| Theoretical study1. ObjectivesTo investigate the origin and development, Etiological factors and pathomechanism and treatment of blood-stasis syndrome in essential hypertension (EH).2. The origin and development of blood-stasis syndrome and the treatment of promoting blood circulation and removing stasis2.1 The related theories in NeijingThere are many contents relating to "stagnant blood" in the classical traditional Chinese medicine book Neijing, which is of systematic reorganizations in blood-stasis syndrome, including its etiological factors, pathogenesis, clinical symptoms and treatments. The related contents can be sketched as following. Firstly, the elements reasoning for blood-stasis syndrome are exogenous pathogens, excessive emotion-thought, diets without temperance, wounds, oldness, and invalidism. Secondly, the treatment principle is:dredge the stasis of Blood and Qi in order to make them go smoothly. Thirdly, a prescription under the principle of promoting blood circulation and removing stasis has been recorded. Last but not the least, some complications such as apoplexy has been fully discussed.2.2 The related theories in Medicine Book of Eastern Han Dynasy (25BC---220AD) in Wuwei, Gansu ProvinceThe treatment of promoting blood circulation and removing stasis is firstly recorded in Medicine Book of Eastern Han Dynasy (25BC---220AD) in Wuwei, Gansu Province, which is discovered in 1927. The book has also recorded some prescriptions, which are called "stasis-relieving prescriptions" with the effects of promoting blood circulation and removing stasis. 2.3 The related theories in Shanghan Zabing Lun by Zhang ZhongjingThe classical traditional Chinese medicine book Shanghan Zabing Lun, which was accomplished by the late Eastern Han Dynasy, is of vital importance to the theory of blood-stasis syndrome and the coherent treatment. Above all, the disease of "Yu Xue (stagnant blood)" was firstly named. Secondly, the clinical symptoms as well as the treatment principal, namely "the stagnant blood should be treated by dissipation" were recorded. Thirdly, the features of the treatment of promoting blood circulation and removing stasis were formed, which is the usage of both herb medicine and animal medicine. The theory of blood-stasis syndrome in Shanghan Zabing Lun, which was a relatively complete system, has settled the basis of the theory.2.4 The related theories in Tang Dynasty (618AD---907AD) and Song Dynasty (960AD---1279AD)Based on the theory of blood-stasis syndrome, the medicine specialists of those days discovered numbers of herbs and prescriptions, richening the medical choices and spreading the applications.2.5 The related theories in Jin Dynasty (1115AD---1234AD) and Yuan Dynasty (1206AD---1368AD)Of the four medicine specialists in those days, Li Dongyuan and Zhu Danxi both attached great importance to the treatment of promoting blood circulation and removing stasis. The book of Danxi's experiential therapy, said "If the blood and Qi go smoothly and harmoniously, the body is healthy; If they are hindered, the body is susceptible to many diseases", which underline the significance of keeping blood and Qi going smoothly.2.6 The related theories in Ming Dynasty (1368AD---1644AD) and Qing Dynasty (1616AD---1911AD)The theory of "stagnant blood causing vertigo", which was invented by the medicine specialist Yu Tuan in Ming Dynasty, is considered as the milestone in the reorganization of vertigo. Another medicine specialist Pan Ji in Qing Dynasty inherited and developed Yu's theory, who thought that Qi and nutrition to the head will be blocked by the stagnant blood, so the lack of Qi and nutrition in the head causing vertigo. Those theories of Yu and Pan developed the study of vertigo, and provided a new way to the research of hypertension.In Qing Dynasty, the specialist Ye Tianshi, who took to using instinct medicine, stated the viewpoint of "In blood related disease, it is essential to cool blood and dissipate stasis, as well as avoid hematozemia or hemorrhage".Wang Qingren, another medicine specialist in Qing Dynasty, made a great dedication to the blood-stasis theory. He put great significance to the relationship of blood and Qi in the treatment of blood-stasis syndrome, and examples of that are the prescriptions called "buyang huanwu tang" used to treat apoplexy, and "xuefu zhuyu tang"used to treat pectoral stuffiness pain. Both of the diseases are the complication of hypertension. Tang rongchuan, still another medicine specialist in Qing Dynasty, wrote hemorrhagic zheng. In the book, he recorded in detail the symptoms and treatments of blooding syndrome, the relationship of stagnant blood and blooding and the principle of treatment emphasizing removing blood stasis.In modern times, medicine specialist Zhang Xichun, who wrote medical records of Chinese and Western medicine, had many developing opinions in the theory of blood-stasis syndrome, and treat apoplexy complicated with hypertension with the prescription that can promote blood circulation.3. The presentation of blood-stasis syndrome in Essential hypertensionEH, a conception of Western medicine, can't be found in the incunabula of traditional Chinese medicine. In the past, the treatment of EH with traditional Chinese medicine usually focus on "the liver and the kidney" or "Yin and Yang", according to the symptoms such as vertigo and headache. However, in the clinical practice, many patients of EH don't have any symptom, and EH do great harm to target organs, particularly cordis, brain and kidney, leading to high rates of disabling and death. Therefore, how to recover the impairing target organ in the early stage is an significant responsibility that attach to modern medicine researchers.The past studies have proved that blood-stasis is a vital pathomechanism and penetrates the whole procedure of EH. Besides, Western medicine also acknowledge that blood viscosity is high of EH patients. However, there is few articles about blood-stasis syndrome in EH.4. The Etiological factors and pathomechanism of blood-stasis syndrome in EH4.1 Etiological factors4.1.1 Native endowmentThe abnormity of native endowment will influence the movement of blood and Qi, which results in blood stasis.4.1.2 Excessive emotion-thoughtThe depression of liver-qi can lead to stagnation of qi stagnancy and blood stasis4.1.3 Defatigation or lack of exercises4.1.4 Diets without temperanceTaking in too much salt can hurt blood vessels and cause blood stasis; Favorite of sweet or fat can produce dampness and phlegm, which will block the meridians and result in blood stasis; Favorite of pungent food or alcohol can rob Yin-fluid and cause blood stasis.4.1.5 Coldness irritationBy the irritation of coldness, on one hand, the blood moves slowly and freezes; on the other hand, the blood vessels contract. Both lead to the rise of blood pressure.4.1.6 Oldness and invalidismAs an result of oldness or invalidism, the deficiency of Yang-Qi make it hard to push the blood to move and result in blood stasis.4.2 Pathomechanism4.2.1 Qi stagnancy and blood stasis4.2.2 Liver heat and blood stasis& Yang hyperactivities and blood stasis4.2.3 Phlegm and blood stasis4.2.4 Qi asthenia and blood stasis4.2.5 Yin deficiency and blood stasis4.2.6 Cold coagulation and blood stasis4.2.7 Yang deficiency and blood stasis4.2.8 Yin yang concurrent deficiency and blood stasisAbove all, the relationship of blood and Qi is most important of all the Pathomechanism. The diseases located in the liver as well as Qi, blood and vessels.4.3 Pathomechanism of the complications attached to the blood-stasis syndrome in EHThe modern medicine recognize that the failure of control to EH for a long time will do harm to the target organs such as cadiovascular, cerebrovascular and kidney, resulting in complications such as left ventricular hypertrophy, heart failure, cerebral Arteriosclerosis, apoplexy(including cerebral ischemic stroke and hemorrhagic apoplexy), chronic kidney failure, etc. Most of these complications, which decrease quality of patients'lives and threat their lives seriously, closely relate to blood-stasis syndrome.5. The treatment of blood-stasis syndrome in EH5.1 The treatment of absolute blood-stasis syndrome in EHPromote blood circulation and remove stasis, using the prescription "huoxue jiangya tang", which includes dan-shen root, tree peony root-bark, motherwort, gambirplant, medicinal cyathula officinalis root, red peony root, etc.5.2 The treatment of blood-stasis syndrome accompanied with other syndrome in EH5.2.1 Qi stagnancy and blood stasisPromote qi to activate blood, using the prescription "xuefu zhuyu tang".5.2.2 Liver heat and blood stasisCool the liver as well as promote blood circulation and remove stasis, using the prescriptions "longdan xiegan tang" and "danshen drink".5.2.3 Phlegm and blood stasisDissipate phlegm and promote blood circulation, using the prescription "xihua huoxue fang"5.2.4 Qi asthenia and blood stasisReinforcing Qi and promote blood circulation, using the prescription "buyang huanwu tang".5.2.5 Yin deficiency and blood stasisNourish Yin and promote blood circulation, using the prescriptions "liuwei dihuang wan" and "danshen drink". 5.2.6 Cold coagulation and blood stasisWarm the body and promote blood circulation, using the prescriptions "mahuang fuzi xixin tang" and "siwu tang".5.2.7 Yang deficiency and blood stasisWarm Yang and promote blood circulation, using the prescriptions "zhenwu tang" and "xuefu zhuyu tang".5.2.8 Yin yang concurrent deficiency and blood stasisReinforce Yin Yang and promote blood circulation, using the prescriptions "erxian tang" and "shixiao san".Clinical studyObjectivesTo investigate the effect of the prescriptions of promoting blood circulation and removing stasis on EH and the rate of blood pressure up to target valueMethods80 examples of EH patients over the age of 18 years and below 75 years, which are in the high cardiovascular risk team or the team below (with the diagnostic criteria of cardiovascular risk stratification of hypertension), were randomly divided into control group and treatment group. The control group is treated with losartan potassium 50mg/d; the treatment group is treated with losartan potassium 50mg once a day and herbal medicine 200ml twice a day, prescribed on the principle of promoting blood circulation and removing stasis.2 weeks later, if the blood pressure does not reach the target value, add extended release nifedipine tablet lOmg twice a day or Indapamide-Lisheng 2.5-5mg once a day. The target value of blood pressure is < 140/90mmHg of EH patients without diabetes mellitus, and≤140/90mmHg of EH patients with diabetes mellitus. The course of treatment is 4 weeks. The indexes are symptoms, signs, blood pressure, the rate of blood pressure up to target value, C-reactive protein(CRP), D-Ⅱdimer(DD) and fibrinogen (FIB).Results 1. Effect on blood pressure1.1 Systolic blood pressure (SBP)After 2 weeks treatment, SBP in treatment group were decreased from 152.32±12.25mmHg to 133.62±9.17mmHg, SBP in control group were decreased from153.25±13.42mmHg to 138.58±11.09mmHg; after 4 weeks treatment, SPB in treatment group were decreased to 127.78±5.69mmHg, SPB in control group were decreased to 131.18±6.37mmHg.The level of SBP decreasing were superior to those in control group, significant difference control group.1.2 Diastolic blood pressure (DBP)After 2 weeks of treatment by the DBP treatment group were decreased from 94.95±10.71mmHg mmHg to 83.80±6.28mmHg, the control group were decreased from the 94.92±9.02 mmHg to 85.15±7.54mmHg; 4 weeks after treatment,DBP in treatment group were decreased to 80.95±4.01 mmHg, DBP in control group were decreased to 81.15±4.13mmHg, no significant difference between the two groups.2. Effect on the rate of blood pressure up to target valueThe effect on the rate of blood pressure up to target value of treatment group was better than control group. In the 2nd week, the rate of treatment group was 72.5% and the control group was 45.0%; in the 4th week, the rate of treatment group is 95.0% and the control group was 87.5%.3. Effect on scores of symptoms and signsHeadache, dizziness, palpitations and other symptoms in treatment group were improved and superior to those in control group. Afer 4 weeks treatment symptom scores were improved and superior to those in control group, P<0.01; the signs of blood stasis-syndrome were improved and superior to those in control group,P= 0.024.4. Effect on C-reactive protein (CRP)After treatment, CRP in treatment group were decreased from 5.93±4.94mg/L to 2.14±0.97mg/L, the control group were decreased 6.96±5.03mg/L to 4.63±4.90mg/L. CRP in treatment group decreasing were superior to those in control group(P= 0.015). 5. Effect on D-dimer (DD)After treatment, DD in treatment group were decreased from 124.40±84.64ug/ L to 42.64±36.91ug/L, the control group were decreased from 142.93±105.69ug/ L to 110.41±74.44ug/L. DD in treatment group decreasing were superior to those in control group (P<0.01).6. Effect on Fibrinogen (FIB)After treatment, FIB in treatment group were decreased from 2.932±0.858g/L down 1.876±0.792g/L, the control group were decreased from 3.068±0.736g/L to 2.366±0.41 Og/L.FIB in treatment group decreasing were superior to those in control group (P=0.006).ConclusionsThe results indicate that the treatment group is better than the control group in the effect on decreasing systolic pressure, while is similar to the control group in the effect on decreasing diastolic pressure. Therefore, the prescriptions of promoting blood circulation and removing stasis have superior effects on decreasing systolic pressure as well as reaching the target value. The study shows the advantages of prescriptions of promoting blood circulation and removing stasis, manifests their status in the EH treatment and provides a new choice to the EH patients, especially the ones who are difficult to reach the target value.The results shows the advantages of prescriptions of promoting blood circulation and removing stasis on improving EH symptoms and signs, especially in the symptoms of vertigo and headache.The prescription "huoxue jianya fang" has the effect of promoting blood circulation and removing stasis as well as deceasing blood pressure, the levels of CRP, DD and FIB, which prompts that the prescription of promoting blood circulation and removing stasis may improve the blood situation of the EH patients with blood-stasis syndrome by the effects of reducing blood viscosity and relieving chronic inflammatory reactions.The study introduced the conception of "making blood pressure up to the target value". In order to protect the benefits of patients, antihypertensive drugs were added in time when the blood pressure fails to reach the target value. As a result, the rates of blood pressure up to target value are 99.5% of the treatment group and 98.75% of the control group.The study reveals the status and effects of the prescription of promoting blood circulation and removing stasis in the treatment of EH, and provides a new way to the further researches.SummariesThe first part of this study, the review of historical documents, the order of modern research, combined with teacher experience and previous research based on defined hypertension as blood-stasis syndrome type theory of an independent origin, necessity and clinical relevance, of its pathology and clinical features, proposed treatment. Thus enriching the theory of the pathogenesis of hypertension and clinical classification system for the clinical treatment of hypertension provides new ideas and methods.Modern medicine, high blood pressure treatment benefit from blood pressure lowering itself, and " lowering blood pressure to achieve targets". Clinical study showed that the herbs of promoting blood circulation and removing stasis would improving the rate of blood pressure achieving targets than losartan alone, and more conducive to the control of systolic blood pressure. Promoting blood circulation and removing stasis is very importance in treatment of hypertension.
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