Domains of Physical Activity in Relation to Stiffness Index in the General Population.

Background Regular exercise training represents an important modifier of arterial stiffness (AS). Therefore, sex‐specific relations between domains of physical activity (PA; commuting, domestic, and leisure‐time PA, including active sport and occupational PA) with AS were investigated. Methods and Results Stiffness index by digital photoplethysmography was investigated in 12 650 subjects from the GHS (Gutenberg Health Study). Self‐reported PA was evaluated by the “Short Questionnaire to Assess Health‐Enhancing Physical Activity” and reported as activity score peer week, being a combined measure of duration, frequency, and intensity of PA. Multivariable linear regression analysis demonstrat…

Type-D personality and depersonalization are associated with suicidal ideation in the German general population aged 35–74: Results from the Gutenberg Heart Study

Suicidal ideation (SID) is a major risk factor for suicide attempts. Mental disorders are among the strongest correlates of suicide, with depression and anxiety disorders playing a major role. The present study aims to investigate the contribution of under researched factors contributing to SID such as depersonalization, Type-D personality and cardiovascular risk factors.Factors associated with SID were investigated in a sample of N=5000 participants (aged 35-74 years) of the community-based survey "Gutenberg Heart Study". The factors were assessed by self-report instruments, computer-assisted interviews and medical examination.7.5% of the sample reported SID over the last 2 weeks. In the u…

Coagulation and inflammation in long‐term cancer survivors: results from the adult population

Essentials The increase of cancer survival remains curtailed by cardiovascular mortality. We studied a large range of inflammatory and coagulation biomarkers in long-term cancer survivors. Cancer history has an important impact on mortality independent of cardiovascular risk factors. Fibrinogen and von Willebrand factor are potential biomarkers in survivors of increased mortality. Summary Background The advances in cancer treatment and detection of early cancer have resulted in a steady increase in the number of of cancer survivors over the years. However, because of the long-term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular disease (CVD) is increasing in …

New susceptibility locus for coronary artery disease on chromosome 3q22.3

We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in approximately 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.44 x 10(-13); OR = 1.15, 95% CI = 1.11-1.19), and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43 (P = 4.81 x 10(-7); OR = 1.08, 95% CI = 1.05-1.11).

Telemedicine-Based Specialized Care Improves the Outcome of Anticoagulated Individuals with Venous Thromboembolism-Results from the thrombEVAL Study.

Venous thromboembolism (VTE) is a life-threatening disease with risk of recurrence. Oral anticoagulation (OAC) with vitamin K antagonists (VKA) is effective to prevent thromboembolic recurrence. We aimed to investigate the quality of OAC of VTE patients in regular medical care (RMC) compared to a telemedicine-based coagulation service (CS). The thrombEVAL study (NCT01809015) is a prospective, multi-center study to investigate OAC treatment (recruitment: January 2011&ndash

Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.31 within the FNDC3B gene (P = 4.19 x 10(-8) for rs6445055), two on chromosome 9 (P = 2.80 x 10(-11) for rs2472493 near ABCA1 and P = 6.39 x 10(-11) for rs8176693…

Prevalence of Strabismus and Its Impact on Vision-Related Quality of Life

Purpose This study investigates the prevalence of manifest strabismus and its subtypes in adulthood and analyzes the risk factors and its impact on vision-related quality of life (VRQoL). Design The Gutenberg Health Study (GHS) is a population-based, observational cohort study. A cross-sectional analysis of the baseline examination was conducted. Participants Participants aged 35 to 74 years were included (n = 15  010). Methods All participants were examined with a comprehensive ophthalmologic and general examination including the Hirschberg corneal reflex test to detect manifest strabismus. The following risk factors were analyzed: age, sex, socioeconomic status, birth weight, maternal age…

A prospective cohort study to identify and evaluate endotypes of venous thromboembolism: Rationale and design of the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism project (GMP-VTE)

Abstract Several clinical, genetic and acquired risk factors for venous thromboembolism (VTE) have been identified. However, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. This is reflected by uncertainties regarding the primary and secondary prevention of VTE and the optimal duration of antithrombotic therapy. A growing body of literature points to clinically relevant differences between VTE phenotypes (e.g. deep vein thrombosis (DVT) versus pulmonary embolism (PE), unprovoked versus provoked VTE). Extensive links to cardiovascular, inflammatory and immune-related morbidities are testament to the complexity of the disease. The GMP-VTE project …

New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

Item does not contain fulltext Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic ne…

Birthweight and its association with retinal vessel equivalents – Results from the population‐based German Gutenberg Health Study

Refined atrial fibrillation screening and cost-effectiveness in the German population

ObjectiveLittle is known on optimal screening population for detecting new atrial fibrillation (AF) in the community. We describe characteristics and estimate cost-effectiveness for a single timepoint electrocardiographic screening.MethodsWe performed a 12-lead ECG in the German population-based Gutenberg Health Study between 2007 and 2012 (n=15 010), mean age 55±11 years, 51% men and collected more than 120 clinical and biomarker variables, including N-terminal pro B-type natriuretic peptide (Nt-proBNP), risk factors, disease symptoms and echocardiographic variables.ResultsOf 15 010 individuals, 466 (3.1%) had AF. New AF was found in 32 individuals, 0.2% of the total sample, 0.5% of indivi…

Soluble Platelet Release Factors as Biomarkers for Cardiovascular Disease

Platelets are the main players in thrombotic diseases, where activated platelets not only mediate thrombus formation but also are involved in multiple interactions with vascular cells, inflammatory components, and the coagulation system. Although in vitro reactivity of platelets provides information on the function of circulating platelets, it is not a full reflection of the in vivo activation state, which may be relevant for thrombotic risk assessment in various disease conditions. Therefore, studying release markers of activated platelets in plasma is of interest. While this type of study has been done for decades, there are several new discoveries that highlight the need for a critical a…

KCND3 is a novel susceptibility locus for early repolarization

AbstractThe presence of an early repolarization pattern (ERP) on the surface electrocardiogram (ECG) is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait but molecular genetic determinants are unknown. We assessed the ERP in 12-lead ECGs of 39,456 individuals and conducted a two-stage meta-analysis of genome-wide association studies (GWAS). In the discovery phase, we included 2,181 cases and 23,641 controls from eight European ancestry studies and identified 19 genome-wide significant (p<5E-8) variants in the KCND3 (potassium voltage gated channel subfamily D member 3) gene with a p-value of 4.6E-10. …

Early discharge and home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: an international multicentre single-arm clinical trial.

Abstract Aims To investigate the efficacy and safety of early transition from hospital to ambulatory treatment in low-risk acute PE, using the oral factor Xa inhibitor rivaroxaban. Methods and results We conducted a prospective multicentre single-arm investigator initiated and academically sponsored management trial in patients with acute low-risk PE (EudraCT Identifier 2013-001657-28). Eligibility criteria included absence of (i) haemodynamic instability, (ii) right ventricular dysfunction or intracardiac thrombi, and (iii) serious comorbidities. Up to two nights of hospital stay were permitted. Rivaroxaban was given at the approved dose for PE for ≥3 months. The primary outcome was sympto…

Multiple biomarkers and atrial fibrillation in the general population.

BACKGROUND: Different biological pathways have been related to atrial fibrillation (AF). Novel biomarkers capturing inflammation, oxidative stress, and neurohumoral activation have not been investigated comprehensively in AF. METHODS AND RESULTS: In the population-based Gutenberg Health Study (n = 5000), mean age 56 ± 11 years, 51% males, we measured ten biomarkers representing inflammation (C-reactive protein, fibrinogen), cardiac and vascular function (midregional pro adrenomedullin [MR-proADM], midregional pro atrial natriuretic peptide [MR-proANP], N-terminal pro-B-type natriuretic peptide [Nt-proBNP], sensitive troponin I ultra [TnI ultra], copeptin, and C-terminal pro endothelin-1), a…

Association of mental distress with smoking status in the community: Results from the Gutenberg Health Study.

Abstract Background Exposition to tobacco smoke is among the major modifiable risk factors in the general population. There is strong evidence for a close association between smoking exposure and mental disorders. Methods Cross-sectional associations of different conditions of smoking status (former, current, and second hand smoking (SHS)) with indicators of mental distress were analyzed in a sample of N =5000 participants (aged 35–74 years) of the population-based survey “Gutenberg Health Study”. Results In the general population clinically significant depression (OR 1.59, 95%CI 1.17–2.17) and a previous diagnosis of depression (OR 1.50, 95%CI 1.16–1.94) were associated with current smokin…

Removing Batch Effects from Longitudinal Gene Expression - Quantile Normalization Plus ComBat as Best Approach for Microarray Transcriptome Data

International audience; Technical variation plays an important role in microarray-based gene expression studies, and batch effects explain a large proportion of this noise. It is therefore mandatory to eliminate technical variation while maintaining biological variability. Several strategies have been proposed for the removal of batch effects, although they have not been evaluated in large-scale longitudinal gene expression data. In this study, we aimed at identifying a suitable method for batch effect removal in a large study of microarray-based longitudinal gene expression. Monocytic gene expression was measured in 1092 participants of the Gutenberg Health Study at baseline and 5-year fol…

Assessment of microRNAs in patients with unstable angina pectoris.

Aims While cardiac troponin measurements have significantly improved the early diagnosis of myocardial infarction, the timely biomarker-based diagnosis of unstable angina pectoris (UAP) remains a major unmet clinical challenge. The aim of this study was to assess levels of circulating microRNAs (miRNAs) as possible novel biomarkers in patients with UAP. Methods and results A three-phase approach was conducted, comprising (i) profiling of miRNAs in patients with UAP and controls groups; (ii) replication of significant miRNAs in an independent patient cohort, (iii) validation of a multi-miRNAs panel in a third cohort. Out of 25 miRNAs selected for replication, 8 miRNAs remained significantly …

The Prevalence of Amblyopia in Germany

Amblyopia is a condition in which reduced visual acuity is not directly caused by an organic defect (1). Amblyopia can develop when an infant or small child suffers from strabismus. Although both eyes are healthy, different images are formed on each fovea centralis (where vision is sharpest) and on other corresponding locations on the retina; this is in contrast to individuals without strabismus. To prevent double vision the child’s brain suppresses the image produced by one eye. Complete visual ability cannot develop in this eye during the sensitive phase of visual development (2). Approximately half of amblyopia cases (3) are caused by uncorrected higher refractive errors, which are frequ…

Freehand three-dimensional assessment of left ventricular volumes and ejection fraction with ultrasound contrast agent LK565

Accurate assessment of left ventricular function by determining left ventricular volumes and ejection fraction is important in evaluating the prognoses of patients with heart failure. Two-dimensional (2D) echocardiography suffers from low correlation with reference methods like ventriculography. Three-dimensionally (3D) assessed data have been proved to have better conformity. Endocardial border delineation remains a problem, however, especially in patients with suboptimal recordings. Few data exist on 3D-echocardiographic volumetry with ultrasound contrast agents (UCAs). We evaluated the second-generation UCA LK565 for its boundary-tracing capacities in freehand 3D echocardiography in a ph…

Prevalence of refractive errors in the European adult population: the Gutenberg Health Study (GHS).

Objective To study the distribution of refractive errors among adults of European descent. Design Population-based eye study in Germany with15 010 participants aged 35–74 years. Methods The study participants underwent a detailed ophthalmic examination according to a standardised protocol. Refractive error was determined by an automatic refraction device (Humphrey HARK 599) without cycloplegia. Definitions for the analysis were myopia +0.5 D, astigmatism >0.5 cylinder D and anisometropia >1.0 D difference in the spherical equivalent between the eyes. Exclusion criterion was previous cataract or refractive surgery. Results 13 959 subjects were eligible. Refractive errors ranged from −21.5 to…

One simple claudication question as first step in Peripheral Arterial Disease (PAD) screening: A meta-analysis of the association with reduced Ankle Brachial Index (ABI) in 27,945 subjects

Purpose and methods A meta-analysis using data from seven German population-based cohorts was performed by the German Epidemiological consortium of Peripheral Arterial Disease (GEPArD) to investigate whether one question about claudication is more efficient for PAD screening than established questionnaires. Claudication was defined on the basis of the answer to one question asking for pain in the leg during normal walking. This simple question was compared with established questionnaires, including the Edinburgh questionnaire. The associations of claudication with continuous ABI values and decreased ABI were analyzed by linear and logistic regression analysis, respectively. The results of t…

Association of MR-proadrenomedullin with cardiovascular risk factors and subclinical cardiovascular disease.

Abstract Aims and background Midregional proadrenomedullin (MR-proADM) is a protein, which exerts various effects on the cardiovascular system. Recent studies underscored its prognostic implications in patients with acute dyspnea and cardiovascular diseases. Therefore, we aimed to determine the distribution of MR-proADM in the general population and to reveal potential associations of MR-proADM with cardiovascular risk factors and measures of subclinical cardiovascular disease. Methods and results MR-proADM plasma concentrations were determined in individuals of the population-based cohort of the Gutenberg Health Study ( N  = 5000) using a commercially available fluoroimmunoassay. Individua…

C4BPB/C4BPA is a new susceptibility locus for venous thrombosis with unknown protein S-independent mechanism: results from genome-wide association and gene expression analyses followed by case-control studies

3 Figures. 2 Tables. The online version of this article contains a data supplement.

c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans

Essentials Prekallikrein (PK) deficiency is a recessive trait with isolated aPTT prolongation. KLKB1 c.451dupT is common in Nigerians (7/600 alleles) and absent in a European group (0/600). To date, all genotyped PK-deficient patients of African ancestry were homozygous for 451dupT. Diagnostics of isolated aPTT prolongation in African descendants should include PK testing. ABSTRACT: Background Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Afri…

Genome-Wide Haplotype Analysis of Cis Expression Quantitative Trait Loci in Monocytes

In order to assess whether gene expression variability could be influenced by several SNPs acting in cis, either through additive or more complex haplotype effects, a systematic genome-wide search for cis haplotype expression quantitative trait loci (eQTL) was conducted in a sample of 758 individuals, part of the Cardiogenics Transcriptomic Study, for which genome-wide monocyte expression and GWAS data were available. 19,805 RNA probes were assessed for cis haplotypic regulation through investigation of ∼2,1×109 haplotypic combinations. 2,650 probes demonstrated haplotypic p-values >104-fold smaller than the best single SNP p-value. Replication of significant haplotype effects were tested f…

ADMA and arginine derivatives in relation to non-invasive vascular function in the general population.

Nitric oxide produced from l-arginine is central to vascular homeostasis. Little is known about the relationship between arginine derivatives including asymmetric dimethylarginine (ADMA) and non-invasive vascular function measures in the general population.In 5000 individuals (median age 56; 25th/75th percentile: 46, 65; 49% women) taking part in the population-based Gutenberg Health Study (Mainz area, Germany), we measured the relationship between the arginine derivatives asymmetric dimethylarginine (ADMA), N-monomethyl l-arginine (NMMA), symmetric dimethylarginine (SDMA) and l-arginine with flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT). Weak bivariate correlations w…

Association of Low Birth Weight With Altered Corneal Geometry and Axial Length in Adulthood in the German Gutenberg Health Study

IMPORTANCE: Low birth weight is associated with altered ocular organ development in childhood, including the morphology of the eye. However, no population-based data exist about this association in adulthood. OBJECTIVE: To evaluate whether low birth weight has a long-term association with anterior segment anatomy and axial length in adulthood. DESIGN, SETTING, AND PARTICIPANTS: The Gutenberg Health Study is a population-based, observational cohort study in Germany. All participants underwent ocular biometry. Among the participants with follow-up and self-reported birth weight available, associations were assessed between low birth weight and anterior segment anatomy and axial length using m…

Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project.

Background— Cardiovascular risk estimation by novel biomarkers needs assessment in disease-free population cohorts, followed up for incident cardiovascular events, assaying the serum and plasma archived at baseline. We report results from 2 cohorts in such a continuing study. Methods and Results— Thirty novel biomarkers from different pathophysiological pathways were evaluated in 7915 men and women of the FINRISK97 population cohort with 538 incident cardiovascular events at 10 years (fatal or nonfatal coronary or stroke events), from which a biomarker score was developed and then validated in the 2551 men of the Belfast Prospective Epidemiological Study of Myocardial Infarction (PRIME) co…

Association of ocular, cardiovascular, morphometric and lifestyle parameters with retinal nerve fibre layer thickness.

BACKGROUND Glaucoma is a neurodegenerative disease, leading to thinning of the retinal nerve fibre layer (RNFL). The exact influence of ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFL thickness (RNFLT) is unknown and was analysed in a subgroup of the Gutenberg Health Study (GHS). METHODS Global peripapillary RNFLT was measured in 3224 eyes of 1973 subjects (49% female) using spectral-domain optical coherence tomography (SD-OCT). The association of age, sex, ocular, cardiovascular, morphometric, lifestyle and cognitive factors on RNFLT was analysed using Pearson correlation coefficient and fitting a linear mixed model. RESULTS In the univariable analysis highest…

Isolated Pulmonary Embolism Is Associated With a High Risk of Arterial Thrombotic Disease

Background Isolated PE is associated with a higher burden of atherosclerotic disease than other manifestations of VTE. Research Question We hypothesized that the presence of isolated PE may signal a chronically elevated risk of arterial thrombotic disease. Study Design and Methods Data from the VTEval Study, a prospective cohort study enrolling individuals with clinical suspicion and imaging-based diagnosis or exclusion of VTE, were analyzed. Patients with PE received whole-leg ultrasonography to assess presence of DVT. Regularized logistic regression identified features that discriminate between isolated PE and other VTE phenotypes at clinical presentation. Survival analyses were performed…

Assessing Planning Ability Across the Adult Life Span in a Large Population-Representative Sample: Reliability Estimates and Normative Data for the Tower of London (TOL-F) Task

AbstractObjectives:The Tower of London (TOL) test has probably become the most often used task to assess planning ability in clinical and experimental settings. Since its implementation, efforts were made to provide a task version with adequate psychometric properties, but extensive normative data are not publicly available until now. The computerized TOL-Freiburg Version (TOL-F) was developed based on theory-grounded task analyses, and its psychometric adequacy has been repeatedly demonstrated in several studies but often with small and selective samples.Method:In the present study, we now report reliability estimates and normative data for the TOL-F stratified for age, sex, and education …

High efficacy of face masks explained by characteristic regimes of airborne SARS-CoV-2 virus abundance

Abstract Airborne transmission is an important transmission pathway for viruses, including SARS-CoV-2. Regions with a higher proportion of people wearing masks show better control of COVID-19, but the effectiveness of masks is still under debate due to their limited and variable efficiencies in removing respiratory particles. Here, we analyze experimental data and perform model calculations to show that this contrast can be explained by the different regimes of abundance of particles and viruses. Because of the large number of particles exhaled during human respiration and vocalization, indoor environments are usually in a particle-rich regime which means that masks cannot prevent the inhal…

PO-58 - Cardiovascular risk profile in survivors of adult cancer - results from the general population study.

The advancements in cancer treatment and detection of early cancer have resulted in steady increase of adult cancer survivors over the years. However, due to the long term toxic effects of chemotherapy and radiotherapy, the incidence of cardiovascular diseases (CVD) is increasing in survivors. Identifying risk factors and interventions to reduce the excess burden of CVD in this vulnerable population is urgently needed.To investigate the cardiovascular risk factors (CVRFs), inflammation and coagulation profile in cancer survivors from a large population-based study.Presence of CVRFs and laboratory markers have been compared in individuals with (n=1,359) and without (n=13,626) history of canc…

Loneliness predicts suicidal ideation and anxiety symptoms in long-term childhood cancer survivors.

Abstract Background/Objective Long-term childhood cancer survivors (CCS) are at risk for adverse late effects. However, not all of them are well understood. The present study addressed loneliness, a previously under-researched mental health risk in cancer survivor populations. We assessed the prevalence of loneliness and its impact on psychological symptoms over time. Method: A registry-based sample of N = 633 adult long-term CCS underwent medical and psychological assessments and took part in a follow-up survey 2.5 years later. Psychological symptoms (somatic, anxiety, depression symptoms, and suicidal ideation) were measured using the Patient Health Questionnaire. We calculated linear reg…

Adaptive linear rank tests for eQTL studies

Expression quantitative trait loci (eQTL) studies are performed to identify single-nucleotide polymorphisms that modify average expression values of genes, proteins, or metabolites, depending on the genotype. As expression values are often not normally distributed, statistical methods for eQTL studies should be valid and powerful in these situations. Adaptive tests are promising alternatives to standard approaches, such as the analysis of variance or the Kruskal-Wallis test. In a two-stage procedure, skewness and tail length of the distributions are estimated and used to select one of several linear rank tests. In this study, we compare two adaptive tests that were proposed in the literatur…

Prevalence and associations of diabetic retinopathy in a large cohort of prediabetic subjects: The Gutenberg Health Study

Abstract Aims To evaluate the prevalence of diabetic retinopathy/maculopathy (DR/DMac) and its associations with cardiovascular risk factors (CRF) in participants with prediabetes (PwPD) in a large European cohort within the population-based Gutenberg Health Study (GHS). Methods The study was based on a sub-cohort of the GHS (n=5,000, age: 35–74 y). Prediabetes was diagnosed according to HbA 1c levels (5.7–6.4%). DR/DMac was graded from fundus photographs. Blood samples and comprehensive questionnaires served for evaluation of laboratory results and CRF. Results The prevalence of prediabetes was 22.4%, and of DR/DMac 8.1%/0.2%, respectively. The majority of participants had mild DR (7.2%). …

ADMA, subclinical changes and atrial fibrillation in the general population.

Abstract Background Pathways of oxidative stress, nitric oxide bioavailability and l-arginine derivatives are hypothesized to be related to atrial fibrillation (AF). Circulating methylated l-arginine metabolites can be assessed in the general population and may show an association with AF. Methods We determined l-arginine and its metabolites asymmetric dimethylarginine (ADMA), l-N ω -monomethylarginine (NMMA) and symmetric dimethylarginine (SDMA) in the population-based Gutenberg Health Study (n=5000), mean age 55±11years, 51% men, in association with clinical variables of AF such as electrocardiographic and echocardiographic measures and manifest AF. Results Individuals with AF (N=161), 71…

What's past is prologue: Recalled parenting styles are associated with childhood cancer survivors' mental health outcomes more than 25 years after diagnosis

Abstract Background With the increased survival rates of childhood cancer, long-term survivors' well-being over the life span has come into focus. A better understanding of the determinants of childhood cancer survivors' (CCS) mental health outcomes contributes to the identification of vulnerable individuals as well as to the development of evidence-based prevention and intervention efforts. It has been noted that psychosocial factors such as parental rearing behavior shape individual differences in mental health. There is also evidence that parents show altered parenting behavior in the face of childhood cancer, e. g. that they express more emotional support, but also more worries. However…

Mean Platelet Volume and Arterial Stiffness - Clinical Relationship and Common Genetic Variability

AbstractVessel wall stiffening is an important clinical parameter, but it is unknown whether platelets, key elements in the pathogenesis of arterial thrombosis, are associated with arterial stiffness. The present studies sought to determine whether mean platelet volume (MPV), a potential marker of platelet activation, is linked to vascular elasticity as assessed by the augmentation index (AIx), in 15,010 individuals from the population-based Gutenberg Health Study. Multivariable analysis showed that MPV in both males (β 0.776; 95thCI [0.250;1.16]; p = 0.0024) and females (β 0.881[0.328;1.43]; p = 0.0018) is strongly associated with AIx. Individuals with MPV and AIx above the sex-specific me…

Cardiovascular medication and intraocular pressure: results from the Gutenberg Health Study

BACKGROUND Intraocular pressure (IOP) is well known to be associated with blood pressure and other cardiovascular risk factors. The influence of systemic cardiovascular, in particular antihypertensive, medication on IOP is still controversial. This study analyses the association between the use of cardiovascular medications and IOP in a large European cohort. METHODS The Gutenberg Health Study is a population-based, prospective,observational cohort study in mid-western Germany. IOP was measured using a non-contact tonometer. The medication classes examined were peripheral vasodilators, diuretics, β-blockers (overall, selective and non-selective), calcium channel blockers, renin-angiotensin …

Disturbed Glucose Metabolism and Left Ventricular Geometry in the General Population

Background: This study sought to investigate the prevalence and clinical outcome of left ventricular (LV) geometry in prediabetes and type 2 diabetes mellitus (T2DM) and the impact of glucose metabolism on the incidence of left ventricular hypertrophy (LVH). Methods: 15,010 subjects (35–74 years) of the population-based Gutenberg Health Study were categorized into euglycemia, prediabetes, and T2DM according to clinical and metabolic (HbA1c) information. Clinical outcome was assessed via structured follow-up. Results: The study comprised 12,121 individuals with euglycemia (81.6%), 1415 with prediabetes (9.5%), and 1316 with T2DM (8.9%). Prevalence of LVH increased from euglycemia (10.2%) ove…

The relationship of ocular geometry with refractive error in normal and low birth weight adults

Purpose Low birth weight (BW) individuals have an increased risk for myopic refractive error. However, it is unclear which ocular geometric alterations lead to an increase in myopic refractive error. This study aims to evaluate the impact of ocular biometry in interaction with BW on refractive error. Methods Participants of the prospective, observational, population-based Gutenberg Health Study (GHS) with self-reported BW aged 40–80 years and objective refraction and optical biometry were included. Linear regression analyses were conducted to evaluate associations between spherical equivalent with corneal power, anterior chamber depth, lens thickness and axial length and its interaction wit…

Meta-analysis of genome-wide association studies from the CHARGE consortium identifies common variants associated with carotid intima media thickness and plaque

Carotid intima media thickness (cIMT) and plaque determined by ultrasonography are established measures of subclinical atherosclerosis that each predicts future cardiovascular disease events. We conducted a meta-analysis of genome-wide association data in 31,211 participants of European ancestry from nine large studies in the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. We then sought additional evidence to support our findings among 11,273 individuals using data from seven additional studies. In the combined meta-analysis, we identified three genomic regions associated with common carotid intima media thickness and two different regions a…

Homoarginine Levels are Regulated by L-Arginine: Glycine Amidinotransferase and Affect Stroke Outcome: Results from Human and Murine Studies

Background— Endogenous arginine homologues, including homoarginine, have been identified as novel biomarkers for cardiovascular disease and outcomes. Our studies of human cohorts and a confirmatory murine model associated the arginine homologue homoarginine and its metabolism with stroke pathology and outcome. Methods and Results— Increasing homoarginine levels were independently associated with a reduction in all-cause mortality in patients with ischemic stroke (7.4 years of follow-up; hazard ratio for 1-SD homoarginine, 0.79 [95% confidence interval, 0.64–0.96]; P =0.019; n=389). Homoarginine was also independently associated with the National Institutes of Health Stroke Scale+age score …

Predictive Value for Increased Factor XIa and Plasma Kallikrein Activity in Acute Venous Thromboembolism

Abstract Venous thromboembolism (VTE) is associated with increased coagulation activity, which in part can be attributed to the contact pathway of coagulation. Evidence from pre-clinical and epidemiological studies suggests that deficiency in factors of contact activation (e.g. coagulation factors (F) XI and FXII) protects against VTE. However, limited information exists regarding the activation of the contact system in the setting of acute VTE. In the current study, patients with confirmed VTE events (n=321) from the VTEval study and controls (n=300) from the population-based PREVENT-it pilot study were included. Plasma samples were collected from patients after confirmed VTE events or con…

Comparison of HapMap and 1000 genomes reference panels in a large-scale genome-wide association study

An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were ass…

The Choice of the Filtering Method in Microarrays Affects the Inference Regarding Dosage Compensation of the Active X-Chromosome

BackgroundThe hypothesis of dosage compensation of genes of the X chromosome, supported by previous microarray studies, was recently challenged by RNA-sequencing data. It was suggested that microarray studies were biased toward an over-estimation of X-linked expression levels as a consequence of the filtering of genes below the detection threshold of microarrays.Methodology/principal findingsTo investigate this hypothesis, we used microarray expression data from circulating monocytes in 1,467 individuals. In total, 25,349 and 1,156 probes were unambiguously assigned to autosomes and the X chromosome, respectively. Globally, there was a clear shift of X-linked expressions toward lower levels…

Cystatin C and cardiovascular mortality in patients with coronary artery disease and normal or mildly reduced kidney function: results from the AtheroGene study

Aims Chronic kidney disease is associated with increased risk of cardiovascular disease. Cystatin C is a promising marker to reliably mirror renal function. The role of cystatin C in patients with coronary artery disease (CAD) and normal or mildly reduced kidney function is the subject of current investigation. Methods and results In 2162 patients, over the whole spectrum of CAD, baseline cystatin C concentrations were measured. Patients with an estimated glomerular filtration rate of ≤60 mL/min per 1.73 m2 ( n = 295) were excluded. In patients with complete follow-up information ( n = 1827), 66 cardiovascular deaths were registered during a median follow-up of 3.65 years. Logarithmically t…

Prevalence of corneal arcus and associated factors in a German population-Results from the Gutenberg Health Study.

Purpose We aimed to determine the prevalence of corneal arcus and to identify associated factors in the general population of Germany. Methods The Gutenberg Health Study (GHS) is a population-based cohort study in Germany, which includes an ophthalmological assessment. Refraction, distance-corrected visual acuity, non-contact tonometry and anterior segment imaging were performed for the five-year follow-up examination. Anterior segment photographs were graded for the presence of corneal arcus. Prevalence estimates were computed, and multivariable logistic regression analysis was applied to determine associated factors for corneal arcus including sex, age, spherical equivalent, central corn…

International, multicenter evaluation of a new D-dimer assay for the exclusion of venous thromboembolism using standard and age-adjusted cut-offs.

We sought to determine the test characteristics of an automated INNOVANCE D-dimer assay for the exclusion of pulmonary embolism (PE) and deep venous thrombosis (DVT) in emergency department (ED) patients using standard and age-adjusted cut-offs.Cross-sectional, international, multicenter study of consecutive patients with suspected DVT or PE in 24 centers (18 USA, 6 Europe). Evaluated patients had low or intermediate Wells PE or DVT scores. For the standard cut-off, a D-dimer result500 ng/ml was negative. For the age adjusted cut-off, we used the formula: Age (years) ∗ 10. The diagnostic standard was imaging demonstrating PE or DVT within 3 months. We calculated test characteristics using s…

Management of Oral Anti-Coagulation in Patients with Heart Failure-Insights from the ThrombEVAL Study

AbstractPatients with heart failure (HF) are frequently anti-coagulated with vitamin K-antagonists (VKAs). The use of long-acting VKA may be preferable for HF patients due to higher stability of plasma concentrations. However, evidence on phenprocoumon-based oral anti-coagulation (OAC) therapy in HF is scarce. The aim of this study was to assess the impact of the presence of HF on quality of phenprocoumon-based OAC and the subsequent clinical outcome. Quality of OAC therapy and the incidence of adverse events were analysed in a cohort of regular care (n = 2,011) from the multi-centre thrombEVAL study program (NCT01809015) stratified by the presence of HF. To assess the modifiability of outc…

Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome.

Early and adequate risk stratification is essential in patients with suspected acute coronary syndrome (ACS). The aim of the present study was to investigate whether glycogen phosphorylase BB (GPBB) could add prognostic information in the context of contemporary sensitive troponin I determination and B-type natriuretic peptide (BNP). Patients with suspected ACS were consecutively enrolled at 3 German study centers from January 2007 through December 2008. Troponin I, GPBB, and BNP were determined at admission. Follow-up information on the combined end point of death, myocardial infarction, revascularization, and hospitalization owing to a cardiovascular cause was obtained 6 months after enro…

Genetic variants associated with cardiac structure and function: a meta-analysis and replication of genome-wide association data.

Context Echocardiographic measures of left ventricular (LV) structure and function are heritable phenotypes of cardiovascular disease. Objective To identify common genetic variants associated with cardiac structure and function by conducting a meta-analysis of genome-wide association data in 5 population-based cohort studies (stage 1) with replication (stage 2) in 2 other community-based samples. Design, Setting, and Participants Within each of 5 community-based cohorts comprising the EchoGen consortium (stage 1; n = 12 612 individuals of European ancestry; 55% women, aged 26-95 years; examinations between 1978-2008), we estimated the association between approximately 2.5 million single-nuc…

An epidemiological study exploring a possible impact of treatment with ACE inhibitors or angiotensin receptor blockers on ACE2 plasma concentrations

Comprehensive exploration of the effects of miRNA SNPs on monocyte gene expression.

We aimed to assess whether pri-miRNA SNPs (miSNPs) could influence monocyte gene expression, either through marginal association or by interacting with polymorphisms located in 3'UTR regions (3utrSNPs). We then conducted a genome-wide search for marginal miSNPs effects and pairwise miSNPs × 3utrSNPs interactions in a sample of 1,467 individuals for which genome-wide monocyte expression and genotype data were available. Statistical associations that survived multiple testing correction were tested for replication in an independent sample of 758 individuals with both monocyte gene expression and genotype data. In both studies, the hsa-mir-1279 rs1463335 was found to modulate in cis the expres…

Face masks effectively limit the probability of SARS-CoV-2 transmission.

Masking out air sharing The effectiveness of masks in preventing the transmission of severe acute respiratory syndrome coronavirus 2 has been debated since the beginning of the COVID-19 pandemic. One important question is whether masks are effective despite the forceful expulsion of respiratory matter during coughing and sneezing. Cheng et al. convincingly show that most people live in conditions in which the airborne virus load is low. The probability of infection changes nonlinearly with the amount of respiratory matter to which a person is exposed. If most people in the wider community wear even simple surgical masks, then the probability of an encounter with a virus particle is even fur…

Effects of oral niacin on endothelial dysfunction in patients with coronary artery disease: Results of the randomized, double-blind, placebo-controlled INEF study

High-density-lipoproteins-cholesterol (HDL-C) is invertedly related to the incidence of cardiovascular events. Recent studies suggest that HDL-C directly improves endothelial function. Nicotinic acid (niacin) effectively raises serum HDL-C. We therefore hypothesized that treatment with niacin improves endothelial dysfunction in patients with coronary artery disease (CAD). One hundred seven patients with CAD were randomly assigned to double-blinded treatment for 12 weeks with extended-release (ER)-niacin 1000 mg/day (N) or placebo (C), respectively. Flow-mediated dilation (FMD) of the brachial artery, nitroglycerin-mediated endothelium-independent dilation (NMD) and serum lipid concentration…

Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional…

Epidemiologic Analysis of Asteroid Hyalosis and Associations: The Gutenberg Health Study

Thrombin generation in cardiovascular disease and mortality – results from the Gutenberg Health Study

Thrombin generation may be a potential tool to improve risk stratification for cardiovascular diseases. The aim of this study was to explore the relation between thrombin generation and cardiovascular risk factors, cardiovascular diseases, and total mortality. For this study, 5,000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. Thrombin generation was assessed by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor triggers in platelet-poor plasma. Lag time, endogenous thrombin potential, and peak height were derived from the thrombin generation curve. Sex-specific multivariable linear regression analysis adjusted…

Abstract 13257: FEV1 and FVC predict Mortality in Individuals Without Manifest Lung Disease Independent of Cardiac Performance - Results From the Population-based Gutenberg Health Study

Background: Pulmonary disease has consistently been related to increased mortality. We investigated central spirometry variables in relation to total mortality in individuals from the general population without diagnosed lung disease also accounting for cardiac function. Methods: In 15,010 individuals from the general population (mean age 55±11 years, age range 35-74 years, 50.5% men) in the Gutenberg Health Study we performed spirometry and multimodal transthoracic echocardiography. The biomarkers N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (TnI) were measured in the first 5000 individuals using commercially available assays. Multivariable Cox regre…

Distribution of Anterior Chamber Angle Width and Correlation With Age, Refraction, and Anterior Chamber Depth—The Gutenberg Health Study

PURPOSE Scheimpflug imaging allows quantitative analysis of the width of the anterior chamber angle. We report the population-based distribution of the anterior chamber angle width using this noncontact imaging technique and investigate associated factors. METHODS A population-based cross-sectional study was carried out in Germany. A comprehensive ophthalmologic examination including refraction, biometry, and Scheimpflug imaging was performed. Automated measurement of the anterior chamber angle was performed in each anterior chamber quadrant. Exclusion criteria were previous ocular surgery or inadequate image quality. Association analyses were carried out to determine independently associat…

Hypertension in Germany

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 Examina…

Birth weight and its association with optic nerve head morphology - results from the population-based German Gutenberg Health Study.

e-Health-based management of patients receiving oral anticoagulation therapy: results from the observational thrombEVAL study

Essentials e-Health based health care by an expert centre may advance management of oral anticoagulation. Outcome of patients was compared between an e-health based coagulation service and regular care. Patients in the coagulation service cohort experienced a significantly better clinical outcome. Lower risk for adverse events was related to anticoagulation-specific and non-specific outcome. SummaryBackground Management of oral anticoagulation (OAC) therapy is essential to minimize adverse events in patients receiving vitamin K-antagonists (VKAs). Data on the effect of e-health-based anticoagulation management systems on the clinical outcome of OAC patients are limited. Objectives To compar…

The desire for children among adult survivors of childhood cancer: Psychometric evaluation of a cancer-specific questionnaire and relations with sociodemographic and psychological characteristics.

OBJECTIVE Long-term childhood cancer survivors (CCS) are less likely to become parents than their peers of the same age. Previous research has suggested that besides fertility, this outcome is shaped by psychosocial factors such as emotional motives toward having a child. Drawing from a sample of CCS with survival times >25 years, we present the validation of a questionnaire assessing cancer-specific reproductive motives and concerns. METHODS We evaluated the cancer-specific version of the Leipzig Questionnaire of Motives to have a Child (LKM-C) in a register-based sample of adult CCS (N = 632, 31% had children, 44.5% women). We conducted a confirmatory factor analysis and tested associatio…

Biomarkers for characterization of heart failure - Distinction of heart failure with preserved and reduced ejection fraction.

Heart failure (HF) incidence is rising worldwide and HF with preserved ejection fraction (HFpEF) represents nearly half of all cases. Treatment options are still limited in HFpEF in comparison to HF with reduced ejection fraction (HFrEF).We analyzed biomarkers in the general population to characterize HFpEF and HFrEF and defined a biomarker index to differentiate HFpEF from HFrEF. Growth differentiation factor-15 (GDF-15), soluble source of tumorigenicity 2 (sST2), C-reactive protein (CRP) and NT-proBNP were measured in 5000 individuals of the population-based Gutenberg Health Study (GHS). The median follow-up time for all-cause mortality was 7.3years with 213 events.Identification of subje…

Relations of Metabolically Healthy and Unhealthy Obesity to Digital Vascular Function in Three Community‐Based Cohorts: A Meta‐Analysis

Background Microvascular dysfunction is a marker of early vascular disease that predicts cardiovascular events. Whether metabolically healthy obese individuals have impaired microvascular function remains unclear. The aim of this study was to evaluate the relation of obesity phenotypes stratified by metabolic status to microvascular function. Methods and Results We meta‐analyzed aggregate data from 3 large cohorts (Brazilian Longitudinal Study of Adult Health, the Framingham Heart Study, and the Gutenberg Heart Study; n=16 830 participants, age range 19–90, 51.3% men). Regression slopes between cardiovascular risk factors and microvascular function, measured by peripheral arterial tonometr…

Parenting in the face of serious illness: Childhood cancer survivors remember different rearing behavior than the general population

Objective A child's cancer diagnosis and treatment affect the whole family. While it has been recognized that parents are an important resource for their children, little is known about the specifics of parenting in the face of serious illness. Methods We used the Recalled Parental Rearing Behavior Questionnaire in a register-based cohort of adult childhood cancer survivors (CCS) (N = 951) and a representative population sample of the same age range (N = 2042). The questionnaire assesses behavior of mothers and fathers with three scales (emotional warmth, rejection/punishment, and control/overprotection) by querying the (former) child. We compared the two groups using general linear models.…

Association of Serum Procalcitonin With Cardiovascular Prognosis in Coronary Artery Disease

Background: Procalcitonin (PCT) is an established biomarker for the diagnosis of sepsis. Evidence is growing that PCT concentration correlates with the extent of atherosclerosis and prognosis in patients with coronary artery disease (CAD). Methods and Results: A total of 2,131 patients with CAD were followed up for a median of 3.6 years. During follow-up, death from cardiovascular causes was registered in 95 patients and non-fatal myocardial infarction in 85 patients. Median and quartile 1 and 3 are reported for PCT concentration. Patients who died of cardiovascular causes had higher PCT concentrations [0.021 (0.012/0.036) ng/ml vs. 0.015 (0.010/0.023) ng/ml; P<0.0001]. Patients with acute …

Birth Weight and Diabetic Retinopathy: Results From the Population-Based Gutenberg Health Study (GHS).

Purpose: This study investigates the relationship between diabetic retinopathy (DR) and birth weight (BW) in diabetic subjects sampled from the general population. Methods: The Gutenberg Health Study (GHS) is a population-based, observational cohort study in participants aged from 35 to 74 years. Criteria for diabetes diagnosis were HbA1c ≥6.5% at study entry, a doctor-diagnosis of diabetes, or diabetes medication. The presence of DR was determined by evaluating fundus photographs. BW was assessed by self-reports. GHS participants were divided into three different BW groups (low: &lt;2500 g; normal: 2500–4000 g; high:&gt;4000 g). Logistic regression analysis was conducted as uni- and multiv…

Genome-wide association meta-analysis of PR interval identifies 47 novel loci associated with atrial and atrioventricular electrical activity

ABSTRACTElectrocardiographic PR interval measures atrial and atrioventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. We performed a genome-wide association study in over 92,000 individuals of European descent and identified 44 loci associated with PR interval (34 novel). Examination of the 44 loci revealed known and novel biological processes involved in cardiac atrial electrical activity, and genes in these loci were highly over-represented in several cardiac disease processes. Nearly half of the 61 independent index variants in the 44 loci were associated with atrial or blood transcript expression levels, or were i…

KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern

BACKGROUND: The presence of an early repolarization pattern (ERP) on the surface ECG is associated with risk of ventricular fibrillation and sudden cardiac death. Family studies have shown that ERP is a highly heritable trait, but molecular genetic determinants are unknown. METHODS: To identify genetic susceptibility loci for ERP, we performed a GWAS and meta-analysis in 2,181 cases and 23,641 controls of European ancestry. RESULTS: We identified a genome-wide significant (P < 5 × 10(–8)) locus in the potassium voltage-gated channel subfamily D member 3 (KCND3) gene that was successfully replicated in additional 1,124 cases and 12,510 controls. A subsequent joint meta-analysis of the discov…

Prevalence of cardiovascular late sequelae in long-term survivors of childhood cancer: A systematic review and meta-analysis

Background Cardiovascular diseases are well-known late effects of childhood cancer and research on these late effects is a highly important emerging field. We conducted a systematic review with a meta-analysis to give an overview of the current evidence and the prevalence of late cardiovascular events. Procedure We included publications in which the study populations were children and adolescents who survived cancer. Outcome was defined as all cardiovascular clinical and subclinical endpoints or diagnoses appearing at least one year after cancer diagnosis. A systematic overview is presented for all included studies. A quantitative meta-analysis was conducted for hypertension and stroke. Res…

Noise annoyance is associated with depression and anxiety in the general population : the contribution of aircraft noise

BACKGROUND: While noise annoyance has become recognized as an important environmental stressor, its association to mental health has hardly been studied. We therefore determined the association of noise annoyance to anxiety and depression and explored the contribution of diverse environmental sources to overall noise annoyance. PATIENTS AND METHODS: We investigated cross-sectional data of n = 15.010 participants of the Gutenberg Health Study (GHS), a population-based, prospective, single-center cohort study in Mid-Germany (age 35 to 74 years). Noise annoyance was assessed separately for road traffic, aircraft, railways, industrial, neighborhood indoor and outdoor noise ("during the day"; "i…

Subclinical impairment of lung function is related to mild cardiac dysfunction and manifest heart failure in the general population.

Lung function impairment has previously been related to heart failure, although no overt cardiovascular or structural heart disease is present. The extent to which pulmonary function is related to subclinical left ventricular impairment in the general population remains to be investigated.15010 individuals from the general population (mean age 55±11years, 50.5% men) in the Gutenberg Health Study underwent spirometry, transthoracic echocardiography and biomarker measurement. Forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) in percent of the predicted value and FEV1/FVC ratio were associated with echocardiographic measures of cardiac structure, systolic and diastolic func…

Subclinical levels of anxiety but not depression are associated with planning performance in a large population-based sample

BackgroundMajor depression and anxiety disorders are known to negatively influence cognitive performance. Moreover, there is evidence for greater cognitive decline in older adults with generalized anxiety disorder. Except for clinical studies, complex executive planning functions and subclinical levels of anxiety have not been examined in a population-based sample with a broad age range.MethodsPlanning performance was assessed using the Tower of London task in a population-based sample of 4240 participants aged 40–80 years from the Gutenberg Health Study (GHS) and related to self-reported anxiety and depression by means of multiple linear regression analysis.ResultsHigher anxiety ratings we…

Abstract 13812: Pulmonary Function Predicts Cardiac Function, Structure &amp; Clinical Outcome in Chronic Heart Failure: Results From the Myovasc Study

Introduction: A growing body of evidence suggests a relevance of pulmonary function in the pathophysiology of heart failure (HF). Comprehensive data on the role of forced expiratory volume in 1 second (FEV1) in the development &amp; progression of HF is limited. Hypothesis: Given this background, we hypothesized, that (FEV1) is associated with deteriorated left ventricular (LV) functional as well as structural status, &amp; predicts specific clinical outcome in HF. Methods: Data from the MyoVasc Study (n=3,289) were analysed. Comprehensive clinical phenotyping including body plethysmography for the evaluation of FEV1 &amp; standardized echocardiography were performed during a five-hour inv…

Abstract 18540: Heme Oxygenase 1 Activity and Expression Suppresses a Proinflammatory Phenotype in Monocytes and Correlates With Endothelial Function in Mice and Humans

Background: Heme oxygenase-1 (HO-1) confers protection to the vasculature and suppresses inflammatory properties of monocytes and macrophages. It is unclear how HO-1 activity and expression determine the extent of vascular dysfunction in mice and humans. Methods and results: Decreasing HO activity was parallelled by decreasing aortic HO-1, eNOS and phospho-eNOS (ser1177) protein expression in HO-1 deficient mice, whereas aortic expression of nox2 showed a stepwise increase in HO-1+/- and HO-1-/- mice as compared to HO-1+/+ controls. Aortic superoxide formation increased depending on the extent of HO-1 deficiency and was blunted by the PKC inhibitor chelerythrine, indicating activation of t…

Impact of diesel exposure on human health: the saga continues ….

Prevalence and risk factors of retinal vein occlusion: the Gutenberg Health Study.

SummaryObjective To determine the age- and sex-specific prevalence and determinants of retinal vein occlusions (RVOs) in a large population-based German cohort. Methods The investigation included 15 010 participants (aged 35–74 years) from the Gutenberg Health Study. We determined the prevalence of RVO (central retinal vein occlusion [CRVO] and branch retinal vein occlusion [BRVO]) for the local population by assessing fundus photographs of 12 954 (86.3%; 49.8% women and 50.2% men) participants. Further, we analyzed the associations of RVO with cardiovascular, anthropometric, and ophthalmic parameters. Results The weighted prevalences of RVO, CRVO, and BRVO were 0.40%, 0.08%, and 0.32%, res…

Fragment reconstruction of coronary arteries using transesophageal echocardiography for coronary diagnostics

Aims Ultrasound differs procedurally from the established methods for non-invasive coronary visualization and is therefore an interesting alternative for non-invasive diagnostics. In this study, fragment reconstruction of coronary arteries by transesophageal echocardiography (FRC-TEE) was investigated for the first time in a patient population being evaluated for coronary angiography. Methods and results Ultrasonic and angiographic findings were compared visually and using quantitative measurements in 50 patients. One hundred and seventy-one vessels were examined by FRC-TEE. The total lengths visualized were 9.6+ 1.7 cm for the right coronary artery, 7.0+ 1.1 cm for left circumflex, 3.9+ 1.…

Large-scale association analysis identifies new risk loci for coronary artery disease

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r 2 &lt; 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes …

Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: Data from the German CVSS-study.

Aims: The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results: In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German po…

Non-invasive peripheral vascular function, incident cardiovascular disease, and mortality in the general population

AIMS Evidence suggests that peripheral vascular function is related to cardiovascular disease (CVD) and mortality. We evaluated the associations of noninvasive measures of flow-mediated dilatation and peripheral arterial tonometry with incident CVD and mortality. METHODS AND RESULTS In a post-hoc analysis of the community-based Gutenberg Health Study, median age 55 years (25th/75th percentile 46/65) and 49.5% women, we measured brachial artery flow-mediated dilatation (N = 12,599) and fingertip peripheral arterial tonometry (N = 11,125). After a follow-up of up to 11.7 years, we observed 595 incident CVD events, 106 cardiac deaths, and 860 deaths in total. Survival curves showed decreased e…

The Prevalence of Glaucoma in Young People.

BACKGROUND Earlier information on the prevalence of glaucoma among children in Germany was based solely on estimates. Reported values for congenital glaucoma range from 1 in 10 000 to 1 in 68 000 depending on ethnic origin. The estimate for juvenile glaucoma is 1 in 44 000. METHODS The Gutenberg Health Study is a populationbased, prospective, monocentric cohort study with 15 010 participants aged 35 to 74. To determine the history-based prevalence of childhood glaucoma, participants were asked about the diagnosis of glaucoma, any operations for glaucoma that were performed, regular use of drugs for glaucoma, and the age of onset of glaucoma. The affected individuals were classified in four …

Copeptin Improves Early Diagnosis of Acute Myocardial Infarction

ObjectivesEarly identification of myocardial infarction in chest pain patients is crucial to identify patients at risk and to maintain a fast treatment initiation.BackgroundThe aim of the current investigation is to test whether determination of copeptin, an indirect marker for arginin-vasopressin, adds diagnostic information to cardiac troponin in early evaluation of patients with suspected myocardial infarction.MethodsBetween January 2007 and July 2008, patients with suspected acute coronary syndrome were consecutively enrolled in this multicenter study. Copeptin, troponin T (TnT), myoglobin, and creatine kinase-myocardial band were determined at admission and after 3 and 6 h.ResultsOf 1,…

No evidence for an association of plasma homocysteine levels and refractive error – Results from the population-based Gutenberg Health Study (GHS)

Purpose There is a strong association between severe hyperhomocysteinemia and myopia. Thus we studied the hypothesis that even moderately increased levels of homocysteine (Hcy) might be a potentially treatable risk factor for myopia. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74 at recruitment. The baseline examination was conducted from 2007–2012. Refraction was measured using autorefraction (HARK 599, Carl Zeiss AG, Jena, Germany). Hcy was measured by an immunoassay. We included only phakic participants without a history of corneal surgery or corneal laser treatment. …

Sensitive Troponin I Assay in Early Diagnosis of Acute Myocardial Infarction

BACKGROUND Cardiac troponin testing is central to the diagnosis of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction. METHODS In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission. RESULTS For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with t…

Noise annoyance predicts symptoms of depression, anxiety and sleep disturbance 5 years later. Findings from the Gutenberg Health Study

Abstract Background Cross-sectional studies have shown that noise annoyance is strongly associated with mental distress, however, its long-term effects on mental health is unknown. We therefore investigated whether noise annoyance predicts depression, anxiety and sleep disturbance in a large, representative sample 5 years later. Methods We investigated longitudinal data of N = 11 905 participants of the Gutenberg Health Study, a population-based, prospective, single-centre cohort study in mid-Germany (age at baseline 35–74 years). Noise annoyance was assessed at baseline and 5-year follow-up (sources: road traffic, aircraft, railways, industrial, neighbourhood indoor and outdoor noise; and …

Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies

Background: The pathogenesis of arterial and venous thrombosis is in large part interlaced. How much platelet phenotype relates to acute venous thromboembolism (VTE) independent of the underlying cardiovascular profile is presently poorly investigated.Methods: Platelet count and mean platelet volume (MPV), platelet aggregation in whole blood and platelet rich plasma (PRP), platelet-dependent thrombin generation (TG) and platelet surface activation markers were measured under standardized conditions. Machine learning was applied to identify the most relevant characteristics associated with VTE from a large array (N = 58) of clinical and plateletrelated variables.Findings: VTE cases (N = 159)…

Association Between Chromosome 9p21 Variants and the Ankle-Brachial Index Identified by a Meta-Analysis of 21 Genome-Wide Association Studies

Background— Genetic determinants of peripheral arterial disease (PAD) remain largely unknown. To identify genetic variants associated with the ankle-brachial index (ABI), a noninvasive measure of PAD, we conducted a meta-analysis of genome-wide association study data from 21 population-based cohorts. Methods and Results— Continuous ABI and PAD (ABI ≤0.9) phenotypes adjusted for age and sex were examined. Each study conducted genotyping and imputed data to the ≈2.5 million single nucleotide polymorphisms (SNPs) in HapMap. Linear and logistic regression models were used to test each SNP for association with ABI and PAD using additive genetic models. Study-specific data were combined using fi…

Crucial role for Nox2 and sleep deprivation in aircraft noise-induced vascular and cerebral oxidative stress, inflammation, and gene regulation

Abstract Aims Aircraft noise causes endothelial dysfunction, oxidative stress, and inflammation. Transportation noise increases the incidence of coronary artery disease, hypertension, and stroke. The underlying mechanisms are not well understood. Herein, we investigated effects of phagocyte-type NADPH oxidase (Nox2) knockout and different noise protocols (around-the-clock, sleep/awake phase noise) on vascular and cerebral complications in mice. Methods and results C57BL/6j and Nox2 −/− (gp91phox −/−) mice were exposed to aircraft noise (maximum sound level of 85 dB(A), average sound pressure level of 72 dB(A)) around-the-clock or during sleep/awake phases for 1, 2, and 4 days. Adverse effec…

PCSK9: A link between air pollution and cardiovascular disease?

Genome- wide association study with additional genetic and post-transcriptional analyses reveals novel regulators of plasma factor XI levels

International audience; Coagulation factor XI (FXI) has become increasingly interesting for its role in pathogenesis of thrombosis. While elevated plasma levels of FXI have been associated with venous thromboembolism and ischemic stroke, its deficiency is associated with mild bleeding. We aimed to determine novel genetic and post-transcriptional plasma FXI regulators.We performed a genome-wide association study (GWAS) for plasma FXI levels, using novel data imputed to the 1000 Genomes reference panel. Individual GWAS analyses, including a total of 16,169 European individuals from the ARIC, GHS, MARTHA and PROCARDIS studies, were meta-analysed and further replicated in 2,045 individuals from…

Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation

Common Genetic Variation in Relation to Brachial Vascular Dimensions and Flow-Mediated Vasodilation

Midregional Proadrenomedullin for Prediction of Cardiovascular Events in Coronary Artery Disease: Results from the AtheroGene Study

Abstract BACKGROUND Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR-proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation. METHODS We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years. RESULTS The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individu…

A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including similar to 120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci ; of which, 18 …

Psychosomatische Medizin in der Gutenberg- Gesundheitsstudie (GHS) – Fragestellungen, Messverfahren, ausgewählte Ergebnisse

Psychosomatic medicine in the Gutenberg Health Study (GHS) - research questions, measurement instruments, selected results Goal: Main questions from the Gutenberg Health Study (GHS) related to psychosomatic medicine are presented: (1) Prevalence and incidence of mental illnesses, (2) Sex-specific risk- and protective factors for mental health, (3) Interplay between psychological and somatic diseases and (4) methodical-psychometric developments. Methods: The GHS is an ongoing, prospective and interdisciplinary cohort study in Mainz. The comprehensive examinations include psychological characteristics and clinical and laboratory tests. 15010 respondents were selected in the baseline study fro…

FEV1 Predicts Cardiac Status and Outcome in Chronic Heart Failure

Background COPD is an established predictor of clinical outcome in patients with chronic heart failure (HF). However, little evidence is available about the predictive value of FEV1 in chronic HF. Research Question Is pulmonary function related to the progression of chronic HF? Study Design and Methods The MyoVasc study ( ClinicalTrials.gov Identifier: NCT04064450) is a prospective cohort study of HF. Information on pulmonary and cardiac functional and structural status was obtained by body plethysmography and echocardiography. The primary study end point was worsening of HF. Results Overall 2,998 participants (age range, 35-84 years) with available FEV1 data were eligible for analysis. Lin…

The diagnostic performance of renal function-adjusted D-dimer testing in individuals suspected of having venous thromboembolism

Renal impairment, a source of chronic hypercoagulability[1][1] and inflammation,[2][2] is known to reduce the specificity of the D-dimer test in the diagnosis of venous thromboembolism (VTE).[3][3] This leads to many false positives in such patients and consequently to additional costs, as well as

Sex differences in correlates of intermediate phenotypes and prevalent cardiovascular disease in the general population

Background: There are marked sex differences in cardiovascular disease (CVD) manifestation. It is largely unknown how the distribution of CVD risk factors or intermediate phenotypes explain sex-specific differences. Methods and Results: In 5000 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 51% males, we examined sex-specific associations of classical CVD risk factors with intima-media thickness, ankle-brachial index, flow-mediated dilation, peripheral arterial tonometry, echocardiographic, and electrocardiographic variables. Intermediate cardiovascular phenotypes were related to prevalent CVD [coronary artery disease, heart failure, stroke, myocardial i…

Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluat…

O78. Which phenotype adds to cardiovascular risk assessment? Lessons from the Gutenberg heart study: A prospective, population-based cohort study in cardiovascular epidemiology

Distribution of HOMA-IR in a population-based cohort and proposal for reference intervals

Abstract Objectives Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (DM). The homeostatic model assessment of insulin resistance (HOMA-IR) provides an estimate for IR from fasting glucose and insulin serum concentrations. The aim of this study was to obtain a reference interval for HOMA-IR for a specific insulin immunoassay. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, single-center cohort study in Germany with 15,030 participants aged 35–74 years. Fasting glucose, insulin, and C-peptide were available in 10,340 participants. HOMA-IR was calculated in this group and three reference subgroups with increasingly more stringent inclusion criteri…

Cross-Sectional Associations between Homoarginine, Intermediate Phenotypes, and Atrial Fibrillation in the Community—The Gutenberg Health Study

Homoarginine has come into the focus of interest as a biomarker for cardiovascular disease. Atrial fibrillation (AF) causes a substantial increase in morbidity and mortality. Whether circulating homoarginine is associated with occurrence or persistence of AF and may serve as a new predictive biomarker remains unknown. We measured plasma levels of homoarginine in the population-based Gutenberg health study (3761 patients included, of them 51.7% males), mean age 55.6 &plusmn

Multiple marker approach to risk stratification in patients with stable coronary artery disease

Aims Multimarker approaches for risk prediction in coronary artery disease have remained inconsistent. We assessed multiple biomarkers representing distinct pathophysiological pathways in relation to cardiovascular events in stable angina. Methods and results We investigated 12 biomarkers reflecting inflammation [C-reactive protein, growth-differentiation factor (GDF)-15, neopterin], lipid metabolism (apolipoproteins AI, B100), renal function (cystatin C, serum creatinine), and cardiovascular function and remodelling [copeptin, C-terminal-pro-endothelin-1, mid-regional-pro-adrenomedullin (MR-proADM), mid-regional-pro-atrial natriuretic peptide (MR-proANP), N-terminal-pro-B-type natriuretic …

Transcriptome-Wide Analysis Identifies Novel Associations With Blood Pressure.

Hypertension represents a major cardiovascular risk factor. The pathophysiology of increased blood pressure (BP) is not yet completely understood. Transcriptome profiling offers possibilities to uncover genetics effects on BP. Based on 2 populations including 2549 individuals, a meta-analyses of monocytic transcriptome-wide profiles were performed to identify transcripts associated with BP. Replication was performed in 2 independent studies of whole-blood transcriptome data including 1990 individuals. For identified candidate genes, a direct link between long-term changes in BP and gene expression over time and by treatment with BP-lowering therapy was assessed. The predictive value of pro…

Relevance of depression for anticoagulation management in a routine medical care setting: results from the ThrombEVAL study program

Summary Background Depressive symptoms have detrimental effects on quality of life and mortality. Poor adherence to a treatment regimen is a potential mechanism for the increased risk of adverse medical events associated with depression. Regarding oral anticoagulation with vitamin K antagonists, adherence is crucial for the outcome. Little is known about the clinical relevance of current depressiveness for anticoagulation treatment. Objectives To examine the impact of current depressiveness on anticoagulation treatment in regular medical care. Patients/Methods We examined the association between clinically significant depressiveness as assessed by the Patient Health Questionnaire-2 ≥ 2 (PHQ…

Relapse Rate in Survivors of Acute Autoimmune Thrombotic Thrombocytopenic Purpura Treated with or without Rituximab.

Background Autoimmune thrombotic thrombocytopenic purpura (iTTP) is caused by autoantibody-mediated severe a disintegrin and metalloprotease with thrombospondin type 1 repeats, member 13 (ADAMTS13) deficiency leading to micro-angiopathic haemolytic anaemia (MAHA) and thrombocytopenia with organ damage. Patients survive with plasma exchange (PEX), fresh frozen plasma replacement and corticosteroid treatment. Anti-CD20 monoclonal antibody rituximab is increasingly used in patients resistant to conventional PEX or relapsing after an acute bout. Objective This retrospective observational study focused on the relapse rate and possible influencing factors including treatment with rituximab first…

Survival and quality of life after early discharge in low-risk pulmonary embolism.

IntroductionEarly discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes.MethodsThe multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, …

Traffic-associated air pollution as a risk factor for cancer in individuals with coronary artery disease.

Distribution and categorization of left ventricular measurements in the general population: results from the population-based Gutenberg Heart Study.

Background— Echocardiography, the dominant imaging modality for quantification of left ventricular metrics, has undergone continuing development in the past few decades. However, given the lack of population-based data, current guidelines are still based on restricted and small data sets analyzed with methods including expert opinion. This work presents empirically derived reference values from a large-scale, epidemiologic study conducted with state-of-the-art imaging technology and methods. Methods and Results— The distribution of echocardiographic measurements of the left ventricle was analyzed in a population-based sample of 5000 mid-Europeans from the Gutenberg Heart Study in Germany. …

Characteristics and pathologies of the vitreo‐macular interface—results from the Gutenberg Health Study

Purpose We aimed to determine the prevalence of characteristics and pathologies of the vitreo-macular interface within the general population. Methods The Gutenberg Health Study is a population-based study in Germany, including an ophthalmological examination with refraction, biometry and optical coherence tomography (OCT) imaging. Characteristics of the vitreo-macular interface were graded on volume scans including visibility of an epiretinal membrane, full-thickness macular hole, lamellar hole and pseudohole. Overall and age-specific prevalences including 95% confidence intervals [95%-CI] were calculated. Association analyses were conducted to determine systemic and ocular factors that ar…

Potential of Multidimensional, Large-scale Biodatabases to Elucidate Coagulation and Platelet Pathways as an Approach towards Precision Medicine in Thrombotic Disease

Cardiovascular and especially thrombotic diseases remain a major cause of morbidity and mortality worldwide. In past years, significant improvements in understanding disease processes, risk assessment, and prediction of clinical outcome in the field of thrombosis and haemostasis have been made by using large-scale biodatabases. These important research resources enable a comprehensive research approach by integrating clinical, environmental, genomic, and molecular information. Cutting edge, high throughput technologies open new data dimensions for clinical large-scale investigations. Joining multiple information levels from several pathophysiological pathways in contrast to a single marker …

The Prevalence of Visual Impairment in the Adult Population

Background The distribution of visual impairment is an indicator of the health status of the population and for the frequency of diseases of the eye. Methods The Gutenberg Health Study (GHS) is a population-based cohort study in Germany concerning adults aged 35 to 74. 15 010 subjects from the Mainz-Bingen region underwent general medical and ophthalmological examination, with measurement of the distance-corrected visual acuity in each eye separately. As per the World Health Organization criteria, visual impairment was defined as an acuity below 0.3 in the better eye, and blindness as an acuity below 0.05. All patients who were found to be visually impaired or blind underwent further indivi…

Subtherapeutic Anticoagulation Control under Treatment with Vitamin K-Antagonists—Data from a Specialized Coagulation Service

AbstractIn contrast to overanticoagulation, evidence on risk factors and outcome of subtherapeutic oral anticoagulation (OAC) with vitamin K-antagonists (VKAs) under optimum care is limited. We investigated the clinical phenotype, anticoagulation control, and clinical outcome of 760 VKA patients who received OAC therapy by a specialized coagulation service in the thrombEVAL study (NCT01809015). During 281,934 treatment days, 278 patients experience ≥ 1 episode of subtherapeutic anticoagulation control and had lower quality of OAC therapy compared to 482 patients without subtherapeutic international normalized ratio: 67.6%, interquartile range (IQR) 54.9%/76.8% versus 81.0%, IQR 68.5%/90.4%;…

Sex-Specific Relationship Between Parathyroid Hormone and Platelet Indices in Phenotypes of Heart Failure—Results From the MyoVasc Study

Background: Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF.Aim: This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF.Methods and Results: PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk …

Atrial Fibrillation Manifestations Risk Factors and Sex Differences in a Population-Based Cohort (From the Gutenberg Health Study)

Sex differences in cardiovascular risk factors, cardiac structure and function, and disease and symptom burden in the common arrhythmia atrial fibrillation (AF) have not been investigated systematically at the population level. Cross-sectional data of 14,796 subjects (age range 35 to 74 years, 50.5% men) from the population-based Gutenberg Health Study were examined to show the distribution of cardiovascular risk factors by AF status and sex, and to determine sex-specific predictors for AF. The prevalence of AF was higher in men (4.3%) than in women (1.9%). Men had a worse cardiovascular risk factor profile, a higher prevalence of cardiovascular disease, but fewer symptoms than women. Age-a…

Genetics and Beyond – The Transcriptome of Human Monocytes and Disease Susceptibility

BACKGROUND: Variability of gene expression in human may link gene sequence variability and phenotypes; however, non-genetic variations, alone or in combination with genetics, may also influence expression traits and have a critical role in physiological and disease processes. METHODOLOGY/PRINCIPAL FINDINGS: To get better insight into the overall variability of gene expression, we assessed the transcriptome of circulating monocytes, a key cell involved in immunity-related diseases and atherosclerosis, in 1,490 unrelated individuals and investigated its association with >675,000 SNPs and 10 common cardiovascular risk factors. Out of 12,808 expressed genes, 2,745 expression quantitative trait …

Association of Type D personality with cognitive functioning in individuals with and without cardiovascular disease: The Gutenberg health study

ObjectiveDistressed (‘Type D’) personality is associated with adverse health outcomes in patients with cardiovascular disease (CVD). While personality traits from the Five-Factor Model are related to cognitive functioning, neither Type D personality nor its underlying traits negative affectivity (NA) and social inhibition (SI) have been investigated regarding cognition. We therefore compared the predictive value of Type D classification and its subcomponents NA and SI on planning performance in individuals with and without CVD.MethodsType D personality traits (DS14) were determined in a population-based sample of 4026 participants (including 549 with CVD) aged 40–80 years from the Gutenberg…

Linking cancer and mental health in men and women in a representative community sample

Abstract Objective In aging populations, a growing number of individuals are affected by cancer. However, the relevance of the disease for mental health is still controversial, especially after treatment. We drew from a representative community sample to explore the link of cancer with mental health assessing different dimensions and different periods of time. Methods A cohort of 14,375 men and women (35–74 years) underwent medical assessments and was queried about cancer history, previous diagnoses of mental disorders, current mental distress symptoms, and current subjective health appraisal. Results 1066 participants (7.4%) reported a diagnosis of cancer (survival time M = 9.79 (SD = 9.07…

History of deep vein thrombosis is a discriminator for concomitant atrial fibrillation in pulmonary embolism.

Pulmonary embolism (PE) is the consequence of deep vein thrombosis (DVT) in 70% of all cases. Although, PE and DVT are commonly related to risk factors of Virchow's triad, both entities are linked to cardiovascular risk factors, but risk factors seem differently important in both entities.We aimed to investigate clinical profile and outcome of patients with PE history stratified by concomitant DVT.Data from the observational multi-center thrombEVAL-study were analyzed.The sample (N=2,318) comprised 295 PE patients, of whom 69.2% (N=204) had DVT. Individuals without DVT were older and had higher prevalence of concomitant atrial fibrillation (AF), chronic lung diseases, coronary artery diseas…

Quality of Life 3 and 12 Months Following Acute Pulmonary Embolism

BACKGROUND Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact …

Physical Activity, Incidence, and Progression of Age-Related Macular Degeneration: A Multicohort Study.

Contains fulltext : 249581.pdf (Publisher’s version ) (Closed access) PURPOSE: To investigate the impact of physical activity (PA) on the incidence or progression of age-related macular degeneration (AMD) in the general population. DESIGN: Meta-analysis of longitudinal cohort studies. METHODS: We included 14,630 adults with no or early AMD at baseline from 7 population-based studies and examined associations of PA with AMD incidence and progression using multistate models (MSM) per study and subsequent random effects meta-analysis. Age effects were assessed using meta-regression. The main outcome measure was the hazard ratio (HR) for incident early or progression to late AMD. RESULTS: At ba…

Sex-specific differences in genetic and nongenetic determinants of mean platelet volume: results from the Gutenberg Health Study.

Mean platelet volume (MPV), a measure of platelet size, is a potential biological marker of platelet function. To date, a comprehensive analysis including known genetic and nongenetic factors that determine MPV is still lacking. MPV has been evaluated in 15 010 individuals from the population-based Gutenberg Health Study. Genetic information was available for 4175 individuals. Our results showed that age (β, 0.0346; 95% confidence interval [CI], 0.0255 to 0.0436), cardiovascular risk factors (CVRFs) such as smoking (β, 0.178; 95% CI, 0.128 to 0.229), hypertension (β, 0.05; 95% CI, 0.00289 to .0981), and high glucose level (β, 0.00179; 95% CI, 0.0006 to 0.00299) were linked with higher MPV i…

Genome-wide Association Studies Identify Genetic Loci Associated with Albuminuria in Diabetes

Elevated concentrations of albumin in the urine, albuminuria, are a hallmark of diabetic kidney disease and are associated with an increased risk for end-stage renal disease and cardiovascular events. To gain insight into the pathophysiological mechanisms underlying albuminuria, we conducted meta-analyses of genome-wide association studies and independent replication in up to 5,825 individuals of European ancestry with diabetes and up to 46,061 without diabetes, followed by functional studies. Known associations of variants in CUBN, encoding cubilin, with the urinary albumin-to-creatinine ratio (UACR) were confirmed in the overall sample (P = 2.4 × 10−10). Gene-by-diabetes interactions were…

Evaluation of oral anticoagulation therapy: Rationale and design of the thrombEVAL study programme

Since decades, oral anticoagulation (OAC) with vitamin K antagonists (VKA) is an established therapy for both prevention and treatment of thromboembolism in daily clinical routine. Increasing life expectancy, demographic changes, and novel oral anticoagulants have led to an increasing complexity of medical therapy. However, data on quality and management of VKA therapy with phenprocoumon in current medical care are limited. Our aim is to investigate the quality of OAC with VKA in current health care and to evaluate the potential for improvements.The investigator-initiated thrombEVAL study programme comprises two cohorts of patients treated with vitamin K antagonists for oral anticoagulation…

Relevance of Polypharmacy for Clinical Outcome in Patients Receiving Vitamin K Antagonists.

BACKGROUND Although polypharmacy is associated with a negative clinical outcome in various settings and commonly observed in patients receiving oral anticoagulation therapy, evidence on the relevance for the clinical outcome of anticoagulated patients is currently limited. The aim of the study was to investigate the effect of polypharmacy on the clinical outcomes among patients taking phenprocoumon. DESIGN Prospective cohort study. SETTING Regular medical care. PARTICIPANTS Information on 2011 individuals receiving vitamin K antagonists was available for analysis from the prospective multicenter thrombEVAL study. MEASUREMENTS Data were obtained from clinical visits, computer-assisted interv…

Schirmer test results: are they associated with topical or systemic medication?

To test whether Schirmer test (ST) results are associated with topical or systemic medication and to evaluate the distribution of tear fluid quantity in a 3-min and 5-min ST.The Gutenberg Health Study is a population-based, prospective, observational cohort study in Germany. ST was assessed in a sub-cohort of 1,999 participants. ST was performed under topical anesthesia for 5 min (ST-5) or of 3 min (ST-3). Anthropometric factors, systemic diseases, use of systemic and eye medications were recorded. We used multivariable quantile regression analysis to assess the influence on ST measurements.The length of wetting of the Schirmer strips for ST-5 was 23.2 ± 9.31 mm for right and 22.9 ± 9.0 mm …

Symptoms of depression and anxiety predict mortality in patients undergoing oral anticoagulation: Results from the thrombEVAL study program

Abstract Background/objectives Depression and anxiety are highly prevalent in cardiovascular patients. Therefore, we examined whether the 4-item Patient Health Questionnaire (PHQ-4, measuring symptoms of depression and anxiety) predicts all-cause mortality in outpatients with long-term oral anticoagulation (OAC). Methods The sample comprised n=1384 outpatients from a regular medical care setting receiving long-term OAC with vitamin K antagonists. At baseline, symptoms of anxiety and depression were assessed with the PHQ-4 and the past medical history was taken. The outcome was all-cause mortality in the 24month observation period. The median follow-up time was 13.3months. Results N=191 pati…

Serum selenium and prognosis in cardiovascular disease: results from the AtheroGene study

Experimental data suggest a protective role of the essential trace element selenium against cardiovascular disease (CVD), whereas epidemiological data remains controversial. We aimed to investigate the impact of serum selenium concentration in patients presenting with stable angina pectoris (SAP) or acute coronary syndrome (ACS) on long term prognosis.Baseline selenium concentration was measured in 1731 individuals (852 with SAP, and 879 with ACS). During a median follow-up of 6.1 years, 190 individuals died from cardiovascular causes.In those ACS patients who subsequently died of cardiac causes, selenium levels were lower compared to survivors (61.0microg/L versus 71.5microg/L; P0.0001). I…

Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 1…

Lipid-Mediated Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample

Abstract Background: Tissue factor pathway inhibitor (TFPI), a Kunitz-type serine protease, is a potent anticoagulant protein in the extrinsic coagulation pathway and acts by inhibiting both the FXa and the Tissue Factor-FVIIa complex. In contrast to total and free TFPI antigen levels, the reference values and clinical determinants of total TFPI activity have not yet been studied in detail in the general population. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and investigate its association with cardiovascular disease (CVD) and total mortality, in a population at large. Methods: For this study, the first 4779 subjects of the population-ba…

Selenium supplementation improves antioxidant capacity in vitro and in vivo in patients with coronary artery disease

Background Selenium is a central determinant of antioxidative glutathione peroxidase 1 (GPx-1) expression and activity. The relevance of selenium supplementation on GPx-1 in coronary artery disease (CAD) needs to be established. We assessed the effect of selenium supplementation on GPx-1 in cell culture and on endothelial function in a prospective clinical trial. Methods Human coronary artery endothelial cells were incubated with 5.78 to 578 nmol/L sodium selenite, Se-methyl-selenocysteine hydrochloride, or seleno-l-methionine. Glutathione peroxidase 1 mRNA and protein expression and activity were measured. Coronary artery disease patients (n = 465) with impaired endothelial function (flow-…

Alterations of a Cellular Cholesterol Metabolism Network Are a Molecular Feature of Obesity-Related Type 2 Diabetes and Cardiovascular Disease

Obesity is linked to type 2 diabetes (T2D) and cardiovascular diseases; however, the underlying molecular mechanisms remain unclear. We aimed to identify obesity-associated molecular features that may contribute to obesity-related diseases. Using circulating monocytes from 1,264 Multi-Ethnic Study of Atherosclerosis (MESA) participants, we quantified the transcriptome and epigenome. We discovered that alterations in a network of coexpressed cholesterol metabolism genes are a signature feature of obesity and inflammatory stress. This network included 11 BMI-associated genes related to sterol uptake (↑LDLR, ↓MYLIP), synthesis (↑SCD, FADS1, HMGCS1, FDFT1, SQLE, CYP51A1, SC4MOL), and efflux (↓A…

Sex-specific differences in the distal versus proximal presenting location of acute deep vein thrombosis

Abstract Background and aims Women present with pulmonary embolism (PE) more often than men, while the opposite is true for proximal deep vein thrombosis (DVT). We investigated whether sex-specific differences exist in the presenting location of acute symptomatic DVT among patients without concomitant PE. Methods We tested our hypothesis in a meta-analysis of studies selected by systematically reviewing PubMed, Embase, and the grey literature. Thereafter, we analysed data of a single-center cohort including patients with first isolated acute DVT to assess the additional impact of age and provoking risk factors on the presenting location of DVT. Results We identified 7 studies for a total of…

Acute deep vein thrombosis suppresses peripheral T cell effector function

Relation between Tissue Factor Pathway Inhibitor Activity and Cardiovascular Risk Factors and Diseases in a Large Population Sample.

Abstract Objective Tissue factor pathway inhibitor (TFPI) is a potent anticoagulant protein in the extrinsic coagulation pathway. In the present study, we aim to identify the cardiovascular determinants for total TFPI activity and its association with cardiovascular disease (CVD) and total mortality. Methods Total TFPI activity was assessed in a selection of the population-based Gutenberg Health Study (n = 5,000). Statistical analysis was performed to identify the determinants for total TFPI activity as well as the associations with CVD and mortality. Results Multivariable linear regression analysis identified smoking (β 0.095 [0.054–0.136]) as a positive determinant for total TFPI activity…

Integrating genome-wide genetic variations and monocyte expression data reveals trans-regulated gene modules in humans.

One major expectation from the transcriptome in humans is to characterize the biological basis of associations identified by genome-wide association studies. So far, few cis expression quantitative trait loci (eQTLs) have been reliably related to disease susceptibility. Trans-regulating mechanisms may play a more prominent role in disease susceptibility. We analyzed 12,808 genes detected in at least 5% of circulating monocyte samples from a population-based sample of 1,490 European unrelated subjects. We applied a method of extraction of expression patterns—independent component analysis—to identify sets of co-regulated genes. These patterns were then related to 675,350 SNPs to identify maj…

Discovery and Fine Mapping of Serum Protein Loci through Transethnic Meta-analysis

Many disorders are associated with altered serum protein concentrations, including malnutrition, cancer, and cardiovascular, kidney, and inflammatory diseases. Although these protein concentrations are highly heritable, relatively little is known about their underlying genetic determinants. Through transethnic meta-analysis of European-ancestry and Japanese genome-wide association studies, we identified six loci at genome-wide significance (p −8 ) for serum albumin ( HPN-SCN1B , GCKR-FNDC4 , SERPINF2-WDR81 , TNFRSF11A-ZCCHC2 , FRMD5-WDR76 , and RPS11-FCGRT , in up to 53,190 European-ancestry and 9,380 Japanese individuals) and three loci for total protein ( TNFRS13B , 6q21.3, and ELL2 , in …

Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study

BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal. METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Se…

Germ-free housing conditions do not affect aortic root and aortic arch lesion size of late atherosclerotic low-density lipoprotein receptor-deficient mice

The microbiota has been linked to the development of atherosclerosis, but the functional impact of these resident bacteria on the lesion size and cellular composition of atherosclerotic plaques in the aorta has never been experimentally addressed with the germ-free low-density lipoprotein receptor-deficient (Ldlr(-/-)) mouse atherosclerosis model. Here, we report that 16 weeks of high-fat diet (HFD) feeding of hypercholesterolemicLdlr(-/-)mice at germ-free (GF) housing conditions did not impact relative aortic root plaque size, macrophage content, and necrotic core area. Likewise, we did not find changes in the relative aortic arch lesion size. However, late atherosclerotic GFLdlr(-/-)mice …

Rationale, design and baseline characteristics of the MyoVasc study: A prospective cohort study investigating development and progression of heart failure.

Abstract Background Heart failure (HF) is a poly-aetiological syndrome with large heterogeneity regarding clinical presentation, pathophysiology, clinical outcome and response to therapy. The MyoVasc study (NCT04064450) is an epidemiological cohort study investigating the development and progression of HF. Methods The primary objective of the study is (a) to improve the understanding of the pathomechanisms of HF across the full spectrum of clinical presentation, (b) to investigate the current clinical classifications of HF, and (c) to identify and characterize homogeneous subgroups regarding disease development using a systems-oriented approach. Worsening of HF, that is, the composite of tr…

Missing value imputation in proximity extension assay-based targeted proteomics data

Targeted proteomics utilizing antibody-based proximity extension assays provides sensitive and highly specific quantifications of plasma protein levels. Multivariate analysis of this data is hampered by frequent missing values (random or left censored), calling for imputation approaches. While appropriate missing-value imputation methods exist, benchmarks of their performance in targeted proteomics data are lacking. Here, we assessed the performance of two methods for imputation of values missing completely at random, the previously top-benchmarked ‘missForest’ and the recently published ‘GSimp’ method. Evaluation was accomplished by comparing imputed with remeasured relative concentrations…

Biomarker des Myokardinfarkts mit nicht obstruierten Koronararterien

ZusammenfassungDer akute Myokardinfarkt mit nicht obstruierten Koronararterien (MINOCA) ist durch ein Fehlen von Koronarstenosen ≥ 50% in der Koronarangiografie gekennzeichnet. Die Datenlage zum MINOCA ist aufgrund der heterogenen Erfassung der Erkrankung und der zumeist ungeklärten Ätiologie in den meisten Studien begrenzt. Der MINOCA weist eine Häufigkeit 5,8 – 11,2% auf und tritt im Schnitt ca. 2 – 3 Jahre früher als der klassische Myokardinfarkt auf. Zum klinischen Profil der Patienten lassen sich aufgrund der Studienlage nur eingeschränkt Aussagen treffen. Diagnostischer Standard ist die kardiale Magnetresonanztomografie, mit der die Klärung der Genese in ca. 75% der Fälle gelingt. Die…

Correlations between central corneal thickness and general anthropometric characteristics and cardiovascular parameters in a large European cohort from the Gutenberg Health Study.

PURPOSE The aim of this study was to evaluate the correlations between general anthropometric features and cardiovascular parameters and central corneal thickness (CCT) in an adult European cohort. METHODS Analysis was based on a Gutenberg Health Study cohort that included 5000 subjects (2540 male, 2460 female), aged 35 to 74 years at enrollment. The participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination (slit-lamp biomicroscopy; autorefractometry; noncontact tonometry; fundus photography; CCT measurements (optical pachymetry); visual field testing; and a thorough general examination focused on cardiovascular parameters, psychosomatic evalu…

The Molecular Genetic Architecture of Self-Employment

Economic variables such as income, education, and occupation are known to affect mortality and morbidity, such as cardiovascular disease, and have also been shown to be partly heritable. However, very little is known about which genes influence economic variables, although these genes may have both a direct and an indirect effect on health. We report results from the first large-scale collaboration that studies the molecular genetic architecture of an economic variable-entrepreneurship-that was operationalized using self-employment, a widely-available proxy. Our results suggest that common SNPs when considered jointly explain about half of the narrow-sense heritability of self-employment es…

Chronic venous insufficiency, cardiovascular disease, and mortality: a population study

Abstract Aims  Evidence regarding the health burden of chronic venous insufficiency (CVI), its clinical determinants, and impact on outcome is scarce. Methods and results  Systematic phenotyping of CVI according to established CEAP (Clinical-Etiologic-Anatomic-Pathophysiologic) classification was performed in 12 423 participants (age range: 40–80 years) of the Gutenberg Health Study from April 2012 to April 2017. Prevalence was calculated age- and sex-specifically. Multivariable Poisson regression models were calculated to evaluate the relation of CVI with cardiovascular comorbidities. Survival analyses were carried out to assess the CVI-associated risk of death. Replication of findings was…

Cigarette Smoking Is Related to Endothelial Dysfunction of Resistance, but Not Conduit Arteries in the General Population—Results From the Gutenberg Health Study

Aims: Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort.Methods and results: 15,010 participants (aged 35–74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit an…

FEV1 and FVC predict all-cause mortality independent of cardiac function - Results from the population-based Gutenberg Health Study.

Abstract Background Lung function has previously been related to increased mortality. Whether pulmonary impairment is associated with an increased mortality independent of cardiac dysfunction remains unclear. Methods In 15010 individuals from the general population (age range 35–74years, 51% men) in the Gutenberg Health Study we performed spirometry and transthoracic echocardiography. N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and high-sensitive troponin I (hsTnI) were measured in all individuals. 1819 individuals with pulmonary diseases were excluded from further analysis. Results The median for forced expiratory volume in 1s (FEV1) was 94.2% and for forced vital capacity (FVC) …

Is assessment of depression equivalent for migrants of different cultural backgrounds? Results from the German population-based Gutenberg Health Study (GHS)

BACKGROUND Bearing in mind the multicultural background of a national population, little is known about the measurement invariance across different cultures or ethnicities of frequently used screeners for depression. For this reason, the main objective of the current study is to assess the measurement invariance of the Patient Health Questionnaire (PHQ-9) across groups with different migration backgrounds. METHODS We provided psychometric analyses (descriptive statistics at item and scale level, reliability analysis, exploratory [EFA] and confirmatory factor analyses [CFA]) comparing a native population with first- and second-generation migrants of the German population-based Gutenberg Heal…

Five-year change in refractive error and its risk factors: results from the Gutenberg Health Study.

Background/AimsTo examine the 5-year change in refractive error in phakic eyes and its risk factors in the general population.MethodsThe Gutenberg Health Study (GHS) is a population-based cohort study including 15 010 participants from Germany aged 35–74 years at baseline examination (2007–2012). After 5 years, a follow-up examination was carried out (83% participation). 5-year change of spherical equivalent (SE) was computed as difference between follow-up and baseline objective refraction. Linear and logistic regression analysis were conducted analysing potential risk factors. Only phakic eyes at follow-up examination were included.ResultsRight eyes of 10 175 subjects were included. An ag…

Annoyance to different noise sources is associated with atrial fibrillation in the Gutenberg Health Study

Abstract Background Annoyance is a common reaction in populations exposed to environmental noise and is associated with cardiovascular diseases. We investigated for the first time the existence of an association between noise annoyance and atrial fibrillation (AF). Methods and results Cross-sectional data from 14,639 participants of the Gutenberg Health Study were collected between 2007 and 2012. Annoyance from road traffic, aircraft, railways, industrial/construction and neighbourhood noise during daytime and sleep were collected from all participants through questionnaires using a 5-point scale. AF was assessed via self-reported medical history and/or documentation of AF on the study elec…

The distribution of whole blood viscosity, its determinants and relationship with arterial blood pressure in the community: cross-sectional analysis from the Gutenberg Health Study.

Background: Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study. Methods and results: Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, mi…

Identification of acute myocardial infarction in elderly patients using optimized highly sensitive troponin I thresholds

Purpose: Established diagnostic thresholds for high-sensitivity cardiac troponins (hs-cTn) might not apply for elderly patients as they are elevated irrespective of the presence of an acute myocardial infarction (AMI). Aim of the present study was to investigate hs-cTnI in elderly patients with suspected AMI and to calculate optimized diagnostic cutoffs. Material and methods: Data from a prospective multi-centre study and from a second independent prospective single-centre cohort study were analysed. A number of 2903 patients were eligible for further analysis. Patients &gt; 70 years were classified as elderly. hs-cTnI was measured upon admission. Results: Around 34.7% of 2903 patients were…

Distribution of Intraocular Pressure and Its Association with Ocular Features and Cardiovascular Risk Factors

Purpose To describe the distribution of intraocular pressure (IOP) and its association with ocular features and cardiovascular risk factors in an adult European cohort. Design Population-based, cross-sectional study. Participants This analysis was based on a Gutenberg Health Study (GHS) cohort that included 4335 eligible enrollees from among 5000 subjects who participated in the survey from 2007 through 2008. The age range was 35 to 74 years at enrollment. Methods Participants underwent a standardized protocol with a comprehensive questionnaire; ophthalmic examination including slit-lamp biomicroscopy, noncontact tonometry, fundus photography, central corneal thickness measurement, and visu…

Specialized Management of Oral Anticoagulation Therapy Improves Outcome in Patients with Chronic Renal Insufficiency

Oral anticoagulation (OAC) is effective at preventing and treating thromboses and thromboembolism in patients with normal renal function. We aimed to research the impact of severe renal failure (RF) on patient outcome and to determine the potential benefit of caring for these patients in a specialized coagulation service (CS). A total of 1516 usual medical care patients and 756 CS-managed patients of the thrombEVAL multicenter (21 centers), prospective, cohort study (NCT01809015) were analyzed in a 3-year follow-up. Patients with RF (serum creatinine &gt

Association of Global Longitudinal Strain With Clinical Status and Mortality in Patients With Chronic Heart Failure.

IMPORTANCE: Global longitudinal strain (GLS) is an emerging echocardiographic biomarker of cardiac function in heart failure (HF). Evidence from large-scale studies comprehensively investigating GLS for its association with clinical phenotypes and mortality in asymptomatic and symptomatic chronic HF is limited. OBJECTIVE: To assess the factors associated with GLS and its prognostic value in patients with chronic HF. DESIGN, SETTING, AND PARTICIPANTS: The observational, prospective MyoVasc cohort study enrolled 3289 individuals with asymptomatic to symptomatic HF between January 17, 2013, and April 27, 2018. The median follow-up was 3.2 years (interquartile range, 2.0-4.0 years). Participant…

Estimated stroke risk, yield, and number needed to screen for atrial fibrillation detected through single time screening: a multicountry patient-level meta-analysis of 141,220 screened individuals.

Background The precise age distribution and calculated stroke risk of screen-detected atrial fibrillation (AF) is not known. Therefore, it is not possible to determine the number needed to screen (NNS) to identify one treatable new AF case (NNS-Rx) (i.e., Class-1 oral anticoagulation [OAC] treatment recommendation) in each age stratum. If the NNS-Rx is known for each age stratum, precise cost-effectiveness and sensitivity simulations can be performed based on the age distribution of the population/region to be screened. Such calculations are required by national authorities and organisations responsible for health system budgets to determine the best age cutoffs for screening programs and d…

Noninvasive peripheral vascular function and atrial fibrillation in the general population.

Background Arterial stiffness is a strong predictor of atrial fibrillation in the community. Whether noninvasively measured conduit artery function and peripheral vascular reactivity are related to atrial fibrillation remains unknown. Methods and results In 15 010 individuals of the population-based Gutenberg Health Study, mean age 55 ± 11 years, 50.5% men, we determined noninvasive vascular function by flow-mediated dilation (FMD) and peripheral arterial tonometry (PAT) in relation to manifest atrial fibrillation (N = 466). Patients with atrial fibrillation exhibited a higher mean brachial artery diameter [4.81 mm (4.17, 5.33) in atrial fibrillation vs. 4.31 mm (3.67, 4.93)] and baseline p…

Genome-wide and gene-centric analyses of circulating myeloperoxidase levels in the charge and care consortia

Increased systemic levels of myeloperoxidase (MPO) are associated with the risk of coronary artery disease (CAD). To identify the genetic factors that are associated with circulating MPO levels, we carried out a genome-wide association study (GWAS) and a gene-centric analysis in subjects of European ancestry and African Americans (AAs). A locus on chromosome 1q31.1 containing the complement factor H (CFH) gene was strongly associated with serum MPO levels in 9305 subjects of European ancestry (lead SNP rs800292; P = 4.89 &times; 10(-41)) and in 1690 AA subjects (rs505102; P = 1.05 &times; 10(-8)). Gene-centric analyses in 8335 subjects of European ancestry additionally identified two rare M…

Incidence of Retinal Detachment in Germany: Results from the Gutenberg Health Study

&lt;b&gt;&lt;i&gt;Purpose:&lt;/i&gt;&lt;/b&gt; To investigate the incidence of retinal detachment in the German population and to assess potential risk factors. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; The Gutenberg Health Study is a population-based cohort study in Mainz, Germany, including subjects (&lt;i&gt;n&lt;/i&gt; = 15,010) with an age range from 35 to 74 years at baseline examination. Study participants underwent a comprehensive ophthalmological examination including distant-corrected visual acuity, refraction and slit-lamp examination at baseline examination. A computer-assisted telephone interview was conducted after 2.5 and 5 years, and health events were recorded. The 5-y…

Symptoms of depersonalization/derealization are independent risk factors for the development or persistence of psychological distress in the general population: Results from the Gutenberg health study

Abstract Background Symptoms of depersonalization (DP) and derealization (DR) have a high prevalence in patient and community samples. Previous studies suggested that DP/DR symptoms might represent a marker of disease severity and poor prognosis. However, population-based studies investigating the impact of DP/DR symptoms on the course of depression and anxiety are sparse. Therefore, we aimed to analyze whether symptoms of DP/DR are longitudinally associated with the persistence or incidence of elevated symptoms of depression/anxiety. Methods We analyzed observational data from a sample of 13.182 participants of the Gutenberg Health Study. The outcomes were elevated symptoms of depression/a…

Type D personality as a cardiovascular risk marker in the general population: results from the Gutenberg health study.

&lt;i&gt;Background:&lt;/i&gt; Type D personality is considered as an independent risk factor for morbidity and mortality in cardiovascular patients and a vulnerability factor for distress in the general population. Because representative community studies are rare, we sought to determine the prevalence of type D personality and its relationship with demographic characteristics, different features of mental disorders, cardiovascular risk factors, health behavior, endothelial function and cardiovascular biomarkers in the general population. &lt;i&gt;Methods:&lt;/i&gt; The prevalence of type D personality and its correlates were analyzed cross-sectionally in a population-based sample of 5,000…

Profile of the Immune and Inflammatory Response in Individuals With Prediabetes and Type 2 Diabetes.

OBJECTIVE The inflammatory and immune systems are altered in type 2 diabetes. Here, the aim was to profile the immune and inflammatory response in subjects with prediabetes and diabetes in a large population-representative sample. RESEARCH DESIGN AND METHODS In total, 15,010 individuals were analyzed from the population-based Gutenberg Health Study. Glucose status was classified according to HbA1c concentration and history of diagnosis. All samples were analyzed for white blood cells (WBCs), granulocytes, lymphocytes, monocytes, platelets, C-reactive protein (CRP), albumin, fibrinogen, and hematocrit. Interleukin-18 (IL-18), IL-1 receptor antagonist (IL-1RA), and neopterin concentrations w…

Large-scale genome-wide analysis identifies genetic variants associated with cardiac structure and function

BACKGROUND: Understanding the genetic architecture of cardiac structure and function may help to prevent and treat heart disease. This investigation sought to identify common genetic variations associated with inter-individual variability in cardiac structure and function. METHODS: A GWAS meta-analysis of echocardiographic traits was performed, including 46,533 individuals from 30 studies (EchoGen consortium). The analysis included 16 traits of left ventricular (LV) structure, and systolic and diastolic function. RESULTS: The discovery analysis included 21 cohorts for structural and systolic function traits (n = 32,212) and 17 cohorts for diastolic function traits (n = 21,852). Replication …

Sex-related differences in D-dimer levels for venous thromboembolism screening.

Background D-dimer is generally considered positive above 0.5 mg/L irrespective of sex. However, women have been shown to be more likely to have a positive D-dimer after controlling for other factors. Thus, differences may exist between males and females for using D-dimer as a marker of venous thromboembolic (VTE) disease. We hypothesized that the accuracy of D-dimer tests may be enhanced by using appropriate cutoff values that reflect sex-related differences in D-dimer levels. Methods This research is a secondary analysis of a multicenter, international, prospective, observational study of adult (18+ years) patients suspected of VTE, with low-to-intermediate pretest probability based on We…

Relative Telomere Length and Cardiovascular Risk Factors

(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status…

Abstract 147: The Role of Thrombin Generation in Cardiovascular Disease and Mortality - Results from the Population-based Gutenberg Health Study

Background: Thrombin formation is one of the key enzymatic processes that direct the activity of the hemostatic system. Thrombin generation (TG), a method addressing the overall potential of a given plasma sample to form thrombin, may be a potential tool to improve risk stratification for cardiovascular diseases (CVD). This study aims to explore the relation between TG and cardiovascular risk factors (CVRFs), CVD, and total mortality. Methods: For this study, N=5000 subjects from the population-based Gutenberg Health Study were analyzed in a highly standardized setting. TG was measured by the Calibrated Automated Thrombogram method at 1 and 5 pM tissue factor (TF) trigger in platelet poor …

Novel DNA Methylation Sites Influence GPR15 Expression in Relation to Smoking

Smoking is a major risk factor for cardiovascular diseases and has been implicated in the regulation of the G protein-coupled receptor 15 (GPR15) by affecting CpG methylation. The G protein-coupled receptor 15 is involved in angiogenesis and inflammation. An effect on GPR15 gene regulation has been shown for the CpG site CpG3.98251294. We aimed to analyze the effect of smoking on GPR15 expression and methylation sites spanning the GPR15 locus. DNA methylation of nine GPR15 CpG sites was measured in leukocytes from 1291 population-based individuals using the EpiTYPER. Monocytic GPR15 expression was measured by qPCR at baseline and five-years follow up. GPR15 gene expression was upregulated i…

New onset of depression in aging women and men: contributions of social, psychological, behavioral, and somatic predictors in the community.

AbstractBackgroundBased on the vulnerability–stress model, we aimed to (1) determine new onset of depression in individuals who had not shown evidence of depression at baseline (5 years earlier) and (2) identify social, psychological, behavioral, and somatic predictors.MethodsLongitudinal data ofN= 10 036 participants (40–79 years) were evaluated who had no evidence of depression at baseline based on Patient Health Questionnaire (PHQ-9), no history of depression, or intake of antidepressants. Multivariate logistic regression models were used to predict the onset of depression.ResultsPrevalence of new cases of depression was 4.4%. Higher rates of women (5.1%) than men (3.8%) were due to thei…

Assessing Planning Ability Across the Adult Life Span: Population-Representative and Age-Adjusted Reliability Estimates for the Tower of London (TOL-F).

Planning ahead the consequences of future actions is a prototypical executive function. In clinical and experimental neuropsychology, disc-transfer tasks like the Tower of London (TOL) are commonly used for the assessment of planning ability. Previous psychometric evaluations have, however, yielded a poor reliability of measuring planning performance with the TOL. Based on theory-grounded task analyses and a systematic problem selection, the computerized TOL-Freiburg version (TOL-F) was developed to improve the task's psychometric properties for diagnostic applications. Here, we report reliability estimates for the TOL-F from two large samples collected in Mainz, Germany (n = 3,770; 40-80 y…

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation o…

History of depression but not current depression is associated with signs of atherosclerosis: data from the Gutenberg Health Study.

ObjectivesTo test the vascular depression hypothesis in the general population, we analyzed the association between current depression, medical history of depression, cognitive and somatic depressive symptom dimensions and measures of atherosclerosis [intima–media thickness (IMT) and carotid plaques].MethodWe included a representative sample of 5000 participants from the Gutenberg Health Study (GHS). Depression was assessed by the nine-item Patient Health Questionnaire (PHQ-9), and IMT and carotid plaques were measured at both common carotid arteries using an edge detection system. Regression analyses were performed separately for participants with and without cardiovascular disease, adjust…

Prevalence of distress, comorbid conditions and well being in the general population.

Abstract Background The purposes of this paper are to determine the prevalence of distress in the community, to identify its determinants and to assess its relationship to somatic conditions and subjective well being. Methods Distress and associated factors were investigated in a random sample of 5000 participants (35–74 years) of a community-based, prospective, observational cohort study in western Mid-Germany (“Gutenberg Heart Study”) between 04/2007 and 10/2008. The sample was stratified 1:1 for gender and residence and in equal strata for decades of age. Data were assessed by self-report instruments, interviews and medical examination. Results We found a prevalence rate for depression o…

A targeted proteomics investigation of the obesity paradox in venous thromboembolism

Abstract The obesity paradox, the controversial finding that obesity promotes disease development but protects against sequelae in patients, has been observed in venous thromboembolism (VTE). The aim of this investigation was to identify a body mass–related proteomic signature in VTE patients and to evaluate whether this signature mediates the obesity paradox in VTE patients. Data from the Genotyping and Molecular Phenotyping in Venous ThromboEmbolism Project, a prospective cohort study of 693 VTE patients, were analyzed. A combined end point of recurrent VTE or all-cause death was used. Relative quantification of 444 proteins was performed using high-throughput targeted proteomics technolo…

The relevance of depressive symptoms for the outcome of patients receiving vitamin K antagonists: results from the thrombEVAL cohort study.

Abstract Aims Although depressive symptoms are highly prevalent in patients receiving oral anticoagulation (OAC), the relevance of depression for the outcome of anticoagulated individuals is unknown. Methods and results We analysed data from the multicentre cohort study thrombEVAL (NCT01809015) investigating the efficacy of OAC with vitamin K antagonists. There was an independent study monitoring, and an independent review panel assessed the endpoints. Out of n = 1558 participants, information about depressive symptoms, as measured by the two-item screener of the patient health questionnaire (PHQ-2), was available in n = 1405 individuals. The mean follow-up period was 28.04 months, with a s…

Analyzing Illumina Gene Expression Microarray Data from Different Tissues: Methodological Aspects of Data Analysis in the MetaXpress Consortium

Microarray profiling of gene expression is widely applied in molecular biology and functional genomics. Experimental and technical variations make meta-analysis of different studies challenging. In a total of 3358 samples, all from German population-based cohorts, we investigated the effect of data preprocessing and the variability due to sample processing in whole blood cell and blood monocyte gene expression data, measured on the Illumina HumanHT-12 v3 BeadChip array. Gene expression signal intensities were similar after applying the log(2) or the variance-stabilizing transformation. In all cohorts, the first principal component (PC) explained more than 95% of the total variation. Technic…

Protein expression profiling suggests relevance of noncanonical pathways in isolated pulmonary embolism

Abstract Patients with isolated pulmonary embolism (PE) have a distinct clinical profile from those with deep vein thrombosis (DVT)-associated PE, with more pulmonary conditions and atherosclerosis. These findings suggest a distinct molecular pathophysiology and the potential involvement of alternative pathways in isolated PE. To test this hypothesis, data from 532 individuals from the Genotyping and Molecular Phenotyping of Venous ThromboEmbolism Project, a multicenter prospective cohort study with extensive biobanking, were analyzed. Targeted, high-throughput proteomics, machine learning, and bioinformatic methods were applied to contrast the acute-phase plasma proteomes of isolated PE pa…

Adrenomedullin and arterial stiffness: integrative approach combining monocyte ADM expression, plasma MR-Pro-ADM, and genome-wide association study.

Background— Adrenomedullin (ADM) is a circulating vasoactive peptide involved in vascular homeostasis and endothelial function. Single nucleotide polymorphisms of the ADM gene are associated with blood pressure variability, and elevated levels of plasma midregional proadrenomedullin (MR-pro-ADM) are associated with cardiovascular diseases. Methods and Results— We investigated the sources of variability of ADM gene expression and plasma MR-pro-ADM concentrations in the general population, and their relationship with markers of atherosclerosis. MR-pro-ADM levels were assessed in 4155 individuals who underwent evaluation of carotid intima-media thickness and arterial rigidity (reflection inde…

LipiDisease: associate lipids to diseases using literature mining

Abstract Summary Lipids exhibit an essential role in cellular assembly and signaling. Dysregulation of these functions has been linked with many complications including obesity, diabetes, metabolic disorders, cancer and more. Investigating lipid profiles in such conditions can provide insights into cellular functions and possible interventions. Hence the field of lipidomics is expanding in recent years. Even though the role of individual lipids in diseases has been investigated, there is no resource to perform disease enrichment analysis considering the cumulative association of a lipid set. To address this, we have implemented the LipiDisease web server. The tool analyzes millions of recor…

CD40L controls obesity-associated vascular inflammation, oxidative stress, and endothelial dysfunction in high fat diet-treated and db/db mice

Abstract Aims CD40 ligand (CD40L) signaling controls vascular oxidative stress and related dysfunction in angiotensin-II-induced arterial hypertension by regulating vascular immune cell recruitment and platelet activation. Here we investigated the role of CD40L in experimental hyperlipidemia. Methods and results Male wild type and CD40L−/− mice (C57BL/6 background) were subjected to high fat diet for sixteen weeks. Weight, cholesterol, HDL, and LDL levels, endothelial function (isometric tension recording), oxidative stress (NADPH oxidase expression, dihydroethidium fluorescence) and inflammatory parameters (inducible nitric oxide synthase, interleukin-6 expression) were assessed. CD40L exp…

New loci associated with kidney function and chronic kidney disease

Chronic kidney disease (CKD) is a significant public health problem, and recent genetic studies have identified common CKD susceptibility variants. The CKDGen consortium performed a meta-analysis of genome-wide association data in 67,093 individuals of European ancestry from 20 predominantly population-based studies in order to identify new susceptibility loci for reduced renal function as estimated by serum creatinine (eGFRcrea), serum cystatin c (eGFRcys) and CKD (eGFRcrea 60 ml/min/1.73 m 2; n = 5,807 individuals with CKD (cases)). Follow-up of the 23 new genome-wide-significant loci (P 5 × 10 8) in 22,982 replication samples identified 13 new loci affecting renal function and CKD (in or…

Defining a reference population to determine the 99th percentile of a contemporary sensitive cardiac troponin I assay

Abstract Background Diagnosis of acute myocardial infarction (AMI) according to the universal definition is based on ischemic symptoms, imaging findings and elevated myocardial necrosis markers, preferably cardiac troponin I/T with diagnostic threshold representing the 99th percentile of a reference population. It is not clearly defined if this should be an unselected population-based or a healthy cohort with respect to cardiac diseases. Aim of the current study was to describe the distribution of troponin I using a sensitive assay and to evaluate the impact of cardiac diseases and cardiovascular risk factors in apparently healthy individuals. Methods Troponin I was determined using a conte…

Association of Birth Weight with Central and Peripheral Corneal Thickness in Adulthood-Results from the Population-Based German Gutenberg Health Study.

Low birth weight (BW) is associated with altered ocular geometry such as a steeper corneal shape in adulthood. However, it is unclear whether low birth weight affects corneal thickness development in the center or periphery in adulthood which may contribute to ocular disease. The purpose of this study was to investigate corneal thickness in former low birth weight individuals in adulthood. Methods: The German Gutenberg Health Study is a prospective, population-based study in which every participant (age range 40–80 years) was measured with Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany). BW was collected by self-reports. The relationship between birth weight and…

Prevalence of myopic maculopathy in the German population: results from the Gutenberg health study.

AimsTo determine the prevalence of myopic maculopathy in the general population in Germany and to analyse potential associations with ocular and systemic factors.DesignThe Gutenberg Health Study is a population-based study, including 15 010 participants aged 35–74 years.MethodsMyopic maculopathy was graded in phakic eyes with spherical equivalent ≤−6 D by assessing fundus photographs according to a recent international photographic classification system (META-PM). 801 eyes of 519 participants (mean age 51.0±0.77 years) met the conditions and had gradable fundus photographs. Age-specific prevalence estimates were computed. Multivariable logistic regression analysis was used to assess associa…

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively.METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin …

Risk factors for suicidal ideation in a large, registry-based sample of adult long-term childhood cancer survivors

Abstract Introduction Long-term childhood cancer survivors (CCS) are at risk for physical and psychosocial late effects. Previous research has attested to increased rates of suicidal ideation (SI) in CCS, an especially dangerous indicator of distress. However, little was known about risk factors of SI among CCS which go beyond illness- and treatment related variables. Methods A registry-based sample of 916 adult long-term CCS (Mage=34.58 years [SD=5.53], Mage at diagnosis=6.15 years [SD=4.28]) underwent medical assessments and filled out questionnaires. We conducted a linear regression analysis on SI, testing predictors of different areas: sociodemographic, social, physical health and healt…

Clinical Determinants of Thrombin Generation Measured in Presence and Absence of Platelets-Results from the Gutenberg Health Study.

AbstractThe tendency of a plasma sample to generate thrombin, a central enzyme in blood coagulation, might be an important indicator of prothrombotic risk linked to cardiovascular disease (CVD), but the presence of platelets may be a critical determinant. Clinical data, laboratory markers and thrombin generation (TG), investigated in both platelet-rich plasma (PRP) and platelet-free plasma (PFP) at 1 pM TF, were available in 407 individuals from the Gutenberg Health Study. Given the well-known effect of anticoagulants on TG, subjects taking anticoagulants (n = 15) have been excluded resulting in 392 subjects for further analysis. Lag time, endogenous thrombin potential (ETP) and peak height…

Association of Birth Weight With Foveolar Thickness in Adulthood: Results From a Population-Based Study

Purpose Low birth weight (BW) is associated with alterations of foveal shape development in childhood—leading to an increased retinal thickness of the fovea. The aim of the present study was to assess whether BW has a long-term effect on foveal retinal thickness (RT) and is still present in adulthood. Methods In the German population-based Gutenberg Health Study (GHS), participants were examined with spectral-domain optical coherence tomography. The association between self-reported BW and RT in the foveolar and perifoveal locations was assessed. Multivariable linear regression analyses with adjustment for potential confounders and grading of foveal hypoplasia were performed. Results Overal…

Depression in Atrial Fibrillation in the General Population

BACKGROUND: Initial evidence suggests that depressive symptoms are more frequent in patients with atrial fibrillation. Data from the general population are limited. METHODS AND RESULTS: In 10,000 individuals (mean age 56±11 years, 49.4% women) of the population-based Gutenberg Health Study we assessed depression by the Patient Health Questionnaire (PHQ-9) and a history of depression in relation to manifest atrial fibrillation (n = 309 cases). The median (25th/75th percentile) PHQ-9 score of depressive symptoms was 4 (2/6) in atrial fibrillation individuals versus 3 (2/6) individuals without atrial fibrillation, P(X2-Test) = 0.32. Multivariable regression analyses of the severity of depressi…

Similarities and Differences of Mental Health in Women and Men: A Systematic Review of Findings in Three Large German Cohorts

In Germany, large, population-based cohort studies have been implemented in order to identify risk and protective factors for maintaining health across the life span. The purpose of this systematic review is to analyse findings from three large ongoing cohorts and to identify sex-specific prevalence rates, risk and protective factors for mental health. Published studies from the Cooperative Health Research in the Region Augsburg (KORA), the Study of Health in Pomerania (SHIP) and the Gutenberg Health Study (GHS)), representing the southern, north-eastern and middle parts of Germany, were identified through searches of the databases PubMed and Web of Science. A total of 52 articles was ident…

Distribution, genetic and cardiovascular determinants of FVIII:c - Data from the population-based Gutenberg Health Study

Background: Elevated levels of FVIII:c are associated with risk for both venous and arterial thromboembolism. However, no population-based study on the sex-specific distribution and reference ranges of plasma FVIII: c and its cardiovascular determinants is available. Methods: FVIII:c was analyzed in a randomly selected sample of 2533 males and 2440 females from the Gutenberg Health Study in Germany. Multivariable regression analyses for FVIII:c were performed under adjustment for genetic determinants, cardiovascular risk factors and cardiovascular disease. Results and conclusions: Females (126.6% (95% CI: 125.2/128)) showed higher FVIII:c levels than males (121.2% (119.8/122.7)). FVIII:c le…

Codierung der Tätigkeitsangaben im Basiskollektiv der Gutenberg-Gesundheitsstudie unter Anwendung der Klassifikation der Berufe KldB 2010 — Darstellung des Vorgehens und der Datenqualität

In der Basiserhebung der Gutenberg- Gesundheitsstudie Mainz wurden die Berufsbiografien von 15.010 Probanden erfasst. Um die Textangaben aus 67.389 einzelnen Tatigkeitsphasen fur epidemiologische Auswertungen nutzen zu konnen, wurde eine Codierung nach der deutschen Klassifikation der Berufe KldB 2010 durchgefuhrt. Ziel des Artikels ist, das methodische Vorgehen und die Qualitat der angewandten Berufscodierung darzustellen.

Effects of noise on vascular function, oxidative stress, and inflammation: mechanistic insight from studies in mice

Aims Epidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon. Methods and results We developed a novel animal model to study the vascular consequences of aircraft noise exposure. Peak sound levels of 85 and mean sound level of 72 dBA applied by loudspeakers for 4 days caused an increase in systolic blood pressure, plasma noradrenaline and angiotensin II lev…

Distinctiveness and overlap of depersonalization with anxiety and depression in a community sample: results from the Gutenberg Heart Study.

Depersonalization disorder is considered to be a common clinical phenomenon and disorder with an enormous gap between prevalence and detection partly due to the common interpretation of depersonalization (DP) being a negligible variant of anxiety and depression. Therefore, we sought to analyze (1) the prevalence rate of DP in a large community sample (n=5000) according to a recently developed ultra brief two-item depersonalization screener; (2) the associations with depression, anxiety, physical and mental health status; and 93) whether DP contributes independently to the health status beyond anxiety and depression. The prevalence of clinically significant DP was 0.8% (n=41), and 8.5% (n=42…

Peripheral corneal thickness and associated factors - results from the population-based German Gutenberg Health Study.

PURPOSE Changes in peripheral corneal thickness are described in various corneal diseases such as corneal ectasia. However, few data exist describing the increase in corneal thickness from central to peripheral and reporting the normal distribution of corneal thickness in rings around the corneal centre. The aim of this study was to report these cornea characteristics and investigate associated factors in a population-based setting. METHODS The Gutenberg Health Study is a prospective, population-based study examining participants in a 5-year follow-up (age range 40-80 years) using Scheimpflug imaging. Corneal thickness was assessed in each participant at the apex, as well as in the corneal …

Recalled parental rearing behavior in adult women and men with depressive and anxiety symptoms: Findings from a community study.

Objectives: Addressing the lack of population-based data, the purpose of this representative study was to assess sex- and age-specific associations of maternal and paternal rearing behavior with depressiveness and anxiety controlling for sociodemographic and somatic variables. Methods: 8,175 subjects participating in a population-based study completed standardized questionnaires measuring Recalled Parental Rearing Behavior and distress. Results: Women recalled their fathers as more controlling and warmer, and their mothers as more rejecting than men. Comparisons between age groups (≤ 60 vs. > 60 years) revealed that younger participants recalled more parental control and emotional warmth. I…

Prevalence of pterygium and identification of associated factors in a German population - results from the Gutenberg Health Study.

Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population‐Based Gutenberg Health Study

Background Preclinical data have indicated a link between use of vitamin K antagonists ( VKA ) and detrimental effects on vascular structure and function. The objective of the present study was to determine the relationship between VKA intake and different phenotypes of subclinical cardiovascular disease in the population. Methods and Results Clinical and laboratory data, as well as medical–technical examinations were assessed from 15 010 individuals aged 35 to 74 years during a highly standardized 5‐hour visit at the study center of the population‐based Gutenberg Health Study. In total, the study sample comprised 287 VKA users and 14 564 VKA nonusers. Multivariable analysis revealed an in…

Mortality risk among 5‐year survivors of childhood cancer in Germany—Results from the CVSS study (Cardiac and Vascular late Sequelae in long‐term Survivors of childhood cancer study)

The growing population of long-term childhood cancer survivors is at increased risk for severe, therapy-related late effects and premature mortality. The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS) study is a cohort of patients from Germany diagnosed with a neoplasia prior to 15 years of age in the time period 1980 to 1990. Late mortality was evaluated in a total of 4505 individuals who survived 5 years or more after the initial diagnosis (5-year survivors). Survivors with a second primary tumor were excluded. Standardized mortality ratios (SMRs) were calculated. By December 2014, 400 patients had died. Available cause of death information from 188 i…

Variation of platelet function in clinical phenotypes of acute venous thromboembolism – Results from the GMP‐VTE project

Background The role of platelets in the pathogenesis of venous thromboembolism (VTE) is receiving increasing attention; however, limited information is available on platelet function in the acute phase of the disease. Objective To characterize platelet function according to VTE phenotypes. Patients/Methods In total, 154 subjects (isolated pulmonary embolism [iPE], n = 28; isolated deep vein thrombosis [iDVT], n = 35; DVT+PE, n = 91) were included. In this study platelet function analyzer (PFA)-200, light transmission aggregometry (LTA), thrombin generation (TG) in presence (PRP) and absence (PFP) of platelets and platelet flow cytometry were investigated. LASSO regression was used to select…