Air Pollution and Cardiac Risk: Mechanisms & Time-course

描述（由申请人提供）：虽然已经确定了环境PM污染与心血管疾病之间的一致关联，但尚未充分了解PM引起毒性作用的确切机制、时间过程以及不同PM物种的影响。本研究探讨PM2.5影响（浓度和种类）的临床相关心律失常、心脏自主控制、复极、心肌缺血、血压、炎症、凝血和纤溶的机制和时间过程。具体来说，个人短期暴露于高浓度的环境PM2.5与：(1)心律失常发作的发生(2)心律失常的频率较高(3)心率变异性（HRV）指数较低直接相关吗？(4) QT指数测定延长复极？(5) st段水平？这种关联是否完全或部分归因于HRV和QT的改变？(6)动态血压升高（收缩压、舒张压和心压）？上面1-6所列的影响的时间过程（从分钟到小时）是多少？(7)个人短期暴露于较高的环境PM2。S（24小时累积暴露）与炎症、凝血和纤溶活性标志物升高直接相关？(8)主要由燃煤电厂和车辆燃烧排放/形成的环境PM2.5物种的24小时累积浓度是否与上述端点相关（假设1-7）？(9)环境PM2.5浓度与心脏终点之间的关联（假设1-7）是否被PM2.5规格类型所修正？（10）上述关系中pm2.5与长期心脏风险之间是否存在协同作用？（二）老年、糖尿病、高血压人群是否更容易受到上述PM2.5的影响？我们将(1)招募100例只有中度心律失常的患者；(2)进行一系列心脏检查，以确定心脏结构和功能状态；(3)同时测量24小时动态心电图、动态血压和个人PM2.5暴露，得出每个参与者的实时PM2.5浓度、EGG和血压数据；(4)分析过滤器，评估主要PM2.5种类；(5)采集监测前后的血液样本，评估炎症和纤溶活性；(6)评估心脏事件的长期风险；(7)采用时间序列和横断面分析（多变量线性回归和过渡模型）对上述研究假设进行检验。这项研究需要环境、心血管和生物统计学研究人员的多学科合作。研究结果将有助于我们更好地了解PM2.5影响心脏系统的机制和时间过程，并确定导致PM易感性差异的因素，指导监管机构制定空气污染控制标准。

DESCRIPTION (provided by applicant): Although consistent associations between ambient PM pollution and cardiovascular disease have been identified, the exact mechanisms, the time course by which PM causes the toxic effects, and effects of different PM species are not adequately understood. This study investigates clinically relevant arrhythmogenic, cardiac autonomic control, repolarization, myocardial ischemia, blood pressure (BP), inflammatory, coagulation, and fibrinolytic mechanisms and time course of PM2.5 effects (both concentration and species). Specifically, is personal short-term exposure to elevated ambient PM2.5 directly related to: (I) the onset of arrhythmic episodes (2) higher frequency of arrhythmias (3) lower heart rate variability (HRV) indices? (4) prolonged repolarization measured by QT index? (5) ST-segment level? Can this association be totally or partially attributed to the change of HRV and QT? (6) elevated ambulatory BP (SBP, DBP, and PP)? What are the time-courses (from minutes to hours) of the effects listed from 1-6 above? (7) Is personal short-term exposure to elevated ambient PM2.s (24-hour cumulative exposure) directly related to elevated markers of inflammation, blood coagulation, and fibrinolytic activity? (8) Are 24-hour cumulative concentrations of the ambient PM2.5 species, mostly emitted/formed from coal-fire power plant and vehicle combustion, associated with the above endpoints (Hypotheses 1-7)? (9) Are the associations between ambient PM2.5 concentration and cardiac endpoints (Hypotheses 1-7) modified by the types of PM2.5 spec/es? (10) Is there a synergistic interaction between PM2.5and long-term cardiac risk in the above relationships? (II) Are persons with older age, diabetes, and hypertension more susceptible to the above PM2.5 effects? We will (1) Recruit 100 patients with only arrhythmias of moderate frequency; (2) Perform a battery of cardiac tests to determine cardiac structural and functional status; (3) Measure concurrently 24-hour Holter ECG, ambulatory BP, and personal PM2.5 exposure, and derive real-time PM2.5 concentration, EGG, and BP data on each participant; (4) Analyze filters to assess major PM2.5 species; (5) Collect pre- and post- monitoring blood samples to assess inflammation and fibrinolytic activities; (6) Assess long-term risks of cardiac events; and (7) use time-series and cross-sectional analyses (both multivariable linear regression, transition models) to test the above research hypotheses. This study requires multidisciplinary collaborations of environmental, cardiovascular, and biostatistics researchers. The results will allow us to better understand the mechanisms and time course by which PM2.5 affects the cardiac system, and identify factors that lead to differential susceptibility to PM, and guide regulatory agencies in designing air pollution control standards.