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  • 1.
    Abrahamsson, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center of Paediatrics and Gynaecology and Obstetrics, Department of Paediatrics in Linköping.
    Editorial Material: Not all probiotic strains prevent necrotising enterocolitis in premature infants in LANCET, vol 387, issue 10019, pp 624-6252016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10019, p. 624-625Article in journal (Other academic)
    Abstract [en]

    n/a

  • 2.
    Aerts, Marc
    et al.
    Interuniversity Institute for Biostatistics and Statistical Bioinformatics.
    Minalu, Girma
    Interuniversity Institute for Biostatistics and Statistical Bioinformatics.
    Bösner, Stefan
    Department of General Practice and Family Medicine, Philipps University Marburg, Germany..
    Buntinx, Frank
    Department of Public Health and Primary Care, KU Leuven, Belgium; Department of General Practice, Maastricht University, The Netherlands..
    Burnand, Bernard
    Institute of Social and Preventive Medicine, Lausanne University Hospital, Switzerland..
    Haasenritter, Jörg
    Department of General Practice and Family Medicine, Philipps University Marburg, Germany..
    Herzig, Lilli
    Institute of Family Medicine, University of Lausanne, Switzerland..
    Knottnerus, J André
    Department of General Practice, Maastricht University, The Netherlands..
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Primary Care Center, Primary Health Care Center Vikbolandet.
    Renier, Walter
    Department of Public Health and Primary Care, KU Leuven, Belgium.
    Sox, Carol
    Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, USA..
    Sox, Harold
    Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, NH , USA; Patient-Centered Outcomes Research Institute, Washington, USA..
    Donner-Banzhoff, Norbert
    Department of General Practice and Family Medicine, Philipps University Marburg, Germany..
    Pooled individual patient data from five countries were used to derive a clinical prediction rule for coronary artery disease in primary care.2017In: Journal of Clinical Epidemiology, ISSN 0895-4356, E-ISSN 1878-5921, Vol. 81, p. 120-128Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To construct a clinical prediction rule for coronary artery disease (CAD) presenting with chest pain in primary care.

    STUDY DESIGN AND SETTING: Meta-Analysis using 3,099 patients from five studies. To identify candidate predictors, we used random forest trees, multiple imputation of missing values, and logistic regression within individual studies. To generate a prediction rule on the pooled data, we applied a regression model that took account of the differing standard data sets collected by the five studies.

    RESULTS: The most parsimonious rule included six equally weighted predictors: age ≥55 (males) or ≥65 (females) (+1); attending physician suspected a serious diagnosis (+1); history of CAD (+1); pain brought on by exertion (+1); pain feels like "pressure" (+1); pain reproducible by palpation (-1). CAD was considered absent if the prediction score is <2. The area under the ROC curve was 0.84. We applied this rule to a study setting with a CAD prevalence of 13.2% using a prediction score cutoff of <2 (i.e., -1, 0, or +1). When the score was <2, the probability of CAD was 2.1% (95% CI: 1.1-3.9%); when the score was ≥ 2, it was 43.0% (95% CI: 35.8-50.4%).

    CONCLUSIONS: Clinical prediction rules are a key strategy for individualizing care. Large data sets based on electronic health records from diverse sites create opportunities for improving their internal and external validity. Our patient-level meta-analysis from five primary care sites should improve external validity. Our strategy for addressing site-to-site systematic variation in missing data should improve internal validity. Using principles derived from decision theory, we also discuss the problem of setting the cutoff prediction score for taking action.

  • 3.
    Ageno, Walter
    et al.
    University of Insubria, Italy.
    Buller, Harry R.
    Academic Medical Centre, Netherlands.
    Falanga, Anna
    Hospital Papa Giovanni XXIII, Italy; Hospital Papa Giovanni XXIII, Italy.
    Hacke, Werner
    Heidelberg University, Germany.
    Hendriks, Jeroen
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. University of Adelaide, Australia.
    Lobban, Trudie
    Arrhythmia Alliance and AF Assoc, England.
    Merino, Jose
    University of La Paz, Spain.
    Milojevic, Ivan S.
    Gen Hospital Cuprija, Serbia.
    Moya, Francisco
    Vithas Xanit Int Hospital, Spain.
    Bart van der Worp, H.
    University of Medical Centre Utrecht, Netherlands.
    Randall, Gary
    SAFE, England.
    Tsioufis, Konstantinos
    University of Athens, Greece.
    Verhamme, Peter
    University of Leuven, Belgium.
    John Camm, A.
    St Georges University of London, England; Imperial Coll, England.
    Managing reversal of direct oral anticoagulants in emergency situations Anticoagulation Education Task Force White Paper2016In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 116, no 6, p. 1003-1010Article in journal (Refereed)
    Abstract [en]

    Anticoagulation is the cornerstone of prevention and treatment of venous thromboembolism (VTE) and stroke prevention in patients with atrial fibrillation (AF). However, the mechanisms by which anticoagulants confer therapeutic benefit also increase the risk of bleeding. As such, reversal strategies are critical. Until recently, the direct oral anticoagulants (DOACs) dabigatran, rivaroxaban, apixaban, and edoxaban lacked a specific reversal agent. This report is based on findings from the Anticoagulation Education Task Force, which brought together patient groups and professionals representing different medical specialties with an interest in patient safety and expertise in AF, VTE, stroke, anticoagulation, and reversal agents, to discuss the current status of anticoagulation reversal and fundamental changes in management of bleeding associated with DOACs occasioned by the approval of idarucizumab, a specific reversal agent for dabigatran, as well as recent clinical data on specific reversal agents for factor Xa inhibitors. Recommendations are given for when there is a definite need for a reversal agent (e.g. in cases of life-threatening bleeding, bleeding into a closed space or organ, persistent bleeding despite local haemostatic measures, and need for urgent interventions and/or interventions that carry a high risk for bleeding), when reversal agents may be helpful, and when a reversal agent is generally not needed. Key stakeholders who require 24-7/around-the-clock access to these agents vary among hospitals; however, from a practical perspective the emergency department is recommended as an appropriate location for these agents. Clearly, the advent of new agents requires standardised protocols for treating bleeding on an institutional level.

  • 4.
    Agvall, Björn
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Paulsson, Thomas
    Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Belgium.
    Foldevi, Mats
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Primary Health Care in Central County.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Resource use and cost implications of implementing a heart failure program for patients with systolic heart failure in Swedish primary health care2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 176, p. 731-738Article in journal (Refereed)
    Abstract [en]

    Aim: Heart failure (HF) is a common but serious condition which involves a significant economic burden on the health care economy. The purpose of this study was to evaluate cost and quality of life (QoL) implications of implementing a HF management program (HFMP) in primary health care (PHC).

    Methods and results: This was a prospective randomized open-label study including 160 patientswith a diagnosis of HF from five PHC centers in south-eastern Sweden. Patients randomized to the intervention group received information about HF from HF nurses and from a validated computer-based awareness program. HF nurses and physicians followed the patients intensely in order to optimize HF treatment according to current guidelines. The patients in the control group were followed by their regular general practitioner (GP) and received standard treatment according to local management routines. No significant changes were observed in NYHA class and quality-adjusted life years (QALY), implying that functional class and QoL were preserved. However, costs for hospital care (HC) and PHC were reduced by EUR 2167, or 33%. The total cost was EUR 4471 in the intervention group and EUR 6638 in the control group.

    Conclusions: Introducing HFMP in Swedish PHC in patients with HF entails a significant reduction in resource utilization and costs, and maintains QoL. Based on these results, a broader implementation of HFMP in PHC may be recommended. However, results should be confirmed with extended follow-up to verify  long-term effects.

  • 5.
    Ahlander, Britt-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Magnetic Resonance Imaging of the Heart: Image quality, measurement accuracy and patient experience2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Non-invasive diagnostic imaging of atherosclerotic coronary artery disease (CAD) is frequently carried out with cardiovascular magnetic resonance imaging (CMR) or myocardial perfusion single photon emission computed tomography (MPS). CMR is the gold standard for the evaluation of scar after myocardial infarction and MPS the clinical gold standard for ischemia. Magnetic Resonance Imaging (MRI) is at times difficult for patients and may induce anxiety while patient experience of MPS is largely unknown.

    Aims: To evaluate image quality in CMR with respect to the sequences employed, the influence of atrial fibrillation, myocardial perfusion and the impact of patient information. Further, to study patient experience in relation to MRI with the goal of improving the care of these patients.

    Method: Four study designs have been used. In paper I, experimental cross-over, paper (II) experimental controlled clinical trial, paper (III) psychometric crosssectional study and paper (IV) prospective intervention study. A total of 475 patients ≥ 18 years with primarily cardiac problems (I-IV) except for those referred for MRI of the spine (III) were included in the four studies.

    Result: In patients (n=20) with atrial fibrillation, a single shot steady state free precession (SS-SSFP) sequence showed significantly better image quality than the standard segmented inversion recovery fast gradient echo (IR-FGRE) sequence (I). In first-pass perfusion imaging the gradient echo-echo planar imaging sequence (GREEPI) (n=30) had lower signal-to-noise and contrast–to-noise ratios than the steady state free precession sequence (SSFP) (n=30) but displayed a higher correlation with the MPS results, evaluated both qualitatively and quantitatively (II). The MRIAnxiety Questionnaire (MRI-AQ) was validated on patients, referred for MRI of either the spine (n=193) or the heart (n=54). The final instrument had 15 items divided in two factors regarding Anxiety and Relaxation. The instrument was found to have satisfactory psychometric properties (III). Patients who prior CMR viewed an information video scored significantly (lower) better in the factor Relaxation, than those who received standard information. Patients who underwent MPS scored lower on both factors, Anxiety and Relaxation. The extra video information had no effect on CMR image quality (IV).

    Conclusion: Single shot imaging in atrial fibrillation produced images with less artefact than a segmented sequence. In first-pass perfusion imaging, the sequence GRE-EPI was superior to SSFP. A questionnaire depicting anxiety during MRI showed that video information prior to imaging helped patients relax but did not result in an improvement in image quality.

    List of papers
    1. Image quality and myocardial scar size determined with magnetic resonance imaging in patients with permanent atrial fibrillation: a comparison of two imaging protocols
    Open this publication in new window or tab >>Image quality and myocardial scar size determined with magnetic resonance imaging in patients with permanent atrial fibrillation: a comparison of two imaging protocols
    Show others...
    2010 (English)In: CLINICAL PHYSIOLOGY AND FUNCTIONAL IMAGING, ISSN 1475-0961, Vol. 30, no 2, p. 122-129Article in journal (Refereed) Published
    Abstract [en]

    Pandgt;Background: Magnetic resonance imaging (MRI) of the heart generally requires breath holding and a regular rhythm. Single shot 2D steady-state free precession (SS_SSFP) is a fast sequence insensitive to arrhythmia as well as breath holding. Our purpose was to determine image quality, signal-to-noise (SNR) and contrast-to-noise (CNR) ratios and infarct size with a fast single shot and a standard segmented MRI sequence in patients with permanent atrial fibrillation and chronic myocardial infarction. Methods: Twenty patients with chronic myocardial infarction and ongoing atrial fibrillation were examined with inversion recovery SS_SSFP and segmented inversion recovery 2D fast gradient echo (IR_FGRE). Image quality was assessed in four categories: delineation of infarcted and non-infarcted myocardium, occurrence of artefacts and overall image quality. SNR and CNR were calculated. Myocardial volume (ml) and infarct size, expressed as volume (ml) and extent (%), were calculated, and the methodological error was assessed. Results: SS_SSFP had significantly better quality scores in all categories (P = 0 center dot 037, P = 0 center dot 014, P = 0 center dot 021, P = 0 center dot 03). SNRinfarct and SNRblood were significantly better for IR_FGRE than for SS_SSFP (P = 0 center dot 048, P = 0 center dot 018). No significant difference was found in SNRmyocardium and CNR. The myocardial volume was significantly larger with SS_SSFP (170 center dot 7 versus 159 center dot 2 ml, P andlt; 0 center dot 001), but no significant difference was found in infarct volume and infarct extent. Conclusion: SS_SSFP displayed significantly better image quality than IR_FGRE. The infarct size and the error in its determination were equal for both sequences, and the examination time was shorter with SS_SSFP.

    Keywords
    atrial fibrillation, magnetic resonance imaging, myocardial infarction, segmented inversion recovery 2D fast gradient echo, single shot inversion recovery 2D steady-state free precession
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-54159 (URN)10.1111/j.1475-097X.2009.00914.x (DOI)000274438800006 ()
    Available from: 2010-02-26 Created: 2010-02-26 Last updated: 2016-08-24
    2. An echo-planar imaging sequence is superior to a steady-state free precession sequence for visual as well as quantitative assessment of cardiac magnetic resonance stress perfusion
    Open this publication in new window or tab >>An echo-planar imaging sequence is superior to a steady-state free precession sequence for visual as well as quantitative assessment of cardiac magnetic resonance stress perfusion
    Show others...
    2017 (English)In: Clinical Physiology and Functional Imaging, ISSN 1475-0961, E-ISSN 1475-097X, Vol. 37, no 1, p. 52-61Article in journal (Refereed) Published
    Abstract [en]

    Background To assess myocardial perfusion, steady-state free precession cardiac magnetic resonance (SSFP, CMR) was compared with gradient-echo–echo-planar imaging (GRE-EPI) using myocardial perfusion scintigraphy (MPS) as reference. Methods Cardiac magnetic resonance perfusion was recorded in 30 patients with SSFP and in another 30 patients with GRE-EPI. Timing and extent of inflow delay to the myocardium was visually assessed. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated. Myocardial scar was visualized with a phase-sensitive inversion recovery sequence (PSIR). All scar positive segments were considered pathologic. In MPS, stress and rest images were used as in clinical reporting. The CMR contrast wash-in slope was calculated and compared with the stress score from the MPS examination. CMR scar, CMR perfusion and MPS were assessed separately by one expert for each method who was blinded to other aspects of the study. Results Visual assessment of CMR had a sensitivity for the detection of an abnormal MPS at 78% (SSFP) versus 91% (GRE-EPI) and a specificity of 58% (SSFP) versus 84% (GRE-EPI). Kappa statistics for SSFP and MPS was 0·29, for GRE-EPI and MPS 0·72. The ANOVA of CMR perfusion slopes for all segments versus MPS score (four levels based on MPS) had correlation r = 0·64 (SSFP) and r = 0·96 (GRE-EPI). SNR was for normal segments 35·63 ± 11·80 (SSFP) and 17·98 ± 8·31 (GRE-EPI), while CNR was 28·79 ± 10·43 (SSFP) and 13·06 ± 7·61 (GRE-EPI). Conclusion GRE-EPI displayed higher agreement with the MPS results than SSFP despite significantly lower signal intensity, SNR and CNR.

    Place, publisher, year, edition, pages
    John Wiley & Sons, 2017
    Keywords
    cardiac imaging techniques, coronary heart disease, Magnetic Resonance Imaging, nuclear medicine, perfusion
    National Category
    Radiology, Nuclear Medicine and Medical Imaging Medical Laboratory and Measurements Technologies Medical Image Processing Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-130795 (URN)10.1111/cpf.12267 (DOI)000390688200008 ()26147785 (PubMedID)
    Note

    Funding agencies: Medical Research Council of Southeast Sweden [12437]; Futurum, the County council of Jonkoping [12440, 81851, 217261]; Linkoping University; County Council of Ostergotland [281281]; Swedish Heart-Lung Foundation [20120449]

    Available from: 2016-08-24 Created: 2016-08-24 Last updated: 2017-11-28Bibliographically approved
    3. Development and validation of a questionnaire evaluating patient anxiety during Magnetic Resonance Imaging: the Magnetic Resonance Imaging-Anxiety Questionnaire (MRI-AQ)
    Open this publication in new window or tab >>Development and validation of a questionnaire evaluating patient anxiety during Magnetic Resonance Imaging: the Magnetic Resonance Imaging-Anxiety Questionnaire (MRI-AQ)
    Show others...
    2016 (English)In: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 72, no 6, p. 1368-1380Article in journal (Refereed) Published
    Abstract [en]

    Aim. To develop and validate a new instrument measuring patient anxiety during Magnetic Resonance Imaging examinations, Magnetic Resonance Imaging-Anxiety Questionnaire. Background. Questionnaires measuring patients anxiety during Magnetic Resonance Imaging examinations have been the same as used in a wide range of conditions. To learn about patients experience during examination and to evaluate interventions, a specific questionnaire measuring patient anxiety during Magnetic Resonance Imaging is needed. Design. Psychometric cross-sectional study with test-retest design. Methods. A new questionnaire, Magnetic Resonance Imaging-Anxiety Questionnaire, was designed from patient expressions of anxiety in Magnetic Resonance Imaging-scanners. The sample was recruited between October 2012-October 2014. Factor structure was evaluated with exploratory factor analysis and internal consistency with Cronbachs alpha. Criterion-related validity, known-group validity and test-retest was calculated. Results. Patients referred for Magnetic Resonance Imaging of either the spine or the heart, were invited to participate. The development and validation of Magnetic Resonance Imaging-Anxiety Questionnaire resulted in 15 items consisting of two factors. Cronbachs alpha was found to be high. Magnetic Resonance Imaging-Anxiety Questionnaire correlated higher with instruments measuring anxiety than with depression scales. Known-group validity demonstrated a higher level of anxiety for patients undergoing Magnetic Resonance Imaging scan of the heart than for those examining the spine. Test-retest reliability demonstrated acceptable level for the scale. Conclusion. Magnetic Resonance Imaging-Anxiety Questionnaire bridges a gap among existing questionnaires, making it a simple and useful tool for measuring patient anxiety during Magnetic Resonance Imaging examinations.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 2016
    Keywords
    anxiety; instrument development; magnetic resonance imaging; nurse; nursing; reliability; validity
    National Category
    Other Medical Sciences not elsewhere specified
    Identifiers
    urn:nbn:se:liu:diva-129145 (URN)10.1111/jan.12917 (DOI)000376007400014 ()26893007 (PubMedID)
    Note

    Funding Agencies|Swedish Heart and Lung Foundation; Futurum County Council of Jonkoping

    Available from: 2016-06-13 Created: 2016-06-13 Last updated: 2017-11-28
  • 6.
    Ahlin, Fredrik
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Wilhelminen Hospital, Austria.
    Arfvidsson, John
    Linköping University, Faculty of Medicine and Health Sciences. Wilhelminen Hospital, Austria.
    Vargas, Kris G.
    Wilhelminen Hospital, Austria.
    Stojkovic, Stefan
    Medical University of Vienna, Austria; Ludwig Boltzmann Cluster Cardiovasc Research, Austria.
    Huber, Kurt
    Wilhelminen Hospital, Austria; Ludwig Boltzmann Cluster Cardiovasc Research, Austria; Sigmund Freud University, Austria.
    Wojta, Johann
    Medical University of Vienna, Austria; Ludwig Boltzmann Cluster Cardiovasc Research, Austria; Medical University of Vienna, Austria.
    MicroRNAs as circulating biomarkers in acute coronary syndromes: A review2016In: Vascular pharmacology, ISSN 1537-1891, E-ISSN 1879-3649, Vol. 81, p. 15-21Article, review/survey (Refereed)
    Abstract [en]

    Coronary artery disease (CAD) and its complications remain the most common cause of death worldwide. Cardiac troponins (cTn) are standard biomarkers used today for diagnosis and risk stratification of myocardial infarction (MI). Increasing efforts are made to develop additional, new biomarkers for more effective and safe rule-in and rule-out of MI patients at the emergency department. During the past decade, microRNAs (miRNAs) have emerged as new, potential diagnostic biomarkers in several diseases, including MI. In this review, we aimed to summarize some of the prominent studies in the field, and discuss the potential value of miRNAs in the diagnosis of MI. (C) 2016 Elsevier Inc. All rights reserved.

  • 7.
    Ahmad, Tariq
    et al.
    Yale Univ, CT USA; Yale Univ, CT USA.
    Lund, Lars H.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Rao, Pooja
    Qure Ai, India.
    Ghosh, Rohit
    Qure Ai, India.
    Warier, Prashant
    Qure Ai, India.
    Vaccaro, Benjamin
    Yale Univ, CT USA; Yale Univ, CT USA.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    OConnor, Christopher M.
    Duke Univ, NC USA.
    Felker, G. Michael
    Duke Univ, NC USA.
    Desai, Nihar R.
    Yale Univ, CT USA; Yale Univ, CT USA.
    Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 8, article id e008081Article in journal (Refereed)
    Abstract [en]

    Background-Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. Methods and Results-The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, )i-blockers, and nitrates, Pamp;lt;0.001, all). Conclusions-Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics. Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.

  • 8.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Baranowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Dahlin, Lars-Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Transvenous Implantation of a Stent Valve in Patients With Degenerated Mitral Prostheses and Native Mitral Stenosis2016In: Annals of Thoracic Surgery, ISSN 0003-4975, E-ISSN 1552-6259, Vol. 101, no 6, p. 2279-2284Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The purpose of this study was to report the use of a transvenous transseptal approach using a stent valve in patients with degenerated biological mitral valve prostheses, regurgitation after mitral repair, and native mitral stenosis.

    METHODS: Ten patients (median age, 74 years; range, 20-89 years; 5 men and 5 women) with degenerated mitral bioprosthetic valves (n = 7), failed mitral repair (n = 1), or calcified native stenotic valves (n = 2) underwent transvenous implantation of a stent valve.

    RESULTS: The procedure was initially successful in all patients. Predilation was performed for balloon sizing only in the 2 patients with native mitral stenosis. The stent valve was deployed during 1 period of rapid pacing. A guidewire, as a loop from the right femoral vein and through the left ventricular apex, facilitated a good angle and secure positioning of the stent valve. An ultrasonographically guided puncture of the apex was carried out in 6 patients, and in the other 4 we performed a minithoracotomy before apical puncture. All valves were implanted in a good position with improved function and without significant paravalvular leakage (PVL). There were no periprocedural deaths. The 30-day survival was 80% (8 of 10 patients), and 60% (6 of 10) of patients were still alive a median time of 290 days after the procedure.

    CONCLUSIONS: Transvenous transseptal implantation of a stent valve was performed in 10 patients with mitral valve disease, with good early functional results. These high-risk patients must be carefully selected by a multidisciplinary team because the procedure carries a high mortality.

  • 9.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Holm, Jonas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Najar, Azad
    Scandinavian Real Heart AB, Vasteras, Sweden.
    Hellers, Goran
    Scandinavian Real Heart AB, Vasteras, Sweden.
    Szabó, Zoltán
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    A New Total Artificial Heart Concept Allowing Replacement or Support of the Native Heart2018In: Journal of Clinical & Experimental Cardiology, E-ISSN 2155-9880, Vol. 9, no 2, article id 1000569Article in journal (Refereed)
    Abstract [en]

    A total artificial heart (TAH) is typically used to bridge the time to heart transplantation. A device designed by Robert Jarvik has been improved through the years and under the name of Syncardia™ this has been the most successful commercially available TAH so far. Since 2008 the Carmat™ heart has been under development in Europe. The Scandinavian Real Heart™ is based on a unique physiological concept where the atrio-ventricular valve plane is of utmost importance in the pumping function of the heart. It consists of two identical parts driven separately by independent motors and in this first animal study we have used one part as a left ventricular assist device. This new concept makes the device flexible as it may be used not only as a TAH but also as a separate pump for left or right ventricular assist.

  • 10.
    Ahn, Henrik Casimir
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Baranowski, Jacek
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Can predilatation in transcatheter aortic valve implantation be omitted? - a prospective randomized study2016In: Journal of Cardiothoracic Surgery, ISSN 1749-8090, E-ISSN 1749-8090, Vol. 11, no 124Article in journal (Refereed)
    Abstract [en]

    Background: The use of a balloon expandable stent valve includes balloon predilatation of the aortic stenosis before valve deployment. The aim of the study was to see whether or not balloon predilatation is necessary in transcatheter aortic valve replacement (TAVI). Methods: Sixty consecutive TAVI patients were randomized to the standard procedure or to a protocol where balloon predilatation was omitted. Results: There were no significant differences between the groups regarding early hemodynamic results or complication rates. Conclusions: TAVI can be performed safely without balloon predilatation and with the same early results as achieved with the standard procedure including balloon predilatation. The reduction in the number of pacing periods required may be beneficial for the patient.

  • 11.
    Alabas, Oras A.
    et al.
    University of Leeds, England.
    Gale, Chris P.
    University of Leeds, England; York Teaching Hospital NHS Fdn Trust, England.
    Hall, Marlous
    University of Leeds, England.
    Rutherford, Mark J.
    University of Leicester, England.
    Szummer, Karolina
    Department Med, Sweden.
    Sederholm Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Bertil
    Uppsala University, Sweden; Uppsala University, Sweden.
    Jernberg, Tomas
    Karolinska Institute, Sweden.
    Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007123Article in journal (Refereed)
    Abstract [en]

    Background-This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction. Methods and Results-A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]). Conclusions-Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

  • 12.
    Albertsson-Wikland, Kerstin
    et al.
    University of Gothenburg, Sweden.
    Mårtensson, Anton
    University of Gothenburg, Sweden; Stat Konsultgrp, Sweden.
    Savendahl, Lars
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Niklasson, Aimon
    University of Gothenburg, Sweden.
    Bang, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Dahlgren, Jovanna
    University of Gothenburg, Sweden.
    Gustafsson, Jan
    Uppsala University, Sweden.
    Kriström, Berit
    Umeå University, Sweden.
    Norgren, Svante
    Karolinska University Hospital, Sweden; Karolinska University Hospital, Sweden.
    Pehrsson, Nils-Gunnar
    Stat Konsultgrp, Sweden.
    Oden, Anders
    Stat Konsultgrp, Sweden; Chalmers, Sweden.
    Mortality Is Not Increased in Recombinant Human Growth Hormone-treated Patients When Adjusting for Birth Characteristics2016In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 101, no 5, p. 2149-2159Article in journal (Refereed)
    Abstract [en]

    Objective: This study aimed to investigate whether reported high mortality in childhood recombinant human GH (rhGH)-treated patients was related to birth-characteristics and/or rhGH treatment. Design and Setting: We sought to develop a mortality model of the Swedish general population born between 1973 and 2010, using continuous-hazard functions adjusting for birth characteristics, sex, age intervals, and calendar year to estimate standardized mortality ratio (SMR) and to apply this model to assess expected deaths in Swedish rhGH-treated patients with idiopathic isolated GH deficiency (IGHD), idiopathic short stature (155) or born small for gestational age (SGA). Participants:The general population: Swedish Medical Birth Register (1973-2010: 1 880 668 males; 1 781 131 females) and Cause of Death Register (1985-2010). Intervention Population: Three thousand eight hundred forty-seven patients starting rhGH treatment between 1985 and 2010 and followed in the National GH Register and/or in rhGH trials diagnosed with IGHD (n = 1890), ISS (n = 975), or SGA (n=982). Main Outcome Measures: Death. Results: Using conventional models adjusting for age, sex, and calendar-year, the SMR was 1.43 (95% confidence interval, 0.89-2.19), P = .14, observed/expected deaths 21/14.68. The rhGH population differed (P amp;lt; .001) from the general population regarding birth weight, birth length, and congenital malformations. Application of an Advanced Model: When applying the developed mortality model of the general population, the ratio of observed/expected deaths in rhGH-treated patients was 21/21.99; SMR = 0.955 (0.591-1.456)P = .95. Model Comparison: Expected number of deaths were 14.68 (14.35-14.96) using the conventional model, and 21.99 (21.24-22.81) using the advanced model, P amp;lt; .001, which had at all ages a higher gradient of risk per SD of the model, 24% (range, 18-42%; P amp;lt; .001). Conclusions: Compared with the general Swedish population, the ratio of observed/expected deaths (21/21.99) was not increased in childhood rhGH-treated IGHD, ISS, and SGA patients when applying an advanced sex-specific mortality model adjusting for birth characteristics.

  • 13.
    Al-Dury, Nooraldeen
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Rawshani, Araz
    University of Gothenburg, Sweden.
    Israelsson, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden; Linnaeus University, Sweden.
    Stromsoe, Anneli
    School Health Care and Social Welf, Sweden.
    Aune, Solveig
    Sahlgrens University Hospital, Sweden.
    Agerstrom, Jens
    Linnaeus University, Sweden.
    Karlsson, Thomas
    University of Gothenburg, Sweden.
    Ravn-Fischer, Annica
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Herlitz, Johan
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden; University of Boras, Sweden.
    Characteristics and outcome among 14,933 adult cases of in-hospital cardiac arrest: A nationwide study with the emphasis on gender and age2017In: American Journal of Emergency Medicine, ISSN 0735-6757, E-ISSN 1532-8171, Vol. 35, no 12, p. 1839-1844Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate characteristics and outcome among patients suffering in-hospital cardiac arrest (IHCA) with the emphasis on gender and age. Methods: Using the Swedish Register of Cardiopulmonary Resuscitation, we analyzed associations between gender, age and co-morbidities, etiology, management, 30-day survival and cerebral function among survivors in 14,933 cases of IHCA. Age was divided into three ordered categories: young (18-49 years), middle-aged (5064 years) and older (65 years and above). Comparisons between men and women were age adjusted. Results: The mean age was 72.7 years and women were significantly older than men. Renal dysfunction was the most prevalent co-morbidity. Myocardial infarction/ischemia was the most common condition preceding IHCA, with men having 27% higher odds of having MI as the underlying etiology. A shockable rhythm was found in 31.8% of patients, with men having 52% higher odds of being found in VT/VF. After adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30 days. Older individuals were managed less aggressively than younger patients. Increasing age was associated with lower 30-day survival but not with poorer cerebral function among survivors. Conclusion: When adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30 days after in-hospital cardiac arrest. Older individuals were managed less aggressively than younger patients, despite a lower chance of survival. Higher age was, however, not associated with poorer cerebral function among survivors. (C) 2017 Elsevier Inc. All rights reserved.

  • 14.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Johansson, Peter
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0193120Article in journal (Refereed)
    Abstract [en]

    Background Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. Methods From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. Findings After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95% CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. Conclusions This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating.

  • 15.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hosp, Norway; Hedmark Univ Coll, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Svensson, Erland
    Swedish Def Res Agcy, Linkoping, Sweden.
    Johansson, Peter
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10A mechanism behind reduced cardiovascular mortality?2018In: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 44, no 2, p. 137-147Article in journal (Refereed)
    Abstract [en]

    Background: In an intervention study where 221 healthy elderly persons received selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4 years we observed improved cardiac function and reduced cardiovascular mortality. As fibrosis is central in the aging process, we investigated the effect of the intervention on biomarkers of fibrogenic activity in a subanalysis of this intervention study. Material and Methods: In the present subanalysis 122 actively treated individuals and 101 controls, the effect of the treatment on eight biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin S, Endostatin, Galectin 3, Growth Differentiation Factor-15 (GDF-15), Matrix Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and Suppression of Tumorigenicity 2 (ST-2). Blood concentrations of these biomarkers after 6 and 42 months were analyzed by the use of T-tests, repeated measures of variance, and factor analyses. Results: Compared with placebo, in those receiving supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed significant decreased concentrations in blood. The changes in concentrations, that is, effects sizes as given by partial eta(2) caused by the intervention were considered small to medium. Conclusion: The significantly decreased biomarker concentrations in those on active treatment with selenium and coenzyme Q10 compared with those on placebo after 36 months of intervention presumably reflect less fibrogenic activity as a result of the intervention. These observations might indicate that reduced fibrosis precedes the reported improvement in cardiac function, thereby explaining some of the positive clinical effects caused by the intervention. (c) 2017 BioFactors, 44(2):137-147, 2018

  • 16.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.2015In: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 41, no 6, p. 443-452Article in journal (Refereed)
    Abstract [en]

    Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MR-proADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P = 0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P=0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P=0.0001, and P=0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MR-proADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation. © 2015 BioFactors, 41(6):443-452, 2015.

  • 17.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, article id e0157541Article in journal (Refereed)
    Abstract [en]

    Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 mu g Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 mu g/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; amp;lt;65 mu g/L, 65-85 mu g/L, and amp;gt;85 mu g/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of amp;gt;85 mu g/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. Conclusions In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 mu g/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations amp;lt; 65 mu g/L in comparison with those having a selenium concentration amp;gt; 85 mu g/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, amp;lt;= 85 at inclusion. In those with serum seleniumamp;gt; 85 mu g/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted.

  • 18.
    Alfredsson, Joakim
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
    Management and Outcome in Non ST-Elevation Acute Coronary Syndromes: Similarities and Differences Between Women nad Men2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Non ST-elevation Acute Coronary Syndromes are the most frequent manifestations of acute ischemic heart disease. Gender differences in treatment intensity, including differences in level of care, have been reported. Also differences in benefit from certain treatments, especially invasive treatment, have been discussed. Finally, difference in outcome between men and women, have been proposed. Results have been inconsistent, partly depending on if and how adjustment for differences in background characteristics has been made. The aims of the studies in this thesis were to assess differences between the genders in baseline characteristics, level of care, medical treatment and non-invasive and invasive cardiac procedures. The aims were also to determine gender differences in short and long-term mortality, including impact of level of care, and to determine differences between the genders in benefit from an invasive strategy, with special reference to benefit in women.

    Method: We used prospectively collected data from the RIKS-HIA registry in two studies (Paper I and IV). In one study we merged data from patients admitted to general wards in the south-east region of Sweden (The AKUT registry), with data from patients admitted to CCU´s (RIKS-HIA) at participating hospitals during the same time (Paper II). We also randomly assigned women to a routine invasive or a selective invasive treatment strategy, and performed a meta-analysis, to determine gender differences in benefit from a routine invasive strategy (Paper III).

    Results: Women were older than men and more likely to have a history of diabetes and hypertension, while men were more likely to have a history of myocardial infarction and revascularisation. Women were also more likely to have normal coronary arteries on the angiogram. After adjustment for baseline differences there were only minor, and directionally inconsistent, differences between women and men in pharmacological treatment. Men were more often referred for coronary angiography, even after adjustment. While CABG-rate was lower in women, after adjustment PCI-rate was similar or even higher compared to men. After adjustment for differences in age, longterm outcome was better in women. In our small but randomised trial there was no benefit from a routine invasive strategy in women. A meta-analysis indicated interaction between gender and treatment strategy, with lack of benefit in women, in contrast to in men. However, our large observational study indicated no gender difference with an invasive strategy. Moreover, benefit was similar in women and men with invasive treatment.

    Conclusion: There are substantial differences between women and men in baseline characteristics that affect management and outcome more than gender per se. After adjustment women have better long-term outcome than men. There appear to be a difference in benefit from a routine invasive strategy between the genders, with less benefit in women, but in routine clinical management there was no difference between women and men managed with an invasive strategy.

    List of papers
    1. Gender differences in management and outcome in non-ST-elevation acute coronary syndrome
    Open this publication in new window or tab >>Gender differences in management and outcome in non-ST-elevation acute coronary syndrome
    2007 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 93, no 11, p. 1357-1362Article in journal (Refereed) Published
    Abstract [en]

    Objective: To study gender differences in management and outcome in patients with non-ST-elevation acute coronary syndrome. Design, setting and patients: Cohort study of 53 781 consecutive patients (37% women) from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), with a diagnosis of either unstable angina pectoris or non-ST-elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 1998 and 2002, and followed for 1 year. Main outcome measures: Treatment intensity and in-hospital, 30-day and 1 -year mortality. Results: Women were older (73 vs 69 years, p<0.001) and more likely to have a history of hypertension and diabetes, but less likely to have a history of myocardial infarction or revascularisation. After adjustment, there were no major differences in acute pharmacological treatment or prophylactic medication at discharge. Revascularisation was, however, even after adjustment, performed more often in men (OR 1.15, 95% CI, 1.09 to 1.21). After adjustment, there was no significant difference in in-hospital (OR 1.03, 95% CI, 0.94 to 1.13) or 30-days (OR 1.07, 95% CI, 0.99 to 1.15) mortality, but at 1 year being male was associated with higher mortality (OR 1.12, 95% CI, 1.06 to 1.19). Conclusion: Although women are somewhat less intensively treated, especially regarding invasive procedures, after adjustment for differences in background characteristics, they have better long-term outcomes than men.

    Place, publisher, year, edition, pages
    BMJ Publishing group Ltd, 2007
    Keywords
    acute coronary syndrome, gender
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-47844 (URN)10.1136/hrt.2006.102012 (DOI)17085528 (PubMedID)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    2. Although women are less likely to be admitted to coronary care units, they are treated equally to men and have better outcome: A prospective cohort study in patients with non ST-elevation acute coronary syndromes
    Open this publication in new window or tab >>Although women are less likely to be admitted to coronary care units, they are treated equally to men and have better outcome: A prospective cohort study in patients with non ST-elevation acute coronary syndromes
    2009 (English)In: Acute cardiac care, ISSN 1748-295X, Vol. 11, no 3, p. 173-180Article in journal (Refereed) Published
    Abstract [en]

    Background: The aim of this study was to assess gender differences in admission level of care, management and outcome in patients with non ST-elevation acute coronary syndromes (NSTE-ACS), initially admitted to either coronary care units (CCU) or general wards. Method: Patients admitted to CCUs were routinely registered in the RIKS-HIA registry. In addition, patients admitted to general wards with suspected ACS were also identified and registered. Multivariable regression analysis was used to adjust for baseline differences between the genders. Results: We included 570 consecutive patients with a discharge diagnosis of NSTE-ACS. Women were less likely to be admitted to coronary care units (56% versus 69%, P=0.002), even after adjustment (odds ratio (OR), 0.65; 95% confidence interval (CI): 0.43-0.98). After adjustment for differences in baseline characteristics, women were treated similarly to men. We found no significant differences in crude short-, or long-term mortality between the genders. However, adjustment for background characteristics revealed lower one-year mortality in women (OR: 0.58; 95% CI: 0.34-0.99). Conclusion: In this study on patients with NSTE-ACS, women were less likely to be admitted to coronary care units. However, the overall treatment was as intensive for women as for men. Moreover, after adjustment, one-year mortality was lower in women.

    Place, publisher, year, edition, pages
    Informa Healthcare, 2009
    Keywords
    Myocardial infarction; NSTE-ACS; gender differences; level of care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53576 (URN)10.1080/17482940903215190 (DOI)19742351 (PubMedID)
    Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2013-09-11
    3.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    4. Similar outcome with an invasive strategy in men and women with Non ST-Elevation Acute Coronary Syndromes
    Open this publication in new window or tab >>Similar outcome with an invasive strategy in men and women with Non ST-Elevation Acute Coronary Syndromes
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Gender differences in benefit from an early invasive strategy in patients with Non ST-elevation Acute Coronary Syndromes (NSTE ACS) have been debated and results are conflicting. Some studies have even indicated harm for women associated with a routine invasive strategy.

    Method: We included 46 455 patients ( 14 819 women (32%) and 31 636 men (68%)) from The Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), with a diagnosis of either unstable angina pectoris or non-ST-elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 2000 and 2006, and followed for 1 year. Adjustment for baseline differences between the genders was made.

    Results: In the non-invasive strategy arm relative risk (RR) of death was (women vs. men) 1.02 (95% CI, 0.94-1.11) and in the invasive strategy arm 1.12 (95% CI, 0.96-1.29). After adjustment for baseline differences between the genders with propensity score and discharge medication there was a trend towards lower mortality among women, RR 0.90 (95% CI, 0.82-0.99) in the early non-invasive group but still no difference in the early invasive cohort RR 0.90 (95% CI, 0.76-1.06). Results were similar with the combined end-point death/MI. The risk reduction with an invasive strategy was similar in women (RR 0.46 (95% CI 0.38-0.55)) and men (RR 0.45 (95% CI 0.40-0.52).

    Conclusion: In this large cohort of patients with NSTE ACS, reflecting real life management, women and men had similar outcome and similar benefit with an early invasive strategy.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53578 (URN)
    Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2013-09-11
  • 19.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Gustafsson, Kerstin M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Logander, Elisabeth
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel: Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 2, p. 335-340Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.

    METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.

    CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.

  • 20.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Duke Clin Research Institute, NC USA.
    Neely, Benjamin
    Duke Clin Research Institute, NC USA.
    Neely, Megan L.
    Duke Clin Research Institute, NC USA.
    Bhatt, Deepak L.
    Brigham and Womens Hospital, MA 02115 USA; Harvard Medical Sch, MA USA.
    Goodman, Shaun G.
    St Michaels Hospital, Canada; University of Alberta, Canada; University of Alberta, Canada.
    Tricoci, Pierluigi
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Mahaffey, Kenneth W.
    Stanford University, CA 94305 USA.
    Cornel, Jan H.
    Medical Centre Alkmaar, Netherlands.
    White, Harvey D.
    Auckland City Hospital, New Zealand.
    Fox, Keith A. A.
    University of Edinburgh, Scotland.
    Prabhakaran, Dorairaj
    Centre Chron Disease Control and Public Health Fdn India, India.
    Winters, Kenneth J.
    Eli Lilly and Co, IN 46285 USA.
    Armstrong, Paul W.
    University of Alberta, Canada; University of Alberta, Canada.
    Magnus Ohman, E.
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Roe, Matthew T.
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 15, p. 1168-1176Article in journal (Refereed)
    Abstract [en]

    Objectives Dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome (ACS), with shorter durations considered for patients with increased bleeding risk. However, there are no decision support tools available to predict an individual patients bleeding risk during DAPT treatment in the post-ACS setting. Methods To develop a longitudinal bleeding risk prediction model, we analysed 9240 patients with unstable angina/non-ST segment elevation myocardial infarction (NSTEMI) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, who were managed without revascularisation and treated with DAPT for a median of 14.8 months. Results We identified 10 significant baseline predictors of non-coronary artery bypass grafting (CABG)-related Global Use of Strategies to Open Occluded Arteries (GUSTO) severe/life-threatening/moderate bleeding: age, sex, weight, NSTEMI (vs unstable angina), angiography performed before randomisation, prior peptic ulcer disease, creatinine, systolic blood pressure, haemoglobin and treatment with beta-blocker. The five significant baseline predictors of Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding included age, sex, angiography performed before randomisation, creatinine and haemoglobin. The models showed good predictive accuracy with Therneaus C-indices: 0.78 (SE=0.024) for the GUSTO model and 0.67 (SE=0.023) for the TIMI model. Internal validation with bootstrapping gave similar C-indices of 0.77 and 0.65, respectively. External validation demonstrated an attenuated C-index for the GUSTO model (0.69) but not the TIMI model (0.68). Conclusions Longitudinal bleeding risks during treatment with DAPT in patients with ACS can be reliably predicted using selected baseline characteristics. The TRILOGY ACS bleeding models can inform riskbenefit considerations regarding the duration of DAPT following ACS.

  • 21.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Roe, Matthew T
    Duke Clinical Research Institute, Durham, NC.
    Balancing the risks and benefits of long-term antiplatelet therapies for cardiovascular disease: clinical, research, and regulatory implications.2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 3, article id e001897Article in journal (Other academic)
  • 22.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Gustafsson, Kerstin M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Logander, Elisabeth
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Individual long-term variation of platelet reactivity in patients with dual antiplatelet therapy after myocardial infarction.2018In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, p. 1-7Article in journal (Refereed)
    Abstract [en]

    There is a large inter-individual variation in response to clopidogrel treatment, and previous studies have indicated higher risk of thrombotic events in those with high residual platelet reactivity (HPR). Less is known about individual variation over time. The aim of this prospective cohort study was to investigate intra-individual variation in platelet reactivity. Platelet aggregation in whole blood was assessed in 77 patients, at 3 days, 8 days and 6 months after admission for acute myocardial infarction and loading dose of clopidogrel. All patients were treated with aspirin and clopidogrel through 6-month follow-up. We found a significant increase in median ADP-stimulated aggregation from third to eighth day (195 vs. 250 AU*min, p-value = 0.001) but not from day 8 to 6 months (250 vs. 223 AU*min, p-value = 0.666). There was no significant change in the overall rate of HPR (15.6% vs 20.8%, p-value 0.503) or low platelet reactivity (LPR) (37.7% vs 33.8%, p-value = 0.609) from day 8 to 6-month follow-up. In contrast, more than one in four changed HPR status, 15.6% from non-HPR to HPR and 10.4% HPR to non-HPR. A shift in LPR status appeared even more frequent, occurring in about one of three patients. In spite of similar median aggregation and rate of HPR during 6-month follow-up, about one in four of the patients changed HPR status and one in three changed LPR status. This may be important information for a concept of risk stratification based on a single aggregation value early after an acute coronary syndromes.

  • 23.
    Alhede, Christina
    et al.
    Herlev Gentofte University Hospital, Denmark.
    Johannessen, Arne
    Herlev Gentofte University Hospital, Denmark.
    Dixen, Ulrik
    Hvidovre University Hospital, Denmark.
    Jensen, Jan S.
    Herlev Gentofte University Hospital, Denmark.
    Raatikainen, Pekka
    Helsinki University Hospital, Finland.
    Hindricks, Gerhard
    Leipzig University Hospital, Germany.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kongstad, Ole
    Lund University Hospital, Sweden.
    Pehrson, Steen
    Rigshosp, Denmark.
    Englund, Anders
    Örebro University Hospital, Sweden.
    Hartikainen, Juha
    Kupio University Hospital, Finland.
    Hansen, Peter S.
    Varde Heart Centre, Denmark.
    Nielsen, Jens C.
    Aarhus University Hospital, Denmark.
    Jons, Christian
    Rigshosp, Denmark.
    Higher burden of supraventricular ectopic complexes early after catheter ablation for atrial fibrillation is associated with increased risk of recurrent atrial fibrillation2018In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, no 1, p. 50-57Article in journal (Refereed)
    Abstract [en]

    Aims Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and amp;gt;= 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF amp;gt;= 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (amp;gt;= 783 SVEC: HR 4.6 [1.9-11.5], P amp;lt; 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence amp;lt; 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC amp;gt;= 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.

  • 24.
    Alhede, Christina
    et al.
    Herlev Gentofte University Hospital, Denmark.
    Lauridsen, Trine K.
    Herlev Gentofte University Hospital, Denmark.
    Johannessen, Arne
    Herlev Gentofte University Hospital, Denmark.
    Dixen, Ulrik
    Hvidovre University Hospital, Denmark.
    Jensen, Jan S.
    Herlev Gentofte University Hospital, Denmark.
    Raatikainen, Pekka
    Helsinki University Hospital, Finland.
    Hindricks, Gerhard
    Leipzig University Hospital, Germany.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kongstad, Ole
    Lund University Hospital, Sweden.
    Pehrson, Steen
    Rigshosp, Denmark.
    Englund, Anders
    Örebro University Hospital, Sweden.
    Hartikainen, Juha
    Kupio University Hospital, Finland.
    Hansen, Peter S.
    Varde Heart Centre, Denmark.
    Nielsen, Jens C.
    Aarhus University Hospital, Denmark.
    Jons, Christian
    Rigshosp, Denmark.
    Antiarrhythmic medication is superior to catheter ablation in suppressing supraventricular ectopic complexes in patients with atrial fibrillation2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 244, p. 186-191Article in journal (Refereed)
    Abstract [en]

    Background: Supraventricular ectopic complexes (SVEC) originating in the pulmonary veins are known triggers of atrial fibrillation (AF) which led to the development of pulmonary vein isolation for AF. However, the long-term prevalence of SVEC after catheter ablation (CA) as compared to antiarrhythmic medication (AAD) is unknown. Our aims were to compare the prevalence of SVEC after AAD and CA and to estimate the association between baseline SVEC burden and AF burden during 24 months of follow-up. Methods: Patients with paroxysmal AF (N = 260) enrolled in the MANTRA PAF trial were treated with AAD (N = 132) or CA (N = 128). At baseline and 3, 6, 12, 18 and 24 months follow-up patients underwent 7-day Holter monitoring to assess SVEC and AF burden. We compared SVEC burden between treatments with Wilcoxon sum rank test. Results: Patients treated with AAD had significantly lower daily SVEC burden during follow-up as compared to CA (AAD: 19 [6-58] versus CA: 39 [14-125], p = 0.003). SVEC burden increased post-procedurally followed by a decrease after CA whereas after AAD SVEC burden decreased and stabilized after 3 months of follow-up. Patients with low SVEC burden had low AF burden after both treatments albeit this was more pronounced after CA at 24 months of follow-up. Conclusion: AAD was superior to CA in suppressing SVEC burden after treatment of paroxysmal AF. After CA SVEC burden increased immediately post-procedural followed by a decrease whereas after AAD an early decrease was observed. Lower SVEC burden was highly associated with lower AF burden during follow-up especially after CA. (C) 2017 Elsevier B.V. All rights reserved.

  • 25.
    Alhede, Christina
    et al.
    Herlev Gentofte University Hospital, Denmark.
    Lauridsen, Trine K.
    Herlev Gentofte University Hospital, Denmark.
    Johannessen, Arne
    Herlev Gentofte University Hospital, Denmark.
    Dixen, Ulrik
    Hvidovre University Hospital, Denmark.
    Jensen, Jan S.
    Herlev Gentofte University Hospital, Denmark.
    Raatikainen, Pekka
    Helsinki University Hospital, Finland.
    Hindricks, Gerhard
    Leipzig University Hospital, Germany.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Kongstadf, Ole
    Lund University Hospital, Sweden.
    Pehrson, Steen
    Rigshosp, Denmark.
    Englund, Anders
    Örebro University Hospital, Sweden.
    Hartikainen, Juha
    Kupio University Hospital, Finland.
    Hansen, Peter S.
    Varde Heart Centre, Denmark.
    Nielsen, Jens C.
    Aarhus University Hospital, Denmark.
    Jons, Christian
    Rigshosp, Denmark.
    The impact of supraventricular ectopic complexes in different age groups and risk of recurrent atrial fibrillation after antiarrhythmic medication or catheter ablation2018In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 250, p. 122-127Article in journal (Refereed)
    Abstract [en]

    Introduction: Supraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients +/- 57 years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA). Methods: In total, 260 patients with LVEF amp;gt;40% and age amp;lt;= 70 years were randomized to AAD (N = 132) or CA (N = 128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24 months and were categorized according to median age +/- 57 years. We used multi-variate Cox regression analyses and we defined high SVEC burden at 3 months of follow-up as the upper 75th percentile amp;gt;195 SVEC/day. AF recurrence was defined as AF amp;gt;= 1 min, AF-related cardioversion or hospitalization. Results: Age amp;gt;57 years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p = 0.02). After CA, we observed a higher SVEC burden during follow-up in patients amp;gt;57 years which was not observed in the younger age group treatedwith CA (p = 0.006). High SVEC burden at 3 months after CA was associated with AF recurrence in older patients but not in younger patients (amp;gt;57 years: HR 3.4 [1.4-7.9], p = 0.005). We did not find any age-related differences after AAD. Conclusion: We found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients. (C) 2017 Elsevier B.V. All rights reserved.

  • 26.
    Andell, Pontus
    et al.
    Lund Univ, Sweden.
    Berntorp, Karolina
    Lund Univ, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Denmark.
    Gudmundsdottir, Ingibjorg J.
    Univ Hosp Iceland, Iceland.
    Sandhall, Lennart
    Helsingborg Hosp, Sweden.
    Venetsanos, Dimitrios
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Erlinge, David
    Lund Univ, Sweden.
    Frobert, Ole
    Orebro Univ, Sweden.
    Koul, Sasha
    Lund Univ, Sweden.
    Reitan, Christian
    Lund Univ, Sweden.
    Gotberg, Matthias
    Lund Univ, Sweden.
    Reclassification of Treatment Strategy With Instantaneous Wave-Free Ratio and Fractional Flow Reserve A Substudy From the iFR-SWEDEHEART Trial2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 20, p. 2084-2094Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). BACKGROUND iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking. METHODS The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements. RESULTS In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p amp;lt; 0.01). CONCLUSIONS Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated. (c) 2018 by the American College of Cardiology Foundation.

  • 27.
    Andersson, Per
    et al.
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Karlsson, Jan-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Department of Internal Medicine, County Council of Jönköping, Jönköping.
    Landberg, Eva
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Festin, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Staffan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Norrköping, Sweden.
    Consequences of high-sensitivity troponin T testing applied in a primary care population with chest pain compared with a commercially available point-of-care troponin T analysis: an observational prospective study2015In: BMC Research Notes, ISSN 1756-0500, E-ISSN 1756-0500, Vol. 8, no 1, p. 1-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:There is a demand for a highly sensitive and specific point-of care test to detect acute myocardial infarction (AMI). It is unclear if a high-sensitivity troponin assay will have enough discriminative power to become a decision support in primary care. The aim of this study was to evaluate a high-sensitivity troponin T assay performed in three primary health care centres in southeast Sweden and to compare the outcome with a point-of-care troponin T test.METHODS:This study included 115 patients who consulted their general practitioner for chest pain, dyspnoea on exertion, unexplained weakness and/or fatigue in the last 7days. Troponin T was analysed by a point-of-care test and a high-sensitivity method together with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatinine. All patients were checked for AMI or unstable angina (UA) within 30days of study enrolment. Univariate and multivariate logistic regression was carried out to examine possible connections between troponin T[greater than or equal to]15ng/L, clinical variables and laboratory findings at baseline. In addition, 21 patients with troponin T[greater than or equal to]15ng/L and no signs of AMI or UA were followed up for 2-3years.RESULTS:Three patients were diagnosed with AMI and three with UA. At the [greater than or equal to]15ng/L cut-off, the troponin T method had 100% sensitivity, 75% specificity for AMI and a positive predictive value of 10%. The troponin T point-of-care test missed one case of AMI and the detection limit was 50ng/L. Troponin T[greater than or equal to]15ng/L was correlated to age [greater than or equal to]65years (odds ratio (OR), 10.9 95% CI 2.28-51.8) and NT-proBNP in accordance with heart failure (OR 8.62 95% CI 1.61-46.1). Fourteen of the 21 patients, without signs of AMI or UA at baseline, still had increased troponin T at follow-up after 2-3years.CONCLUSIONS:A high-sensitivity troponin T assay could become useful in primary care as a point-of-care test for patients <65years. For patients older than 65-70years, a higher decision limit than [greater than or equal to]15ng/L should be considered and used in conjunction with clinical parameters and possibly with NT-proBNP.

  • 28.
    Andreae, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Appetite in patients with heart failure: Assessment, prevalence and related factors2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Appetite is an important component in nutrition for maintaining the food intake needed by the body. Decreased appetite is a common clinical problem in patients with heart failure. It has a negative impact on food intake and possibly on malnutrition and health outcomes. There is a lack of evidence on how to assess appetite in heart failure. Furthermore, there are knowledge gaps about factors associated with appetite and which role appetite plays for health status in heart failure.  

    Aim: The overall aim of the thesis was to investigate appetite in patients with heart failure. Four studies were conducted with the goal to evaluate the psychometric properties of the Council on Nutrition Appetite Questionnaire (CNAQ) (I) and to explore the prevalence of decreased appetite and related factors associated with appetite in patients with heart failure (II-IV).  

    Methods: A multicenter study was conducted in three outpatient heart failure clinics in the center of Sweden during 2009-2012. Data were collected through a baseline measurement (I-IV) and an 18-month follow-up (IV). The first study was a psychometric evaluation study (I), while the other studies had an observational cross-sectional design (II-III) and an observational prospective design (IV). One hundred and eighty-six patients diagnosed with heart failure and experiencing heart failure symptoms participated at baseline. At the 18-month follow-up study (IV), one hundred and sixteen participants from the baseline participated. Data were collected from medical records (pharmacological treatment, comorbidity, left ventricle ejection fraction, time of diagnosis), self-reported questionnaires (demographic background data, appetite, symptoms of depression, health status, sleep, self-reported physical activity), objective measurements (anthropometric assessment of body size, blood samples, six minutes’ walk test, and physical activity measured with an actigraph) and clinical assessment (New York Heart Association (NYHA) functional classification, and cognitive assessment). The main outcome variables included appetite (I, II and IV) and health status (III). Descriptive and inferential statistics were used in the studies (I-IV).  

    Results: The majority of the participants had moderate heart failure symptoms, i.e., NYHA class II (n=114, 61%). Most of the participants were men (n=130, 70%). Mean age was 70,7 years, (SD=11,0), and mean BMI was 28.7 (SD=5.3). The CNAQ showed acceptable psychometric properties for assessing appetite in patients with heart failure (I). This thesis shows that 38% of the participants experienced an appetite level that put them at risk of weight loss (I). It was shown that factors such as biological, medical, psychological (II) and physical activity/exercise capacity (IV) are associated with appetite. Also, appetite was associated with impaired health status. However, this association was found to be moderated by symptoms of depression (III). Neither appetite nor physical activity changed during the 18-month follow-up (IV).  

    Conclusion: Decreased appetite is a serious phenomenon that needs attention in the care of patients with heart failure. Health care professionals can now use a validated and simple appetite instrument to assess appetite in heart failure. In addition, attention should be paid to elderly patients and those who have symptoms of depression, sleep problems, impaired cognitive function and impaired physical activity, as well as to patients on suboptimal medical treatment. Higher appetite was shown to contribute to a better health status, but this was only evident in patients without symptoms of depression. Therefore, special attention should be paid to symptoms of depression, as this risk factor affected the association between appetite and health status. This thesis enhances the understanding of the magnitude of the problem with decreased appetite in heart failure both in numbers and factors. New priorities in nutrition care and new ideas can be established, both in practice and in research, in order to improve a nutrition care that is vital for patients with heart failure.  

    List of papers
    1. Psychometric Evaluation of Two Appetite Questionnaires in Patients With Heart Failure
    Open this publication in new window or tab >>Psychometric Evaluation of Two Appetite Questionnaires in Patients With Heart Failure
    2015 (English)In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 21, no 12, p. 954-958Article in journal (Refereed) Published
    Abstract [en]

    Background: Decreased appetite in heart failure (HF) may lead to undemutrition which could negatively influence prognosis. Appetite is a complex clinical issue that is often best measured with the use of self-report instruments. However, there is a lack of self-rated appetite instruments. The Council on Nutrition Appetite Questionnaire (CNAQ) and the Simplified Nutritional Appetite Questionnaire (SNAQ) are validated instruments developed primarily for elderly people. Yet, the psychometric properties have not been evaluated in HF populations. The aim of the present study was to evaluate the psychometric properties of CNAQ and SNAQ in patients with HE Methods and Results: A total of 186 outpatients with reduced ejection fraction and New York Heart Association (NYHA) functional classifications II-IV were included (median age 72 y; 70% men). Data were collected with the use of a questionnaire that included the CNAQ and SNAQ. The psychometric evaluation included data quality, factor structure, construct validity, known-group validity, and internal consistency. Unidimensionality was supported by means of parallel analysis and confirmatory factor analyses (CFAs). The CFA results indicated sufficient model fit. Both construct validity and known-group validity were supported. Internal consistency reliability was acceptable, with ordinal coefficient alpha estimates of 0.82 for CNAQ and 0.77 for SNAQ. Conclusions: CNAQ and SNAQ demonstrated sound psychometric properties and can be used to measure appetite in patients with HF.

    Place, publisher, year, edition, pages
    CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS, 2015
    Keywords
    Appetite; heart failure; outpatient; psychometrics
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-123773 (URN)10.1016/j.cardfail.2015.10.006 (DOI)000366230900004 ()26497759 (PubMedID)
    Note

    Funding Agencies|Center for Clinical Research and Sormland County Council, Sweden; Swedish Heart and Lung Foundation; King Gustaf V and Queen Victorias Freemason Foundation; Medical Research Council of Southeast Sweden; Canadian Institutes of Health Research

    Available from: 2016-01-11 Created: 2016-01-11 Last updated: 2018-03-14
    2. Prevalence and associated factors for decreased appetite among patients with stable heart failure
    Open this publication in new window or tab >>Prevalence and associated factors for decreased appetite among patients with stable heart failure
    2016 (English)In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 25, no 11-12, p. 1703-1712Article in journal (Refereed) Published
    Abstract [en]

    Aims and objectivesTo explore the prevalence of decreased appetite and factors associated with appetite among patients with stable heart failure. BackgroundDecreased appetite is an important factor for the development of undernutrition among patients with heart failure, but there are knowledge gaps about prevalence and the factors related to appetite in this patient group. DesignObservational, cross-sectional study. MethodsA total of 186 patients with mild to severe heart failure were consecutively recruited from three heart failure outpatient clinics. Data were obtained from medical records (heart failure diagnosis, comorbidity and medical treatment) and self-rated questionnaires (demographics, appetite, self-perceived health, symptoms of depression and sleep). Blood samples were taken to determine myocardial stress and nutrition status. Heart failure symptoms and cognitive function were assessed by clinical examinations. The Council on Nutrition Appetite Questionnaire was used to assess self-reported appetite. Bivariate correlations and multivariate linear regression analyses were conducted to explore factors associated with appetite. ResultsSeventy-one patients (38%) experienced a loss of appetite with a significant risk of developing weight loss. The final multiple regression model showed that age, symptoms of depression, insomnia, cognitive function and pharmacological treatment were associated with appetite, explaining 27% of the total variance. ConclusionIn this cross-sectional study, a large share of patients with heart failure was affected by decreased appetite, associated with demographic, psychosocial and medical factors. Relevance to clinical practiceLoss of appetite is a prevalent problem among patients with heart failure that may lead to undernutrition. Health care professionals should routinely assess appetite and discuss patients experiences of appetite, nutrition intake and body weight and give appropriate nutritional advice with respect to individual needs.

    Place, publisher, year, edition, pages
    WILEY-BLACKWELL, 2016
    Keywords
    age; appetite; cognitive function; depression; heart failure; insomnia; outpatient; pharmacological treatment
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-128929 (URN)10.1111/jocn.13220 (DOI)000375866200022 ()26879764 (PubMedID)
    Note

    Funding Agencies|Centre for Clinical Research Sormland, Uppsala University, Eskilstuna, Sweden; Swedish Heart and Lung Foundation; King Gustaf V and Queen Victorias Freemason Foundation; Medical Research Council of Southeast Sweden

    Available from: 2016-06-09 Created: 2016-06-07 Last updated: 2018-03-14
    3. Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure
    Open this publication in new window or tab >>Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure
    Show others...
    2018 (English)In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 2, p. E15-E20Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Decreased appetite and depressive symptoms are clinical problems in patients with heart failure. Both may result in impaired health status.

    OBJECTIVE: The aims of this study were to investigate the association between appetite and health status in patients with heart failure and to explore whether depressive symptoms moderate this association.

    METHODS: In this cross-sectional study, patients with heart failure (n = 186; mean age, 71 years), New York Heart Association class II to IV, participated. Data on appetite (Council of Nutrition Appetite Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and health status (EQ-5D 3-level scale [EQ-5D-3L] descriptive system, EQ-5D-3L index, and EQ Visual Analog Scale) were collected by self-rating questionnaires. Pearson correlation was used to investigate the association between appetite and health status. Multiple regression was performed to examine whether depressive symptoms moderate the association between appetite and health status.

    RESULTS: There was a significant association between appetite and health status for EQ-5D-3L descriptive system, mobility (P < .001), pain/discomfort (P < .001), and anxiety/depression (P < .001). This association was also shown in EQ-5D-3L index (P < .001) and EQ Visual Analog Scale (P < .001). Simple slope analysis showed that the association between appetite and health status was only significant for patients without depressive symptoms (B = 0.32, t = 4.66, P < .001).

    CONCLUSIONS: Higher level of appetite was associated with better health status. In moderation analysis, the association was presented for patients without depressive symptoms. Decreased appetite is an important sign of poor health status. To improve health status, health professionals should have greater attention on appetite, as well on signs of depressive symptoms.

    Place, publisher, year, edition, pages
    Wolters Kluwer, 2018
    Keywords
    appetite, association, depression, health status, heart failure, nutritional status
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-139105 (URN)10.1097/JCN.0000000000000428 (DOI)000440241700003 ()28574973 (PubMedID)2-s2.0-85020167287 (Scopus ID)
    Available from: 2017-07-01 Created: 2017-07-01 Last updated: 2018-09-27Bibliographically approved
  • 29.
    Andreae, Christina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Chung, Misook L
    College of Nursing, University of Kentucky, Lexington, USA.
    Hjelm, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Årestedt, Kristofer
    Linnaeus University, Kalmar, Kalmar County Hospital, Kalmar Sweden.
    Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure2018In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 2, p. E15-E20Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Decreased appetite and depressive symptoms are clinical problems in patients with heart failure. Both may result in impaired health status.

    OBJECTIVE: The aims of this study were to investigate the association between appetite and health status in patients with heart failure and to explore whether depressive symptoms moderate this association.

    METHODS: In this cross-sectional study, patients with heart failure (n = 186; mean age, 71 years), New York Heart Association class II to IV, participated. Data on appetite (Council of Nutrition Appetite Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and health status (EQ-5D 3-level scale [EQ-5D-3L] descriptive system, EQ-5D-3L index, and EQ Visual Analog Scale) were collected by self-rating questionnaires. Pearson correlation was used to investigate the association between appetite and health status. Multiple regression was performed to examine whether depressive symptoms moderate the association between appetite and health status.

    RESULTS: There was a significant association between appetite and health status for EQ-5D-3L descriptive system, mobility (P < .001), pain/discomfort (P < .001), and anxiety/depression (P < .001). This association was also shown in EQ-5D-3L index (P < .001) and EQ Visual Analog Scale (P < .001). Simple slope analysis showed that the association between appetite and health status was only significant for patients without depressive symptoms (B = 0.32, t = 4.66, P < .001).

    CONCLUSIONS: Higher level of appetite was associated with better health status. In moderation analysis, the association was presented for patients without depressive symptoms. Decreased appetite is an important sign of poor health status. To improve health status, health professionals should have greater attention on appetite, as well on signs of depressive symptoms.

  • 30.
    Andreassen, A.K.
    et al.
    University of Oslo, Norway .
    Andersson, B.
    Sahlgrens University Hospital, Sweden .
    Gustafsson, F.
    Rigshosp, Denmark .
    Eiskjaer, H.
    Aarhus University Hospital, Denmark .
    Rdegran, G.
    Skåne University Hospital, Sweden Lund University, Sweden .
    Gude, E.
    University of Oslo, Norway .
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Solbu, D.
    Novartis Norge AS, Norway .
    Sigurdardottir, V.
    Sahlgrens University Hospital, Sweden .
    Arora, S.
    University of Oslo, Norway .
    Dellgren, G.
    Sahlgrens University Hospital, Sweden .
    Gullestad, L.
    University of Oslo, Norway University of Oslo, Norway University of Oslo, Norway .
    Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial2014In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, no 8, p. 1828-1838Article in journal (Refereed)
    Abstract [en]

    In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6 ng/mL) with reduced-exposure cyclosporine (n 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean +/- SD: 79.8 +/- 17.7 mL/min/1.73m 2 vs. 61.5 +/- 19.6 mL/min/1.73m 2; pless than0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, pless than0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.

  • 31.
    Appelros, Peter
    et al.
    University of Örebro, Sweden.
    Hals Berglund, Maria
    University Hospital Norrland, Sweden.
    Ström, Jakob O.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry. University of Örebro, Sweden.
    Long-Term Risk of Stroke after Transient Ischemic Attack2017In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 43, no 1-2, p. 25-30Article in journal (Refereed)
    Abstract [en]

    Background: In the absence of active management, the stroke risk after a transient ischemic attack (TIA) may be high. Almost 10 years ago, the results of the EXPRESS and SOS-TIA studies called for a more rapid management of TIA patients. The purpose of this study was to investigate the other stroke risks in the longer term, after the implementation of a more active approach to TIA. We also wanted to assess the predictive value of the ABCD2 score in this context. Methods: Riksstroke is the national stroke registry in Sweden. Data from Riksstrokes TIA module, and the national cause-of-death register, for the years 2011 and 2012 were used in this study. Stroke occurrence was monitored via Riksstroke. Coxs regression was used for risk evaluation. The predictive value of the ABCD2 score was assessed by calculating the area under the receiver operating characteristics curve. Results: A total of 15,068 TIA episodes occurred in 14,102 patients. The follow-up time varied between 0 and 819 days, with an average of 417 days. The mortality for all TIA patients during the follow-up time was 7.1%. Of the unique patients, 545 had one or more strokes (3.9%), corresponding to 34 events per 1,000 person years. Significant risk factors for stroke were: age, previous TIA, atrial fibrillation (AF), oral anticoagulant (OAC) treatment, hypertension treatment, and the ABCD2 items speech impairment, unilateral weakness, and diabetes mellitus. The ABCD2 score correlated with a subsequent stroke, but its predictive value was low. Conclusion: The risk of stroke is low after the acute phase of a TIA, probably lower than in previous studies. This may be due to better secondary prevention in recent years. Several risk factors predict stroke, notably hypertensive treatment, which may be inadequate; and AF, where OACs may be under-used. It is difficult to identify the role of the ABCD2 score in clinical practice. (C) 2016 S. Karger AG, Basel

  • 32.
    Bagai, Akshay
    et al.
    Univ Toronto, Canada.
    Goodman, Shaun G.
    Univ Toronto, Canada; Univ Toronto, Canada.
    Cantor, Warren J.
    Univ Toronto, England.
    Vicaut, Eric
    Hop Lariboisiere, France.
    Bolognese, Leonardo
    Azienda Osped Arezzo, Italy.
    Cequier, Angel
    Univ Barcelona, Spain.
    Chettibi, Mohamed
    Ctr Hosp Univ Frantz Fanon, Algeria.
    Hammett, Christopher J.
    Royal Brisbane and Womens Hosp, Australia.
    Huber, Kurt
    Wilhelminenhosp, Austria; Sigmund Freud Private Univ, Austria.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lapostolle, Frederic
    Hop Avicenne, France.
    Lassen, Jens Flensted
    Univ Copenhagen, Denmark.
    Merkely, Bela
    Semmelweis Univ, Hungary.
    Storey, Robert F.
    Univ Sheffield, England.
    ten Berg, Jurrien M.
    St Antonius Hosp Nieuwegein, Netherlands.
    Zeymer, Uwe
    Klinikum Ludwigshafen, Germany; Inst Herzinfarktforsch Ludwigshafen, Germany.
    Diallo, Abdourahmane
    Hop Lariboisiere, France; Hop Fernand Widal, France.
    Hamm, Christian W.
    Kerckhoff Klin, Germany.
    Tsatsaris, Anne
    AstraZeneca, France.
    El Khoury, Jad
    AstraZeneca, England.
    vant Hof, Arnoud W.
    Maastricht Hart Vaat Ctr MUMC, Netherlands.
    Montalescot, Gilles
    Sorbonne Univ Paris 6, France.
    Duration of ischemia and treatment effects of pre- versus in-hospital ticagrelor in patients with ST-segment elevation myocardial infarction: Insights from the ATLANTIC study2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 196, p. 56-64Article in journal (Refereed)
    Abstract [en]

    Background Among patients with STEMI in the ATLANTIC study, pre-hospital administration of ticagrelor improved post-PCI ST-segment resolution and 30-day stent thrombosis. We investigated whether this clinical benefit with pre-hospital ticagrelor differs by ischemic duration. Methods In a post hoc analysis we compared absence of ST-segment resolution post-PCI and stent thrombosis at 30 days between randomized treatment groups (pre-versus in-hospital ticagrelor) stratified by symptom onset to first medical contact (FMC) duration [amp;lt;= 1 hour (n = 773), amp;gt;1 to amp;lt;= 3 hours (n = 772), and amp;gt;3 hours (n = 311)], examining the interaction between randomized treatment strategy and duration of symptom onset to FMC for each outcome. Results Patients presenting later after symptom onset were older, more likely to be female, and have higher baseline risk. Patients with symptom onset to FMC amp;gt;3 hours had the greatest improvement in post-PCI ST-segment elevation resolution with pre-versus in-hospital ticagrelor (absolute risk difference: amp;lt;= 1 hour, 2.9% vs. amp;gt;1 to amp;lt;= 3 hours, 3.6% vs. amp;gt;3 hours, 12.2%; adjusted p for interaction = 0.13), while patients with shorter duration of ischemia had greater improvement in stent thrombosis at 30 days with pre-versus in-hospital ticagrelor (absolute risk difference: amp;lt;= 1 hour, 1.3% vs. amp;gt;1 hour to amp;lt;= 3hours, 0.7% vs. amp;gt;3 hours, 0.4%; adjusted p for interaction = 0.55). Symptom onset to active ticagrelor administration was independently associated with stent thrombosis at 30 days (adjusted OR 1.89 per 100 minute delay, 95% CI 1.20-2.97, P amp;lt; .01), but not post-PCI ST-segment resolution (P = .41). Conclusions The effect of pre-hospital ticagrelor to reduce stent thrombosis was most evident when given early within 3 hours after symptom onset, with delay in ticagrelor administration after symptom onset associated with higher rate of stent thrombosis. These findings re-emphasize the need for early ticagrelor administration in primary PCI treated STEMI patients.

  • 33.
    Bank, Ingrid E. M.
    et al.
    University of Medical Centre Utrecht, Netherlands.
    Gijsberts, Crystel M.
    University of Medical Centre Utrecht, Netherlands; ICIN Netherlands Heart Institute, Netherlands.
    Teng, Tiew-Hwa K.
    Singhealth, Singapore.
    Benson, Lina
    Karolinska Institute, Sweden.
    Sim, David
    Singhealth, Singapore.
    Shuan Daniel Yeo, Poh
    Tan Tock Seng Hospital, Singapore.
    Yee Ong, Hean
    Khoo Teck Puat Hospital, Singapore.
    Jaufeerally, Fazlur
    Singapore Gen Hospital, Singapore.
    Leong, Gerard K. T.
    Changi Gen Hospital, Singapore.
    Ling, Lieng H.
    National University, Singapore; National University of Health Syst, Singapore.
    Richards, A. Mark
    National University, Singapore; University of Otago, New Zealand.
    de Kleijn, Dominique P. V.
    University of Medical Centre Utrecht, Netherlands; National University, Singapore.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska University Hospital, Sweden.
    Lam, Carolyn S. P.
    Singhealth, Singapore; National University, Singapore; National University, Singapore; Duke NUS Medical Sch, Singapore.
    Prevalence and Clinical Significance of Diabetes in Asian Versus White Patients With Heart Failure2017In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 5, no 1, p. 14-24Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The study sought to compare the prevalence, clinical correlates and prognostic impact of diabetes in Southeast Asian versus white patients with heart failure (HF) with preserved or reduced ejection fraction. BACKGROUND Diabetes mellitus is common in HF and is associated with impaired prognosis. Asia is home to the majority of the worlds diabetic population, yet data on the prevalence and clinical significance of diabetes in Asian patients with HF are sparse, and no studies have directly compared Asian and white patients. METHODS Two contemporary population-based HF cohorts were combined: from Singapore (n 1,002, median [25th to 75th percentile] age 62 [54 to 70] years, 76% men, 19.5% obesity) and Sweden (n =19,537, 77 [68 to 84] years, 60% men, 24.8% obesity). The modifying effect of ethnicity on the relationship between diabetes and clinical correlates or prognosis (HF hospitalization and all-cause mortality) was examined using interaction terms. RESULTS Diabetes was present in 569 (57%) Asian patients versus 4,680 (24%) white patients (p amp;lt; 0.001). Adjusting for clinical covariates, obesity was more strongly associated with diabetes in white patients (odds ratio [OR]: 3.45;. 95% confidence interval [CI]: 2.86 to 4.17) than in Asian patients (OR: 1.82; 95% CI: 1.13 to 2.96; P-interaction = 0.026). Diabetes was more strongly associated with increased HF hospitalization and all-cause mortality in Asian patients (hazard ratio: 1.50; 95% CI: 1.21 to 1.87) than in white patients (hazard ratio: 1.29; 95% CI: 1.22 to 1.36; P-interaction = 0.045). CONCLUSIONS Diabetes was 3-fold more common in Southeast Asian compared to white patients with HF, despite younger age and less obesity, and more strongly associated with poor outcomes in Asian patients than white patients. These results underscore the importance of ethnicity-tailored aggressive strategies to prevent diabetes and its complications. (C) 2017 by the American College of Cardiology Foundation.

  • 34. Baranowski, Jacek
    et al.
    Nielsen, Niels-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    TAVI without BAV2014Conference paper (Refereed)
  • 35.
    Baranowski, Jacek
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nielsen, Niels-Erik
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    A simplified protocol for transcatheter aortic valve implantation that reduces procedure-related risk2016In: Journal of Cardiovascular Diseases & Diagnosis, E-ISSN 2329-9517, Vol. 4, no 3, article id 1000241Article in journal (Refereed)
    Abstract [en]

    Objectives: Transcatheter Aortic Valve Implantation is now a well-established procedure and continuous development has improved the technique. The object of this paper is to describe the successive steps taken at our department to improve our protocol, resulting in a more effective and patient-safe procedure.

    Design: An echo-guided method for aortic cusp alignment was used in 229 patients. In 139 patients pre-dilatation was excluded from the protocol. In the last 47 of the patients we exchanged the stiff guide-wire in the left ventricle with a soft wire for valve placement.

    Results: There was a significant decrease in the use of contrast medium during the period with 90% of patients receiving less than 50 ml contrast and 35% no contrast at all. In more than half the patients we only used rapid pacing in association with deployment of the stent valve. We had six cases ofpericardial bleeding due to penetration of the stiff guide wire through the left ventricular (LV) wall. This complication was avoided in all subsequent patients where we exchanged the stiff catheter to a soft guidewire in the ascending aorta before introduction of the wire and stent valve into the LV.

    Conclusions: We have successively modified our standard protocol for implantation of a balloon-expandable transcatheter aortic valve. This has simplified the procedure and reduced the risk for certain procedure-related complications.

  • 36. Baranowski, Jacek
    et al.
    Nielsen, Niels-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Total percutaneuous transcatheter valve implantation in native mitral stenosis in a patient with previous transapical TAVI2014Conference paper (Refereed)
  • 37. Baranowski, Jacek
    et al.
    Wallby, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Ahn, Henrik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Dahlin, Lars-Göran
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lindgren, B
    Freter, W
    Johansson, M
    Nielsen, Niels-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    TAVI without balloon predilation. A ramdomized single centre study.2014Conference paper (Refereed)
  • 38. Baranowski, Jacek
    et al.
    Wallby, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Boano, Gabriella
    Vanky, Farkas
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Löfstöm, Lars
    Johansson, Mats
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nielsen, Niels-Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    MitraClip after myocardial infarction with papillary muscle rupture and as treatment of systolic anterior motion of the mitral valve.2014Conference paper (Refereed)
  • 39.
    Baubeta Fridh, Erik
    et al.
    Ryhov Cty Hosp, Sweden; Gothenburg Univ, Sweden.
    Andersson, Manne
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov Cty Hosp, Sweden.
    Thuresson, Marcus
    Statisticon AB, Sweden.
    Sigvant, Birgitta
    Karlstad Cent Hosp, Sweden; Uppsala Univ, Sweden.
    Kragsterman, Bjorn
    Uppsala Univ, Sweden.
    Johansson, Saga
    AstraZeneca Nord Balt, Sweden.
    Hasvold, Pal
    AstraZeneca Gothenburg, Sweden.
    Nordanstig, Joakim
    Gothenburg Univ, Sweden.
    Falkenberg, Marten
    Gothenburg Univ, Sweden.
    Editors Choice - Impact of Comorbidity, Medication, and Gender on Amputation Rate Following Revascularisation for Chronic Limb Threatening Ischaemia2018In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 56, no 5, p. 681-688Article in journal (Refereed)
    Abstract [en]

    Objective/background: Chronic limb threatening ischaemia (CLTI) has a high risk of amputation and mortality. Increased knowledge on how sex, comorbidities, and medication influence these outcomes after revascularisation may help optimise results and patient selection. Methods: This population based observational cohort study included all individuals revascularised for CLTI in Sweden during a five year period (10,617 patients in total). Data were retrieved and merged from mandatory national healthcare registries, and specifics on amputations were validated with individual medical records. Results: Mean age at revascularisation was 76.8 years. Median follow up was 2.7 years (range 0-6.6 years). Male sex (hazard ratio [HR] 1.20, 95% confidence interval [CI] 1.09-1.33), renal insufficiency (HR 1.57, 95% CI 1.32-1.87), diabetes (HR 1.45, 95% CI 1.32-1.60), and heart failure (HR 1.17, 95% CI 1.05-1.31) were independently associated with an increased amputation rate, whereas the use of statins (HR 0.71, 95% CI 0.64-0.78) and low dose acetylsalicylic acid (HR 0.77, 95% CI 0.70-0.86) were associated with a reduced amputation rate. For the combined end point of amputation or death, an association with increased rates was found for male sex (HR 1.25, 95% CI 1.18-1.32), renal insufficiency (HR 1.94, 95% CI 1.75-2.14), heart failure (HR 1.50, 95% CI 1.40-1.60), and diabetes (HR 1.31, 95% CI 1.23-1.38). The use of statins (HR 0.74, 95% CI 0.67-0.82) and low dose acetylsalicylic acid (HR 0.82, 95% CI 0.77-0.881) were related to a reduced risk of amputation or death. Conclusions: Renal insufficiency is the strongest independent risk factor for both amputation and amputation/ death in revascularised CLTI patients, followed by diabetes and heart failure. Men with CLTI have worse outcomes than women. These results may help govern patient selection for revascularisation procedures. Statin and low dose acetylsalicylic acid are associated with an improved limb outcome. This underlines the importance of preventive medication to reduce general cardiovascular risk and increase limb salvage. (C) 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

  • 40.
    Baubeta Fridh, Erik
    et al.
    Ryhov County Hospital, Sweden; University of Gothenburg, Sweden.
    Andersson, Manne
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Ryhov County Hospital, Sweden.
    Thuresson, Marcus
    Statisticon AB, Sweden.
    Sigvant, Birgitta
    Karlstad Central Hospital, Sweden; Karolinska Institute, Sweden.
    Kragsterman, Björn
    Uppsala University, Sweden.
    Johansson, Saga R.
    AstraZeneca Gothenburg, Sweden.
    Hasvold, Pål
    AstraZeneca Nordic Balt, Sweden.
    Falkenberg, Mårten
    University of Gothenburg, Sweden.
    Nordanstig, Joakim
    Gothenburg University, Sweden; Gothenburg University, Sweden.
    Amputation Rates, Mortality, and Pre-operative Comorbidities in Patients Revascularised for Intermittent Claudication or Critical Limb Ischaemia: A Population Based Study2017In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 54, no 4, p. 480-486Article in journal (Refereed)
    Abstract [en]

    Objectives

    The aims of this population based study were to describe mid- to long-term amputation risk, cumulative incidence of death or amputation, and differences in pre-operative comorbidities in patients revascularised for lower limb peripheral artery disease (PAD).

    Methods

    This was an observational cohort study. Data from the Swedish National Quality Registry for Vascular Surgery (Swedvasc) were combined with mandatory national health care registries and patient medical records. All patients who underwent revascularisation in Sweden between May 2008 and May 2013 for intermittent claudication (IC) or critical limb ischaemia(CLI), aged 50 years and older, were identified through the Swedvasc database. The mandatory national health care registries and medical records provided data on comorbidities, mortality, and major amputations.

    Results

    A total of 16,889 patients with PAD (IC, n = 6272; CLI, n = 10,617) were studied. The incidence of amputations in IC patients was 0.4% (range 0.3%–0.5%) per year. Among CLI patients, the amputation rate during the first 6 months following revascularisation was 12.0% (95% CI 11.3–12.6). Thereafter, the incidence declined to approximately 2% per year. The cumulative combined incidence of death or amputation 3 years after revascularisation was 12.9% (95% CI 12.0–13.9) in IC patients and 48.8% (95% CI 47.7–49.8) in CLI patients. Among CLI patients, compared with IC patients, the prevalence of diabetes, ischaemic stroke, heart failure, and atrial fibrillation was approximately doubled and renal failure was nearly tripled, even after age standardisation.

    Conclusion

    The risk of amputation is particularly high during the first 6 months following revascularisation for CLI. IC patients have a benign course in terms of limb loss. Mortality in both IC and CLI patients is substantial. Revascularised CLI patients have different comorbidities from IC patients.

  • 41.
    Bell, Katy J. L.
    et al.
    Univ Sydney, Australia.
    Azizi, Lamiae
    Univ Sydney, Australia.
    Nilsson, Peter M.
    Lund Univ, Sweden.
    Hayen, Andrew
    UTS, Australia.
    Irwig, Les
    Univ Sydney, Australia.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Sundrom, Johan
    Uppsala Univ, Sweden.
    Prognostic impact of systolic blood pressure variability in people with diabetes2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0194084Article in journal (Refereed)
    Abstract [en]

    Objective Blood pressure variability (BPV) has been associated with risk of cardiovascular events in observational studies, independently of mean BP levels. In states with higher autonomic imbalance, such as in diabetes, the importance of BP variability may theoretically be even greater. We aimed to investigate the incremental value of BPV for prediction of cardiovascular and all-cause mortality in patients with type 2 diabetes. Methods We identified 9,855 patients without pre-existing cardiovascular disease who did not change BP-lowering treatment during the observation period from a Swedish primary health care cohort of patients with type 2 diabetes. BPV was summarized as the standard deviation (SD), coefficient of variation (CV), or variation independent of mean (VIM). Patients were followed for a median of 4 years and associations with cardiovascular and all-cause mortality were investigated using Cox proportional hazards models. Results BPV was not associated with cardiovascular specific or all-cause mortality in the total sample. In patients who were not on BP-lowering drugs during the observation period (n = 2,949), variability measures were associated with all-cause mortality: hazard ratios were 1.05, 1.04 and 1.05 for 50% increases in SD, CV and VIM, respectively, adjusted for Framingham risk score risk factors, including mean BP. However, the addition of the variability measures in this subgroup only led to very minimal improvement in discrimination, indicating they may have limited clinical usefulness (change in C-statistic ranged from 0.000-0.003 in all models). Conclusions Although BPV was independently associated with all-cause mortality in diabetes patients in primary care who did not have pre-existing cardiovascular disease or BP-lowering drugs, it may be of minimal clinical usefulness above and beyond that of other routinely measured predictors, including mean BP.

  • 42.
    Berggren, Daniel Moreno
    et al.
    Uppsala Univ, Sweden.
    Folkvaljon, Yasin
    Uppsala Univ Hosp, Sweden.
    Engvall, Marie
    Uppsala Univ, Sweden.
    Sundberg, Johan
    Uppsala Univ, Sweden.
    Lambe, Mats
    Uppsala Univ Hosp, Sweden; Karolinska Inst, Sweden.
    Antunovic, Petar
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Haematology.
    Garelius, Hege
    Sahlgrens Univ Hosp, Sweden.
    Lorenz, Fryderyk
    Umea Univ, Sweden.
    Nilsson, Lars
    Skane Univ Hosp, Sweden.
    Rasmussen, Bengt
    Orebro Univ Hosp, Sweden.
    Lehmann, Soren
    Uppsala Univ, Sweden.
    Hellstrom-Lindberg, Eva
    Karolinska Inst, Sweden.
    Jadersten, Martin
    Karolinska Inst, Sweden.
    Ejerblad, Elisabeth
    Uppsala Univ, Sweden.
    Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register2018In: British Journal of Haematology, ISSN 0007-1048, E-ISSN 1365-2141, Vol. 181, no 5, p. 614-627Article in journal (Refereed)
    Abstract [en]

    The myelodysplastic syndromes (MDS) have highly variable outcomes and prognostic scoring systems are important tools for risk assessment and to guide therapeutic decisions. However, few population-based studies have compared the value of the different scoring systems. With data from the nationwide Swedish population-based MDS register we validated the International Prognostic Scoring System (IPSS), revised IPSS (IPSS-R) and the World Health Organization (WHO) Classification-based Prognostic Scoring System (WPSS). We also present population-based data on incidence, clinical characteristics including detailed cytogenetics and outcome from the register. The study encompassed 1329 patients reported to the register between 2009 and 2013, 14% of these had therapy-related MDS (t-MDS). Based on the MDS register, the yearly crude incidence of MDS in Sweden was 2amp;lt;boldamp;gt;amp;lt;/boldamp;gt;9 per 100000 inhabitants. IPSS-R had a significantly better prognostic power than IPSS (Pamp;lt;0amp;lt;boldamp;gt;amp;lt;/boldamp;gt;001). There was a trend for better prognostic power of IPSS-R compared to WPSS (P=0amp;lt;boldamp;gt;amp;lt;/boldamp;gt;05) and for WPSS compared to IPSS (P=0amp;lt;boldamp;gt;amp;lt;/boldamp;gt;07). IPSS-R was superior to both IPSS and WPSS for patients aged 70years. Patients with t-MDS had a worse outcome compared to de novo MDS (d-MDS), however, the validity of the prognostic scoring systems was comparable for d-MDS and t-MDS. In conclusion, population-based studies are important to validate prognostic scores in a real-world setting. In our nationwide cohort, the IPSS-R showed the best predictive power.

  • 43.
    Berglund, Elisabeth
    et al.
    Umeå University, Sweden.
    Johansson, Bengt
    Umeå University, Sweden.
    Dellborg, Mikael
    University of Gothenburg, Sweden.
    Sörensson, Peder
    Karolinska Institute, Sweden.
    Christersson, Christina
    Uppsala University, Sweden.
    Nielsen, Niels Erik
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Rinnstrom, Daniel
    Umeå University, Sweden.
    Thilen, Ulf
    Lund University, Sweden; Skåne University Hospital, Sweden.
    High incidence of infective endocarditis in adults with congenital ventricular septal defect2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 22, p. 1835-+Article in journal (Refereed)
    Abstract [en]

    Objective Ventricular septal defects (VSDs), if haemodynamically important, are closed whereas small shunts are left without intervention. The long-term prognosis in congenital VSD is good but patients are still at risk for long-term complications. The aim of this study was to clarify the incidence of infective endocarditis (IE) in adults with VSD. Methods The Swedish registry for congenital heart disease (SWEDCON) was searched for adults with VSD. 779 patients were identified, 531 with small shunts and 248 who had the VSD previously closed. The National Patient Register was then searched for hospitalisations due to IE in adults during a 10-year period. Results Sixteen (2%) patients were treated for IE, 6 men and 10 women, with a mean age of 46.3 +/- 12.2 years. The incidence of IE was 1.7-2.7/1000 years in patients without previous intervention, 20-30 times the risk in the general population. Thirteen had small shunts without previous intervention. There was no mortality in these 13 cases. Two patients had undergone repair of their VSD and also aortic valve replacement before the episode of endocarditis and a third patient with repaired VSD had a bicuspid aortic valve, all of these three patients needed reoperation because of their IE and one patient died. No patient with isolated and operated VSD was diagnosed with IE. Conclusions A small unoperated VSD in adults carries a substantially increased risk of IE but is associated with a low risk of mortality.

  • 44.
    Bergström, Ida
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Pro- and anti-inflammatory actions in coronary artery disease: with focus on CD56+ T cells and Annexin A12015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    ¨The atherosclerotic process is considered to be driven by an imbalance between proand anti-inflammatory actions. Still, the inflammatory state in patients with coronary artery disease (CAD) remains to be clarified. Annexin A1 (AnxA1) is a glucocorticoidinduced protein which may have a key role in the anti-inflammatory response as a mediator of glucocorticoid effects.

    The general aim of this thesis was to deepen the knowledge of pro- and antiinflammatory mechanisms in CAD via phenotypic assessments of immune cell subsets, in particular CD56+ T cells, and exploration of AnxA1. The long-term goal is to reveal basic mechanisms that will lead to the development of biomarkers, which may be used for individualized treatment and monitoring.

    The AnxA1 protein was constitutively expressed in both neutrophils and peripheral blood mononuclear cells (PBMCs). However, it varied considerably across PBMC subsets, being most abundantly expressed in monocytes. The AnxA1 expression was also higher in CD56+ T cells than in CD56- T cells.

    The expression of total AnxA1 protein in neutrophils was higher in patients with stable angina (SA) compared with controls. However, this was not accompanied by altered neutrophil activation status. Instead, the neutrophils from patients exhibited an enhanced anti-inflammatory response to exogenous AnxA1, emphasizing the potential of AnxA1 as an inhibitor of neutrophil activity. Only patients with acute coronary syndrome (ACS) showed an increase in cell surface-associated AnxA1.

    CAD patients, independent of clinical presentation, had increased proportions of CD56+ T cells compared with controls, a phenomenon likely to represent immunological aging. The CD56+ T cells were found to exhibit a distinct proinflammatory phenotype compared with CD56- T cells. In all T cell subsets, the expression of cell surface-associated AnxA1 was significantly increased in ACS patients, while it tended to be increased in post-ACS patients. In addition, dexamethasone clearly inhibited activation of CD56+ T cells in in vitro assays, whereas AnxA1 did not. The findings highlight the need to clarify whether the role of AnxA1 is different in T cells than in innate immune cells.

    In PBMCs, the mRNA levels of AnxA1 were increased in CAD patients, particularly in ACS patients. Correspondingly, the monocytes in ACS patients exhibited increased AnxA1 protein levels, both totally and on the cell surface. However, only cell surface-associated AnxA1 in monocytes correlated with the glucocorticoid sensitivity of PBMCs ex vivo. We propose the expression of cell surfaceassociated AnxA1 to be a promising candidate marker of glucocorticoid sensitivity, which needs further investigations in larger cohorts and intervention trials. Furthermore, the fact that PBMCs in post-ACS patients exhibited pro-inflammatory activity but no increase in cell surface-associated AnxA1 allow us to speculate that the glucocorticoid action and/or availability might be insufficient in these patients.

    List of papers
    1. Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease
    Open this publication in new window or tab >>Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease
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    2010 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 59, no 3, p. 443-440Article in journal (Refereed) Published
    Abstract [en]

    Background: A dysregulated cortisol response in patients with stable coronary artery disease (CAD) is related to systemic inflammatory activity. Moreover, a dysfunctional activation status of neutrophils in CAD has been discussed. The anti-inflammatory actions of glucocorticoids are mediated by annexin-1 (ANXA1), a protein mainly expressed by innate immune cells. An altered expression of glucocorticoid receptors (GR) and ANXA1 has been associated with glucocorticoid resistance.

    Methods and Results: Salivary cortisol levels were measured in the morning and evening during 3 consecutive days in 30 CAD patients and 30 healthy individuals. The neutrophil expression of GR and ANXA1 was determined by flow cytometry. The effect of exogenous ANXA1 was determined in neutrophil stimulation assays. The patients showed a flattened diurnal cortisol pattern compared to healthy subjects, involving higher levels in the evening. The neutrophil expression of GRtotal and GRα, as well as the ratio of GRα:GRβ expression was significantly decreased in patients, whereas the GRβ expression did not differ compared to controls. The neutrophil expression of ANXA1 was significantly increased in patients. Ex vivo, ANXA1 suppressed LTB4-induced ROS production in neutrophils from patients, but not from controls. On the other hand, ANXA1 impaired the LTB4-induced up-regulation of β2-integrins in both patients and controls.

    Conclusion: CAD patients displayed a more flattened diurnal cortisol rhythm caused by higher cortisol levels in the evening compared to healthy subjects. Our findings indicate a chronic overactivation of the hypothalamic-pituitary-adrenal (HPA) axis but give no conclusive evidence for glucocorticoid resistance, as assessed by the neutrophil expression of GR and ANXA1. The data rather point towards an increased anti-inflammatory potential in neutrophils from patients with stable CAD.

    Keywords
    Coronary artery disease, cortisol, neutrophil, glucocorticoid receptor, annexin-1
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-17247 (URN)10.1016/j.metabol.2009.07.044 (DOI)000276761800021 ()
    Note
    Original Publication: Eva Särndahl, Ida Bergström, Johnny Nijm, Tony Forslund, Mauro Perretti and Lena Jonasson, Enhanced Neutrophil Expression of Annexin-1 in Coronary Artery Disease, 2010, Metabolism: Clinical and Experimental, (59), 3, 443-440. http://dx.doi.org/10.1016/j.metabol.2009.07.044 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-03-12 Created: 2009-03-12 Last updated: 2017-12-13
    2. Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease
    Open this publication in new window or tab >>Persistent accumulation of interferon-gamma-producing CD8(+)CD56(+) T cells in blood from patients with coronary artery disease
    Show others...
    2012 (English)In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 224, no 2, p. 515-520Article in journal (Refereed) Published
    Abstract [en]

    Objective: There is emerging evidence for CD8(+) T cell alterations in blood from patients with coronary artery disease (CAD). We examined whether the distribution and phenotype of CD8(+)CD56(+) T cells differed according to the clinical manifestation of CAD. less thanbrgreater than less thanbrgreater thanMethods: Patients with acute coronary syndrome (ACS, n = 30), stable angina (SA, n = 34) and controls (n = 36) were included. Blood was collected before and up to 12 months after referral for coronary investigation. CD8(+)CD56(+) T cells were assessed by flow cytometry for expression of surface markers, apoptosis, and intracellular expression of cytokines. less thanbrgreater than less thanbrgreater thanResults: The proportions of CD8(+)CD56(+) T cells were significantly higher in both ACS and SA patients compared with controls, and remained so after 3 and 12 months. This was independent of age, sex, systemic inflammation and cytomegalovirus seropositivity. CD8(+)CD56(+) T cells differed from CD8(+)CD56(-) T cells in terms of lower CD28 expression and fewer apoptotic cells. Both CD8(+) T cell subsets were positive for interferon (IFN)-gamma and tumor necrosis factor, although IFN-gamma was significantly more confined to the CD8(+)CD56(+) T cells. less thanbrgreater than less thanbrgreater thanConclusion: The persistent accumulation of CD8(+)CD56(+) T cells in ACS and SA patients share several features with immunological aging. It also contributes to a larger IFN-gamma(+) pool in blood, and may thereby hypothetically drive the atherosclerotic process in a less favorable direction.

    Place, publisher, year, edition, pages
    Elsevier, 2012
    Keywords
    Acute coronary syndrome, Coronary artery disease, Cytokines, Immune system, Leukocytes
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-84895 (URN)10.1016/j.atherosclerosis.2012.07.033 (DOI)000309261400039 ()
    Note

    Funding Agencies|Swedish Research Council||Swedish Heart-Lung Foundation||County Council of Ostergotland, Sweden||Eleanora Demeroutis Foundation, Linkoping, Sweden||Heart Foundation at Linkoping University, Linkoping, Sweden||

    Available from: 2012-10-26 Created: 2012-10-26 Last updated: 2017-12-07
    3. Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease
    Open this publication in new window or tab >>Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease
    Show others...
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased proportions of circulating proinflammatory CD56+ T cells have been reported in patients with coronary artery disease (CAD). Yet, little is known about regulation of these cells. In the present study, we investigated the expression and potential role of the glucocorticoid-mediated protein annexin A1 (AnxA1) in CD56+ and CD56-T cell subsets, with focus on CAD.

    Methods and Results: We included totally 52 healthy individuals, 28 patients with acute coronary syndrome (ACS) and 57 patients with a history of ACS. AnxA1 mRNA expression was assessed in peripheral blood mononuclear cells. AnxA1 protein expression (total and cell surface-associated) was measured by whole blood flow cytometry in circulating CD56+ and CD56- T cell subsets. Furthermore, inhibitory effects of dexamethasone and/or recombinant AnxA1 on cytokine secretion by CD56+ and CD56- T cells were explored in vitro. We found that CD56+ T cells (the majority CD8+), expressed higher levels of AnxA1 mRNA and protein than did CD56- T cells. When comparing CAD patients with healthy controls, significantly higher levels of cell surface-associated AnxA1 expression were seen in patients, most pronounced in ACS patients. In vitro, dexamethasone reduced cytokine secretion by CD56+ T cells, whereas AnxA1 alone had no effect, and AnxA1 combined with dexamethasone abolished the dexamethasone-induced suppressive effects.

    Conclusion: AnxA1 was expressed more abundantly in proinflammatory CD56+ T cells. Patients with ACS exhibited increased levels of cell surface-associated AnxA1, thus indicating increased activation of the AnxA1 pathway. Our data further suggested that AnxA1 might counteract glucocorticoid mediated anti-inflammatory effects in T cells.

    Keywords
    Annexin A1, T cell, CD56, coronary artery disease, acute coronary syndrome
    National Category
    Cardiac and Cardiovascular Systems Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-114121 (URN)
    Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2018-01-11Bibliographically approved
    4. Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease
    Open this publication in new window or tab >>Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease
    Show others...
    2014 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.

    We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.

    AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.

    AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.

    Keywords
    Annexin A1, monocytes, glucocorticoids, coronary artery disease, acute coronary syndrome
    National Category
    Cardiac and Cardiovascular Systems Cell and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-114122 (URN)
    Available from: 2015-02-10 Created: 2015-02-10 Last updated: 2018-01-11Bibliographically approved
  • 45.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Jönsson, Simon
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Särndahl, Eva
    Department of Clinical Medicine, School of Health and Medical Sciences, and iRiSC - Inflammatory 18 Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Annexin A1 expression in blood mononuclear cells: a potential marker of glucocorticoid activity in patients with coronary artery disease2014Manuscript (preprint) (Other academic)
    Abstract [en]

    An imbalance between pro- and anti-inflammatory actions is believed to drive progression of atherosclerosis. Annexin A1 (AnxA1) is a key player in resolution of inflammation and a mediator of anti-inflammatory effects of glucocorticoids. Here, we investigated whether expression of AnxA1 in peripheral blood mononuclear cells (PBMCs) was altered in patients with coronary artery disease (CAD) and also related findings to glucocorticoid sensitivity ex vivo.

    We included 57 patients 6-12 months after acute coronary syndrome (ACS), 10 patients with ACS, and healthy controls. AnxA1 mRNA was measured in PBMCs and AnxA1 protein was assessed in monocytes and lymphocyte subsets by flow cytometry. In post-ACS patients and controls, glucocorticoid sensitivity was determined by measuring inhibitory effects of dexamethasone on LPS46 induced cytokine secretion.

    AnxA1 mRNA levels in PBMCs were higher in patients compared with controls, although most pronounced in ACS patients. AnxA1 protein was most abundant in the monocyte fraction. ACS patients exhibited the highest levels of cell surface-associated AnxA1 protein while levels in post-ACS patients and controls were similar. Ex vivo assays showed that PBMCs from post-ACS patients were more prone to release IL-6. Glucocorticoid sensitivity correlated with cell surface-associated AnxA1 protein in peripheral monocytes. Dexamethasone also induced upregulation of AnxA1 mRNA.

    AnxA1 expression in PBMCs is closely associated with glucocorticoid actions and cell surface associated AnxA1 appears to be a marker of glucocorticoid sensitivity. Although still speculative, a “normal” expression of cell surface-associated AnxA1 in post-ACS patients may suggest that glucocorticoid actions in vivo are insufficient to provide adequate anti-inflammatory effects in these patients.

  • 46.
    Bergström, Ida
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Lundberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Reutelingsperger, Chris
    Department of Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
    Ernerudh, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
    Särndahl, Eva
    Department of Clinical Medicine, School of Health and Medical Sciences, and iRiSC - Inflammatory 18 Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Higher expression of annexin A1 in 1 CD56+ than in CD56-T cells: Potential implications for coronary artery disease2014Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Increased proportions of circulating proinflammatory CD56+ T cells have been reported in patients with coronary artery disease (CAD). Yet, little is known about regulation of these cells. In the present study, we investigated the expression and potential role of the glucocorticoid-mediated protein annexin A1 (AnxA1) in CD56+ and CD56-T cell subsets, with focus on CAD.

    Methods and Results: We included totally 52 healthy individuals, 28 patients with acute coronary syndrome (ACS) and 57 patients with a history of ACS. AnxA1 mRNA expression was assessed in peripheral blood mononuclear cells. AnxA1 protein expression (total and cell surface-associated) was measured by whole blood flow cytometry in circulating CD56+ and CD56- T cell subsets. Furthermore, inhibitory effects of dexamethasone and/or recombinant AnxA1 on cytokine secretion by CD56+ and CD56- T cells were explored in vitro. We found that CD56+ T cells (the majority CD8+), expressed higher levels of AnxA1 mRNA and protein than did CD56- T cells. When comparing CAD patients with healthy controls, significantly higher levels of cell surface-associated AnxA1 expression were seen in patients, most pronounced in ACS patients. In vitro, dexamethasone reduced cytokine secretion by CD56+ T cells, whereas AnxA1 alone had no effect, and AnxA1 combined with dexamethasone abolished the dexamethasone-induced suppressive effects.

    Conclusion: AnxA1 was expressed more abundantly in proinflammatory CD56+ T cells. Patients with ACS exhibited increased levels of cell surface-associated AnxA1, thus indicating increased activation of the AnxA1 pathway. Our data further suggested that AnxA1 might counteract glucocorticoid mediated anti-inflammatory effects in T cells.

  • 47.
    Beygui, Farzin
    et al.
    Caen University Hospital, France.
    Castren, Maaret
    Helsinki University Hospital and Helsinki University, Finland; Karolinska Institutet, Stockholm, Sweden.
    Brunetti, Natale Daniele
    University of Foggia, Italy.
    Rosell-Ortiz, Fernando
    Empresa Pública de Emergencias Sanitarias de Andalucía, Spain.
    Christ, Michael
    Paracelsus Medical University, Nuremberg, Germany.
    Zeymer, Uwe
    Klinikum der Stadt Ludwigshafen am Rhein gGmbH, Germany.
    Huber, Kurt
    Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria.
    Folke, Fredrik
    Copenhagen University Hospital, Gentofte, Denmark.
    Svensson, Leif
    Karolinska Institutet, Solna, Sweden.
    Bueno, Hector
    Hospital 12 de Octubre, Madrid, Spain.
    Van't Hof, Arnoud
    Interventional Cardiology, Zwolle, The Netherlands.
    Nikolaou, Nikolaos
    Konstantopouleio General Hospital, Athens, Greece.
    Nibbe, Lutz
    Medizinische Klinik m.S. Intensivmedizin und Nephrologie, Berlin, Germany.
    Charpentier, Sandrine
    University Hospital of Rangueil, Toulouse, France.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Tubaro, Marco
    San Filippo Neri Hospital, Rome, Italy.
    Goldstein, Patrick
    Lille University Hospital, France.
    Gestione pre-ospedaliera dei pazienti con dolore toracico e/o dispnea di origine cardiaca[Pre-hospital management of patients with chest pain and/or dyspnoea of cardiac origin]2017In: Recenti progressi in medicina, ISSN 2038-1840, Vol. 108, no 1, p. 27-51Article in journal (Refereed)
    Abstract [en]

    Chest pain and acute dyspnoea are frequent causes of emergency medical services activation. The pre-hospital management of these conditions is heterogeneous across different regions of the world and Europe, as a consequence of the variety of emergency medical services and absence of specific practical guidelines. This position paper focuses on the practical aspects of the pre-hospital treatment on board and transfer of patients taken in charge by emergency medical services for chest pain and dyspnoea of suspected cardiac aetiology after the initial assessment and diagnostic work-up. The objective of the paper is to provide guidance, based on evidence, where available, or on experts' opinions, for all emergency medical services' health providers involved in the pre-hospital management of acute cardiovascular care.

  • 48.
    Bilchick, Kenneth C.
    et al.
    University of Virginia Health Syst, VA USA.
    Wang, Yongfei
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Cheng, Alan
    Johns Hopkins Medical Institute, MD 21205 USA.
    Curtis, Jeptha P.
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Dharmarajan, Kumar
    Yale New Haven Medical Centre, CT 06504 USA; Yale University, CT USA.
    Stukenborg, George J.
    University of Virginia, VA USA.
    Shadman, Ramin
    Southern Calif Permanente Medical Grp, CA USA.
    Anand, Inder
    University of Minnesota, MN USA.
    Lund, Lars H.
    Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Sartipy, Ulrik
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Maggioni, Aldo
    Italian Assoc Hospital Cardiologists, Italy.
    Swedberg, Karl
    University of Gothenburg, Sweden; Imperial Coll, England.
    OConner, Chris
    Inova Healthcare Syst, VA USA.
    Levy, Wayne C.
    University of Washington, WA USA.
    Seattle Heart Failure and Proportional Risk Models Predict Benefit From Implantable Cardioverter-Defibrillators2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 21, p. 2606-2618Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Recent clinical trials highlight the need for better models to identify patients at higher risk of sudden death. OBJECTIVES The authors hypothesized that the Seattle Heart Failure Model (SHFM) for overall survival and the Seattle Proportional Risk Model (SPRM) for proportional risk of sudden death, including death from ventricular arrhythmias, would predict the survival benefit with an implantable cardioverter-defibrillator (ICD). METHODS Patients with primary prevention ICDs from the National Cardiovascular Data Registry (NCDR) were compared with control patients with heart failure (HF) without ICDs with respect to 5-year survival using multivariable Cox proportional hazards regression. RESULTS Among 98,846 patients with HF (87,914 with ICDs and 10,932 without ICDs), the SHFM was strongly associated with all-cause mortality (p amp;lt; 0.0001). The ICD-SPRM interaction was significant (p amp;lt; 0.0001), such that SPRM quintile 5 patients had approximately twice the reduction in mortality with the ICD versus SPRM quintile 1 patients (adjusted hazard ratios [HR]: 0.602; 95% confidence interval [CI]: 0.537 to 0.675 vs. 0.793; 95% CI: 0.736 to 0.855, respectively). Among patients with SHFM-predicted annual mortality amp;lt;= 5.7%, those with a SPRM-predicted risk of sudden death below the median had no reduction in mortality with the ICD (adjusted ICD HR: 0.921; 95% CI: 0.787 to 1.08; p = 0.31), whereas those with SPRM above the median derived the greatest benefit (adjusted HR: 0.599; 95% CI: 0.530 to 0.677; p amp;lt; 0.0001). CONCLUSIONS The SHFM predicted all-cause mortality in a large cohort with and without ICDs, and the SPRM discriminated and calibrated the potential ICD benefit. Together, the models identified patients less likely to derive a survival benefit from primary prevention ICDs. (J Am Coll Cardiol 2017;69:2606-18) (C) 2017 by the American College of Cardiology Foundation.

  • 49.
    Blomstrand, Peter
    et al.
    County Hospital Ryhov, Jönköping, Sweden.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Festin, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences.
    Lindström, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Endocrinology.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Maret, Eva
    Karolinska University Hospital, Stockholm.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Maret-Ouda, John
    Karolinska University Hospital, Stockholm.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in West Östergötland, Primary Health Care in Motala.
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Left ventricular diastolic function, assessed by echocardiography and tissue Doppler imaging, is a strong predictor of cardiovascular events, superior to global left ventricular longitudinal strain, in patients with type 2 diabetes.2015In: European heart journal cardiovascular Imaging, ISSN 2047-2412, Vol. 16, no 9, p. 1000-1007Article in journal (Refereed)
    Abstract [en]

    AIMS: The aim of the study was to determine whether left ventricular systolic function, in terms of global left ventricular longitudinal strain (GLS), and diastolic function, expressed as the ratio between early diastolic transmitral flow and mitral annular motion velocities (E/e'), can predict cardiovascular events in patients with diabetes mellitus type 2.

    METHODS AND RESULTS: We prospectively investigated 406 consecutive patients, aged 55-65 years, with diabetes mellitus, who participated in the CARDIPP study. Echocardiography, pulse pressure (pp), and glycosylated haemoglobin (HbA1c) were analysed. Twelve cases of myocardial infarction and seven cases of stroke were identified during the follow-up period of 67 ± 17 months. Univariate Cox regression analysis showed that E/e' was a strong predictor of cardiovascular events (hazards ratio 1.12; 95% confidence interval 1.06-1.18, P < 0.001). E/e' was prospectively associated with cardiovascular events independent of age, sex, GLS, left ventricular ejection fraction (LVEF), pp, and HbA1c in multivariate analysis. Receiver operating characteristic curves showed that E/e' and HbA1c were the strongest predictors for cardiovascular events, both having an area under the curve (AUC) of 0.71 followed by LVEF with an AUC of 0.65 and GLS of 0.61. In a Kaplan-Meyer analysis, the cumulative probability of an event during the follow-up period was 8.6% for patients with an E/e' ratio >15 compared with 2.6% for patients with E/e' ≤15, P = 0.011.

    CONCLUSION: In middle-aged patients with type 2 diabetes, E/e' is a strong predictor of myocardial infarction and stroke, comparable with HbA1c and superior to GLS and LVEF.

  • 50.
    Blomstrand, Peter
    et al.
    Cty Hosp Ryhov, Sweden; Jonkoping Univ, Sweden.
    Sjöblom, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Mats
    Acad Hlth and Care, Sweden.
    Wijkman, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Engvall, Martin
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Nyström, Fredrik H
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Endocrinology.
    Östgren, Carl Johan
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, "Primary Health Care in Motala".
    Engvall, Jan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Overweight and obesity impair left ventricular systolic function as measured by left ventricular ejection fraction and global longitudinal strain2018In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 17, article id 113Article in journal (Refereed)
    Abstract [en]

    Aims: Obesity is associated with type 2 diabetes mellitus, left ventricular diastolic dysfunction and heart failure but it is unclear to which extent it is related to left ventricular systolic dysfunction. The aim of the study was to explore the effects of overweight and obesity on left ventricular systolic function in patients with type 2 diabetes mellitus and a control group of non-diabetic persons. Methods: We prospectively investigated 384 patients with type 2 diabetes mellitus, and 184 controls who participated in the CARDIPP and CAREFUL studies. The participants were grouped according to body mass index (normal weight amp;lt; 25 kg/m(2), overweight 25-29 kg/m(2), and obesity amp;gt;= 30 kg/m(2) ). Echocardiography was performed at the beginning of the study and after 4-years in the patient group. Results: Univariable and multivariable regression analysis revealed that variations in left ventricular ejection fraction, global longitudinal strain, left ventricular mass and diastolic function expressed as E/e (the ratio between early diastolic mitral flow and annular motion velocities) all are related to body mass index. The mean and standard deviation of left ventricular ejection fraction and global longitudinal strain values were 57% (8%) vs. - 18.6% (2.3%) for normal weight patients, 53% (8%) vs. - 17.5% (2.3%) for overweight, and 49% (9%) vs. - 16.2% (3.0%) for obese (p amp;lt; 0.05 vs. p amp;lt;0.05). Corresponding results in the control group were 58% (6%) vs. -22.3% (3.0%), 55% (7%) vs. - 20.8% (3.1%) and 54% (8%) - 19.6% (4.0%) (p amp;lt;0.05 vs. p amp;lt;0.05). Patients who gained weight from baseline to follow-up changed left ventricular ejection fraction (median and interquartile range) by - 1.0 (9.0) % (n =187) and patients who lost weight changed left ventricular ejection fraction by 1.0 (10.0) % (n =179) (p amp;lt;0.05). Conclusion: Overweight and obesity impair left ventricular ejection fraction and global longitudinal strain in both patients with type 2 diabetes mellitus and non-diabetic persons.

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