冠心病患者短时心血管时间序列分析研究

发布时间：2018-09-05 16:55

【摘要】：冠心病(CAD)的发病率、致死率逐年升高,且呈现年轻化态势,对人类社会和家庭的危害日益加剧。遏制冠心病发病甚至致残、致死的根本出路在于早期预警,研究如何在临床早期/亚临床期无创无损识别冠心病高危个体具有十分重要的临床医学意义和显著的经济社会效益。心血管时间序列的非线性分析提供了解决上述问题的可能。本文主旨在于探究利用短时间窗口(5 min)测量的心血管时间序列进行无创无损冠心病检测的潜在价值。围绕这一目的,本文系统设计并开展了三次临床试验,分别研究了静息状态和经袖带改变外周血管阻力状态下各心血管时间序列的单变量变异性和双变量耦合性特征在健康志愿者、轻度冠脉狭窄患者和冠心病患者中的变化规律,并研究了心血管时间序列的上述非线性特征在经皮冠状动脉介入术(PCI)后恢复期的变化规律。本文的研究内容为通过短时心血管时间序列识别冠心病高危个体提供了一种潜在标准化的分析思路,主要工作及创新点包括以下几方面:(1)发展了模糊熵算法。传统模糊熵忽略了采样误差和系统扰动的影响,本研究类比传感器灵敏域静态特性,定义了物理模糊隶属函数,提出了改进模糊熵和改进互模糊熵。仿真试验结果表明:改进模糊熵具有显著提高的统计稳定性和抗噪声鲁棒性,在进行短时时间序列分析时改进算法的统计优势更加明显。(2)拓展了心血管时间序列分析的范畴,研究了静息状态下短时心脏电-机械活动时间序列变异性和耦合性特征在冠心病患者中的改变,揭示了心血管系统的心脏机械活动功能状态及对其起调控作用的自主神经系统功能状态随冠脉狭窄程度的变化规律,为冠心病无损检测提供了有益思路。试验结果表明:相较于健康志愿者和轻度冠脉狭窄患者,冠心病患者的短时心率变异性(HRV)、舒张间期变异性(DTIV)以及心动周期—舒张间期(HRV-DTIV)、心动周期—收缩间期(HRV-STIV)和舒张间期—收缩间期(DTIV-STIV)耦合性均显著降低(p0.05或p0.01),并且舒张间期变异性及心动周期—收缩间期和舒张间期—收缩间期耦合性在轻度冠脉狭窄患者中也较健康志愿者显著降低(p0.05),提示冠脉狭窄可能导致调控心血管系统活动的自主神经系统功能和心脏机械功能的减退,以及二者之间相互关联性的退化,而且其对心脏机械功能的影响在冠脉狭窄早期即表现出来。(3)利用上肢袖带施压刺激,开创性地研究了外周血管阻力变化对短时心动周期序列变异性的影响,为无创无损检测冠心病提供了创新思路与方法。试验结果表明:对健康人群而言,健康老年志愿者的心率变异性各指标低于青年志愿者,但改变外周血管阻力过程对两组受试者的心率变异性均没有显著性影响(p0.05);对冠脉狭窄患者而言,改变外周血管阻力过程可使轻度冠脉狭窄患者和冠心病患者的改进模糊熵显著降低(p0.01)。提示冠脉狭窄可能导致心血管系统对外界环境变化的适应能力降低,进行经袖带改变外周血管阻力状态下的心率变异性分析可进一步辅助冠心病的无损检测。(4)探究了冠心病患者心血管时间序列特征在经皮冠状动脉介入术后的动态变化情况,为术中检测和预后分析提供了具有潜在价值的工具。试验结果表明:心率变异性和舒张间期变异性的改进模糊熵及心动周期-舒张间期、舒张周期-收缩间期和心动周期-脉搏波传播时间间期(HRV-PTTV)的耦合性在术后1天并未出现明显改变,但在术后14天较术前和术后1天均出现显著性升高(p0.05或p0.01);脉搏波传播时间在手术后1天时即出现显著升高(p0.01)。提示调控心血管系统的自主神经功能需要较长时间才能得到改善,而动脉弹性和左室功能在经皮冠状动脉介入术后短期内即可得到显著改善,心血管时间序列分析有助于经皮冠状动脉介入术后冠心病患者心血管系统功能状态的评价。
[Abstract]:The morbidity and mortality of coronary heart disease (CAD) are increasing year by year, and it is becoming younger and younger. The fundamental way to prevent the occurrence and even disability of CAD lies in early warning. It is very important to study how to noninvasively identify the high-risk individuals of CAD in the early / subclinical stage. Nonlinear analysis of cardiovascular time series provides the possibility to solve the above problems. This paper aims to explore the potential value of noninvasive noninvasive coronary heart disease detection using cardiovascular time series measured at short time windows (5 minutes). Three clinical trials were conducted to investigate the variations of univariate variability and bivariate coupling characteristics of cardiovascular time series in resting and cuff-altered peripheral vascular resistance in healthy volunteers, patients with mild coronary stenosis, and patients with coronary heart disease. The above-mentioned nonlinearity of cardiovascular time series was also studied. This study provides a potentially standardized analytical approach for identifying individuals at high risk of coronary artery disease by short-term cardiovascular time series. The main work and innovations are as follows: (1) Fuzzy entropy algorithm has been developed. Traditional fuzzy entropy has been ignored. The influence of sampling error and system disturbance is analogous to the static characteristics of sensor sensitivity domain, the physical fuzzy membership function is defined, and the improved fuzzy entropy and cross fuzzy entropy are proposed. The statistical advantage of the improved algorithm is more obvious. (2) The range of cardiovascular time series analysis is expanded. The variability and coupling characteristics of short-term cardiac electro-mechanical activity time series in resting state are studied in patients with coronary heart disease, and the functional state of cardiac mechanical activity and the self-regulation of cardiovascular system are revealed. The results showed that short-term heart rate variability (HRV), diastolic interval variability (DTIV) and cardiac cycle-diastolic interval (HRV-DTIV) were significantly higher in patients with coronary artery disease than in healthy volunteers and patients with mild coronary artery stenosis. Cardiac cycle-systolic interval (HRV-STIV) and diastolic-systolic interval (DTIV-STIV) coupling were significantly reduced (p0.05 or p0.01), and the variability of diastolic interval and the coupling of cardiac cycle-systolic interval and diastolic-systolic interval were significantly lower in patients with mild coronary stenosis than in healthy volunteers (p0.05). Stenosis may lead to the decline of autonomic nervous system function and cardiac mechanical function regulating cardiovascular system activity, and the deterioration of their correlation, and its effect on cardiac mechanical function appears in the early stage of coronary stenosis. (3) Using upper limb cuff pressure stimulation, peripheral vascular resistance was studied pioneering. The results showed that the heart rate variability of healthy elderly volunteers was lower than that of young volunteers, but the variation of peripheral vascular resistance did not affect the heart rate variability of both groups. Significant effect (p0.05); For patients with coronary artery stenosis, changing the process of peripheral vascular resistance can significantly reduce the improved fuzzy entropy in patients with mild coronary artery stenosis and patients with coronary heart disease (p0.01). It suggests that coronary artery stenosis may lead to a decrease in the cardiovascular system's ability to adapt to changes in the external environment and change the resistance of peripheral vessels through the cuff. Heart rate variability (HRV) analysis under state of mind can further assist in non-destructive detection of coronary heart disease (CHD). (4) To explore the dynamic changes of cardiovascular time series in patients with CHD after percutaneous coronary intervention (PCI), and provide a potential tool for intraoperative detection and prognosis analysis. The improved fuzzy entropy of variability and the coupling of cardiac cycle-diastolic interval, diastolic cycle-systolic interval and cardiac cycle-pulse wave propagation time interval (HRV-PTTV) did not change significantly at 1 day postoperatively, but significantly increased at 14 days postoperatively (p0.05 or p0.01) as compared with preoperative and postoperative 1 day postoperatively. It is suggested that the autonomic nervous function of the cardiovascular system needs a long time to be improved, while the arterial elasticity and left ventricular function can be significantly improved in the short term after percutaneous coronary intervention. Cardiovascular time series analysis is helpful to the patients with coronary heart disease after percutaneous coronary intervention. Evaluation of cardiovascular system functional status.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R541.4

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