高血压病血瘀证研究与中药干预
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摘要
高血压病血瘀证研究(理论研究)
1.研究目的
探讨血瘀证作为高血压病的一个独立证型的理论渊源、必要性、可行性及临床意义和特点。
2.血瘀证及活血化瘀治法源流
2.1《内经》对血瘀证的贡献
《内经》中有众多“瘀血”相关的描述,对其病因,病机,临床表现及治疗有了较为系统的认识。其对血瘀证成因的认识主要为：感受外邪、情志所伤、饮食不节、跌打损伤、年迈久病及久病致瘀。《内经》提出了血瘀证总的治疗原则：“疏其血气,令其调达”。并记载了一首活血化瘀的方剂。《内经》对高血压病并发症中风的论述详细,并认为与出血有关。
2.2《武威汉代医简》对血瘀证的贡献
1972年出土的“武威汉代医简”最早提出了活血化瘀治法,同时其中记载了一些活血化瘀功效的“瘀方”。
2.3张仲景对血瘀证的贡献
东汉末年成书的《伤寒杂病论》对血瘀证及活血化瘀治则贡献巨大,首先提出了“瘀血”病名；提出了血瘀证的临床表现及“是瘀血也,当下之”的治法原则。并形成了植物类药物、动物类药物并用的用药特点。
2.4唐宋医家对血瘀证的贡献
唐宋医家发展丰富了活血化瘀方药,使其应用更加广泛。
2.5金元四大家对血瘀证的贡献
金元四家中的李东垣及朱丹溪均重视活血化瘀方法的应用。《丹溪心法》指出：“气血冲和,百病不生,一有怫郁,诸病生焉”,强调疏通气血,畅达郁滞的重要性。
2.6“瘀血致眩”的提出及明清医家对血瘀证的贡献
明代医家虞抟在《医学正传·眩运》中提出了“瘀血致眩”,被认为是中医对眩晕认识的里程碑。清·潘楫《医灯续焰》认为：“眩晕者,有因于死血者……诸阳上行于头,诸经上行于目,血死则脉凝泣,脉凝则上注之薄矣,薄则上虚而眩晕生。”潘氏继承并发展了虞抟的学说。二者为眩晕治疗提供了新的思路与途径,并为后世高血压病从血瘀论治提供了可供借鉴的思路。
清代温病学医家叶天士提出“入血尤恐耗血动血,直须凉血散血”的观点,并喜用虫类药物活血通络。
王清任对血瘀学说贡献巨大,他在血瘀证的治疗中尤其重视气血的关系,其为高血压病并发症中风创制的补阳还五汤,高血压病心脏损害“胸痹”创制的血府逐瘀汤一直沿用至今。唐容川著有《血证论》,详述了各种出血证的证治,同时阐明了瘀血和出血之间的关系,强调祛瘀为治疗血证原则,提出“以祛瘀为治血要法”,祛瘀方可生新。
近代医家张锡纯,著有《医学衷中参西录》,对血瘀理论多有创见,且用活血药物治疗高血压并发症中风的“脑中瘀血”。
3.高血压病血瘀证理论的提出
高血压是西医学的一个概念,中医古籍不可能有血压及高血压的概念,更无高血压的相关记载,既往高血压的研究多根据高血压导致的“眩晕”、“头痛”等症状,从“肝、肾”,“阴、阳”论治,取得了一定的效果,但高血压毕竟是一个西医的病名,我们在临床中亦发现,大量高血压患者,在血压明显升高时,也不会出现任何临床症状；另一方面,高血压的主要危害来自于它导致的靶器官损害,主要是心、脑、肾的损害,均有较高的致残率、致死率,严重危害着人们的身体健康。而上述两类患者,多存在血瘀证。
已有的研究证实：血瘀是高血压病重要的病理机制之一,瘀血的形成贯穿于整个病变过程。西医研究发现：高血压过程中存在血黏度增高的病理改变。但对于高血压病血瘀证,尚缺乏系统的论述及认识。
4.高血压血瘀证的病理机制
4.1高血压血瘀证的病因
4.1.1先天禀赋
先天禀赋异常,脏腑气血偏盛或偏衰,均可直接或间接影响血脉及气血的运行,气血运行失常及血脉异常,可导致血瘀证的形成。
4.1.2情志失调
肝气郁结,气滞血瘀。
4.1.3长期过劳睡眠不足或过逸
长期过度劳累或睡眠不足亦可血瘀。
4.1.4饮食不节
水谷入于胃,五味各走其脏,饮食偏嗜,咸味过度,可伤及血脉导致血瘀。过食肥甘厚味,酿湿生痰,痰浊阻滞,闭阻经脉成瘀。长期偏食辛辣,饮酒过量,阴液受劫,亦可生瘀。
4.1.5寒冷刺激
寒冷刺激,因寒致瘀。一是寒邪侵入血分,血寒而凝,形成血瘀,脉道受阻而血压升高；二则寒主收引,受寒以后,血脉拘挛,脉道阻力增大,而出现血压升高。
4.1.6年老体衰
年老体衰,阳气虚损,鼓动无力,因而致瘀。
4.2高血压血瘀证的病理机制
4.2.1气滞血瘀
4.2.2肝热血瘀
4.2.3痰浊血瘀
4.2.4气虚血瘀
4.2.5阴虚血瘀
4.2.6寒凝血瘀
4.2.7阳虚血瘀
4.2.8阴阳两虚血瘀
高血压病血瘀形成的因素很多,如气、血、虚、寒、热(火)、痰以及精神情志,饮食习惯等都可以导致血瘀。其中尤以气血关系的失调最为重要。《医学正传·气血》言：“人之一身,皆气血之所循行,气非血不和,血非气不运。”病位除既往认为的主要在“肝”外,更与“气、血、脉”关系密切。
4.3高血压血瘀证并发症的病理机制
现代医学认为,高血压长期控制不佳,可影响心脏、脑血管、肾脏等靶器官,导致左心室肥厚,心力衰竭,脑动脉硬化,脑卒中(包括缺血性卒中与出血性卒中),慢性肾功能衰竭等并发症,严重影响患者生活质量,甚则危及生命。而这些并发症的发生与血瘀证关系密切,经临床观察,大部分存在血瘀证。
5.高血压病血瘀证的临床证治
5.1高血压病血瘀证独立存在时的临床证治：应活血化瘀降压,方用活血降压汤加减(丹参、牡丹皮、益母草、钩藤、川牛膝、赤芍等)。
5.2与其他证型共存时的临床证治：
5.2.1血瘀因于气滞者,应行气活血,方用血府逐瘀汤加减。
5.2.2血瘀因于肝热者,应清肝泻热,活血化瘀,方用龙胆泻肝汤和丹参饮加味。
5.2.3血瘀因于痰浊者,应化痰活血,方用息化活血方(天麻、汉防己、半夏、陈皮、茯苓、栀子、胆星等)。
5.2.4血瘀因于气虚者,应补气活血,方用补阳还五汤。
5.2.5血瘀因于阴虚者,应养阴活血,方用六味地黄丸合丹参饮。
5.2.6血瘀因于寒凝者,应散寒活血,方用麻黄附子细辛汤合四物汤。
5.2.7血瘀因于阳虚者,应温阳活血,方用真武汤合血府逐瘀汤。
5.2.8血瘀因于阴阳两虚者,应调补阴阳,活血化瘀,方用二仙汤合失笑散加减。
6.小结
高血压病血瘀证在可由情志、饮食、天气变化、年迈体衰等多种因素引起,其在高血压病中广泛存在,且血瘀证贯穿高血压病始终。在高血压病治疗中应重视血瘀证的存在,及早、合理加用活血化瘀药物。
高血压病血瘀证中药干预研究(临床研究)
目的
探讨活血化瘀方药治疗高血压病的有效性及对血压达标率的影响。
方法
1.研究对象
年龄在18-75岁之间,符合高血压病、血瘀证诊断标准；心血管危险分层为高危及以下组的原发性高血压患者。同时制订病例排除标准、病例剔除标准、病例脱落标准。
2.诊断标准
高血压诊断、分级及危险分层标准：执行《中国高血压防治指南(2005年版)》标准；高血压病血瘀证诊断标准：参照1986年全国血瘀证诊断标准及2002年《中药新药临床研究指导原则》(试行)制订。
3.研究方法
80例符合纳入标准的入选患者以1：1比例随机分为对照组(西药)40例,治疗组(中药+西药)40例。对照组给予氯沙坦钾50mg每日1次；治疗组给予氯沙坦钾50mg每日1次,活血降压方药,每次200ml,每日2次。治疗2周后,如血压控制未达靶目标值,加用硝苯地平缓释片1Omg,每日2次,或吲达帕胺片2.5mg-5mg,每日1次。靶目标血压对未合并糖尿病者设定为140/90mmHg以下。合并糖尿病者,设定为130/80mmHg以下。
疗程均为4周。
观察指标：患者症状、体征、血压、血压达标率、血清C反应蛋白、血浆纤维蛋白原、血浆D-Ⅱ聚体。
4.统计方法
计量资料,符合正态分布和基本符合正态分布的资料统计描述采用均数±标准差表示,两组资料的比较采用t检验；计量资料,非正态分布者采取秩和检验；计数资料采用x2检验,等级资料采用秩和检验；应用SPSS软件包统计。
结果
80例入选高血压病患者,其基线水平相近,在性别比例、年龄、高血压分级和心血管危险度分层,血压水平等方面均具有可比性,治疗组中合并2型糖尿病者12例,对照组中14例。
1.对血压的影响
对收缩压(SBP)的影响：治疗2周后治疗组SBP由152.32±12.25mmHg下降至133.62±9.17mmHg,对照组由153.25±13.42mmHg下降至138.58±11.09mmHg,两组比较P=0.033,治疗组优于对照组；治疗4周后,治疗组下降至127.78±5.69mmHg,对照组131.18±6.37mmHg,治疗组优于对照组。对舒张压(DBP)的影响：治疗2周后治疗组DBP由94.95±10.71mmHg下降至mmHg下降至83.80±6.28mmHg,对照组由94.92±9.02mmHg下降至85.15±7.54mmHg,两组比较P=0.387；治疗4周后,治疗组下降至80.95±4.01mmHg,对照组81.15±4.13mmHg,组间比较无统计学差异。
2.对血压达标率的影响
2周时,治疗组降压达标率为72.5%,对照组为45%；4周时治疗组降压达标率为95%,对照组为87.5%。治疗组优于对照组。
3.对高血压血瘀证患者症状及体征积分的影响
在改善患者头痛、头晕、心悸等症状方面,治疗组优于对照组,疗后两组症状积分比较P<0.01；在改善患者血瘀证体征方面,治疗组优于对照组,疗后体征积分比较P=0.024。
4.对血清C反应蛋白(CRP)的影响
经治疗,治疗组CRP由5.93±4.94mg/L降至2.14±0.97mg/L,对照组由6.96±5.03mg/L降至4.63±4.90mg/L,两组比较P=0.015。治疗组CRP降低更明显。
5.对血浆D-Ⅱ(DD)聚体的影响
经治疗,治疗组DD由124.40±84.64ug/L降至42.64±36.91ug/L,对照组由142.93±105.69ug/L降至110.41±74.44ug/L,两组比较P<0.01。治疗组DD降低更明显。
6.活血降压方对血浆纤维蛋白原(FIB)的影响
经治疗,治疗组FIB由2.932±0.858g/L降至1.876±0.792g/L,对照组由3.068±0.736g/L降至2.366±0.410g/L,两组比较P=0.006。治疗组FIB降低更明显。
讨论
研究结果显示,与对照组比较,加用活血化瘀方药的治疗组收缩压下降更明显,治疗2周时即效果明显,治疗4周时,在对照组联合用药后,治疗组收缩压的下降仍优于对照组。提示了活血化瘀方药在降低收缩压方面的优势,也初步揭示了其在高血压联合治疗方案中的地位及运用时机,即活血化瘀方药更适用于收缩压控制困难的高血压患者。
本试验引入了现代医学“降压达标”理念,在血压达标率方面,加用活血化瘀方药后,血压达标率亦明显提高。2周时,治疗组降压达标率为72.5%,对照组为45%；4周时治疗组降压达标率为95%,对照组为87.5%。治疗组优于对照组。本研究在证实活血化瘀方药对降压达标的益处的同时,在试验中及时对未达标患者加用降压药物,在试验结束使两组的血压达标率均较高,在完成试验的同时,最大限度的保证了受试者的权益。
研究结果证明了活血化瘀方药在改善高血压病患者临床症状及体征上的优势,可以明显改善头痛、头晕等症状,并较对照组为优。提示活血降压方药可用于血压控制未达标,同时临床症状明显的高血压病患者。
活血降压方具有活血化瘀、降压功效。本研究显示,可以明显降低高血压病患者的血清CRP、血浆DD及FIB含量,提示活血化瘀方药降低血压的原因可能与减轻高血压患者存在的慢性炎症反应,改善高血压血瘀证患者高凝、高黏滞状态有关,同时可能对高血压导致的动脉硬化有益。需要疗程更长的临床试验进一步证实。
本研究结果初步揭示了活血化瘀方药在高血压病治疗中的地位和作用,提示了在西药治疗基础上,加用活血化瘀方药可提高降压达标率,尤其对降低收缩压有益,为进一步的研究提供了思路。
总结
本研究第一部分,在复习古代文献,整理现代研究进展,结合导师经验及既往研究成果的基础上,明确了血瘀证作为高血压病一个独立证型的理论渊源、必要性和临床实用性,探讨了其病理机制及临床特点,提出了治疗方案。从而丰富了高血压病的病机理论和临床分型体系,为高血压病的临床治疗提供了新的思路与方法。
现代医学认为,高血压治疗的获益首先来自于血压降低本身,并提出了“降压达标”的概念,同时更多的研究认识到收缩压的危害,比过去更加重视收缩压的控制。本文临床研究部分,引入了“降压达标”这一现代医学理念,摒弃了既往以“舒张压下降幅度”作为降压有效率的判断标准的方法；同时关注受试者权益,在临床试验设计中对血压未达标者及时加用降压药物,在完成临床试验的同时更好的保证了受试者的权益。试验结果显示,加用活血化瘀方药较单用西药氯沙坦钾降压达标率明显提高,且更有利于收缩压的控制。在高血压病治疗中重视血瘀证的存在,及早、合理加用活血化瘀药物。
Theoretical study
1. Objectives
To 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 stasis
2.1 The related theories in Neijing
There 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 Province
The 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 Zhongjing
The 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 hypertension
EH, 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 EH
4.1 Etiological factors
4.1.1 Native endowment
The abnormity of native endowment will influence the movement of blood and Qi, which results in blood stasis.
4.1.2 Excessive emotion-thought
The depression of liver-qi can lead to stagnation of qi stagnancy and blood stasis
4.1.3 Defatigation or lack of exercises
4.1.4 Diets without temperance
Taking 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 irritation
By 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 invalidism
As 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 Pathomechanism
4.2.1 Qi stagnancy and blood stasis
4.2.2 Liver heat and blood stasis& Yang hyperactivities and blood stasis
4.2.3 Phlegm and blood stasis
4.2.4 Qi asthenia and blood stasis
4.2.5 Yin deficiency and blood stasis
4.2.6 Cold coagulation and blood stasis
4.2.7 Yang deficiency and blood stasis
4.2.8 Yin yang concurrent deficiency and blood stasis
Above 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 EH
The 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 EH
5.1 The treatment of absolute blood-stasis syndrome in EH
Promote 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 EH
5.2.1 Qi stagnancy and blood stasis
Promote qi to activate blood, using the prescription "xuefu zhuyu tang".
5.2.2 Liver heat and blood stasis
Cool 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 stasis
Dissipate phlegm and promote blood circulation, using the prescription "xihua huoxue fang"
5.2.4 Qi asthenia and blood stasis
Reinforcing Qi and promote blood circulation, using the prescription "buyang huanwu tang".
5.2.5 Yin deficiency and blood stasis
Nourish Yin and promote blood circulation, using the prescriptions "liuwei dihuang wan" and "danshen drink".
5.2.6 Cold coagulation and blood stasis
Warm the body and promote blood circulation, using the prescriptions "mahuang fuzi xixin tang" and "siwu tang".
5.2.7 Yang deficiency and blood stasis
Warm Yang and promote blood circulation, using the prescriptions "zhenwu tang" and "xuefu zhuyu tang".
5.2.8 Yin yang concurrent deficiency and blood stasis
Reinforce Yin Yang and promote blood circulation, using the prescriptions "erxian tang" and "shixiao san".
Clinical study
Objectives
To investigate the effect of the prescriptions of promoting blood circulation and removing stasis on EH and the rate of blood pressure up to target value
Methods
80 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 pressure
1.1 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 value
The 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 signs
Headache, 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).
Conclusions
The 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.
Summaries
The 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.
1.研究目的
探讨血瘀证作为高血压病的一个独立证型的理论渊源、必要性、可行性及临床意义和特点。
2.血瘀证及活血化瘀治法源流
2.1《内经》对血瘀证的贡献
《内经》中有众多“瘀血”相关的描述,对其病因,病机,临床表现及治疗有了较为系统的认识。其对血瘀证成因的认识主要为：感受外邪、情志所伤、饮食不节、跌打损伤、年迈久病及久病致瘀。《内经》提出了血瘀证总的治疗原则：“疏其血气,令其调达”。并记载了一首活血化瘀的方剂。《内经》对高血压病并发症中风的论述详细,并认为与出血有关。
2.2《武威汉代医简》对血瘀证的贡献
1972年出土的“武威汉代医简”最早提出了活血化瘀治法,同时其中记载了一些活血化瘀功效的“瘀方”。
2.3张仲景对血瘀证的贡献
东汉末年成书的《伤寒杂病论》对血瘀证及活血化瘀治则贡献巨大,首先提出了“瘀血”病名；提出了血瘀证的临床表现及“是瘀血也,当下之”的治法原则。并形成了植物类药物、动物类药物并用的用药特点。
2.4唐宋医家对血瘀证的贡献
唐宋医家发展丰富了活血化瘀方药,使其应用更加广泛。
2.5金元四大家对血瘀证的贡献
金元四家中的李东垣及朱丹溪均重视活血化瘀方法的应用。《丹溪心法》指出：“气血冲和,百病不生,一有怫郁,诸病生焉”,强调疏通气血,畅达郁滞的重要性。
2.6“瘀血致眩”的提出及明清医家对血瘀证的贡献
明代医家虞抟在《医学正传·眩运》中提出了“瘀血致眩”,被认为是中医对眩晕认识的里程碑。清·潘楫《医灯续焰》认为：“眩晕者,有因于死血者……诸阳上行于头,诸经上行于目,血死则脉凝泣,脉凝则上注之薄矣,薄则上虚而眩晕生。”潘氏继承并发展了虞抟的学说。二者为眩晕治疗提供了新的思路与途径,并为后世高血压病从血瘀论治提供了可供借鉴的思路。
清代温病学医家叶天士提出“入血尤恐耗血动血,直须凉血散血”的观点,并喜用虫类药物活血通络。
王清任对血瘀学说贡献巨大,他在血瘀证的治疗中尤其重视气血的关系,其为高血压病并发症中风创制的补阳还五汤,高血压病心脏损害“胸痹”创制的血府逐瘀汤一直沿用至今。唐容川著有《血证论》,详述了各种出血证的证治,同时阐明了瘀血和出血之间的关系,强调祛瘀为治疗血证原则,提出“以祛瘀为治血要法”,祛瘀方可生新。
近代医家张锡纯,著有《医学衷中参西录》,对血瘀理论多有创见,且用活血药物治疗高血压并发症中风的“脑中瘀血”。
3.高血压病血瘀证理论的提出
高血压是西医学的一个概念,中医古籍不可能有血压及高血压的概念,更无高血压的相关记载,既往高血压的研究多根据高血压导致的“眩晕”、“头痛”等症状,从“肝、肾”,“阴、阳”论治,取得了一定的效果,但高血压毕竟是一个西医的病名,我们在临床中亦发现,大量高血压患者,在血压明显升高时,也不会出现任何临床症状；另一方面,高血压的主要危害来自于它导致的靶器官损害,主要是心、脑、肾的损害,均有较高的致残率、致死率,严重危害着人们的身体健康。而上述两类患者,多存在血瘀证。
已有的研究证实：血瘀是高血压病重要的病理机制之一,瘀血的形成贯穿于整个病变过程。西医研究发现：高血压过程中存在血黏度增高的病理改变。但对于高血压病血瘀证,尚缺乏系统的论述及认识。
4.高血压血瘀证的病理机制
4.1高血压血瘀证的病因
4.1.1先天禀赋
先天禀赋异常,脏腑气血偏盛或偏衰,均可直接或间接影响血脉及气血的运行,气血运行失常及血脉异常,可导致血瘀证的形成。
4.1.2情志失调
肝气郁结,气滞血瘀。
4.1.3长期过劳睡眠不足或过逸
长期过度劳累或睡眠不足亦可血瘀。
4.1.4饮食不节
水谷入于胃,五味各走其脏,饮食偏嗜,咸味过度,可伤及血脉导致血瘀。过食肥甘厚味,酿湿生痰,痰浊阻滞,闭阻经脉成瘀。长期偏食辛辣,饮酒过量,阴液受劫,亦可生瘀。
4.1.5寒冷刺激
寒冷刺激,因寒致瘀。一是寒邪侵入血分,血寒而凝,形成血瘀,脉道受阻而血压升高；二则寒主收引,受寒以后,血脉拘挛,脉道阻力增大,而出现血压升高。
4.1.6年老体衰
年老体衰,阳气虚损,鼓动无力,因而致瘀。
4.2高血压血瘀证的病理机制
4.2.1气滞血瘀
4.2.2肝热血瘀
4.2.3痰浊血瘀
4.2.4气虚血瘀
4.2.5阴虚血瘀
4.2.6寒凝血瘀
4.2.7阳虚血瘀
4.2.8阴阳两虚血瘀
高血压病血瘀形成的因素很多,如气、血、虚、寒、热(火)、痰以及精神情志,饮食习惯等都可以导致血瘀。其中尤以气血关系的失调最为重要。《医学正传·气血》言：“人之一身,皆气血之所循行,气非血不和,血非气不运。”病位除既往认为的主要在“肝”外,更与“气、血、脉”关系密切。
4.3高血压血瘀证并发症的病理机制
现代医学认为,高血压长期控制不佳,可影响心脏、脑血管、肾脏等靶器官,导致左心室肥厚,心力衰竭,脑动脉硬化,脑卒中(包括缺血性卒中与出血性卒中),慢性肾功能衰竭等并发症,严重影响患者生活质量,甚则危及生命。而这些并发症的发生与血瘀证关系密切,经临床观察,大部分存在血瘀证。
5.高血压病血瘀证的临床证治
5.1高血压病血瘀证独立存在时的临床证治：应活血化瘀降压,方用活血降压汤加减(丹参、牡丹皮、益母草、钩藤、川牛膝、赤芍等)。
5.2与其他证型共存时的临床证治：
5.2.1血瘀因于气滞者,应行气活血,方用血府逐瘀汤加减。
5.2.2血瘀因于肝热者,应清肝泻热,活血化瘀,方用龙胆泻肝汤和丹参饮加味。
5.2.3血瘀因于痰浊者,应化痰活血,方用息化活血方(天麻、汉防己、半夏、陈皮、茯苓、栀子、胆星等)。
5.2.4血瘀因于气虚者,应补气活血,方用补阳还五汤。
5.2.5血瘀因于阴虚者,应养阴活血,方用六味地黄丸合丹参饮。
5.2.6血瘀因于寒凝者,应散寒活血,方用麻黄附子细辛汤合四物汤。
5.2.7血瘀因于阳虚者,应温阳活血,方用真武汤合血府逐瘀汤。
5.2.8血瘀因于阴阳两虚者,应调补阴阳,活血化瘀,方用二仙汤合失笑散加减。
6.小结
高血压病血瘀证在可由情志、饮食、天气变化、年迈体衰等多种因素引起,其在高血压病中广泛存在,且血瘀证贯穿高血压病始终。在高血压病治疗中应重视血瘀证的存在,及早、合理加用活血化瘀药物。
高血压病血瘀证中药干预研究(临床研究)
目的
探讨活血化瘀方药治疗高血压病的有效性及对血压达标率的影响。
方法
1.研究对象
年龄在18-75岁之间,符合高血压病、血瘀证诊断标准；心血管危险分层为高危及以下组的原发性高血压患者。同时制订病例排除标准、病例剔除标准、病例脱落标准。
2.诊断标准
高血压诊断、分级及危险分层标准：执行《中国高血压防治指南(2005年版)》标准；高血压病血瘀证诊断标准：参照1986年全国血瘀证诊断标准及2002年《中药新药临床研究指导原则》(试行)制订。
3.研究方法
80例符合纳入标准的入选患者以1：1比例随机分为对照组(西药)40例,治疗组(中药+西药)40例。对照组给予氯沙坦钾50mg每日1次；治疗组给予氯沙坦钾50mg每日1次,活血降压方药,每次200ml,每日2次。治疗2周后,如血压控制未达靶目标值,加用硝苯地平缓释片1Omg,每日2次,或吲达帕胺片2.5mg-5mg,每日1次。靶目标血压对未合并糖尿病者设定为140/90mmHg以下。合并糖尿病者,设定为130/80mmHg以下。
疗程均为4周。
观察指标：患者症状、体征、血压、血压达标率、血清C反应蛋白、血浆纤维蛋白原、血浆D-Ⅱ聚体。
4.统计方法
计量资料,符合正态分布和基本符合正态分布的资料统计描述采用均数±标准差表示,两组资料的比较采用t检验；计量资料,非正态分布者采取秩和检验；计数资料采用x2检验,等级资料采用秩和检验；应用SPSS软件包统计。
结果
80例入选高血压病患者,其基线水平相近,在性别比例、年龄、高血压分级和心血管危险度分层,血压水平等方面均具有可比性,治疗组中合并2型糖尿病者12例,对照组中14例。
1.对血压的影响
对收缩压(SBP)的影响：治疗2周后治疗组SBP由152.32±12.25mmHg下降至133.62±9.17mmHg,对照组由153.25±13.42mmHg下降至138.58±11.09mmHg,两组比较P=0.033,治疗组优于对照组；治疗4周后,治疗组下降至127.78±5.69mmHg,对照组131.18±6.37mmHg,治疗组优于对照组。对舒张压(DBP)的影响：治疗2周后治疗组DBP由94.95±10.71mmHg下降至mmHg下降至83.80±6.28mmHg,对照组由94.92±9.02mmHg下降至85.15±7.54mmHg,两组比较P=0.387；治疗4周后,治疗组下降至80.95±4.01mmHg,对照组81.15±4.13mmHg,组间比较无统计学差异。
2.对血压达标率的影响
2周时,治疗组降压达标率为72.5%,对照组为45%；4周时治疗组降压达标率为95%,对照组为87.5%。治疗组优于对照组。
3.对高血压血瘀证患者症状及体征积分的影响
在改善患者头痛、头晕、心悸等症状方面,治疗组优于对照组,疗后两组症状积分比较P<0.01；在改善患者血瘀证体征方面,治疗组优于对照组,疗后体征积分比较P=0.024。
4.对血清C反应蛋白(CRP)的影响
经治疗,治疗组CRP由5.93±4.94mg/L降至2.14±0.97mg/L,对照组由6.96±5.03mg/L降至4.63±4.90mg/L,两组比较P=0.015。治疗组CRP降低更明显。
5.对血浆D-Ⅱ(DD)聚体的影响
经治疗,治疗组DD由124.40±84.64ug/L降至42.64±36.91ug/L,对照组由142.93±105.69ug/L降至110.41±74.44ug/L,两组比较P<0.01。治疗组DD降低更明显。
6.活血降压方对血浆纤维蛋白原(FIB)的影响
经治疗,治疗组FIB由2.932±0.858g/L降至1.876±0.792g/L,对照组由3.068±0.736g/L降至2.366±0.410g/L,两组比较P=0.006。治疗组FIB降低更明显。
讨论
研究结果显示,与对照组比较,加用活血化瘀方药的治疗组收缩压下降更明显,治疗2周时即效果明显,治疗4周时,在对照组联合用药后,治疗组收缩压的下降仍优于对照组。提示了活血化瘀方药在降低收缩压方面的优势,也初步揭示了其在高血压联合治疗方案中的地位及运用时机,即活血化瘀方药更适用于收缩压控制困难的高血压患者。
本试验引入了现代医学“降压达标”理念,在血压达标率方面,加用活血化瘀方药后,血压达标率亦明显提高。2周时,治疗组降压达标率为72.5%,对照组为45%；4周时治疗组降压达标率为95%,对照组为87.5%。治疗组优于对照组。本研究在证实活血化瘀方药对降压达标的益处的同时,在试验中及时对未达标患者加用降压药物,在试验结束使两组的血压达标率均较高,在完成试验的同时,最大限度的保证了受试者的权益。
研究结果证明了活血化瘀方药在改善高血压病患者临床症状及体征上的优势,可以明显改善头痛、头晕等症状,并较对照组为优。提示活血降压方药可用于血压控制未达标,同时临床症状明显的高血压病患者。
活血降压方具有活血化瘀、降压功效。本研究显示,可以明显降低高血压病患者的血清CRP、血浆DD及FIB含量,提示活血化瘀方药降低血压的原因可能与减轻高血压患者存在的慢性炎症反应,改善高血压血瘀证患者高凝、高黏滞状态有关,同时可能对高血压导致的动脉硬化有益。需要疗程更长的临床试验进一步证实。
本研究结果初步揭示了活血化瘀方药在高血压病治疗中的地位和作用,提示了在西药治疗基础上,加用活血化瘀方药可提高降压达标率,尤其对降低收缩压有益,为进一步的研究提供了思路。
总结
本研究第一部分,在复习古代文献,整理现代研究进展,结合导师经验及既往研究成果的基础上,明确了血瘀证作为高血压病一个独立证型的理论渊源、必要性和临床实用性,探讨了其病理机制及临床特点,提出了治疗方案。从而丰富了高血压病的病机理论和临床分型体系,为高血压病的临床治疗提供了新的思路与方法。
现代医学认为,高血压治疗的获益首先来自于血压降低本身,并提出了“降压达标”的概念,同时更多的研究认识到收缩压的危害,比过去更加重视收缩压的控制。本文临床研究部分,引入了“降压达标”这一现代医学理念,摒弃了既往以“舒张压下降幅度”作为降压有效率的判断标准的方法；同时关注受试者权益,在临床试验设计中对血压未达标者及时加用降压药物,在完成临床试验的同时更好的保证了受试者的权益。试验结果显示,加用活血化瘀方药较单用西药氯沙坦钾降压达标率明显提高,且更有利于收缩压的控制。在高血压病治疗中重视血瘀证的存在,及早、合理加用活血化瘀药物。
Theoretical study
1. Objectives
To 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 stasis
2.1 The related theories in Neijing
There 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 Province
The 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 Zhongjing
The 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 hypertension
EH, 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 EH
4.1 Etiological factors
4.1.1 Native endowment
The abnormity of native endowment will influence the movement of blood and Qi, which results in blood stasis.
4.1.2 Excessive emotion-thought
The depression of liver-qi can lead to stagnation of qi stagnancy and blood stasis
4.1.3 Defatigation or lack of exercises
4.1.4 Diets without temperance
Taking 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 irritation
By 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 invalidism
As 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 Pathomechanism
4.2.1 Qi stagnancy and blood stasis
4.2.2 Liver heat and blood stasis& Yang hyperactivities and blood stasis
4.2.3 Phlegm and blood stasis
4.2.4 Qi asthenia and blood stasis
4.2.5 Yin deficiency and blood stasis
4.2.6 Cold coagulation and blood stasis
4.2.7 Yang deficiency and blood stasis
4.2.8 Yin yang concurrent deficiency and blood stasis
Above 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 EH
The 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 EH
5.1 The treatment of absolute blood-stasis syndrome in EH
Promote 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 EH
5.2.1 Qi stagnancy and blood stasis
Promote qi to activate blood, using the prescription "xuefu zhuyu tang".
5.2.2 Liver heat and blood stasis
Cool 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 stasis
Dissipate phlegm and promote blood circulation, using the prescription "xihua huoxue fang"
5.2.4 Qi asthenia and blood stasis
Reinforcing Qi and promote blood circulation, using the prescription "buyang huanwu tang".
5.2.5 Yin deficiency and blood stasis
Nourish Yin and promote blood circulation, using the prescriptions "liuwei dihuang wan" and "danshen drink".
5.2.6 Cold coagulation and blood stasis
Warm the body and promote blood circulation, using the prescriptions "mahuang fuzi xixin tang" and "siwu tang".
5.2.7 Yang deficiency and blood stasis
Warm Yang and promote blood circulation, using the prescriptions "zhenwu tang" and "xuefu zhuyu tang".
5.2.8 Yin yang concurrent deficiency and blood stasis
Reinforce Yin Yang and promote blood circulation, using the prescriptions "erxian tang" and "shixiao san".
Clinical study
Objectives
To investigate the effect of the prescriptions of promoting blood circulation and removing stasis on EH and the rate of blood pressure up to target value
Methods
80 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 pressure
1.1 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 value
The 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 signs
Headache, 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).
Conclusions
The 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.
Summaries
The 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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