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Abstract Left atrial (LA) physiology and hemodynamics are intimately connected to cardiac and lung function in health and disease. This study examined the relationship between MRI-based left atrial (LA) size and function with MRI-based lung volume and pulmonary function testing (PFT) parameters in the population-based KORA study cohort of 400 participants without overt cardiovascular disease. MRI quantification assessed LA size/function in sequences with and without ECG synchronization, alongside lung volume. Regression analysis explored the relationship of LA with MRI lung volume and PFT parameters. Among 378 participants (average age 56.3 ± 9.2 years; 42.3% women), non-gated LA size averaged 16.8 cm2, while maximal and minimal LA size from gated measurements were 19.6 cm2 and 11.9 cm2 respectively. The average MRI-derived lung volume was 4.0 L, with PFT showing a total lung capacity of 6.2 L, residual lung volume of 2.1 L, and forced vital capacity of 4.1 L. Multivariate regression analysis, adjusted for age, gender, and cardiovascular risk factors, revealed an inverse association between maximum LA size, non-gated LA, and LA area fraction with lung volume (ß = − 0.03, p = 0.006; ß = − 0.03, p = 0.021; ß = − 0.01, p = 0.012), with no significant association with PFT parameters. This suggests that MRI-based assessment may offer greater sensitivity in detecting subclinical LA impairment than PFT.

Abstract Background Obesity is associated with alterations in the hypothalamic–pituitary–adrenal (HPA) axis. Effects of glucocorticoids on adipose tissues appear to depend on the specific adipose depot, in which they take place. In this study, we aimed to investigate the role of MRI-based adrenal gland volume as an imaging marker in association with different adipose tissue compartments. Methods The study cohort derives from the population-based research platform KORA (Cooperative Health Research in the Augsburg Region, Germany) MRI sub-study, a cross-sectional sub-study investigating the interactions between subclinical metabolic changes and cardiovascular disease in a study sample of 400 participants. Originally, eligible subjects underwent a whole-body MRI. MRI-based segmentations were performed manually and semi-automatically for adrenal gland volume, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), epi- and pericardial fat and renal sinus fat. Hepatic and pancreatic lipid content were measured as pancreatic proton density fraction (PDFF) and MR-spectroscopic hepatic fat fraction (HFF). Multivariable linear regression analyses were performed. Results A number of 307 participants (56.2 ± 9.1 years, 60.3% male, 14.3% with type 2 diabetes (T2DM), 30.6% with obesity, 34.2% with hypertension) were included. In multivariable analyses, strong positive associations between adrenal gland volume and VAT, total adipose tissue (TAT) as well as HFF persisted after extensive step-wise adjustment for possible metabolic confounders (VAT: beta = 0.31, 95%-CI [0.71, 0.81], p

Abstract Aim of this study was to analyse the associations of cardiovascular health and adrenal gland volume as a rather new imaging biomarker of chronic hypothalamic–pituitary–adrenal (HPA) axis activation. The study population originates from the KORA population-based cross-sectional prospective cohort. 400 participants without known cardiovascular disease underwent a whole-body MRI. Manual segmentation of adrenal glands was performed on VIBE-Dixon gradient-echo sequence. MRI based evaluation of cardiac parameters was achieved semi-automatically. Cardiometabolic risk factors were obtained through standardized interviews and medical examination. Univariate and multivariate associations were derived. Bi-directional causal mediation analysis was performed. 351 participants were eligible for analysis (56 ± 9.1 years, male 58.7%). In multivariate analysis, significant associations were observed between adrenal gland volume and hypertension (outcome hypertension: Odds Ratio = 1.11, 95% CI [1.01, 1.21], p = 0.028), left ventricular remodelling index (LVRI) (outcome LVRI: β = 0.01, 95% CI [0.00, 0.02], p = 0.011), and left ventricular (LV) wall thickness (outcome LV wall thickness: β = 0.06, 95% CI [0.02, 0.09], p = 0.005). In bi-directional causal mediation analysis adrenal gland volume had a borderline significant mediating effect on the association between hypertension and LVRI (p = 0.052) as well as wall thickness (p = 0.054). MRI-based assessment of adrenal gland enlargement is associated with hypertension and LV remodelling. Adrenal gland volume may serve as an indirect cardiovascular imaging biomarker.

Abstract Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees (“fixed-rate model”, FRM) and up-front staffing and consumables (“up-front allocation model”, UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM). The study protocol activities, which were derived from data management systems, underwent validation through standardized quality checks by multiple stakeholders. The PBRM output (first funding period) was compared among centres and cohorts, and the cost-efficiency of the models was evaluated. Cases per centre varied from one to 164. The mean case reimbursement differed among the cohorts (1173.21€ [95% CI 645.68–1700.73] to 3863.43€ [95% CI 1468.89–6257.96]) and centres and mostly fell short of the expected amount. Model comparisons revealed higher cost-efficiency of the PBRM compared to FRM and UFAM, especially for low recruitment outliers. In conclusion, we have developed a reimbursement model that is transparent, accurate, and flexible. In multi-centre collaborations where heterogeneity between centres is expected, a PBRM could be used as a model to address performance discrepancies. Trial registration: https://clinicaltrials.gov/ct2/show/NCT04768998 ; https://clinicaltrials.gov/ct2/show/NCT04747366 ; https://clinicaltrials.gov/ct2/show/NCT04679584 .

Abstract With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.

Abstract Obesity is characterized by the accumulation of adipose tissue in different body compartments. Whether adipose tissue directly affects kidney function is still unknown. We aimed to investigate the role of the adipose tissue and circulating creatinine, cystatin C and kidney function in subjects free of cardio-renal diseases. In the KORA-MRI population-based study, 377 subjects (mean age 56.2 ± 9.2 years; 41.6% female) underwent whole-body 3T-MRI examination. Adipose tissue defined as visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were quantified from T1-DIXON sequence using a semi-automatic algorithm. Serum creatinine and cystatin C were measured using standard laboratory and estimated glomerular filtration rate (e-GFR) was performed based on creatinine (e-GFRcrea), cystatin C (e-GFRcys) and creatinine-cystatin C (e-GFRcc). Linear regression analysis, adjusted for risk factors, was used to investigate the relationship between adipose tissue and circulating creatinine, cystatin C, and kidney function. In multivariate analyses VAT was inversely associated with eGFRcys (ß = − 4.88, p = 30. VAT is positively associated with serum cystatin C and inversely with eGFR based on cystatin C, suggesting a direct involvement of visceral adipose tissue in increased metabolism of cystatin C and consequently decreased kidney function.

Background: In magnetic resonance imaging (MRI), the comparability of gated and non-gated measurements of the left atrial (LA) area and function and their association with cardiovascular risk factors have not been firmly established. Methods: 3-Tesla MRIs were performed on 400 subjects enrolled in the KORA (Cooperative Health Research in the Augsburg Region) MRI study. The LA maximum and minimum sizes were segmented in gated CINE four-chamber sequences (LAmax and LAmin) and non-gated T1 VIBE-Dixon (NGLA). The area-based LA function was defined as LAaf = (LAmax − LAmin)/LAmax. Inter-and intra-reader reliability tests were performed (n = 31). Linear regression analyses were conducted to link LA size and function with cardiovascular risk factors. Results: Data from 378 subjects were included in the analysis (mean age: 56.3 years, 57.7 % male). The measurements were highly reproducible (all intraclass correlation coefficients ≥ 0.98). The average LAmax was 19.6 ± 4.5 cm2, LAmin 11.9 ± 3.5 cm2, NGLA 16.8 ± 4 cm2 and LAaf 40 ± 9%. In regression analysis, hypertension was significantly associated with larger gated LAmax (β = 1.30), LAmin (β = 1.07), and non-gated NGLA (β = 0.94, all p ≤ 0.037). Increasing age was inversely associated with LAaf (β = −1.93, p < 0.001). Conclusion: LA enlargement, as measured in gated and non-gated CMR is associated with hypertension, while the area-based LA function decreases with age.

Abstract Background Skeletal muscle mass is subjected to constant changes and is considered a good predictor for outcome in various diseases. Bioelectrical‐impedance analysis (BIA) and magnetic resonance imaging (MRI) are approved methodologies for its assessment. However, muscle mass estimations by BIA may be influenced by excess intramuscular lipids and adipose tissue in obesity. The objective of this study was to evaluate the feasibility of quantitative assessment of skeletal muscle mass by MRI as compared with BIA. Methods Subjects from a population‐based cohort underwent BIA (50 kHz, 0.8 mA) and whole‐body MRI including chemical‐shift encoded MRI (six echo times). Abdominal muscle mass by MRI was quantified as total and fat‐free cross‐sectional area by a standardized manual segmentation‐algorithm and normalized to subjects' body height2 (abdominal muscle mass indices: AMMIMRI). Results Among 335 included subjects (56.3 ± 9.1 years, 56.1% male), 95 (28.4%) were obese (BMI ≥ 30 kg/m2). MRI‐based and BIA‐based measures of muscle mass were strongly correlated, particularly in non‐obese subjects [r

Background: Specification of adipose tissues by whole-body magnetic resonance imaging (MRI) was performed and related to pulmonary function parameters in a population-based cohort. Methods: 203 study participants underwent whole-body MRI and pulmonary function tests as part of the KORA (Cooperative Health Research in the Augsburg Region) MRI study. Both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were derived from the T1-Dixon sequence, and hepatic adipose tissue from the proton density fat fraction (PDFFhepatic). Associations between adipose tissue parameters and spirometric indices such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and Tiffeneau-index (FEV1/FVC) were examined using multivariate linear regression analysis excluding cofounding effects of other clinical parameters. Results: VAT (β = −0.13, p = 0.03) and SAT (β = −0.26, p < 0.001), but not PDFFhepatic were inversely associated with FEV1, while VAT (β = −0.27, p < 0.001), SAT (β = −0.41, p < 0.001), and PDFFhepatic (β = −0.17, p = 0.002) were inversely associated with FVC. PDFFhepatic was directly associated with the Tiffeneau index (β = 2.46, p < 0.001). Conclusions: In the adjusted linear regression model, VAT was inversely associated with all measured spirometric parameters, while PDFFhepatic revealed the strongest association with the Tiffeneau index. Non-invasive adipose tissue quantification measurements might serve as novel biomarkers for respiratory impairment.

Abstract To evaluate the relationship of cardiac function, including time-volume-curves, with lung volumes derived from pulmonary function tests (PFT) and MRI in subjects without cardiovascular diseases. 216 subjects underwent whole-body MRI and spirometry as part of the KORA-FF4 cohort study. Lung volumes derived semi-automatically using an in-house algorithm. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and residual volume were measured. Cardiac parameters derived from Cine-SSFP-sequence using cvi42, while left ventricle (LV) time-volume-curves were evaluated using pyHeart. Linear regression analyses assessed the relationships of cardiac parameters with PFT and MRI-based lung volumes. Mean age was 56.3 ± 9.2 years (57% males). LV and right ventricular (RV) end-diastolic-, end-systolic-, stroke volume, LV peak ejection- and early/late diastolic filling rate were associated with FEV1, FVC, and residual volume (excluding late diastolic filling rate with FEV1, LV end-systolic/stroke volume and RV end-diastolic/end-systolic volumes with residual volume). In contrast, LV end-diastolic volume (ß = − 0.14, p = 0.01), early diastolic filling rate (ß = − 0.11, p = 0.04), and LV/RV stroke volume (ß = − 0.14, p = 0.01; ß = − 0.11, p = 0.01) were inversely associated with MRI-based lung volume. Subclinical cardiac impairment was associated with reduced FEV1, FVC, and residual volume. Cardiac parameters decreased with increasing MRI-based lung volume contrasting the results of PFT.

Abstract Background The association of longitudinal trajectories of cardiovascular risk factors with cardiovascular magnetic resonance (CMR)-measures of cardiac structure and function in the community is not well known. Therefore we aimed to relate risk factor levels from different examination cycles to CMR-measures of the left ventricle (LV) and right ventricle in a population-based cohort. Methods We assessed conventional cardiovascular disease risk factors in 349 participants (143 women; aged 25–59 years) at three examination cycles (Exam 1 [baseline], at Exam 2 [7-years follow-up] and at Exam 3 [14-years follow-up]) of the KORA S4 cohort and related single-point measurements of individual risk factors and longitudinal trajectories of these risk factors to various CMR-measures obtained at Exam 3. Results High levels of diastolic blood pressure, waist circumference, and LDL-cholesterol at the individual exams were associated with worse cardiac function and structure. Trajectory clusters representing higher levels of the individual risk factors were associated with worse cardiac function and structure compared to low risk trajectory clusters of individual risk factors. Multivariable (combining different risk factors) trajectory clusters were associated with different cardiac parameters in a graded fashion (e.g. decrease of LV stroke volume for middle risk cluster β = − 4.91 ml/m2, 95% CI − 7.89; − 1.94, p

Abstract To identify the most important parameters associated with cerebral white matter hyperintensities (WMH), in consideration of potential collinearity, we used a data-driven machine-learning approach. We analysed two independent cohorts (KORA and SHIP). WMH volumes were derived from cMRI-images (FLAIR). 90 (KORA) and 34 (SHIP) potential determinants of WMH including measures of diabetes, blood-pressure, medication-intake, sociodemographics, life-style factors, somatic/depressive-symptoms and sleep were collected. Elastic net regression was used to identify relevant predictor covariates associated with WMH volume. The ten most frequently selected variables in KORA were subsequently examined for robustness in SHIP. The final KORA sample consisted of 370 participants (58% male; age 55.7 ± 9.1 years), the SHIP sample comprised 854 participants (38% male; age 53.9 ± 9.3 years). The most often selected and highly replicable parameters associated with WMH volume were in descending order age, hypertension, components of the social environment (i.e. widowed, living alone) and prediabetes. A systematic machine-learning based analysis of two independent, population-based cohorts showed, that besides age and hypertension, prediabetes and components of the social environment might play important roles in the development of WMH. Our results enable personal risk assessment for the development of WMH and inform prevention strategies tailored to the individual patient.

Introduction As white matter hyperintensities (WMHs) of the brain are associated with an increased risk of stroke, cognitive decline, and depression, elucidating the associated risk factors is important. In addition to age and hypertension, pre-diabetes and diabetes may play important roles in the development of WMHs. Previous studies have, however, shown conflicting results. We aimed to investigate the effect of diabetes status and quantitative markers of glucose metabolism on WMH volume in a population-based cohort without prior cardiovascular disease.Research design and methods 400 participants underwent 3 T MRI. WMHs were manually segmented on 3D fluid-attenuated inversion recovery images. An oral glucose tolerance test (OGTT) was administered to all participants not previously diagnosed with diabetes to assess 2-hour serum glucose concentrations. Fasting glucose concentrations and glycated hemoglobin (HbA1c) levels were measured. Zero-inflated negative binomial regression analyses of WMH volume and measures of glycemic status were performed while controlling for cardiovascular risk factors and multiple testing.Results The final study population comprised 388 participants (57% male; age 56.3±9.2 years; n=98 with pre-diabetes, n=51 with diabetes). Higher WMH volume was associated with pre-diabetes (p=0.001) and diabetes (p=0.026) compared with normoglycemic control participants after adjustment for cardiovascular risk factors. 2-hour serum glucose (p

Abstract Background Mortality attributable to heart failure remains high. The prevalence of heart failure in patients with diabetes mellitus ranges from 19 to 26%. It is estimated that up to 21.1 million adults in the United States have diagnosed diabetes mellitus and around 80.8 million have impaired fasting glucose. We investigated the associations of fasting glucose (FG) and fasting insulin (FI), the homeostasis model assessment-insulin resistance index (HOMA-IR) and 2-h postload glucose (2HG) and insulin (2HI) with parameters of left ventricular geometry and function and arterial stiffness determined by magnetic resonance imaging in individuals without diagnosed type 2 diabetes. Methods Cross-sectional analyses of 1001 individuals (453 women, 45.3%), aged 21 to 80 years, from two independent population-based studies, the Study of Health in Pomerania (SHIP-TREND-0) and KORA FF4 Study. FG, FI, HOMA-IR, 2HG and 2HI, as well as glucose tolerance categories, were analyzed for associations with heart and arterial parameters using multivariable-adjusted linear regression models. Results In total, 390 individuals (39%) had prediabetes (isolated impaired fasting glucose, isolated glucose tolerance or both), and 49 (4.9%) were found to have unknown type 2 diabetes. In the multivariable-adjusted analysis, positive linear associations of FG, FI, HOMA-IR, 2HG and 2HI with arterial stiffness index and left ventricular wall-thickness and concentricity and inverse linear associations with left ventricular end-diastolic volume were observed. A 1 mmol/l higher FG was associated with a 1.18 ml/m2.7 (1.80 to 0.57; p

ObjectiveThis study aims to investigate the correlation between spinopelvic parameters in supine position (pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), lumbar lordosis (LL)), disc degeneration and herniation of the thoracolumbar spine, as well as cardiovascular risk factors and back pain in a southern German cohort from the general population.MethodsThis study is a cross-sectional, case-control study drawn from a prospective cohort of the "Cooperative Health Research in the Region of Augsburg/Kooperative Gesundheitsforschung in der Region Augsburg" study (KORA). In total, 374 participants (mean age 56.4 ± 9.2 years; 57.8% male) from the whole-body MRI cohort (FF4) were included. All participants underwent a standardized whole-body MRI on which disc degeneration of the thoracic and lumbar spine was evaluated using a sequence adapted Pfirrmann score. PI, PT, SS and LL were measured according to the description in the literature, using sagittal imaging. Furthermore, disc bulging and protrusion were assessed. Correlations were estimated by logistic regression models providing odds ratios.ResultsMean PI was 54.0° ± 11.1°, PT 13.0° ± 5.8°, SS 40.2° ± 8.8° and LL 36.2° ± 9.6°. SS was greater in men (pConclusionIn conclusion, spinopelvic parameters, measured in supine position, are significantly correlated with disc bulging alone; there is no significant correlation between supine spinopelvic parameters and disc degeneration, back pain or cardiovascular risk factors.

PURPOSE:We hypothesize that MRI-based renal compartment volumes, particularly renal sinus fat as locally and potentially independently acting perivascular fat tissue, increase with glucose intolerance. We therefore analyze the distribution of renal volumes in individuals with normal glucose levels and prediabetic and diabetic individuals and investigate potential associations with other typical cardiometabolic biomarkers. MATERIAL AND METHODS:The sample comprised N = 366 participants who were either normoglycemic (N = 230), had prediabetes (N = 87) or diabetes (N = 49), as determined by Oral Glucose Tolerance Test. Other covariates were obtained by standardized measurements and interviews. Whole-body MR measurements were performed on a 3 Tesla scanner. For assessment of the kidneys, a coronal T1w dual-echo Dixon and a coronal T2w single shot fast spin echo sequence were employed. Stepwise semi-automated segmentation of the kidneys on the Dixon-sequences was based on thresholding and geometric assumptions generating volumes for the kidneys and sinus fat. Inter- and intra-reader variability were determined on a subset of 40 subjects. Associations between glycemic status and renal volumes were evaluated by linear regression models, adjusted for other potential confounding variables. Furthermore, the association of renal volumes with visceral adipose tissue was assessed by linear regression models and Pearson's correlation coefficient. RESULTS:Renal volume, renal sinus volume and renal sinus fat increased gradually from normoglycemic controls to individuals with prediabetes to individuals with diabetes (renal volume: 280.3±64.7 ml vs 303.7±67.4 ml vs 320.6±77.7ml, respectively, p < 0.001). After adjustment for age and sex, prediabetes and diabetes were significantly associated to increased renal volume, sinus volume (e.g. βPrediabetes = 10.1, 95% CI: [6.5, 13.7]; p

OBJECTIVE:To investigate the impact of metabolic syndrome and its components on osteoarthritis of the hip joints compared to a healthy cohort in the KORA MRI-study. METHODS:Randomly selected men and women from the general population were classified as having metabolic syndrome, defined as presence of central obesity plus two of the following four components: elevated blood pressure (BP), elevated fasting glucose, elevated triglycerides (TG) and low HDL-cholesterol (HDL-c), or as controls without metabolic syndrome. Therefore, each subject underwent detailed assessment of waist circumference as well as fasting glucose, systolic and diastolic BP, TG, and HDL-c concentrations as well as a full-body MR scan. MR measurements were performed on a 3 Tesla scanner (Magnetom Skyra, Siemens) including a dual-echo Dixon and a T2 SS-FSE sequence for anatomical structures. In order to quantify osteoarthritis of the hip, assessment was performed by two independent, experienced radiologists for joint gap narrowing, osteophytic lipping and subchondral changes (e.g. sclerosis, pseudocysts). Associations between metabolic syndrome components and hip degeneration were estimated by logistic regression models providing odds ratios. RESULTS:Among 354 included participants (mean age: 56.1 ± 9.2 years; 55.4% male), 119 (34%) had metabolic syndrome, while 235 (66%) were part of the control group. Except for elevated blood glucose (p = 0.02), none of the metabolic syndromes' component was independently associated with osteoarthritis. Multivariable adjusted ORs for osteoarthritis of the right hip were 1.00 (95% CI 0.98;1.03), 1.00 (95% CI 0.99;1.00), 1.01 (95% CI 0.99;1.03), 1.00 (95% CI 0.97;1.04) and 1.01 (95% CI 0.96;1.06), and for the left hip 1.00 (95% CI 0.98;1.03), 1.00 (95% CI 1.00;1.01), 1.01 (95% CI 0.99;1.03), 0.99 (95% CI 0.96;1.02) and 1.04 (95% CI 0.99;1.09) for waist circumference, triglyceride, HDL-c and systolic and diastolic BP, respectively. Blood glucose was a borderline non-dependent factor for osteoarthritis of the right hip (OR: 1.02 (95% CI 1.0;1.04); p = 0.05). Furthermore, the compound metabolic syndrome was not significantly associated (OR left hip: 1.53 (95% CI 0.8;2.92), p = 0.20; OR right hip: 1.33 (95% CI 0.72;2.45), p = 0.37) with osteoarthritis of the hip joint. Age as well as gender (left hip) were the only parameters in univariate and multivariate analysis to be significantly associated with osteoarthritis of the hip joint. CONCLUSION:The compound metabolic syndrome showed no association with osteoarthritis of the hip joint. Age was the only parameter to be dependently and independently associated to osteoarthritis of both hip joints, while elevated blood glucose was independently associated with degeneration of the right hip joint.

Obesity increases the risk of cardiovascular diseases (CVD), however, whether adipose tissue relates to dyslipidemia, and consequently to cardiovascular events remains unknown. Thus, we investigated the association of adipose tissue with circulating lipoproteins and triglycerides (TG) in subjects without CVD. 384 participants from the KORA-MRI study (mean age 56.2 ± 9.2 years; 41.9% female) underwent whole-body 3T-MRI. Visceral (VAT) and subcutaneous adipose tissue (SAT) derived from T1-DIXON-sequence using a semi-automatic algorithm. Total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and TG were measured. Linear regression was applied to examine the relationships between adipose tissue, circulating lipoproteins, and TG, adjusting for risk factors. VAT was associated with total cholesterol (per SD increase) (ß = 0.39, p < 0.001). Total adipose tissue (TAT) and VAT were inversely associated with HDL (ß = −0.09, p = 0.009; ß = −0.14, p < 0.001), and positively associated with LDL (ß = 0.32, p < 0.001; ß = 0.37, p < 0.001). All adipose tissues were associated with TG (ß = 0.20, p < 0.001; ß = 0.27, p < 0.001; ß = 0.11, p = 0.004). Stratified analysis by sex and body mass index (BMI) was confirmatory in women and in individuals with BMI < 30. Our results suggest that adipose tissue plays an important role in increasing CVD risk independent of BMI, whereas gender imbalance may be explained by accurate characterization and quantification of adipose tissue.

Abstract Background Left ventricular (LV) hypertrophy and changes in LV geometry are associated with increased cardiovascular mortality. Subjects with type 2 diabetes have an increased risk of such alterations in cardiac morphology. We sought to assess the association of glycemic status and LV wall thickness measured by cardiac magnetic resonance (CMR), and potential interactions of hypertension and diabetes. Methods CMR was performed on 359 participants from a cross-sectional study nested in a population-based cohort (KORA FF4) free of overt cardiovascular disease. Participants were classified according to their glycemic status as either control (normal glucose metabolism), prediabetes or type 2 diabetes. Segmentation of the left ventricle was defined according to the American Heart Association (AHA) 16-segment model. Measurements of wall thickness were obtained at end-diastole and analyzed by linear regression models adjusted for traditional cardiovascular risk factors. Results LV wall thickness gradually increased from normoglycemic controls to subjects with prediabetes and subjects with diabetes (8.8 ± 1.4 vs 9.9 ± 1.4 vs 10.5 ± 1.6 mm, respectively). The association was independent of hypertension and traditional cardiovascular risk factors (β-coefficient: 0.44 mm for prediabetes and 0.70 mm for diabetes, p-values compared to controls: p = 0.007 and p = 0.004, respectively). Whereas the association of glycemic status was strongest for the mid-cavity segments, the association of hypertension was strongest for the basal segments. Conclusion Abnormal glucose metabolism, including pre-diabetes, is associated with increased LV wall thickness independent of hypertension.

Abstract Objectives Local, abdominal fat depots may be related to alterations in cardiac function and morphology due to a metabolic linkage. Thus, we aimed to determine their association with subtle cardiac changes and the potential interaction with hyperglycemic metabolic states. Methods Subjects from the general population and without history of cardiovascular disease were drawn from the Cooperative Health Research in the Region of Augsburg FF4 cohort and underwent 3 T cardiac and body MRI. Measures of abdominal adiposity such as hepatic proton-density fat fraction [PDFFhepatic], subcutaneous (SAT) and visceral abdominal fat (VAT) as well as established cardiac left-ventricular (LV) measures including LV remodeling index (LVCI) were derived. Associations were determined using linear regression analysis based on standard deviation normalized predictors. Results Among a total of 374 subjects (56.2 ± 9.1 years, 58% males), 49 subjects had diabetes, 99 subjects had prediabetes and 226 represented normal controls. Only subtle cardiac alterations were observed (e.g. LVCI: 1.13 ± 0.30). While SAT was not associated, increasing VAT and increasing PDFFhepatic were independently associated with increasing LVCI (β = 0.11 and 0.06, respectively), decreasing LV end-diastolic volume (β = − 6.70 and 3.23, respectively), and decreasing LV stroke volume (β = − 3.91 and − 2.20, respectively). Hyperglycemic state did not modify the associations between VAT or PDFF and LV measures (interaction term: all p ≥ 0.29). Conclusion In a healthy population, VAT but also PDFFhepatic were associated with subclinical measures of LV remodeling without evidence for a modifying effect of hyperglycemic state.

Hepatic iron overload can cause severe organ damage; therefore, an early diagnosis and the identification of potential risk factors is crucial. We aimed to investigate the sex-specific distribution of hepatic iron content (HIC) in a population-based cohort and identify relevant associated factors from a panel of markers. We analyzed N = 353 participants from a cross-sectional sample (KORA FF4) who underwent whole-body magnetic resonance imaging. HIC was assessed by single-voxel spectroscopy with a high-speed T2-corrected multi-echo technique. A large panel of markers, including anthropometric, genetic, and laboratory values, as well as behavioral risk factors were assessed. Relevant factors associated with HIC were identified by variable selection based on LASSO regression with bootstrap resampling. HIC in the study sample (mean age at examination: 56.0 years, 58.4% men) was significantly lower in women (mean ± SD: 39.2 ± 4.1 s−1) than in men (41.8 ± 4.7 s−1, p < 0.001). Relevant factors associated with HIC were HbA1c as well as prediabetes for men and visceral adipose tissue as well as age for women. Hepatic fat, alcohol consumption, and genetic risk score for iron levels were associated with HIC in both sexes. In conclusion, there are sex-specific associations of HIC with markers of body composition, glucose metabolism, and alcohol consumption.

Iron-related disorders of the liver can result in serious health conditions, such as liver cirrhosis. Evidence on the role of modifiable lifestyle factors like nutrition in liver iron storage is lacking. Thus, we aimed to assess the association of habitual diet with liver iron content (LIC). We investigated 303 participants from the population-based KORA-MRI study who underwent whole-body magnetic resonance imaging (MRI). Dietary habits were evaluated using repeated 24 h food lists and a food frequency questionnaire. Sex-stratified multiple linear regression models were applied to quantify the association between nutrition variables of interest and LIC, adjusting for liver fat content (LFC), energy intake, and age. Mean age of participants was 56.4 ± 9.0 years and 44.2% were female. Mean LIC was 1.23 ± 0.12 mg/g dry weight, with higher values in men than in women (1.26 ± 0.13 and 1.20 ± 0.10 mg/g, p < 0.001). Alcohol intake was positively associated with LIC (men: β = 1.94; women: β = 4.98, p-values < 0.03). Significant negative associations with LIC were found for fiber (β = −5.61, p < 0.001) and potassium (β = −0.058, p = 0.034) for female participants only. Furthermore, LIC was highly correlated with liver fat content in both sexes. Our findings suggests that there are sex-specific associations of habitual dietary intake and LIC. Alcohol, fiber, and potassium may play a considerable role in liver iron metabolism.

PURPOSE AND METHODS:A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire. The associations of claudication with continuous ABI values and decreased ABI were analyzed by linear and logistic regression analysis, respectively. The results of the studies were pooled in a random effect meta-analysis, which included data from 27,945 individuals (14,052 women, age range 20-84 years). RESULTS:Meta-analysis revealed a significant negative association between claudication and ABI, which was stronger in men (β = -0.07; 95%CI -0.10, -0.04) than in women (β = -0.02; 95%CI -0.02, -0.01). Likewise, the presence of claudication symptoms was related to an increased odds of a decreased ABI in both men (Odds ratio = 5.40; 95%CI 4.20, 6.96) and women (Odds ratio = 1.99; 95%CI 1.58, 2.51). CONCLUSIONS:Asking only one question about claudication was able to identify many individuals with a high likelihood of a reduced ABI with markedly higher sensitivity and only slightly reduced specificity compared to more complex questionnaires. At least in men, this question should be established as first screening step.

Subclinical effects of coffee consumption (CC) with regard to metabolic, cardiac, and neurological complications were evaluated using a whole-body magnetic resonance imaging (MRI) protocol. A blended approach was used to estimate habitual CC in a population-based study cohort without a history of cardiovascular disease. Associations of CC with MRI markers of gray matter volume, white matter hyperintensities, cerebral microhemorrhages, total and visceral adipose tissue (VAT), hepatic proton density fat fraction, early/late diastolic filling rate, end-diastolic/-systolic and stroke volume, ejection fraction, peak ejection rate, and myocardial mass were evaluated by linear regression. In our analysis with 132 women and 168 men, CC was positively associated with MR-based cardiac function parameters including late diastolic filling rate, stroke volume (p < 0.01 each), and ejection fraction (p < 0.05) when adjusting for age, sex, smoking, hypertension, diabetes, Low-density lipoprotein (LDL), triglycerides, cholesterol, and alcohol consumption. CC was inversely associated with VAT independent of demographic variables and cardiovascular risk factors (p < 0.05), but this association did not remain significant after additional adjustment for alcohol consumption. CC was not significantly associated with potential neurodegeneration. We found a significant positive and independent association between CC and MRI-based systolic and diastolic cardiac function. CC was also inversely associated with VAT but not independent of alcohol consumption.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

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.

INTRODUCTION:Morphological characterization of leg arteries is of significant importance to detect vascular remodeling triggered by atherosclerotic changes. We determined reference values of vessel diameters and assessed prevalence of stenosis and arterial variations of the lower limb arteries in a healthy male population sample. METHODS:Gadolinium-enhanced magnetic resonance angiography at 1.5 Tesla was performed in 756 male participants (median age = 52 years, range = 21-82 years) of the population-based Study of Health in Pomerania. Vessel diameters were measured in 9 predefined segments of the pelvic and leg arteries and 95th percentiles were used for upper reference values of means of left and right side arteries. RESULTS:Reference values of vascular diameters decreased from proximal to distal arteries: common iliac = 1.18cm; internal iliac = 0.75cm; external iliac = 1.03cm; proximal femoral = 1.02cm; distal femoral = 0.77cm; popliteal = 0.69cm; anterior tibial = 0.42cm; posterior tibial = 0.38cm; fibular = 0.40cm. Body-surface area indexed reference values increased with age in all segments. A number of 53 subjects (7.0%) had at least one stenosis, mainly in the lower leg arteries anterior tibial (n = 28, 3.7%), posterior tibial (n = 18, 2.4%) and fibular (n = 20, 2.6%). The risk of stenosis increased considerably with age (odds ratio = 1.08; p

The aim of our study was to determine the relation of alcohol consumption and cigarette smoking on continuous-measured hepatic fat fraction (HFF) in a population free of cardiovascular disease. We suggested a direct correlation of alcohol consumption with HFF and increased HFF in former smokers compared to current smokers.Data from 384 subjects (mean age: 56 years, 58% men) of a population-based cohort study (KORA) were included in a cross-sectional design. Liver fat was assessed by 3 Tesla magnetic resonance imaging (MRI) using a multi-echo Dixon sequence and T2-corrected single voxel multi-echo spectroscopy (1H-MRS). Smoking status was classified as never, former or current smoker and alcohol consumption as non-, moderate (0.1-39.9 g/day for men and 0.1-19.9 g/day for women), or heavy drinker (≥ 40 g/day for men and ≥ 20 g/day for women). Fatty liver disease was defined as HFF≥5.56%.Average HFF was 8.8% by 1H-MRS and 8.5% by MRI. Former smokers showed a higher HFF (MRI: β = 2.64; p = 0.006) and a higher FLD prevalence (MRI: OR = 1.91; p = 0.006) compared to never smokers. Current smokers showed decreased odds for FLD measured by 1H-MRS after multivariable adjustment (OR = 0.37; p = 0.007) with never smoker as reference. Heavy drinking was positively associated with HFF (1H-MRS: β = 2.99; p = 0.003) and showed highest odds for FLD (1H-MRS: OR = 3.05; p = 0.008) with non-drinker as reference. Moderate drinking showed a positive association with HFF (1H-MRS: β = 1.54; p = 0.061 and MRI: β = 1.75; p = 0.050).Our data revealed lowest odds for FLD in current smokers, moderate drinkers showing higher HFF than non-drinkers and heavy drinkers showing highest HFF and odds for FLD. These findings partly conflict with former literature and underline the importance of further studies to investigate the complex effects on liver metabolism.

Objectives: Occupational exposure to asbestos is associated with increased mortality which, however, has not been thoroughly validated in a general population. We have aimed at exploring whether this association may be confirmed within a population-based setting after adjustment for confounders. Furthermore, the impact of tobacco consumption on the association between occupational exposure to asbestos and mortality is assessed. Material and Methods: We used data from 2072 (224 exposed) male participants of the Study of Health in Pomerania. Information on exposure to asbestos is based on a selfreport. Median follow-up time was 11.3 years. All-cause mortality and cause-specific mortality of exposed and non-exposed men were compared using mortality rate ratios, Kaplan-Meier analyses and multivariable Cox regression. Results: During the follow-up, 52 (23.2%) exposed and 320 (17.3%) non-exposed participants deceased. Exposed subjects had increased hazard ratios (HR) for all-cause mortality (HR=1.48, 95% CI: 1.1–2), benign lung disease mortality (HR=3, 95% CI: 1.18– 7.62) and stomach cancer mortality (HR=4.59, 95% CI: 1.53–13.76). The duration of exposure (per 10 years) was associated with all-cause (HR=1.21, 95% CI: 1.07–1.36) and benign lung disease mortality (HR=1.68, 95% CI: 1.26–2.22). Smokers occupationally exposed to asbestos had the highest risk for all-cause (HR=3.70, 95% CI: 2.19–6.27) and cancer mortality (HR=4.56, 95% CI: 1.99–10.48) as compared to non-asbestos exposed non-smokers. Conclusions: Our results confirm associations of occupational exposure to asbestos with all-cause, benign lung disease, and stomach cancer mortality and underline the impact of joint effects of asbestos and smoking on mortality.

BACKGROUND/OBJECTIVE:Despite the relevance of pancreatic fat content in the development of metabolic diseases, its association with impaired glucose metabolism, diabetes, and other adipose tissue compartments remains unclear. Thus, we determined differences in pancreatic fat content by magnetic resonance imaging (MRI) between subjects with prediabetes, diabetes, and normal controls in a cohort from the general population. METHODS:Subjects without history of cardiovascular disease with established diabetes or prediabetes as well as normal controls were included and underwent whole-body MRI on a 3T scanner. Pancreatic fat content was quantified by measuring the proton-density fat fraction (PDFFpanc) using a 3D multi-echo GRE sequence (increment: 1.23 ms, 6 echoes) by placing ROIs in the pancreatic head, body, and tail by independent readers. In addition, hepatic fat content as well as abdominal subcutaneous and visceral adipose tissue (SAT and VAT) were measured by multi-echo GRE and 3D 2-point volume-interpolated DIXON MRI, respectively. Univariate and multivariate analyses were employed to determine associations. RESULTS:A total of 385 subjects were included in the analysis (median age: 57 years, 58.2% males), of them 53 were classified as subjects with diabetes, 95 as prediabetes, and 237 as controls (13.8%, 24.7%, and 61.6%; respectively). The median PDFFpanc was 5.2% [IQR 3.3-9.4], and significantly higher in subjects with prediabetes and diabetes as compared to controls (PDFFpanc: 6.2% [IQR: 3.5-12] vs. 8.6% [IQR: 4.3-17.5] vs. 4.9% [3.1-7.4], p0.12). While in univariate analysis BMI, PDFFhepatic, SAT and VAT were associated with PDFFpanc (all p

We investigated the association between subclinical cardiovascular diseases assessed by MRI examination and symptoms of dizziness and vertigo in participants of a population-based sample.Data from 400 participants (169 women) aged from 39 to 73 of a cross-sectional MRI sub-study of the "Kooperative Gesundheitsforschung in der Region Augsburg" (KORA) FF4 study from the south of Germany was used. MRI determined subclinical cardiovascular diseases include left and right ventricular structure and function as well as the presence of carotid plaque and carotid wall thickness. Cerebrum diseases include white matter lesions (WML) and cerebral microbleeds (CMB). The main outcomes of dizziness and vertigo were assessed by standardized interview. Logistic regression models were applied and adjusted odds ratios (OR) with 95% confidence intervals (CI) were provided.Lifetime and 12-month prevalence of dizziness and vertigo were 30% (95%CI 26% to 35%) and 21% (95%CI 17% to 26%) respectively in this sample. On multivariable analysis, cardiac and carotid measurements were not associated with dizziness and vertigo excluding orthostatic vertigo (20%, 95CI 16% to 24%). Only in male participants, there was a significant association between WML and the presence of dizziness and vertigo (OR = 2.95, 95%CI 1.08 to 8.07). There was no significant association of CMB with dizziness and vertigo. However, CMB and WML were tending to associate with a higher risk of dizziness and vertigo in the whole sample (CMB: OR = 1.48, 95%CI 0.70; 3.15; WML: OR = 1.71, 95%CI 0.80 to 3.67;), in persons with prediabetes and diabetes (WML: OR = 2.71, 95%CI 0.89 to 8.23) and in men with normal glucose metabolism (CMB: OR = 2.60, 95%CI 0.56 to 12.0; WML: OR = 3.08, 95%CI 0.58 to 16.5).In this sample of participants without manifest cardiovascular diseases, subclinical left and right ventricular function and carotid structure were consistently not associated with dizziness and vertigo. Subclinical cerebrum measurements, however, tend to increase the risk for dizziness and vertigo, especially in men and in persons with prediabetes or diabetes.

The present study investigated the association of carbohydrate intake and isocaloric substitution with different types of fat with visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and hepatic fat content as determined by magnetic resonance imaging (MRI). Data from 283 participants (mean age 56.1 ± 9.0 years) from the MRI sub study of the KORA FF4 study were included. VAT, SAT and total body fat were quantified by a volume-interpolated VIBE-T1w-Dixon MR sequence. Hepatic fat content was determined as the proton density fat-fraction (PDFF) derived from multiecho-T1w MR sequence. Dietary intake was estimated using information provided by two different instruments, that is, repeated 24-h food lists and a food frequency questionnaire. Replacing total carbohydrates with an isoenergetic amount of total fat was significantly positively associated with VAT and hepatic fat, while there was no significant association with SAT. The multivariable adjusted β-coefficient for replacing 5% of total energy (5E%) carbohydrates with total fat was 0.42 L (95% CI: 0.04, 0.79) for VAT. A substitution in total fat intake by 5E% was associated with a significant increase in liver fat content by 23% (p-value 0.004). If reproduced in prospective studies, such findings would strongly argue for limiting dietary fat intake.

The functional consequences of trait associated SNPs are often investigated using expression quantitative trait locus (eQTL) mapping. While trait-associated variants may operate in a cell-type specific manner, eQTL datasets for such cell-types may not always be available. We performed a genome-environment interaction (GxE) meta-analysis on data from 5,683 samples to infer the cell type specificity of whole blood cis-eQTLs. We demonstrate that this method is able to predict neutrophil and lymphocyte specific cis-eQTLs and replicate these predictions in independent cell-type specific datasets. Finally, we show that SNPs associated with Crohn's disease preferentially affect gene expression within neutrophils, including the archetypal NOD2 locus.

A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD) as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men) aged 25-85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL) and pocket probing depth (PPD) as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005). Measurements of FMD and nitroglycerin-mediated dilation (NMD) were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥ 6 mm with FMD (p(trend)=0.048), with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p