Region Of Augsburg Research Articles

Vertebral Bone Marrow Fat Is independently Associated to VAT but Not to SAT: KORA FF4-Whole-Body MR Imaging in a Population-Based Cohort.

The objective of the current study was to assess the relationship of bone marrow adipose tissue (BMAT) content to abdominal fat depots, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), as well as cardiovascular risk factors (CVRF) beyond physical activity in a population-based cohort study undergoing whole-body magnetic resonance (MR) imaging. Subjects of the Cooperative Health Research in the Augsburg Region (KORA) FF4 study without known cardiovascular disease underwent fat fraction quantification in vertebrae (BMATL1/L2) via a 2-point T1-weighted volumetric interpolated breath-hold examination (VIBE) Dixon sequence. The same MR sequence was applied to quantify VAT and SAT volume. Subjects’ characteristics, including physical activity, were determined through standardized exams and self-assessment questionnaires. Univariate and multivariate linear regression were applied. In the cohort of 378 subjects (56 ± 9.1years; 42.1% female), BMATL1/L2 was 54.3 ± 10.1%, VAT was 4.54 ± 2.71 L, and SAT was 8.10 ± 3.68 L. VAT differed significantly across BMATL1/L2 tertiles (3.60 ± 2.76 vs. 4.92 ± 2.66 vs. 5.11 ± 2.48; p < 0.001), there was no significant differences for SAT (p = 0.39). In the fully adjusted model, VAT remained positively associated with BMATL1/L2 (β = 0.53, p = 0.03). Furthermore, BMATL1/L2 was associated with age (β = 5.40 per 10-years, p < 0.001), hemoglobin A1c (HbA1c; β = 1.55 per 1%, p = 0.04), lipids (β = 0.20 per 10 mg/dL triglycerides; β = 0.40 per 10 mg/dL low-density lipoprotein (LDL); β =−3.21 lipid-lowering medication; all p < 0.05), and less physical activity (β = 3.7 “no or nearly no exercise” as compared to “≥2 h per week, regularly”, p = 0.003); gender was not significantly different (p = 0.57). In the population-based cohort, VAT but not SAT were associated with higher BMATL1/L2 independently of physical activity and other cardiovascular risk factors. Further, BMATL1/L2 increased with older age, less physical activity, higher HbA1c, and increased lipids but decreased with lipid-lowering medication.

Association between unrealistic comparative optimism and self-management in individuals with type 2 diabetes: Results from a cross-sectional, population-based study.

Background and aimsUnrealistic comparative optimism (UO), as the erroneous judgement of personal risks to be lower than the risks of others, could help explain differences in diabetes self‐management. The present study tested the hypothesis that individuals with type 2 diabetes who underestimate their comparative heart attack risk, have a lower adherence regarding recommended self‐management.MethodsWe used data from individuals with type 2 diabetes participating in the German KORA (Cooperative Health Research in the Region of Augsburg) GEFU 4 (self‐administered health questionnaire 2016) study. UO was estimated by comparing participants' subjective comparative risk for having a heart attack within the next 5‐years (ie, “higher than others,” “average,” “lower than others”), with their objective comparative 10‐year cardiovascular disease risk based on the Framingham equations. We estimated binary logistic and linear regression models to analyze which characteristics were associated with UO and to test the association between UO and participants' self‐management behaviors (ie, regular self‐monitoring of body weight, blood sugar, and blood pressure, regular foot care, keeping a diabetes diary, and having a diet plan), and their sum score, respectively. All models were adjusted for socio‐demographic and disease‐related variables.ResultsThe studied sample included n = 633 individuals with type 2 diabetes (mean age 70.7 years, 45% women). Smokers and males were more likely to show UO than nonsmokers and females. Furthermore, a higher blood pressure and a higher body mass index were associated with a higher likelihood of UO regarding heart attack risk. However, UO was not significantly associated with patient self‐management.ConclusionsUnfavorable health behavior and risk factors are associated with UO. However, our results suggest that UO with regard to perceived heart attack risk may not be a relevant factor for patient self‐management in those with type 2 diabetes.

Proinsulin to insulin ratio is associated with incident type 2 diabetes but not with vascular complications in the KORA F4/FF4 study

IntroductionWe investigated the association of the proinsulin to insulin ratio (PIR) with prevalent and incident type 2 diabetes (T2D), components of the metabolic syndrome, and renal and cardiovascular outcomes in...

Serum uromodulin and decline of kidney function in older participants of the population-based KORA F4/FF4 study.

BackgroundUromodulin, a tissue-specific tubular glycoprotein, has recently emerged as a promising biomarker for kidney function and tubular integrity. However, the association of serum uromodulin (sUmod) with renal function decline is still unknown in an older general population.MethodsWe analysed the association of sUmod with the estimated glomerular filtration rate (eGFR) and albuminuria in 1075 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study, ages 62–81 years, at baseline and prospectively after a mean follow-up time of 6.5 years (n = 605) using logistic and linear regression models as well as receiver operating characteristics (ROC) analyses.ResultsCross-sectionally, sUmod was positively associated with eGFR (β = 0.31 ± 0.02 per higher standard deviation sUmod; P < 0.001) and inversely associated with the urinary albumin:creatinine ratio (β = −0.19 ± 0.04; P < 0.001) after adjustment for sex, age, body mass index, arterial hypertension, prediabetes and diabetes. After multivariable adjustment including baseline eGFR, sUmod was not associated with incident chronic kidney disease (CKD), defined as a decrease in eGFR <60 mL/min/1.73 m2 after 6.5 years of follow-up {odds ratio [OR] 1.02 [95% confidence interval (CI) 0.77–1.36] per higher SD sUmod} but was inversely associated with advanced CKD, defined as incident eGFR <45 mL/min/1.73 m2 [OR 0.64 (95% CI 0.42–0.98)]. The ROC showed no added predictive value of sUmod for kidney function decline in the fully adjusted model.ConclusionsHigher sUmod was inversely associated with progression to advanced kidney disease but does not provide additional predictive value for the development of CKD in elderly participants of the population-based KORA study.

Long-term effect of physical inactivity on thoracic and lumbar disc degeneration—an MRI-based analysis of 385 individuals from the general population

BACKGROUND CONTEXTThe correlation between physical inactivity, thoracolumbar disc degeneration, and back pain remains unclear. PURPOSEThis study investigated the relationship between short- and long-term physical inactivity and degenerative changes of the thoracic and lumbar spine in a southern German cohort from the general population over a time period of 14 years. STUDY DESIGN/SETTINGThis study was designed as a cross-sectional case–control study, nested in a prospective cohort from the “Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung in der Region Augsburg” (KORA) study. PATIENT SAMPLEAll participants in the population-based KORA study were assessed using a physical activity questionnaire to establish a baseline in 1999–2001 (exam 1), within an initial follow up questionnaire in 2006–2008 (exam 2), and a second follow-up questionnaire between 2013 and 2014 (exam 3). A subsample of this group (400 subjects) underwent full body MR scan performed on a 3T magnetic resonance imaging scanner current with exam 3. OUTCOME MEASUREData regarding physical inactivity over a time period of 14 years and back pain, and quantification of thoracic and lumbar disc degeneration on magnetic resonance imaging. METHODSQuantification of thoracic and lumbar disc degeneration was performed using the Pfirrmann score. Physical activity was grouped as no physical activity, irregularly for 1 hour, regularly for 1 hour, or regularly for ≥2 hours. This was used to calculate another variable “physical inactivity,” with the options of irregular activity ≤1 hour per week or regularly ≥1 hour. Physical labor, walking, and cycling activity were additionally investigated. Correlations between physical inactivity measurements and thoracic and lumbar disc degeneration were analyzed via linear regression models adjusted for age, sex, BMI, hypertension, diabetes, and back pain. RESULTSIn total, 385 individuals (mean age: 56 years, SD ± 9.19; 58.2% male) were included in this study. Mean summed Pfirrmann score was 2.41 (SD ± 4.19) in the thoracic and 1.78 (SD ± 1.81) in the lumbar spine. The level of current exercise in our cohort varied with 113 (29.4%) subjects exercising regularly ≥2 hours per week, 118 (30.7%) regularly 1 hour per week, 57 (14%) irregularly for about 1 hour per week, and 97 (25.2%) stated not to exercise at exam 3. Disc degeneration was more apparent in those with irregular activity <1 hour compared to those with regular activity of ≥1 hour and more per week (p<.01) and in those with no activity compared to those with regular activity of ≥2 (p<.001) measured using exam 3. Less physical activity over a time period of 14 years correlated with an increase of disc degeneration of the thoracic and lumbar spine after adjustment for age, sex, BMI, hypertension and diabetes mellitus (p<.05). There was no statistically significant association between physical labor, walking activity, or cycling activity with disc degeneration. Additionally, no significant correlations between degree of disc degeneration (p=.990), degree of physical inactivity (p=.158), and back pain were observed. CONCLUSIONDegree of physical inactivity as measured over a time period of 14 years demonstrated a strong correlation with disc degeneration of the thoracic and lumbar spine.

Investigation of Adiposity Measures and Operational Taxonomic unit (OTU) Data Transformation Procedures in Stool Samples from a German Cohort Study Using Machine Learning Algorithms.

The analysis of the gut microbiome with respect to health care prevention and diagnostic purposes is increasingly the focus of current research. We analyzed around 2000 stool samples from the KORA (Cooperative Health Research in the Region of Augsburg) cohort using high-throughput 16S rRNA gene amplicon sequencing representing a total microbial diversity of 2089 operational taxonomic units (OTUs). We evaluated the combination of three different components to assess the reflection of obesity related to microbiota profiles: (i) four prediction methods (i.e., partial least squares (PLS), support vector machine regression (SVMReg), random forest (RF), and M5Rules); (ii) five OTU data transformation approaches (i.e., no transformation, relative abundance without and with log-transformation, as well as centered and isometric log-ratio transformations); and (iii) predictions from nine measurements of obesity (i.e., body mass index, three measures of body shape, and five measures of body composition). Our results showed a substantial impact of all three components. The applications of SVMReg and PLS in combination with logarithmic data transformations resulted in considerably predictive models for waist circumference-related endpoints. These combinations were at best able to explain almost 40% of the variance in obesity measurements based on stool microbiota data (i.e., OTUs) only. A reduced loss in predictive performance was seen after sex-stratification in waist–height ratio compared to other waist-related measurements. Moreover, our analysis showed that the contribution of OTUs less prevalent and abundant is minor concerning the predictive power of our models.

Abstract 21: Deciphering the Plasma Proteome of Type 2 Diabetes

Introduction: With an estimated prevalence of 425 million individuals, type 2 diabetes (T2D) is a major challenge to health care systems worldwide. It is a multifactorial complex disease characterized by insulin resistance and hyperinsulinemia, and involves widespread complications. We performed hypothesis-free association and Mendelian randomization (MR) based causal inference analyses of T2D, investigating 1,100 plasma proteins in cross-sectional and longitudinal settings. Methods: The population-based cohort studies KORA (Cooperative health research in the Region of Augsburg) and HUNT3 (Third wave of the Nord-Trøndelag Health Study) were used for discovery and replication, respectively. Proteins were quantified using the SOMAscan proteomics platform in 999 KORA and 1007 HUNT participants. After quality control, we log2-transformed and (0,1)-standardized the proteomics data. We validated T2D using clinical and oral glucose tolerance test data in KORA, and clinical data only in HUNT3. We computed logistic regression models adjusted for age, sex, body mass index, smoking status and hypertension status and accounted for multiple testing using the Benjamini-Hochberg false discovery rate (FDR) method (FDR&lt;0.05). Subsequently, we used two-sample bi-directional MR to infer the causal relationship between T2D and the replicated proteins. Results: The cross-sectional analysis with prevalent T2D (KORA 110 cases and HUNT 149) yielded 24 replicated proteins, of which the three yielding the highest odds ratios were aminoacylase 1, complement C2 and plasma protease C1 inhibitor. Longitudinal analysis with incident T2D (KORA 74 cases and HUNT 103) yielded three replicated proteins namely aminoacylase-1, growth hormone receptor and insulin like growth factor binding protein 2. The MR analysis testing the causal effect of T2D on the replicated proteins, using 120 SNPs as instrumental variables (IV), yielded nominally significant p-values (p&lt;0.05) for cathepsin Z and renin. The estimated causal effects went into the same direction as the results for both proteins suggested. In the MR analyses testing the causal effects of the proteins on T2D, using cis-acting SNPs as IVs, sex hormone-binding globulin (SHBG) had nominally significant causal effect that went into the same direction as its result suggested. None of the MR analysis results was statistically significant at the FDR threshold. Conclusion: Using an aptamer-based technique, we replicated previously reported prevalent and incident T2D-protein associations, including SHBG, complement C2 and renin as well as identified novel ones, like aminoacylase-1. Causality analyses using MR identified SHBG as a potential protein directly involved in the pathogenesis of T2D, and suggested a causal effect of T2D on both cathepsin Z and renin, both known to have roles in the pathophysiological pathways of cardiovascular disease.

The times we are born into and our lifestyle choices determine our health trajectories in older age - Results from the KORA -Age study

Health projections often extrapolate from observations in current ageing cohorts, but health in older age may depend not only on individual characteristics but also on a person's historical context. Our objective was to investigate how health deficit accumulation trajectories after age 65 differed in five adjacent birth cohorts and according to individual life course characteristics.Data originate from the 2008/09 KORA (Cooperative Health Research in the Region of Augsburg)-Age cohort study from Southern Germany and their 2012 and 2016 follow-ups. Deficit accumulation was assessed using a Frailty Index. The effects of birth cohort membership and individual life course characteristics on deficit accumulation trajectories were analyzed using generalized linear mixed models.Out of 2701 participants (49% male) from five birth cohorts (1919–23, 1924–28, 1929–33, 1934–38, 1939–43), we included 2512 individuals with 5560 observations. Frailty Index levels were higher for women, smokers, alcohol abstainers, obese participants and persons with a sedentary lifestyle or living below the poverty threshold. We found higher age-specific Frailty Index levels for the two most recent birth cohorts (e.g. 61%, CI: [13%; 130%] for the 1934–38 as compared to the 1919–23 cohort), but the rate of deficit accumulation with age (7% per life year, (CI: [5%, 9%]) was cohort-independent. Results indicate that the historical context (birth cohort membership) may influence the number of accumulated health deficits after age 65 in addition to poverty and other individual life course characteristics, but BMI, physical activity and smoking remain the modifiable risk factors offering the highest prevention potential.

A multi-cohort consortium for GEnder-Sensitive Analyses of mental health trajectories and implications for prevention (GESA) in the general population in Germany

IntroductionMental health is marked by gender differences. We formed a multi-cohort consortium to perform GEnder-Sensitive Analyses of mental health trajectories and study their implications for prevention (GESA). GESA aims at...

The Challenges and Opportunities of Energy-Flexible Factories: A Holistic Case Study of the Model Region Augsburg in Germany

Economic solutions for the integration of volatile renewable electricity generation are decisive for a socially supported energy transition. So-called energy-flexible factories can adapt their electricity consumption process efficiently to power generation. These adaptions can support the system balance and counteract local network bottlenecks. Within part of the model region Augsburg, a research and demonstration area of a federal research project, the potential, obstacles, effects, and opportunities of the energy-flexible factory were considered holistically. Exemplary flexibilization measures of industrial companies were identified and modeled. Simulations were performed to analyze these measures in supply scenarios with advanced expansion of fluctuating renewable electricity generation. The simulations demonstrate that industrial energy flexibility can make a positive contribution to regional energy balancing, thus enabling the integration of more volatile renewable electricity generation. Based on these fundamentals, profiles for regional market mechanisms for energy flexibility were investigated and elaborated. The associated environmental additional expenses of the companies for the implementation of the flexibility measures were identified in a life-cycle assessment, with the result that the negative effects are mitigated by the increased share of renewable energy. Therefore, from a technical perspective, energy-flexible factories can make a significant contribution to a sustainable energy system without greater environmental impact. In terms of a holistic approach, a network of actors from science, industry, associations, and civil society organizations was established and actively collaborated in a transdisciplinary work process. Using design-thinking methods, profiles of stakeholders in the region, as well as their mutual interactions and interests, were created. This resulted in requirements for the development of suitable business models and reduced regulatory barriers.

Magnetic Resonance-based Assessment of Myocardial 2-Dimensional Strain Using Feature Tracking: Association With Cardiovascular Risk Factors in a Population-based Cohort Free of Cardiovascular Disease.

Myocardial strain analysis is a promising tool for the detection of subtle but relevant alterations of left ventricular function, also in asymptomatic subjects. Thus, we determined the feasibility of cardiac magnetic resonance-based 2D global strain analysis using feature tracking and its association with cardiovascular risk factors in a sample from the general population. Subjects without a history of cardiocerebrovascular disease were enrolled in a substudy of the population-based KORA (Cooperative Health Research in the Region of Augsburg) cohort. In all participants with the absence of late gadolinium enhancement, longitudinal and circumferential global strains were measured on Cine SSFP imaging (TR: 29.97 ms, TE: 1.46 ms, ST: 8 mm), using a semiautomatic segmentation algorithm (CVI42, Circle, Canada). Differences in strain values according to age, sex, body mass index, hypertension, diabetes mellitus, and hyperlipidemia were derived using linear regression analysis. Among 360 subjects (mean age, 56.2±9.2 y, 57% male), the average global systolic radial strain was 40.1±8.2%, circumferential 19.9±2.7%, and longitudinal 19.8±3.2%. Male sex was associated with decreased global strain values, independent of the strain direction (all P<0.001). Although many cardiovascular risk factors were correlated with strain in univariate analysis, mainly waist-to-hip ratio and HbA1c remained associated with decreased radial and circumferential strains in fully adjusted models. Similarly, higher radial and circumferential strains were observed in older subjects (β=0.14, P=0.01 and β=0.11, P=0.04, respectively). Strain analysis using magnetic resonance feature tracking is feasible in population-based cohort studies and shows differences with respect to age and sex as well as an independent association with markers of metabolic syndrome.

Validation of metabotypes identified in an Irish population in the German KORA FF4 study

AbstractPrevious work in an Irish cross-sectional study in adults identified three metabolic subgroups (metabotypes) of individuals using k-means cluster analysis based on four fasting clinical standard parameters (triacylglycerols, total cholesterol, HDL cholesterol and glucose). We aimed to validate these metabotypes in another large population-based study. We assigned 2221 participants aged 38–88 years from the German Cooperative Health Research in the Region of Augsburg (KORA) FF4 study (2013/2014) to the three metabotype clusters identified previously by minimizing the Euclidean distances. These clusters were characterized and compared with one another by metabolic characteristics as well as by cardiometabolic disease prevalence. Further, usual dietary intake of various foods/nutrients was estimated based on a food frequency questionnaire and multiple 24-hour food lists and was investigated across clusters. We identified three metabolically distinct clusters in the KORA FF4 study. Cluster 3 represented the group of participants with the most unfavorable metabolic characteristics (e.g. parameters of glucose and lipid metabolism, inflammatory markers), followed by clusters 2 and 1. Individuals in cluster 3 had the highest prevalence of metabolic diseases. Furthermore, they were characterized by the most unfavorable diet with significantly lowest intakes of vegetables, dairy products and fibers as well as significantly highest intakes of total, red and processed meat. Our finding of distinct metabolic subgroups in the KORA FF4 study suggest a successful validation of the metabotypes originally identified based on four commonly measured clinical parameters. Based on these metabotypes, targeted dietary recommendations may be developed for metabolic disease prevention.

Alcohol consumption is associated with widespread changes in blood DNA methylation: Analysis of cross-sectional and longitudinal data.

DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart. Using the Illumina HumanMethylation450 BeadChip, DNA methylation was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 of them, these measures were repeated using blood samples collected a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models. Independent data from the London Life Sciences Prospective Population (LOLIPOP) (N = 4042) and Cooperative Health Research in the Augsburg Region (KORA) (N = 1662) cohorts were used to replicate associations discovered in the MCCS. Cross-sectional analyses identified 1414 CpGs associated with alcohol intake at P < 10-7 , 1243 of which had not been reported previously. Of these novel associations, 1078 were replicated (P < .05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated 403 of 518 previously reported associations. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1414 CpGs, 530 were differentially methylated (P < .05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1414 cross-sectional associations. Our study indicates that alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with alcohol consumption changes in adulthood.

Association of smoking and physical inactivity with MRI derived changes in cardiac function and structure in cardiovascular healthy subjects

We aimed to investigate the association of smoking and physical exercise on ventricular function and structure, determined by cardiac magnetic resonance imaging (CMR), in subjects without known cardiovascular diseases. A total of 381 participants (median age 57 years) of the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort underwent CMR. The participants’ smoking and sporting habits were measured by a questionnaire. Physical inactivity was associated with a reduction of left ventricular ejection fraction (LV-EF), stroke volume, early diastolic peak filling rate and peak ejection rate of the left ventricle as well as right ventricular stroke volume. LV-EF was reduced in subjects with almost no physical activity compared to subjects with regular physical activity (68.4%, 95%CI 66.8–70.1% vs. 70.8%, 95%CI 69.2–72.3%, p < 0,05). Smokers had lower right ventricular end-diastolic volumes (80.6 ml/m², 95%CI 76.7–84.5 ml/m²; never-smokers: 85.5 ml/m², 95%CI 82.6–88.3 ml/m²; p < 0.05) but higher extracellular volume fractions (ECV) and fibrosis volumes (34.3 ml, 95%CI 32.5–36.0 ml, vs. 31.0 ml, 95%CI 29.6–32.3 ml, p < 0.01). We conclude that asymptomatic individuals without known cardiovascular diseases show differences in cardiac function and structure depending on their physical activity and smoking habits. This underlines the importance of prevention and health education.

Association of Circulating Metabolites With Risk of Coronary Heart Disease in a European Population

Risk stratification for coronary heart disease (CHD) remains challenging because of the complex causative mechanism of the disease. Metabolomic profiling offers the potential to detect new biomarkers and improve CHD risk assessment. To evaluate the association between circulating metabolites and incident CHD in a large European cohort. This population-based study used the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) case-cohort to measure circulating metabolites using a targeted approach in serum samples from 10 741 individuals without prevalent CHD. The cohort consisted of a weighted, random subcohort of the original cohort of more than 70 000 individuals. The case-cohort design was applied to 6 European cohorts: FINRISK97 (Finland), Monitoring of Trends and Determinants in Cardiovascular Diseases/Cooperative Health Research in the Region of Augsburg (MONICA/KORA; Germany), MONICA-Brianza and Moli-sani (Italy), DanMONICA (Denmark), and the Scottish Heart Health Extended Cohort (United Kingdom). Associations with time to CHD onset were assessed individually by applying weighted and adjusted Cox proportional hazard models. The association of metabolites with CHD onset was examined by C indices. In 10 741 individuals (4157 women [38.7%]; median [interquartile range] age, 56.5 [49.2-62.2] years), 2166 incident CHD events (20.2%) occurred over a median (interquartile range) follow-up time of 9.2 (4.5-15.0) years. Among the 141 metabolites analyzed, 24 were significantly associated with incident CHD at a nominal P value of .05, including phosphatidylcholines (PCs), lysoPCs, amino acids, and sphingolipids. Five PCs remained significant after correction for multiple testing: acyl-alkyl-PC C40:6 (hazard ratio [HR], 1.13 [95% CI, 1.07-1.18]), diacyl-PC C40:6 (HR, 1.10 [95% CI, 1.04-1.15]), acyl-alkyl-PC C38:6 (HR, 1.11 [95% CI, 1.05-1.16]), diacyl-PC C38:6 (HR, 1.09 [95% CI, 1.04-1.14]) and diacyl-PC C38:5 (HR, 1.10 [95% CI, 1.05-1.16]). Lower levels of these metabolites were associated with increased risk of incident CHD. The strength of the associations competes with those of classic risk factors (C statistics: acyl-alkyl-PC C40:6, 0.756 [95% CI, 0.738-0.774], diacyl-PC C40:6, 0.754 [95% CI, 0.736-0.772], acyl-alkyl-PC C38:6, 0.755 [95% CI, 0.736-0.773], diacyl-PC C38:6, 0.754 [95% CI, 0.736-0.772]), diacyl-PC C38:5, 0.754 [95% CI, 0.736-0.772]). Adding metabolites to a base risk model including classic risk factors high-sensitivity C-reactive protein and high-sensitivity troponin I did not improve discrimination by C statistics. Five PCs were significantly associated with increased risk of incident CHD and showed comparable discrimination with individual classic risk factors. Although these metabolites do not improve CHD risk assessment beyond that of classic risk factors, these findings hold promise for an improved understanding of the pathophysiology of CHD.

New approaches for integrating sex/gender into environmental health research

PDS 69: Methods and statistics, Johan Friso Foyer, Floor 1, August 26, 2019, 4:30 PM - 5:30 PM Background/Aim. Up to now, the environmental health paradigm is predominantly based upon the distinction of sex-linked biological characteristics. A dichotomous category “male/female” is used for stratified analyses or merely for adjusting as confounder, assuming static differences between men and women on an individual level. However, gender refers to socially influenced behaviours, living conditions and thereby exposure opportunities. Moreover, gender-related factors and stressors (discrimination experiences, social role relations) may modify health effects of environmental exposures. Gender-theoretical concepts like embodiment and intersectionality are promising to advance integration of gender as multidimensional, dynamic category into environmental health research. The aim of the collaborative research project INGER is to develop innovative methods for gender-sensitive data collection and analyses in environmental health studies. Methods. The current state of knowledge and methodological approaches to study the impact of sex/gender on environmental health was assessed by systematic literature reviews for selected topics. Gender-theoretical concepts and proposals for operationalization of gender dimensions (e.g. gender bundle) were evaluated for their applicability. Results. Two questionnaire modules were developed for analyses of sex/gender impact to be applied in (1) KORA (Cooperative Health Research in the Augsburg Region): associations of air pollution and noise with cardiovascular health, of green space availability with self-rated health; (2) German Environmental Specimen Bank: body burden with environmental chemicals. Understandability and feasibility of KORA module was tested in a pilot study (response rate 53% among N=109), 6705 participants will be contacted in the main study. In the German Environmental Specimen Bank 600 participants are being contacted in four cities (so far in one city response rate 80%). Conclusion. The newly collected data will be used to identify methodological approaches of multivariable data analyses which are adequate to quantify sex/gender impacts on environmental exposures and health outcomes. Thus INGER will contribute to gender-sensitive prevention and environmental health protection.

Performance of the UKPDS Outcomes Model2 for Predicting Death and Cardiovascular Events in Patients with Type 2 Diabetes Mellitus from a German Population-Based Cohort.

Accurate prediction of relevant outcomes is important for targeting therapies and to support health economic evaluations of healthcare interventions in patients with diabetes. The United Kingdom Prospective Diabetes Study (UKPDS) risk equations are some of the most frequently used risk equations. This study aims to analyze the calibration and discrimination of the updated UKPDS risk equations as implemented in the UKPDS Outcomes Model2 (UKPDS-OM2) for predicting cardiovascular (CV) events and death in patients with type2 diabetes mellitus (T2DM) from population-based German samples. Analyses are based on data of 456 individuals diagnosed with T2DM who participated in two population-based studies in southern Germany (KORA (Cooperative Health Research in the Region of Augsburg)-A: 1997/1998, n = 178; KORA-S4: 1999-2001, n = 278). We compared the participants' 10-year observed incidence of mortality, CV mortality, myocardial infarction (MI), and stroke with the predicted event rate of the UKPDS-OM2. The model's calibration was evaluated by Greenwood-Nam-D'Agostino tests and discrimination was evaluated by C-statistics. Of the 456 participants with T2DM (mean age 65years, mean diabetes duration 8years, 56% male), over the 10-year follow-up time 129 died (61 due to CV events), 64 experienced an MI, and 46 a stroke. The UKPDS-OM2 significantly over-predicted mortality and CV mortality by 25% and 28%, respectively (Greenwood-Nam-D'Agostino tests: p < 0.01), but there was no significant difference between predicted and observed MI and stroke risk. The model poorly discriminated for death (C-statistic [95% confidence interval] = 0.64 [0.60-0.69]), CV death (0.64 [0.58-0.71]), and MI (0.58 [0.52-0.66]), and failed to discriminate for stroke (0.57 [0.47-0.66]). The study results demonstrate acceptable calibration and poor discrimination of the UKPDS-OM2 for predicting death and CV events in this population-based German sample. Those limitations should be considered when using the UKPDS-OM2 for economic evaluations of healthcare strategies or using the risk equations for clinical decision-making.

Visceral adiposity index (VAI), lipid accumulation product (LAP), and product of triglycerides and glucose (TyG) to discriminate prediabetes and diabetes

The present study evaluated the ability of the visceral adiposity index (VAI), the lipid accumulation product (LAP), and product of triglycerides and glucose (TyG), three novel, insulin resistance-related markers, to discriminate prediabetes/diabetes in the general German population. Altogether 2,045 Germans (31–72 years, 53.3% women) without known diabetes and a history of Myocardial Infarction (MI)/stroke from the Cooperative Health Research in the Region of Augsburg (KORA) F4 Study were eligible. The discriminatory accuracy of the markers for oral glucose tolerance test (OGTT)-defined prediabetes/diabetes according to the American Diabetes Association (ADA) criteria was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). The Youden Index (YI) was used to determine optimal cut-off values, and a non-parametric ROC regression was used to examine whether the discriminatory accuracy varied by sex and age. 365 men (38.2%) and 257 women (23.6%) were newly diagnosed with prediabetes/diabetes. AUCs for TyG, LAP and VAI were 0.762 (95% CI 0.740–0.784), 0.743 (95% CI 0.720–0.765), and 0.687 (95% CI 0.662–0.712), respectively. The optimal cut-off values for the LAP and TyG were 56.70 and 8.75 in men, and 30.40 and 8.53 in women. In conclusion, TyG and LAP provide good discrimination of persons with prediabetes/diabetes.

Exposure to anticholinergic and sedative medications using the Drug Burden Index and its association with vertigo, dizziness and balance problems in older people - Results from the KORA-FF4 Study.

This study examines exposure to anticholinergic and sedative (AS) medications in the general aging population using the Drug Burden Index (DBI) and to analyze the association of AS burden with vertigo, dizziness and balance problems (VDB, primary outcome) and falls (secondary outcome). We performed a cross-sectional analysis of data from the second follow-up (FF4) in 2013/14 of the Cooperative Health Research in the Region of Augsburg (KORA)-S4 study. AS burden was classified as DBI > 0. Self-reported data of VDB and falls during the previous 12 months were collected. Multivariable logistic regression was used to estimate the association of AS burden with VDB and falls. 883 participants were included in this study (mean age 73.8 years, 48.4% female). AS burden was present in 167 (18.9%) participants, with the highest prevalence in those aged ≥80 years old (26.3%). In the adjusted analysis, AS burden was independently and significantly associated with VDB (Adjusted Odds Ratio (AOR): 1.73 [95% CI: 1.16, 2.56]). This study provides reliable prevalence estimates of AS burden in older people using the DBI in Germany, also indicating a positive and significant association with VDB. As VDB are among the main reasons for falls, we do recommend including the AS burden calculation as routine risk assessment in ambulatory medical care.

Methylome-wide association study provides evidence of particulate matter air pollution-associated DNA methylation

BackgroundDNA methylation (DNAm) may contribute to processes that underlie associations between air pollution and poor health. Therefore, our objective was to evaluate associations between DNAm and ambient concentrations of particulate matter (PM) ≤2.5, ≤10, and 2.5–10 μm in diameter (PM2.5; PM10; PM2.5–10). MethodsWe conducted a methylome-wide association study among twelve cohort- and race/ethnicity-stratified subpopulations from the Women's Health Initiative and the Atherosclerosis Risk in Communities study (n = 8397; mean age: 61.5 years; 83% female; 45% African American; 9% Hispanic/Latino American). We averaged geocoded address-specific estimates of daily and monthly mean PM concentrations over 2, 7, 28, and 365 days and 1 and 12 months before exams at which we measured leukocyte DNAm in whole blood. We estimated subpopulation-specific, DNAm-PM associations at approximately 485,000 Cytosine-phosphate-Guanine (CpG) sites in multi-level, linear, mixed-effects models. We combined subpopulation- and site-specific estimates in fixed-effects, inverse variance-weighted meta-analyses, then for associations that exceeded methylome-wide significance and were not heterogeneous across subpopulations (P < 1.0 × 10−7; PCochran's Q > 0.10), we characterized associations using publicly accessible genomic databases and attempted replication in the Cooperative Health Research in the Region of Augsburg (KORA) study. ResultsAnalyses identified significant DNAm-PM associations at three CpG sites. Twenty-eight-day mean PM10 was positively associated with DNAm at cg19004594 (chromosome 20; MATN4; P = 3.33 × 10−8). One-month mean PM10 and PM2.5–10 were positively associated with DNAm at cg24102420 (chromosome 10; ARPP21; P = 5.84 × 10−8) and inversely associated with DNAm at cg12124767 (chromosome 7; CFTR; P = 9.86 × 10−8). The PM-sensitive CpG sites mapped to neurological, pulmonary, endocrine, and cardiovascular disease-related genes, but DNAm at those sites was not associated with gene expression in blood cells and did not replicate in KORA. ConclusionsAmbient PM concentrations were associated with DNAm at genomic regions potentially related to poor health among racially, ethnically and environmentally diverse populations of U.S. women and men. Further investigation is warranted to uncover mechanisms through which PM-induced epigenomic changes may cause disease.