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导致毒性效应的确切机制、时间过程以及不同PM种类的影响。本研究调查了临床相关的致炎性、心脏自主控制、复极、心肌缺血、血压（BP）、炎症、凝血和纤溶机制以及PM2.5效应的时间过程（浓度和种类）。具体而言，个人短期暴露于升高的环境PM2.5是否与以下因素直接相关：（1）哮喘发作（2）心律失常频率较高（3）心率变异性（HRV）指数较低？(4)用QT指数测量复极延长？(5)ST段水平？心率变异性和QT间期的改变是否是导致这种联系的全部或部分原因？(6)动态血压（SBP、DBP和PP）升高？以上1-6所列效应的时间过程（从分钟到小时）是什么？(7)个人短期暴露于升高的环境PM2.s（24小时累积暴露）是否与炎症、凝血和纤溶活性的升高标志物直接相关？(8)环境中PM2.5的24小时累积浓度（主要由燃煤发电厂和汽车燃烧排放/形成）是否与上述终点（假设1-7）相关？(9)环境PM2.5浓度与心脏终点（假设1-7）之间的关联是否因PM2.5规格类型而改变？(10)在上述关系中，PM2.5与长期心脏病风险之间是否存在协同作用？(II)老年人、糖尿病患者和高血压患者是否更容易受到上述PM2.5的影响？我们将（1）招募100例中度心律失常患者;（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小时霍尔特ECG、动态血压和个人PM2.5暴露，并获得每位参与者的实时PM2.5浓度、EGG和BP数据;（4）分析过滤器以评估主要PM2.5种类;（5）收集监测前和监测后的血液样品以评估炎症和纤维蛋白溶解活性;（6）评估心脏事件的长期风险;（7）采用时间序列分析和横断面分析（多变量线性回归、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。研究结果将使我们更好地了解PM2.5影响心脏系统的机制和时间过程，并确定导致对PM敏感性差异的因素，并指导监管机构设计空气污染控制标准。

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.