基于心率变异性分析的稳定型心绞痛证候与自主神经功能关联性研究

发布时间：2018-04-30 04:02

本文选题：稳定型心绞痛 + 虚实证候　；参考：《中国中医科学院》2017年博士论文

【摘要】：目的研究采用反映人体自主神经功能状态的心率变异性(heart rate variability,HRV)时域和频域指标,观察稳定型心绞痛(stable angina pectoris,SAP)实证、虚证及虚实夹杂证患者自主神经功能状态;采用能描述人体生理病理非线性混沌特征及程度的HRV非线性参数指标,观察SAP实证、虚证及虚实夹杂证患者自主神经功能不同状态下的混沌特征,探索揭示SAP实证、虚证及虚实夹杂证与自主神经功能变化及其非线性特征的关系。方法共纳入231例SAP患者,采用中医症状及四诊信息问卷表(见附表)采集SAP患者的辨证信息,依据《中医病证诊断疗效标准》、《冠心病中医辨证标准》及《中医内科学》“胸痹虚实辨证要点”作为虚实证候分类标准,对每个研究对象进行虚实辨证。依据中医虚实辨证结果,分为三组:实证42例(18.18%),虚证48例(20.78%),虚实夹杂证141例(61.04%)。采用美国DMS动态心电图记录仪采集患者全天24 h心电信号,计算全天时域、频域及非线性参数(复杂度、近似熵和关联维值)指标。同时利用小波变化技术,从全部24 h动态心电数据中提取出不同频段(HF、LF、VLF、ULF)的HRV信息指标,并将分布在各个频段下(全频段、HF、LF、VLF、ULF)的24h动态心电数据的HRV信息,按时间顺序分成每小时一段,计算各个小时中HRV的复杂度、近似熵、关联维等非线性参数。利用SPSS19.0统计软件,采用方差分析、非参数检验、重复测量的方差分析的方法对不同虚实证候患者自主神经功能状态、混沌程度及其在不同频段下的昼夜动态变化趋势特征进行分析研究。结果(1)SAP不同虚实证候患者的HRV时域指标不同,表现为反映自主神经功能总能量的SDNN、反映迷走张力的rMSSD指标均呈实证组虚实夹杂证组≈虚证组;杂证组与虚证组间虽无统计学差异,但呈杂证虚证的趋势。根据SDNN的正常参考值,SDNN100ms为正常,因此实证组的SDNN仍在正常范围内,而虚实夹杂证和虚证组的SDNN值均低于正常范围。(2)与HRV时域指标的结果近似,本组资料频域指标研究结果表明:总功率(TP)、高频(HF)、低频(LF)指标均呈实证组虚实夹杂证组≈虚证组;杂证组与虚证组间虽无统计学差异,但呈杂证虚证的趋势。(3)本组资料非线性参数的研究结果表明:非线性分析采用复杂度(反映数据在时间序列上的复杂性,表达系统非线性变化速度)、近似熵(反映数据在结构上的复杂性,表达系统变化模式复杂程度)、关联维(反映系统维度复杂性)指标。复杂度表现为实证组虚实夹杂证组虚证组;近似熵虚实杂3组间虽无统计学差异,但仍呈实证组虚实夹杂证组虚证组的趋势;而关联维则表现为杂证组虚证组,其余组间无明显差异。(4)全频频段下HRV非线性指标的昼夜动态变化特征:①虚实杂3组间复杂度曲线的分布位置呈实证组杂证组虚证组,3组复杂度参数曲线的昼夜动态变化趋势一致;②虚实杂3组间近似熵曲线的分布位置间无明显差异;3组近似熵参数曲线的昼夜动态变化趋势一致;③虚实杂3组间关联维曲线的分布位置呈实证组杂证组虚证组,3组关联维参数曲线的昼夜动态变化趋势一致。(5)HF频段下HRV非线性指标的昼夜动态变化特征:①虚实杂3组间复杂度曲线的分布位置呈实证杂证≈虚证,3组复杂度参数曲线的昼夜动态变化趋势一致;②虚实杂3组间近似熵曲线的分布位置呈实证杂证≈虚证,3组近似熵参数曲线的昼夜动态变化趋势一致;③虚实杂3组间关联维曲线的分布位置间无明显差异,3组关联维参数曲线的昼夜动态变化趋势一致。(6)LF频段下HRV非线性指标的昼夜动态变化特征:①虚实杂3组间复杂度曲线的分布位置呈实证杂证≈虚证,3组复杂度参数曲线的昼夜动态变化趋势不一致,实证复杂度水平全天的波动幅度较大,虚证和虚实夹杂证复杂度水平全天的波动幅度较小;②LF频段下虚实杂3组间近似熵曲线的分布位置间无明显差异,近似熵参数曲线的昼夜动态变化趋势一致;③虚实杂3组间关联维曲线的分布位置呈实证组杂证组虚证组,3组关联维参数曲线的昼夜动态变化趋势一致。(7)VLF频段下HRV非线性指标的昼夜动态变化特征:①虚实杂3组间复杂度曲线的分布位置间无明显差异,但呈实证组≈杂证组虚证组的趋势;3组复杂度参数曲线的昼夜动态变化趋势一致;②虚实杂3组间近似熵曲线的分布位置间无明显差异;3组近似熵参数曲线的昼夜动态变化趋势一致;③虚实杂3组间关联维曲线的分布位置呈实证组≈杂证组虚证组;3组关联维参数曲线的昼夜动态变化趋势一致。(8)ULF频段下HRV非线性指标的昼夜动态变化特征:①虚实杂3组间复杂度曲线的分布位置间无明显差异;3组复杂度参数曲线的昼夜动态变化趋势一致;②虚实杂3组间近似熵曲线的分布位置间无明显差异;3组近似熵参数曲线的昼夜动态变化趋势一致;③虚实杂3组间关联维曲线的分布位置间无明显差异;3组关联维参数曲线的昼夜动态变化趋势一致。结论1.实证患者不伴有明显的自主神经功能损伤,虚证患者伴有明显的自主神经功能损伤。与实证相比,虚证患者的自主神经功能总能量、迷走神经张力以及交感神经张力均明显降低。2.证候演变过程中,由实证转变为虚实夹杂证时,自主神经张力降低,表现为迷走和交感张力活性均降低,可能以迷走张力受损为主;而虚实夹杂证向虚证转化时,自主神经张力降低,主要以交感张力活性降低为主。3.非线性指标的分析结果提示,实证证候的混沌特征较虚证证候更加明显,而虚证证候更容易伴有人体混沌特性的衰减和丧失,这符合目前非线性研究领域中对疾病及预后不良的定义。4.本研究的观察结果显示,无论复杂度、近似熵、关联维这3个指标都呈实证最大,虚证最小的趋势,提示非线性参数的研究结果与时域、频域指标的观察结果相互支撑。5.不同非线性参数在不同频段对虚实证候的区分度和敏感性不一样,提示复杂度、近似熵、关联维三个指标可从不同侧面、不同程度反映系统的混沌特征。
[Abstract]:Objective to study the parameters of heart rate variability (HRV) in time domain and frequency domain, which reflect the state of human autonomic nervous function (HRV), and to observe the autonomic nervous function state of patients with stable angina pectoris (stable angina pectoris, SAP), deficiency syndrome and false and real inclusion syndrome, and to describe the characteristics and degree of nonlinear chaos in human body's physiological and pathological characteristics. The HRV nonlinear parameter index was used to observe the chaotic characteristics of the patients with SAP demonstration, deficiency syndrome and false and real inclusion syndrome in different state of autonomic nervous function, and explore the relationship between SAP demonstration, deficiency syndrome and false and real inclusion syndrome and the change of autonomic nervous function and its nonlinear characteristics. Methods 231 cases of SAP patients were included, the symptoms of traditional Chinese medicine and the four diagnosis information questionnaire were adopted. The table (see table) collects the syndrome differentiation information of SAP patients. According to the standard of TCM syndrome diagnosis, TCM syndrome differentiation, TCM internal medicine and TCM internal medicine, the syndrome differentiation criterion of deficiency and actual syndrome is used for the syndrome differentiation. According to the syndrome differentiation results of Chinese medical deficiency and reality, three groups are divided into 42 cases (18.18%), There were 48 cases (20.78%) and 141 cases (61.04%) of false and real inclusion syndrome. The whole day 24 h cardiac electrical signal was collected by DMS dynamic electrocardiogram recorder in the United States. The whole day time domain, frequency domain and nonlinear parameters (complexity, approximate entropy and associated dimension) were calculated. At the same time, the different frequency bands (HF) were extracted from all 24 h dynamic ECG data by using the wavelet transform technique. The HRV information index of LF, VLF, ULF) and HRV information of the 24h dynamic ECG data distributed in each frequency band (all frequency bands, HF, LF, VLF, ULF), divided into each hour in order of time, calculating the complexity, approximate entropy, correlation dimension and other non linear parameters of HRV in each hour. Using the SPSS19.0 statistics software, the variance analysis, non parametric test, The method of variance analysis of repeated measurements was used to analyze the autonomic nervous function status of patients with different deficiency and solid syndromes, the chaotic degree and the trend characteristics of day and night dynamic changes under different frequency bands. Results (1) the HRV time domain index of patients with different deficiency and solid syndrome of SAP was different, showing the SDNN reflecting the total energy of autonomic nerve function, reflecting the vagal walk. The rMSSD indexes of tension were all in the group of false and solid syndrome group, although there was no statistical difference between the group and the deficiency syndrome group, but the normal reference value of SDNN, SDNN100ms was normal, so the SDNN of the positive group was still in the normal range, and the SDNN value of the deficiency and real inclusion complex and the deficiency syndrome group were all lower than that of the normal range. (2) The results of the data frequency domain index of this group showed that the total power (TP), high frequency (HF) and low frequency (LF) index were all the deficiency syndrome group in the empirical group, although there was no statistical difference between the miscellaneous and the false evidence groups, but the trend of the false evidence of miscellaneous evidence was found. (3) the research results of the nonlinear parameters of this group showed that the nonlinearity was nonlinear. The analysis uses complexity (reflecting the complexity of the data in time series, expressing the nonlinear changing speed of the system), the approximate entropy (reflecting the complexity of the data in the structure, expressing the complexity of the system change pattern), the correlation dimension (reflecting the complexity of the system dimension). The complex degree of complexity is represented by the false evidence group of the false and real inclusion group in the empirical group, and the approximate entropy deficiency. Although there was no statistical difference between the 3 groups, there were still the trend of deficiency syndrome group in the positive group, but the correlation dimension was the deficiency syndrome group of the mixed syndrome group, and there was no significant difference between the other groups. (4) the Diurnal Dynamic Change Characteristics of the HRV nonlinear indexes under the full frequency band: (1) the distribution of the complex degree curve between the 3 groups of virtual and solid groups showed the deficiency of the empirical group. The circadian dynamic variation trend of the 3 groups of complex parameter curves is consistent, and there is no obvious difference between the distribution positions of the approximate entropy curves between the 3 groups of virtual and real complex; the trend of the day and night dynamic change of the 3 groups of approximate entropy parameter curves is the same. (3) the distribution position of the correlation dimension curves between the 3 groups of the virtual and solid groups shows the false evidence group of the demonstration group and the 3 groups of correlation dimension parameter curves. The trend of day and night dynamic changes is consistent. (5) the characteristics of the Diurnal Dynamic Changes of the HRV nonlinear indexes under the HF frequency band: (1) the distribution position of the complexity curves between the 3 groups of virtual and real complex is an empirical evidence, and the trend of the day and night dynamic change of the 3 groups of complex parameter curves is consistent; and the distribution position of the approximate entropy curves between the 3 groups of the virtual and solid groups is an empirical miscellaneous evidence The trend of the circadian dynamic changes in the 3 groups of approximate entropy parameter curves is consistent. (3) there is no obvious difference between the distribution positions of the correlation dimension curves between the 3 groups of virtual and solid groups, and the trend of the Diurnal Dynamic Changes of the 3 groups of correlation dimension parameters is consistent. (6) the Diurnal Dynamic Change Characteristics of the HRV nonlinear index under the LF band: (1) the distribution position of the complexity curve between the 3 groups of virtual and solid groups The circadian dynamic variation trend of the 3 groups of complex parameter curves is not consistent, the volatility of the empirical complexity level is larger throughout the day, and the complexity of the deficiency syndrome and the false and real inclusion complex level is smaller throughout the day; there is no obvious difference between the approximate entropy curves between the 3 groups of virtual and real miscellaneous groups under the LF band, and the approximate entropy parameters are not found. The trend of the circadian dynamic change of the curve is consistent; (3) the distribution position of the 3 groups of associated dimension curves between the virtual and solid groups shows the false evidence group of the demonstration group, and the trend of the Diurnal Dynamic Changes of the 3 groups of association dimension parameters is consistent. (7) the Diurnal Dynamic Change Characteristics of the HRV nonlinear index under the VLF band: (1) the distribution of the complex degree curve between the 3 groups of the virtual and solid groups is not clear The trend of the deficiency syndrome group in the 3 groups of complex parameter curves is consistent, and there is no obvious difference between the distribution positions of the approximate entropy curves between the 3 groups of virtual and real complex; the trend of the Diurnal Dynamic Changes of the approximate entropy parameter curves of the 3 groups is the same; (3) the distribution position of the correlation dimension curves between the 3 groups of virtual and real miscellaneous groups is real The diurnal dynamic change trend of the 3 groups of correlation dimension parameter curves in the 3 groups is consistent. (8) the Diurnal Dynamic Change Characteristics of the HRV nonlinear indexes under the ULF frequency band: (1) there is no obvious difference between the distribution positions of the complexity curves between the 3 groups of virtual and solid groups; the trend of the day and night dynamic change of the 3 groups of complex parameter curves is the same; (2) the 3 groups of virtual and real miscellaneous groups are close between the two groups. There is no obvious difference between the distribution positions of the entropy like curve, and the trend of the circadian dynamic changes in the 3 groups of approximate entropy parameter curves is consistent, and there is no obvious difference between the distribution positions of the associated dimension curves between the 3 groups of virtual and solid complex; the trend of the Diurnal Dynamic Changes of the 3 groups of correlation dimension curves is consistent. Conclusion 1. positive patients have no obvious impairment of autonomic nervous function. The total energy of the autonomic nervous function, the vagus nerve tension and the sympathetic nerve tension of the patients with deficiency syndrome significantly reduced the evolution process of.2. syndrome, and the tension of autonomic nerve decreased and the activity of vagus and sympathetic tension decreased. When the syndrome of false and solid inclusion is transformed to the deficiency syndrome, the tension of the autonomic nerve is reduced, and the analysis results of the decrease in the activity of sympathetic tensility mainly based on the.3. nonlinear index indicate that the chaotic characteristic of the syndrome is more obvious than the deficiency syndrome, and the deficiency syndrome is more likely to be accompanied by the attenuation and loss of the human body's chaotic characteristics. This is in line with the current research on the definition of disease and poor prognosis in the field of nonlinear research. The results of the.4. study show that the 3 indexes of complexity, approximate entropy and correlation dimension are the most positive, and the trend of the least false evidence suggests that the results of the nonlinear parameter study and the time domain and the observation results of the frequency domain index support the different nonlinearity of the.5.. The degree and sensitivity of parameters in different frequency bands are different in the area of virtual and real syndrome. It suggests that three indexes of complexity, approximate entropy and correlation dimension can be from different sides, and the chaotic characteristics of the system are reflected in different degrees.

【学位授予单位】：中国中医科学院
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R541.4

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