Showing papers by "Marcus Dörr published in 2016"
Wellcome Trust Sanger Institute1, University of Michigan2, University of Oxford3, University of Geneva4, University of Exeter5, Greifswald University Hospital6, National Research Council7, University of Bristol8, University of Colorado Boulder9, Fred Hutchinson Cancer Research Center10, University of Washington11, SUNY Downstate Medical Center12, Erasmus University Rotterdam13, University of Trieste14, VU University Amsterdam15, South London and Maudsley NHS Foundation Trust16, King's College London17, University of Edinburgh18, Harvard University19, National Institutes of Health20, Harokopio University21, Innsbruck Medical University22, Broad Institute23, Lund University24, University of Helsinki25, Norwegian University of Science and Technology26, University of Cambridge27, University of Minnesota28, Technische Universität München29, University of North Carolina at Chapel Hill30, University of Toronto31, McGill University32, Leiden University33, University of Pennsylvania34, University of Groningen35, Utrecht University36, Churchill Hospital37
TL;DR: A reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies.
Abstract: We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
2,149 citations
01 Jan 2016
TL;DR: In this article, a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry is presented.
Abstract: We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently.
1,261 citations
Boston University1, Washington University in St. Louis2, University of Michigan3, University of Washington4, University of North Carolina at Chapel Hill5, University of Texas Health Science Center at Houston6, Icahn School of Medicine at Mount Sinai7, University of Greifswald8, Los Angeles Biomedical Research Institute9, Columbia University Medical Center10, George Washington University11, University of Cambridge12, University College London13, University of Bristol14, University of Liverpool15, University of Leicester16, University of Wisconsin–Milwaukee17, Brigham and Women's Hospital18, Vanderbilt University Medical Center19, Wake Forest University20, Erasmus University Rotterdam21, University of Mississippi Medical Center22, Bill & Melinda Gates Foundation23, University of Iceland24, Harvard University25, Broad Institute26, Glenfield Hospital27, Technische Universität München28, King Abdulaziz University29, Queen Mary University of London30, European Academy of Bozen31, University of Regensburg32, National Institutes of Health33, Pennington Biomedical Research Center34, Cedars-Sinai Medical Center35, Northwestern University36, Johns Hopkins University School of Medicine37, Greifswald University Hospital38, National Yang-Ming University39, Chung Shan Medical University40, Wake Forest Baptist Medical Center41, Geneva College42
TL;DR: This large collection of blood pressure–associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
Abstract: Meta-analyses of association results for blood pressure using exome-centric single-variant and gene-based tests identified 31 new loci in a discovery stage among 146,562 individuals, with follow-up and meta-analysis in 180,726 additional individuals (total n = 327,288). These blood pressure-associated loci are enriched for known variants for cardiometabolic traits. Associations were also observed for the aggregation of rare and low-frequency missense variants in three genes, NPR1, DBH, and PTPMT1. In addition, blood pressure associations at 39 previously reported loci were confirmed. The identified variants implicate biological pathways related to cardiometabolic traits, vascular function, and development. Several new variants are inferred to have roles in transcription or as hubs in protein-protein interaction networks. Genetic risk scores constructed from the identified variants were strongly associated with coronary disease and myocardial infarction. This large collection of blood pressure-associated loci suggests new therapeutic strategies for hypertension, emphasizing a link with cardiometabolic risk.
218 citations
TL;DR: Trends of HF‐related hospitalizations, hospital days and in‐hospital deaths during a 14‐year period (2000–2013) in Germany are analyzed.
Abstract: Aims
Considerable differences in the long-term trends of heart failure (HF) exist between different countries. To extend the existing knowledge on HF epidemiology in Germany, we analysed trends of HF-related hospitalizations, hospital days and in-hospital deaths during a 14-year period (2000–2013).
Methods and results
Data were derived from the official German Federal Health Monitoring System, which includes an annual and complete enumeration of inpatients at the time of discharge from the hospital. HF cases were identified by the primary diagnosis code for HF (I50). From 2000 to 2013, the absolute number of HF-related hospitalizations increased by 65.4% (239 694–396 380 cases) and by 28.4% after age-standardization (261–335 per 100 000 population). Accordingly, the absolute number of HF-related hospital days increased by 22.1% (3.4–4.2 million hospital days), despite a marked decrease by 25.9% in average length of stay (14.3–10.6 days). With approximately 35 000 in-hospital deaths (∼45 per 100 000 population), the annual number of HF-related in-hospital deaths remained consistently high, and in-hospital mortality rate in HF patients constituted 9.3% in 2013. Patients aged >65 years were disproportionately affected. In 2013, HF was the leading cause of disease-related hospitalizations and in-hospital deaths, representing 2.1% and 8.8% of all cases, respectively.
Conclusion
In Germany, the burden of HF is growing further, and the risk of death in HF remains high. These trends can only be partly attributed to demographic developments suggesting an exigent need for increased awareness and enhanced efforts in the prevention and management of HF.
111 citations
TL;DR: A genome-wide association meta-analysis of 4 QRS traits in up to 73,518 individuals of European ancestry provides new insights into genes and biological pathways controlling myocardial mass and may help identify novel therapeutic targets.
109 citations
Utrecht University1, Uppsala University2, University of Bordeaux3, Greifswald University Hospital4, Erasmus University Medical Center5, University College London6, Radboud University Nijmegen7, Karolinska University Hospital8, university of lille9, Leiden University Medical Center10, Karolinska Institutet11, Wellcome Trust Centre for Human Genetics12, University of Texas Health Science Center at Houston13, University of North Carolina at Chapel Hill14, University of Washington15, United States Department of Veterans Affairs16, University of Bristol17, National Institute for Health Research18, Ludwig Maximilian University of Munich19, University of Virginia20, University of Lübeck21, Technische Universität München22, University of Oxford23, University Hospital of North Norway24, University of Tromsø25, University of Essex26, University Medical Center Groningen27, University of Pennsylvania28, University of Glasgow29, Stanford University30
TL;DR: Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD, and therapeutics targeted at lowering circulating cyStatin C are unlikely to be effective in preventing CVD.
99 citations
University of Cambridge1, Oslo University Hospital2, University of Gothenburg3, Technische Universität München4, University of Milan5, National Taiwan University6, Paris Descartes University7, Erasmus University Rotterdam8, Paracelsus Private Medical University of Salzburg9, University of Tromsø10, Uppsala University11, Odense University Hospital12, Aristotle University of Thessaloniki13, University of Edinburgh14, University of Miami15, University of Washington16, University of Greifswald17, Tufts University18, Harvard University19, Greifswald University Hospital20, University of Eastern Finland21, EHESP22
TL;DR: Inflammation was independently associated with CCA-IMT cross-sectionally and the findings for ‘inflammatory load’ suggest important combined effects of the three inflammatory markers on early atherosclerosis.
Abstract: BackgroundLarge-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudina...
83 citations
Erasmus University Medical Center1, University of Washington2, Boston University3, University of Iceland4, University of Texas Health Science Center at Houston5, Leiden University6, Brigham and Women's Hospital7, University of Auckland8, Greifswald University Hospital9, University College Cork10, Wake Forest University11, Harvard University12, University of Minnesota13, Merck & Co.14, University of North Carolina at Chapel Hill15, Robertson Centre for Biostatistics16, National Institutes of Health17, Erasmus University Rotterdam18, Fred Hutchinson Cancer Research Center19, Pasteur Institute of Lille20, University of Strasbourg21, Group Health Research Institute22, University of Toulouse23, United States Department of Veterans Affairs24, Novartis25, New York Academy of Medicine26, Umeå University27, University of California, Los Angeles28, Queen's University Belfast29, University of Jyväskylä30, University of Helsinki31, University of Glasgow32, Leiden University Medical Center33, University of Hamburg34, Baylor College of Medicine35
TL;DR: The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.
Abstract: Background Data are limited on genome-wide association studies (GWAS) for incident coronary heart disease (CHD). Moreover, it is not known whether genetic variants identified to date also associate with risk of CHD in a prospective setting. Methods We performed a two-stage GWAS analysis of incident myocardial infarction (MI) and CHD in a total of 64,297 individuals (including 3898 MI cases, 5465 CHD cases). SNPs that passed an arbitrary threshold of 5x10(-6) in Stage I were taken to Stage II for further discovery. Furthermore, in an analysis of prognosis, we studied whether known SNPs from former GWAS were associated with total mortality in individuals who experienced MI during follow-up. Results In Stage I 15 loci passed the threshold of 5x10(-6); 8 loci for MI and 8 loci for CHD, for which one locus overlapped and none were reported in previous GWAS meta-analyses. We took 60 SNPs representing these 15 loci to Stage II of discovery. Four SNPs near QKI showed nominally significant association with MI (p-value<8.8x10(-3)) and three exceeded the genome-wide significance threshold when Stage I and Stage II results were combined (top SNP rs6941513: p = 6.2x10(-9)). Despite excellent power, the 9p21 locus SNP (rs1333049) was only modestly associated with MI (HR = 1.09, p-value = 0.02) and marginally with CHD (HR = 1.06, p-value = 0.08). Among an inception cohort of those who experienced MI during follow-up, the risk allele of rs1333049 was associated with a decreased risk of subsequent mortality (HR = 0.90, p-value = 3.2x10(-3)). Conclusions QKI represents a novel locus that may serve as a predictor of incident CHD in prospective studies. The association of the 9p21 locus both with increased risk of first myocardial infarction and longer survival after MI highlights the importance of study design in investigating genetic determinants of complex disorders.
70 citations
Erasmus University Medical Center1, Erasmus University Rotterdam2, University of Bern3, Leiden University Medical Center4, University Hospital of Lausanne5, University of Cambridge6, University of Glasgow7, University of Groningen8, Robertson Centre for Biostatistics9, University of Western Australia10, University of Pittsburgh11, Faculdade de Medicina de Marília12, Federal University of São Paulo13, University of Washington14, Group Health Research Institute15, National Institutes of Health16, University of Copenhagen17, University of Parma18, Radiation Effects Research Foundation19, Harvard University20, University of Birmingham21, University of California, San Francisco22, Sir Charles Gairdner Hospital23, National Health Service24, University of Pennsylvania25
TL;DR: Higher levels of TSH within the reference range may decrease the risk of stroke, highlighting the need for further research focusing on the clinical consequences associated with differences within thereference range of thyroid function.
Abstract: Context: The currently applied reference ranges for thyroid function are under debate. Despite evidence that thyroid function within the reference range is related with several cardiovascular disorders, its association with the risk of stroke has not been evaluated previously. Design and Setting: We identified studies through a systematic literature search and the Thyroid Studies Collaboration, a collaboration of prospective cohort studies. Studies measuring baseline TSH, free T4, and stroke outcomes were included, and we collected individual participant data from each study, including thyroid function measurements and incident all stroke (combined fatal and nonfatal) and fatal stroke. The applied reference range for TSH levels was between 0.45 and 4.49 mIU/L. Results: We collected individual participant data on 43 598 adults with TSH within the reference range from 17 cohorts, with a median follow-up of 11.6 years (interquartile range 5.1–13.9), including 449 908 person-years. Age- and sex-adjusted poole...
57 citations
National Institutes of Health1, Icahn School of Medicine at Mount Sinai2, Université de Montréal3, Vanderbilt University4, University of Washington5, University of Edinburgh6, University of Greifswald7, Stanford University8, University of Virginia9, University of Tartu10, Brigham and Women's Hospital11, University of Minnesota12, Erasmus University Medical Center13, University of Texas Health Science Center at Houston14, University of Iceland15, Stony Brook University16, GlaxoSmithKline17, Imperial College London18, University of Ioannina19, Johns Hopkins University School of Medicine20, Greifswald University Hospital21, University of North Carolina at Chapel Hill22, Wake Forest University23, University of Tampere24, Uppsala University25, Harvard University26, Broad Institute27, Erasmus University Rotterdam28, Baylor College of Medicine29, Morehouse School of Medicine30, University of California, Los Angeles31, Group Health Cooperative32, University of Auckland33, University of Michigan34, University of Mississippi Medical Center35, University of Vermont36, Fred Hutchinson Cancer Research Center37, University of Wisconsin–Milwaukee38
TL;DR: An exome array-based meta-analysis of total WBC and subtype counts in a multi-ancestry discovery and replication sample of ∼157,622 individuals suggests a prominent shared genetic architecture with inflammatory and autoimmune diseases.
Abstract: White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of ∼157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3′ UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.
54 citations
Broad Institute1, University of Michigan2, Wake Forest University3, University of North Carolina at Chapel Hill4, University of California, Los Angeles5, National Institutes of Health6, Maastricht University7, Erasmus University Rotterdam8, Leiden University9, University of Queensland10, University of Edinburgh11, Washington University in St. Louis12, Kanazawa University13, Utrecht University14, University of Iceland15, Johns Hopkins University16, University of Maryland, Baltimore17, Icahn School of Medicine at Mount Sinai18, Regeneron19, Boston University20, Cedars-Sinai Medical Center21, University of Washington22, Harvard University23, Veterans Health Administration24, University of Pittsburgh25, Merck & Co.26, University of Groningen27, University of Minnesota28, University of Turku29, Mayo Clinic30, Greifswald University Hospital31, University of Vermont32, Group Health Cooperative33, University of Texas Health Science Center at Houston34, Imperial College London35, University of Pennsylvania36, University of Mississippi37, University of Greifswald38
TL;DR: APOE &egr;2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities, as well as clinical coronary heart disease, and exome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical Atherosclerosis.
Abstract: Background —The burden of subclinical atherosclerosis in asymptomatic individuals is heritable and associated with elevated risk of developing clinical coronary heart disease (CHD). We sought to identify genetic variants in protein-coding regions associated with subclinical atherosclerosis and the risk of subsequent CHD.
Methods and Results —We studied a total of 25,109 European ancestry and African-American participants with coronary artery calcification (CAC) measured by cardiac computed tomography and 52,869 with common carotid intima media thickness (CIMT) measured by ultrasonography within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Participants were genotyped for 247,870 DNA sequence variants (231,539 in exons) across the genome. A meta-analysis of exome-wide association studies was performed across cohorts for CAC and CIMT. APOB p.Arg3527Gln was associated with four-fold excess CAC ( P = 3×10 -10 ). The APOE e2 allele (p.Arg176Cys) was associated with both 22.3% reduced CAC ( P = 1×10 -12 ) and 1.4% reduced CIMT ( P = 4×10 -14 ) in carriers compared with non-carriers. In secondary analyses conditioning on LDL cholesterol concentration, the e2 protective association with CAC, although attenuated, remained strongly significant. Additionally, the presence of e2 was associated with reduced risk for CHD (OR 0.77; P = 1×10 -11 ). Conclusions —Exome-wide association meta-analysis demonstrates that protein-coding variants in APOB and APOE associate with subclinical atherosclerosis. APOE e2 represents the first significant association for multiple subclinical atherosclerosis traits across multiple ethnicities as well as clinical CHD.
TL;DR: It is indicated that moderately elevated serum liver enzymes, but not sonographic liver hyperechogenicity, were associated with increased AF prevalence in the general adult population.
TL;DR: New data add evidence for lower BP in Germany, and future research based on population-based data should place a special focus on blood pressure data in young men.
Abstract: Background: Hypertension is a key risk factor. However, population data based on blood pressure measurements in Germany are scarce. Methods: Standardized blood pressure (BP) measurements and medication data from seven population-based studies conducted in Germany between 1994 and 2012 (66 845 participants, 25-74 years) were analyzed: the EPIC-Potsdam study (1994-1998, EPIC), the KORA-S4 Study (1999-2001) in Augsburg, and the Gutenberg Health Study (2007-2012, GHS) in Mainz/Mainz-Bingen provided data for descriptive comparisons. Time trends were analyzed based on identical study regions for the German National Health Interview and Examination Survey 1998 (BGS98) and the German Health Examination Survey for Adults (2008-11, DEGS1) as well as the Study of Health in Pomerania (SHIP) in Northeast Germany (1997-2001) and the SHIP-TREND study (2008-2012). BP data were adjusted for study-specific measurement devices based on calibration studies. Results: After adjustment for study-specific measurement devices, mean systolic and diastolic BP values were lower and treatment proportions higher in recent (2007-2012) compared to older (1994-2001) studies. Mean BP decrease was most pronounced (systolic >= 10 mmHg) in the elderly (55-74 years). The regional SHIP-TREND data for Northeast Germany showed a decrease in mean systolic BP in young men aged 25 to 34 years;on a national level according to the DEGS1 data, however, no such decrease was observed for this group. Conclusion: New data add evidence for lower BP in Germany. However, the prevention potential remains high. Future research based on population-based data should place a special focus on blood pressure data in young men.
TL;DR: In this article, the authors investigated a broad range of clinical correlates of sex hormones in women from a large population-based sample and found associations between clinical correlates including waist circumference, smoking, cohabitation, systolic blood pressure, cholesterol, and metabolic syndrome with sex hormones.
Abstract: Background Despite associations of sex hormones in women with increased cardiometabolic risk and mortality, the clinical correlates of altered sex hormone concentrations in women are less clearly understood. We investigated a broad range of clinical correlates of sex hormones in women from a large population-based sample. Methods Data from 2560 women from two cohorts of the Study of Health in Pomerania were used. Stepwise multivariable regression models were implemented to investigate a broad range of behavioral, socio-demographic, and cardiometabolic clinical correlates related to total testosterone (TT), free testosterone (fT), androstenedione (ASD), dehydroepiandrosterone-sulfate (DHEAS), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG). Results Waist circumference and BMI (β-coefficient: − 0.03; 95% CI: − 0.04; 0.03) were inversely related to SHBG, and BMI was positively related to TT (β-coefficient: 0.005; 95% CI: 0.001; 0.009), fT, E1, and E2. Smoking was positively related to TT (β-coefficient: 0.04; 95% CI: 0.01; 0.06), ASD, and fT. Systolic blood pressure (TT: β-coefficient: 0.002; 95% CI: 0.001; 0.003), hypertension (TT: β-coefficient: 0.05; 95% CI: 0.003; 0.11), low-density lipoprotein (LDL) cholesterol (TT: β-coefficient: 0.02; 95% CI: 0.01; 0.05), and total cholesterol (TT: β-coefficient: − 0.03; 95% CI: 0.01; 0.05) were positively related to TT and ASD. Finally, type 2 diabetes mellitus (T2DM), and metabolic syndrome (MetS) were positively related to fT, but inversely related to SHBG. Conclusions Our population-based study, with sex hormone concentrations measured by liquid chromatography tandem mass spectrometry, revealed associations between clinical correlates including waist circumference, smoking, cohabitation, systolic blood pressure, cholesterol, and MetS with sex hormones. Thus, sex hormones and SHBG may play a role in the cardiovascular risk profile of women.
TL;DR: High TSH serum levels were positively associated with current anthropometric markers, even in the study-specific reference ranges, as well as in the full range of serum TSH.
Abstract: Background: Except from associations study with body weight, there are few longitudinal data regarding the association between thyroid function and anthropometric measurements such as waist circumference, waist-to-hip ratio, or waist-to height ratio. Objective: This study aimed to investigate the association of thyrotropin (TSH) at baseline with changes in different anthropometric markers between baseline and follow-up in the general population. Method: Data were used from four population-based longitudinal cohort studies and one population-based cross-sectional study. A total of 16,902 (8204 males) subjects aged 20–95 years from the general population were studied. Body mass index, waist circumference, waist-to-hip ratio, and waist-to-height ratio were measured. Multivariable median regression models were calculated adjusting for the following covariates: age, sex, baseline value of the respective anthropometric marker, smoking status, follow-up-time period, and study site. Results: In cross-sectional an...
TL;DR: Improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression.
Abstract: Immunoadsorption with subsequent immunoglobulin substitution (IA/IgG) represents a therapeutic approach for patients with dilated cardiomyopathy (DCM). Here, we studied which molecular cardiac alterations are initiated after this treatment. Transcription profiling of endomyocardial biopsies with Affymetrix whole genome arrays was performed on 33 paired samples of DCM patients collected before and 6 months after IA/IgG. Therapy-related effects on myocardial protein levels were analysed by label-free proteome profiling for a subset of 23 DCM patients. Data were analysed regarding therapy-associated differences in gene expression and protein levels by comparing responders (defined by improvement of left ventricular ejection fraction ≥20 % relative and ≥5 % absolute) and non-responders. Responders to IA/IgG showed a decrease in serum N-terminal proBNP levels in comparison with baseline which was accompanied by a decreased expression of heart failure markers, such as angiotensin converting enzyme 2 or periostin. However, despite clinical improvement even in responders, IA/IgG did not trigger general inversion of DCM-associated molecular alterations in myocardial tissue. Transcriptome profiling revealed reduced gene expression for connective tissue growth factor, fibronectin, and collagen type I in responders. In contrast, in non-responders after IA/IgG, fibrosis-associated genes and proteins showed elevated levels, whereas values were reduced or maintained in responders. Thus, improvement of LV function after IA/IgG seems to be related to a reduced gene expression of heart failure markers and pro-fibrotic molecules as well as reduced fibrosis progression.
TL;DR: The present cross-sectional, population-based study observed sex-specific associations of androgens, E2, and SHBG with sleep apnea and daytime sleepiness, and multivariable-adjusted analyses confirmed the impact of body composition and health-related lifestyle on the association between sex hormones and sleep.
Abstract: Context and Objectives: Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry. Design, Setting, and Participants: We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND. Main Outcome and Measures: Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea-hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models. Results: In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46–0.83), free T, and SHBG with AHI were rendered nonsign...
TL;DR: Some BSA-adjusted median aortic diameters are smaller in men than in women and all diameters increase with age, diastolic blood pressure and HDL-C and decrease as systolic BP increases.
Abstract: Objectives
To generate reference values for thoracic and abdominal aortic diameters determined by magnetic resonance imaging (MRI) and analyse their association with cardiovascular risk factors in the general population.
TL;DR: Despite several sex-specific associations of androgens and SHBG with subclinical CVD, the present representative study for the age group ≥45 years among men and women from the general population detected no consistent associations in longitudinal analyses.
TL;DR: The data suggest that especially younger (presumably pre-menopausal) females with MDD are more likely to have MetS than those without major depressive disorders, and that age extenuates this association.
Abstract: Background and aims: Major depressive disorder (MDD) has been associated with the Metabolic Syndrome (MetS). As previous data strongly suggested sex and age effects on this association, this study aimed to analyse the association between MDD and MetS in two general population samples under explicit consideration of sex and age.Methods: This study analysed cross-sectional data based on two independent general population samples: SHIP-0 (n = 4083; 20–81 years; 49.4% male) and SHIP-TREND-0 (n = 3957; 20–83 years; 49.0% male) that were part of the Study of Health in Pomerania. MDD (SHIP-0: 12.6%; SHIP-TREND-0: 27.2%) was assessed using the Composite International Diagnostic-Screener (CID-S) in both samples. Interview assessment of MDD diagnosis according to Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria was performed in SHIP-TREND-0 (18.1% MDD). MetS was defined by abdominal obesity, elevated blood pressure, elevated glucose, elevated triglycerides and reduced high-density ...
TL;DR: Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys).
Abstract: Background
An intact angiopoietin/Tie-2 ligand receptor system is indispensable for life. High circulating angiopoietin-2 (Ang-2) concentrations are strongly associated with kidney disease involving the progressive loss of glomerular filtration. The aim of our study was to investigate the associations between renal function and serum Ang-2 or serum Tie-2 concentrations in the general population.
Methods
Data of 3081 and 4088 subjects from two population-based studies, the Study of Health in Pomerania (SHIP-1) and SHIP-Trend, were used. Renal function was assessed by serum creatinine, cystatin C concentration, creatinine-based estimated glomerular filtration rate [eGFR(crea)], cystatin C-based eGFR [eGFR(cys)] and urinary albumin-to-creatinine ratio (uACR). Analyses of variance and linear regression models were calculated.
Results
In both cohorts, strong positive associations between serum cystatin C concentrations and serum Ang-2 or Tie-2 concentrations as well as inverse associations between eGFR(cys) and serum Ang-2 or Tie-2 concentrations were found. These relations were also present in a subpopulation without hypertension or diabetes mellitus type 2. Furthermore, we detected weak U-shaped associations between serum creatinine concentrations or eGFR(crea) and serum Ang-2 concentrations. With respect to uACR a strong positive association with serum Ang-2 concentrations was revealed.
Conclusion
Serum Ang-2 concentrations are strongly associated with sensitive parameters of renal impairment like serum cystatin C, uACR and eGFR(cys). These findings persisted even after exclusion of subjects with hypertension or diabetes mellitus type 2, conditions that predispose to chronic renal disease and are associated with increased Ang-2 concentrations. Interestingly, we did not detect the same strong relations between serum creatinine and eGFR(crea) with serum Ang-2 concentration. Additionally, significant association of serum Tie-2 concentrations with cystatin C and eGFR(cys) were detected.
National Institutes of Health1, Boston University2, Ludwig Maximilian University of Munich3, University of Iceland4, Johns Hopkins University5, Cleveland Clinic6, University of Washington7, Wake Forest University8, Heidelberg University9, Harvard University10, University of Groningen11, Leiden University12, Erasmus University Rotterdam13, University of Greifswald14, Broad Institute15, Technische Universität München16, University of Minnesota17, University of California, Los Angeles18, Group Health Cooperative19, University of Colorado Denver20, University of Glasgow21, Greifswald University Hospital22, Emory University23, Synlab Group24, Medical University of Graz25
TL;DR: A large-scale association analysis of gene-gene interactions with AF performed in 8,173 AF cases and 65,237 AF-free referents collected from 15 studies for discovery did not find significant interactions that were associated with AF susceptibility.
Abstract: Atrial fibrillation (AF) is a heritable disease that affects more than thirty million individuals worldwide. Extensive efforts have been devoted to the study of genetic determinants of AF. The objective of our study is to examine the effect of gene-gene interaction on AF susceptibility. We performed a large-scale association analysis of gene-gene interactions with AF in 8,173 AF cases, and 65,237 AF-free referents collected from 15 studies for discovery. We examined putative interactions between genome-wide SNPs and 17 known AF-related SNPs. The top interactions were then tested for association in an independent cohort for replication, which included more than 2,363 AF cases and 114,746 AF-free referents. One interaction, between rs7164883 at the HCN4 locus and rs4980345 at the SLC28A1 locus, was found to be significantly associated with AF in the discovery cohorts (interaction OR = 1.44, 95% CI: 1.27–1.65, P = 4.3 × 10–8). Eight additional gene-gene interactions were also marginally significant (P < 5 × 10–7). However, none of the top interactions were replicated. In summary, we did not find significant interactions that were associated with AF susceptibility. Future increases in sample size and denser genotyping might facilitate the identification of gene-gene interactions associated with AF.
TL;DR: Reduced bone stiffness was associated with clinical attachment and tooth loss in women but not in men, and the OFR showed a significant association with mean CAL for both pre- and postmenopausal women.
Abstract: The authors evaluated the association of reduced bone stiffness of the calcaneus with clinical attachment loss (CAL) and tooth loss. The authors analyzed data from 4,678 subjects (2,384 women), aged 20 to 88 y, from the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) and the baseline examination of the SHIP-Trend cohort. Bone stiffness, characterized by the stiffness index (SI) and the osteoporotic fracture risk (OFR), was assessed by quantitative ultrasound of the heel. SI and OFR were significantly associated with the mean CAL in women. While 1) the SI showed a significant association with the mean CAL and 2) the OFR with the median number of teeth in just the postmenopausal women, the OFR showed a significant association with mean CAL for both pre- and postmenopausal women. In postmenopausal women, a 10-unit increase in the SI was associated with a decrease in the mean CAL of 0.05 mm (95% confidence interval [CI]: -0.10 to 0.00; P = 0.046). Moreover, the adjusted median number of teeth was 21.4 (95% CI: 20.9 to 21.9) among the postmenopausal women with a low OFR, while it was 19.1 (95% CI: 17.8 to 20.3; P = 0.001) among the postmenopausal women with a high OFR. For the premenopausal women with a low OFR, the mean CAL was 1.60 mm (95% CI: 1.53 to 1.66), while for the premenopausal women with a high OFR, it was 2.24 mm (95% CI: 1.78 to 2.69; P = 0.006). Reduced bone stiffness was associated with clinical attachment and tooth loss in women but not in men.
TL;DR: It is demonstrated that AWT values increase with increasing serum TSH concentrations, indicating that a hypothyroid state may be indicative for aortic atherosclerosis, and these results fit very well to the findings of previous studies pointing towards increased atherosclerotic risk in the hypothy thyroid state.
Abstract: Our aim was to investigate the association of thyroid function defined by serum concentrations of thyroid-stimulating hormone (TSH) with thoracic aortic wall thickness (AWT) as a marker of atherosclerotic processes. We pooled data of 2,679 individuals from two independent population-based surveys of the Study of Health in Pomerania. Aortic diameter and AWT measurements were performed on a 1.5-T MRI scanner at the concentration of the right pulmonary artery displaying the ascending and the descending aorta. TSH, treated as continuous variable, was significantly associated with descending AWT (β = 0.11; 95 % confidence interval (CI) 0.02–0.21), while the association with ascending AWT was not statistically significant (β = 0.20; 95 % CI −0.01–0.21). High TSH (>3.29 mIU/L) was significantly associated with ascending (β = 0.12; 95 % CI 0.02–0.23) but not with descending AWT (β = 0.06; 95 % CI −0.04–0.16). There was no consistent association between TSH and aortic diameters. Our study demonstrated that AWT values increase with increasing serum TSH concentrations. Thus, a hypothyroid state may be indicative for aortic atherosclerosis. These results fit very well to the findings of previous studies pointing towards increased atherosclerotic risk in the hypothyroid state. • Serum TSH concentrations are positively associated with aortic wall thickness.
• Serum TSH concentrations are not associated with the aortic diameters.
• Serum 3,5-diiodothyronine concentrations may be positively associated with aortic wall thickness.
TL;DR: SCORE-estimates using 5- or 10-year-old total cholesterol had a high sensitivity, specificity and test accuracy to identify subjects at high cardiovascular disease risk and resulted in low misclassification rates.
Abstract: BackgroundMeasurement of total cholesterol is part of cardiovascular disease risk assessment in primary prevention. Frequently, old total cholesterol values are available. We assessed whether previ...
TL;DR: Since angiopoietin‐2 levels strongly correlate with cardiovascular mortality and subclinical cardiovascular disease, it was hypothesized that levels of Ang‐2 and its soluble receptor (sTie‐2) were associated with the metabolic syndrome and individual MetS components.
Abstract: Objective: Since angiopoietin-2 (Ang-2) levels strongly correlate with cardiovascular mortality and subclinical cardiovascular disease, it was hypothesized that levels of Ang-2 and its soluble receptor (sTie-2) were associated with the metabolic syndrome (MetS) and individual MetS components. Methods: Within the population-based Study of Health in Pomerania, two sets of analyses were performed. First, Ang-2 and sTie-2 were related to the prevalence of MetS and its components cross-sectionally (n=3,205). Second, the association between baseline Ang-2 and sTie-2 and incident MetS or longitudinal changes in its components in 1,295 individuals was investigated. Results: High Ang-2 levels (90th percentile), compared with low Ang-2 levels (10th percentile), were positively associated with MetS (OR: 1.78) and with the following MetS criteria: increased triglycerides, lower HDL cholesterol, and higher non-fasting glucose. Furthermore, high sTie-2 levels (90th percentile), compared with low levels (10th percentile), were positively related to MetS (OR: 1.58) and most of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or longitudinal change in components of MetS. Conclusions: Ang-2 and sTie-2 levels were cross-sectionally associated with MetS and several of its components. However, Ang-2 and sTie-2 levels were not associated with incident MetS or changes in individual MetS components during follow-up.
13 May 2016
TL;DR: In this paper, the authors examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry, and found associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples.
Abstract: Context and Objectives: Associations between sex hormones and sleep habits originate mainly from small and selected patient-based samples. We examined data from a population-based sample with various sleep characteristics and the major part of sex hormones measured by mass spectrometry. Design, Setting, and Participants: We used data from 204 men and 213 women of the cross-sectional Study of Health in Pomerania-TREND. Main Outcome and Measures: Associations of total T (TT) and free T, androstenedione (ASD), estrone, estradiol (E2), dehydroepiandrosterone-sulphate, SHBG, and E2 to TT ratio with sleep measures (including total sleep time, sleep efficiency, wake after sleep onset, apnea-hypopnea index [AHI], Insomnia Severity Index, Epworth Sleepiness Scale, and Pittsburgh Sleep Quality Index) were assessed by sex-specific multivariable regression models. Results: In men, age-adjusted associations of TT (odds ratio 0.62; 95% confidence interval (CI) 0.46–0.83), free T, and SHBG with AHI were rendered nonsign...
TL;DR: The associations of 3 primary exposures (glycemic status, diabetes mellitus control, and insulin resistance as assessed by homeostasis model assessment-estimated insulin resistance quintiles) with cardiac structure and function by modern echocardiographic techniques are investigated.
Abstract: Type 2 diabetes mellitus (T2DM) is the most frequent metabolic disease and is a major risk factor for cardiovascular diseases and mortality. About 9% of the worldwide population, around 347 million people, is expected to present this condition with 50% to 80% of them having a future fatal cardiovascular complication like myocardial infarction, stroke, or heart failure.1 Even more concerning, estimations from the National Health and Nutrition Examination Survey demonstrated that ≤35.3% of the adult US population has prediabetes.2 This is 4 times the number of subjects currently having already a diagnosis of T2DM.2 However, not much is known about the preclinical cardiovascular changes, such as alterations of left ventricular (LV) structure and function, associated with dysglycemic conditions before the diagnosis of T2DM.
See Article by Demmer et al
The study by Demmer et al3 in this issue of Circulation: Cardiovascular Imaging investigated the associations of 3 primary exposures (glycemic status, diabetes mellitus control, and insulin resistance as assessed by homeostasis model assessment-estimated insulin resistance quintiles) with cardiac structure and function by modern echocardiographic techniques. Although the diabetes mellitus status was based on American Diabetes Association criteria, the definitions were a little mixed with the use of glycohemoglobin (HbA1c), fasting plasma glucose, and 2-hour postload plasma glucose. The agreement among fasting plasma glucose, 2-hour postload plasma glucose, and HbA1c for the definition of groups of nondiabetic, prediabetic, and diabetic is not perfect, and individuals included in each group are expected to be different depending on the test used.4 Accordingly, a more preferable approach would be the use of just one definition. The study sample consisted of 1818 individuals (57% women) aged >45 years (average age: 56 years) with Hispanic/Latino ethnicity (predominant self-identifying …