Heart Disease, Inflammatory Markers and Particulates

描述(由申请人提供)：流行病学证据支持颗粒性空气污染与心血管疾病发病率和死亡率之间的联系，但这种关系的生物学机制尚未阐明。最近的研究表明，炎症标志物是心血管结局的可行指标，暴露于颗粒性空气污染可能会升高某些炎症标志物。利用护士健康研究中嵌套的冠心病(CHD)病例对照研究数据和卫生专业人员的随访研究，我们建议检查慢性颗粒物暴露、炎症标志物和CHD之间的关系。为了获得更准确的颗粒物暴露估计，将应用复杂的地理信息系统(CIS)模型。我们还将使用结构方程模型(SEM)来研究颗粒物暴露、炎症标志物和冠心病之间的复杂相互关系。假设1：慢性颗粒物暴露会增加与冠心病相关的炎症标记物。具体目标：检查炎症标志物与长期暴露于PM2.5和PM10之间的关系。假设2：长期接触颗粒物会增加患冠心病的风险。具体目标：评估冠心病患者的颗粒物暴露是否增加，以及炎性标志物是否改变颗粒物暴露与冠心病之间的关系。假设3：炎症标记物在冠心病和慢性颗粒物暴露之间的关系中起中介作用。具体目的：使用扫描电子显微镜检查颗粒物暴露对冠心病的直接和间接贡献。

DESCRIPTION (provided by applicant): Epidemiologic evidence supports an association between particulate air pollution and cardiovascular morbidity and mortality, however biological mechanisms for this relationship have not yet been elucidated. Recent research suggests that inflammatory markers are feasible indicators of cardiovascular outcomes and that exposure to particulate air pollution may elevate certain inflammatory markers. Using data from nested case-control studies of coronary heart disease (CHD) embedded in the Nurses' Health Study and the Health Professionals' Follow-up Study, we propose to examine the relationships among chronic particulate exposure, inflammatory markers and CHD. To obtain more accurate estimates of particulate exposure, a complex Geographic Information System (CIS) model will be applied. We will also use Structural Equation Models (SEM) to examine the complex interrelationships among particulate exposure, inflammatory markers and CHD. Hypothesis 1: Chronic particulate exposure increases inflammatory markers related to CHD. Specific Aims: Examine the association between inflammatory markers and chronic exposure to PM2.5 and PM10. Hypothesis 2: Chronic particulate exposure increases the risk of CHD. Specific Aims: Assess whether particulate exposures are elevated among persons with CHD and whether inflammatory markers modify the relationship between particulate exposure and CHD. Hypothesis 3: Inflammatory markers mediate the relationship between CHD and chronic particulate exposure. Specific Aims: Use SEM to examine the direct and indirect contribution of particulate exposure to CHD.