Environmental Epidemiology of Arrhythmogenesis in WHI

WHI 心律失常发生的环境流行病学

• 批准号: 6599396
• 负责人: Eric A. Whitsel
• 金额: $ 56.47万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-08 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6599396
• 关键词: air pollution; arrhythmia; cardiovascular disorder epidemiology; cardiovascular disorder risk; cardiovascular function; clinical research; electrocardiography; female; gene environment interaction; geographic site; human data; human middle age (35-64); human morbidity; human old age (65+); human population study; longitudinal human study; mathematical model; postmenopause; socioeconomics; sudden cardiac death; women's health

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.

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律失常发生的研究。此外，现有研究尚未评估暴露于环境空气污染物的急性、促心律失常效应是否会被环境、社会经济和临床背景的三个潜在重要标志所改变，在这些标志中，此类暴露表面上会增加女性的心血管风险：长期暴露状态、居住地附近以及猝死的疾病特异性易感因素。我们将在 40 个临床中心及其卫星中心参与妇女健康倡议临床试验（WHI，1993-1998）基线检查的 68,133 名 59-70 岁绝经后妇女中调查这些问题。我们将使用经过验证的空间模型来估计地理编码参与者地址的环境空气中标准污染物（PM10；NO2；SO2；CO；03）的暴露量，该模型依赖于美国环境保护局航空信息中相邻固定地点监测器记录的污染物浓度检索系统。空间插值暴露量将采用基线检查当天以及基线检查前 1、2 和 3 天以及 1、2 和 3 年以及第三年随访的平均污染物浓度的形式。我们将根据 WHI 检查中记录的静息、标准 12 导联心电图可靠地评估自主神经功能、房室传导、心室除极、心室复极和异位。在消除季节变化和长期趋势，并调整人口和气象协变量后，我们将探讨空气污染物和心电图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会因长期暴露状态、参与者居住的地理区域的社会经济特征以及心源性猝死的临床危险因素而改变。最后，我们将评估我们的研究结果对因空气污染物环境浓度的个人暴露空间插值而产生的暴露测量误差进行调整的敏感性。因此，我们的辅助研究将评估生物学相关的致心律失常机制和背景特征，将环境空气污染与大量、种族和地域不同的绝经后妇女群体的心血管疾病发病率和死亡率联系起来。这样做将增进对空气污染物与心血管疾病死亡率之间关系的了解，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源性猝死率相对逐渐下降的情况。