自主神经系统与个体应激压力状况对TIA和轻型卒中后缺血事件复发风险预测的研究

Transient ischemic attack (TIA) and minor stroke have high risks of recurrence and deterioration into severe ischemic strokes; while the predictive value of the current risk stratification tools is compromised. We found that most risk factors of ischemic stroke can be considered as either chronic or acute stressors that are progressively superimposed on the body and are correlated with the Autonomic Nervous System (ANS). We also found in our previous research that the heart rate variability (HRV) can be used as an independent predictor to determine the personal risk of a secondary ischemic event after TIA or minor stroke. Accordingly, we propose the following hypothesis: ANS function and stress profile may predict the secondary ischemic events after initial TIA or minors stroke; more specifically, 1) the dynamic high frequency (HF) power of HRV will be the best predictor of development of secondary ischemic events after acute TIA or minor stroke, with expected negative correlation; 2) people who have a higher level of hair cortisol or plasma copeptin will have a higher risk of occurrence of secondary ischemic events, compared to those with a lower level of stress hormones; and 3) people who have a higher level of perceived psychological stress will have a higher risk of occurrence of secondary ischemic events, compared to those with lower level of psychological stress. The overarching objective of the study is to investigate the use of ANS and individual stress profile on risk stratification for TIA or minor stroke; and thus, their predictive value on secondary ischemic events. We expect to establish the HRV-based comprehensive stress model to help identify high-risk population and to direct appropriate medical care for affected patients.

短暂性脑缺血发作（TIA）和轻型卒中早期复发风险高，现有复发风险预测系统效度不高。申请人发现大多数卒中危险因素可视为慢性或急性应激压力源，进行性叠加作用于机体，并与自主神经系统功能密切相关；心率变异性可作为TIA和轻型卒中后卒中复发的独立预测指标。据此我们提出科学假说：自主神经系统和个体应激压力状况与急性TIA和轻型卒中后缺血事件复发风险具有相关性：（1）心率变异性动态高频参数与TIA或轻型卒中后缺血事件复发风险成负相关；（2）头发皮质醇或血浆和肽素水平较高的患者缺血事件复发风险较高；（3）感受性心理压力水平较高的患者缺血事件的复发风险较高。为验证上述假说，本研究拟在多中心前瞻性研究中验证自主神经系统与应激压力状况对TIA和轻型卒中风险分级和复发缺血事件的预测作用，并建立更完整的“基于心率变异性的综合应激压力预测模型”，为临床探寻高危人群和实施个体化医疗提供科学依据。

大多数血管病危险因素致病过程可看做应激因素与自主神经功能（ANS）的相互作用过程。传统血管危险因素经长期持续累积影响应激调控系统，从而影响靶器官功能并引起代谢紊乱如高血压，糖尿病和血脂异常。这些代谢紊乱作为“次级”应激源，进一步损害自主神经调节功能，最终导致心脑血管病变。在此过程中应激源和神经功能失调互为因果。本研究拟通过自主神经功能评估（心率变异性，HRV）与多维应激源的综合测量，建立TIA和轻型卒中后血管事件复发综合预测模型。主要研究内容为：针对TIA和轻型卒中患者1.筛选90天内血管事件复发最佳独立预测指标。2.压力激素水平与血管事件复发风险相关性分析。3.心理压力水平与血管事件复发风险相关性分析。4. 通过对重点预测指标的筛选，建立基于HRV的综合应激预测模型。研究结果（未发表）显示多个HRV频域参数均与TIA和轻型卒中后血管事件复发风险相关，其中日间变化参数和昼夜变化参数预测性最好（AUC>0.75）。血浆和肽素与头发皮质醇在复发血管事件的患者（较无复发事件患者）中含量更高。个体感受性压力在血管事件复发与未复发组中具有显著差异- PSS分数可预测TIA和轻型卒中后血管事件复发风险。经预测指标筛选，基于HRV的综合预测模型为：血管事件复发风险=HRV日间（或昼夜）动态变化+压力激素+个体感知性压力+ABCD2，该模型预测能力较ABCD2具有显著提高。因研究结果显示白日间或昼夜间动态变化均具有良好预测能力，可根据不同需要选取特定时间段测量，增加监测时间灵活性。本研究成果显示无创自主神经功能和个体应激监测可应用于家庭，社区和医院环境，有效筛选高危血管病发生人群，为实施个体化医疗提供帮助。

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