Chronic exposure to particulate air pollution and progression of subclinical atherosclerosis- Investigation based on the Heinz Nixdorf Recall Study

长期的颗粒物（PM）空气污染和住宅暴露于高交通流量与急性心血管事件的发生率有关。有人提出，细粒PM可能在动脉粥样硬化潜在慢性过程的发展中具有生物学作用，这一观点得到了动物研究和一项高选择性人群的前瞻性研究的支持。本研究第一阶段最重要的发现是，在随机选择的人群队列中，颗粒空气污染与亚临床动脉粥样硬化进展之间存在关联。在横断面分析中，我们发现与左侧颈动脉内膜中膜厚度（CIMT）的5年进展明显相关，并且与颈动脉斑块的患病率明显相关。在这个更新提案中，我们建议(1)研究来源特异性PM和PM的单个化学成分对亚临床动脉粥样硬化进展的影响。这对于确定城市空气污染中最有害的因素至关重要。(2)我们希望将目前对长期空气污染暴露和CIMT的分析扩展到冠状动脉（CAC）和胸主动脉（TAC）血管床钙化进展的研究。冠状动脉和胸主动脉钙化不仅可能以不同的方式受到环境危险因素的影响，而且它们还代表了动脉粥样硬化疾病的不同阶段，比CIMT更能预测冠状动脉事件。(3)我们建议深入分析动脉粥样硬化通路相关基因与环境的相互作用，以确定PM的相关生物学机制。我们的调查将基于亨氏尼克道夫召回研究。在基线和5年检查之后，将在项目阶段提供CIMT 10年检查的数据。此外，我们将能够使用特定来源和成分的暴露数据，应用在dfg项目（JO 170/8-1）框架内进行的模型计算和在EU-ESCAPE项目框架内开发的土地利用回归模型。由于细颗粒暴露无处不在，尚未确定安全阈值，毒性最大的颗粒特征或成分仍不清楚，因此结果将具有重大的公共卫生相关性，并且结果对心脑血管疾病的发病率至关重要。

Long-term particulate matter (PM) air pollution and residential exposure to high traffic are linked to the incidence of acute cardiovascular events. It has been proposed that fine PM might have a biologic role in the development of the underlying chronic processes of atherosclerosis, which is supported by animal studies and one prospective study in a highly selected population. The most important finding from the first phase of our study is an association of particulate air pollution with progression of subclinical atherosclerosis in a randomly selected population-based cohort. We found a clear association with the 5-year progression of the left carotid intima media thickness (CIMT) and, in a cross-sectional analysis, with prevalence of carotid plaque. In this renewal proposal, we propose to (1) investigate effects of source-specific PM and individual chemical constituents of PM on the progression of subclinical atherosclerosis. This is of utmost importance for identifying the most harmful elements of urban air pollution. (2) We want to extend the current analysis of long-term air pollution exposure and CIMT to the investigation of progression of calcification in the coronary (CAC) and the thoracic aortic (TAC) vascular bed. Coronary and thoracic aortic calcification might not only be influenced by environmental risk factors in a different way, they also represent different stages of the atherosclerotic disease and predict coronary events better than CIMT. (3) We propose to conduct in depth analyses of gene x environment interactions of genes involved in pathways of atherogenesis to identify relevant biologic mechanisms of PM.We will base our investigations on the Heinz Nixdorf Recall Study. Next to the baseline and the 5-year examination, data from the 10-year examination of CIMT will become available during the project phase. Furthermore, we will be able to use source- and constituent-specific exposure data, applying model calculations that were conducted in the framework of a DFG-project (JO 170/8-1) and from a land use regression model, which was developed in the framework of the EU-ESCAPE project. The results will be of great public health relevance because fine particle exposure is ubiquitous, no safe threshold has been identified yet, the most toxic particle characteristics or components are still unclear, and the outcome is of utmost importance for the incidence of cardiovascular and cerebrovascular disease.