Interaction of Air Pollution and Psychosocial Stress on Cardiovascular Disease.

描述（由申请人提供）： 该提案旨在了解空气污染和心理社会压力对炎症和亚临床心血管疾病（CVD）标志物之间的相互作用。在Joel考夫曼博士的指导下，这项培训和研究计划将建立在Hajat博士在社会流行病学方面的专业知识基础上，并为她研究社会和环境因素的关系及其对CVD的影响做好准备。在K99阶段，Hajat博士将使用教学指导和独立研究来获得以下方面的额外培训：1）压力和心血管疾病的生物学2）空间统计方法和3）暴露产生和评估。这项培训将为Hajat博士提供跨学科的技能和知识，因为她将走向独立的研究生涯。在K99阶段，Hajat博士将描述压力的生物标志物，社区水平的心理社会压力源和个人水平的心理社会压力源与环境空气污染物的空间相关程度，特别是空气动力学直径<2.5 μ 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博士以前使用多种族动脉粥样硬化研究（MESA）的工作基础上，MESA是一项对从美国六个大都市招募的老年人队列进行的亚临床CVD纵向研究。在完成该奖项的培训阶段后，Hajat博士将在该项目的R00阶段进行研究，这将使她成为一名独立的研究者。本研究的目的是（1）评估空气污染和心理社会压力的协同效应（客观和主观测量）炎症标志物（C-反应蛋白、白细胞介素-6（IL-6）和纤维蛋白原）以及不同血管床中动脉粥样硬化的进展，通过内膜-中层厚度测量，冠状动脉钙化和踝臂指数，以及（2）进行交叉研究，将参与者暴露于吸入设施和实验室的柴油废气（DE），基于心理应激测试，以评估两种暴露对生理结果如血压、心率变异性、儿茶酚胺水平和IL-6的协同效应。R00阶段的研究提出了两个互补的现存数据来源的流行病学研究，MESA和国家健康和营养检查调查，美国人口的横截面全国代表性样本。这两项研究都有关于空气污染、心理社会压力、炎症和亚临床心血管疾病的数据，并共同涵盖了整个生命过程中更大的地理区域和人口。R00阶段还建议进行实验研究。该研究将在美国为数不多的受控吸入设施中进行，受试者将暴露于DE和实验室产生的急性精神应激源。心理学中经常使用的急性精神应激暴露将包括执行言语任务和算术任务。了解空气污染和心理压力的协同效应将有助于我们进一步了解环境健康差异背后的生物学机制。

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.