Interaction of Air Pollution and Psychosocial Stress on Cardiovascular Disease.

描述(由申请人提供)： 这项建议试图了解空气污染和心理社会应激对炎症和亚临床心血管疾病(CVD)标志物的相互作用。在Joel Kaufman博士的指导下，这项培训和研究计划将以Hajat博士在社会流行病学方面的专业知识为基础，为她的职业生涯做好准备，研究社会和环境因素的关系及其对心血管疾病的影响。在K99阶段，哈贾特博士将通过授课和独立研究获得额外的培训：1)压力和心血管疾病的生物学；2)空间统计方法；3)暴露的产生和评估。这一培训将为Hajat博士提供跨学科的技能和知识，帮助她迈向独立的研究生涯。在K99阶段，Hajat博士将描述压力的生物标记物、邻里层面的心理社会应激源和个人层面的心理社会应激源与环境空气污染物的空间关联程度，特别是空气动力学直径为2.5？m的颗粒物、二氧化氮、氮氧化物和黑碳。这项工作将建立在Hajat博士之前使用动脉粥样硬化多种族研究(MESA)进行的工作的基础上，MESA是一项关于亚临床心血管疾病的纵向研究，研究对象是从美国六个大都市招募的一群老年人。在完成该奖项的培训阶段后，Hajat博士将在项目的R00阶段进行研究，这将使她成为一名独立的研究员。这项研究的目的是(1)评估空气污染和心理社会应激(客观和主观测量)对炎症标记物(C-反应蛋白、白介素6(IL-6)和纤维蛋白原)以及不同血管床动脉粥样硬化进展的协同影响，通过测量内膜中层厚度、冠状动脉钙化和踝臂指数；(2)进行交叉研究，使参与者暴露于从吸入设施排放的柴油废气(DE)和基于实验室的心理应激测试，以评估两种暴露对血压、心率变异性、儿茶酚胺水平和IL-6等生理结果的协同影响。R00阶段的研究建议对两个现有的互补数据来源进行流行病学研究，MESA和国家健康和营养检查调查，这是一个具有全国代表性的美国人口横断面样本。这两项研究都有关于空气污染、心理社会压力源、炎症和亚临床心血管疾病的数据，共同捕捉了整个生命过程中更大的地理区域和人口。R00阶段还提议进行一项实验研究。这项研究将在美国为数不多的受控吸入设施之一进行，受试者将同时暴露在DE和实验室产生的急性精神应激源中。心理学中经常使用的急性心理应激暴露包括执行一项言语任务和一项算术任务。了解空气污染和心理社会压力的协同效应将有助于促进我们对环境健康差异背后的生物学机制的理解。

DESCRIPTION (provided by applicant): This proposal seeks to understand the interaction between air pollution and psychosocial stress on markers of inflammation and subclinical cardiovascular disease (CVD). Under the mentorship of Dr. Joel Kaufman, this training and research plan will build upon Dr. Hajat's expertise in social epidemiology and prepare her for a career studying the nexus of social and environmental factors and their impact on CVD. During the K99 phase, Dr. Hajat will use didactic instruction and independent study to gain additional training in 1) the biology of stress and CVD 2) spatial statistical methods and 3) exposure generation and assessment. This training will provide Dr. Hajat with interdisciplinary skills and knowledge as she moves towards an independent research career. During the K99 phase Dr. Hajat will characterize the extent to which biomarkers of stress, neighborhood-level psychosocial stressors and individual level psychosocial stressors are spatially correlated with ambient air pollutants, specifically particulae matter <2.5 ¿m in aerodynamic diameter, nitrogen dioxide, oxides of nitrogen and black carbon. This work will build upon Dr. Hajat's previous work using the Multi-Ethnic Study of Atherosclerosis (MESA), a longitudinal study of subclinical CVD in a cohort of older adults recruited from six metropolitan areas across the US. Upon completion of the training phase of this award, Dr. Hajat will undertake research during the R00 phase of the project that will transition her to an independent investigator. The aims of this research are (1) to assess the synergistic effects of air pollution and psychosocial stress (measured objectively and subjectively) on markers of inflammation (C-reactive protein, interleukin-6 (IL-6) and fibrinogen) as well as on the progression of atherosclerosis in different vascular beds, measured by intima media thickness, coronary calcification and ankle brachial index and (2) to conduct a crossover study which exposes participants to both diesel exhaust (DE) from an inhalation facility and a laboratory-based mental stress test to assess the synergistic effect of both exposures on physiological outcomes such as blood pressure, heart rate variability, catecholamine levels and IL-6. The research in the R00 phase proposes epidemiologic studies of two complementary extant data sources, MESA and the National Health and Nutrition Examination Survey, a cross-sectional nationally representative sample of the US population. Both studies have data on air pollution, psychosocial stressors, inflammation and subclinical CVD and together capture a larger geographic area and populations across the life course. The R00 phase also proposes conducting an experimental study. The study will be conducted in one of the nation's few controlled inhalation facilities where subjects will be exposed to both DE and a laboratory generated acute mental stressor. The acute mental stress exposure, which is often used in psychology, will consist of administering a speech task and an arithmetic task. Understanding the synergistic effects of air pollution and psychosocial stress will help advance our understanding of the biological mechanisms behind environmental health disparities.