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Low Emission Zones (LEZs) were implemented as a measure for improving the quality of ambient air. As of February 2018, 58 LEZs were in operation in Germany; however they differ significantly, especially regarding their size.The effectiveness of LEZs has been investigated by dispersion modelling as well as by analysis of PM10 (particles which pass through a size-selective inlet with a 50 % efficiency cut-off at 10 μm aerodynamic diameter) and nitrogen dioxide (NO2) measurement values. Recent studies show a clear trend. In sufficiently large and strictly regulated LEZs, a reduction of PM10 concentration between 5 and 10% can be shown, and at some traffic sites above 10%. The current (currently valid) limit values for PM10 were introduced in 2005, mainly due to the adverse health effects of fine particles on respiratory and cardiovascular morbidity and mortality. The most health-relevant PM10 particle fraction consists mainly of traffic-related particles and here especially of diesel soot particles. Therefore, the German regulations for LEZs promote using diesel particulate filters in diesel cars.Unfortunately, the evaluation of the LEZ effects is mostly restricted to PM10, a particle fraction containing only a comparatively small portion of highly toxic exhaust-related particles. The analysis of air pollutants that are more traffic specific (such as elemental carbon, ultrafine particles, PM2.5 [particles which pass through a size-selective inlet with a 50 % efficiency cut-off at 10 μm aerodynamic diameter]) would be more adequate. For "powerful" LEZs, more pronounced reductions of such pollutants have clearly been shown. This also means that the benefit of LEZs on human health is by far greater than is presently visible from routine measurements of PM10.Since the stickers for LEZs are in fact meant to reduce particulate matter, it is not surprising that the introduction of LEZs has not resulted in a demonstrable reduction in NO2 concentrations.

Our environment is a major factor in determining health and well-being throughout life, from conception into old age. This overview illustrates the most important epidemiological studies and health monitoring systems in Germany, which investigate environmental influences in various population subgroups and estimate related health effects. Environmental factors examined in each study are described. The mentioned studies in children and adults build the basis for predictions and preventive measures. The number of the assessed environmental factors, the depth of the examinations as well as the (phenotypical) characterization of the study participants differ. Still, the obtained data build a base for important future research. However, for this, a permanent and Germany-wide assessment of environmental factors is necessary.The proportion of the European population living in urban areas is projected to increase in the future. Therefore, environmental factors such as air pollution, air temperature, and noise, but also social inequality, are likely to have a negative effect on health and quality of life of the population. The challenge of the aging population as well as potential adaptation processes to the diverse environmental stimuli requires multidisciplinary approaches. From an environmental epidemiology view, the collected data from the described studies are of immense value because only with this data can associations between environment and health be investigated and public health-relevant preventive measures be identified.The NAKO health study will be the largest resource of health data and should therefore be included in future activities related to the investigation of environmental health effects in Germany.

Unsere Umwelt beeinflusst Gesundheit und Wohlbefinden des Menschen, von der Geburt bis ins hohe Alter. In diesem Überblick werden die wichtigsten epidemiologischen Studien und Gesundheitsmonitoringsysteme in Deutschland erläutert, die unter anderem auch Umwelteinflüsse in verschiedenen Bevölkerungsgruppen untersuchen und Gesundheitseffekte abschätzen. Die darin jeweils untersuchten Umweltfaktoren werden beschrieben. Diese Studien an Kindern und Erwachsenen schaffen eine Basis für Vorhersagen und präventive Maßnahmen. Die hohe Anzahl der erfassten umweltbezogenen Faktoren und die Intensität ihrer Untersuchung unterscheiden sich in den Studien, ebenso wie die (phänotypische) Charakterisierung der Studienteilnehmenden. Dennoch bilden die gewonnenen Daten eine Grundlage für die zukünftige Forschungsarbeit. Hierzu ist allerdings eine flächendeckende dauerhafte Erfassung der Daten zu den verschiedenen Umweltfaktoren notwendig. Da der Anteil der in städtischen Gebieten lebenden Bevölkerung in Zukunft weiter steigen wird, werden Umweltfaktoren wie Luftverschmutzung, Lufttemperatur, Lärm, aber auch soziale Ungerechtigkeit zukünftig die Gesundheit und Lebensqualität der Bevölkerung maßgeblich beeinflussen. Die Herausforderung einer alternden Gesellschaft, aber auch die mögliche Adaptation der Bevölkerung an diverse Umweltstimuli machen einen multidisziplinären Ansatz erforderlich. Gerade aus umweltepidemiologischer Sicht sind hier die gesammelten Daten der in diesem Artikel aufgezeigten Kohortenstudien in Deutschland ein wertvoller Schatz, denn nur damit können Zusammenhänge zwischen Umwelteinflüssen und Gesundheit erforscht und public-health-relevante präventive Maßnahmen identifiziert werden. Die NAKO-Gesundheitsstudie, die in den kommenden Jahrzehnten die größte verfügbare Ressource für Gesundheitsdaten sein wird, sollte in zukünftige Aktivitäten zur Erforschung von Umwelteinflüssen eingebunden werden., Our environment is a major factor in determining health and well-being throughout life, from conception into old age. This overview illustrates the most important epidemiological studies and health monitoring systems in Germany, which investigate environmental influences in various population subgroups and estimate related health effects. Environmental factors examined in each study are described. The mentioned studies in children and adults build the basis for predictions and preventive measures. The number of the assessed environmental factors, the depth of the examinations as well as the (phenotypical) characterization of the study participants differ. Still, the obtained data build a base for important future research. However, for this, a permanent and Germany-wide assessment of environmental factors is necessary. The proportion of the European population living in urban areas is projected to increase in the future. Therefore, environmental factors such as air pollution, air temperature, and noise, but also social inequality, are likely to have a negative effect on health and quality of life of the population. The challenge of the aging population as well as potential adaptation processes to the diverse environmental stimuli requires multidisciplinary approaches. From an environmental epidemiology view, the collected data from the described studies are of immense value because only with this data can associations between environment and health be investigated and public health-relevant preventive measures be identified. The NAKO health study will be the largest resource of health data and should therefore be included in future activities related to the investigation of environmental health effects in Germany.

Background/aim Long-term exposure to ambient air pollution contributes to the burden of disease and particularly affects cardiovascular (CV) causes of death. We investigated the association between particle number concentration (PNC), a marker for ultrafine particles (UFP), and other air pollutants and high sensitivity C-reactive protein (hs-CRP) as a potential link between air pollution and CV disease. Methods A cross-sectional analysis was performed on data of the second follow-up of the KORA S4 survey in Augsburg, Germany (2013–2014). Residential long-term exposure to PNC, particulate matter Results The results pointed to a positive association between PNC, PM10, PMcoarse, PM2.5abs, NO2 and NOx and hs-CRP. For PNC, an interquartile-range (IQR, 2000 particles/cm3) increase was associated with a 3.63% [95% confidence interval (CI): −0.86% to 8.33%] increase in hs-CRP. Effect estimates were higher for women, non-obese and participants without history of CVD. Effect modification was also seen for participants without diabetes with the highest effect estimate of 14.71% [95% CI: 5.47% to 24.77%] for an IQR increase of 2.1 µg/m³ in PM10. In two-pollutant models, adjustment for PM2.5 strengthened the effect estimates for PNC and PM10 (increase per IQR 6.31% [95% CI: 0.42% to 12.53%] and 7.34% [95%CI: 0.40% to 14.77%], respectively). Conclusion Our results highlight the role of UFP within the complex mixture of ambient air pollution and their inflammatory potential and help fill a research gap since studies on chronic exposure to ultrafine particles are still scarce.

Background/aim Exposure to outdoor air pollution has been associated with systemic inflammation but results have been inconsistent. Evidence for deleterious effects on glucose metabolism and insulin resistance is still limited. We investigated the association of long-term air pollution exposure on biomarkers of systemic inflammation, glycaemia, and insulin resistance measured up to three times. Methods We used baseline survey (1999–2001), first follow-up (2006–2008) and second follow-up (2013–2014) from the KORA study in Augsburg, Southern Germany. At each examination, we measured plasma high-sensitivity C-reactive protein (hsCRP), glycosylated haemoglobin (HbA1c) and homeostatic model assessment of insulin resistance (HOMA-IR) calculated from fasting glucose and insulin. We estimated residential long-term exposure to ultrafine particles (UFP), different size fractions of particulate matter, soot, nitrogen oxides and ozone by land use regression. Associations between annual pollutants and biomarkers were modelled using generalised estimating equations adjusting for socio-demographic, lifestyle and clinical covariates. Potential effect-modifiers were examined by use of interaction terms. Results We included 9590 observations from 4255 participants aged 25 to 75 years at baseline in the analyses. Air pollutant concentrations at the participants’ residences were well below the EU guidelines for regulated pollutants. Except for ozone, all pollutants were positively associated with at least one of the biomarkers. For UFP, the highest effect was seen for hsCRP with an increase of 3% (95% CI: 0.4 to 5.6) per 1900 particles/cm3 increase. Particulate matter between 2.5 and 10 µg/m³, soot and nitrogen dioxides were significantly associated with HbA1c and HOMA-IR. For the latter, effect estimates tended to be higher for males and elderly participants while this was not the case for the other two biomarkers. Conclusion The findings of this longitudinal study add to a scarce body of literature on cardiometabolic health effects in association with chronic exposure to air pollution and help to fill the existing research gap, especially with regard to the effects of ultrafine particles.

Background: Long-term exposure to ambient air pollution contributes to the global burden of disease by particularly affecting cardiovascular (CV) causes of death. We investigated the association between particle number concentration (PNC), a marker for ultrafine particles, and other air pollutants and high sensitivity C-reactive protein (hs-CRP) as a potential link between air pollution and CV disease.Methods: We cross-sectionally analysed data from the second follow up (2013 and 2014) of the German KORA baseline survey which was conducted in 1999-2001. Residential long-term exposure to PNC and various other size fractions of particulate matter (PM10 with size of < 10 mu m in aerodynamic diameter, PMcoarse, 2.5-10 mu m or PM2.5 < 2.5 mu m, respectively), soot (PM(2.5)abs: absorbance of PM2.5), nitrogen oxides (nitrogen dioxide NO2 or oxides NOx, respectively) and ozone (O-3) were estimated by land-use regression models. Associations between annual air pollution concentrations and hs-CRP were modeled in 2252 participants using linear regression models adjusted for several confounders. Potential effect-modifiers were examined by interaction terms and two pollutant models were calculated for pollutants with Spearman inter-correlation < 0.70.Results: Single pollutant models for PNC, PM10 PMcoarse, PM(2.5)abs, NO2 and NOx showed positive but nonsignificant associations with hs-CRP. For PNC, an interquartile range (2000 particles/cm(3)) increase was associated with a 3.6% (95% CI: -0.9%, 8.3%) increase in hs-CRP. A null association was found for PM2.5. Effect estimates were higher for women, non-obese participants, for participants without diabetes and without a history of cardiovascular disease whereas ex-smokers showed lower estimates compared to smokers or non-smokers. For O-3, the dose-response function suggested a non-linear relationship. In two-pollutant models, adjustment for PM2.5 strengthened the effect estimates for PNC and PM10 (6.3% increase per 2000 particles/cm(3) [95% CI: 0.4%; 12.5%] and 7.3% per 16.5 mu g/m(3) [95% CI: 0.4%; 14.8%], respectively).Conclusion: This study adds to a scarce but growing body of literature showing associations between long-term exposure to ultrafine particles and hs-CRP, one of the most intensely studied blood biomarkers for cardiovascular health. Our results highlight the role of ultrafine particles within the complex mixture of ambient air pollution and their inflammatory potential.

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 day-time 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 six hours. 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 non-linear 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

PURPOSE OF THE REVIEW: The purpose of this review is to highlight the latest developments in the field of weather and health with a focus on the elderly. The current state of knowledge is summarized and open questions and emerging fields of research are discussed. RECENT FINDINGS: It is expected that climate change will lead to higher global average surface temperatures and more extreme climatic conditions. Previous studies have shown that non-optimal temperatures are associated with increased morbidity and mortality, specifically in elderly people. Future research fields comprise e.g., synergistic effects between meteorological variables and air pollution; long-term impacts of temperature changes; novel unraveling the underlying pathways using blood biomarkers; the association between temperature and mental health; and urban planning and adaptation processes. Understanding the health impacts associated with changes in thermal conditions requires multidisciplinary approaches. Adaptation processes, as well as improvements in urban planning and warning systems, can help reduce the predicted burden of climate change, especially in the elderly.

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.

ACS,American Cancer Society;AD,Alzheimer’s disease;AMI,acute myocardial infarction;APHEA,air pollution and health effects—a European approach;APHENA,air pollution and health: a European and North A...

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).This study evaluated the role of PM and POC with regard to daily symptoms.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 diameter2.5 μm (PM(2.5)), particle number concentration (PNC), PM(2.5)-bound hopanes, and polycyclic aromatic hydrocarbons (PAH) were quantified. Data were analyzed using generalized estimating equations adjusting for meteorological and other time-variant confounders.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/m(3) 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/m(3) 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%).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.

Background: Increasing evidence suggests a proatherogenic role for lipoprotein-associated phospholipase A2 (Lp-PLA2). A meta-analysis of published cohorts has shown that Lp-PLA2 is an independent predictor of coronary heart disease events and stroke. Objective: In this study, we investigated whether the association between air pollution and cardiovascular disease might be partly explained by increased Lp-PLA2 mass in response to exposure. Methods: A prospective longitudinal study of 200 patients who had had a myocardial infarction was performed in Augsburg, Germany. Up to six repeated clinical examinations were scheduled every 4–6 weeks between May 2003 and March 2004. Supplementary to the multicenter AIRGENE protocol, we assessed repeated plasma Lp-PLA2 concentrations. Air pollution data from a fixed monitoring site representing urban background concentrations were collected. We measured hourly means of particle mass [particulate matter (PM) < 10 µm (PM10) and PM < 2.5 µm (PM2.5) in aerodynamic diameter] and particle number concentrations (PNCs), as well as the gaseous air pollutants carbon monoxide (CO), sulfur dioxide (SO2), ozone (O3), nitric oxide (NO), and nitrogen dioxide (NO2). Data were analyzed using mixed models with random patient effects. Results: Lp-PLA2 showed a positive association with PM10, PM2.5, and PNCs, as well as with CO, NO2, NO, and SO2 4–5 days before blood withdrawal (lag 4–5). A positive association with O3 was much more immediate (lag 0). However, inverse associations with some pollutants were evident at shorter time lags. Conclusion: These preliminary findings should be replicated in other study populations because they suggest that the accumulation of acute and subacute effects or the chronic exposure to ambient particulate and gaseous air pollution may result in the promotion of atherosclerosis, mediated, at least in part, by increased levels of Lp-PLA2.

Background: Among the numerous emerging biomarkers, high-sensitivity C-reactive protein (hsCRP) and interleukin-6 (IL-6) have received widespread interest, and a large database has been accumulated on their potential role as predictors of cardiovascular risk. The concentrations of inflammatory biomarkers, however, are influenced, among other things, by physiological variation, which is the natural within-individual variation occurring over time. Implementation of hsCRP and IL-6 measurement into clinical practice requires data on the reliability of such measurements. Methods: We serially measured hsCRP and IL-6 concentrations in up to 6 blood samples taken at monthly intervals from 200 post–myocardial infarction patients who participated in the AIRGENE study. Results: The mean (SD) of the ln-transformed plasma concentrations (in milligrams per liter for hsCRP and nanograms per liter for IL-6) for all participants over all samples was 0.16 (1.04) for hsCRP and 0.76 (0.57) for IL-6, with no significant differences between men and women. The within-individual and analytical variance component for the ln-transformed hsCRP data was 0.37, and the between-individual variance component was 0.73. For the ln-transformed IL-6 data, these values were 0.11 and 0.22, respectively. A substantial part of the total variation in plasma hsCRP and IL-6 concentrations was explained by the between-individual variation (as a percentage of the total variance, 66.1% for the ln-transformed hsCRP data and 66.2% for the ln-transformed IL-6 data). For both markers, 2 measurements were needed to reach a sufficient reliability. Conclusions: Our results demonstrate considerable stability and good reproducibility for serial hsCRP and IL-6 measurements. Thus, there should be no major concern about misclassification in clinical practice if at least 2 subsequent measurements are taken.

Epidemiologic studies report associations between particulate air pollution and increased mortality from pulmonary diseases. This study was performed to examine whether the exposure to ambient gaseous and particulate air pollution leads to an alteration of the differential white blood cell count in patients with chronic pulmonary diseases like chronic bronchitis, chronic obstructive pulmonary disease, and asthma. A prospective panel study was conducted in Erfurt, Eastern Germany, with 12 repeated differential white blood cell counts in 38 males with chronic pulmonary diseases. Hourly particulate and gaseous air pollutants and meteorological data were acquired. Mixed models with a random intercept adjusting for trend, meteorology, weekday, and other risk variables were used. In this explorative analysis, we found an immediate decrease of polymorphonuclear leukocytes in response to an increase of most gaseous and particulate pollutants. Lymphocytes increased within 24 h in association with all gaseous pollutants but showed only minor effects in regard to particulate air pollution. Monocytes showed an increase associated with ultrafine particles, and nitrogen monoxide. The effect had two peaks in time, one 0-23 h before blood withdrawal and a second one with a time lag of 48-71 h. The increase of particulate and gaseous air pollution was associated with multiple changes in the differential white blood cell count in patients with chronic pulmonary diseases.

Given the accumulating evidence that people with underlying heart disease are a particularly vulnerable group for triggers like changing meteorological parameters, the objective of this longitudinal study was to analyze the influence of weather parameters on blood pressure, arrhythmia and ischemia in cardiovascular patients. A panel study with repeated measurements was conducted in a rehabilitation clinic in Timmendorfer Strand (Baltic Sea, Germany) with 872 cardiovascular patients. Heart rate, blood pressure and electrocardiography changes were measured during repeated bicycle ergometries. Generalized Estimating Equations were used for regression analyses of immediate, delayed and cumulative influences of the daily measured meteorological data. For men, a decrease in air temperature and in water vapor pressure doubled the risk of ST-segment depression during ergometry [odds ratio (OR) for 1 day delay: 1.88 (1.24; 2.83) for air temperature] with a delay of 1-2 days. For women, an increase of their heart rate before the start of the ergometry [same day: 4.36 beats/min (0.99; 7.74) for air temperature] and a 2- to 3-fold higher risk for ventricular ectopic beats [1 day delay: OR 2.43 (1.17; 5.05) for air temperature] was observed with an increase in temperature and water vapor pressure in almost all analyzed time-windows. The study indicates that meteorological parameters can induce changes in heart function which may lead to adverse cardiovascular events especially in susceptible, diseased individuals. The observed effect on ST-segment depression could be a link between the association of weather changes and cardiovascular morbidity and mortality.

Background: Of the numerous emerging biomarkers for coronary heart disease (CHD), lipoprotein-associated phospholipase A2 (Lp-PLA2), an enzyme involved in lipid metabolism and inflammatory pathways, seems to be a promising candidate. Implementation of Lp-PLA2 measurement into clinical practice, however, requires data on the reliability of such measurements. Methods: We measured Lp-PLA2 concentrations by ELISA in blood samples drawn from 200 post–myocardial infarction patients (39–76 years) at 6 monthly intervals between May 2003 and February 2004, for a total of 1143 samples. We estimated analytical, within-individual, and between-individual variation, the critical difference, and the intraclass correlation coefficient of reliability (ICC) to assess the reliability of serial Lp-PLA2 measurements. Results: The mean (SD) plasma Lp-PLA2 concentration for the study participants was 188.7 (41.8) μg/L, with no significant difference between men and women. The analytical CV for Lp-PLA2 was 4.4%, the within-individual biological CV was 15%, and the between-individual CV was 22%. The ICC was 0.66. An important part of the total variation in plasma Lp-PLA2 concentration was explained by the between-individual variation (as a percentage of the total variance, 66.1%), whereas the within-individual variance was 31.3%. The analytical variance was as low as 2.6%. Conclusions: Between-individual variation in Lp-PLA2 concentration was substantially greater than within-individual variation. In general, our data demonstrate considerable stability and good reproducibility of serial Lp-PLA2 measurements, results that compared favorably with those for the more commonly measured lipid markers.

Ambient particulate air pollution has been associated with altered cardiac function and systemic inflammation. We reported repolarization changes and variations in markers of inflammation in association with ambient particulate exposure in a panel of male coronary artery disease (CAD) patients. The objective of this analysis was to identify the specific sources associated with these effects. A panel of male CAD patients participated in 12 clinical visits in Erfurt, Germany. We used 56 patients’ 5 min ECG recordings for the analysis of repolarization parameters QT interval and T wave amplitude, and 57 patients’ plasma samples to determine the biomarkers von Willebrand factor (vWF) and C-reactive protein (CRP). Linear and logistic regression models were used to analyze the associations between five particle source factors (airborne soil, local traffic-related ultrafine particles, combustion-generated aerosols, diesel traffic-related particles, and secondary aerosols) and these health parameters adjusting for trend, weekday and meteorological variables. An increase in QT interval and a decrease in T wave amplitude were observed in association with traffic-related particles exposure during 0–23 h before the ECG recordings. The inflammatory marker vWF increased in association with both traffic-related particles and combustion-generated aerosols at different exposure lags. All source particles had positive associations with CRP levels above the 90th percentile (8.5 mg/l). These results suggest that traffic-related and combustion-generated particles show stronger adverse health impact with regard to cardiac effects, and that particles from different sources induce an acute phase response in these patients.

Ambient air pollution has been associated with an increased risk of hospital admission and mortality in potentially susceptible subpopulations, including myocardial infarction (MI) survivors. The multicenter epidemiological study described in this report was set up to study the role of air pollution in eliciting inflammation in MI survivors in six European cities, Helsinki, Stockholm, Augsburg, Rome, Barcelona, and Athens. Outcomes of interest are plasma concentrations of the proinflammatory cytokine interleukin 6 (IL-6) and the acute-phase proteins C-reactive protein (CRP) and fibrinogen. In addition, the study was designed to assess the role of candidate gene polymorphisms hypothesized to lead to a modification of the short-term effects of ambient air pollution. In total, 1003 MI survivors were recruited and assessed with at least 2 repeated clinic visits without any signs of infections. In total, 5813 blood samples were collected, equivalent to an average of 5.8 repeated clinic visits per subject (97% of the scheduled 6 repeated visits). Subjects across the six cities varied with respect to risk factor profiles. Most of the subjects were nonsmokers, but light smokers were included in Rome, Barcelona, and Athens. Substantial inter- and intraindividual variability was observed for IL-6 and CRP. The study will permit assessing the role of cardiovascular disease risk factors, including ambient air pollution and genetic polymorphisms in candidate genes, in determining the inter- and the intraindividual variability in plasma IL-6, CRP, and fibrinogen concentrations in MI survivors.

Background: Few studies have investigated the impact of air temperature on blood pressure (BP) and endothelial function. We examined short-term effects of air temperature on BP and endothelial func...

The authors conducted an investigation of the association between air pollution and arrhythmia.A prospective panel study (October 2000-April 2001) was conducted in Erfurt, Germany. Fifty-seven men with coronary heart disease were subjected to six 24-hour electrocardiogram recordings. Runs of supraventricular and ventricular tachycardia were associated with continuous ultrafine particle counts (UFP), accumulation mode particle counts (ACP), PM2.5, and gaseous pollutants. Poisson and linear regression models were applied adjusting for trend, weekday, and meteorologic data.Elevated concentrations of UFP, ACP, PM2.5, and nitrogen dioxide increased the risk for supraventricular runs and the number of ventricular runs at almost all lags. Statistically significant associations were found predominantly in the previous 24 to 71 hours and with the 5-day moving average.Elevated concentrations of fine and ultrafine particle increased the risk of arrhythmia in men with coronary heart disease.

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 24 hour 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. Keywords: Air pollution, Inflammation, Diabetes, CRP, GSTM1, Coagulation

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.

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%e0.8%) and plasminogen activator inhibitor type 1 (6.0%e10.1%) in association with a 58C temperature decrement. Participants with a body mass index above 30 kg/m 2 as well as females showed particularly strong fibrinogen effects. In participants with the special genetic background, 58C 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.

SummaryElevated fibrinogen levels are strongly and consistently associated with incident coronary heart disease (CHD). A possible causal contribution of fibrinogen in the pathway leading to atherothrombotic cardiovascular disease complications has been suggested. However, for implementation in clinical practice, data on validity and reliability, which are still scarce, are needed that are still scarce, especially in subjects with a history of CHD. For the present study, levels of plasma fibrinogen were measured in 200 post-myocardial infarction (post-MI) patients aged 39–76 years, with approximately six blood samples collected at monthly intervals between May 2003 and March 2004, giving a total of 1,144 samples. Inter-individual variability (between-subject variance component, VCb and coefficient of variation, CVb), intra-individual and analytical variability (VCw+a and CVw+a), intraclass correlation coefficient (ICC) and the number of measurements required for an ICC of 0.75 were estimated to assess the reliability of serial fibrinogen measurements. Mean fibrinogen concentration of all subjects over all samples was 3.34 g/l (standard deviation 0.67). Between-subject variation for fibrinogen was VCb = 0.34 (CVb,=17.5%) whereas within-subject and analytical variation was estimated as VCw+a = 0.14 (CVw+a=11.0%). The variation was mainly explained by between-subject variability, shown by the proportion of total variance of 71.3%. Two different measurements were required to reach sufficient reliability, if subjects with extreme values were not excluded. The present study indicates a fairly good reproducibility of serial individual fibrinogen measurements in post-MI subjects.

Background and Aims: The pathophysiological pathways linking particulate air pollution to cardiovascular disease are still not fully understood. We examined the association between ambient air poll...

The aim of environmental epidemiology is to detect a possible risk or to investigate the exposure-response relation with time, duration, location and amount of exposure being the major determinants for that relationship. The assessment of health effects in environmental epidemiology can for example be done by using routine data such as emergency room visits or death certificates. It is very well known that the health of a population is very dependent on a stable and functioning ecosystem. Air as well as climate has a major impact on the function and procedures within the ecosystem.

Background and Objective Exposure to ambient particles has been shown to be responsible for cardiovascular effects, especially in elderly with cardiovascular disease. The study assessed the association between deceleration capacity (DC) as well as heart rate variability (HRV) and ambient particulate matter (PM) in patients with coronary artery disease (CAD). Methods A prospective study with up to 12 repeated measurements was conducted in Erfurt, Germany, between October 2000 and April 2001 in 56 patients with physician-diagnosed ischemic heart disease, stable angina pectoris or prior myocardial infarction at an age of at least 50 years. Twenty-minute ECG recordings were obtained every two weeks and 24-hour ECG recordings every four weeks. Exposure to PM (size range from 10 nm to 2.5 μm), and elemental (EC) and organic (OC) carbon was measured. Additive mixed models were used to analyze the association between PM and ECG recordings. Results The short-term recordings showed decrements in the high-frequency component of HRV as well as in RMSSD (root-mean-square of successive differences of NN intervals) in association with increments in EC and OC 0-23 hours prior to the recordings. The long-term recordings revealed decreased RMSSD and pNN50 (% of adjacent NN intervals that differed more than 50 ms) in association with EC and OC 24-47 hours prior to the recordings. In addition, highly significant effects were found for DC which decreased in association with PM2.5, EC and OC concurrent with the ECG recordings as well as with a lag of up to 47 hours. Conclusions The analysis showed significant effects of ambient particulate air pollution on DC and HRV parameters reflecting parasympathetic modulation of the heart in patients with CAD. An air pollution-related decrease in parasympathetic tone as well as impaired heart rate deceleration capacity may contribute to an increased risk for cardiac morbidity and sudden cardiac death in vulnerable populations.

Background and Objective Air temperature changes are associated with increased cardiovascular and respiratory risk, but the roles of inflammatory and coagulation markers are not well understood. We investigated the associations between temperature and several blood markers in patients with coronary heart disease (CHD) and pulmonary disease (PD). Methods Two studies were conducted in Erfurt, Germany, over two successive winters. 578 and 381 repeated blood measurements were collected from 57 CHD and 38 PD patients, respectively. Data on patient characteristics and disease history were gathered at baseline. Meteorological data were collected from existing networks. Associations were analysed using additive mixed models with random patient effects. Effect modification by diabetes status was investigated only in CHD patients, as only two PD patients had diabetes. Results Mean daily air temperature varied between � 138C and 168C in both study periods. A 108C decrease in the 5-day temperature average before blood withdrawal led to an increase in platelet counts (% change from the mean: 3.0%, 95% CI 0.6% to 5.5%) and fibrinogen (5.5%, 1.3% to 9.7%), no change in C-reactive protein in PD patients, and a decrease in C-reactive protein in CHD patients. A 2-day delayed increase in factor VII associated with temperature decrease was seen in CHD patients (4.9%; 0.7% to 9.2%), while PD patients showed no effect. ‘Effects in CHD patients without diabetes’ into ‘Effects on factor VII in CHD patients without diabetes’. Conclusions This study suggests that temperature decrease is associated with change in several blood parameters. The complex interplay of blood markers at low temperature may contribute to the observed association between cold and cardiovascular mortality and morbidity.

Background Growing evidence indicates that ambient air pollution is associated with exacerbation of chronic diseases like chronic pulmonary disease. A prospective panel study was conducted to investigate short-term changes of blood markers of inflammation and coagulation in response to daily changes in air pollution in Erfurt, Germany. 12 clinical visits were scheduled and blood parameters were measured in 38 male patients with chronic pulmonary disease during winter 2001/2002. Additive mixed models with random patient intercept were applied, adjusting for trend, weekday, and meteorological parameters. Hourly data on ultrafine particles (UFP, 0.01-0.1 μm), accumulation mode particles (ACP, 0.1-1.0 μm), PM10 (particulate matter 2], carbon monoxide [CO], and sulphur dioxide [SO2]) were collected at a central monitoring site and meteorological data were received from an official network. For each person and visit the individual 24-hour average of pollutants immediately preceding the blood withdrawal (lag 0) up to day 5 (lag1-4) and 5-day running means were calculated. Results Increased levels of fibrinogen were observed for an increase in one interquartile range of UFP, PM10, EC, OC, CO, and NO revealing the strongest effect for lag 3. E-selectin increased in association with ACP and PM10 with a delay of one day. The ACP effect was also seen with the 5-day-mean. The pattern found for D-dimer was inconsistent. Prothrombin fragment 1+2 decreased with lag 4 consistently for all particulate pollutants. Von Willebrand factor antigen (vWF) showed a consistent decrease in association with almost all air pollutants with all lags except for lag 0. No associations were found for C-reactive protein, soluble intercellular adhesion molecule 1, serum amyloid A and factor VII. Conclusion These results suggest that elevated concentrations of air pollution are associated with changes in some blood markers of inflammation and coagulation in patients with chronic pulmonary disease. The clinical implications of these findings need further investigation.

We identify determinants of plasma interleukin-6 (IL-6) levels in a multicenter panel study of myocardial infarction (MI) survivors, using repeated measurements to evaluate both baseline and time-varying factors.Survivors of MI (N= 1003) recruited in six European cities had repeated measurements (median: 6/patient) of IL-6. At baseline, participants' behaviour and medical histories were determined by interview, and blood pressure, anthropometry, cholesterol and N-terminal B-type natriuretic peptide (NT-proBNP) were measured. Short-term exposures and medication intake were recorded at each visit. Generalized additive mixed models were used to analyze associations of IL-6 with baseline and time-varying risk factors, taking into account repeated measurements.Age, hour of blood withdrawal, body mass index, pack-years of smoking, NT-proBNP, systolic blood pressure, high-density lipoprotein cholesterol, persistent cough/phlegm and statin use were significantly and independently associated with IL-6 after adjustment for city, recurrent MI, baseline alcohol intake, current active smoking, tea consumption and extreme anger or stress.Among MI survivors, IL-6 levels are associated with many traditional cardiovascular risk factors. Patients with elevated NT-proBNP, respiratory symptoms or obesity had higher IL-6 concentrations and may potentially be at greater risk for coronary artery disease progression.

Ambient particulate matter has been associated with systemic inflammation indicated by blood markers such as fibrinogen, implicated in promoting atherothrombosis.This study evaluated whether single-nucleotide polymorphisms (SNPs) within the fibrinogen genes modified the relationship between ambient particles and plasma fibrinogen.In 854 myocardial infarction survivors from five European cities plasma fibrinogen levels were determined repeatedly (n = 5,082). City-specific analyses were conducted to assess the impact of particulate matter on fibrinogen levels, applying additive mixed models adjusting for patient characteristics, time trend, and weather. City-specific estimates were pooled by meta-analysis methodology.Seven SNPs in the FGA and FGB genes shown to be associated with differences in fibrinogen levels were selected. Promoter SNPs within FGA and FGB were associated with modifications of the relationship between 5-day averages of particulate matter with an aerodynamic diameter below 10 microm (PM(10)) and plasma fibrinogen levels. The PM(10)-fibrinogen relationship for subjects with the homozygous minor allele genotype of FGB rs1800790 compared with subjects homozygous for the major allele was eightfold higher (P value for the interaction, 0.037).The data suggest that susceptibility to ambient particulate matter may be partly genetically determined by polymorphisms that alter early physiological responses such as transcription of fibrinogen. Subjects with variants of these frequent SNPs may have increased risks not only due to constitutionally higher fibrinogen concentrations, but also due to an augmented response to environmental inflammatory stimuli such as ambient particulate matter.

Background: C-reactive protein (CRP), a sensitive marker of the acute-phase response, has been associated with future cardiovascular endpoints independently of other risk factors. A joint analysis of the role of risk factors in predicting mean concentrations and variation of high-sensitivity CRP (hsCRP) in serum has not been carried out previously. Methods: We used data from 1003 myocardial infarction (MI) survivors who had hsCRP measured monthly up to 8 times and multivariate mixed effects statistical models to study the role of time-variant and -invariant factors on the geometric mean of and the intraindividual variation in hsCRP concentrations. Results: Patients with ≥6.5% glycosylated hemoglobin (HbA1c) had 26.2% higher hsCRP concentrations (95% CI, 7.2%–48.6%) and 20.7% greater variation in hsCRP values (P = 0.0034) than patients with lower baseline Hb A1c values ( Conclusions: One or 2 hsCRP measurements may not be sufficient to adequately characterize different patient groups after MI with similar precisions. We found hsCRP concentrations to be especially variable in males, smokers, and patients with increased Hb A1c values.

Introduction Increased levels of interleukin 6 (IL-6), a marker for systemic inflammation, have been associated with cardiovascular morbidity and mortality. Materials and Methods We investigated the influence of IL6 gene polymorphisms on mean level and variability of plasma IL-6 in a population of myocardial infarction survivors recruited in six European cities as part of the AIRGENE study. DNA from each individual was collected and genotyped for eight functional and tagging single nucleotide polymorphisms (SNPs) in the IL6 gene. Results We analyzed 946 subjects with 5520 repeated plasma samples for IL-6 levels. For four IL6 SNPs in high linkage disequilibrium, heterozygous and homozygous minor allele genotypes were associated with an increase in mean plasma IL-6 levels. SNP rs1800795 was associated with a 6.3% increase in IL-6 (95% confidence interval [CI] 1.7-11,2%) For these SNPs, we found that genotypes associated with higher IL-6 levels also tended to be associated to higher between-individual variability of IL-6 levels on the log-scale than other genotypes. Variability over time within individuals varied little by genotype. Conclusions We found four genetic polymorphisms in the IL6 gene associated with mean level and variability of plasma IL-6 between individuals in myocardial infarction survivors.

Background ECG (electrocardiogram) markers reflecting abnormal heart rate variability and abnormal repolarization as well as several biochemical markers reflecting inflammation, endothelial dysfunction, and procoagulation states were reported to show an association with increased cardiovascular mortality. ECG and biochemical markers could operate independently or they could interrelate in pathogenetic pathways of coronary disease. In this study, we aimed to explore the relationship between ECG and biochemical markers in a longitudinal study of coronary patients. Methods A total of 499 observations from 52 patients with up to 12 repeated measurements were collected providing data on series of ECG (heart rate variability and repolarization) parameters and biochemical parameters. Generalized estimating equation models adjusting for repeated measurements were used for the analyses. Results There was a significant association between ECG parameters reflecting abnormal repolarization (prolonged QT interval, lower T wave amplitude) and elevated levels of C-reactive protein and fibrinogen. Abnormal heart rate variability, increased sympathetic tone (low-frequency power) was associated with increased concentrations of soluble E-selectin, a marker of endothelial cell activation. There was no association between ECG markers and parameters reflecting increased procoagulation states. Conclusion These results indicate that there is an association between ECG parameters and blood markers reflecting endothelial function and inflammation in coronary artery disease patients. The pathophysiologic mechanisms of these associations remain to be elucidated.

Epidemiologic studies report associations between particulate air pollution and cardiovascular morbidity and mortality, but the underlying pathophysiologic mechanisms are still unclear. We tested the hypothesis that patients with preexisting coronary heart disease experience changes in the repolarization parameters in association with rising concentrations of air pollution. A prospective panel study was conducted in Erfurt, East Germany, with 12 repeated electrocardiogram (ECG) recordings in 56 males with ischemic heart disease. Hourly particulate and gaseous air pollution and meteorologic data were acquired. The following ECG parameters reflecting myocardial substrate and vulnerability were measured: QT duration, T-wave amplitude, T-wave complexity, and variability of T-wave complexity. Fixed effect regression analysis was used adjusting for subject, trend, weekday, and meteorology. The analysis showed a significant increase in QT duration in response to exposure to organic carbon; a significant decrease in T-wave amplitude with exposure to ultrafine, accumulation mode, and PM2.5 particles (particles < 2.5 μm in aerodynamic diameter); and a corresponding significant increase of T-wave complexity in association with PM2.5 particles for the 24 hr before ECG recordings. Variability of T-wave complexity showed a significant increase with organic and elemental carbon in the same time interval. This study provides evidence suggesting an immediate effect of air pollution on repolarization duration, morphology, and variability representing myocardial substrate and vulnerability, key factors in the mechanisms of cardiac death.

Given the accumulating evidence that people with underlying heart disease are a particularly vulnerable group for triggers like changing meteorological parameters, the objective of this longitudinal study was to analyze the influence of weather parameters on blood pressure, arrhythmia and ischemia in cardiovascular patients. A panel study with repeated measurements was conducted in a rehabilitation clinic in Timmendorfer Strand (Baltic Sea, Germany) with 872 cardiovascular patients. Heart rate, blood pressure and electrocardiography changes were measured during repeated bicycle ergometries. Generalized Estimating Equations were used for regression analyses of immediate, delayed and cumulative influences of the daily measured meteorological data. For men, a decrease in air temperature and in water vapor pressure doubled the risk of ST-segment depression during ergometry [odds ratio (OR) for 1 day delay: 1.88 (1.24; 2.83) for air temperature] with a delay of 1-2 days. For women, an increase of their heart rate before the start of the ergometry [same day: 4.36 beats/min (0.99; 7.74) for air temperature] and a 2- to 3-fold higher risk for ventricular ectopic beats [1 day delay: OR 2.43 (1.17; 5.05) for air temperature] was observed with an increase in temperature and water vapor pressure in almost all analyzed time-windows. The study indicates that meteorological parameters can induce changes in heart function which may lead to adverse cardiovascular events especially in susceptible, diseased individuals. The observed effect on ST-segment depression could be a link between the association of weather changes and cardiovascular morbidity and mortality.

Epidemiological studies on health effects of air pollution have consistently shown adverse cardiovascular effects. Toxicological studies have provided evidence for thrombogenic effects of particles. A prospective panel study in a susceptible population was conducted in Erfurt, Germany, to study the effects of daily changes in ambient particles on various blood cells and soluble CD40ligand (sCD40L, also known as CD154), a marker for platelet activation that can cause increased coagulation and inflammation. Blood cells and plasma sCD40L levels were repeatedly measured in 57 male patients with coronary heart disease (CHD) during winter 2000/2001. Fixed effects linear regression models were applied, adjusting for trend, weekday and meteorological parameters. Hourly data on ultrafine particles (UFP, number concentration of particles from 0.01 to 0.1 μm), mass concentration of particles less than 10 and 2.5 μm in diameter (PM10, PM2.5), accumulation mode particle counts (AP, 0.1–1.0 μm), elemental and organic carbon, gaseous pollutants and meteorological data were collected at central monitoring sites. An immediate increase in plasma sCD40L was found in association with UFP and AP (% change from geometric mean: 7.1; CI: [0.1, 14.5] and 6.9; CI: [0.5, 13.8], respectively). Platelet counts decreased in association with UFP showing an immediate, a three days delayed (lag 3) and a 5-day average response (% change from the mean: -1.8; CI: [-3.4,-0.2]; -2.4; CI: [-4.5,-0.3] and -2.2; CI: [-4.0,-0.3] respectively). The increased plasma sCD40L levels support the hypothesis that higher levels of ambient air pollution lead to an inflammatory response in patients with CHD thus providing a possible explanation for the observed association between air pollution and cardiovascular morbidity and mortality in susceptible parts of the population.