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Author (up) Gemes, K.; Malmo, V.; Laugsand, L.E.; Loennechen, J.P.; Ellekjaer, H.; Laszlo, K.D.; Ahnve, S.; Vatten, L.J.; Mukamal, K.J.; Janszky, I. url  doi
  Title Does Moderate Drinking Increase the Risk of Atrial Fibrillation? The Norwegian HUNT (Nord-Trondelag Health) Study Type Journal Article
  Year 2017 Publication Journal of the American Heart Association Abbreviated Journal J Am Heart Assoc  
  Volume 6 Issue 10 Pages  
  Keywords Hunt; alcohol; atrial fibrillation; cohort study; epidemiology; moderate alcohol  
  Abstract BACKGROUND: Compelling evidence suggests that excessive alcohol consumption increases the risk of atrial fibrillation (AF), but the effect of light-moderate alcohol consumption is less certain. We investigated the association between alcohol consumption within recommended limits and AF risk in a light-drinking population. METHODS AND RESULTS: Among 47 002 participants with information on alcohol consumption in a population-based cohort study in Norway, conducted from October 2006 to June 2008, 1697 validated AF diagnoses were registered during the 8 years of follow-up. We used Cox proportional hazard models with fractional polynomials to analyze the association between alcohol intake and AF. Population attributable risk for drinking within the recommended limit (ie, at most 1 drink per day for women and 2 drinks per day for men without risky drinking) compared with nondrinking was also calculated. The average alcohol intake was 3.8+/-4.8 g/d. The adjusted hazard ratio for AF was 1.38 (95% confidence interval, 1.06-1.80) when we compared participants consuming >7 drinks per week with abstainers. When we modeled the quantity of alcohol intake as a continuous variable, the risk increased in a curvilinear manner. It was higher with heavier alcohol intake, but there was virtually no association at <1 drink per day for women and <2 drinks per day for men in the absence of risky drinking. The population attributable risk among nonrisky drinkers was 0.07% (95% confidence interval, -0.01% to 0.13%). CONCLUSIONS: Although alcohol consumption was associated with a curvilinearly increasing risk of AF in general, the attributable risk of alcohol consumption within recommended limits among participants without binge or problem drinking was negligible in this population.  
  Address Regional Center for Health Care Improvement, St Olav's Hospital, Trondheim, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2047-9980 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29054845; PMCID:PMC5721892 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1901  
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Author (up) Halvorsen, S.; Ghanima, W.; Fride Tvete, I.; Hoxmark, C.; Falck, P.; Solli, O.; Jonasson, C. url  doi
  Title A nationwide registry study to compare bleeding rates in patients with atrial fibrillation being prescribed oral anticoagulants Type Journal Article
  Year 2017 Publication European Heart Journal. Cardiovascular Pharmacotherapy Abbreviated Journal Eur Heart J Cardiovasc Pharmacother  
  Volume 3 Issue 1 Pages 28-36  
  Keywords Apixaban; Atrial fibrillation; Bleeding; Dabigatran; Non-vitamin K antagonist oral anticoagulants; Oral anticoagulants; Rivaroxaban; Warfarin  
  Abstract AIMS: We aimed to evaluate bleeding risk in clinical practice in patients with atrial fibrillation (AF) being prescribed dabigatran, rivaroxaban, or apixaban compared with warfarin. METHODS: Using nationwide registries (Norwegian Patient Registry and Norwegian Prescription Database), we identified AF patients with a first prescription of oral anticoagulants between January 2013 and June 2015. Patients were followed until discontinuation or switching of oral anticoagulants, death, or end of follow-up. The primary endpoint was major or clinically relevant non-major (CRNM) bleeding. RESULTS: In total 32 675 AF patients were identified (58% men, median age 74 years): 11 427 patients used warfarin, 7925 dabigatran, 6817 rivaroxaban, and 6506 apixaban. After a median follow-up of 173 days (25th, 75th percentile 84, 340), 2081 (6.37%) patients experienced a first major or CRNM bleeding. Using a Cox proportional hazard model adjusting for baseline characteristics, use of apixaban [hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.61-0.80, P < 0.001] and dabigatran (HR 0.74, 95% CI 0.66-0.84, P < 0.001) were associated with a lower risk of major or CRNM bleeding compared with warfarin whereas use of rivaroxaban was not (HR: 1.05, 95% CI 0.94-1.17, P = 0.400). Use of dabigatran and rivaroxaban were associated with higher risk of gastrointestinal bleeding, whereas use of apixaban and dabigatran were associated with lower risk of intracranial bleeding, compared with warfarin. CONCLUSION: In this nationwide cohort study in AF patients, apixaban and dabigatran were associated with a lower risk of major or CRNM bleeding compared with warfarin. The risk of gastrointestinal bleeding was higher with rivaroxaban and dabigatran compared with warfarin.  
  Address HUNT Research Center, Faculty of Medicine, NTNU-Norwegian University of Science and Technology, Trondheim, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2055-6845 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:27680880; PMCID:PMC5216196 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1920  
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Author (up) Nielsen, J.B.; Fritsche, L.G.; Zhou, W.; Teslovich, T.M.; Holmen, O.L.; Gustafsson, S.; Gabrielsen, M.E.; Schmidt, E.M.; Beaumont, R.; Wolford, B.N.; Lin, M.; Brummett, C.M.; Preuss, M.H.; Refsgaard, L.; Bottinger, E.P.; Graham, S.E.; Surakka, I.; Chu, Y.; Skogholt, A.H.; Dalen, H.; Boyle, A.P.; Oral, H.; Herron, T.J.; Kitzman, J.; Jalife, J.; Svendsen, J.H.; Olesen, M.S.; Njolstad, I.; Lochen, M.-L.; Baras, A.; Gottesman, O.; Marcketta, A.; O'Dushlaine, C.; Ritchie, M.D.; Wilsgaard, T.; Loos, R.J.F.; Frayling, T.M.; Boehnke, M.; Ingelsson, E.; Carey, D.J.; Dewey, F.E.; Kang, H.M.; Abecasis, G.R.; Hveem, K.; Willer, C.J. url  doi
  Title Genome-wide Study of Atrial Fibrillation Identifies Seven Risk Loci and Highlights Biological Pathways and Regulatory Elements Involved in Cardiac Development Type Journal Article
  Year 2018 Publication American Journal of Human Genetics Abbreviated Journal Am J Hum Genet  
  Volume 102 Issue 1 Pages 103-115  
  Keywords Atrial Fibrillation/*genetics; *Genetic Loci; *Genetic Predisposition to Disease; *Genome-Wide Association Study; Heart/*embryology; Humans; Inheritance Patterns/genetics; Multifactorial Inheritance/genetics; Organ Specificity/genetics; Physical Chromosome Mapping; Quantitative Trait Loci/genetics; Regulatory Sequences, Nucleic Acid/*genetics; Reproducibility of Results; Risk Factors; *Cdkn2c; *Dmrta2; *Gwas; *Ttn; *atrial fibrillation; *cardiomyopathy; *fetal; *genetic risk score; *heart; *pathway  
  Abstract Atrial fibrillation (AF) is a common cardiac arrhythmia and a major risk factor for stroke, heart failure, and premature death. The pathogenesis of AF remains poorly understood, which contributes to the current lack of highly effective treatments. To understand the genetic variation and biology underlying AF, we undertook a genome-wide association study (GWAS) of 6,337 AF individuals and 61,607 AF-free individuals from Norway, including replication in an additional 30,679 AF individuals and 278,895 AF-free individuals. Through genotyping and dense imputation mapping from whole-genome sequencing, we tested almost nine million genetic variants across the genome and identified seven risk loci, including two novel loci. One novel locus (lead single-nucleotide variant [SNV] rs12614435; p = 6.76 x 10(-18)) comprised intronic and several highly correlated missense variants situated in the I-, A-, and M-bands of titin, which is the largest protein in humans and responsible for the passive elasticity of heart and skeletal muscle. The other novel locus (lead SNV rs56202902; p = 1.54 x 10(-11)) covered a large, gene-dense chromosome 1 region that has previously been linked to cardiac conduction. Pathway and functional enrichment analyses suggested that many AF-associated genetic variants act through a mechanism of impaired muscle cell differentiation and tissue formation during fetal heart development.  
  Address Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109, USA; K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health, Norwegian University of Science and Technology, Trondheim 7491, Norway; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: cristen@umich.edu  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0002-9297 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29290336; PMCID:PMC5777936 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2143  
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Author (up) Rutherford, O.-C.W.; Jonasson, C.; Ghanima, W.; Holst, R.; Halvorsen, S. url  doi
  Title New score for assessing bleeding risk in patients with atrial fibrillation treated with NOACs Type Journal Article
  Year 2018 Publication Open Heart Abbreviated Journal Open Heart  
  Volume 5 Issue 2 Pages e000931  
  Keywords anticoagulants; atrial fibrillation; cardiac arrhythmias; epidemiology; haemorrhage  
  Abstract Background: Information is needed on bleeding risk factors specific for patients with atrial fibrillation (AF) treated with non-vitamin K oral anticoagulants (NOACs). We aimed to identify risk factors in a large real-world cohort and to derive a bleeding risk score for patients with AF treated with NOACs. Methods: From nationwide registries (the Norwegian Patient Registry and the Norwegian Prescription Database), we identified patients with AF with a first prescription of a NOAC between January 2013 and June 2015. Cox proportional-hazards analysis was used to identify the strongest risk factors for major or clinically relevant non-major (CRNM) bleeding. Based on these, a risk prediction score was derived. Discrimination was assessed with Harrel's C-index. C-indexes for the modified Hypertension, Age, Stroke, Bleeding tendency/predisposition, Labile international normalised ratios, Elderly age, Drugs or alcohol excess (HAS-BLED), the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) and the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT) scores were also calculated from the same cohort. Results: Among 21 248 NOAC-treated patients with a median follow-up time of 183 days, 1257 (5.9%) patients experienced a major or CRNM bleeding. Ten independent risk factors for bleeding were identified, which when included in a risk prediction model achieved a C-index of 0.68 (95% CI 0.66 to 0.70). A simplified score comprising three variables; age, history of bleeding and non-bleeding related hospitalisation within the last 12 months, yielded a c-index of 0.66 (95% CI 0.65 to 0.68). In the same cohort, the modified HAS-BLED, ATRIA and ORBIT scores achieved c-indexes of 0.62 (95% CI 0.60 to 0.63), 0.66 (95% CI 0.64 to 0.67) and 0.66 (95% CI 0.64 to 0.67), respectively. Conclusions: Our proposed simplified bleeding score could be a useful clinical tool for quick estimation of risk of bleeding in patients with AF treated with NOACs.  
  Address Department of Cardiology, Oslo University Hospital, Ulleval, Oslo, Norway  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2053-3624 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:30613418; PMCID:PMC6307577 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 2147  
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