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PURPOSE: Hip osteoarthritis (HOA) is known to have a multifactorial pathogenesis. Recent studies suggest that spinopelvic alignment may represent an important additional pathogenic abnormality resulting in HOA. This study aims to assess the correlation between spinopelvic parameters (pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS) and lumbar lordosis (LL)) obtained in the supine position on MRI and HOA, lateral center edge (LCE) angle, and patient reported back pain. METHODS: Asymptomatic participants from the whole-body MRI cohort (FF4) from the cross-sectional case-control "Cooperative Health Research in the Region of Augsburg" study (KORA) were included. Whole-body MRI was performed in a standardized fashion in each case, on which hip osteoarthritis (HOA), anatomical spinopelvic parameters and lateral center edge angle were measured. Presence of back pain was assessed using a standardized questionnaire. Correlations were estimated by logistic regression models providing odds ratio. RESULTS: Among 340 subjects (mean age 56.3±9.3 years; 56.5% male), HOA was present in 89.1% (male: 87.0%, female: 91.7%, p=0.17). The LCE angle was 30.0° ± 5.5 (men: 29.8° ± 5.9; women: 30.1° ± 5.1; p=0.696). Mean PI was 54.0° ± 11.3°, PT was 13.7° ± 5.9°, SS was 40.3° ± 8.8° (significantly smaller in women p

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.

The COVID-19 pandemic has urged the need to set up, conduct and analyze high-quality epidemiological studies within a very short time-scale to provide timely evidence on influential factors on the pandemic, e.g. COVID-19 severity and disease course. The comprehensive research infrastructure developed to run the German National Pandemic Cohort Network within the Network University Medicine is now maintained within a generic clinical epidemiology and study platform NUKLEUS. It is operated and subsequently extended to allow efficient joint planning, execution and evaluation of clinical and clinical-epidemiological studies. We aim to provide high-quality biomedical data and biospecimens and make its results widely available to the scientific community by implementing findability, accessibility, interoperability and reusability – i.e. following the FAIR guiding principles. Thus, NUKLEUS might serve as role model for FAIR and fast implementation of clinical epidemiological studies within the setting of University Medical Centers and beyond.

Background Little is known about the associations between cardiovascular risk factors (CRF) and disc degeneration (DD). Purpose To evaluate the potential association between CRFs and intervertebral DD in a population-based sample. Methods A total of 400 participants from the community-based KORA-study were assessed in terms of CRFs, specifically obesity, hypertension, diabetes, elevated LDL-c, low HDL-c, elevated triglycerides, smoking status, and alcohol consumption. The patients additionally underwent whole-body magnetic resonance imaging (MRI) using T2-weighted single-shot fast-spin-echo and T1 dual-echo gradient-echo Dixon pulse sequences. Thoracic and lumbar DD were assessed using the Pfirrmann score and for the presence of disc bulging/protrusion. Cross-sectional associations between CRFs and MR-based Pfirrmann score were then analyzed. Results A total of 385 individuals (58.2% men; mean age 56.3 ± 9.2 years) were included. Prevalence of DD was 76.4%. Older age (β = 0.18; 95% CI 0.12–0.25; P Conclusion A significant independent association exists between age, BMI, and intervertebral DD. In contrast, there is no significant association between cardiovascular risk factors and DD. Providing strong evidence that the pathologic process undergirding DD is mechanical, rather than microvascular, in nature.

Background Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study. Methods From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors. Results In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (β = −12.43, P < 0.001), end-systolic volume (β = −7.12, P < 0.001), stroke volume (β = −5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (β = −0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes. Conclusions Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.

The correlation between physical inactivity, thoracolumbar disc degeneration, and back pain remains unclear.This 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.This 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.All 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.Data 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.Quantification 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.In 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 activity1 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.Degree 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.

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON’s goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By December 01, 2021, 34 university and 34 non-university hospitals have enrolled 4,241 patients with local data quality reviews performed on 2,812 (66%). 47% were female, the median age was 53 (IQR: 38-63)) and 3 pediatric cases were included. 30% of patients were hospitalized, 11% admitted to an intensive care unit, and 4% of patients deceased while enrolled. 7,143 visits with biosampling in 3,595 patients were conducted by November 29, 2021. In this overview article, we summarize NAPKON’s design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registration:· https://clinicaltrials.gov/ct2/show/NCT04768998· https://clinicaltrials.gov/ct2/show/NCT04747366· https://clinicaltrials.gov/ct2/show/NCT04679584

The German government initiated the Network University Medicine (NUM) in early 2020 to improve national research activities on the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic. To this end, 36 German Academic Medical Centers started to collaborate on 13 projects, with the largest being the National Pandemic Cohort Network (NAPKON). The NAPKON’s goal is creating the most comprehensive Coronavirus Disease 2019 (COVID-19) cohort in Germany. Within NAPKON, adult and pediatric patients are observed in three complementary cohort platforms (Cross-Sectoral, High-Resolution and Population-Based) from the initial infection until up to three years of follow-up. Study procedures comprise comprehensive clinical and imaging diagnostics, quality-of-life assessment, patient-reported outcomes and biosampling. The three cohort platforms build on four infrastructure core units (Interaction, Biosampling, Epidemiology, and Integration) and collaborations with NUM projects. Key components of the data capture, regulatory, and data privacy are based on the German Centre for Cardiovascular Research. By April 01, 2022, 34 university and 40 non-university hospitals have enrolled 5298 patients with local data quality reviews performed on 4727 (89%). 47% were female, the median age was 52 (IQR 36–62-) and 50 pediatric cases were included. 44% of patients were hospitalized, 15% admitted to an intensive care unit, and 12% of patients deceased while enrolled. 8845 visits with biosampling in 4349 patients were conducted by April 03, 2022. In this overview article, we summarize NAPKON’s design, relevant milestones including first study population characteristics, and outline the potential of NAPKON for German and international research activities.Trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04768998.https://clinicaltrials.gov/ct2/show/NCT04747366.https://clinicaltrials.gov/ct2/show/NCT04679584

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.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 heightAmong 335 included subjects (56.3 ± 9.1 years, 56.1% male), 95 (28.4%) were obese (BMI ≥ 30 kg/mMRI-based assessment of muscle mass is feasible in population-based imaging and strongly correlated with BIA. However, the observed weaker correlation in obese subjects may explain the known limitation of BIA in obesity and promote MRI-based assessments. Thus, skeletal muscle mass parameters by MRI may serve as practical imaging biomarkers independent of subjects' body weight.

ContextHepatic iron overload can cause severe organ damage. Therefore, an early diagnosis is crucial, and identification of modifiable risk factors could help to prevent manifestations of iron-driven complications.ObjectiveTo investigate the sex-specific distribution of hepatic iron content (HIC) in a population-based sample, and to identify relevant associated factors from a panel of markers.MethodsWe analysed N=353 participants from a cross-sectional, population-based cohort in Southern Germany (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 behavioural risk factors were assessed. Relevant factors associated with HIC were identified by variable selection based on LASSO regression with bootstrap resampling.ResultsHIC in the study sample (mean age at examination was 56.0 years, 58.4% were men) was significantly lower in women (mean±SD: 39.2±4.1 s-1) than in men (41.8±4.7 s-1, pConclusionThere are sex-specific associations of HIC with markers of body composition, glucose metabolism and alcohol consumption.

BACKGROUND Mapping of T1 and T2 relaxation times in cardiac MRI is an invaluable tool for the diagnosis and risk stratification of a wide spectrum of cardiac diseases. PURPOSE To investigate the global and regional reproducibility of native T1 and T2 mapping and to analyze the influence of demographic factors, physiological parameters, slice position, and myocardial regions on reproducibility. STUDY TYPE Prospective single-center cohort-study. POPULATION Fifty healthy volunteers (29 female, 21 male) with a mean age of 39.4 ± 13.7 years. FIELD STRENGTH/SEQUENCE Each volunteer was investigated twice at 1.5 T using a modified look-locker inversion-recovery (MOLLI) sequence (T1 mapping) and a T2-prepared steady-state free precession (SSFP) sequence (T2 mapping). ASSESSMENT Global T1 and T2 values were quantified for the entire left ventricle in three short-axis slices. Regional T1 and T2 values were measured for each myocardial segment and for myocardial segments grouped by slice position and anatomical region. STATISTICAL TESTS Test-retest reproducibility was assessed using intraclass correlation coefficient (ICC) and Bland-Altman statistics. A P value

Background 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. Methods 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. Results 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. Conclusion 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.

IntroductionAs 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 methods400 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.ResultsThe 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 (pConclusionOur results indicate that high 2-hour serum glucose concentration in OGTT, but not fasting glucose levels, may be an independent risk factor for the development of WMHs, with the potential to inform intensified prevention strategies in individuals at risk of WMH-associated morbidity.

To investigate the association between Aorta (Ao), pulmonary artery (PA) diameters and the PA/Ao ratio with right (RV) and left ventricle (LV) volumetric properties in subjects free of cardiovascular diseases. In the KORA-MRI study, 339 subjects (mean age 56.3 ± 9.1 years; 43.7% female) underwent whole-body 3T-MRI. Ao and PA were measured on DIXON sequences. Cvi42 quantified cardiac functional parameters from a SSFP sequence. The relationship between ascending (AAo), and descending aorta (DAo), as well as PA diameters, and RV and LV function were assessed using linear regression models adjusted for age, sex, and cardiovascular risk factors. AAo and DAo diameter were associated with LV end-diastolic volume (β = 4.52, p = 0.015; ß = 7.1, p ≤ 0.001), LV end-systolic volume (β = 2.37, p = 0.031; ß = 3.66, p = 0.002), while DAo associated with RV end-diastolic volume (β = 6.45, p = 0.006) and RV end-systolic volume (β = 3.9, p = 0.011). PA diameter was associated with LV end-diastolic volume (β = 4.81, p = 0.003). Interestingly, the PA/Ao ratio was only associated with RV end-diastolic and end-systolic volume (β = 4.48, p = 0.029; ß = 2.82, p = 0.037). Furthermore, we found different relationships between men and women. Ao and PA diameter were associated with LV and RV volumetric parameters in subjects free of cardiovascular diseases suggesting that ventricular volumetric performance directly relates to vascular diameter properties.

Objectives Management of incidental findings (IF) remains controversial but highly relevant. Our aim was to assess the frequency, management and psychosocial consequences of IF reporting in a population-based cohort study undergoing whole-body MR imaging. Methods The study was nested in a prospective cohort from a longitudinal, population-based cohort (KORA-FF4) in southern Germany. All MR obtained on 3 T MR scanner were reviewed by board-certified radiologists regarding clinically relevant IF. A baseline and follow-up questionnaires including PHQ-9 were completed prior to and 6-month after to the scan. Results Of 400 participants (56.3 ± 9.2years, 58 % male) undergoing whole-body MR, IF were found in 22 % of participants (n = 89); most frequently located in the abdominal sequences. In the pre-scan survey, most participants stated as the motivation that they wanted to “contribute to a scientific purpose” (91 %), while “knowing whether I’m healthy” was the most frequent motivation reported 6 months post-scan (88 %). The desire for IF reporting increased over time (pre- vs. 6-months-post-scan), also for clinically less important IF (72 % vs. 84 %, p = 0.001). Regarding psychosocial impact, a small portion (3.4 %) reported that awaiting the IF report added “definitely” or “very probably” additional stress burden. Of participants with reported IF, 56.8 % classified the results as “very helpful”. In the post-scan survey moderate depression was observed in 3.3 % and severe depression in 1.2 %. This did not differ between participants with and without reported IF. Conclusion In a cohort with whole-body MR imaging, the prevalence of IF was high. Participants considered reporting of IF highly important and added only minor psychological burden.

To identify the most important factors that impact brain volume, while accounting for potential collinearity, we used a data-driven machine-learning approach. Gray Matter Volume (GMV) was derived from magnetic resonance imaging (3T, FLAIR) and adjusted for intracranial volume (ICV). 93 potential determinants of GMV from the categories sociodemographics, anthropometric measurements, cardio-metabolic variables, lifestyle factors, medication, sleep, and nutrition were obtained from 293 participants from a population-based cohort from Southern Germany. Elastic net regression was used to identify the most important determinants of ICV-adjusted GMV. The four variables age (selected in each of the 1000 splits), glomerular filtration rate (794 splits), diabetes (323 splits) and diabetes duration (122 splits) were identified to be most relevant predictors of GMV adjusted for intracranial volume. The elastic net model showed better performance compared to a constant linear regression (mean squared error = 1.10 vs. 1.59, p

To assess the prevalence and severity of perirenal hyperintensities (PRHs) on T2-weighted magnetic resonance imaging (MRI) and their risk factors in the general population.1752 participants (910 women, 842 men, median age: 52 years) of the Study of Health in Pomerania were included. A visual classification system was established to assess the severity of PRHs (stage 0: no PRHs visible to stage 3: extensive PRHs visible). The MRI-derived thickness of the perirenal and posterior pararenal space and additional risk factors were determined and associated with PRH stages.The overall prevalence of PRHs was 40.7% and was higher in men than in women. PRHs were more common around the left compared to the right kidney (p 0.001). On both sides, the presence of PRHs was associated with age (p 0.001). Multivariable-adjusted regression models revealed male sex (OR = 13.2, 95%CI 9.7; 17.9, p 0.001), older age (OR = 1.1, 95%CI 1.1; 1.1, p 0.001), higher body mass index (BMI; OR = 1.1, 95%CI 1.0; 1.1, p 0.001), current smoking status (OR = 1.9, 95%CI 1.4; 2.6, p 0.001), and greater thickness of the posterior pararenal space (OR = 1.2, 95%CI 1.2; 1.2, p 0.001) as independent significant risk factors of left-sided PRHs. The same risk factors were confirmed for right PRHs. Glomerular filtration rate was not associated with PRHs on either sides (OR = 1.00, 95%CI 1.0;1.0, p 0.05).PRHs are common in the general population, with a higher prevalence in men, elderly individuals, and around the left kidney. Furthermore, BMI, posterior pararenal space thickness, and current smoking, but not renal function itself, are associated with the presence of PRHs.

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

ObjectiveIt is still controversial if increased hepatic fat independently contributes to cardiovascular risk. We aimed to assess the association between hepatic fat quantified by MRI and various subclinical vascular disease parameters.DesignWe included two cross-sectional investigations embedded in two independent population-based studies (Study of Health in Pomerania (SHIP): n=1341; Cooperative Health Research in the Region of Augsburg (KORA): n=386). The participants underwent a whole-body MRI examination. Hepatic fat content was quantified by proton-density fat fraction (PDFF). Aortic diameters in both studies and carotid plaque-related parameters in KORA were measured with MRI. In SHIP, carotid intima-media thickness (cIMT) and plaque were assessed by ultrasound. We used (ordered) logistic or linear regression to assess associations between hepatic fat and subclinical vascular disease.ResultsThe prevalence of fatty liver disease (FLD) (PDFF >5.6%) was 35% in SHIP and 43% in KORA. In SHIP, hepatic fat was positively associated with ascending (β, 95% CI 0.06 (0.04 to 0.08)), descending (0.05 (0.04 to 0.07)) and infrarenal (0.02 (0.01 to 0.03)) aortic diameters, as well as with higher odds of plaque presence (OR, 95% CI 1.22 (1.05 to 1.42)) and greater cIMT (β, 95% CI 0.01 (0.004 to 0.02)) in the age-adjusted and sex-adjusted model. However, further adjustment for additional cardiometabolic risk factors, particularly body mass index, attenuated these associations. In KORA, no significant associations were found.ConclusionsThe relation between hepatic fat and subclinical vascular disease was not independent of overall adiposity. Given the close relation of FLD with cardiometabolic risk factors, people with FLD should still be prioritised for cardiovascular disease screening.

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.

Objective: Since angiopoietin-2 (Ang-2) levels strongly correlate with cardiovascular mortality and subclinical cardiovascular disease, it was hypothesized that levels of Ang-2 and its soluble receptor (sTie-2) were associated with the metabolic syndrome (MetS) and individual MetS components. Methods: Within the population-based Study of Health in Pomerania, two sets of analyses were performed. First, Ang-2 and sTie-2 were related to the prevalence of MetS and its components cross-sectionally (n=3,205). Second, the association between baseline Ang-2 and sTie-2 and incident MetS or longitudinal changes in its components in 1,295 individuals was investigated. Results: High Ang-2 levels (90th percentile), compared with low Ang-2 levels (10th percentile), were positively associated with MetS (OR: 1.78) and with the following MetS criteria: increased triglycerides, lower HDL cholesterol, and higher non-fasting glucose. Furthermore, high sTie-2 levels (90th percentile), compared with low levels (10th percentile), were positively related to MetS (OR: 1.58) and most of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or longitudinal change in components of MetS. Conclusions: Ang-2 and sTie-2 levels were cross-sectionally associated with MetS and several of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or changes in individual MetS components during follow-up.

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. Electronic supplementary material The online version of this article (10.1186/s12872-018-0900-7) contains supplementary material, which is available to authorized users.

To assess the prevalence and size of renal cysts and to analyze associated risk factors in a general population using magnetic resonance imaging (MRI). Data of 2063 participants (1052 women) of the Study of Health in Pomerania who underwent whole-body MRI were included. Renal cyst prevalence was calculated separately for men and women and for 10-year age groups. The association between risk factors and occurrence of renal cysts was estimated. The prevalence of renal cysts was 27% and higher in men (34%) than in women (21%; p

OBJECTIVE Cutoff values for increased exercise blood pressure (BP) are not established in hypertension guidelines. The aim of the study was to assess optimal cutoff values for increased exercise BP to predict incident hypertension. METHODS Data of 661 normotensive participants (386 women) aged 25-77 years from the Study of Health in Pomerania (SHIP-1) with a 5-year follow-up were used. Exercise BP was measured at a submaximal level of 100 W and at maximum level of a symptom-limited cycle ergometry test. Cutoff values for increased exercise BP were defined at the maximum sum of sensitivity and specificity for the prediction of incident hypertension. The area under the receiver-operating characteristic curve (AUC) and net reclassification index (NRI) were calculated to investigate whether increased exercise BP adds predictive value for incident hypertension beyond established cardiovascular risk factors. RESULTS In men, values of 160 mmHg (100 W level; AUC = 0.7837; NRI = 0.534, P

Background— Endothelial growth factors including angiopoietin-2 (Ang-2), its soluble receptor Tie-2 (sTie-2), and hepatocyte growth factor play important roles in angiogenesis, vascular remodeling, local tumor growth, and metastatic potential of various cancers. Circulating levels of these biomarkers have a heritable component (between 13% and 56%), but the underlying genetic variation influencing these biomarker levels is largely unknown. Methods and Results— We performed a genome-wide association study for circulating Ang-2, sTie-2, and hepatocyte growth factor in 3571 Framingham Heart Study participants and assessed replication of the top hits for Ang-2 and sTie-2 in 3184 participants of the Study of Health in Pomerania. In multivariable-adjusted models, sTie-2 and hepatocyte growth factor concentrations were associated with single-nucleotide polymorphisms in the genes encoding the respective biomarkers (top P =2.40×10 −65 [rs2273720] and 3.64×10 −19 [rs5745687], respectively). Likewise, rs2442517 in the MCPH1 gene (in which the Ang-2 gene is embedded) was associated with Ang-2 levels ( P =5.05×10 −8 in Framingham Heart Study and 8.39×10 −5 in Study of Health in Pomerania). Furthermore, single-nucleotide polymorphisms in the AB0 gene were associated with sTie-2 (top single-nucleotide polymorphism rs8176693 with P =1.84×10 −33 in Framingham Heart Study; P =2.53×10 −30 in Study of Health in Pomerania) and Ang-2 (rs8176746 with P =2.07×10 −8 in Framingham Heart Study; P =0.001 in Study of Health in Pomerania) levels on a genome-wide significant level. The top genetic loci were explained between 1.7% (Ang-2) and 11.2% (sTie-2) of the interindividual variation in biomarker levels. Conclusions— Genetic variation contributes to the interindividual variation in growth factor levels and explains a modest proportion of circulating hepatocyte growth factor, Ang-2, and Tie-2. This may potentially contribute to the familial susceptibility to cancer, a premise that warrants further studies.

Objectives: The aim of this study was to assess subclinical changes in right ventricular volumes and function in subjects with prediabetes and diabetes and controls without a history of cardiovascular disease. Methods: Data from 400 participants in the KORA FF4 study without self-reported cardiovascular disease who underwent 3-T whole-body MRI were obtained. The right ventricle was evaluated using the short axis and a four-chamber view. Diabetes was defined according to WHO criteria. Associations between glucose tolerance and right ventricular parameters were assessed using multivariable adjusted linear regression models. Results: Data from 337 participants were available for analysis. Of these, 43 (13%) had diabetes, 87 (26%) had prediabetes, and 207 (61%) were normoglycaemic controls. There was a stepwise decrease in right ventricular volumes in men with prediabetes and diabetes in comparison with controls, including right ventricular end-diastolic volume (β = −20.4 and β = −25.6, respectively; p ≤ 0.005), right ventricular end-systolic volume (β = −12.3 and β = −12.7, respectively; p ≤ 0.037) and right ventricular stroke volume (β = −8.1 and β = −13.1, respectively, p ≤ 0.016). We did not observe any association between prediabetes or diabetes and right ventricular volumes in women or between prediabetes or diabetes and right ventricular ejection fraction in men and women. Conclusions: This study points towards early subclinical changes in right ventricular volumes in men with diabetes and prediabetes. Key Points: • MRI was used to detect subclinical changes in right ventricular parameters.• Diabetes mellitus is associated with right ventricular dysfunction.• Impairment of right ventricular volumes seems to occur predominantly in men.

Background: Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce. Methods: Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPIC-Potsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies. Results: After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic >= 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years;on a national level according to the DEGS1 data, however, no such decrease was observed for this group. Conclusion: New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.

Objective: To analyze the associations between epicardial and paracardial fat and impaired glucose tolerance as well as left ventricular (LV) alterations.Methods: 400 subjects underwent 3 T MRI and fat depots were delineated in the four chamber-view of the steady-state free precession cine sequence (repetition time: 29.97 ms; echo time 1.46 ms). LV parameters were also derived from MRI. Oral glucose tolerance tests were performed.Results: Epi- and paracardial fat was derived in 372 (93%) subjects (220 healthy controls, 100 persons with prediabetes, 52 with diabetes). Epi- and paracardial fat increased from normal glucose tolerance (NGT) to prediabetes and diabetes (7.7 vs 9.2 vs 10.3 cm(2) and 14.3 vs 20.3 vs 27.4 cm(2), respectively; all p < 0.001). However, the association between impaired glucose metabolism and cardiac fat attenuated after adjustment, mainly confounded by visceral adipose tissue (VAT). 93 subjects (27%) had LV impairment, defined as late gadolinium enhancement, ejection fraction < 55% or LV concentricity index > 1.3 g ml(-1). Mean epicardial fat was higher in subjects with LV impairment (11.0 vs 8.1 cm(2), p < 0.001). This association remained independent after adjustment for traditional risk factors and VAT [beta: 1.13 (0.22; 2.03), p = 0.02].Conclusion: Although epicardial and paracardial fat are increased in prediabetes and diabetes, the association is mostly confounded by VAT. Epicardial fat is independently associated with subclinical LV impairment in subjects without known cardiovascular disease.Advances in knowledge: This study contributes to the picture of epicardial fat as a pathogenic local fat depot that is independently associated with MR-derived markers of left ventricular alterations.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Since angiopoietin-2 (Ang-2) levels strongly correlate with cardiovascular mortality and subclinical cardiovascular disease, it was hypothesized that levels of Ang-2 and its soluble receptor (sTie-2) were associated with the metabolic syndrome (MetS) and individual MetS components.Within the population-based Study of Health in Pomerania, two sets of analyses were performed. First, Ang-2 and sTie-2 were related to the prevalence of MetS and its components cross-sectionally (n = 3,205). Second, the association between baseline Ang-2 and sTie-2 and incident MetS or longitudinal changes in its components in 1,295 individuals was investigated.High Ang-2 levels (90th percentile), compared with low Ang-2 levels (10th percentile), were positively associated with MetS (OR: 1.78) and with the following MetS criteria: increased triglycerides, lower HDL cholesterol, and higher non-fasting glucose. Furthermore, high sTie-2 levels (90th percentile), compared with low levels (10th percentile), were positively related to MetS (OR: 1.58) and most of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or longitudinal change in components of MetS.Ang-2 and sTie-2 levels were cross-sectionally associated with MetS and several of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or changes in individual MetS components during follow-up.

Research activities dealing with economic aspects of Individualized Medicine (IM) are part of many multidisciplinary IM-related projects in Germany. One important example is the Greifswald Approach to Individualized Medicine (GANI_MED). This paper presents basic principles of data protection and research ethics which are indispensable in order to guarantee that IM-related economic research which uses encoded, but reidentifiable data is in accordance with the regulatory framework and well established ethical standards in Germany. With respect to the patient-related economic research activities in GANI_MED the article also provides an example of a complete integration of an economic sub-project into the Informed Consent and Data Management Concept of a complex IM project. Last but not least the article provides initial data on the response of the GANI_MED patients to those modules of the GANI_MED consent form which enable the economic research group to receive patient-related data from health insurance companies and the “Kassenarztliche Vereinigung”. The response pattern confirms the hypothesis that patients who take part in an IM study do not automatically agree with the scientific usage of data dealing with the costs of their treatment.

Objective— Because population-based data are lacking, we assessed the cross-sectional association between serum testosterone levels and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in men from the population-based Study of Health in Pomerania. Methods and Results— Personal characteristics, including major cardiovascular confounders, were collected in 722 men, aged 25 to 85 years. Serum total testosterone and sexual hormone-binding globulin (SHBG) levels were determined by chemiluminescence immunoassays. Free testosterone levels were calculated according to the law of mass action. FMD and NMD measurements were performed using standardized ultrasound techniques. FMD and NMD values below the 20th percentile were considered decreased. Multivariable logistic regression analyses revealed an association for each decrement of total testosterone standard deviation (6.0 nmol/L) with decreased FMD after adjustment for potential confounders (odds ratio 1.30, 95% confidence interval 1.04–1.63; P =0.023). Multiple adjusted findings for free testosterone were similar (odds ratio 1.37, 95% confidence interval 1.06–1.76; P =0.016). There was no such association of SHBG levels with decreased FMD. Neither testosterone nor SHBG levels were significantly associated with decreased NMD. Conclusion— Lower serum total and free testosterone levels are associated with impaired endothelial function in this population-based sample of men.

Studies on the relation between thyroid function and exercise blood pressure (EBP) are rare and not population-based, and have yielded inconsistent results. The aim of this study was to investigate whether serum thyrotropin (TSH) levels are related to increased EBP.Cross-sectional data from 1438 subjects (711 women) aged 25-83 years without histories of cardiovascular diseases from the 5-year follow-up of the population-based Study of Health in Pomerania (SHIP-1) were analyzed. Blood pressure was measured at the 100 W stage of a symptom-limited bicycle ergometry test. Increased EBP was defined as a value above the sex- and age-specific 80th percentile of participants with serum TSH levels within the reference range (0.25-2.12 mIU/L).There was no association between serum TSH levels and EBP after adjusting for sex, age, waist circumference, diabetes mellitus, smoking status, and antihypertensive medication. The odds for increased systolic EBP (odds ratio 1.24, 95% confidence interval 0.88; 1.76) and diastolic EBP (odds ratios 0.98, 95% confidence interval 0.70; 1.39) as well as for exercise-induced increase of systolic and diastolic blood pressure were not significantly different between subjects with high and low serum TSH levels within the reference range. Similar findings were found for both subjects with TSH levels below and above the reference range, respectively.We conclude that serum TSH levels are not associated with exercise-related blood pressure response.

Henry Volzke, y Dietrich Alte,1y Carsten Oliver Schmidt, Dorte Radke, Roberto Lorbeer, Nele Friedrich, Nicole Aumann, Katharina Lau, Michael Piontek, Gabriele Born, Christoph Havemann, Till Ittermann, Sabine Schipf, Robin Haring, Sebastian E Baumeister, Henri Wallaschofski, Matthias Nauck, Stephanie Frick, Andreas Arnold, Michael Junger, Julia Mayerle, Matthias Kraft, Markus M Lerch, Marcus Dorr, Thorsten Reffelmann, Klaus Empen, Stephan B Felix, Anne Obst, Beate Koch, Sven Glaser, Ralf Ewert, Ingo Fietze, Thomas Penzel, Martina Doren, Wolfgang Rathmann, Johannes Haerting, Mario Hannemann, Jurgen Ropcke, Ulf Schminke, Clemens Jurgens, Frank Tost, Rainer Rettig, Jan A Kors, Saskia Ungerer, Katrin Hegenscheid, Jens-Peter Kuhn, Julia Kuhn, Norbert Hosten, Ralf Puls, Jorg Henke, Oliver Gloger, Alexander Teumer, Georg Homuth, Uwe Volker, Christian Schwahn, Birte Holtfreter, Ines Polzer, Thomas Kohlmann, Hans J Grabe, Dieter Rosskopf, Heyo K Kroemer, Thomas Kocher, Reiner Biffar,17,y Ulrich John20y and Wolfgang Hoffmann1y

Objective The aim of the present study was to investigate the association of fatty liver disease (FLD) with blood pressure (BP) and hypertension in a general population sample with prospective 5-year follow-up examinations. Design and methods We used data from the Study of Health in Pomerania, conducted in the northeastern part of Germany. The study population comprised 3191 individuals aged 20-79 years. FLD was defined as the presence of a hyperechogenic pattern of the liver and increased serum alanine transferase (ALT) levels. Results Multivariable analyses revealed that FLD was associated with increased DBP and hypertension at baseline and with increased SBP and hypertension at follow-up. In individuals with FLD, the chance of hypertension at baseline and follow-up was three-fold higher [odds ratio (OR) 2.8; 95% confidence interval (CI) 1.3-6.2 and OR 3.1; 95% CI 1.7―5.8, respectively] compared to individuals without FLD. In the subgroup of individuals not receiving antihypertensive medication, FLD was associated with all BP-related variables at baseline and follow-up. Analyses further suggest that these associations were independent of alcohol consumption and further confounders. Conclusion FLD defined by liver hyperechogenity and increased ALT levels is associated with progression of BP over time and incident hypertension. In individuals with FLD, BP should be checked regularly and interventions addressing behavioural risk factors for FLD and hypertension should be initiated if necessary. Ultrasound should be implemented as a method to detect FLD in individuals with increased ALT levels in routine medical care.

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

Aortic valve sclerosis (AVS) and mitral annulus calcification (MAC) might predict future adverse events. We undertook the present study to investigate the association of AVS and MAC with all-cause and cardiovascular mortality. We further studied whether a combined presence of AVS and MAC is more strongly associated with mortality than the single items and sought to disclose possible gender differences in the investigated associations.We used data from 2081 participants agedor =45 years (1063 women) of the Study of Health in Pomerania (SHIP). AVS and MAC were determined echocardiographically, and a heart valve sclerosis score was calculated by summing up the AVS and MAC variables. The median duration of mortality follow-up was 8.6 years (17,162 person-years).There were 528 subjects (25.4%) with isolated AVS, 35 with isolated MAC (1.7%) and 89 with both AVS and MAC (4.3%). A total number of 228 deaths (11.0%) occurred during follow-up, including 133 (21.6%) with AVS and 95 subjects (6.5%) without AVS (incidence rate ratio 3.49, 95% CI 2.77; 4.40, p0.001). Likewise, mortality rates were higher for subjects with MAC than subjects without MAC (incidence rate ratio 3.79, 95% CI 2.82; 5.02, p0.001). Multivariable analyses revealed that the associations of AVS and MAC with all-cause and cardiovascular mortality were independent of major confounders and strongest for highest values of the heart valve sclerosis score. AVS-related mortality was more pronounced in women than in men.AVS and MAC are associated with all-cause and cardiovascular mortality. The association between AVS and mortality is gender-specific with women with AVS being at a higher mortality risk than men with AVS. The summation of AVS and MAC to a heart valve sclerosis score improves the predictability with respect to mortality.

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., Author Summary Many variants in the genome, including variants associated with disease, affect the expression of genes. These so-called expression quantitative trait loci (eQTL) can be used to gain insight in the downstream consequences of disease. While it has been shown that many disease-associated variants alter gene expression in a cell-type dependent manner, eQTL datasets for specific cell types may not always be available and their sample size is often limited. We present a method that is able to detect cell type specific effects within eQTL datasets that have been generated from whole tissues (which may be composed of many cell types), in our case whole blood. By combining numerous whole blood datasets through meta-analysis, we show that we are able to detect eQTL effects that are specific for neutrophils and lymphocytes (two blood cell types). Additionally, we show that the variants associated with some diseases may preferentially alter the gene expression in one of these cell types. We conclude that our method is an alternative method to detect cell type specific eQTL effects, that may complement generating cell type specific eQTL datasets and that may be applied on other cell types and tissues as well.

Clinical epidemiological research is an important approach within Individualized Medicine. This research allows for the identification of possible biomarkers for specific diseases through the use of data from clinical treatments. From a research ethical point of view it needs to be noted that respective studies are mostly very complex. Therefore a variety of different normative requirements of both ethical and legal natures need to be met. On the one hand those studies aim for the scientific use of clinical records. On the other hand samples of biomaterial are to be collected, stored and analyzed using -omics methods. Sometimes there are also study examinations included in these studies which may produce incidental findings.

To generate reference values for thoracic and abdominal aortic diameters determined by magnetic resonance imaging (MRI) and analyse their association with cardiovascular risk factors in the general population.Data from participants (n = 1759) of the Study of Health in Pomerania were used for analysis in this study. MRI measurement of thoracic and abdominal aortic diameters was performed. Parameters for calculation of reference values according to age and sex analysis were provided. Multivariable linear regression models were used for determination of aortic diameter-related risk factors, including smoking, blood pressure (BP), high-density lipoprotein cholesterol (HDL-C).For the ascending aorta (β = -0.049, p 0.001), the aortic arch (β = -0.061, p 0.001) and the subphrenic aorta (β = -0.018, p = 0.004), the body surface area (BSA)-adjusted diameters were lower in men. Multivariable-adjusted models revealed significant increases in BSA-adjusted diameters with age for all six aortic segments (p 0.001). Consistent results for all segments were observed for the positive associations of diastolic BP (β = 0.001; 0.004) and HDL (β = 0.035; 0.087) with BSA-adjusted aortic diameters and for an inverse association of systolic BP (β = -0.001).Some BSA-adjusted median aortic diameters are smaller in men than in women. All diameters increase with age, diastolic blood pressure and HDL-C and decrease as systolic BP increases.• Median aortic diameter increases with age and diastolic blood pressure. • Median aortic diameter is larger in men than in women. • Some BSA-adjusted median aortic diameters are smaller in men than in women.

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

Background: There is only limited data on the potential association between thyroid dysfunction and peripheral arterial disease (PAD). Objective: The aim of our study was to investigate the potential association of thyroid function, as defined by serum concentrations of the clinically used primary thyroid function marker thyrotropin [i.e. thyroid-stimulating hormone (TSH)] and 3,5-diiodothyronine (3,5-T2), with the ankle-brachial index (ABI) as a marker of PAD. Methods: We used data from 5,818 individuals from three cross-sectional population-based studies conducted in Northeast (SHIP-2 and SHIP-TREND) and Central Germany (CARLA). Measurement of serum TSH concentrations was conducted in one central laboratory for all three studies. In a randomly selected subpopulation of 750 individuals of SHIP-TREND, serum 3,5-T2 concentrations were measured with a recently developed immunoassay. ABI was measured either by a hand-held Doppler ultrasound using the Huntleigh Dopplex D900 or palpatorily by the OMRON HEM-705CP device. Results: Serum TSH concentrations were not significantly associated with ABI values in any of the three studies. Likewise, groups of individuals with a TSH

To evaluate the association of cardiovascular risk factors with wall thickness of the ascending and descending thoracic aorta in the general population.The study included 1,176 individuals (523 women) 21-83 years old from the Study of Health in Pomerania without history of stroke or myocardial infarction. Aortic wall thickness (AWT) was determined by cine magnetic resonance imaging. The associations of AWT with the cardiovascular risk factors male sex, age, smoking, body mass index (BMI), systolic and diastolic blood pressure, hemoglobin A1c, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides were assessed by multivariable linear regression models, and interaction effects were tested.Male sex (β = .086, P.001), age (β = .006, P.001), and BMI (β = .013, P.001) were positively associated with the AWT of the ascending aorta. Male sex (β = .105, P.001), age (β = .006, P.001), current smoker (β = .044, P = .010), BMI (β = .013, P.001), and HDL-C (β = .057, P = .008) revealed a positive association with AWT of the descending aorta. LDL-C (β = -.024, P = .009; β = -.018, P = .010) was inversely associated with the AWT of the ascending and descending aorta, respectively. Triglyceride levels (β = .024, P = .027; β = .018, P = .024) showed a positive association with the AWT of the ascending and descending aorta, respectively, in men, but not in women.Established cardiovascular risk factors, including male sex, older age, smoking, high BMI, and high triglyceride levels, were associated with increasing thoracic AWT of the ascending and descending aorta. High HDL-C and low LDL-C levels were correlated with AWT.