Chronic exposure to particulate air pollution and progression of subclinical atherosclerosis- Investigation based on the Heinz Nixdorf Recall Study
Final Report Abstract
Goal: The overall goal of this research was to investigate the effect of particulate matter air pollution on the development and progression of atherosclerosis. To this end, we analysed the effect of PM and PM components on the progression of carotid intima media thickness (CIMT), and coronary and thoracic aortic calcification (CAC and TAC, respectively), and investigating gene x environment interactions in order to increase knowledge on potentially involved biological pathways. Methods: We used data from the Heinz Nixdorf Recall (HNR) study, a prospective cohort of 4,814 middle-aged to elderly residents of the highly industrial Ruhr area (Essen, Mülheim, Bochum) of Germany that started in 2000 and had 2 follow-up examinations in 2006-2008 and 2011-2015. For long-term exposure assessment at baseline and during follow-up, we employed the European Air Pollution Dispersion (EURAD) chemistry transport model. Briefly, for the HNR study area (~600 km2), the EURAD model is able to estimate hourly levels of particulate matter (PM10, PM2.5, source-specificPM), gaseous pollutants (NO2, SO2, O3, NO, NH3, CO), and size-specific total particle numbers (PN; nucleation, accumulation, and coarse modes), that were averages to annual averages. The outcome of interest was the progression of subclinical atherosclerosis over the observation period. Mean CIMT value [mm] was defined side-specifically as the mean of all available images for each available time point. Progression (yes/no) was operationalized as a difference of mean CIMT >0, while extent of progression was assessed as annual μm-change in cIMT for the left and right body side. Progression (yes/no) of CAC and TAC, respectively, was operationalized as 𝐶𝐴𝐶 − 𝐶𝐴𝐶 > 0 and 𝑇𝐴𝐶 − 𝑇𝐴𝐶 > 0 respectively. Due to its exponential nature, extent of progression was assessed as the growth rate in Agatston score: (𝑙𝑜𝑔(𝐶𝐴𝐶 + 1) − 𝑙𝑜𝑔(𝐶𝐴𝐶 + 1))/years of follow-up and (𝑙𝑜𝑔(𝑇𝐴𝐶 + 1) − 𝑙𝑜𝑔(𝑇𝐴𝐶 + 1))/ years of follow-up, respectively. Analysis were conducted with Poisson and linear regression. we investigated genome-wide the association between the natural logarithm of CIMT, i.e. ln(CIMT), and the interaction of PM2.5 with single SNPs (HNR: 5,521,460 SNPs, KORA F4: 5,370,940 SNPs) in the linear regression model: ln(CIMT) = β + β SNP + β PM . + β SNP × PM . + β Age + β Sex + ∑ β PC (1) with the regression coefficients 𝛽 (j=0, …, 10). We assumed an additive mode of inheritance and adjusted for age as well as sex and accounted for population stratification by inclusion of the first five principal components (PCs) derived from smartPCA. For each SNP, we tested the (2df) joint null hypothesis β = β = 0 by a 2df test recommend. Results: In the full sample analysis, we did not observe an association between long-term exposure to any of the considered air pollutants and progression of CAC, TAC or CIMT or extent of progression. In contrast, analysis in participants free of CAC, respectively TAC, or minimal CAC, respectively TAC, at baseline suggested a positive association with dichotomous progression and extent of progression. Similarly, in participants with baseline CIMT values below the median, we observed positive associations with long-term exposure to particulate matter. However, this observation was restricted to the left carotid artery. These results were robust to a range of different sensitivity analyses. Effect estimates were independent of personal characteristics and concurrent long-term noise exposure. We could not observe relevant differences in the pattern of associations for different particle components or sources. Main effects of genetic variants seemed to be more important than G x E effects (at least within the limits of this project and the particular E (PM2.5 component which we explored). In conclusion, we could show that long-term exposure to air pollution and road traffic noise are independently associated with progression of atherosclerosis in subjects with no or minor atherosclerotic disease. No specific component of the particle mixture could be identified as being consistently more strongly related to the outcome than the already regulated air pollutants PM10, PM2.5 and NO2. Focussing on PM2.5 we observed no evidence for strong G x E associations for the outcome CIMT even though we were able to detect and validate reported genetic main effects.
Publications
- (2014): Are air pollution and traffic noise independently associated with atherosclerosis: the Heinz Nixdorf Recall Study. In: European heart journal 35 (13),853–860
Kälsch H, Hennig F, Moebus S, Möhlenkamp S, Dragano N, Jakobs H et al.
(See online at https://doi.org/10.1093/eurheartj/eht426) - (2015): Ankle-Brachial Index but Neither Intima Media Thickness Nor Coronary Artery Calcification is Associated With Mild Cognitive Impairment. In: Journal of Alzheimer's disease : JAD 47 (2),433–442
Weimar C, Winkler A, Dlugaj M, Lehmann N, Hennig F, Bauer M et al.
(See online at https://doi.org/10.3233/JAD-150218) - (2016): Association of long-term exposure to local industry- and traffic-specific particulate matter with arterial blood pressure and incident hypertension. In: International journal of hygiene and environmental health 219 (6), 527–535
Fuks K B, Weinmayr G, Hennig F, Tzivian L, Moebus S, Jakobs H et al.
(See online at https://doi.org/10.1016/j.ijheh.2016.05.008) - (2016): Comparison of Land-Use Regression Modeling with Dispersion and Chemistry Transport Modeling to Assign Air Pollution Concentrations within the Ruhr Area. In: Atmosphere 7 (3),48
Hennig F, Sugiri D, Tzivian L, Fuks K, Moebus S, Jöckel K H et al.
(See online at https://doi.org/10.3390/atmos7030048) - (2016): Linkage and Association Analysis Identifies TRAF1 Influencing Common Carotid Intima-Media Thickness. In: Stroke 47 (12), 2904–2909
Heßler N, Geisel M H, Coassin S, Erbel R, Heilmann S, Hennig F et al.
(See online at https://doi.org/10.1161/STROKEAHA.116.013943) - (2016): Update of the effect estimates for common variants associated with carotid intima media thickness within four independent samples: The Bonn IMT Family Study, the Heinz Nixdorf Recall Study, the SAPHIR Study and the Bruneck Study. In: Atherosclerosis 249,83–87
Geisel M H, Coassin S, Heßler N, Bauer M, Eisele L, Erbel R et al.
(See online at https://doi.org/10.1016/j.atherosclerosis.2016.03.042) - Heinz Nixdorf Recall study. Comparison of coronary artery calcification, carotid intima-media thickness and ankle-brachial index for predicting 10-year incident cardiovascular events in the general population. Eur Heart J. 2017 Jun14;38(23):1815-1822
Geisel MH, Bauer M, Hennig F, Hoffmann B, Lehmann N, Möhlenkamp S, Kröger K, Kara K, Müller T, Moebus S, Erbel R, Scherag A, Jöckel KH, Mahabadi AA
(See online at https://doi.org/10.1093/eurheartj/ehx120) - (2018): Air Pollution and Glucose Metabolism: An Analysis in Non-Diabetic Participants of the Heinz Nixdorf Recall Study. In: Environmental health perspectives 126 (4),047001
Lucht S A, Hennig F, Matthiessen C, Ohlwein S, Icks A, Moebus S et al.
(See online at https://doi.org/10.1289/EHP2561) - (2019): Investigation of air pollution and noise on progression of thoracic aortic calcification: results of the Heinz Nixdorf Recall Study. In: European journal of preventive cardiology, 2019 Jun 12
Hennig F, Moebus S, Reinsch N, Budde T, Erbel R, Jöckel K H et al.
(See online at https://doi.org/10.1177/2047487319854818)
