT+H12xGGT(2)where H11 0.808 and H12= 0.750 are the impact weighting coefficientsN = N11×CR+N12×UA(3)whereN11=0.737 and N12=0.598 are the impact weighting coefficientsM ＝ M11×TG+M12×CK(4)whereM11=0.737 and M12 = 0.598 are the impact weighting coefficientsBMI = Body weight(Kg)/Square of the Height of the body(m2)(5)7.These four integrated factors,H,N,M and B affect the risk of ICVD.By using of them,we proposed amultiple-variable regression model of RM2 that is presented as equation(6).RS = 11.417 +0.222×H-0.101×N+1.914×M+0.425×B(6)Conclusion1.A high risk of morbidity related to ICVD is observed in civil servants.Lifestyle and personalized health management should be promoted to reduce the risk factors.2.By using of PCA for the data analysis,we revealed that the H,N,M and B can impact the RS to access the risk of ICVD for the population selected.We conclude that our proposed model is valued by using of physiological chemicals(markers)in blood to assess the risk of ICVD.IntroductionAtherosclerosis(atherosclerosis,AS)is a pathological basis of many disease of cardiac blood-vessel,is also the most of major causes of ischemic cardiovascular disease.Atherosclerosis can occur in the first ten years before clinical symptoms appear.It is an important subject in the field of epidemiology to establish an effective method to predict atherosclerosis.Lots of studies have shown that the oxidant is critical for the development of atherosclerosis.Therefore,a variety of natural and synthetic substances that can produce antioxidants alone and in combination should be able to help in the fight against atherosclerosis.Carotenoid pigments are widely distributed in nature,where they play an important role in protecting cells and organisms against oxidation and free radical.Carotenoids are natural plant pigments that produce the bright and vibrant colors that associate with fresh fruits and vegetables.β-carotene is a well-known antioxidant of the carotenoid family,it supplies the bright orange color of carrots,apricots,cantaloupe,sweet potatoes and acorn squash.Epidemiological studies have shown the more fruits and vegetables we eat,the lower our risk of heart disease se will get.A strong association between β-carotene consumption from foods and risk of heart disease has also been described.β-Carotene is one of antioxidant micronutrients that can be favorably manipulated without side effects.Basic research provides a plausible mechanism by which antioxidant is associated with reducing the risk of atherosclerosis.One aim of this study is to understand better the effects of β-carotene on atherosclerosis and thrombosis by using of atherosclerotic rabbit model.Then,arterial pulse detection can be performed on atherosclerotic the rabbit model.By using of variances of arterial pulse to predict and diagnosis cardiovascular disease has been investigated for decades,however,ischemic cardiovascular disease via the variances of cardiac arterial pulse is still difficult to establish the relevance.Basically,clinicians rely on the stethoscope and ECG to complete the caustic process analysis,which may result in missed diagnosis or misdiagnosis.If we can use the information of arterial pulse wave to judge and predict the ischemic cardiovascular disease,the mortality of the heart disease should be reduced.In the epidemiological research,we can establish an atherosclerotic animal model to understand the characteristics of atherosclerotic arterial pulse,and find out the relevant parameters.Based on the results of animal experiments,a causal predictive model based on cardiac pulse signal was established and thus,we may set up the causal parameters to diagnosis of ischemic cardiovascular disease.Object1.To establish rabbit model of atherosclerosis and analyze the drug intervention effect of beta carotene.2.To established a prediction model for ischemic cardiovascular disease through brachial cardiac arterial pulse signal in comparing with the ECGMethods1.Establishment of an animal model of atherosclerosis:Twenty-eight New Zealand White rabbits were divided into 4 groups:normal rabbits as control-control(Group Ⅰ,n=4);atherosclerosis,non-thrombus triggered and non-β-carotene treatment as control(Group Ⅱ,n=8);atherosclerosis,thrombus triggered by Russell’s viper venom and histamine but non-β-carotene treatment(Group Ⅲ,n=8);atherosclerosis,thrombus triggering and β-carotene(30 mg/Kg/d.)treatment(Group Ⅳ,n=8).Rabbits in GroupsⅡ,Ⅲ and Ⅳ underwent balloon deendothelialization and were then maintained on a 1%cholesterol enriched diet for a total of 6 months.Only the atherosclerotic rabbits(Groups Ⅲ and Ⅳ)had pharmacological triggering.2.Aorta detection:The total surface area of the aorta,the surface area of aorta covered with atherosclerotic plaque and the surface area of aorta covered with ante mortem thrombus were measured.The surface area was measured from images obtained by a camera and digitized by computer with a color image processing subsystem.Histological sections and HE staining were used to observe the aortic wall.3.Metallothionein(MT)detection:Metallothionein concentration as an index of oxidation was measured with Cd-hemoglobin saturation method.4.Detection of serum glucose,total protein and cholesterol:The contents of glucose,protein and cholesterol in serum were detected by automatic biochemistry analyzer.5.Detection of total protein and glucose:The protein content was determined using the Bradford method.Glucose-6-phosphatase activity was measured by colorimetric method.6.Rabbit common carotid artery pulse detection:Before the rabbits were sacrificed,Arterial pulse was recorded and analyzed by left common carotid artery intubation.7.Clinical trial:ECG and brachial artery pulse were collected from 387 subjects.Based on clinical data,calculating the parameters of the ROC curve and its AUC indicators to assess and establish a regression model and causal path were conducted.Statistical principle component analysis was used to analyze the characteristics of clinical brachial artery pulse wave and its efficacy was examined by ROC and AUC.After analysis,the correlation coefficient of isokinetic contraction and pulse cycle was calculated from the blood ejection and ventricular septal parameters of 387 subjects in experimental sample.Further screening of 28 subjects with the lowest variants was analyzed statistically.The subjects were judged to be diseased and non-diseased by ECG in two categories,and ECG interpretation related myocardial ischemia was associated with QT values.ROC curve and its AUC index were calculated and the regression model for causal process were evaluated and established.Results1.The atherosclerosis model was established successfully,and 24 New Zealand white rabbits completed the experiment.2.Aorta:The average surface area of aorta of the four groups was 1634±257 mm2.There was no significant difference for surface area of aorta within the four groups.All the rabbits that were fed a 1%cholesterol diet and underwent endothelial debridement had visible diffuse atherosclerosis.Half of triggered rabbits developed thrombosis.The ratio of the thrombus surface area on the aorta in Group Ⅲ rabbits to that on the aorta inGroup Ⅳ rabbits was 1.65(81.5±38.0 vs 49.4±26.7,p<0.05).The number of thrombi in Group Ⅲ rabbits was 1.8 times as that in β-carotene treatment rabbits(Group Ⅳ)(4.8±4.1 vs 2.6±1.5,p<0.05).3.Metallothionein(MT):MT in liver,kidney and heart tissues of Group Ⅲ rabbits was significantly higher than that in GroupⅠ(ratios were:liver 3.3,p<0.03;kidney 4.3,p<0.02;heart 8.9,p<0.05),GroupⅡ(ratios were:liver 2.1,p<0.05;kidney 1.5,p<0.05;heart 1.6,p<0.05)and Group Ⅳ(ratios were:liver 2.4,p<0.03;kidney 1.3,p<0.05;heart 2.3,p<0.05)rabbits.There were no significant differences for MT content among the 4 groups in aorta and femoral arteries.4.Glucose,Protein and cholesterol in Serum:The serum glucose content in the 4 groups was GroupⅢ>GroupⅡ>Group Ⅳ>GroupⅠ(p<0.05-0.01).Serum glucose of Group Ⅲ rabbits was significantly higher than that of Group Ⅳ rabbits(p<0.03)and there was no significant difference between Group Ⅱ and Group Ⅲ rabbits.There was no significant difference for the serum protein content among the 4 rabbit groups.Serum cholesterol of Group Ⅰ was significantly lower than that of the other 3 groups and there was no significant difference among the 3 groups.5.Liver Proteinv and liver Glucose-6-phosphatase(G-6-Pase):There was no significant difference for the liver protein content among the 4 rabbit groups.Liver G-6-Pase of non-β-carotene rabbits was significantly higher than that of other 3 groups(p<0.05)and there was no significant difference for liver G-6-Pase among the 3 groups.6.Pulse detection of rabbits:In the case of atherosclerosis and thrombosis,changes in biochemical parameters and changes in cardiac function were transmitted by pulse wave.7.Clinical trial:This study establishes an effective parametric regression model,which uses ECG-QT time interval to predict ischemic cardiovascular disease-related heart disease,relatively comparative auscultation and ECG professional interpretation,which is simple and easy to perform.According to the comparison of variance and the disease and disease-free classification of ECG experts’ interpretation data,the test data of heart pulse and EEG were used as the basis of modeling,and the correlation of each parameter and ROC-AUC were calculated.Model path analysis to find out the causal relationship between variables was carried out.Path analysis parameters were used to predict the causal patterns of these related parameters,and the method of estimating the normalized regression equation in regression analysis was used to identify and analyze the effects of ischemic cardiovascular disease via the pulse wave wavelengths,isovolumic contraction,and ventricular systolic,ventricular diastolic and isovolumic relaxation.The result has shown that the causal relationship between the "experimental results" and the establishment of ischemic cardiovascular disease prediction.Conclusions1.β-Carotene has potential pharmacological effects on atherosclerotic animal.2.In this study,five parameters were selected for the pulse waveform which are pulse wave wavelength,isovolumic contraction time,ventricular systolic time,ventricular diastolic and isovolumic relaxation time were analyzed by the method of shape differential analysis in the brachial artery pulse wave type.Judgment parameters were thus constructed for the prediction model.3.By the establishment of rabbit model and the clinical experimental result,the cardiac arterial pulse performance of basic ischemic cardiovascular disease prediction model was successfully completed. |
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