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

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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.