Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP).

BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

Time trend analysis of Injury Severity score of adult trauma patients with emergent CT examination.

PURPOSE: Controversy exists about whole-body computed tomography (CT) as a primary screening modality for suspected multiple trauma patients. Therefore, the aim of this study was to analyze time trends of CT examinations for trauma patients in relation to the Injury Severity Score (ISS). METHODS: We retrospectively analyzed 561 adult trauma patients (mean age = 54 years) who were admitted to the trauma room of our hospital, immediately followed by a CT examination, in 2009, 2013 und 2017. Review of electronic patient charts was performed to determine the cause of injury. ISS was either calculated upon hospital charts and CT imaging reports or documented in the TraumaRegister DGU® for trauma patients with ICU treatment or ISS ≥ 16. RESULTS: An increasing number of CT examinations of acute trauma patients were performed at our hospital with 117 patients in 2009 compared to 192 in 2013 and 252 in 2017. Their mean age increased (50 years in 2009, 54 in 2013 and 55 in 2017;p = 0.046), whereas their mean ISS decreased over time (15.2 in 2009 compared to 12.1 in 2013 and 10.6 in 2017;p = 0.001), especially in women (15.1 in 2009, 11.8 in 2013 and 7.4 in 2017;p = 0.001 both), younger age groups (18 to 24 years:15.6 in 2009, 6.5 in 2013 and 8.9 in 2017; p = 0.033 and 25 to 49 years:15.0 in 2009, 11.2 in 2013 and 8.3 in 2017;p = 0.001) as well as motor vehicle collision (MVC) victims (16.2 in 2009, 11.8 in 2013 and 6.1 in 2017; p < 0.001). Trauma patients with a high ISS were especially more likely of older age (OR 1.02,p < 0.001) and with the type of incident being a fall (< 3 m: OR3.84,p < 0.001;>3 m: OR6.22,p < 0.001) compared to MVC. CONCLUSION: Previous studies suggesting a benefit of primary whole-body CT for trauma patients might not reflect the current patient population with decreasing ISS. Especially females, younger age groups and MVC patients might benefit from stricter selection criteria for receiving whole-body CT. Our results also emphasize the importance of prevention of fall or tumble for elderly people.

Ethical and coordinative challenges in setting up a national cohort study during the COVID-19 pandemic in Germany.

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.

Association of MRI-based adrenal gland volume and impaired glucose metabolism in a population-based cohort study.

OBJECTIVES: The aim of this study was to assess adrenal gland volume by using magnetic resonance imaging (MRI) and to study its role as an indirect marker of impaired glucose metabolism and hypothalamic-pituitary-adrenal (HPA) axis activation in a population-based cohort. METHODS: Asymptomatic participants were enrolled in a nested case-control study and underwent a 3-T MRI, including T1w-VIBE-Dixon sequences. For the assessment of adrenal gland volume, adrenal glands were manually segmented in a blinded fashion. Impaired glucose metabolism was determined using fasting glucose and oral glucose tolerance test. Cardiometabolic risk factors were also obtained. Inter- and intrareader reliability as well as univariate and multivariate associations were derived. RESULTS: Among 375 subjects included in the analysis (58.5% male, 56.1 ± 9.1 years), 25.3% participants had prediabetes and 13.6% had type 2 diabetes (T2DM). Total adrenal gland volume was 11.2 ± 4.2 ml and differed significantly between impaired glucose metabolism and healthy controls with largest total adrenal gland volume in T2DM (healthy controls: 10.0 ± 3.9 ml, prediabetes: 12.5 ± 3.8 ml, T2DM: 13.9 ± 4.6 ml; p < 0.001). In the multivariate analysis, association of T2DM and increased adrenal gland volume was independent of age, sex, hypertension, triglycerides and body mass index (BMI), but was attenuated in subjects with prediabetes after adjustment for BMI. CONCLUSIONS: T2DM is significantly associated with increased adrenal gland volume by MRI in an asymptomatic cohort, independent of age, sex, dyslipidaemia, hypertension and BMI. Adrenal gland volume may represent an indirect marker of impaired glucose metabolism and HPA axis dysfunction.

The German National Pandemic Cohort Network (NAPKON): rationale, study design and baseline characteristics.

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 registration https://clinicaltrials.gov/ct2/show/NCT04768998 . https://clinicaltrials.gov/ct2/show/NCT04747366 . https://clinicaltrials.gov/ct2/show/NCT04679584.

Association between cardiovascular risk factors and degenerative disc disease of the thoracolumbar spine in the general population: results from the KORA MRI Study.

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 (ß = 0.18; 95% CI 0.12-0.25; P < 0.001) and higher body mass index (BMI) (ß = 0.19; 95% CI 0.06-0.30; P = 0.003) were significantly associated with DD of the thoracolumbar spine. Diabetes was significantly associated with DD at T7/8 (P = 0.029) and L3/4 (P = 0.017). Hypertension correlated significantly with DD in univariate analysis, but the association did not persist using multivariate analysis (ß = 0.53; 95% CI -0.74 to 1.81; P = 0.41). None of the other CRFs (P ≥ 0.11) were associated with advanced DD. Disc bulging was independently associated with hypertension (ß = 0.47; 95% CI 0.27-0.81; P = 0.01). 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.

Global and Regional Test-Retest Reproducibility of Native T1 and T2 Mapping in Cardiac Magnetic Resonance Imaging.

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 < 0.05 was considered statistically significant. RESULTS: Reproducibility was good for global T1 values (ICC 0.88) and excellent for global T2 values (ICC 0.91). Reproducibility of T1 values was excellent (ICC 0.91) for midventricular slice and good for apical (ICC 0.86) and basal slice (ICC 0.81). Reproducibility of T1 mapping values was highest in the septum (ICC 0.90) compared to the anterior (0.81), lateral (0.86), and inferior (0.86) wall. For T2 mapping, reproducibility was good for all slice positions (ICC 0.86 for midventricular, 0.83 for basal, and 0.80 for apical slice). Reproducibility of T2 mapping was significantly lower for the inferior wall (ICC 0.58) than for septum (0.89), anterior (0.85), and lateral (0.87) wall. DATA CONCLUSION: Native T1 and T2 mapping has good to excellent reproducibility with significant regional differences. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Distribution patterns of intramyocellular and extramyocellular fat by magnetic resonance imaging in subjects with diabetes, prediabetes and normoglycaemic controls.

AIM: To evaluate the distribution of intramyocellular lipids (IMCLs) and extramyocellular lipids (EMCLs) as well as total fat content in abdominal skeletal muscle by magnetic resonance imaging (MRI) using a dedicated segmentation algorithm in subjects with type 2 diabetes (T2D), prediabetes and normoglycaemic controls. MATERIALS AND METHODS: Subjects from a population-based cohort were classified with T2D, prediabetes or as normoglycaemic controls. Total myosteatosis, IMCLs and EMCLs were quantified by multiecho Dixon MRI as proton-density fat-fraction (in %) in abdominal skeletal muscle. RESULTS: Among 337 included subjects (median age 56.0 [IQR: 49.0-64.0] years, 56.4% males, median body mass index [BMI]: 27.2 kg/m2 ), 129 (38.3%) were classified with an impaired glucose metabolism (T2D: 49 [14.5%]; prediabetes: 80 [23.7%]). IMCLs were significantly higher than EMCLs in subjects without obesity (5.7% [IQR: 4.8%-7.0%] vs. 4.1% [IQR: 2.7%-5.8%], P < .001), whereas the amounts of IMCLs and EMCLs were shown to be equal and significantly higher in subjects with obesity (both 6.7%, P < .001). Subjects with prediabetes and T2D had significantly higher amounts of IMCLs and EMCLs compared with normoglycaemic controls (P < .001). In univariable analysis, prediabetes and T2D were significantly associated with both IMCLs (prediabetes: ß: 0.76, 95% CI: 0.28-1.24, P = .002; T2D: ß: 1.56, 95% CI: 0.66-2.47, P < .001) and EMCLs (prediabetes: ß: 1.54, 95% CI: 0.56-2.51, P = .002; T2D: ß: 2.15, 95% CI: 1.33-2.96, P < .001). After adjustment for age and gender, the association of IMCLs with prediabetes attenuated (P = 0.06), whereas for T2D, both IMCLs and EMCLs remained significantly and positively associated (P < .02). CONCLUSION: There are significant differences in the amount and distribution ratio of IMCLs and EMCLs between subjects with T2D, prediabetes and normoglycaemic controls. Therefore, these patterns of intramuscular fat distribution by MRI might serve as imaging biomarkers in both normal and impaired glucose metabolism.

Association of antecedent cardiovascular risk factor levels and trajectories with cardiovascular magnetic resonance-derived cardiac function and structure.

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 ß = - 4.91 ml/m2, 95% CI - 7.89; - 1.94, p < 0.01 and high risk cluster ß = - 7.00 ml/m2, 95% CI - 10.73; - 3.28, p < 0.001 compared to the low risk cluster). The multivariable longitudinal trajectory clusters added significantly to explain variation in CMR traits beyond the multivariable risk profile obtained at Exam 3. CONCLUSIONS: Cardiovascular disease risk factor levels, measured over a time period of 14 years, were associated with CMR-derived measures of cardiac structure and function. Longitudinal multivariable trajectory clusters explained a greater proportion of the inter-individual variation in cardiac traits than multiple risk factor assessed contemporaneous with the CMR exam.

Bone marrow fat fraction assessment in regard to physical activity: KORA FF4-3-T MR imaging in a population-based cohort.

OBJECTIVES: To establish the effect of different degrees and kinds of physical activity on bone marrow fat (BMAT) content at different anatomical locations in a population-based cohort study undergoing whole-body MR imaging. METHODS: Subjects of the KORA FF4 study without known cardiovascular disease underwent BMAT fat fraction (FF) quantification in L1 and L2 vertebrae and femoral heads/necks (hip) via a 2-point T1-weighted VIBE Dixon sequence. BMAT-FF was calculated as mean value (fat image) divided by mean value (fat + water image). Physical activity was determined by self-assessment questionnaire regarding time spent exercising, non-exercise walking, non-exercise cycling, and job-related physical activity. RESULTS: A total of 385 subjects (96% of 400 available; 56 ± 9.1 years; 58% male) were included in the analysis. Exercise was distributed quite evenly (29% > 2 h/week; 31% ~ 1 h/week (regularly); 15% ~ 1 h/week (irregularly); 26% no physical activity). BMAT-FF was 52.6 ± 10.2% in L1, 56.2 ± 10.3% in L2, 87.4 ± 5.9% in the right hip, and 87.2 ± 5.9% in the left hip (all p < 0.001). Correlation of BMAT-FF between spine and hip was only moderate (r 0.42 to 0.46). Spinal BMAT-FF, but not hip BMAT-FF, was inversely associated with exercise > 2 h/week (p ≤ 0.02 vs. p ≥ 0.35, respectively). These associations remained significant after adjusting for age, gender, waist circumference, and glucose tolerance. No coherent association was found between BMAT-FF and physical activity in the less active groups. CONCLUSIONS: In our study, exercise was inversely correlated with vertebral BMAT-FF, but not hip BMAT-FF, when exercising for more than 2 h per week. Physical activity seems to affect the spine at least preferentially compared to the hip. KEY POINTS: • In our population-based cohort, at least 2 h of physical activity per week were required to show lower levels of bone marrow adipose tissue fat fraction in MRI. • Physical activity seems to affect bone marrow adipose tissue at least preferentially at the spine in contrast to the proximal femur.

Glucose and insulin levels are associated with arterial stiffness and concentric remodeling of the heart.

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 < 0.001) lower left ventricular end-diastolic volume index, a 0.042 mm/m2.7 (0.014 to 0.070) higher left ventricular wall-thickness index, a 0.12 mmHg m2.7/ml (0.06 to 0.17; p < 0.001) greater arterial stiffness index and a 0.037 g/ml (0.018 to 0.056; p < 0.001) higher left ventricular concentricity. CONCLUSIONS: Our findings suggest that higher glucose levels in the prediabetic range and insulin resistance might lead to higher arterial stiffness and concentric remodeling of the heart.

Automated MR-based lung volume segmentation in population-based whole-body MR imaging: correlation with clinical characteristics, pulmonary function testing and obstructive lung disease.

OBJECTIVES: Whole-body MR imaging is increasingly utilised; although for lung dedicated sequences are often not included, the chest is typically imaged. Our objective was to determine the clinical utility of lung volumes derived from non-dedicated MRI sequences in the population-based KORA-FF4 cohort study. METHODS: 400 subjects (56.4 ± 9.2 years, 57.6% males) underwent whole-body MRI including a coronal T1-DIXON-VIBE sequence in inspiration breath-hold, originally acquired for fat quantification. Based on MRI, lung volumes were derived using an automated framework and related to common predictors, pulmonary function tests (PFT; spirometry and pulmonary gas exchange, n = 214) and obstructive lung disease. RESULTS: MRI-based lung volume was 4.0 ± 1.1 L, which was 64.8 ± 14.9% of predicted total lung capacity (TLC) and 124.4 ± 27.9% of functional residual capacity. In multivariate analysis, it was positively associated with age, male, current smoking and height. Among PFT indices, MRI-based lung volume correlated best with TLC, alveolar volume and residual volume (RV; r = 0.57 each), while it was negatively correlated to FEV1/FVC (r = 0.36) and transfer factor for carbon monoxide (r = 0.16). Combining the strongest PFT parameters, RV and FEV1/FVC remained independently and incrementally associated with MRI-based lung volume (ß = 0.50, p = 0.04 and ß = - 0.02, p = 0.02, respectively) explaining 32% of the variability. For the identification of subjects with obstructive lung disease, height-indexed MRI-based lung volume yielded an AUC of 0.673-0.654. CONCLUSION: Lung volume derived from non-dedicated whole-body MRI is independently associated with RV and FEV1/FVC. Furthermore, its moderate accuracy for obstructive lung disease indicates that it may be a promising tool to assess pulmonary health in whole-body imaging when PFT is not available. KEY POINTS: • Although whole-body MRI often does not include dedicated lung sequences, lung volume can be automatically derived using dedicated segmentation algorithms • Lung volume derived from whole-body MRI correlates with typical predictors and risk factors of respiratory function including smoking and represents about 65% of total lung capacity and 125% of the functional residual capacity • Lung volume derived from whole-body MRI is independently associated with residual volume and the ratio of forced expiratory volume in 1 s to forced vital capacity and may allow detection of obstructive lung disease.

Hepatic fat is superior to BMI, visceral and pancreatic fat as a potential risk biomarker for neurodegenerative disease.

OBJECTIVES: Prior studies relating body mass index (BMI) to brain volumes suggest an overall inverse association. However, BMI might not be an ideal marker, as it disregards different fat compartments, which carry different metabolic risks. Therefore, we analyzed MR-based fat depots and their association with gray matter (GM) volumes of brain structures, which show volumetric changes in neurodegenerative diseases. METHODS: Warp-based automated brain segmentation of 3D FLAIR sequences was obtained in a population-based study cohort. Associations of temporal lobe, cingulate gyrus, and hippocampus GM volume with BMI and MR-based quantification of visceral adipose tissue (VAT), as well as hepatic and pancreatic proton density fat fraction (PDFFhepatic and PDFFpanc, respectively), were assessed by linear regression. RESULTS: In a sample of 152 women (age 56.2 ± 9.0 years) and 199 men (age 56.1 ± 9.1 years), we observed a significant inverse association of PDFFhepatic and cingulate gyrus volume (p < 0.05) as well as of PDFFhepatic and hippocampus volume (p < 0.05), when adjusting for age and sex. This inverse association was further enhanced for cingulate gyrus volume after additionally adjusting for hypertension, smoking, BMI, LDL, and total cholesterol (p < 0.01) and also alcohol (p < 0.01). No significant association was observed between PDFFhepatic and temporal lobe and between temporal lobe, cingulate gyrus, or hippocampus volume and BMI, VAT, and PDFFpanc. CONCLUSIONS: We observed a significant inverse, independent association of cingulate gyrus and hippocampus GM volume with hepatic fat, but not with other obesity measures. Increased hepatic fat could therefore serve as a marker of high-risk fat distribution. KEY POINTS: • Obesity is associated with neurodegenerative processes. • In a population-based study cohort, hepatic fat was superior to BMI and visceral and pancreatic fat as a risk biomarker for decreased brain volume of cingulate gyrus and hippocampus. • Increased hepatic fat could serve as a marker of high-risk fat distribution.

Characteristics and associated risk factors of diverticular disease assessed by magnetic resonance imaging in subjects from a Western general population.

OBJECTIVES: Diverticular disease represents an increasing pathology and healthcare burden worldwide. Our aim was to study the prevalence, extent and distribution of asymptomatic diverticular disease assessed by magnetic resonance imaging (MRI) in a sample of a Western population. METHODS: Subjects from a population-based cohort study who underwent 3-T MRI were analyzed for the prevalence and extent of diverticula of the colon using an isotropic VIBE-Dixon gradient-echo sequence. The extent of diverticular disease was categorized according to the number of diverticula in each colonic segment. Univariate and adjusted analyses were performed to assess associated characteristics and risk factors. RESULTS: Among 393 subjects included in the analysis (56.4 ± 9.2 years, 57.5% males), 164 (42%) had diverticular disease, with the highest prevalence in the left-sided colonic segments (93% diverticular disease in the descending and sigmoid segment). Subjects with advanced diverticular disease were older (62.1 vs. 54.4 years) and had a higher body mass index (BMI), LDL cholesterol levels and systolic blood pressure (30.2 ± 5.1 vs. 27.8 ± 4.9 kg/m2, 149.8 ± 29.3 vs. 135.2 ± 32.9 mg/dl and 128.2 ± 14.1 vs. 118.4 ± 16.1 mmHg, respectively; all p > 0.003) compared with subjects without diverticular disease. In contrast, no significant correlation could be found for gender, physical activity, smoking status and alcohol consumption (all p > 0.31). Intra-rater reliability was excellent for all colonic segments (intra-class correlation [ICC] = 0.99-1.00), and inter-rater reliability was excellent for left- and right-sided colonic segments (ICC = 0.84-0.97). CONCLUSIONS: These findings provide insights into the disease mechanism of asymptomatic diverticular disease and may help to improve prevention of diverticulosis and its associated complications. KEY POINTS: • Overall prevalence of asymptomatic diverticular disease assessed by MRI was 42%, affecting predominantly the left-sided colon. • Asymptomatic diverticular disease was associated with age and cardiometabolic risk factors. • Magnetic resonance imaging reveals insights into the pathophysiologic mechanism of asymptomatic diverticular disease.

Association between abdominal adiposity and subclinical measures of left-ventricular remodeling in diabetics, prediabetics and normal controls without history of cardiovascular disease as measured by magnetic resonance imaging: results from the KORA-FF4 Study.

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 (ß = 0.11 and 0.06, respectively), decreasing LV end-diastolic volume (ß = - 6.70 and 3.23, respectively), and decreasing LV stroke volume (ß = - 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.

Subclinical changes in MRI-determined right ventricular volumes and function in subjects with prediabetes and diabetes.

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 (ß = -20.4 and ß = -25.6, respectively; p ≤ 0.005), right ventricular end-systolic volume (ß = -12.3 and ß = -12.7, respectively; p ≤ 0.037) and right ventricular stroke volume (ß = -8.1 and ß = -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.

Association of glycemic status and segmental left ventricular wall thickness in subjects without prior cardiovascular disease: a cross-sectional study.

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 (ß-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.

Cell Specific eQTL Analysis without Sorting Cells.

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.

High levels of thyroid-stimulating hormone are associated with aortic wall thickness in the general population.

OBJECTIVES: Our aim was to investigate the association of thyroid function defined by serum concentrations of thyroid-stimulating hormone (TSH) with thoracic aortic wall thickness (AWT) as a marker of atherosclerotic processes. METHODS: We pooled data of 2,679 individuals from two independent population-based surveys of the Study of Health in Pomerania. Aortic diameter and AWT measurements were performed on a 1.5-T MRI scanner at the concentration of the right pulmonary artery displaying the ascending and the descending aorta. RESULTS: TSH, treated as continuous variable, was significantly associated with descending AWT (ß = 0.11; 95 % confidence interval (CI) 0.02-0.21), while the association with ascending AWT was not statistically significant (ß = 0.20; 95 % CI -0.01-0.21). High TSH (>3.29 mIU/L) was significantly associated with ascending (ß = 0.12; 95 % CI 0.02-0.23) but not with descending AWT (ß = 0.06; 95 % CI -0.04-0.16). There was no consistent association between TSH and aortic diameters. CONCLUSIONS: Our study demonstrated that AWT values increase with increasing serum TSH concentrations. Thus, a hypothyroid state may be indicative for aortic atherosclerosis. These results fit very well to the findings of previous studies pointing towards increased atherosclerotic risk in the hypothyroid state. KEY POINTS: • Serum TSH concentrations are positively associated with aortic wall thickness. • Serum TSH concentrations are not associated with the aortic diameters. • Serum 3,5-diiodothyronine concentrations may be positively associated with aortic wall thickness.

Thoracic and abdominal aortic diameters in a general population: MRI-based reference values and association with age and cardiovascular risk factors.

OBJECTIVES: 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. METHODS: 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). RESULTS: For the ascending aorta (ß = -0.049, p < 0.001), the aortic arch (ß = -0.061, p < 0.001) and the subphrenic aorta (ß = -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 (ß = 0.001; 0.004) and HDL (ß = 0.035; 0.087) with BSA-adjusted aortic diameters and for an inverse association of systolic BP (ß = -0.001). CONCLUSIONS: 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. KEY POINTS: • 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.