Ute Kraus

Associations between ambient air pollution and blood markers of inflammation and coagulation/fibrinolysis in susceptible populations

The pathophysiological pathways linking particulate air pollution to cardiovascular disease are still not fully understood. We examined the association between ambient air pollutants and blood markers of inflammation and coagulation/fibrinolysis in three potentially susceptible populations. Three panels of non-smoking individuals were examined between 3/2007 and 12/2008: 1) with type 2 diabetes mellitus (T2D, n=83), 2) with impaired glucose tolerance (IGT, n=104), and 3) with a potential genetic predisposition which could affect detoxifying and inflammatory pathways (n=87) defined by the null polymorphism for glutathione S-transferase M1 (GSTM1) in combination with a certain single nucleotide polymorphism on the C-reactive protein (CRP) or the fibrinogen gene. Study participants had blood drawn up to seven times every four to six weeks. In total, 1765 blood samples were analysed for CRP, interleukin (IL)-6, soluble CD40 ligand (sCD40L), fibrinogen, myeloperoxidase (MPO), and plasminogen activator inhibitor-1 (PAI-1). Hourly mean values of particulate air pollutants, particle number concentrations in different size ranges and gaseous pollutants were collected at fixed monitoring sites and individual 24hour averages calculated. Associations between air pollutants and blood markers were analysed for each panel separately and taking the T2D panel and the IGT panel together, using additive mixed models adjusted for long-term time trend and meteorology. For the panel with potential genetic susceptibility, CRP and MPO increased for most lags, especially with the 5-day average exposure (% change of geometric mean and 95% confidence interval: 22.9% [12.0;34.7] for CRP and 5.0% [0.3;9.9] for MPO per interquartile range of PM2.5). Small positive associations were seen for fibrinogen while sCD40L, PAI-1 and IL-6 mostly decreased in association with air pollution concentrations. Except for positive associations for fibrinogen we did not see significant results with the two other panels. Participants with potential genetic susceptibility showed a clear association between inflammatory blood biomarkers and ambient air pollutants. Our results support the hypothesis that air pollution increases systemic inflammation especially in susceptible populations which may aggravate atherosclerotic diseases and induce multi-organ damage.

Individual Daytime Noise Exposure during Routine Activities and Heart Rate Variability in Adults: A Repeated Measures Study

Background: Epidemiological studies have demonstrated associations between noise exposure and cardiovascular events. However, there have been few studies of possible underlying mechanisms. Objectives: We examined the association between individual daytime noise exposure and heart rate variability (HRV). Methods: In a prospective panel study in Augsburg, Germany (March 2007–December 2008), 110 individuals participated in 326 electrocardiogram recordings with a mean duration of 6 hr. Five-minute averages of heart rate (HR) and HRV parameters were determined. Individual noise exposure was measured as A-weighted equivalent continuous sound pressure levels (Leq). Effects were estimated using additive mixed models adjusted for long- and short-term time trends and physical activity. Due to nonlinear exposure–response functions, we performed piecewise linear analyses with a cut-off point at 65 dB(A). Results: Concurrent increases of 5dB(A) in Leq < 65dB(A) were associated with increases in HR (percent change of mean value: 1.48%; 95% CI: 1.37, 1.60%) and the ratio of low-frequency (LF) to high-frequency (HF) power (4.89%; 95% CI: 3.48, 6.32%), and with decreases in LF (–3.77%; 95% CI: –5.49, –2.02%) and HF (–8.56%; 95% CI: –10.31, –6.78%) power. Standard deviation of normal-to-normal intervals (SDNN) was positively associated with concurrent noise < 65dB(A) (5.74%; 95% CI: 5.13, 6.36) but negatively associated with noise lagged by 5–15 min (–0.53% to –0.69%). Associations with cardiac function were less pronounced for noise ≥ 65dB(A), with some in opposite directions from associations with noise < 65dB(A). Concurrent associations were modified by sex and age. Conclusions: Individual daytime noise exposure was associated with immediate changes in HRV, suggesting a possible mechanism linking noise to cardiovascular risk. Noise at lower levels may have health consequences beyond those resulting from “fight-or-flight” responses to high levels of noise.

Short-term effects of air temperature on blood markers of coagulation and inflammation in potentially susceptible individuals

Objectives Changes in air temperature are associated with an increase in cardiovascular events, but the role of procoagulant and proinflammatory blood markers is still poorly understood. The authors investigated the association between air temperature and fibrinogen, plasminogen activator inhibitor type 1, interleukin-6 and high-sensitivity C reactive protein in two potentially susceptible groups. Methods This prospective panel study was conducted between March 2007 and December 2008 in Augsburg, Germany. The study population comprised 187 participants with type 2 diabetes mellitus or impaired glucose tolerance and 87 participants with genetic polymorphisms on the detoxification and inflammation pathways. Overall, 1766 repeated blood measurements were collected. Hourly meteorology data were available from a central measurement site. The association between temperature and blood markers was analysed with additive mixed models. Results For type 2 diabetes mellitus and impaired glucose tolerance participants, the authors observed immediate, lagged and cumulative increases in fibrinogen (range of percentage changes in geometric mean: 0.6%–0.8%) and plasminogen activator inhibitor type 1 (6.0%–10.1%) in association with a 5°C temperature decrement. Participants with a body mass index above 30 kg/m2 as well as females showed particularly strong fibrinogen effects. In participants with the special genetic background, 5°C decreases in the 5-day average of temperature led to a change of 8.0% (95% CI 0.5% to 16.2%) in interleukin-6 and of −8.4% (95% CI −15.8% to −0.3%) in high-sensitivity C reactive protein, the latter driven by physically active individuals. Conclusions The authors observed different temperature effects on blood markers in two potentially susceptible groups probably indicating varying underlying biological mechanisms. This study results might provide a link between temperature and cardiovascular events.

Acute air pollution effects on heart rate variability are modified by SNPs involved in cardiac rhythm in individuals with diabetes or impaired glucose tolerance.

BACKGROUND Epidemiological studies have shown associations between particulate matter (PM) and heart rate variability (HRV). OBJECTIVES We investigated the effects of air pollution on the root mean square of successive differences (RMSSD) and the standard deviation of normal-to-normal intervals (SDNN) and effect modifications by single nucleotide polymorphisms (SNP). METHODS Between March 2007 and December 2008 207 ECG recordings comprising 1153 1 h-intervals were measured in 61 individuals with type 2 diabetes or impaired glucose tolerance (IGT) from Augsburg, Germany. Associations between 1 h-averages of air pollutants (PM, sulphate, black carbon, and ultrafine particles) and ECG parameters were analyzed using additive mixed models. Genotypes of 139 SNPs supposed to be involved in cardiac rhythm were identified in the literature. Using regression trees for longitudinal data, SNPs associated with ECG parameters were determined and included as potential air pollution effect modifiers. RESULTS We observed concurrent and lagged decreases in SDNN by about 2-5% in association with all air pollutants, especially in participants with at least one minor allele of rs332229. Increases in PM<2.5 μm (PM(2.5)) were associated with 4 h-lagged decreases of -6.6% [95%-confidence interval:-10.6;-2.6%] and -13.0% [-20.7;-5.1%] in SDNN in individuals with one or two minor alleles. We observed a -7.2% [-12.2;-1.8%] reduction in RMSSD associated with concurrent increases in PM(2.5.) Individuals with at least one minor allele of rs2096767 or at most one minor allele of rs2745967 exhibited stronger PM(2.5) effects. CONCLUSIONS We identified a genetic predisposition in persons with diabetes or IGT making them potentially more susceptible to air pollutants with regard to changes in HRV.

Particle-associated organic compounds and symptoms in myocardial infarction survivors

Context: The aerosol components responsible for the adverse health effects of the exposure to particulate matter (PM) have not been conclusively identified, and there is especially little information on the role of particulate organic compounds (POC). Objective: This study evaluated the role of PM and POC with regard to daily symptoms. Methods: One hundred and fifty-three myocardial infarction survivors from Augsburg, Germany, recorded daily occurrence of different symptoms in winter 2003/2004. Ambient concentrations of PM with a diameter <2.5 μm (PM2.5), particle number concentration (PNC), PM2.5-bound hopanes, and polycyclic aromatic hydrocarbons (PAH) were quantified. Data were analyzed using generalized estimating equations adjusting for meteorological and other time-variant confounders. Results: The odds for avoidance of physically demanding activities due to heart problems increased immediately associated with most POC measures (e.g. 5% per 1.08 ng/m3 increase in benzo[a]pyrene, 95%-confidence interval (CI):1–9%) and tended to a delayed decrease. After a 2-day delayed decrease associated with hopanes, the odds for shortness of breath increased consistently after 3 days with almost all POC measures (e.g. 4% per 0.21 ng/m3 increase in 17α(H), 21β(H)-hopane, CI: 1–8%). The odds for heart palpitations marginally increased immediately in association with PNC (8% per 8146 cm−3 increase in PNC, CI: 0–16%). Conclusions: The study showed an association between PM, particle-bound POC, and daily symptoms. The organic compounds may be causally related with cardiovascular health or act rather as indicators for traffic- and combustion-related particles.

Short-term effects of air temperature on blood pressure and pulse pressure in potentially susceptible individuals.

BACKGROUND Only few epidemiological studies have investigated the association between air temperature and blood pressure (BP) or pulse pressure (PP), with inconsistent findings. We examined whether short-term changes in air temperature were associated with changes in BP or PP in three different populations. METHODS Between March 2007 and December 2008, 371 systolic and diastolic BP measurements were collected in 30 individuals with type-2 diabetes mellitus (T2D), 30 persons with impaired glucose tolerance and 42 healthy individuals without a metabolic disorder from Augsburg, Germany. Hourly means of ambient meteorological data were obtained from a fixed measurement station. Personal temperature measurements were conducted using data loggers. Temperature effects were evaluated using additive mixed models adjusting for time trend and relative humidity. RESULTS Decreases in air temperature were associated with an increase in systolic BP, diastolic BP and PP in individuals with T2D. For example, a 1°C decrease in ambient temperature was associated with an immediate increase in systolic BP of 1.0 mmHg (95%-confidence interval: [0.5;1.4]mmHg). Effects of personally measured air temperature were similar. Temperature effects were modified by age, body mass index, gender, antihypertensive medication and whereabouts, such as being indoors. CONCLUSIONS We observed associations between decreases in air temperature and increases in BP as well as PP in persons with T2D indicating that these people might be potentially more susceptible to changes in air temperature. Our findings may provide a hypothesis for a mechanism between air temperature decreases and short-term increases of cardiovascular events.

Impact of personally measured pollutants on cardiac function

Epidemiological studies have shown associations between ambient air pollution and changes in heart rate variability (HRV). However, studies using personal air pollution measurements, especially with exposure averages <24h, are still rare. Between February and March 2008 HRV data as well as personal exposure to particulate matter <2.5μm (PM2.5), and particle number concentrations (PNC) were collected in five volunteers for up to 8.3h on a 5min resolution. Information about the participants whereabouts was also collected. Mixed models were used to analyze concurrent and up to 30min delayed effects of air pollutants as well as being in traffic on 5min-averages of heart rate (HR), high and low frequency power (HF and LF), standard deviation of all normal-to-normal intervals (SDNN), and the root mean square of successive interval differences (RMSSD). Results are presented as %-change from the mean per increase in interquartile range of air pollutant. In total, 474 5-min segments were available for analysis. We observed concurrent and delayed reductions in SDNN of about 0.8-1.0% in association with a 5.4μg/m(3) increase in PM2.5. However, being in traffic by car led to an increase of about 20% 10-14min and 15-19min later. An increase in PM2.5 or PNC was associated with lagged decreases for RMSSD and HF. We detected concurrent reductions in RMSSD (-17.6% [95%-confidence interval: 29.1; -4.3]) when being in traffic by bike/foot. Being in traffic by car was associated with an immediate reduction in LF while more delayed increases in LF were observed when being in traffic by bike/foot. Air pollution and traffic effects on HR were less consistent. These rapid changes in HRV within 30min might be mediated by the autonomic nervous system in response to direct reflexes from receptors in the lungs.

Association of novel metrics of particulate matter with vascular markers of inflammation and coagulation in susceptible populations -results from a panel study.

BACKGROUND AND AIMS Epidemiological studies have shown adverse effects of ambient air pollutants on health with inflammation and oxidative stress playing an important role. We examine the association between blood biomarkers of inflammation and coagulation and physical attributes of particulate matter which are not routinely measured such as particle length or surface area concentration and apparent density of PM. METHODS Between 3/2007 and 12/2008 187 non-smoking individuals with type 2 diabetes mellitus (T2D) or impaired glucose tolerance (IGT) were examined within the framework of the KORA Study in Augsburg, Germany. In addition, we selected 87 participants with a potential genetic predisposition on detoxifying and inflammatory pathways. This was defined by the null polymorphism for glutathione S-transferase M1 in combination with a certain single nucleotide polymorphism on the C-reactive protein (CRP) gene (rs1205) or the fibrinogen gene (rs1800790). Participants had blood drawn up to seven different times, resulting in 1765 blood samples. Air pollutants were collected at a central measurement station and individual 24-h averages calculated. Associations between air pollutants and high sensitivity CRP, myeloperoxidase (MPO), interleukin (IL)-6 and fibrinogen were analysed using additive mixed models. RESULTS For the panel with genetic susceptibility, increases were seen for CRP and MPO with most attributes, specifically particle length and active surface concentration. The %change of geometric mean and 95% confidence intervals for the 5-day average exposure for CRP and MPO were 34.6% [21.8;48.8] and 8.3% [3.2;13.6] per interquartile range increase of particle length concentration and 29.8% [15.9;45.3] and 10.4 [4.4;16.7] for active surface area. Results for the panel of T2D and IGT and the other blood biomarkers were less conclusive. CONCLUSIONS Particle length concentration and active surface concentration showed strong positive associations with blood biomarkers reflecting inflammation. These air pollution metrics might reflect harmful aerosol properties better than particulate mass or number concentration. They might therefore be important for epidemiological studies.

Individual daytime noise exposure in different microenvironments

BACKGROUND Numerous studies showed that chronic noise exposure modeled through noise mapping is associated with adverse health effects. However, knowledge about real individual noise exposure, emitted by several sources, is limited. OBJECTIVES To explain the variation in individual daytime noise exposure regarding different microenvironments, activities and individual characteristics. MATERIALS AND METHODS In a repeated measures study in Augsburg, Germany (March 2007-December 2008), 109 individuals participated in 305 individual noise measurements with a mean duration of 5.5h. Whereabouts and activities were recorded in a diary. One-minute averages of A-weighted equivalent continuous sound pressure levels (Leq) were determined. We used mixed additive models to elucidate the variation of Leq by diary-based information, baseline characteristics and time-invariant variables like long-term noise exposure. RESULTS Overall noise levels were highly variable (median: 64 dB(A); range: 37-105 dB(A)). Highest noise levels were measured in traffic during bicycling (69 dB(A); 49-97 dB(A)) and lowest while resting at home (54 dB(A); 37-94 dB(A)). Nearly all diary-based information as well as physical activity, sex and age-group had significant influences on individual noise. In an additional analysis restricted to times spent at the residences, long-term noise exposure did not improve the model fit. CONCLUSIONS Individual exposures to day-time noise were moderate to high and showed high variations in different microenvironments except when being in traffic. Individual noise levels were greatly determined by personal activities but also seemed to depend on environmental noise levels.

OP IX – 4 Quantification of environmental burden of disease related to nitrogen dioxide exposure in germany

Background/aim Epidemiological studies have shown associations of nitrogen dioxide (NO2) with numerous health outcomes. EU-wide air quality limit values for NO2 are in place but regularly exceeded at measuring stations near roads in Germany. Therefore, a health risk assessment for the NO2-exposure of the German population was conducted. Methods For 2007 up to 2014, maps of the annual spatial 1*1 km2 distribution of a population-weighted NO2 concentration indicator were calculated based on assimilated modelling data of background NO2 within a 7*8 km2 grid and population density within a 250*250 m2 grid. For three model regions a small scale assessment of the NO2 exposure was achieved by considering concentrations in the higher resolved urban background as well as close to highly polluted street sections. A systematic literature search of epidemiological studies was performed to ascertain the current evidence on long-term health effects of NO2 and to identify exposure-response-functions transferrable to Germany. The Environmental Burden of Disease-concept was applied to quantify the NO2-associated health risks for relevant outcomes. Results The yearly mean of background NO2 slightly decreased from 13 μg/m3 (range: 4.3 to 37.3 μg/m3) in 2007 to 11.8 μg/m3 (3.4 to 32.7 μg/m3) in 2014. Using a counterfactual value of 10 µg/m3, 5966 (95%-confidence interval: 2031 to 9,893) premature deaths and 49,726 (16,929 to 82,456) Years of Live Lost (YLL) due to cardiovascular mortality attributable to NO2 long-term exposure were estimated for the year 2014. Between 2007 and 2014 an overall slightly decreasing trend was observed for attributable premature deaths. The higher resolution of NO2-concentration for the three model regions led to a substantial increase in the estimated number of premature deaths due to cardiovascular disease by 40% to 165%. Conclusion The present estimates are based on NO2 concentrations reflecting background exposure and thus underestimate the burden of disease. A better accuracy of the NO2 exposure estimation accounting for the higher concentrations in urban areas close to traffic improves the burden of disease quantification and may enhance the distinction of health effects related to fine and ultrafine particles.