Hypertensive Carotid Atherosclerosis Syndrome Characteristics And Tcm Intervention Study

Hypertension is a systemic disease,which is characterized by an elevated diastolic and/or systolic blood pressure as well as functional or organic disorders of heart,brain,kidney,retina, etc.Hypertension is the most common cardiovascular disease and does much harm to people's health.It is investigated that the prevalence of hypertension is wider year by year.In 2006,the number of hypertensive patients in our country has reached 200 millions.Hypertension is not only a kind of disease,but also a major risk factor for coronary artery disease,heart failure, apoplexy,etc.Therefore,when treating hypertension,it is vital to lower blood pressure, improve the symptoms,as well as protect the target organs.Atherosclerosis is one of the most important elements in the target organ damage caused by hypertension.The high blood pressure irritates vein wall of arteries and then causes scleratheroma and plaques,which impacts the arteries' physiological function and even leads to a series of pathological changes.Nowadays,carotid arteries have become the windows of the whole body's arteries,which is for 2 reasons.Firstly,carotid arteries are superficial,easy to observe and competent to impact the whole arteries' situation.Secondly,carotid ultrasound imaging is direct-viewing,convenient,costless and non-invasive,what's more,it can detect the extent and place of atherosclerosis early.Treating hypertension with zheng differentiation-classification is a feature of traditional Chinese medicine and its effectiveness has been conformed by many clinical and empirical studies gradually.However,nowadays, neither the syndrome characters of the hypertensive patients with carotid arterial atherosclerosis is fully reported,or the researches of treating it with traditional Chinese medicine.For the harm and particularity of hypertension-caused carotid arterial atherosclerosis,it is essential to investigate it.In the study,on one hand,the general states of health,syndromes,indexes of carotid ultrasound imaging and laboratory examination have been investigated,which interprets the syndrome characters of the hypertensive patients with carotid arterial atherosclerosis.On the other hand,the effectiveness and availability of treating the disease with treatment of combining zheng differentiation-treatment with activating blood circulation-treatment has been studied,which provide accordance for treating atherosclerosis caused by hypertension with traditional Chinese medicine.The study contains the following three parts:1.Theoretical studyBy searching and reading the relevant incunabula and modern articles,the literature of carotid atherosclerosis caused by hypertension,the literature of treating hypertension with traditional Chinese medicine,the literature of treating atherosclerosis with traditional Chinese medicine, etc has been overviewed.The breakthrough points of the research,the common syndromes of the disease and the main kinds of therapies as well as the mainly-used herbal medicine for the disease have been generalized,which offers theoretical accordance for the following clinical investigation and experimental research.2.Clinical investigation2.1 ObjectivesTo investigate the syndrome characters of the hypertensive patients with carotid arterial atherosclerosis,mainly in different blood pressure(BP) levels,different cardiovascular risk stratification,other types of diseases combines with,etc.And then analyze the characters' relationship and illuminate their disposition rule.2.2 MethodsHypertensive patients over the age of 18 years and below 75 years,which are inpatients of general internal department of guang'an men hospital,were interviewed.The syndrome types of the patients were among yin deficiency yang hyperactivity syndrome,qi-yin asthenia syndrome,yin yang concurrent deficiency syndrome and liver wind stirring syndrome, meanwhile,they were classified with the blood stasis syndrome,phlegm syndrome,phlegm mixing blood stasis syndrome and non accompanied syndrome.We made clinical investigation through questionnaire and medical examination.Trained doctors completed questionnaires regarding to general states of health,treatment history, symptoms,physical signs,etc.Doppler ultrasound exams of carotid artery were done by special operators.The indexes of plaque,intima-media thickness(IMT) and hemodynamic were measured.All of the data was managed and statistically analyzed by software SPSS 13.0. The normal distribution data was tested by One-Way ANOVA.Non-normal distribution Data were tested by NPAR test,such as Mann-Whitney test,Kruskal-Wallis test,Chi-square analyses.The correlations of two continuous variables were tested by Pearson Correlation.2.3 Results2.3.1 General states of healthA total of 120 hypertensive patients with carotid arterial atherosclerosis were enrolled.Among them,62 are male(51.7%),58 are female(48.3%);From age part,the youngest is 40 year-old, the oldest is 75 year-old,the mean age is 67.43+8.03 year-old;From BP levels part,74 (61.7%) in grade 1,26(21.7%) in grade 2,20(16.7%) in grade 3;From cardiovascular risk stratifications part,5(4.2%) with low added risk,13(10.8%) with moderate risk,24(20.0%) with low high risk,78(65.0%) with very high risk;From carotid arterial atherosclerosis part, 19(15.8%) with increased IMT thickness(IMT≥0.9mm),101 with increased IMT thickness and atherosclerotic plaque.From syndrome part,in the aspect of principal syndromes,29(24.2%) have yin deficiency yang hyperactivity syndrome,53(44.2%) have qi-yin asthenia syndrome,27 (22.5%) have yin yang concurrent deficiency syndrome and 11(9.2%) have liver wind stirring syndrome;in the aspect of accompanied syndromes,43(35.8%) have blood stasis syndrome,39(32.5%) have phlegm syndrome,35(29.2%) have phlegm mixing blood stasis syndrome and 3(2.5%) don't have accompanied syndrome.2.3.2 The main characters of hypertension-caused carotid arterial atherosclerosisFirstly,the results shows that carotid arterial atherosclerosis become worse while the BP levels gets higher(P＜0.05,P＜0.01 orP＜0.001 );Carotid arterial atherosclerosis become worse while the cardiovascular risk stratification gets higher(P＜0.05orP＜0.01)Secondly,carotid arterial atherosclerosis become worse as the age grows or the history of hypertension turns longer.Thirdly,if there are other types of diseases combined with,such as heart failure,TIA,etc, the IMT increases(P＜0.05,P＜0.01orP＜0.001).Fourthly,the IMT decreases while the of quantity of smoking decreases (P＜0.05orP＜0.001);The IMT increases while the body weight gets higher(P＜0.05).Fifthly,the IMT and the largest plaque thickness increase while the GLU,CHO,TG,LDL,VLDL,CRP,UA concentration in blood plasma gets higher or the HDL concentration in blood plasma gets lower.The inner diameter shows oppositely. 2.3.3 The syndrome characters of hypertension-caused carotid arterial atherosclerosis2.3.3.1 Analysis of the characters in different patterns of syndromesWhen grouping by principal syndromes,from IMT part,yin yang concurrent deficiency syndrome＞qi-yin asthenia syndrome＞yin deficiency yang hyperactivity syndrome＞liver wind stirring syndrome(P＜0.05);From the thickness of the largest plaque part,yin yang concurrent deficiency syndrome＞yin deficiency yang hyperactivity syndrome＞qi-yin asthenia syndrome＞liver wind stirring syndrome(P＜0.05);The inner diameters and the lengths of the largest plaque show no difference among groups(P＞0.05)When grouping by accompanied syndromes,from IMT part,phlegm mixing blood stasis syndrome＞blood stasis syndrome＞phlegm syndrome＞non accompanied syndrome(P＜0.05); From the inner diameters part,non accompanied syndrome＞phlegm syndrome＞blood stasis syndrome＞phlegm mixing blood stasis syndrome(P＜0.05 );The thicknesses and lengths of the largest plaque show no difference among groups(P＞0.05 ).Combining the principal syndromes with accompanied syndromes to analyze the characters,it shows that the worsening of the disease complies with the pathogenesis's succession in traditional Chinese medicine roughly.2.3.3.2 Analysis of the characters in different symptomsThe scores of vertigo,dizziness,etc are growing with the increasing of IMT(P＜0.05 );The scores of vertigo,dizziness,etc are decreasing with the increasing of inner diameters(P＜0.05 ); The scores of vertigo,top-heavy,etc are growing with the increasing of the thickness of largest plaque(P＜0.05 );The characters of carotid arterial atherosclerosis shows no difference among the groups of other symptoms' scores(P＞0.05).2.3.3.3 Analysis of the characters in different physical signsThe scores of darkening lip,etc are growing with the increasing of IMT(P＜0.05);The scores of darkening lip,etc are decreasing with the increasing of inner diameters(P＜0.05);The scores of darkening orbit,etc are growing with the increasing of the thickness of largest plaque (P＜0.05);The characters of carotid arterial atherosclerosis shows no difference among the groups of other physical signs' scores(P＞0.05).2.3.3.4 Analysis of symptoms and physical signs of carotid arterial atherosclerosis from principal syndromes and accompanied syndromes part Combining the principal syndromes with accompanied syndromes to analyze the sieved symptoms and signs,it shows that within the same principal syndrome,the more serious of the accompanied syndrome is,the more serious the symptoms and physical signs are.2.3.3.5 Analysis of the characters in different tongue and pulse presentationsFrom tongue proper part,the IMT and thickness of the largest plaque both show that dark red and ecchymosis group＞dark red group＞reddish group＞bright red group(P＜0.01or P＜0.001);Internal diameter shows no difference among different tongue proper groups (P＞0.05);Characters of carotid arterial atherosclerosis shows no difference among different tongue-body groups or tongue-fur groups(P＞0.05).The characters of carotid arterial atherosclerosis show no difference among pulse presentation groups(P＞0.05).2.4 ConclusionsOn one hand,according to the results,it is recognized that the characters of the disease,such as IMT,are related with BP levels,cardiovascular risk stratification and other types of diseases combined with.That means while the BP levels getting higher,the cardiovascular risk stratification getting higher,the history of hypertension turning longer,and there being other types of diseases combined with,the IMT and the thickness of largest plaque gets larger and the inner diameter gets smaller.The conclusion reminds that the characters of the disease, such as IMT,can be used to evaluate the risk of the patient suffering,to predict the possible diseases combined,to prevent and treat hypertension-caused atherosclerosis better.On the other hand,from the research,it is realized that characters of the disease are in line with the characters of blood stasis syndrome roughly,which is mainly showed by the guiding symptoms,physical signs and tongue presentations.Our early research has proved that blood stasis syndrome penetrates the whole procedure of hypertension,and the treatment of combining zheng differentiation-treatment with activating blood circulation-treatment is better than the pure zheng differentiation-treatment.Therefore,it is supposed that blood stasis is one of the most important pathogenesis in hypertension-caused carotid arterial atherosclerosis,and it is vital to pay more attention to the blood stasis syndrome when preventing and treating carotid arterial atherosclerosis and other arteriosclerosis caused by hypertension.3.Experimental research 3.1 AimTo investigate the effect of Tianmashuxinkeli in BP and carotid artery vascular remodeling in the spontaneous hypertensive rats(SHR).3.2 MethodsFifty SHR were randomly divided into the large,middle and small dose of Tianmashuxin treated group,blank group and positive control group.Ten Wistar rats were designed as normal group.The groups were treated with the large,middle and small dose of Tianmashuxin extract,captopril tablets and distilled water respectively.Measure systolic caudal arterial pressure fortnightly for 3 months.At the end of the third month measure the left carotid artery intima-media thickness(IMT),lumen radius,IMT/lumen radius,plasma renin activity(PRA) and AngiotensinⅡ(AngⅡ)of plasma.3.3 Results3.3.1 Effect to blood pressureIn the 4^th week,every medicine treated group's systolic caudal arterial pressure is lower than the blank group,among which the positive control group is the most predominant(P＜0.001). In the 6^th,8^th,10^th,12^th week,the systolic caudal arterial pressure of large,middle dose of Tianmashuxin treated group and the positive control group are all lower than the blank group(P＜0.01orP＜0.001)。overall,although the systolic caudal arterial pressure of Tianmashuxin treated groups increases,the range is obviously lower than the blank group(before treatment & 12^th week:large group 162.38±12.86mmHg&182.06±8.80mmHg, middle group 162.89±9.81mmHg & 186.06±15.20mmHg,small group 163.23±12.41mmHg& 197.49±12.19mmHg,blank group 161.87±10.20mmHg & 205.38±17.35mmHg).3.3.2 Effect to carotid arteries3.3.2.1 HistopathologyThe blank group's tunica media of artery thicken obviously,which is shown as muscle-cell proliferation,disordered arrangement and elastic-tunica break.In Tianmashuxin treated groups and positive control group,the thickening of the artery is not obvious,the muscle cell line up in order and there is no elastic-tunica break.3.3.2.2 MorphologyIn the 12^th week,from the IMT part,compared with blank group(383.65±82.93μm),every medicine treated group is smaller(large,middle and small dose of Tianmashuxin treated group, positive control group:271.68±66.48μm,273.57±61.94μm,349.11±48.15μm, 203.71±33.45μm,P＜0.01orP＜0.001);From the lumen radius part,compared with blank group (814.16±98.55μm),the lumen radius of the Tianmashuxin treated groups are larger(large, middle and small dose of Tianmashuxin treated group:1122.23±335.23μm, 942.53±150.87μm,1085.85±322.43μm,P＜0.01orP＜0.001),but the positive control group shows no difference(885.55±55.07μm,P＞0.05);From the IMT/lumen-radius part,compared with blank group(0.49±0.15),every medicine treated group is smaller(large,middle and small dose of Tianmashuxin treated group,positive control group:0.25±0.04,0.29±0.06, 0.36±0.14,0.23±0.04,P＜0.001).3.3.3 PRA,AngⅡIn the 12^th week,compared with blank group(16.67±8.87 ng/ml·h),the PRA of every medicine treated group is lower,among which the middle dose of Tianmashuxin treated group is the most predominant(6.10±3.93 ng/ml·h,P＜0.01);Compared with blank group (1205.79±360.68 pg/ml),the AngⅡof every medicine treated group is lower(large,middle and small dose of Tianmashuxin treated group,positive control group:541.43±147.56 pg/ml, 411.10±128.89 pg/ml,568.18±422.40 pg/ml,850.60±347.10 pg/ml),among which the Tianmashuxin treated groups are the most predominant(P＜0.001).The AngⅡof Tianmashuxin treated groups are lower than the positive control group and shows no difference from normal group(P＞0.05).3.4 ConclusionsTianmashuxinkeli can decrease BP,PRA and AngⅡ,improve carotid artery vascular remodeling.Meanwhile,the outstripping of the large dose group shows its does-effect character.Therefore,Tianmashuxinkeli is beneficial to lighten and reverse carotid arterial atherosclerosis even other atherosclerosis caused by hypertension.From the research,it is supposed that the traditional Chinese medicine treatment for hypertension-caused atherosclerosis,especially the treatment of combining zheng differentiation-treatment with activating blood circulation-treatment,is feasible.