Air Pollution and Progression of Atherosclerosis in Different Vessel Beds—Results from a Prospective Cohort Study in the Ruhr Area, Germany
ABSTRACT: Objectives: Due to inconsistent epidemiological evidence on health effects of air pollution on progression of atherosclerosis, we investigated several air pollutants and their effects on progression of atherosclerosis, using carotid intima media thickness (cIMT), coronary calcification (CAC), and thoracic aortic calcification (TAC). Methods: We used baseline (2000–2003) and 5-y follow-up (2006–2008) data from the German Heinz Nixdorf Recall cohort study, including 4,814 middle-aged adults. Residence-based long-term air pollution exposure, including particulate matter (PM) with aerodynamic diameter Results: While no clear associations were observed in the full study sample (mean age 59.1 ( Conclusion: Our study suggests that development and progression of subclinical atherosclerosis is associated with long-term air pollution in middle-aged participants with no or minor atherosclerotic burden at baseline, while overall no consistent associations are observed. https://doi.org/10.1289/EHP7077
Project description:AIMS:Air pollution and noise are potential risk factors for subclinical atherosclerosis. Longitudinal analyses, especially on the interplay of these environmental factors, are scarce and inconsistent. Hence we investigated long-term traffic-related exposure to air pollution and noise with the development and progression of thoracic aortic calcification, a marker of subclinical atherosclerosis. METHODS:We used baseline (2000-2003) and follow-up (2006-2008) data from the German Heinz Nixdorf Recall cohort study, including 4814 middle-aged adults. Residence-based air pollution (PM2.5 (aerodynamic diameter???2.5?µm), PM10, nitrogen dioxide and particle number), and noise was assessed with dispersion models. Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. The presence and extent of thoracic aortic calcification progression were analysed with multiple logistic and linear regression models, respectively, adjusting for age, sex, lifestyle variables, socioeconomic status and respective co-exposure. RESULTS:We observed no association in the full study sample (n?=?3155, mean age 59.1 (±7.6) years, 52.8% women). While an interquartile range in particle number and night-time noise yielded odds ratios of 1.20 (1.03, 1.40) and 1.21 (1.00, 1.46) for binary thoracic aortic calcification progression, and 0.02 (-0.01, 0.05) and 0.04 (0.00, 0.07) higher growth rates of thoracic aortic calcification in participants with baseline thoracic aortic calcification less than 10, negative findings were observed in those with baseline thoracic aortic calcification of 10 or greater. Results were similar for other pollutants and daytime noise. CONCLUSION:Our study shows no overall associations. Subgroup analyses suggest independent associations of traffic-related air pollution and noise with the development and progression of subclinical atherosclerosis in participants with no or minor thoracic aortic calcification at baseline, in contrast to negative findings in those with advanced calcification.
Project description:Mild cognitive impairment (MCI) describes the intermediate state between normal cognitive aging and dementia. Adverse effects of air pollution (AP) on cognitive functions have been proposed, but investigations of simultaneous exposure to noise are scarce.We analyzed the cross-sectional associations of long-term exposure to AP and traffic noise with overall MCI and amnestic (aMCI) and nonamnestic (naMCI) MCI.At the second examination of the population-based Heinz Nixdorf Recall study, cognitive assessment was completed in 4,086 participants who were 50-80 years old. Of these, 592 participants were diagnosed as having MCI (aMCI, n = 309; naMCI, n = 283) according to previously published criteria using five neuropsychological subtests. We assessed long-term residential concentrations for size-fractioned particulate matter (PM) and nitrogen oxides with land use regression, and for traffic noise [weighted 24-hr (LDEN) and night-time (LNIGHT) means]. Logistic regression models adjusted for individual risk factors were calculated to estimate the association of environmental exposures with MCI in single- and two-exposure models.Most air pollutants and traffic noise were associated with overall MCI and aMCI. For example, an interquartile range increase in PM2.5 and a 10 A-weighted decibel [dB(A)] increase in LDEN were associated with overall MCI as follows [odds ratio (95% confidence interval)]: 1.16 (1.05, 1.27) and 1.40 (1.03, 1.91), respectively, and with aMCI as follows: 1.22 (1.08, 1.38) and 1.53 (1.05, 2.24), respectively. In two-exposure models, AP and noise associations were attenuated [e.g., for aMCI, PM2.5 1.13 (0.98, 1.30) and LDEN 1.46 (1.11, 1.92)].Long-term exposures to air pollution and traffic noise were positively associated with MCI, mainly with the amnestic subtype.Tzivian L, Dlugaj M, Winkler A, Weinmayr G, Hennig F, Fuks KB, Vossoughi M, Schikowski T, Weimar C, Erbel R, Jöckel KH, Moebus S, Hoffmann B, on behalf of the Heinz Nixdorf Recall study Investigative Group. 2016. Long-term air pollution and traffic noise exposures and mild cognitive impairment in older adults: a cross-sectional analysis of the Heinz Nixdorf Recall Study. Environ Health Perspect 124:1361-1368; http://dx.doi.org/10.1289/ehp.1509824.
Project description:BACKGROUND: Long-term exposures to particulate matter air pollution (PM2.5 and PM10) and high traffic load have been associated with markers of systemic inflammation. Epidemiological investigations have focused primarily on total PM, which represents a mixture of pollutants originating from different sources. OBJECTIVE: We investigated associations between source-specific PM and high-sensitive C-reactive protein (hs-CRP), an independent predictor of cardiovascular disease. METHODS: We used data from the first (2000-2003) and second examination (2006-2008) of the Heinz Nixdorf Recall study, a prospective population-based German cohort of initially 4,814 participants (45-75 years of age). We estimated residential long-term exposure to local traffic- and industry-specific fine particulate matter (PM2.5) at participants' residences using a chemistry transport model. We used a linear mixed model with a random participant intercept to estimate associations of source-specific PM and natural log-transformed hs-CRP, controlling for age, sex, education, body mass index, low- and high-density lipoprotein cholesterol, smoking variables, physical activity, season, humidity, and city (8,204 total observations). RESULTS: A 1-?g/m3 increase in total PM2.5 was associated with a 4.53% increase in hs-CRP concentration (95% CI: 2.76, 6.33%). hs-CRP was 17.89% (95% CI: 7.66, 29.09%) and 7.96% (95% CI: 3.45, 12.67%) higher in association with 1-?g/m3 increases in traffic- and industry-specific PM2.5, respectively. RESULTS for PM10 were similar. CONCLUSIONS: Long-term exposure to local traffic-specific PM (PM2.5, PM10) was more strongly associated with systemic inflammation than total PM. Associations of local industry-specific PM were slightly stronger but not significantly different from associations with total PM.
Project description:Despite the importance of understanding the connection between air pollution exposure and diabetes, studies investigating links between air pollution and glucose metabolism in nondiabetic adults are limited.We aimed to estimate the association of medium-term air pollution exposures with blood glucose and glycated hemoglobin A1c (HbA1c) among nondiabetics.This study included observations from nondiabetic participants (nobs=7,108) of the population-based Heinz Nixdorf Recall study at baseline (2000–2003) and follow-up examination (2006–2008). Daily fine particulate matter (aerodynamic?diameter?2.5??m,?PM2.5; aerodynamic?diameter?10??m,?PM10), accumulation mode particle number (PNAM), and nitrogen dioxide (NO2) exposures were estimated at participants’ residences using the spatiotemporal European Air Pollution Dispersion (EURAD) chemistry transport model. We evaluated the associations between medium-term air pollution exposures (28- and 91-d means) and glucose metabolism measures using mixed linear regression and adjusting for season, meteorology, and personal characteristics. A range of other exposure windows (1-, 2-, 3-, 7-, 14-, 45-, 60-, 75-, 105-, 120-, and 182-d means) were also evaluated to identify potentially relevant biological windows.We observed positive associations between PM2.5 and PNAM exposures and blood glucose levels [e.g., 28-d PM2.5: 0.91 mg/dL (95% CI: 0.38, 1.44) per 5.7??g/m3]. PM2.5, PM10, and PNAM exposures were positively associated with HbA1c [e.g., 91-d PM2.5: 0.07 p.p. (95% CI: 0.04, 0.10) per 4.0??g/m3]. Mean exposures during longer exposure windows (75- to 105-d) were most strongly associated with HbA1c, whereas 7- to 45-d exposures were most strongly associated with blood glucose. NO2 exposure was not associated with blood glucose or with HbA1c.Medium-term PM and PNAM exposures were positively associated with glucose measures in nondiabetic adults. These findings indicate that reducing ambient air pollution levels may decrease the risk of diabetes. https://doi.org/10.1289/EHP2561.
Project description:BACKGROUND:Despite the importance of understanding associations of air pollution and noise exposure with loss of neurocognitive performance, studies investigating these exposures and local brain structure are limited. OBJECTIVE:We estimated associations of residential air pollution and noise exposures with neurocognitive test performance and the local gyrification index (lGI), a marker for local brain atrophy, among older adults. METHODS:For n=615 participants from the population-based 1000BRAINS study, based on the German Heinz Nixdorf Recall study, we assessed residential exposures to particulate matter (PM10, PM2.5, PM2.5abs), accumulation mode particle number (PNAM), and nitrogen oxides (NOx, NO2), using land-use regression and chemistry transport models. Weighted 24-h and nighttime noise were modeled according to the European noise directive. We evaluated associations of air pollution and noise exposure at the participants' 2006-2008 residential addresses with neurocognitive test performance and region-specific lGI values (n=590) from magnetic resonance imaging, both assessed in 2011-2015, using linear regression and adjusting for demographic and personal characteristics. RESULTS:Air pollution and noise were associated with language and short-term/working memory and with local atrophy of the fronto-parietal network (FPN), a functional resting-state network associated with these cognitive processes. For example, per 2-?g/m3 PM10, local brain atrophy was more pronounced in the posterior brain regions of the FPN, with a -0.02 [95% confidence interval (CI): -0.04, 0.00] lower lGI. In contrast, in the anterior regions of the FPN, weighted 24-h and nighttime noise were associated with less local brain atrophy [e.g., 0.02 (95% CI: 0.00, 0.04) for 10?dB(A) 24-h noise]. CONCLUSIONS:Air pollution and noise exposures were associated in opposite directions with markers of local atrophy of the FPN in the right brain hemisphere in older adults, suggesting that both chronic air pollution and noise exposure may influence the physiological aging process of the brain. https://doi.org/10.1289/EHP5859.
Project description:BACKGROUND:The association between non-steroidal anti-inflammatory drugs (NSAIDs) and the incidence of valvular and arterial calcification is not well established despite known associations between these drugs and cardiovascular events. OBJECTIVE:To compare the association between the baseline use of aspirin with other NSAID class medications with the incidence and prevalence of aortic valve calcification (AVC) and coronary artery calcification (CAC). METHODS:The relationship of NSAID use to AVC and CAC detected by computed tomography was assessed in 6814 participants within the Multi-Ethnic Study of Atherosclerosis (MESA) using regression modeling. Results were adjusted for age, sex, ethnicity, study site, anti-hypertensive medication use, education, income, health insurance status, diabetes, smoking, exercise, body mass index, blood pressure, serum lipids, inflammatory markers, fasting glucose, statin medication use, and a simple diet score. Medication use was assessed by medication inventory at baseline which includes the use of non-prescription NSAIDs. MESA collects information on both incident and prevalent calcification. The 4814 participants of the Heinz Nixdorf Recall (HNR) Study, a German prospective cohort study with similar measures of calcification, were included in this analysis to enable replication. RESULTS:Mean age of the MESA participants was 62 years (51% female). After adjustment for possible confounding factors, a possible association between aspirin use and incident AVC (Relative Risk(RR): 1.60; 95%Confidence Interval (CI): 1.19-2.15) did not replicate in the HNR cohort (RR: 1.06; 95%CI: 0.87-1.28). There was no significant association between aspirin use and incident CAC in the MESA cohort (RR 1.08; 95%CI: 0.91-1.29) or in the HNR cohort (RR 1.24; 95%CI: 0.87-1.77). Non-aspirin NSAID use was not associated with either AVC or CAC in either cohort. There were no associations between regular cardiac dose aspirin and incident calcification in either cohort. CONCLUSION:Baseline NSAID use, as assessed by medication inventory, appears to have no protective effect regarding the onset of calcification in either coronary arteries or aortic valves.
Project description:BACKGROUND: Recent studies have shown an association of short-term exposure to fine particulate matter (PM) with transient increases in blood pressure (BP), but it is unclear whether long-term exposure has an effect on arterial BP and hypertension. OBJECTIVES: We investigated the cross-sectional association of residential long-term PM exposure with arterial BP and hypertension, taking short-term variations of PM and long-term road traffic noise exposure into account. METHODS: We used baseline data (2000-2003) on 4,291 participants, 45-75 years of age, from the Heinz Nixdorf Recall Study, a population-based prospective cohort in Germany. Urban background exposure to PM with aerodynamic diameter ? 2.5 ?m (PM(2.5)) and ? 10 ?m (PM(10)) was assessed with a dispersion and chemistry transport model. We used generalized additive models, adjusting for short-term PM, meteorology, traffic proximity, and individual risk factors. RESULTS: An interquartile increase in PM2.5 (2.4 ?g/m(3)) was associated with estimated increases in mean systolic and diastolic BP of 1.4 mmHg [95% confidence interval (CI): 0.5, 2.3] and 0.9 mmHg (95% CI: 0.4, 1.4), respectively. The observed relationship was independent of long-term exposure to road traffic noise and robust to the inclusion of many potential confounders. Residential proximity to high traffic and traffic noise exposure showed a tendency toward higher BP and an elevated prevalence of hypertension. CONCLUSIONS: We found an association of long-term exposure to PM with increased arterial BP in a population-based sample. This finding supports our hypothesis that long-term PM exposure may promote atherosclerosis, with air-pollution-induced increases in BP being one possible biological pathway.
Project description:BACKGROUND: Atherosclerosis is the primary cause of coronary heart disease (CHD), preceding the onset of cardiovascular disease by decades in most cases. Here we examine the association between single nucleotide polymorphisms (SNPs) integrated on Metabochip and coronary artery calcification (CAC), a valid risk factor for CHD, in an unselected, population-based German cohort. METHODS: The Metabochip is a custom iSELECT array containing >195,000 SNPs that was designed to support large-scale follow-up of putative associations for metabolic and cardiovascular-associated traits. We used generalized linear regression models to explore the impact of Metabochip SNPs on quantitative CAC in 4,329 participants. RESULTS: The 9p21 variant, rs1537373, was most strongly associated (Beta=0.30; 95% confidence interval (CI)=0.21-0.39; p=4.05x10-11) with quantitative CAC. The second strongest association with CAC was with rs9349379 in the phosphatase and actin regulator 1 gene, PHACTR1, (Beta=0.30; 95% CI=0.22-0.40; p=4.67x10-11). Both SNPs remained nominally significant in dichotomized analyses for the presence of any CAC (odds ratiors1537373 (OR)=1.19; 95% CI=1.07-1.31; p=0.001 and ORrs9349379=1.26; 95% CI=1.14-1.40); p=1.5x10-5). Fine mapping of the 9p21 and PHACTR1 gene region revealed several other SNPs that were strongly associated with CAC. CONCLUSION: We demonstrate that SNPs near 9p21 and in PHACTR1 that have previously been shown to be associated with CHD are strongly associated with CAC in the Heinz Nixdorf Recall Study cohort. Our findings suggest that the 9p21 and 6q24 loci might be involved in cardiac outcome via promoting development of atherosclerosis in the coronary arteries.
Project description:Background:Differences in traffic-related air pollution (TRAP) composition may cause heterogeneity in associations between air pollution exposure and cardiovascular health outcomes. Clustering multi-pollutant measurements allows investigation of effect modification by TRAP profiles. Methods:We measured TRAP components with fixed-site and on-road instruments for two two-week periods in Baltimore, Maryland. We created representative TRAP profiles for cold and warm seasons using predictive k-means clustering. We predicted cluster membership for 1005 participants in the Multi-Ethnic Study of Atherosclerosis and Air Pollution with follow-up between 2000 and 2012. We estimated cluster-specific relationships between coronary artery calcification (CAC) progression and long-term exposure to fine particulate matter (PM2.5) and oxides of nitrogen (NOX). Results:We identified two clusters in the cold season, notable for higher ratios of gases and ultrafine particles, respectively. A 5 ?g/m3 difference in PM2.5 was associated with 17.0 (95% Confidence Interval [CI]: 7.2, 26.7) and 42.6 (95% CI: 25.7, 59.4) Agatston units/year CAC progression among participants in clusters 1 and 2, respectively (effect modification p=0.006). A 40ppb difference in NOX was associated with 22.2 (95% CI: 7.7, 36.7) and 41.9 (95% CI: 23.7, 60.2) Agatston units/year CAC progression in clusters 1 and 2, respectively (p=0.08). Similar trends occurred using clusters identified from warm season measurements. Clusters correlated highly with baseline pollution level. Conclusions:Clustering TRAP measurements identified spatial differences in composition. We found evidence of greater CAC progression rates per unit PM2.5 exposures among people living in areas characterized by high ratios of ultrafine particle counts relative to NOX concentrations.
Project description:Air pollution exposure has been shown to potentiate plaque progression in humans and animals. Our previous studies have suggested a role for oxidized lipids in mediating adverse vascular effect of air pollution. However, the types of oxidized lipids formed in response to air pollutants and how this occurs and their relevance to atherosclerosis are not fully understood.To investigate the mechanisms by which particulate matter <2.5 ?m (PM2.5) induces progression of atherosclerosis.Atherosclerosis-prone ApoE(-/-) or LDLR(-/-) mice were exposed to filtered air or concentrated ambient PM2.5 using a versatile aerosol concentrator enrichment system for 6 months. PM2.5 increased 7-ketocholesterol (7-KCh), an oxidatively modified form of cholesterol, in plasma intermediate density lipoprotein/low-density lipoprotein fraction and in aortic plaque concomitant with progression of atherosclerosis and increased CD36 expression in plaque macrophages from PM2.5-exposed mice. Macrophages isolated from PM2.5-exposed mice displayed increased uptake of oxidized lipids without alterations in their efflux capacity. Consistent with these finding, CD36-positive macrophages displayed a heightened capacity for oxidized lipid uptake. Deficiency of CD36 on hematopoietic cells diminished the effect of air pollution on 7-KCh accumulation, foam cell formation, and atherosclerosis.Our results suggest a potential role for CD36-mediated abnormal accumulations of oxidized lipids, such as 7-KCh, in air pollution-induced atherosclerosis progression.