Air Pollution and Glucose Metabolism: An Analysis in Non-Diabetic Participants of the Heinz Nixdorf Recall Study.

BACKGROUND: 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. OBJECTIVE: We aimed to estimate the association of medium-term air pollution exposures with blood glucose and glycated hemoglobin A1c (HbA1c) among nondiabetics. METHODS: This study included observations from nondiabetic participants (nobs=7,108) of the population-based Heinz Nixdorf Recall study at baseline (2000­2003) and follow-up examination (2006­2008). Daily fine particulate matter (aerodynamic diameter≤2.5 µm, PM2.5; aerodynamic diameter≤10 µm, 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. RESULTS: 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 µg/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 µg/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. CONCLUSIONS: 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.

Long-term exposure to airborne particulate matter and NO2 and prevalent and incident metabolic syndrome - Results from the Heinz Nixdorf Recall Study.

INTRODUCTION: Recently, epidemiological studies have found a link between air pollution (AP) and individual components of the metabolic syndrome (MetS), a condition predisposing to cardiometabolic diseases. However, very few studies have explored a possible association between air pollution and MetS. OBJECTIVE: We analyzed the effects of long-term exposure to airborne particulate matter and NO2 on prevalence and incidence of MetS. METHODS: We used data of the population-based prospective Heinz Nixdorf Recall study (baseline 2000-2003) to investigate the association(s) between AP exposure and MetS prevalence at baseline (n = 4457) and MetS incidence at first follow-up visit (n = 3074; average follow-up: 5.1 years). Mean annual exposure to size-fractioned particulate matter (PM10, PM2.5, PMcoarse, and PM2.5abs) and nitrogen dioxide (NO2) was assessed using a land use regression model. MetS was defined as central obesity plus two out of four additional risk factors (i.e., elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure or elevated plasma glucose). We estimated odds ratios (ORs) of MetS prevalence and incidence per interquartile range (IQR) of exposure, adjusting for demographic and lifestyle variables. RESULTS: We observed a MetS prevalence of 20.7% (n = 922) and an incidence of 9.7% (n = 299). NO2 was positively associated with MetS prevalence, with an OR increase per IQR of 1.12 (95%-CI 1.02-1.24, IQR = 6.1 µg/m3). PM10 and PM2.5 were both borderline positively associated with MetS incidence, with ORs of 1.14 (95%-CI 0.99-1.32, IQR = 2.1 µg/m3) and 1.19 (95%-CI 0.98-1.44, IQR = 1.5 µg/m3) per IQR, respectively. CONCLUSION: In summary, we found a weak positive association between air pollution and MetS. The strongest and most consistent effects were observed between NO2 and prevalent MetS.

Is long-term particulate matter and nitrogen dioxide air pollution associated with incident monoclonal gammopathy of undetermined significance (MGUS)? An analysis of the Heinz Nixdorf Recall study.

BACKGROUND: Exposure to air pollution activates the innate immune system and influences the adaptive immune system in experimental settings. We investigated the association of residential long-term exposure to particulate matter (PM) and NO2 air pollution with monoclonal gammopathy of undetermined significance (MGUS) as a marker of adaptive immune system activation. METHODS: We used data from the baseline (2000-2003), 5-year (2006-2008) and 10-year (2011-2015) follow-up examinations of the German Heinz Nixdorf Recall cohort study of 4814 participants (45-75years). Residential exposure to PM size fractions and NO2 was estimated by land-use regression (ESCAPE-LUR, annual mean 2008/2009) and dispersion chemistry transport models (EURAD-CTM, 3-year mean at baseline). We used logistic regression to estimate the effects of air pollutants on incident MGUS, adjusting for age, sex, education, smoking status, physical activity, and BMI. As a non-linear approach, we looked at quartiles (2-4) of the air pollutants in comparison to quartile 1. RESULTS: Of the 3949 participants with complete data, 100 developed MGUS during the 10-year follow-up. In the main model, only PMcoarse was associated with incident MGUS (OR per IQR (1.9µg/m3): 1.32, 95% CI 1.04-1.67). We further found positive associations between PM size fractions estimated by ESCAPE-LUR and incident MGUS by quartiles of exposure (OR Q4 vs Q1: PM2.5 2.03 (1.08-3.80); PM10 1.97 (1.05-3.67); PMcoarse 1.98 (1.09-3.60)). CONCLUSIONS: Our results indicate that an association between long-term exposure to PM and MGUS may exist. Further epidemiologic studies are needed to corroborate this possible link.

Long-term air pollution and traffic noise exposures and cognitive function:A cross-sectional analysis of the Heinz Nixdorf Recall study.

Investigations of adverse effects of air pollution (AP) and ambient noise on cognitive functions are apparently scarce, and findings seem to be inconsistent. The aim of this study was to examine the associations of long-term exposure to AP and traffic noise with cognitive performance. At the second examination of the population-based Heinz Nixdorf Recall study (2006-2008), cognitive performance was evaluated in 4086 participants. Long-term residential exposure to size-specific particulate matter (PM) and nitrogen oxides (NOx) with land use regression, to and traffic noise (weighted 24-h (LDEN) and nighttime (LNIGHT) means), was assessed according to the European Union (EU) Directive 2002/49/EC. Multiple regression models were calculated for the relationship of environmental exposures with a global cognitive score (GCS) and in five cognitive subtests, using single- and two-exposure models. In fully adjusted models, several AP metrics were negatively associated with four of five subtests and with GCS. For example, an interquartile range increase in PM2.5 was correlated with verbal fluency, labyrinth test, and immediate and delayed verbal recall. A 10 dB(A) elevation in LDEN and LNIGHT was associated with GCS. Similar but not significant associations were found for the cognitive subtests. In two-exposure models including noise and air pollution simultaneously, the associations did not change markedly for air pollution, but attenuated numerically for noise. Long-term exposures to AP and traffic noise are negatively correlated with subtests related to memory and executive functions. There appears to be little evidence for mutual confounding.

Association of long-term exposure to local industry- and traffic-specific particulate matter with arterial blood pressure and incident hypertension.

BACKGROUND: Long-term exposure to fine particulate matter (PM2.5) may lead to increased blood pressure (BP). The role of industry- and traffic-specific PM2.5 remains unclear. OBJECTIVE: We investigated the associations of residential long-term source-specific PM2.5 exposure with arterial BP and incident hypertension in the population-based Heinz Nixdorf Recall cohort study. METHODS: We defined hypertension as systolic BP≥140mmHg, or diastolic BP≥90mmHg, or current use of BP lowering medication. Long-term concentrations of PM2.5 from all local sources (PM2.5ALL), local industry (PM2.5IND) and traffic (PM2.5TRA) were modeled with a dispersion and chemistry transport model (EURAD-CTM) with a 1km(2) resolution. We performed a cross-sectional analysis with BP and prevalent hypertension at baseline, using linear and logistic regression, respectively, and a longitudinal analysis with incident hypertension at 5-year follow-up, using Poisson regression with robust variance estimation. We adjusted for age, sex, body mass index, lifestyle, education, and major road proximity. Change in BP (mmHg), odds ratio (OR) and relative risk (RR) for hypertension were calculated per 1µg/m(3) of exposure concentration. RESULTS: PM2.5ALL was highly correlated with PM2.5IND (Spearman's ρ=0.92) and moderately with PM2.5TRA (ρ=0.42). In adjusted cross-sectional analysis with 4539 participants, we found positive associations of PM2.5ALL with systolic (0.42 [95%-CI: 0.03, 0.80]) and diastolic (0.25 [0.04, 0.46]) BP. Higher, but less precise estimates were found for PM2.5IND (systolic: 0.55 [-0.05, 1.14]; diastolic: 0.35 [0.03, 0.67]) and PM2.5TRA (systolic: 0.88 [-1.55, 3.31]; diastolic: 0.41 [-0.91, 1.73]). We found crude positive association of PM2.5TRA with prevalence (OR 1.41 [1.10, 1.80]) and incidence of hypertension (RR 1.38 [1.03, 1.85]), attenuating after adjustment (OR 1.19 [0.90, 1.58] and RR 1.28 [0.94, 1.72]). We found no association of PM2.5ALL and PM2.5IND with hypertension. CONCLUSIONS: Long-term exposures to all-source and industry-specific PM2.5 were positively related to BP. We could not separate the effects of industry-specific PM2.5 from all-source PM2.5. Estimates with traffic-specific PM2.5 were generally higher but inconclusive.

Long-term residential exposure to urban air pollution, and repeated measures of systemic blood markers of inflammation and coagulation.

BACKGROUND: In several studies, exposure to fine particulate matter (PM) has been associated with inflammation, with inconsistent results. We used repeated measurements to examine the association of long-term fine and ultrafine particle exposure with several blood markers of inflammation and coagulation. METHODS: We used baseline (2000-2003) and follow-up (2006-2008) data from the Heinz Nixdorf Recall Study, a German population-based prospective cohort of 4814 participants. A chemistry transport model was applied to model daily surface concentrations of PM air pollutants (PM10, PM2.5) and particle number on a grid of 1 km(2). Applying mixed regression models, we analysed associations of long-term (mean of 365 days prior to blood draw) particle exposure at each participant's residence with the level of high-sensitivity C reactive protein (hs-CRP), fibrinogen, platelet and white cell count (WCC), adjusting for short-term PM exposure (moving averages of 1-7 days), personal characteristics, season, ambient temperature (1-5 days), ozone and time trend. RESULTS: We analysed 6488 observations: 3275 participants with baseline data and 3213 with follow-up data. An increase of 2.4 µg/m(3) in long-term PM2.5 was associated with an adjusted increase of 5.4% (95% CI 0.6% to 10.5%) in hs-CRP and of 2.3% (95% CI 1.4% to 3.3%) in the platelet count. Fibrinogen and WCC were not associated with long-term particle exposure. CONCLUSIONS: In this population-based cohort, we found associations of long-term exposure to PM with markers of inflammation (hs-CRP) and coagulation (platelets). This finding supports the hypothesis that inflammatory processes might contribute to chronic effects of air pollution on cardiovascular disease.

Long-term exposure to fine particulate matter and incidence of type 2 diabetes mellitus in a cohort study: effects of total and traffic-specific air pollution.

BACKGROUND: Studies investigating the link between long-term exposure to air pollution and incidence of diabetes are still scarce and results are inconsistent, possibly due to different compositions of the particle mixture. We investigate the long-term effect of traffic-specific and total particulate matter (PM) and road proximity on cumulative incidence of diabetes mellitus (mainly type 2) in a large German cohort. METHODS: We followed prospectively 3607 individuals without diabetes at baseline (2000-2003) from the Heinz Nixdorf Recall Study in Germany (mean follow-up time 5.1 years). Mean annual exposures to total as well as traffic-specific PM10 and PM2.5 at residence were estimated using a chemistry transport model (EURAD, 1 km(2) resolution). Effect estimates for an increase of 1 µg/m(3) in PM were obtained with Poisson regression adjusting for sex, age, body mass index, lifestyle factors, area-level and individual-level socio-economic status, and city. RESULTS: 331 incident cases developed. Adjusted RRs for total PM10 and PM2.5 were 1.05 (95%-CI: 1.00;1.10) and 1.03 (95%-CI: 0.95;1.12), respectively. Markedly higher point estimates were found for local traffic-specific PM with RRs of 1.36 (95%-CI: 0.98;1.89) for PM10 and 1.36 (95%-CI: 0.97;1.89) for PM2.5. Individuals living closer than 100 m to a busy road had a more than 30% higher risk (1.37;95%-CI: 1.04;1.81) than those living further than 200 m away. CONCLUSIONS: Long-term exposure to total PM increases type two diabetes risk in the general population, as does living close to a major road. Local traffic-specific PM was related to higher risks for type two diabetes than total PM.

Association between source-specific particulate matter air pollution and hs-CRP: local traffic and industrial emissions.

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-µg/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-µg/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.

Are air pollution and traffic noise independently associated with atherosclerosis: the Heinz Nixdorf Recall Study.

AIMS: Living close to high traffic has been linked to subclinical atherosclerosis, however it is not clear, whether fine particulate matter (PM) air pollution or noise, two important traffic-related exposures, are responsible for the association. We investigate the independent associations of long-term exposure to fine PM and road traffic noise with thoracic aortic calcification (TAC), a reliable measure of subclinical atherosclerosis. METHODS AND RESULTS: We used baseline data (2000-2003) from the German Heinz Nixdorf Recall Study, a population-based cohort of 4814 randomly selected participants. We assessed residential long-term exposure to PM with a chemistry transport model, and to road traffic noise using façade levels from noise models as weighted 24 h mean noise (Lden) and night-time noise (Lnight). Thoracic aortic calcification was quantified from non-contrast enhanced electron beam computed tomography. We used multiple linear regression to estimate associations of environmental exposures with ln(TAC+1), adjusting for each other, individual, and neighbourhood characteristics. In 4238 participants (mean age 60 years, 49.9% male), PM2.5 (aerodynamic diameter ≤2.5 µm) and Lnight are both associated with an increasing TAC-burden of 18.1% (95% CI: 6.6; 30.9%) per 2.4 µg/m(3) PM2.5 and 3.9% (95% CI 0.0; 8.0%) per 5dB(A) Lnight, respectively, in the full model and after mutual adjustment. We did not observe effect measure modification of the PM2.5 association by Lnight or vice versa. CONCLUSION: Long-term exposure to fine PM and night-time traffic noise are both independently associated with subclinical atherosclerosis and may both contribute to the association of traffic proximity with atherosclerosis.

Long-term urban particulate air pollution, traffic noise, and arterial blood pressure.

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 µm (PM(2.5)) and ≤ 10 µm (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 µg/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.

Urban particulate matter air pollution is associated with subclinical atherosclerosis: results from the HNR (Heinz Nixdorf Recall) study.

OBJECTIVES: The aim of this study was to investigate the association of long-term residential exposure to fine particles with carotid intima-media thickness (CIMT). BACKGROUND: Experimental and epidemiological evidence suggest that long-term exposure to air pollution might have a causal role in atherogenesis, but epidemiological findings are still inconsistent. We investigate whether urban particulate matter (PM) air pollution is associated with CIMT, a marker of subclinical atherosclerosis. METHODS: We used baseline data (2000 to 2003) from the HNR (Heinz Nixdorf Recall) study, a population-based cohort of 4,814 participants, 45 to 75 years of age. We assessed residential long-term exposure to PM with a chemistry transport model and measured distance to high traffic. Multiple linear regression was used to estimate associations of air pollutants and traffic with CIMT, adjusting for each other, city of residence, age, sex, diabetes, and lifestyle variables. RESULTS: Median CIMT of the 3,380 analyzed participants was 0.66 mm (interquartile range 0.16 mm). An interdecile range increase in PM(2.5) (4.2 µg/m(3)), PM(10) (6.7 µg/m(3)), and distance to high traffic (1,939 m) was associated with a 4.3% (95% confidence interval [CI]: 1.9% to 6.7%), 1.7% (95% CI: -0.7% to 4.1%), and 1.2% (95% CI: -0.2% to 2.6%) increase in CIMT, respectively. CONCLUSIONS: Our study shows a clear association of long-term exposure to PM(2.5) with atherosclerosis. This finding strengthens the hypothesized role of PM(2.5) as a risk factor for atherogenesis.

Influence of short-term exposure to ultrafine and fine particles on systemic inflammation.

Daily to monthly variations in fine particulate matter have been linked to systemic inflammatory responses. It has been hypothesized that smaller particles resulting from combustion processes confer higher toxicity. We aim to analyze the association between short-term exposure to ultrafine and fine particles and systemic inflammation. We use baseline data (2000-2003) of the Heinz Nixdorf Recall Study, a population-based cohort study of 4,814 participants in the Ruhr Area in Germany. A chemistry transport model was applied to model daily surface concentrations of particulate air pollutants on a grid of 1 km(2). Exposure included particle number (PN) and particulate matter mass concentration with an aerodynamic diameter < or = 2.5 microm (PM(2.5)) and < or = 10 microm (PM(10)). Generalized additive models were used to explore the relation of air pollutants using single day lags and averaging times of up to 28 days with high-sensitivity C-reactive protein (hs-CRP). We adjusted for meteorology, season, time trend, and personal characteristics. Median hs-CRP level in the 3,999 included participants was 1.5 mg/l. Median daily concentration of PN was 8,414 x 10(4)/ml (IQR 4,580 x 10(4)/ml), of PM(2.5) 14.5 microg/m(3) (IQR 11.5 microg/m(3)) and of PM(10) 18.5 microg/m(3) (IQR 13.9 microg/m(3)). A positive association between PN and hs-CRP could be observed only for single day lags and for averaged PN concentrations with higher estimates for longer averaging times. The highest hs-CRP-increase of 7.1% (95%-CI: 1.9, 12.6%) was found for the 21-day average. These results support the hypothesis that short-term exposure to traffic-related particles might lead to detrimental cardiovascular health effects via an inflammatory mechanism.