Environmental Epidemiology of Arrhythmogenesis in WHI

描述（由申请人提供）：空气污染和心血管疾病死亡率明显相关，但尚未在女性中进行基于人群的空气污染和心血管疾病研究。此外，现有的研究还没有评估暴露于环境空气污染物的急性、促孕效应是否被三个潜在的重要环境、社会经济和临床背景标志物所改变，在这些标志物中，这种暴露表面上增加了女性的心血管风险：慢性暴露状态、居住区和猝死的疾病特异性易感因素。我们将在来自40个临床中心及其卫星的68，133名年龄在59-70岁的绝经后妇女中调查这些问题，这些妇女参加了妇女健康倡议临床试验（WHI，1993-1998）的基线检查。我们将估计暴露于标准污染物（PM10; NO2; SO2; CO; 03）在环境空气中的地理编码的参与者地址使用验证，空间模型，依赖于污染物浓度记录在相邻的固定站点监测器在美国环境保护局大气信息检索系统。空间内插的暴露量将采用基线检查和第三年随访前当天、1天、2天和3天以及1年、2年和3年的平均污染物浓度的形式。我们将可靠地评估自主神经功能，房室传导，心室去极化，心室复极和异位从休息，标准12导联心电图记录在WHI检查。在去除季节性变化和长期趋势，并调整人口和气象协变量后，我们将探索空气污染物和ECG测量之间的假定关联。然后，我们将使用贝叶斯分层模型确定这些关联是否被慢性暴露状态、参与者居住的地理区域的社会经济特征以及心脏性猝死的临床风险因素所改变。最后，我们将评估我们的研究结果的敏感性调整暴露测量误差所产生的空间插值的个人暴露环境浓度的空气污染物。因此，我们的辅助研究将评估生物学相关的programmic机制和上下文功能链接环境空气污染心血管疾病的发病率和死亡率在一个大的，种族和地理上不同的绝经后妇女群体。在这样做的过程中，它将提高对空气污染物与心血管疾病死亡率之间关系的理解，促进对美国当前空气质量标准的评估，并深入了解过去十年美国女性心脏病猝死率相对逐渐下降的情况。

DESCRIPTION (provided by applicant): Air pollution and cardiovascular disease mortality are clearly linked, yet population-based studies of air pollution and arrhythmogenesis have not been conducted in women. Moreover, extant studies have not evaluated whether acute, pro-arrhythmic effects of exposure to ambient air pollutants are modified by three potentially important markers of the environmental, socioeconomic and clinical context within which such exposures ostensibly increase cardiovascular risk in women: chronic exposure status, neighborhood of residence, and disease-specific susceptibility factors for sudden death. We will investigate these issues in an ethnically diverse population of 68,133 post-menopausal women aged 59-70 years from the 40 clinical centers and their satellites participating in the baseline examination of the Women's Health Initiative clinical trial (WHI, 1993-1998). We will estimate exposure to criteria pollutants (PM10; NO2; SO2; CO; 03) in ambient air at geocoded participant addresses using validated, spatial models that rely on pollutant concentrations recorded at adjacent fixed-site monitors in the U.S. Environmental Protection Agency Aerometric Information Retrieval System. Spatially interpolated exposures will take the form of average pollutant concentrations on the day of, and for the 1, 2 & 3 days and 1, 2 & 3 years preceding the baseline examination and year three follow-up. We will reliably evaluate autonomic function, atrioventricular conduction, ventricular depolarization, ventricular repolarization and ectopy from resting, standard 12-lead ECGs recorded at the WHI examinations. After removing seasonal variations and long-term trends, and in addition, adjusting for demographic and meteorological covariates, we will explore the putative association between air pollutants and ECG measures. Then we will determine whether the associations are modified by chronic exposure status, socioeconomic characteristics of geographic regions in which participants live, and clinical risk factors for sudden cardiac death using Bayesian, hierarchical models. Lastly, we will assess sensitivity of our findings to adjustment for exposure measurement error arising from spatial interpolation of personal exposures from ambient concentrations of air pollutants. Our ancillary study will thereby evaluate the biologically relevant proarrhythmic mechanisms and contextual features linking ambient air pollution to cardiovascular disease morbidity and mortality in a large, ethnically and geographically diverse group of postmenopausal women. In doing so, it will improve understanding of associations between airborne pollutants and cardiovascular disease mortality, facilitate assessment of current U.S. air quality standards, and yield insight into the relatively gradual decline of sudden cardiac death rates among U.S. women over the last decade.