冠心病证候要素、证候特征及证候演变规律研究

【作者】 常艳鹏；

【导师】 张明雪；

【作者基本信息】 辽宁中医药大学 ， 中医内科学， 2011， 博士

【摘要】 目的:本研究将经全国六大地区1218份《冠心病证候要素、证候特征、证候病机演变规律临床专家调查问卷》的调查结果,录入三维结构化关联数据库,运用频数、聚类、决策树、神经网络、概率转移矩阵等数据挖掘及统计方法进行统计分析,明确冠心病证候要素的判断标准,证实情志、肺气虚、脾气虚、心阴虚、肾阴虚是冠心病的主要证候要素,并明晰其在冠心病发病各个阶段的作用和与不同证候的应证关系;明确冠心病各期的证候特征及冠心病发展过程中各期证候之间的内在演变规律。材料与方法:以中、西医冠心病指南、建议为疾病诊断标准,以大量文献研究、专家咨询建议为基础,从现代心理测量理论出发并采用结构化的决策方式,应用量表学研究方法,研制冠心病证候要素、证候特征、证候病机演变规律临床专家调查问卷。运用三轮德尔菲法对问卷内容进行修改、增删、调整等,以确保问卷的条目与内容能准确的反应冠心病的临床症状及体征,在对问卷内容的信度、效度的考评优良后,进行全国多中心、大样本的临床一线专家调查。将冠心病调查问卷发放于我国六大区,分别为:东北(沈阳)地区、华北(北京)地区、西北(兰州、西宁)地区、东南(广州)地区、西南(重庆)地区、华南(上海)地区,共41家医院的临床一线医生,对其进行问卷调查。共收集1218份合格问卷。利用电脑设备建立Access问卷数据库,进行合格问卷进行电脑录入并二次核查,最终建立冠心病证候要素、证候特征、证候病机演变规律临床专家调查问卷三维结构化关联数据库。使用SAS统计分析软件,运用频数、决策树、神经网络、结构构成比、概率转移矩阵等多种数理统计方法进行统计分析。结果:1.冠心病主要证候要素在四个阶段(发病早期、发作期、缓解期、恢复期)的频数分布结果:情志为:98%,99%,98%,95%;肺气虚为:56%,95%,80%,48%;脾气虚为:63%,86%,65%,32%;心阴虚为:32%,63%,42%,21%;肾阴虚为:41%,65%,53%,34%;表现为发病早期和发作期频次逐高,至缓解期和恢复期下降,显示病情变化由盛至衰的发展趋势。2.冠心病主要证候要素与证候应证统计结果:情志、肺气虚、脾气虚、心阴虚、肾阴虚证候要素在发病各期的证候中的频数分布在3.14%—100%之间;各期的证候在情志、肺气虚、脾气虚、心阴虚、肾阴虚证候要素中的频数分布在5.14%—78.82%之间。3.决策树结果显示出冠心病主要证候要素情志、肺气虚、脾气虚、心阴虚、肾阴虚在冠心病四期的判断规则,神经网络训练显示,预测效果比较一致,训练集、验证集及评估集的正确率均达到了70%—99%之间。4.运用聚类的统计方法对调查问卷数据库进行统计分析,归纳出冠心病四期十二证的证候特征:早期:气滞心胸证、气阴两虚证;发作期:气滞痰阻证、心阳不振证、寒凝心脉证、瘀血阳微证;缓解期:肝脾不调证、心肾阳虚证、心肺气虚证;恢复期:心气虚证、阳虚气滞证、气阴两虚证。5.转移概率矩阵得出的证候演变规律是:5.1早期→发作期:气滞心胸证(64.9%)→心阳不振证;气滞心胸证(21.96%)→气滞痰阻证;气阴两虚证(41.34%)→心阳不振证;气阴两虚证(21.02%)→气滞痰阻证;气阴两虚证(20.32%)→寒凝心脉证;气阴两虚证(17.32%)→瘀血阳微证。故早期发展至发作期的规律是所有证型都易发展为心阳不振证,气滞痰阻证。5.2发作期→缓解期:心阳不振证(55.64%)→心肺气虚证;心阳不振证(34.87%)→肝脾不调证;气滞痰阻证(42.76%)→心肺气虚证;气滞痰阻证(30.92%)→心肾阳虚证;气滞痰阻证(26.32%)→肝脾不调证;瘀血阳微证(66.67%)→心肺气虚证;瘀血阳微证(19.35%)→心肾阳虚证;瘀血阳微证(13.98%)→肝脾不调证;寒凝心脉证(91.43%)→心肺气虚证。发作期至缓解期的规律是所有证型都易发展为心肺气虚证,其中心阳不振证还易发展为肝脾不调证,气滞痰阻证还易发展为心肾阳虚证。5.3缓解期→恢复期:心肺气虚证(61.72%)→气阴两虚证;心肺气虚证(22.72%)→阳虚气滞证;心肺气虚证(15.56%)→心气虚证;肝脾不调证(72.08%)→阳虚气滞证;肝脾不调证(19.8%)→气阴两虚证;心肾阳虚证(46.97%)→阳虚气滞证;心肾阳虚证(28.03%)→气阴两虚证;心肾阳虚证(25%)→心气虚证;缓解期至恢复期的规律是心肺气虚证易发展为气阴两虚证,肝脾不调证和心肾阳虚证均易发展为阳虚气滞证。结论:1证候要素频数分布的结果分析显示,冠心病证候要素主要包括情志、肺气虚、脾气虚、心阴虚、肾阴虚等,在早期和发作期频次增加,至缓解期和恢复期呈总体均衡下降趋势。决策树统计方法对变量重要性的排序研究、证候要素组合与证候应证起到的重要作用,可以明确判断出各个症状变量对不同证候要素的影响情况以及何种证候要素在冠心病发病及发展过程中起作用,为临床诊治冠心病起到了重要的指导作用。神经网络的统计学方法可以判断出证候要素模型的预测情况,保证实验的可行性,同时保证规律的外推性。2症状分布对冠心病问卷中所有变量运用频数分布的统计方法进行统计,并对其在不同阶段的频数分布情况绘制了直方图,运用中医理论,辨证分析每个变量在不同阶段动态变化的机理,结果显示大多数变量存在由早期向发作期集中,病情加重,而由缓解期至恢复期变量逐渐减少,程度渐轻的趋势。其变化符合冠心病的临床表现,为归纳冠心病的证候特征及演变规律提供了理论基础和数据支持。3证候特征运用聚类的统计方法对专家调查问卷数据库进行统计分析,归纳出4个阶段的证候特征为:①早期:气滞心胸证、气阴两虚证。②发作期:气滞痰阻证、心阳不振证、寒凝心脉证、瘀血阳微证。③缓解期:肝脾不调证、心肾阳虚证、心肺气虚证。④恢复期:心气虚证、阳虚气滞证、气阴两虚证。充实并丰富了冠心病的证候学研究内容。4气(阳)虚和情志因素气(阳)虚和情志因素贯穿于冠心病病变全程,其频数分布在各期中占很高比例,其中情志因素在各期中比例均在95%以上,并且在冠心病发展的各期中都有情志因素和气(阳)虚为主的证型,如早期的气滞心胸证和气阴两虚证;发作期的气滞痰阻证和心阳不振证;缓解期的肝脾不调证和心肺气虚证;恢复期的阳虚气滞证和气阴两虚证。表明在冠心病发病中,情志因素和气(阳)虚是极其重要因素,在冠心病防治过程中注重情志的自我调整,气(阳)的自我固护,将可以减少冠心病发病、并减轻病情。5脾胃症状表现在冠心病不同阶段的各个证型中,都不同程度的表现出脘腹痞闷、胃脘胀痛、干呕、恶心呕吐、食欲不振、呃逆或嗳气等脾胃病的临床症状。心与脾通过经脉相连,为母子关系,同时又与宗气有着密切的关系,脾胃之病可导致心病,心病亦可引起脾胃的症状。这与古人“胃心痛”(《内经》)病名及“人参汤”治疗胸痹虚证(《金匮要略》)之义,其理相通。6证候演变规律6.1从各阶段主要证候的构成比分析证候演变规律各阶段由高至低证候构成比依次是:①早期:气滞心胸证、气阴两虚证。②发作期:气滞痰阻证、心阳不振证、寒凝心脉证、瘀血阳微证。③缓解期:肝脾不调证、心肾阳虚证、心肺气虚证。④恢复期:心气虚证、阳虚气滞证、气阴两虚证。6.2转移概率矩阵得出的证候演变规律①早期发展至发作期的规律是:A.气阴两虚证→心阳不振证、气滞痰阻证、寒凝心脉证B.气滞心胸证→心阳不振证、气滞痰阻证;②发作期至缓解期的规律是:所有证候易发展为心肺气虚证,其中心阳不振证还易发展为肝脾不调证,气滞痰阻证易发展为肝脾不调证和心肾阳虚证;③缓解期至恢复期的规律是:所有证候易发展为气阴两虚证和阳虚气滞证,其中心肾阳虚证还易发展为心气虚证。冠心病起病以虚证和情志因素为主;发作期心阳虚衰,阴寒内盛,瘀血阻滞,气机不畅,表现出邪实正虚;缓解期心气不足,气阴两虚,阳虚气滞;恢复期气阴两虚,气机不畅,正虚邪恋。7中医特色通过频数分布和演变规律可以发现:冠心病是以心脏病变为中心,涉及肺、脾、肝、肾这一五脏相关的病变模式,表现为寒、痰、气、瘀、虚等各种证候要素相互交杂,互为因果,作用于机体,表现出全身脏腑的功能失调。由此,在临床治疗上应体现中医的辨证论治:不离于心,不止于心,兼及他脏。更多还原

【Abstract】 Purpose:This research are the survey results about 1218 pieces of clinical expert questionnaire of coronary heart disease syndrome factors、syndrome features、syndrome pathology evolution rules on the six regions, recorded 3d structural correlation database, use various data mining and mathematical statistic methods such as frequency, cluster, decision tree, neural network and the probability transfer matrix etc.to analysis and clear the judgment standards of coronary heart disease syndrome factors, confirm that sentiment, deficient lung system qi, deficient spleen system qi, deficient heart system Yin and deficient kidney system Yin are mainly syndrome factors, clarify their functions during all phases of coronary artery disease and corresponding syndrome relationships with different syndromes, Clear syndrome characteristics of coronary heart disease in each period, also the internal evolution rules among syndromes of the development in each phase.Material and method:Use the TCM and western medicine guides and advices about coronary heart disease for diagnostic criteria, based on large literature studies and experts advices, the theory of modern psychological measurement, decision-making with structural ways and the scale study methods to develop the clinical expert questionnaire of coronary heart disease syndrome factors、syndrome features、syndrome pathology evolution rules. Use three rounds Delphi method to modify, add, delete and adjust the content of the questionnaire repeatedly, in order to ensure the items and contents of questionnaire response clinical symptoms and signs of coronary heart disease accurately, and then after the questionnaire the reliability and validity evaluation were excellent, the large sample of clinical experts investigation will begin in many centers.The questionnaire will send to six regions, they are the Northeast (Shenyang), North of China (Beijing), Northwest (Lanzhou, Xining) , Southeast (Guangzhou), Southwest (Chongqing), South of China (Shanghai), and a total of 41 hospital clinical doctors to be surveyed. At last, we collected 1218 qualified questionnaires. Use the computer equipment to establish the Access questionnaire database, input qualified questionnaire and second check, then build the clinical expert questionnaire 3d structural correlation database of coronary heart disease syndrome factors、syndrome features、syndrome pathology evolution rules eventually. Basing on SAS statistical analysis software, we analyse the data using frequency, decision-making tree, the nerve network, structure, probability transfer matrix and so on.Results:1.Main coronary heart disease syndrome factors in the four stages of frequency results:Yang heart syndrome factor in four phases (early onset period,paroxysm period,remission period,recovery period)frequency distribution as follows: 61%,90%,71%,41%;Phlegm retention for:78%,96%,76%,61%;Blood stasis:58%,83%,66%,51%.Gradually increased frequency in early and paroxysm period,and general equilibrium decline in remission and recovery period,show the changes the development trend from vigorous to failure.2. Relationships of major coronary heart disease syndromes and syndrome factors by statistic results show: The syndromes frequency distribution of sentiment, deficient lung system qi, deficient spleen system qi, deficient heart system Yin and deficient kidney system Yin syndrome factors are among 3.14% -100% in each stage. Conversely, each stage Syndrome frequency distribution in syndrome factors of sentiment, deficient lung system qi, deficient spleen system qi, deficient heart system Yin and deficient kidney system Yin are among 5.14% -78.82%.3. The decision tree results show:The judgment rules of Coronary heart syndrome main factors of Yang heart、phlegm retention、blood stasis in the four stages of coronary heart disease,neural network training,the forecast effect is consistent with that,whether training sets or set of evaluation、test sets accuracy reached 58%-94% between.4. With cluster method to analyse the database, we summarize the syndromes features of four periods and twelve types, they are the early onset period consisted of Qi open-minded syndrome and Qi and Yin deficiency syndrome; paroxysm period contained Qi stagnation and phlegm obstruction syndrome, Yang malaise heart syndrome, Cold coagulation heart vessel syndrome and Blood stasis Yang syndrome; remission period consisted of Liver and spleen no coordination syndrome, yang deficiency of heart and kidney syndrome and cardiopulmonary Qi deficiency syndrome; recovery period have Heart Qi deficiency syndrome, Yang deficiency and Qi stagnation syndrome and Qi and Yin deficiency syndrome.5. Transition probability matrix derived evolution of the syndrome is5.1 Early onset period→paroxysm period:Qi open-minded syndrome(64.9%)→Yang malaise heart syndrome; Qi open-minded syndrome(21.96%)→Qi stagnation and phlegm obstruction syndrome;Qi and Yin deficiency syndrome(41.34%)→Yang malaise heart syndrome;Qi and Yin deficiency syndrome(21.02%)→Qi stagnation and phlegm obstruction syndrome;Qi and Yin deficiency syndrome(20.32%)→Cold coagulation heart vessel syndrome;Qi and Yin deficiency syndrome(17.32%)→Blood stasis Yang syndrome。So, the law of early onset period to paroxysm period is that all syndromes are easy to permit the development of Yang malaise heart syndrome and Qi stagnation and phlegm obstruction Syndrome.5.2paroxysm period→remission period:Yang malaise heart syndrome(55.64%)→cardiopulmonary Qi deficiency syndrome;Yang malaise heart syndrome(34.87%)→Liver and spleen no coordination syndrome;Qi stagnation and phlegm obstruction Syndrome(42.76%)→cardiopulmonary Qi deficiency syndrome;Qi stagnation and phlegm obstruction Syndrome(30.92%)→yang deficiency of heart and kidney syndrome;Qi stagnation and phlegm obstruction Syndrome(26.32%)→Liver and spleen no coordination syndrome;Blood stasis Yang syndrome(66.67%)→cardiopulmonary Qi deficiency syndrome;Blood stasis Yang syndrome(19.35%)→yang deficiency of heart and kidney syndrome;Blood stasis Yang syndrome (13.98%)→Liver and spleen no coordination syndrome;Cold coagulation heart vessel syndrome(91.43%)→cardiopulmonary Qi deficiency syndrome。The law of paroxysm period to remission period is that all syndromes are easy to development of cardiopulmonary Qi deficiency syndrome;Yang malaise heart syndrome is easy to development of Liver and spleen no coordination syndrome,Qi stagnation and phlegm obstruction Syndrome is easy to development of yang deficiency of heart and kidney syndrome.5.3remission period→recovery period:cardiopulmonary Qi deficiency syndrome(61.72%)→Qi and Yin deficiency syndrome;cardiopulmonary Qi deficiency syndrome(22.72%)→Yang deficiency and Qi stagnation syndrome;cardiopulmonary Qi deficiency syndrome(15.56%)→Heart Qi deficiency syndrome;Liver and spleen no coordination syndrome(72.08%)→Yang deficiency and Qi stagnation syndrome;Liver and spleen no coordination syndrome(19.8%)→Qi and Yin deficiency syndrome;yang deficiency of heart and kidney syndrome 46.97%)→Yang deficiency and Qi stagnation syndrome;yang deficiency of heart and kidney syndrome(28.03%)→Qi and Yin deficiency syndrome;yang deficiency of heart and kidney syndrome(25%)→Heart Qi deficiency syndrome;The law of remission period to recovery period is that all syndromes are easy to development of cardiopulmonary Qi deficiency syndrome is easy to development of Qi and Yin deficiency syndrome,Liver and spleen no coordination syndrome and yang deficiency of heart and kidney syndrome is easy to development of Yang deficiency and Qi stagnation syndrome.Conclusion:1. Syndrome factorsThe analysis results of Frequency distribution show that the main coronary heart syndrome factors including sentiment, deficient lung system qi, deficient spleen system qi, deficient heart system Yin and deficient kidney system Yin, and gradually increased in early and paroxysm period, general equilibrium decline in remission and recovery period. The decision trees play an important role in order research on importance of variables, combinations with syndrome factors and syndrome corresponding. That can tell the influence between different syndrome variables and syndrome factors clearly, also which syndrome factors affect in the process of coronary artery disease. It plays a guiding part in clinical diagnosis and treatment. Neural network can judge for predictions of syndrome factors model that guarantee the feasibility of experiments, while ensuring extrapolating of regulation.2. Symptoms distributionAll variables in the questionnaire for coronary heart disease by statistical methods of frequency distribution, drawing their histograms about different stages with all items,analyzing the dynamic changing mechanism of each variable in different stages dialectically with theory of TCM. The results show that the majority of variables concentrate from early to paroxysm period with illness aggravating, but gradually decrease from remission to recovery period with light tendency. The change is according with the clinical manifestations of coronary heart disease that provides theoretical basis and data support for inducting syndromes features and evolution regulation.3 syndrome featuresWith cluster method to analyse the database, we summarize the syndromes features of four periods:①early onset period: Qi open-minded syndrome, Qi and Yin deficiency syndrome.②paroxysm period: Qi stagnation and phlegm obstruction syndrome, Yang malaise heart syndrome, Cold coagulation heart vessel syndrome and Blood stasis Yang syndrome.③remission period: Liver and spleen no coordination syndrome, yang deficiency of heart and kidney syndrome and cardiopulmonary Qi deficiency syndrome.④recovery period: Heart Qi deficiency syndrome, Yang deficiency and Qi stagnation syndrome and Qi and Yin deficiency syndrome. That enriches the content of coronary heart disease syndromes.4 Qi(Yang) difficiency and sentiment factorsQi (Yang) difficiency and sentiment factors run through the whole coronary lesions, which is high proportion of the frequency distribution in each stage, among that sentiment factor reach over 95%.Also each stage consists of syndromes major in Qi(Yang) difficiency and sentiment factors during the development of coronary heart disease,such as Qi open-minded syndrome and Qi and Yin deficiency syndrome in early onset period, Qi stagnation and phlegm obstruction syndrome and Yang malaise heart syndrome of paroxysm period , Liver and spleen no coordination syndrome and cardiopulmonary Qi deficiency syndrome in remission period and Yang deficiency and Qi stagnation syndrome and Qi and Yin deficiency syndrome of recovery period.That indicated both Qi(Yang) difficiency and sentiment factors are primary factors in coronary artery disease,so pays attention to the self regulationg and protect self Qi(Yang) can reduce the disease come out.5 spleen and stomach symptomsThere are mang digest symptoms of different degrees in each syndrome of different stages, such as abdominal fullness and distention, gastral cavity flatulence, retching, nausea and vomiting, inappetence, hiccups or belch etc. Heart and spleen are linked together with meridians, whose relationship is mother and son, connected with ZongQi, so spleen and stomach’s wrong can lead to heart disease also caused by it. They are reached on the principles of the name called "stomach heartache" (《Neijing》) and deficiency treatment of Chest pain with "ginseng soup" (《Jinkuiyaolue》)by ancients.6 syndrome evolution rules6.1 analyze them according to constituent ratio of every stage’s syndromes Constituent ratio of each stage syndromes from high to low in order are:①early onset period: Qi open-minded syndrome, Qi and Yin deficiency syndrome.②paroxysm period: Qi stagnation and phlegm obstruction syndrome, Yang malaise heart syndrome, Cold coagulation heart vessel syndrome and Blood stasis Yang syndrome.③remission period: Liver and spleen no coordination syndrome, yang deficiency of heart and kidney syndrome and cardiopulmonary Qi deficiency syndrome.④recovery period: Heart Qi deficiency syndrome, Yang deficiency and Qi stagnation syndrome and Qi and Yin deficiency syndrome. That enriches the content of coronary heart disease syndromes. 6.2 analyze used by transition probability matrix①rules of development from early to paroxysm period: a. Qi and Yin deficiency syndrome to Yang malaise heart syndrome,Qi stagnation and phlegm obstruction syndrome and Cold coagulation heart vessel syndrome.B.Qi open-minded syndrome to Yang malaise heart syndrome and Qi stagnation and phlegm obstruction syndrome.②rules of development from paroxysm to remission period: all syndromes develop to cardiopulmonary Qi deficiency syndrome easily, Yang malaise heart syndrome goes to Liver and spleen no coordination syndrome,also Qi stagnation and phlegm obstruction syndrome easily develops to Liver and spleen no coordination syndrome and yang deficiency of heart and kidney syndrome both.③rules of development from remission to recovery period: all syndromes develop to Yang Qi and Yin deficiency syndrome and deficiency and Qi stagnation syndrome easily, yang deficiency of heart and kidney syndrome goes to Heart Qi deficiency syndrome.7 characteristics of TCMAccording to the frequency distribution and development regularity we found: coronary heart disease is the center of heart, involving in lung, spleen, liver and kidney as the lesions mode of five zang-organs related, whose various kinds of syndrome factors’performance of cold, phlegm, qi, blood stasis, deficiency etc. that cross reciprocal and interact as both cause and effect on the human body, manifestate dysfunction of viscera. Therefore, we should not depart from heart, ends with heart and ignore it meanwhile in clinical treatment of TCM.更多还原