Air Pollution, Coronary Events and Atherosclerotic Progression in a Susceptible Population

摘要 心血管健康是全球公共卫生的优先事项。动脉粥样硬化是最常见的冠状动脉疾病 心脏病（CHD）每年在全球造成1750万人死亡。在全球范围内，户外和 室内空气污染物被认为是CHD负担的主要贡献者。尽管基于人口 有证据表明，暴露于环境空气污染物和使用固体燃料做饭的原因增加， 尽管空气污染对冠心病的发病率和进展的影响很大，但人们对空气污染对冠心病发病率和进展的影响知之甚少。 例如，暴露于空气污染的程度会加速动脉粥样硬化，引发斑块不稳定 破裂并发展成冠状动脉事件，而其下的机械途径在很大程度上是未知的。一 更好地了解空气污染物作为发展和进展的潜在因素，这一普遍的 疾病将是宝贵的公共卫生保护战略，特别是对易感人群， 动脉粥样硬化患者。在这里，我们提出了一个纵向队列研究，并提出了一个总体的 假设长期暴露于空气污染物会改变冠状动脉生物学过程，加速疾病 进展，并有助于CHD发病率和死亡率。这项研究建立在精心挑选的3500个 从现有队列中检索北京的动脉粥样硬化患者，并将增加两波门诊访视 在1100个亚群中检测疾病进展。该队列包括新的亚临床 来自计算机断层扫描血管造影术（CTA）的反映斑块形态、斑块易损性 血管狭窄和冠状动脉炎症，并收集与其机制相关的生物标志物， 途径。我们亦建议加入先进的空气污染暴露评估，以确定个别 最高质量的室外和室内空气污染暴露水平，以解决我们的研究假设。 首先，我们将确定室外和室内空气污染暴露对冠状动脉事件和总 心血管死亡率其次，我们将调查暴露于空气污染对动脉粥样硬化的影响 以CTA结果为特征的进展和高危斑块形成。第三，我们会研究 空气污染对炎症途径生物标志物的影响，并探讨这些途径是否 介导疾病进展对空气污染暴露的任何反应。最后，我们将采取独特的 最严格的管制期间在北京的空气污染的机会，并评估是否长期 环境空气污染的下降改变了疾病进展和生物反应的恶化， 我们的第二假设除了主要的分析外，我们还将探讨空气的潜在联合影响， 污染物混合物和交通噪声暴露对CHD的独立影响。的结果 这项研究不仅将扩大空气污染和冠心病生理病理学的科学知识， 信息，以指导公共政策，并为有冠心病风险的个人提供临床管理信息。

Abstract Cardiovascular health is a global public health priority. Atherosclerosis is the most common form of coronary heart diseases (CHD) which constitutes 17.5 million deaths worldwide annually. Globally, both outdoor and indoor air pollutants are known as major contributors to the burdens of CHD. Despite population-based evidence suggesting that exposure to ambient air pollutants and use of solid fuel for cooking causes increased mortality from CHD, there is little known about the impact of air pollution on CHD morbidity and progression. For example, the extent to which exposure to air pollution accelerates atherosclerosis, initiate plaque instability to rupture and develop coronary events, and the mechanistic pathways underneath are largely unknown. A better understanding of air pollutants as potential factors to the development and progression of this pervasive disease will be valuable for public health protection strategies, especially for susceptible population such as patients with atherosclerosis. Here we propose a longitudinal cohort study and present an overarching hypothesis that long-term exposure to air pollutants alter coronary biological process, accelerate disease progression, and contribute to CHD morbidity and mortality. This study builds upon a well-selected 3500 patients with atherosclerosis in Beijing retrieved from an existing cohort and will add two waves of clinic visits in 1100 subpopulation to examine disease progression. The cohort includes extensive data of novel subclinical markers from computed tomography angiography (CTA) reflecting plaque morphology, plaque vulnerability, vascular stenosis, and coronary inflammation, and also collects biomarkers related to their mechanistic pathways. We also propose to add state-of-the art air pollution exposure assessment to determine individual level of outdoor and indoor air pollution exposure of the highest quality to address our study hypotheses. Firstly, we will determine the impact of outdoor and indoor air pollution exposures on coronary events and total cardiovascular mortality. Secondly, we will investigate the effects of exposure to air pollution on atherosclerosis progression and high-risk plaque formation characterized by CTA outcomes. Thirdly, we will examine the effects of air pollution on biological markers of inflammation pathways and explore whether these pathways mediate any response of disease progression to air pollution exposure. Lastly, we will take the unique opportunity of the most stringent regulation period on air pollution in Beijing and assess whether long-term decline in ambient air pollution change the worsening of the disease progression and biological responses as our secondary hypothesis. Apart from the main analysis, we will also explore the potential of joint effects of air pollutant mixtures and independent effects of air pollution exposure from traffic noise on CHD. Findings from this study will not only extend scientific knowledge on air pollution and CHD physiopathology, but will provide information to guide public policy and inform clinical management for individuals at-risk of CHD.