Association of transketolase polymorphisms with diabetic polyneuropathy in the general population: The KORA F4 study.

AIMS: We recently reported that genetic variability in the TKT gene encoding transketolase, a key enzyme in the pentose phosphate pathway, is associated with measures of diabetic sensorimotor polyneuropathy (DSPN) in recent-onset diabetes. Here, we aimed to substantiate these findings in a population-based KORA F4 study. MATERIALS AND METHODS: In this cross-sectional study, we assessed seven single nucleotide polymorphisms (SNPs) in the transketolase gene in 952 participants from the KORA F4 study with normal glucose tolerance (NGT; n = 394), prediabetes (n = 411), and type 2 diabetes (n = 147). DSPN was defined by the examination part of the Michigan Neuropathy Screening Instrument (MNSI) using the original MNSI > 2 cut-off and two alternative versions extended by touch/pressure perception (TPP) (MNSI > 3) and by TPP plus cold perception (MNSI > 4). RESULTS: After adjustment for sex, age, BMI, and HbA1c, in type 2 diabetes participants, four out of seven transketolase SNPs were associated with DSPN for all three MNSI versions (all p ≤ 0.004). The odds ratios of these associations increased with extending the MNSI score, for example, OR (95% CI) for SNP rs62255988 with MNSI > 2: 1.99 (1.16-3.41), MNSI > 3: 2.27 (1.26-4.09), and MNSI > 4: 4.78 (2.22-10.26); SNP rs9284890 with MNSI > 2: 2.43 (1.42-4.16), MNSI > 3: 3.46 (1.82-6.59), and MNSI > 4: 4.75 (2.15-10.51). In contrast, no associations were found between transketolase SNPs and the three MNSI versions in the NGT and prediabetes groups. CONCLUSIONS: The link of genetic variation in transketolase enzyme to diabetic polyneuropathy corroborated at the population level strengthens the concept suggesting an important role of pathways metabolising glycolytic intermediates in the evolution of diabetic polyneuropathy.

Differential association of dietary scores with the risk of type 2 diabetes by metabotype.

PURPOSE: We aimed to examine the association between dietary patterns and type 2 diabetes mellitus (T2DM) while considering the potential effect modification by metabolic phenotypes (metabotypes). Additionally, we aimed to explore the association between dietary scores and prediabetes. METHODS: A total of 1460 participants (11.8% with T2DM) from the cross-sectional population-based KORA FF4 study were included. Participants, classified into three metabotype subgroups, had both their FSAm-NPS dietary index (underpinning the Nutri-Score) and ultra-processed foods (UPF) intake (using NOVA classification) calculated. Glucose tolerance status was assessed via oral glucose tolerance tests (OGTT) in non-diabetic participants and was classified according to the American Diabetes Association criteria. Logistic regression models were used for both the overall and metabotype-stratified analyses of dietary scores' association with T2DM, and multinomial probit models for their association with prediabetes. RESULTS: Participants who had a diet with a higher FSAm-NPS dietary index (i.e., a lower diet quality) or a greater percentage of UPF consumption showed a positive association with T2DM. Stratified analyses demonstrated a strengthened association between UPF consumption and T2DM specifically in the metabolically most unfavorable metabotype (Odds Ratio, OR 1.92; 95% Confidence Interval, CI 1.35, 2.73). A diet with a higher FSAm-NPS dietary index was also positively associated with prediabetes (OR 1.19; 95% CI 1.04, 1.35). CONCLUSION: Our study suggests different associations between poorer diet quality and T2DM across individuals exhibiting diverse metabotypes, pointing to the option for stratified dietary interventions in diabetes prevention.

Longitudinal course and predictors of health-related quality of life, mental health, and fatigue, in non-hospitalized individuals with or without post COVID-19 syndrome.

BACKGROUND: Long-term information on health-related quality of life (HRQOL) and mental health of non-hospitalized individuals with "post COVID-19 syndrome" (PCS) is scarce. Thus, the objectives of the present study were to compare HRQOL and mental health of individuals with and without PCS in a German sample of non-hospitalized persons after SARS-CoV-2 infection, to characterize the long-term course up to 2 years and to identify predictors for post COVID-19 impairments. METHODS: Individuals with past SARS-CoV-2 infection were examined at the University Hospital of Augsburg from November 2020 to May 2021 and completed a postal questionnaire between June and November 2022. Participants who self-reported the presence of fatigue, dyspnea on exertion, memory problems or concentration problems were classified as having PCS. HRQOL was assessed using the Veterans RAND 12-Item Health Survey, mental health was measured by the Patient Health Questionnaire and the Fatigue Asessment Scale was used to assess fatigue severity. Multivariable linear regression models with inverse probability weighting were used to determine the association between PCS and health outcomes. RESULTS: From the 304 participants (58.2% women, median age 52 years), 210 (69.1%) were classified as having PCS in median 26 months after SARS-CoV-2 infection. Persons with PCS showed significantly more often depressive and anxiety disorders. PCS was independently and significantly associated with higher levels of depression, post-traumatic stress and fatigue, as well as poorer physical and mental HRQOL in median 9 months as well as 26 months after SARS-CoV-2 infection. A large number of acute symptoms and a prior diagnosis of depression were independently associated with poor mental health and HRQOL. While post-traumatic stress and mental HRQOL improved from 9 months to 26 months post infection onset, depressiveness, fatigue and physical HRQOL remained stable in both, persons with and without PCS. CONCLUSIONS: PCS in non-hospitalized persons after SARS-CoV-2 infection is often associated with long-term impairments of mental health and HRQOL outcomes.

Association between fatty liver index and blood coagulation markers: a population-based study.

BACKGROUND: Population-based studies investigating the association between blood coagulation markers and non-alcoholic fatty liver disease (NAFLD) are rare. Thus, we aimed to investigate the relationship between the Fatty Liver Index (FLI) as a measure of hepatic steatosis and plasma concentrations of antithrombin III, D-dimer, fibrinogen D, protein C, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value and international thromboplastin time (INR) in the general population. METHODS: After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men, aged 54-74 years) of the population-based KORA Fit study with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the associations between FLI and hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the history of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol levels, and diabetes status. In addition, analyses were stratified by diabetes status. RESULTS: In the multivariable models (with or without health conditions), significantly positive associations with FLI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein C, protein S, and quick value, while INR and antithrombin III were inversely associated. These associations were weaker in pre-diabetic subjects and largely disappeared in diabetic patients. CONCLUSION: In this population-based study, an increased FLI is clearly related to changes in the blood coagulation system, possibly increasing the risk of thrombotic events. Due to a generally more pro-coagulative profile of hemostatic factors, such an association is not visible in diabetic subjects.

Association of post-stroke-depression and health-related quality of life three months after the stroke event. Results from the Stroke Cohort Augsburg (SCHANA) study.

Approximately one-third of patients with stroke show depressive symptoms. The so-called post-stroke depression (PSD) has a negative influence on mortality as well as physical and mental conditions. The aim of this study was to analyse the association between PSD and health-related quality of life (HRQOL) in patients with stroke. The analysis was based on data of 326 patients from the Stroke Cohort Augsburg (SCHANA Study) collected after the stroke event by interview and three months later using a postal survey. Depressive symptoms were measured with the Patient-Health Questionnaire (PHQ-9), subjective health status with the EuroQol 5D visual analogue scale (EQ-5D VAS), and HRQOL with the Stroke Impact Scale (SIS). Patients with depressive symptoms were compared to those without depressive symptoms in terms of sociodemographic characteristics and scores of the SIS and the EQ-5D VAS. Multiple linear regression models were calculated to investigate the association between PSD and subjective health status and HRQOL. Three months after the stroke, 17.8% of patients had depressive symptoms. Patients with PSD showed significantly worse SIS and EQ-5D VAS scores. In addition, an independent negative linear association between PSD and subjective health status and between PSD and all domains of SIS could be found. The study confirmed that PSD is common in patients with mild stroke and negatively related to all stroke-specific HRQOL domains. The results underline the importance of early screening for PSD in stroke patients since it may hinder a successful rehabilitation.

The prevalence of vascular complications in SARS-CoV-2 infected outpatients.

BACKGROUND: The risk of thromboembolic events is increased for coronavirus disease (COVID)-19 inpatients. For severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected outpatients, only few data are available so far. METHODS: In our prospective single-center study, 461 SARS-CoV-2-infected outpatients were screened for the presence of deep vein thrombosis. RESULTS: Two outpatients had suffered a deep vein thrombosis. An association with previously known risk factors, such as preexisting thrombosis in the medical history or cardiovascular risk factors, could not be proven. CONCLUSION: General thromboprophylaxis in SARS-CoV-2-infected outpatients is still not recommended.

Body Mass Index and Waist Circumference as Determinants of Hemostatic Factors in Participants of a Population-Based Study.

Background: In contrast to studies in patients, an association between obesity and blood coagulation factors has not been established in the population. If confirmed it could become a target for primary prevention. Objective: To investigate the relationship between Body Mass Index (BMI) and waist circumference (WC) with plasma concentrations of antithrombin III, D-dimers, fibrinogen D, protein S, factor VIII, activated partial thromboplastin time (aPTT), quick value, and international normalized ratio (INR) in the general population. Materials and Methods: Participants of the Cooperative Health Research in the Region of Augsburg (KORA) S4 study who took part in the KORA Fit follow-up (2018-2019, aged 54-74 years) examination were eligible. Citrate plasma samples were collected in fasted participants. After the exclusion of participants with anticoagulative treatment, 776 participants (420 women and 356 men) with analytic data on hemostatic factors were included in the present analysis. Linear regression models were used to explore the association between BMI or WC with hemostatic markers, adjusted for sex, age, alcohol consumption, education, smoking status, and physical activity. In a second model, additional adjustments were made for the prevalence of stroke, hypertension, myocardial infarction, serum non-HDL cholesterol, and serum triglycerides. Results: In the multivariable models (with or without health conditions), significant positive associations with BMI were obtained for plasma concentrations of D-dimers, factor VIII, fibrinogen D, protein S, and quick value, while INR and antithrombin III were inversely associated. Similar to BMI, WC was significantly associated with all hemostatic factors, except for aPTT. Conclusion: In this population-based study, both increasing BMI and WC affect the blood coagulation system. Thus, modification of a prothrombotic coagulation profile emerged as a potential target for primary prevention in obese subjects.

Strategies for Avoiding Typical Drug-Drug Interactions and Drug-Related Problems in Patients with Vascular Diseases.

Background and objectives: Drug-drug interactions and drug-related problems in patients with vascular diseases are common. To date, very few studies have focused on these important problems. The aim of the present study is to investigate the most common drug-drug interactions and DRPs in patients with vascular diseases. Materials and Methods: The medications of 1322 patients were reviewed manually in the time period from 11/2017 to 11/2018; the medications of 96 patients were entered into a clinical decision support system. Potential drug problems were identified, and a read-through consensus was reached between a clinical pharmacist and a vascular surgeon during the clinical curve visits; possible modifications were implemented. The focus was on additional dose adjustment and drug antagonization on drug interactions. Interactions were classified as contraindicated/high-risk combination (drugs must not be combined), clinically serious (interaction can be potentially life-threatening or have serious, possibly irreversible consequences), or potentially clinically relevant and moderate (interaction can lead to therapeutically relevant consequences). Results: A total of 111 interactions were observed. Of these, 6 contraindicated/high-risk combinations, 81 clinically serious interactions, and 24 potentially clinically relevant and moderate interactions were identified. Furthermore, 114 interventions were recorded and categorized. Discontinued use of the drug (36.0%) and drug dose adjustment (35.1%) were the most common interventions. Mostly, antibiotic therapy was continued unnecessarily (10/96; 10.4%), and the adjustment of the dosage to kidney function was overlooked in 40/96; 41.7% of the cases. In the most common cases, a dose reduction was not considered necessary. Here, unadjusted doses of antibiotics were found in 9/96, 9.3% of the cases. Notes for medical professionals summarized information that did not require direct intervention but rather increased attention on the part of the ward doctor. It was usually necessary to monitor laboratory parameters (49/96, 51.0%) or the patients for side effects (17/96, 17.7%), which were expected with the combinations used. Conclusions: This study could help identify problematic drug groups and develop prevention strategies for drug-related problems in patients with vascular diseases. A multidisciplinary collaboration between the different professional groups (clinical pharmacists and surgeons) might optimize the medication process. Collaborative care could have a positive impact on therapeutic outcomes and make drug therapy safer for patients with vascular diseases.

The German version of the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire: reliability, responsiveness and structural validity.

PURPOSE: The Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire is the only existing disease-specific instrument for measuring quality of life after pulmonary embolism (PE). It includes six dimensions: frequency of complaints, limitations in activities of daily living, work-related problems, social limitations, intensity of complaints and emotional complaints. The present study aimed to determine the psychometric properties including responsiveness and structural validity of the German version. METHODS: The analysis used data from participants of the LEA cohort study at University Hospital Augsburg. The PEmb-QoL was administered via postal surveys 3, 6 and 12 months post-PE. Internal consistency and test-retest reliability were evaluated by calculating Cronbach's alpha and intra-class correlation coefficients (ICC). Standardized response means (SRM) were calculated for investigating responsiveness. For evaluating the fit of the factor structure, confirmatory factor analysis (CFA) was conducted. RESULTS: Overall, we used data from 299 patients 3 months after PE. Cronbach's alpha (0.87-0.97) and ICC (0.53-0.90) were in an acceptable to good range. SRM scores showed good responsiveness of all dimensions. CFA revealed the four-factor model including one general factor to have a good model fit. CONCLUSION: Despite existing floor effect, most standard criteria of reliability and validity were met and indications for appropriateness of the PEmb-QoL summary score could be found. Apart from some restrictions concerning the factor structure and the dimension of social limitations, our results support the use of the PEmb-QoL questionnaire for evaluating PE-specific quality of life. Future studies should seek replication in different samples to ensure generalizability of the findings.

Meta-analysis of epigenome-wide association studies of carotid intima-media thickness.

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = -0.0264, p value = 3.5 × 10-8) in the discovery panel and was replicated in replication panel (beta = -0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10-13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease.

Diagonal earlobe crease and long-term survival after myocardial infarction.

BACKGROUND: The association between the presence of a diagonal earlobe crease (DEC) and coronary artery disease has been prescribed earlier. However, it is unclear whether patients with acute myocardial infarction (AMI) and DEC have a higher risk of dying. METHODS: Study participants were persons with AMI who were included in the KORA Myocardial Infarction Registry Augsburg from August 2015 to December 2016. After taking pictures of both earlobes, two employees independently assessed the severity of DEC in 4°. For analysis, the expression of the DEC was dichotomized. Information on risk factors, severity and therapy of the AMI was collected by interview and from the medical record. Vital status post AMI was obtained by population registries in 2019. The relationship between DEC and survival time was determined using Cox proportional hazards models. RESULTS: Out of 655 participants, 442 (67.5%) showed DEC grade 2/3 and 213 (32.5%) DEC grade 0/1. Median observation period was 3.06 years (5-1577 days). During this period, 26 patients (12.2%) with DEC grade 0/1 and 92 patients (20.8%) with grade 2/3 died (hazard ratio 1.91, 95% confidence interval (CI) 1.23-2.96, p = 0.0037). In the fully adjusted model, patients with DEC grade 2/3 had a 1.48-fold increased risk of death compared to the DEC grade 0/1 patient group (CI 0.94-2.34, p = 0.0897). The fully adjusted model applied for 1-year survival revealed a significant, 2.57-fold hazard ratio of death (CI 1.07-6.17, p = 0.0347) for the patients with DEC grade 2/3. CONCLUSIONS: Our results indicate that DEC is independently associated with 1-year AMI survival.

Effort-Reward Imbalance at Work and Overcommitment in Patients with Acute Myocardial Infarction (AMI): Associations with Return to Work 6 Months After AMI.

Purpose Stress-related factors influence the adaptation to life after acute myocardial infarction (AMI), including return to work. The goal of this study was to investigate the effect of work-related stress, (expressed by the effort-reward imbalance (ERI) model) on return to work after AMI. Methods A longitudinal study with AMI patients was conducted in order to assess associations between the independent variables effort, reward, ERI and overcommitment and the outcome return to work after AMI. Return to work was inquired at 6 months follow-up. Logistic regression models were applied in the analysis. The fully-adjusted model included demographic, clinical, social, stress-related and health-related quality of life (HRQOL) covariables. Results Of the 346 enrolled patients aged 31 to 82 years, 239 (69.1%) were included in the regression analysis. In the unadjusted model ERI presented an odds ratio (OR) of 1.72 (95% confidence interval (CI) 0.86-3.42). Associations for effort and overcommitment were 0.98 (95% CI 0.83-1.15) and 1.09 (95% CI 0.99-1.18). However, reward showed a significantly inverse association with return to work with an OR of 0.90 (95% CI 0.83-0.99). In the fully adjusted model the OR of ERI decreased to 1.20 (95% CI 0.49-2.96). Effort, reward and overcommitment also showed attenuated ORs without significant results in all models. Diabetes mellitus, current smoking, low physical and low mental HRQOL presented significantly negative relations with return to work. Conclusions Work-related stress appears less important than HRQOL and resilience in terms of return to work after AMI.

Resilience is strongly associated with health-related quality of life but does not buffer work-related stress in employed persons 1 year after acute myocardial infarction.

PURPOSE: Resilience may facilitate the adaptation after experiencing a severe disease such as acute myocardial infarction (AMI) and attenuate the negative effects of stress on health-related quality of life (HRQOL). However, it is unclear so far whether resilience moderates a negative association between work-related stress and HRQOL in employed patients after AMI. METHODS: Patients with confirmed AMI and regular paid employment admitted to a hospital in the study region of the MONICA/KORA Myocardial Infarction Registry, Germany (04/2014-06/2017) were included and completed questionnaires during their hospital stay and 6 and 12 months after discharge. The Resilience Questionnaire (RS-11) and the Effort-Reward Imbalance (ERI) Questionnaire were used to assess trait resilience and ERI, respectively. HRQOL was measured by the Short Form 36 Health Survey (SF-36) mental and physical component summary scales. Generalized estimating equations (GEE) adjusted for relevant potential confounding variables (demographic, social, stress-related, and clinical) were used to determine the association between resilience and HRQOL in the study course. RESULTS: From the 346 patients enrolled in the study, 270 patients (78.0%) had completed all surveys. High baseline trait resilience was significantly and independently associated with high physical HRQOL (ß = 0.15, p < 0.0001) and high mental HRQOL (ß = 0.37, p < 0.0001) 1 year post AMI. No significant interaction effects between trait resilience and ERI were found in the physical HRQOL GEE model (ß = 0.05, p = 0.7241) and in the mental HRQOL model (ß = 0.05, p = 0.3478). CONCLUSIONS: The results demonstrated that trait resilience is independently and strongly related with post-AMI HRQOL but does not moderate the association between ERI and HRQOL.

Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.

BACKGROUND AND PURPOSE: Although a genetic contribution to ischemic stroke is well recognized, only a handful of stroke loci have been identified by large-scale genetic association studies to date. Hypothesizing that genetic effects might be stronger for early- versus late-onset stroke, we conducted a 2-stage meta-analysis of genome-wide association studies, focusing on stroke cases with an age of onset <60 years. METHODS: The discovery stage of our genome-wide association studies included 4505 cases and 21 968 controls of European, South-Asian, and African ancestry, drawn from 6 studies. In Stage 2, we selected the lead genetic variants at loci with association P<5×10(-6) and performed in silico association analyses in an independent sample of ≤1003 cases and 7745 controls. RESULTS: One stroke susceptibility locus at 10q25 reached genome-wide significance in the combined analysis of all samples from the discovery and follow-up stages (rs11196288; odds ratio =1.41; P=9.5×10(-9)). The associated locus is in an intergenic region between TCF7L2 and HABP2. In a further analysis in an independent sample, we found that 2 single nucleotide polymorphisms in high linkage disequilibrium with rs11196288 were significantly associated with total plasma factor VII-activating protease levels, a product of HABP2. CONCLUSIONS: HABP2, which encodes an extracellular serine protease involved in coagulation, fibrinolysis, and inflammatory pathways, may be a genetic susceptibility locus for early-onset stroke.

Epigenetics meets metabolomics: an epigenome-wide association study with blood serum metabolic traits.

Previously, we reported strong influences of genetic variants on metabolic phenotypes, some of them with clinical relevance. Here, we hypothesize that DNA methylation may have an important and potentially independent effect on human metabolism. To test this hypothesis, we conducted what is to the best of our knowledge the first epigenome-wide association study (EWAS) between DNA methylation and metabolic traits (metabotypes) in human blood. We assess 649 blood metabolic traits from 1814 participants of the Kooperative Gesundheitsforschung in der Region Augsburg (KORA) population study for association with methylation of 457 004 CpG sites, determined on the Infinium HumanMethylation450 BeadChip platform. Using the EWAS approach, we identified two types of methylome-metabotype associations. One type is driven by an underlying genetic effect; the other type is independent of genetic variation and potentially driven by common environmental and life-style-dependent factors. We report eight CpG loci at genome-wide significance that have a genetic variant as confounder (P = 3.9 × 10(-20) to 2.0 × 10(-108), r(2) = 0.036 to 0.221). Seven loci display CpG site-specific associations to metabotypes, but do not exhibit any underlying genetic signals (P = 9.2 × 10(-14) to 2.7 × 10(-27), r(2) = 0.008 to 0.107). We further identify several groups of CpG loci that associate with a same metabotype, such as 4-vinylphenol sulfate and 4-androsten-3-beta,17-beta-diol disulfate. In these cases, the association between CpG-methylation and metabotype is likely the result of a common external environmental factor, including smoking. Our study shows that analysis of EWAS with large numbers of metabolic traits in large population cohorts are, in principle, feasible. Taken together, our data suggest that DNA methylation plays an important role in regulating human metabolism.

Quality assurance in the pre-analytical phase of human urine samples by (1)H NMR spectroscopy.

Metabolomic approaches investigate changes in metabolite profiles, which may reflect changes in metabolic pathways and provide information correlated with a specific biological process or pathophysiology. High-resolution (1)H NMR spectroscopy is used to identify metabolites in biofluids and tissue samples qualitatively and quantitatively. This pre-analytical study evaluated the effects of storage time and temperature on (1)H NMR spectra from human urine in two settings. Firstly, to evaluate short time effects probably due to acute delay in sample handling and secondly, the effect of prolonged storage up to one month to find markers of sample miss-handling. A number of statistical procedures were used to assess the differences between samples stored under different conditions, including Projection to Latent Structure Discriminant Analysis (PLS-DA), non-parametric testing as well as mixed effect linear regression analysis. The results indicate that human urine samples can be stored at 10 °C for 24 h or at -80 °C for 1 month, as no relevant changes in (1)H NMR fingerprints were observed during these time periods and temperature conditions. However, some metabolites most likely of microbial origin showed alterations during prolonged storage but without facilitating classification. In conclusion, the presented protocol for urine sample handling and semi-automatic metabolite quantification is suitable for large-scale epidemiological studies.

Metabolomics approach reveals effects of antihypertensives and lipid-lowering drugs on the human metabolism.

The mechanism of antihypertensive and lipid-lowering drugs on the human organism is still not fully understood. New insights on the drugs' action can be provided by a metabolomics-driven approach, which offers a detailed view of the physiological state of an organism. Here, we report a metabolome-wide association study with 295 metabolites in human serum from 1,762 participants of the KORA F4 (Cooperative Health Research in the Region of Augsburg) study population. Our intent was to find variations of metabolite concentrations related to the intake of various drug classes and--based on the associations found--to generate new hypotheses about on-target as well as off-target effects of these drugs. In total, we found 41 significant associations for the drug classes investigated: For beta-blockers (11 associations), angiotensin-converting enzyme (ACE) inhibitors (four assoc.), diuretics (seven assoc.), statins (ten assoc.), and fibrates (nine assoc.) the top hits were pyroglutamine, phenylalanylphenylalanine, pseudouridine, 1-arachidonoylglycerophosphocholine, and 2-hydroxyisobutyrate, respectively. For beta-blockers we observed significant associations with metabolite concentrations that are indicative of drug side-effects, such as increased serotonin and decreased free fatty acid levels. Intake of ACE inhibitors and statins associated with metabolites that provide insight into the action of the drug itself on its target, such as an association of ACE inhibitors with des-Arg(9)-bradykinin and aspartylphenylalanine, a substrate and a product of the drug-inhibited ACE. The intake of statins which reduce blood cholesterol levels, resulted in changes in the concentration of metabolites of the biosynthesis as well as of the degradation of cholesterol. Fibrates showed the strongest association with 2-hydroxyisobutyrate which might be a breakdown product of fenofibrate and, thus, a possible marker for the degradation of this drug in the human organism. The analysis of diuretics showed a heterogeneous picture that is difficult to interpret. Taken together, our results provide a basis for a deeper functional understanding of the action and side-effects of antihypertensive and lipid-lowering drugs in the general population.

German translation and psychometric evaluation of the Mental Health Literacy Scale (MHLS-GER) in a general population sample and in patients with acute myocardial infarction.

BACKGROUND: The Mental Health Literacy Scale (MHLS) is a scale-based measure with 35 items that assesses various aspects of mental health literacy. The original English version was developed in Australia and has been translated into several languages. The present study aimed to translate and culturally adapt the questionnaire for its use in Germany and to determine the psychometric properties of the German version of the MHLS (MHLS-GER) in two different samples. METHODS: After translation and cultural adaptation, the MHLS-GER was administered via an online survey in a general population sample and via a postal survey in patients with acute myocardial infarction (AMI). Exploratory factor analysis and confirmatory factor analysis were conducted to determine the dimensionality. Furthermore, internal consistency, known-groups-validity and measurement invariance were evaluated. RESULTS: Data of 517 participants of the general population sample and 786 participants of the AMI sample were analyzed. In both samples a four-factor structure yielded good model fit indices. The four subscales of the MHLS-GER including 31 items comprise the topics 'knowledge' (11 items), 'information seeking' (4 items), 'stigmatization' (9 items) and 'social distance' (7 items). All four subscales showed good internal consistency (Cronbach's alpha: 0.80 to 0.90, average inter-item correlation: 0.30-0.59) and were mostly invariant across the two samples. Participants with previous experience with mental disorders (personal or professional context) showed higher scores on the four subscales. CONCLUSION: In contrast to the unidimensional structure of the original version, the MHLS-GER comprises four subscales. All subscales showed acceptable to good psychometric properties and can now be used to assess mental health literacy. Further validation studies to evaluate test-retest-reliability and responsiveness are required.

Prevalence of a large panel of systemic autoantibodies in the Bavarian adult population.

Objective: Autoimmune diseases commonly feature the presence of specific humoral autoantibodies. However, the prevalence of a large panel of systemic autoantibodies has never been assessed in the general population. We, therefore, described the prevalence of about 50 humoral systemic autoantibodies in a sample of the general Bavarian adult population. Methods: Non-fasting venous serum samples from 331 participants were analyzed for 7 autoantibody screening tests (nuclear, cytoplasmic, and mitotic ANA, ANCA, cANCA and pANCA, anti-ENA autoantibodies) and 44 different monospecific humoral non-organ specific/systemic autoantibodies using indirect immunofluorescence tests, ELISAs, and line blots. In order to assess associations between sex, age, BMI, education level, smoking status and the presence of systemic autoantibodies, logistic regression analyses were conducted. Results: At least one screening test was positive in 29.9% of the participants, and 42.3% of the participants were seropositive for at least one monospecific autoantibody. The most frequently found monospecific autoantibodies were rheumatoid factor (35.6%), ß2-glycoprotein 1 IgM (4.8%), and cardiolipin IgG (1.8%). Only few associations between sex, age, BMI, education, smoking status and autoantibody frequencies were observed. Conclusion: Systemic autoantibodies are common in the general Bavarian population, and largely independent of sex, age, BMI, education, or smoking status. The study results may give orientation to clinicians about the occurrence of autoantibodies in the population, not (yet) associated with clinical symptoms.