Search

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values 105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR >105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Introduction Detailed mechanisms in the pathophysiology of diabetes disease are poorly understood, but structural alterations in various organ systems incur an elevated risk for cardiovascular events and adverse outcome. The aim of this study was to compare multiorgan subclinical disease phenotypes by magnetic resonance (MR) imaging to study differences between subjects with prediabetes, diabetes, and normal controls. Materials and Methods Subjects without prior cardiovascular disease were enrolled in a prospective case-control study and underwent multiorgan MR for the assessment of metabolic and arteriosclerotic alterations, including age-related white matter changes, hepatic proton density fat fraction, visceral adipose tissue volume, left ventricular remodeling index, carotid plaque, and late gadolinium enhancement. Magnetic resonance features were summarized in a phenotypic-based score (range, 0-6). Univariate, multivariate correlation, and unsupervised clustering were performed. Results Among 243 subjects with complete multiorgan MR data sets included in the analysis (55.6 ± 8.9 years, 62% males), 48 were classified as subjects with prediabetes and 38 as subjects with diabetes. The MR phenotypic score was significantly higher in subjects with prediabetes and diabetes as compared with controls (mean score, 3.00 ± 1.04 and 2.69 ± 0.98 vs 1.22 ± 0.98, P < 0.001 respectively), also after adjustment for potential confounders. We identified 2 clusters of MR phenotype patterns associated with glycemic status (P < 0.001), independent of the MR score (cluster II-metabolic specific: odds ratio, 2.49; 95% CI, 1.00-6.17; P = 0.049). Discussion Subjects with prediabetes and diabetes have a significantly higher phenotypic-based score with a distinctive multiorgan phenotypic pattern, which may enable improved disease characterization.

Background Although emergency medical services (EMS) use is the recommended mode of transport in case of acute coronary symptoms, many people fail to use this service. Objective The objective of this study was to determine factors associated with EMS use in a population-based sample of German patients with recurrent acute myocardial infarction (AMI). Methods The sample consisted of 998 persons with a first and recurrent AMI, recruited from 1985 to 2011. Logistic regression modeling adjusted for sociodemographic, situational, and clinical variables, previous diseases, and presenting AMI symptoms was applied. Results Emergency medical services was used by 48.8% of the patients at first, and 62.6% at recurrent AMI. In first AMI, higher age, history of hyperlipidemia, ST-segment elevation AMI, more than 4 presenting symptoms, symptom onset in daytime, and later year of AMI were significantly related with EMS use. Pain in the upper abdomen and pain between the shoulder blades were significantly less common in EMS users. In recurrent AMI, EMS use at first AMI, presence of any other symptom except chest pain, ST-segment elevation myocardial infarction, and later year of AMI were significantly related with EMS use. Significant predictors of EMS use in recurrent AMI in patients who failed to use EMS at first AMI were unmarried, experience of any symptom except chest symptoms at reinfarction, bundle branch block (first AMI), any in-hospital complication (first AMI), longer duration between first and recurrent AMI, and later year of reinfarction. Conclusions Patients with AMI and their significant others may profit by education about the benefits of EMS use.

Introduction: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a risk factor for atrial fibrillation and a marker of cardiac function used in detection of heart failure. Few studies evaluated the role of NT-proBNP as risk factor for stroke. Hypothesis: Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke outcomes and to determine the predictive value beyond a panel of established risk factors for stroke. Methods: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project we analysed data of 43,815 participants (48.3% men; mean age 52 yr) free of cardiovascular disease from 6 prospective population-based cohorts across Europe with a maximum follow-up of 22 years. All NT-proBNP measurements were performed on frozen samples in the central BiomarCaRE laboratory. The endpoints considered were validated fatal and non-fatal stroke. Results: We observed 565 stroke events (78 fatal) in men and 290 (54) in women. Growing quartiles of NT-proBNP were associated with increasing risk of stroke (Table; multivariable cox regression analysis adjusted for the base model: age, centre, smoking, BMI, diabetes, hypertension medication, systolic and diastolic blood pressure, total and HDL cholesterol), both in men (p for trend Conclusions: In European individuals free of cardiovascular disease, levels of NT-proBNP in the top quartile (>87.7 pg/mL) are associated with a doubled risk of stroke. However, the addition of NT-proBNP to variables of established risk score poorly improves prediction of stroke disease.

Background— Dimethylarginines (DMA) interfere with nitric oxide formation by inhibiting nitric oxide synthase (asymmetrical DMA [ADMA]) and l -arginine uptake into the cell (ADMA and symmetrical DMA [SDMA]). In prospective clinical studies, ADMA has been characterized as a cardiovascular risk marker, whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterize the environmental and genetic contributions to interindividual variability of these biomarkers. Methods and Results— This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (Framingham Heart Study [FHS; n=2992], Gutenberg Health Study [GHS; n=4354], and Multinational Monitoring of Trends and Determinants in Cardiovascular Disease Study [MONICA]/Cooperative Health Research in the Augsburg Area, Augsburg, Bavaria, Germany [KORA] F3 [n=581]) and identified replicated loci ( DDAH1, MED23, Arg1 , and AGXT2 ) associated with the interindividual variability in ADMA, l -arginine, and SDMA. Experimental in silico and in vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants, and various cardiometabolic risk factors. AGXT2 variants were not associated with poststroke survival in the Leeds study or were they associated with incident stroke in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Conclusions— These genome-wide association study support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and l -arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation.

To examine whether job strain is associated with an increased risk of subsequent Type 2 diabetes mellitus (T2DM) development in a population-based study of men and women.Data were derived from the prospective MONICA/KORA Augsburg study. We investigated 5337 working participants aged 29 to 66 years without diabetes at one of the three baseline surveys. Job strain was measured by the Karasek job content questionnaire. High job strain was defined by the quadrant approach, where high job demands combined with low job control were classified as high job strain. Continuous job strain (quotient of job demands divided by job control) was additionally analyzed as sensitivity analysis. Hazard ratios (HRs) were estimated using multivariable Cox proportional hazards models with adjustment for age, sex, survey, socioeconomic and life-style variables, parental history of diabetes, and body mass index.During a median follow-up of 12.7 years, 291 incident cases of T2DM were observed. The participants with high job strain at baseline had a 45% higher fully adjusted risk to develop T2DM than did those with low job strain (HR = 1.45 [95% confidence interval = 1.00-2.10], p = .048). On the continuous scale, more severe job strain in the magnitude of 1 standard deviation corresponded to a 12% increased fully adjusted T2DM risk (HR = 1.12 [95% confidence interval = 1.00-1.25], p = .045).Men and women who experience high job strain are at higher risk for developing T2DM independently of traditional risk factors. Preventive strategies to combat the globally increasing T2DM epidemic should take into consideration the adverse effects of high strain in the work environment.

Background: The Framingham Risk Score (FRS) is an established tool for the prediction of cardiovascular disease (CVD) risk. The established CVD risk factors age, HDL cholesterol, total cholesterol, systolic blood pressure (SBP), antihypertensive treatment, diabetes mellitus and smoking are used in the calculation of the FRS. The prevalence and distribution of these risk factors in the population have changed within the last decades and especially average levels of SBP have declined. However, the impact of this change on the risk prediction performance of the FRS has not been investigated. Hypothesis: We assessed the hypothesis that the relative contribution of SBP to CVD risk prediction within the FRS framework has changed from 1985 to 2000. Methods: We used N = 11 760 participants aged 30 - 65 years from four prospective population-based cohort studies enrolled in Southern Germany in 1985, 1990, 1995, and 2000. CVD risk was calculated by recalibrated equations of the original FRS. Predicted CVD risks using the actual SBP values were compared to predicted CVD risks using optimal (SBP < 120 mmHg) values for each participant. We assessed the relative contribution of SBP with three performance measures: First, the median difference in predicted risks with actual and optimal SBP, second, the relative positive predictive value of the FRS using actual compared to optimal SBP values and third, the population attributable risk fraction of SBP using Levin’s formula. Results: CVD events occurred in 6.3% of male participants in 1985 and 6.2% in 2000; in women, event rates were 2.4% and 2.3%, respectively. Mean SBP levels decreased from 134 mmHg (Standard Deviation: 17 mmHg) to 132 (SD: 17) mmHg in men and from 127 (SD: 19) mmHg to 121 (SD: 18) mmHg in women. The difference in median predicted risk declined from 1.21 [Interquartile range 0.52, 3.38] in 1985 to 0.93 [0.35, 2.44] in 2000 in men and from 0.26 [-0.05, 1.45] to -0.07 [-0.19, 0.89] in women. The relative positive predictive value dropped from 0.88 to 0.73 in men and from 0.61 to 0.53 in women. The population attributable risk fraction of SBP decreased from 70.2% (95% CI: 42.1, 89.6) to 29.71% (-6.4, 64.7) in men and from 85.7% (62.9, 93.1) to 57.9% (28.0, 82.0) in women. Given the results from 1990 and 1995, the declining trend was nonlinear for all three performance measures. Conclusion: In conclusion, the relative contribution of blood pressure to cardiovascular risk prediction has decreased within the last decades. This affects the future development of CVD risk prediction methods which will have to consider the changing relative importance of SBP. Furthermore, this might also influence public health policies focusing on the management of SBP and hypertension in order to effectively prevent CVD.

Purpose: Physical activity has recently been established as a potential modifier of the inflammatory process, suggesting that it mitigates inflammation and consequently reduces the incidence of several chronic diseases such as cardiovascular events. Methods: This study examined the association between different domains ofself-reported physical activity (work, transportation, household, and leisure time) and three inflammatory markers (fibrinogen, C-reactive protein (CRP), and interleukin 6 (IL-6)). Study subjects included 796 men and women aged 35-74 yr with complete data for the main study variables who participated in the 1989/1990 MONItoring trends and determinants in CArdiovascular disease (MONICA) Augsburg Survey. Data were collected using the MONICA Optional Study on Physical Activity (MOSPA) questionnaire, and activity levels were classified into low, moderate, and vigorous physical activities. Results: Fibrinogen showed an inverse relationship with higher levels of work (Ptrend = 0.038), transportation (Ptrend = 0.025), leisure time (Ptrend = 0.013), and summary physical activity (Ptrend< 0.001). This relationship was still observed after adjusting for age and sex and further correction for body mass index, waist-to-hip ratio, smoking status, hypertension, diabetes, total-to-HDL cholesterol ratio, education, and self-reported limited physical activity due to health problems. IL-6 showed significant results for transportation (Ptrend = 0.031), leisure time (Ptrend = 0.016), and summary physical activity (Ptrend < 0.001), whereas CRP was inversely related with the summary activity (Ptrend = 0.003) in the fully adjusted model. No statistically significant inverse association between household physical activity and any of the investigated markers was found. We observed interactions between summary physical activity and smoking (fibrinogen: P = 0.003) as well as ex-smoking (CRP: P < 0.001; IL-6: P = 0.049). Conclusion: These data indicate that beyond leisure time, work and transportation physical activity may reduce inflammation.

Background— No data exist regarding time trends of 28-day case fatality (CF) of patients with presumed acute myocardial infarction (AMI) using epidemiological criteria, clinical criteria, and AMI classification after validation of presumed in-hospital AMI-related deaths (gold-standard criteria). Methods and Results— From 1985 to 2004, we prospectively examined all 9210 AMI patients consecutively hospitalized in a large teaching hospital by using a broad epidemiological AMI definition (WHO-MONICA). Twenty-eight-day CF decreased significantly from 32% in 1985–1986 to 18% in 2003–2004, mostly because of a reduction in early deaths ( Conclusions— The application of broad epidemiological criteria for AMI overestimates 28-day CF by almost 2-fold compared with gold-standard criteria (after validation of early deaths) and almost 3-fold compared to the clinical definition. The growing similarity in 28-day CF between the clinically based definition and the gold-standard criteria implies that recent clinical-based registries may represent a realistic picture of trends regarding in-hospital AMI mortality.

Background— Recently, genome-wide association studies identified variants on chromosome 9p21.3 as affecting the risk of coronary artery disease (CAD). We investigated the association of this locus with CAD in 7 case-control studies and undertook a meta-analysis. Methods and Results— A single-nucleotide polymorphism (SNP), rs1333049, representing the 9p21.3 locus, was genotyped in 7 case-control studies involving a total of 4645 patients with myocardial infarction or CAD and 5177 controls. The mode of inheritance was determined. In addition, in 5 of the 7 studies, we genotyped 3 additional SNPs to assess a risk-associated haplotype (ACAC). Finally, a meta-analysis of the present data and previously published samples was conducted. A limited fine mapping of the locus was performed. The risk allele (C) of the lead SNP, rs1333049, was uniformly associated with CAD in each study ( P P =0.0001). Haplotype analysis further suggested that this effect was not homogeneous across the haplotypic background (test for interaction, P =0.0079). An autosomal-additive mode of inheritance best explained the underlying association. The meta-analysis of the rs1333049 SNP in 12 004 cases and 28 949 controls increased the overall level of evidence for association with CAD to P =6.04×10 −10 (odds ratio, 1.24; 95% confidence interval, 1.20 to 1.29). Genotyping of 31 additional SNPs in the region identified several with a highly significant association with CAD, but none had predictive information beyond that of the rs1333049 SNP. Conclusion— This broad replication provides unprecedented evidence for association between genetic variants at chromosome 9p21.3 and risk of CAD.

Objective To investigate regional variations in the prevalence and management of hypertension in two communities in the north-east and the south-west of Germany. Study setting Two population-based surveys of men and women aged 25–74 years, using a common standardized protocol: the Study of Health in Pomerania (SHIP; 3744 participants) and the Kooperative Gesundheitsforschung in der Region Augsburg (KORA; 4224 participants). Main outcome measures Comparison of SHIP and KORA with regard to mean systolic (SBP) and diastolic blood pressure (DBP), prevalence of hypertension, percentage of awareness, treatment and control of hypertension in the community, by age and sex. Results The overall age-standardized prevalence of hypertension for men was 60.1% in SHIP and 41.4% in KORA; the corresponding values for women were 38.5 and 28.6%. Mean blood pressure differences were present in each 10-year age group and sex. The overall SBP difference between SHIP and KORA was 8.2 mmHg (95% confidence interval 7.2–9.3) in men and 6.3 mmHg (5.3–7.3) in women, the respective DBP differences were 3.8 mmHg (3.2–4.5) and 3.6 mmHg (3.0–4.2). Nevertheless, the percentage of awareness, treatment and control of hypertension was strikingly similar in the two studies (women, P = 0.858; and men, P = 0.564). Conclusions The entire distribution of diastolic and systolic blood pressure values was shifted upwards in the north-eastern as compared to the south-western German population samples and the prevalences of hypertension differed accordingly. Despite such substantial epidemiologic differences, the community management of hypertension was of almost identical quality.

Background— Oxidized LDL (oxLDL) is thought to play a key role in the inflammatory response in the arterial vessel wall. Methods and Results— In a prospective, nested, case-control study, the association between plasma oxLDL and risk of an acute coronary heart disease (CHD) event was investigated in men without prevalent CHD or diabetes mellitus at baseline. Subjects came from 2 population-based MONICA/KORA Augsburg surveys conducted in the years 1989–1990 and 1994–1995 with follow-up in 1998 (mean±SD follow-up time, 5.6±2.6 years). OxLDL was determined by ELISA in 88 men with incident CHD and in 258 age- and survey-matched controls. Hazard ratios (HRs) were estimated from conditional logistic-regression models with matching for age and survey. Baseline mean plasma oxLDL concentrations were significantly higher in subjects who subsequently experienced an event compared with controls (mean±SD, 110±32 versus 93±28 U/L; P ≤0.001). After adjustment for smoking, hypertension, obesity, physical activity, education, and alcohol consumption, the HR for a future CHD event in a comparison of the upper tertile of the oxLDL distribution with the lower tertile was 4.25 (95% confidence interval, 2.09 to 8.63; P Conclusions— Elevated concentrations of oxLDL are predictive of future CHD events in apparently healthy men. Thus, oxLDL may represent a promising risk marker for clinical CHD complications and should be evaluated in further studies.

Background— Chronic inflammation represents an essential feature of the atherosclerotic process. Lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ), an enzyme mainly produced by monocytes/macrophages, generates potent proinflammatory products. Methods and Results— Plasma concentrations of Lp-PLA 2 were determined by ELISA in 934 apparently healthy men aged 45 to 64 years sampled from the general population in 1984 and followed up until 1998. During this period, 97 men experienced a coronary event diagnosed according to the MONICA (MONItoring of trends and determinants in CArdiovascular disease) protocol. Baseline levels of Lp-PLA 2 were higher in subjects who experienced an event than in event-free subjects (295±113 versus 263±79 ng/mL, P 2 was positively correlated with total cholesterol ( R =0.30, P R =0.12, P =0.001), was only slightly correlated with HDL cholesterol ( R =0.09, P =0.005) and C-reactive protein R =0.06, P =0.06), but was not correlated with body mass index or blood pressure. In a Cox model, a 1-SD increase in Lp-PLA 2 was associated with risk of future coronary events (hazard ratio [HR] 1.37, 95% CI 1.16 to 1.62). After controlling for potential confounders, the HR was attenuated but remained statistically significant (HR 1.23, 95% CI 1.02 to 1.47). Further inclusion of C-reactive protein in the model did not appreciably affect its predictive ability (HR 1.21, 95% CI 1.01 to 1.45). Conclusions— Elevated levels of Lp-PLA 2 appeared to be predictive of future coronary events in apparently healthy middle-aged men with moderately elevated total cholesterol, independent of CRP. This suggests that Lp-PLA 2 and CRP may be additive in their ability to predict risk of coronary heart disease.

Background: The exact etiology and prognostic significance of coronary artery ectasia (CAE) is still unknown. The presence of CAE is influenced by genetic factors and related to the presence of aneurysms in other vascular beds. Bicuspid aortic valve (BAV) disease is frequently accompanied by ascending aortic aneurysm. Since the aortic valve, the ascending aorta, and the proximal parts of the coronary arteries share a common embryonic origin, we hypothesized that CAE is associated with BAV disease. Methods: 181 patients with suspected aortic valve disease (n=101 BAV) underwent both cardiac magnetic resonance (CMR) imaging and coronary angiography. Eighty subjects with tricuspid aortic valve (TAV) disease were similarly studied and served as controls. The readers of the angiograms were blinded to valve type and clinical data. In order to confirm the association of CAE with BAV, the frequency of CAE was evaluated in an in-house BAV registry (n=500) and compared to the frequency of CAE in the German MI family study, in which the heritability of CAE was formerly established (899 with available coronary angiograms), as well as in an observational registry of “real-life patients” undergoing coronary angiography for clinically indicated reasons (n=3471). Furthermore the frequency of CAE was investigated in a subgroup of the KORA MI study, which is a population-based registry that comprises all hospitalized cases of acute non-fatal MI and coronary deaths occurring in inhabitants of a defined study region (n=403). Results: Compared to TAV disease, CAE occured twice as frequently in CMR confirmed BAV disease, (17.5% vs. 41.6%, p=0.0005). Ascending aortic aneurysm or ectasia was diagnosed in 60 subjects with BAV disease (59.4%), but CAE occurred similarly between subjects with (59.5%) and without (40.5%) ascending aortic pathology. The common appearance of CAE in patients with BAV could be independently confirmed in the BAV registry (38.9%), whereas CAE was found less frequently in family history positive MI patients (21.2%), and rarely in unrelated “real-life” catheterization patients (5.2%). Conclusion: To our knowledge, our data show for the first time that ectatic coronary artery disease is a common appearance of BAV disease with and without ascending aortic aneurysm.

Background: High-sensitive (hs) troponin T and I assays as well as ultrasensitive (us) troponin I enable measurement of troponins in 65% to 98% of the general population. We prospectively investigated whether increased concentrations of us-troponin I are associated with an increased risk of coronary heart disease (CHD) after controlling for traditional risk factors. Methods: We conducted a population-based case cohort study in middle-aged healthy men and women within the MONICA/KORA Augsburg studies. Serum levels of us-troponin I (Single Molecule Counting technology, Singulex) were available in 2,745 men and women including 803 incident CHD cases. Geometric mean us-troponin I was 1.56 ng/L. Mean (SD) follow-up was 16.0 (5.8) years. Results: Baseline concentrations of us-troponin I were higher in cases compared to non-cases (geometric mean 2.56 vs. 1.49 ng/L, p Conclusions: Troponin I measured by an us-assay was detectable in almost all subjects. This is the first population-based prospective study with long-term follow-up showing that even modestly increased concentrations of us troponin I are strongly associated with incident CHD independently of a variety of traditional risk factors.

Background. It has been suggested that long-term exposure to air pollution may lead to an increased risk of cardiovascular disease. Hypotheses. In this study, we hypothesized that long-term residential traffic exposure enlarges of intima-media thickness (IMT). Methods. We used data on 2712 individuals aged 31 to 82 years who participated in the cross-sectional KORA F4 (2006–2008) survey conducted in the region of Augsburg, Germany. The residential traffic exposure was assessed by specifying daily traffic intensity of and distance to nearest street, and of daily traffic load (sum of product of traffic intensity and length of all street segments) and total road length within a buffer of 50 and rings of 50 to 100 and 100 to 300 meters around the residences. IMT was measured as mean of first cm of left and right common carotid artery segments from all angles (mm). We used linear regression adjusting for sex, age, adipositas, education, occupation, smoking status, systolic and diastolic blood pressure, HDL- and LDL-cholesterol and statin intake. Results. Road length within a radius of 50 meters of a person’s residence was associated with an increased IMT 1.2% (95% CI, 0.2% to 2.3%) per increase in 140 road length (m). Other measures of traffic exposures showed no or weaker effects; for example the traffic load within a radius of 50 meters of a person’s residence was associated with an increased IMT 0.3% (95% CI, -0.4% to 1.0%) per increase in 600 vehicles per kilometer. No difference was observed between men and women. Conclusions. Long-term residential exposure by road traffic may contribute to the development of atherosclerosis. Additional estimates for traffic related pollution may help interpreting the results of the KORA study.