| Background and Objection:The early diagnosis plays a key role in prevention and treatment of cardiovascular disease. How to diagnose cardiovascular disease early, especially to identify the early stage of vascular disease, which used to be the focus of domestic and oversea research. A great deal of research shows that the abnormality of vascular wall structure and function is the root cause of not only cardiovascular and cerebrovascular diseases, but also acute ardiovascular and cerebrovascular events. Subclinical vascular lesions already occurred before the cardiovascular and cerebrovascular events appears. Subclinical vascular lesions refer to vascular damage and structure change without clinical manifestations of cardiovascular and cerebrovascular diseases, such as dysfunction of vascular endothelial, elasticity of large artery decrease but stiffness increase, carotid intima-media thickness increase led to formation of plaque etc. At present, the way to find and inspect subclinical vascular lesions mainly adopt medical imaging examination such as CT, MRI, as well as vascular non-invasive examination technology except for selective arteriography and intravascular ultrasound. Imaging examination is not easy to populized and widely used because of its expensive and complicated operation. Vascular non-invasive examination technology tends to be a promising technology because of its harmless and acceptant virtue. Some techniques used in clinic such as vascular ultrosound detection, mersuring pulse wave velocity(PWV), calculating artery stiffness parameter β, mersuring augmentation index(AI), examinating artery flow-mediated dilationg(FMD) or ankle-brchial index and so on are part of vascular non-invasive examination technology. However vascular non-invasive examination technology has much shortage such as undeveloped-technology, tending to be interfered, low sensibility and spercificity, bad repeatability and accuracy, and so on. Currently there is no satisfied method or indictor among vascular non-invasive examination technology which can be suited to assess the early changes in artery structure and function during the clinical practice.Atherosclerosis is a gradually progressive disease, pathology change occurs to vascular intima firstly. After a series of complicated pathology and physiological change such as:lipid deposition, change of endothelial function, activation of inflammatory cell, release of inflammatory mediators, cellular matrix hyperplasia and reconstruction, it finally lead to the formation of thicken intima, degradated media and atheromatous plaque. Atherosclerosis is a systemic disease, it usually do harm to large vessels such as carotid artery.Ultrasonic testing of carotid intima-media thickness (IMT) to evaluate early atherosclerosis has been used for many years in clinic, IMT≥ 0.9 mm was defined as intima-media thickening. Now it deem that IMT not only reflect the progress of carotid partial atherosclerosis, but also is a early evaluation indictor of full body’s artery atherosclerosis, but the sensitivity of ultrasonography to reflect artery lesion still need to be improved. Besides, since blood vessel’s ultrasonic detection can only acquire atherosclerosis information for local blood vessel, it can not reflect the status of the overall blood vessel, so the effectiveness of IMT to be used to forecast main Atherosclerotic disease (such as coronary heart disease, stroke etc) is not so high.Pulse Wave Velocity(PWV), used as the indicator to evaluate arterial elasticity, which is widely acknowledged and put in clinical use for many years. PWV also has a high value in prediction of cardiovascular and cerebrovascular events, but the operation of its measurement is complicated and has poor repeatability. Cardio-ankle vascular (CAVI) is a new parameter to be used in diagnosis of ateriosclerosis, it can reflect the integral stiffness of aorta, femoral arteria to ankle arteria. The abnormal features of atherosclerosis are increase of artery stiffness and its elasticity decrease, so CAVI reflect the degree of atherosclerosis, and has good correlation with cardiovascular and cerebrovascular events. The value of CAVI have high repeatability and less influence factors, and the measurement operation is simple, it is regarded as the ideal indicator to evaluate artery structure and dysfunction in early phase, non-invasively and conveniently, and draw extensive attention on the way of becoming focus of recent research. At present the relevant research to CAVI mainly focus on its influence factors, the correlation between CAVI and traditional cardiovascular dangerous factors, the correlation among CAVI and several common cardiovascular disease ie. coronary heart disease, hypertention, diabetes.etc. whether there are the correlation existed between CAVI and early changes of atherosclerosis(subclinical lesions of blood vessel) or not, and whether CAVI can be used to diagnose and forecast early atherosclerosis, all these are not yet shown in the relevant research report.Artery endothelial dysfunction is the important pathological changes in early time in the process of formation of atherosclerosis lesions, and is also key initiating factors to accelerate the process of atherosclerosis. Endothelial function has already been damaged even both light and electron microscopes fail to indentify the structure change of artery wall. In theory, the damage of endothelial function is earlier than increase of artery intima-media thickness in the process of atherosclerosis, that is to say, in clinic endothelial dysfunction has already been occured before the atheromatous plaque can be inspected by ultrasonic, CT, magnetic resonance etc. There are many methods to assess the endothelial function, such as the inspection of plasma endothelial marker (E-selectin, thromboxane etc), circulating endothelial progenitor cells, endothelial micro-particles and flow-mediated dilatation(FMD) etc, among which FMD is the unique non-invasive endothelial function inspection technology, and it was widely used in clinic. Even though the decrease of FMD value can reflect the damage of endothelial function, but there are shortcomings such as long survey time, high skill required, poor tolerance for patients during FMD inspection, which impact its widely use in clinic. EMPs is the micro-paticles with diameter<lum, it will be released when EC get activated or apoptotic, it is becoming the hotspot of research that EMPs is the symbol of lesion of EC. The shortcomings in the inspection of EMPs as:ununiform standard of inspection method, expensive cost let to its limited application in clinic.At present, there are not so many correlation research about CAVI and subclinical lesions of blood vessel in early phase, and it can not be retrieved for the research report about correlation between CAVI, Endothelial microparticles and FMD. Since the definition of subclinical lesions of blood vessel in early phase is short of uniform standard, each researcher define their own subclinical lesions of blood vessel in early phase based on their own situation, which lead to big gap in conclusion of similar research and lack of comparability among the researches.The research aim to study the correlation between CAVI and early subclinical vascular disease, explore the value of CAVI to be used for diagnosing and forecasting of early atherosclerosis, the research objective were chosen from the hypertensive patients with no ischemic cardiovascular disease history.Firstly Separate to study CAVI, IMT’s respective influence factors among this kind of patients, identify the correlation among CAVI and IMT, secondly select the patients with IMT< 1.3mm as a whole for further subgroup analysis, define 0.9mm<IMT< 1.3mm as early atherosclerosis (subclinical lesions of blood vessel in early phase).Study IMT’s influence factors in the kind of patients group, explore the correlation between CAVI and IMT within such patients as well as the value of CAVI to be used to diagnose and forecast early atherosclerosis, as mentioned above, in theory in the progress of atherosclerosis, the lesions of endothelial function will come before the increase of carotid intima-media thickness and the formation of plaque, the lesions of endothelial function also fall into the area of subclinical lesions of blood vessel in early phase. In order to further illustrate the subclinical value that CAVI is used in diagnosing early subclinical lesions of blood vessel, the study select the hypertensive patients with no ischemic cardiovascular disease history and CIMT< 0.9mm, inspect CAVI, FMD and plasma endothelial particles, study if there are the correlation between CAVI, FMD and plasma endothelial particles, since endothelial dysfunction is the earliest change of atherosclerosis, among these patients, if there is correlation among CAVI, FMD and plasma endothelial particles, it can be deduced that CAVI can reflect vascular endothelial function and CAVI can be used to forecast and evaluate arteriosclerotic’s early lesions, which enable it have important theoretical and clinic meanings.MethodsChapter One319 first-hospitalized patients from department of cardiology in Xiamen Haichang Hospital within a period of Nov.2011 to Dec.2013 were selected. Which include 147 male and 172 female with an average age of 62.16 (62.16±11.32), (33< age< 88), These patients were diagnosed as hypertension within time span from one day to 2 years etc. the hospitalized standard are as follows:first-hospitalized essential hypertension, no medication of Antihypertensives in the last 3 months before hospitalization. Exclusive standard:secondary hypertension, with confirmed disease history of coronary heart disease, auricular fibrillation, stroke, diabetes, severe renal disease. Medication of Antihypertensives in the last 3 months before hospitalization. each side of ankle-brachial index (ABI))<0.9, the patients were clearly diagnosed as Peripheral atherosclerosis in clinic.CAVI check: On the day of admission the patients were not allowed to take any medicine, and CAVI check were done with Japan Fukuda VaSera CAVI-1000 detector by special person in the next day, in the meanwhile, basic information ie. age, gender, smoking duration, family disease history etc. were all registered, Body height and weight are measured after taking off the shoe before the check, clothing weight was deducted in winter accordingly, Strictly follow up the CAVI operation process to acquire the data of limbs blood pressure, weight index, left and right CAVI, ankle-brachial index (ABI), take both sides’data of ABI I>0.9.Detailed operation:under the surrounding with quiet temperature around 23 ℃, the patients have a Supine rest for at least 15 minutes, when the measure begin, separate to put 12 cm×40 cm Pressure Cuff to both upper arm, and put the same pressure cuff in the ankle, choose the pressure cuff with suitable size when measurement, put electrocardio-electrode to both wrists, attach heart sound transducer to The second intercostal chest, knee cap parts of Knee pulse sensor need to be put in the knee of the patients, align air bag with the center of Knee fossant then laced, input patients information and begin to measure, thus come out CAVI value.MIT Check:under quiet circumstance, The patients are in supine position, slim pillow on the neck, relexed, head leaned to the opposite side of check area, adopt color ultra-sonic unit acuson sc 20000(Simemens) with 7.0 MHZ detector to check common carotid artery at horizontal direction firstly from internal extremity of clavicle, then move the detector along its steric direction towards the head, observe common carotid artery at vertical direction, the vertical ultrasonic image of Carotid artery wall can be shown as 2 parallel light line with relevant low Echo separation, which is "double line type" image. The internal line is the boundary line between internal cell and lumen, the external line is the boundary line between media and tunica adventitia. the span of which is IMT. Freeze the image lcm below Carotid sinus (no plaque area), do measurement of IMT for 3 times, average its figure of 3 times’measurement, which is IMT of common carotid artery.Biochemical indictor inspection:in the next day of admission, the blood of the patient was drawn without eating anything, and sent to inspection dept. to conduct blood biochemical examination. The blood sample need to be analyzed within 60 minutes by experienced inspector with automatic biochemical analyzer.Inspect fasting blood glucose, triglyceride (TG), total cholesterol (TC), low densith lipoprotein (LDL), HDL, apolipoprotein A 1 (apoA 1), apolipoprotein B100, homocysteine, uric acid, creatinine, urea nitrogen, cystatin C.By using of software SPS18.0, measurement data were indicated with means ± standard deviations, the comparison among various group was adopted with t measurement method, counting data was adopted with χ2 measurement, Logistic regression module was used for multi-factor analysis,adopt ROC curve to evaluate the value of CAVI in diagnosis of early carotid arteriosclerotic, P<0.05 was considered statistically significant.Chapter TwoApril 2013 to October 2013,48 hypertensive patients were hospitalized at their first visit in Xiamen Haichang Hospital, which included 31 male and 17 female with age from 22 to 59, all the selected hypertensive patients are their first visit the hospitalized, the requirement are:Age≤60, no history record in coronary heart disease, stroke, diabetes, no medication in the last 3 months. On the day of admission the patients were not allowed to take any medicine, carotid artery color sonography was done in the same day, the patients with carotid intima-media thickness (CIMT)< 0.9 mm were all studied, Hypertension diagnosis standard refer toChina Prevention and control of hypertension guidelines (2010) with blood pressure in clinic≥ 140/90 mm Hg.The patients were done with CAVI inspection by Japan Fukuda VS-1000 arteriosclerosis detector in quiet environment on the day of their admission, all the inspection were done by a special person, FMD check of Patients has been done in the same afternoon (postprandial>2 h). All the check for the patients were performed by the same ultrasound doctor. The next day of Admission,3.5ml offasting elbowvenous blood sample of patientwas sent to hematology dept. in citrate anticoagulation vacuum tubes for blood testing, the test of endothelial micro-paticles was done by the same speciaperson skilled flow cytometer operating.Take the arithmetic average value of CAVI in both sides to analyze the individual correlation between CAVI, FMD and endothelial function within the 48 patients and to study the theoretical and clinic meanings that CAVI was used to diagnose and evaluate vascular early lesions.By use of SPSS 18.0 software and dual variable Pearson correlation analysis to analyze the correlation between CAVI and FMD, endothelial microparticles, P<0.05 was considered statistically significant.ResultsCharter One1. CAVI independent predictors analysis:319 patients were selected, took CAVI=9.0 as critical value, the data were divided into 2 groups:CAVI≥9.0 and CAVI<9.0, the group of CAVI≥9.0 with 86 patients(27%),another group of CAVI<K9.0 with patients 233(73%). Common data analysis, age, systolic pressure, pulse pressure, uric acid, IMT were was higher in CAVI≥9.0 group than in CAVI<9.0 group (age: 69.27±9.11yeras vs59.53±10.94 years,T=7.365,P<0.001. Pusle pressure:153.00±19.25 mmHg vsl44.99±17.80 mmHg,t=3.490,P=0.001.systolic pressure:90.56±11.22 mmHgvs86.63±10.89mmHg,t=2.838,p=0.005.uricacid:371.59±80.08umol/Lvs348.70 ±81.81umol/L,t=2.230,P=0.026.IMT:0.91±0.41mmvs0.71±0.33mm,t=4.528,P<0.001 ),But weight index, apolipoprotein Al, were lower in CAVI>9.0 group than inCAVI<9.0group(weightindex:21.99±2.86vs23.74±3.69,t=-3.981,P<0.001.apolipopr oteinA11:1.17±034mmol/L vs 1.28±0.40mmol/L,t=-2.252,p=0.025).the gender ratio of 2 groups also have statistical difference, the male’s percentage in the group of CAVI>9.0 is 59.3%, which is higher than 41.2% in the group of CAVI<9.0 (χ2=8.283,P=0.004)Multi-variable Logistic regression analysis shows that the difference among two groups with statistical significant, Take CAVI grouping as dependent variable, age, gender, weight index, systolic pressure, apolipoprotein A 1,urine acid as independent variable to conduct logistic regression gradual analysis, the result show that age, gendor, weight index, systolic pressure are CAVI independent predictors (P<0.05). Among which age, male, systolic pressure are risk factos, female, weight index are protective factors.2. IMT independent predictors analysis:319 patients were selected, in line with IMT, It was split as IMT normal group (IMT<0.9mm) and IMT thickened group (IMT≥0.9mm)based on the available data, IMT normal group with 232 patients (72.7%),IMT thickened group with 7 patients(27.3%). By comparison of two groups, age, pulse pressure, apolipoprotein B100, homocysteine, uric acid, creatinine, urea nitrogen, cystatin C. CAVI in IMT normal group are all lower than in IMT thickened group(age:59.84±11.19 years vs 68.32±9.29 years,t=-6.855, P<0.001.Pulse presure:145.06±18.03mmHgvs152.70±18.76mmHg,t=-3.332,P=0.001.apolipoprotein B100:1.02±0.33vs1.18±0.30,t=-3.866,p<0.001, homocysteine:15.54±5.44vs18.26±7.0 4,t=-3.866,p<0.001.urineacid:349.06±84.50,t--2.081,P=0.038;creatinine:79.76±25.5 9 vs 86.83±19.81,t=-2.328,P=0.021.cystatin C:0.98±0.28 vs 1.05±0.29,t=-2.011,P=0.045.CAVI:7.87±1.17 vs 8.67±13O,t=-5.265,P<0.001),but weight index, apolipoprotein Al in IMT normal group is higher than IMT thickened group(weight index:23.53±3.53 vs 22.59±3.53,t=2.089,.P=0.037.apolipoprotein A1:1.27±0.42 vs 1.17±0.28,t=2.531,P=0.012).After variable screening, take IMT grouping as dependent variable, weight index, systolic pressure, apolipoprotein Al, apolipoprotein B100, homocysteine, uric acid, creatinine, urea nitrogen, cystatin C, CAVI as independent variable, to adopt gradual logistic regression analysis, the result show that apolipoprotein B100, homocysteine,CAVI is IMT’s dangerous factors (P<0.05),but apolipoprotein A1 is its protection factors (P<0.05).3. The value of CAVI in diagnosis and predicting of early carotid atherosclerosis: among 319 patients, take 287 patients with IMT< 1.3mm as a whole for further study. According to the thickness of IMT,287 patients were divided as group of non carotid atherosclerosis (IMT<0.9mm)and early carotid atherosclerosis (IMT>0.9mm), non carotid atherosclerosis with 232 patients(80.8%),early carotid atherosclerosis group with 55 patients(19.2%).The result of common data comparison show: age, pulse pressure, apolipoprotein B100, homocysteine, CAVI in non carotid atherosclerosis group(IMT<0.9mm)were all lower than early carotid atherosclerosis group(IMT≥0.9mm)(age:59.84±11.16 vs 69.27±8.99,t=-5.829,P<0.001.pulse pressure:145.06±18.03 vs 153.02±19.03,t=-2.910,P=0.004.apolipoprotein B100:1.02±0.33 vs 1.15±0.28,t-2.569,p=0.011.homocysteine:15.54±5.44 vs 18.00±7.86,t-2.742,P=0.006.CAVI:7.87±1.17 vs 8.75±1.17,t=-5.010, P<.001),but weight index in non carotid atherosclerosis group is higher than it was in early carotid atherosclerosis group(weight index:23.53±3.53 vs 22.47±3.50,t=1.991,P=0.047)The usage of CAVI in diagnosis and predicting of early carotid atherosclerosis: take multi-factor logistic regression anayliss to create two jointly diagnosis index, that is jointly diagnosis index 1 including CAVI and jointly diagnosis index excluding CAVI.2. Adopt ROC curve to analyze the usage that 2 jointly diagnosis index in diagnosis and forecast of early carotid atherosclerosis, the result revealed that the area under jointly diagnosis index 1 with CAVI is 0.758, but the area under jointly diagnosis index 2 without CAVI is 0.670, the difference of which is 0.088, the difference is statistically significant(χ2=5.9108,p=0.0150)(SAS9.3 software analysis result), which also justify that CAVI have the unique value in diagnosis and forecasting of early carotid atherosclerosis.Charter TwoThe result appeared that there were the following correlations according to the parameter statistics in 48 patients by way of dual variable Pearson correlation analysis: negative correlation (r=-0.475,P=0.001) between CAVI and FMD, positive correlation between CAVI and endothelial microparticles(r=0.342,P=0.017),negative correlation between FMD and endothelial microparticles((r=-0.343, P=0.017).The decrease of FMD and increase of plasma endothelial microparticles all indicated the damage of vascular endothelial function, CAVI negatively correlated to FMD and positively correlated to endothelial microparticles indicated the fact that CAVI could reflect vascular endothelial function well and correlated to damage of vascular endothelial function, The bigger figure of CAVI, the worse damage of the endothecium.Conclusion:1.CAVI is a good indictor to reflect the arteriosclerotic degree among hypertensive patients. Age, gendor, weight index, systolic pressure are CAVI independent predictors.Age, male, systolic pressure are risk factos, while female, weight index are protective factors.2.Among hypertensive patients,APO-B100,APO-A1,homocysteine,CAVI are independ predictors of IMT,APO-B100,homocysteine,CAVI are risk factors,APO-Al is pretective factor.3.CAVI is correlated with early atherosclerosis,CAVI is one of predictors of early atherosclerosis and can be used in early diagnosis of subclinical vascular disease.4.CAVI is negatively correlated with endothelial function,the bigger figure of CAVI, the worse damage of the endothecium.5.CAVI is correlated with early subclinical vascular disease,and can be used to predict early diagnosis of early subclinical vascular disease. |
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