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  • 401.
    Troughton, Richard W.
    et al.
    University of Otago Christchurch, New Zealand .
    Frampton, Christopher M.
    University of Otago Christchurch, New Zealand .
    Brunner-La Rocca, Hans-Peter
    Maastricht University of Medical Centre, Netherlands .
    Pfisterer, Matthias
    University Hospital Basel, Switzerland..
    Eurlings, Luc W. M.
    Maastricht University of Medical Centre, Netherlands .
    Erntell, Hans
    Danderyd Hospital, Stockholm, Sweden..
    Persson, Hans
    Danderyd Hospital, Stockholm, Sweden..
    O'Connor, Christopher M.
    Duke University Medical Center, Durham, NC, USA.
    Moertl, Deddo
    LKH, St Poelten, Austria.
    Karlström, Patric
    County Hospital Ryhov, Jönköping, Sweden.
    Dahlström, Ulf
    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.
    Gaggin, Hanna K.
    Massachusetts General Hospital, Boston, USA.
    Januzzi, James L.
    Massachusetts General Hospital, Boston, USA.
    Berger, Rudolf
    Medical University of Vienna, Austria .
    Richards, A. Mark
    University of Otago Christchurch, New Zealand .
    Pinto, Yigal M.
    Academic Medical Center, Amsterdam, The Netherlands.
    Nicholls, M. Gary
    University of Otago Christchurch, New Zealand .
    Effect of B-type natriuretic peptide-guided treatment of chronic heart failure on total mortality and hospitalization: an individual patient meta-analysis2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 23, p. 1559-1567Article in journal (Refereed)
    Abstract [en]

    Aims Natriuretic peptide-guided (NP-guided) treatment of heart failure has been tested against standard clinically guided care in multiple studies, but findings have been limited by study size. We sought to perform an individual patient data meta-analysis to evaluate the effect of NP-guided treatment of heart failure on all-cause mortality. Methods and results ligible randomized clinical trials were identified from searches of Medline and EMBASE databases and the Cochrane Clinical Trials Register. The primary pre-specified outcome, all-cause mortality was tested using a Cox proportional hazards regression model that included study of origin, age (less than 75 or greater than= 75 years), and left ventricular ejection fraction (LVEF, less than= 45 or greater than 45%) as covariates. Secondary endpoints included heart failure or cardiovascular hospitalization. Of 11 eligible studies, 9 provided individual patient data and 2 aggregate data. For the primary endpoint individual data from 2000 patients were included, 994 randomized to clinically guided care and 1006 to NP-guided care. All-cause mortality was significantly reduced by NP-guided treatment [hazard ratio = 0.62 (0.45-0.86); P = 0.004] with no heterogeneity between studies or interaction with LVEF. The survival benefit from NP-guided therapy was seen in younger (less than 75 years) patients [0.62 (0.45-0.85); P = 0.004] but not older (greater than= 75 years) patients [0.98 (0.75-1.27); P = 0.96]. Hospitalization due to heart failure [0.80 (0.67-0.94); P = 0.009] or cardiovascular disease [0.82 (0.67-0.99); P = 0.048] was significantly lower in NP-guided patients with no heterogeneity between studies and no interaction with age or LVEF. Conclusion Natriuretic peptide-guided treatment of heart failure reduces all-cause mortality in patients aged less than 75 years and overall reduces heart failure and cardiovascular hospitalization.

  • 402.
    Trzebiatowska-Krzynska, Aleksandra
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    The right ventricle in volume or pressure overload: Insights from novel imaging techniques2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This study is inspired by the gap in knowledge regarding the timing of cardiac surgery and interventions in adult patients with congenital heart disease. There are many parameters used assessing right ventricular function; however, most of them have pitfalls. Understanding the pathomechanisms by which the heart adapts to congenital defects is probably key to find the answer when it is time to intervene and start discussing treatment options. Heart defects are the most frequently occurring congenital disorders. Less than 50% of individuals with moderate to severe congenital heart defects, e.g. transposition of the great arteries (TGA) or tetralogy of Fallot (TOF), survive to adulthood without intervention. Advances in cardiac surgery and better identification of individuals at risk for sudden cardiac death have increased survival rates. Currently, more than 96% of patients with congenital heart disease survive to at least 16 years of age; most undergo corrective surgery but are not cured, and only a few have normal physiology and anatomy. In many cases, the heart must develop mechanisms of adaptation to the changed conditions after surgery. Consequently, correction of the defect creates residual disease with a risk of future complications.

    To prevent clinical deterioration and to identify the development of complications, patients need lifelong, regular follow up. The choice of followup modalities depends on the cardiac malformation.

    The right ventricle (RV) plays an important role, as it is often part of the defect or is influenced by the surgery. In the past, research was focused on assessment of left ventricular function (LV), and the RV was “the forgotten ventricle.” Observations and studies in the last few decades brought increased interest into the RV and revealed the importance of the RV in the prognosis of various cardiac diseases.

    An understanding of RV morphology, pathophysiology and adaptive mechanisms is crucial for further studies of prognosis as well as for research linked to the use of particular diagnostic modalities.

    When the RV is exposed to increased pressure load, e.g. in atrially corrected transposition of the great arteries (TGA), adaptation affects the cavity volume as well as the wall thickness. When the RV is volume overloaded, adaptation involves enhancement of the RV cavity volume while the wall thickness often remains unchanged under long time. RV ejection fraction (RVEF) gives some information about changes in RV function, but information on myocardial contractility and contractile reserve is also needed. New functional parameters such as strain—also known as myocardial deformation—provide some information about intrinsic myocardial function.

    In Paper I, we studied functional parameters such as ejection fraction and strain (radial and longitudinal strain for both ventricles) in patients with Tetralogy of Fallot (TOF) and TGA. Longitudinal RV strain was depressed in both patient groups in comparison with that in healthy individuals, and there were additional differences between the two patient groups.

    In Paper II, we validated three-dimensional echocardiography (3DEcho) against the cardiac magnetic resonance (CMR) gold standard. The study population was limited to patients with TOF. In general, 3DEcho underestimated RV volumes but was able to identify patients with RV dilatation on CMR with high sensitivity. RV longitudinal free wall strain measured by CMR with a cut-off set at -14% identified patients with depressed exercise capacity and low peak oxygen uptake.

    In Paper III, we studied a new CMR method to quantify and visualise turbulent flow in the heart and vessels. Turbulent flow can be harmful to tissue, blood cells, and endothelium and can contribute to tissue remodeling. In patients with TOF, turbulent flow can be seen as variance in 2DEcho color Doppler. In CMR, increased turbulent kinetic energy (TKE) could be seen with four-dimensional flow. The RV TKE was increased in patients with TOF with pulmonary regurgitation compared with that in healthy controls.

    In Paper IV, we validated “knowledge-based reconstruction” (KBR), a novel method to calculate RV volume, against CMR in patients with various types of congenital heart defects. Two-dimensional echocardiogram-based threedimensional RV reconstruction is a relatively uncomplicated method that creates a three-dimensional RV model based on a limited number of predefined points of interest (RV structures such as tricuspid annulus, RV free wall, or pulmonary valve).

    KBR showed good agreement with CMR (intraclass correlation coefficient = 0.84 for RV end-diastolic volume and 0.89 for ejection fraction) but tended to underestimate RV volumes, which is in line with other methods based on ultrasound.

    Conclusions: 3DEcho is an evolving modality that is able to identify patients with RV dilatation. It can be used clinically for the follow up of patients with congenital heart diseases, especially those with mildly to moderately dilated RVs. When an intervention seems likely, 3DEcho results should be verified by CMR. CMR-derived measurements of longitudinal and radial strain provide a new understanding of RV remodeling and ventricular interdependence in patients with TOF and TGA. Depressed longitudinal strain may indicate a risk of depressed exercise capacity and, in patients with TGA, clinical deterioration.

    Further studies in larger populations of patients with congenital heart defects are needed, as the altered RV morphology in such patients makes quantitative assessment especially challenging.

    List of papers
    1. Afterload dependence of right ventricular myocardial deformation: A comparison between tetralogy of Fallot and atrially corrected transposition of the great arteries in adult patients
    Open this publication in new window or tab >>Afterload dependence of right ventricular myocardial deformation: A comparison between tetralogy of Fallot and atrially corrected transposition of the great arteries in adult patients
    Show others...
    2018 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 9, article id e0204435Article in journal (Refereed) Published
    Abstract [en]

    Background

    Prior studies suggested that myocardial deformation is superior to conventional measures for assessing ventricular function. This study aimed to evaluate right ventricular (RV) myocardial deformation in response to increased afterload. Patients with the RV in the systemic position were compared with patients with the RV in the sub-pulmonic position with normal or only slightly elevated systolic right ventricular pressure. Correlations between global longitudinal strain (GLS), radial strain, atrioventricular plane displacement (AVPD), and exercise capacity were evaluated.

    Methods

    44 patients with congenital heart defect were enrolled in the study. The control group consisted of seven healthy volunteers. All patients underwent cardiovascular magnetic resonance (CMR) and cardiopulmonary exercise testing. We assessed biventricular myocardial function using CMR based feature tracking and compared the results to anatomic volumes.

    Results

    Strain analysis and displacement measurements were feasible in all participants. RVGLS and RVAVPD were reduced in both study groups compared to the control group (p<0.001). Left ventricular (LV) radial strain was significantly lower in patients with a systemic RV than in those with a subpulmonic RV and lower than in controls (p<0.001). Both LVAVPD and RVAVPD were significantly depressed in patients compared to controls (p<0.05). RVAVPD was more depressed in patients with a high systolic RV pressure than in those with normal RV pressure (p<0.001). RVAVPD did not correlate with exercise capacity in either study group. Exercise capacity in both patient groups was depressed to levels reported in previous studies, and did not correlate with RVGLS.

    Conclusions

    Both study groups had abnormal myocardial deformation and increased RV volumes. RVGLS in patients was lower than in controls, confirming the effect of increased afterload on myocardial performance.

    Place, publisher, year, edition, pages
    San Francisco, CA, United States: Public Library of Science, 2018
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-152085 (URN)10.1371/journal.pone.0204435 (DOI)000445907400049 ()30261015 (PubMedID)2-s2.0-85054059580 (Scopus ID)
    Note

    Funding Agencies|ALF Grant, Region Ostergotland [LIO-281281]

    Available from: 2018-10-17 Created: 2018-10-17 Last updated: 2019-05-01Bibliographically approved
    2. Turbulent kinetic energy in the right ventricle: Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot
    Open this publication in new window or tab >>Turbulent kinetic energy in the right ventricle: Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot
    Show others...
    2018 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 47, no 4, p. 1043-1053Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling.

    Materials and Methods: Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (11%) and one higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. Assessment: The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC).

    Results: The higher PR fraction group had more remodeled RVs (140 6 25 vs. 107 6 22 [lower PR fraction, P < 0.01] and 93 6 15 ml/m2[healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 6 3.15 vs. 2.23 6 0.81 [lower PR fraction, P < 0.01] and 1.91 6 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R25 0.47, P 5 0.002).

    Conclusion: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair.

    Place, publisher, year, edition, pages
    Hoboken: John Wiley & Sons, 2018
    Keywords
    4D flow, MRI, Turbulence, Tetralogy of Fallot, Turbulent kinetic energy
    National Category
    Radiology, Nuclear Medicine and Medical Imaging Cardiac and Cardiovascular Systems Medical Laboratory and Measurements Technologies Anesthesiology and Intensive Care Medical Image Processing
    Identifiers
    urn:nbn:se:liu:diva-143780 (URN)10.1002/jmri.25830 (DOI)000427125300016 ()28766919 (PubMedID)2-s2.0-85026745981 (Scopus ID)
    Note

    Funding agencies:  European Research Council [310612]; Swedish Heart and Lung Foundation [20140398]; County Council of Ostergotland; Medical Research Council of Southeast Sweden (FORSS); Swedish Research Council [2013-6077, 2014-6191]

    Available from: 2017-12-18 Created: 2017-12-18 Last updated: 2019-01-07Bibliographically approved
    3. Knowledge-based 3D reconstruction of the right ventricle: comparison with cardiac magnetic resonance in adults with congenital heart disease
    Open this publication in new window or tab >>Knowledge-based 3D reconstruction of the right ventricle: comparison with cardiac magnetic resonance in adults with congenital heart disease
    Show others...
    2015 (English)In: Echo research and practice, ISSN 2055-0464, Vol. 2, no 4, p. 109-116Article in journal (Refereed) Published
    Abstract [en]

    AIM: Assessment of right ventricular (RV) function is a challenge, especially in patients with congenital heart disease (CHD). The aim of the present study is to assess whether knowledge-based RV reconstruction, used in the everyday practice of an echo-lab for adult CHD in a tertiary referral center, is accurate when compared to cardiac magnetic resonance (CMR) examination.

    SUBJECTS AND METHODS: Adult patients who would undergo CMR for assessment of the RV were asked to undergo an echo of the heart for further knowledge-based reconstruction (KBR). Echocardiographic images were acquired in standard views using a predefined imaging protocol. RV volumes and ejection fraction (EF) calculated using knowledge-based technology were compared with the CMR data of the same patient.

    RESULTS: Nineteen consecutive patients with congenital right heart disease were studied. Median age of the patients was 28 years (range 46 years). Reconstruction was possible in 16 out of 19 patients (85%). RV volumes assessed with this new method were smaller than with CMR. Indexed end diastolic volumes were 114±17 ml vs 121±19 ml, P<0.05 and EFs were 45±8% vs 47±9%, P<0.05 respectively. The correlation between the methods was good with an intraclass correlation of 0.84 for EDV and 0.89 for EF, P value <0.001 in both cases.

    CONCLUSION: KBR enables reliable measurement of RVs in patients with CHDs and can be used in clinical practice for analysis of volumes and EFs.

    Keywords
    congenital heart disease; knowledge-based reconstruction; right ventricle volume; ventripoint system
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-124289 (URN)10.1530/ERP-15-0029 (DOI)26796613 (PubMedID)
    Available from: 2016-01-25 Created: 2016-01-25 Last updated: 2019-01-07
  • 403.
    Trzebiatowska-Krzynska, Aleksandra
    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.
    Driessen, Mieke
    Ahmazon Center of Adult Congenital Heart Disease.
    Sieswerda, Gertjan Tj
    Ahmazon Center of Adult Congenital Heart Disease.
    Wallby, Lars
    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.
    Meijboom, Folkert
    Ahmazon Center of Adult Congenital Heart Disease.
    Knowledge-based 3D reconstruction of the right ventricle: comparison with cardiac magnetic resonance in adults with congenital heart disease2015In: Echo research and practice, ISSN 2055-0464, Vol. 2, no 4, p. 109-116Article in journal (Refereed)
    Abstract [en]

    AIM: Assessment of right ventricular (RV) function is a challenge, especially in patients with congenital heart disease (CHD). The aim of the present study is to assess whether knowledge-based RV reconstruction, used in the everyday practice of an echo-lab for adult CHD in a tertiary referral center, is accurate when compared to cardiac magnetic resonance (CMR) examination.

    SUBJECTS AND METHODS: Adult patients who would undergo CMR for assessment of the RV were asked to undergo an echo of the heart for further knowledge-based reconstruction (KBR). Echocardiographic images were acquired in standard views using a predefined imaging protocol. RV volumes and ejection fraction (EF) calculated using knowledge-based technology were compared with the CMR data of the same patient.

    RESULTS: Nineteen consecutive patients with congenital right heart disease were studied. Median age of the patients was 28 years (range 46 years). Reconstruction was possible in 16 out of 19 patients (85%). RV volumes assessed with this new method were smaller than with CMR. Indexed end diastolic volumes were 114±17 ml vs 121±19 ml, P<0.05 and EFs were 45±8% vs 47±9%, P<0.05 respectively. The correlation between the methods was good with an intraclass correlation of 0.84 for EDV and 0.89 for EF, P value <0.001 in both cases.

    CONCLUSION: KBR enables reliable measurement of RVs in patients with CHDs and can be used in clinical practice for analysis of volumes and EFs.

  • 404.
    Trzebiatowska-Krzynska, Aleksandra
    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.
    Wallby, Lars
    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.
    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.
    Carlhäll, Carljohan
    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.
    Brudin, Lars
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    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).
    Afterload dependence of right ventricular myocardial deformation: A comparison between tetralogy of Fallot and atrially corrected transposition of the great arteries in adult patients2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 9, article id e0204435Article in journal (Refereed)
    Abstract [en]

    Background

    Prior studies suggested that myocardial deformation is superior to conventional measures for assessing ventricular function. This study aimed to evaluate right ventricular (RV) myocardial deformation in response to increased afterload. Patients with the RV in the systemic position were compared with patients with the RV in the sub-pulmonic position with normal or only slightly elevated systolic right ventricular pressure. Correlations between global longitudinal strain (GLS), radial strain, atrioventricular plane displacement (AVPD), and exercise capacity were evaluated.

    Methods

    44 patients with congenital heart defect were enrolled in the study. The control group consisted of seven healthy volunteers. All patients underwent cardiovascular magnetic resonance (CMR) and cardiopulmonary exercise testing. We assessed biventricular myocardial function using CMR based feature tracking and compared the results to anatomic volumes.

    Results

    Strain analysis and displacement measurements were feasible in all participants. RVGLS and RVAVPD were reduced in both study groups compared to the control group (p<0.001). Left ventricular (LV) radial strain was significantly lower in patients with a systemic RV than in those with a subpulmonic RV and lower than in controls (p<0.001). Both LVAVPD and RVAVPD were significantly depressed in patients compared to controls (p<0.05). RVAVPD was more depressed in patients with a high systolic RV pressure than in those with normal RV pressure (p<0.001). RVAVPD did not correlate with exercise capacity in either study group. Exercise capacity in both patient groups was depressed to levels reported in previous studies, and did not correlate with RVGLS.

    Conclusions

    Both study groups had abnormal myocardial deformation and increased RV volumes. RVGLS in patients was lower than in controls, confirming the effect of increased afterload on myocardial performance.

  • 405.
    Tsartsalis, D.
    et al.
    Department of Cardiology, "Hippokration" Hospital, Athens; 1st Department of Cardiology, University of Athens, Medical School, "Hippokration" Hospital, Athens, Greece.
    Dragioti, Elena
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Kontoangelos, K.
    1st Department of Psychiatry, University of Athens, Medical School, Eginition University Hospital, Athens, Greece; University Mental Health Research Institute, Athens, Greece.
    Pitsavos, C.
    1st Department of Cardiology, University of Athens, Medical School, "Hippokration" Hospital, Athens, Greece.
    Sakkas, P.
    1st Department of Psychiatry, University of Athens, Medical School, Eginition University Hospital, Athens, Greece.
    Papadimitriou, G. N.
    1st Department of Psychiatry, University of Athens, Medical School, Eginition University Hospital, Athens, Greece.
    Stefanadis, C.
    1st Department of Cardiology, University of Athens, Medical School, "Hippokration" Hospital, Athens, Greece.
    Kallikazaros, I.
    Department of Cardiology, "Hippokration" Hospital, Athens, Greece.
    The impact of depression and cardiophobia on quality of life in patients with essential hypertension.2016In: Psychiatrike = Psychiatriki, ISSN 1105-2333, Vol. 27, no 3, p. 192-203Article in journal (Refereed)
    Abstract [en]

    Patients with chronic conditions like hypertension may experience many negative emotions which endorse the development of anxiety and depression symptomatology, thus they increase their risk for poor quality of life. Several studies have shown an association between symptoms of psychological distress and hypertension. In this study we aimed to quantify the link between depression, cardiophobia and quality of life in hypertensive patients. A cross-sectional design was employed. A sample of 197 hypertensive patients (89 men-108 women, mean age 53 years, SD=12 ranged 25-78) from a university outpatient hypertension clinic in Greece participated. Ninety-four (47.7%) of the participants suffered from essential grade I hypertension; 68 (34.5%) were grade II; 16 (8.1%) were categorized as grade III, while only 11 (5.6%) patients were recorded as normotensives with high normal values. The questionnaires included: (a) question for the recording of social-demographic characteristics and clinical features, (b) The Short Form (SF-36) Health Survey, (c) The Beck Depression Inventory -I, and (d) The Cardiac Anxiety Questionnaire. There were no significant differences between the two genders with exception of marital status (p=0.010), dyslipidemia (p=0.050), grade of hypertension (p=0.014), cardiac left ventricular hypertrophy (p=0.004), renal failure (p=0.043) and stroke (p=0.024). Lower levels of quality of life and higher levels of depression and cardiophobia were observed compared to the general population. There were no significant differences on psychological measures between the two sexes (p>0.05). Cardiophobia was positively related to depressive symptomatology (r=0.533, p=0.000) while negatively to both physical and mental health summary measures of SF-36 health survey (r=-0.467, p=0.000 r=-0.537, p=0.000 respectively). Multiple linear regression models found that for psychical health depression and cardiac anxiety, avoidance activities had an influence on levels of quality of life in hypertensive patients, after controlling for age and other socio-demographic variables and clinical characteristics (Beta=-0.133, p=0.007, Beta=-0.364 p=0.000 and Beta=-0.167 p=0.006, respectively). For mental component summary depression and cardiophobia, heart focused attention had also impact on mental health in hypertensives (Beta=-0.438, p=0.016, Beta=-0.564, p=0.000 and Beta=-0.223, p=0.037, respectively) after adjustments. Heart focused anxiety symptoms-as avoidance activities and/or attention and monitoring cardiac activity, are related to hypertensive patients' present deteriorated depressive symptoms and levels of quality of life. Both depressive symptomatology and heart focused anxiety may be a mechanism partly responsible for hypertensive patients' present impaired levels of quality of life.

  • 406.
    Ueda, Peter
    et al.
    Karolinska Inst, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Sweden.
    James, Stefan
    Uppsala Univ, Sweden.
    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.
    Erlinge, David
    Lund Univ, Sweden.
    Omerovic, Elmir
    Sahlgrens Univ Hosp, Sweden.
    Persson, Jonas
    Karolinska Inst, Sweden.
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Sweden.
    Tornvall, Per
    Karolinska Inst, Sweden.
    Svennblad, Bodil
    Uppsala Univ, Sweden.
    Varenhorst, Christoph
    Uppsala Univ, Sweden; Pfizer AB, Sweden.
    External Validation of the DAPT Score in a Nationwide Population2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 72, no 10, p. 1069-1078Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The dual antiplatelet therapy (DAPT) score guides decisions on DAPT duration after coronary stenting by simultaneously predicting ischemic and bleeding risk. OBJECTIVES This study sought to assess the performance of the DAPT score in a nationwide real-world population. METHODS The study used register data in Sweden (2006 to 2014) and followed 41,101 patients who had undergone 12 months of event-free DAPT, from months 12 to 30 after stenting. Risk of myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (MACCE) (MI, stroke, and all-cause death), and fatal or major bleeding were compared according to DAPT score. RESULTS The score had a discrimination of 0.58 (95% confidence interval [CI]: 0.56 to 0.60) for MI or stent thrombosis, 0.54 (95% CI: 0.53 to 0.55) for MACCE, and 0.49 (95% CI: 0.45 to 0.53) for fatal or major bleeding. Risk of MI or stent thrombosis was significantly increased at scores of amp;gt;= 3 while MACCE risk followed a J-shaped pattern and increased at scores of amp;gt;= 4. Absolute differences in fatal or major bleeding risk were small between scores. Event rates of ischemic and bleeding outcomes in patients with high (amp;gt;= 2) and low (amp;lt; 2) scores differed compared to the DAPT Study from which the score was derived; fatal or major bleeding rates were approximately one-half of those in the placebo arm of the DAPT Study. CONCLUSIONS In a nationwide population, the DAPT score did not adequately discriminate ischemic and bleeding risk, the relationship between score and ischemic risk did not correspond to the suggested decision rule for extended DAPT, and risk of bleeding was lower compared with the DAPT Study. The score and its decision rule may not be generalizable to real-world populations. (C) 2018 by the American College of Cardiology Foundation.

  • 407.
    Utjes, Deborah
    et al.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Lyth, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Surgery, Orthopedics and Oncology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Regional Board, Research and Development Unit.
    Lapins, Jan
    Karolinska University Hospital, Sweden.
    Eriksson, Hanna
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Reduced disease-specific survival following a diagnosis of multiple primary cutaneous malignant melanomas-a nationwide, population-based study2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 11, p. 2243-2252Article in journal (Refereed)
    Abstract [en]

    Outcome data comparing patients with multiple primary invasive cutaneous malignant melanomas (MPMs) to single primary invasive cutaneous malignant melanomas (SPMs) show conflicting results. We have analyzed differences in disease-specific survival between these patients in a nationwide population-based setting. From the Swedish Melanoma Register, 27,235 patients were identified with a first invasive cutaneous malignant melanoma (CMM) between 1990 and 2007, followed-up through 2013. Of these, 700 patients developed MPMs. Cox proportional hazard regression was used for adjusted cause-specific hazard ratios (HRs). An interval of amp;lt;= 5 years between CMM diagnoses was significantly correlated to a decreased CMM-specific survival in Stage I-II MPM-vs. SPM-patients (HR 1.32; 95% CI 1.04-1.67; p=0.02). MPM-patients with longer time interval between diagnoses experienced similar risk of CMM-death as SPM-patients. The risk of CMM-death increased by almost 50% above the expected outcome according to stage of the index CMM by the diagnosis of a second CMM (HR 1.48; 95% CI 1.19-1.85; p amp;lt; 0.001). MPM vs. SPM-patients had a worse outcome (HR 1.38; 95% CI 1.05-1.83; p=0.001). This emphasizes the importance of prevention efforts in SPM-patients to decrease the risk of subsequent CMMs and has implications for more vigilant follow-up in MPM-patients.

  • 408.
    Vallejo-Vaz, Antonio J.
    et al.
    Imperial Coll London, England.
    Akram, Asif
    Imperial Coll London, England; Nanyang Technology University, Singapore.
    Rao Kondapally Seshasai, Sreenivasa
    St Georges University of London, England.
    Cole, Della
    St Georges University of London, England.
    Watts, Gerald F.
    University of Western Australia, Australia.
    Kees Hovingh, G.
    Academic Medical Centre, Netherlands.
    Kastelein, John J. P.
    Academic Medical Centre, Netherlands.
    Mata, Pedro
    Fdn Hipercolesterolemia Familiar, Spain.
    Raal, Frederick J.
    University of Witwatersrand, South Africa.
    Santos, Raul D.
    University of Sao Paulo, Brazil.
    Soran, Handrean
    Central Manchester University Hospital, England.
    Freiberger, Tomas
    Centre Cardiovasc Surg and Transplantat, Czech Republic; Masaryk University, Czech Republic.
    Abifadel, Marianne
    St Joseph University, Lebanon.
    Aguilar-Salinas, Carlos A.
    Institute Nacl Ciencias Medical and Nutr Salvador Zubiran, Mexico.
    Alnouri, Fahad
    Prince Sultan Cardiac Centre Riyadh, Saudi Arabia.
    Alonso, Rodrigo
    Clin Las Condes, Chile.
    Al-Rasadi, Khalid
    Sultan Qaboos University Hospital, Oman.
    Banach, Maciej
    Medical University of Lodz, Poland.
    Bogsrud, Martin P.
    Oslo University Hospital, Norway.
    Bourbon, Mafalda
    University of Lisbon, Portugal; University of Lisbon, Portugal.
    Bruckert, Eric
    Hop La Pitie Salpetriere, France.
    Car, Josip
    Imperial Coll London, England; Nanyang Technology University, Singapore.
    Ceska, Richard
    Charles University of Prague, Czech Republic.
    Corral, Pablo
    FASTA University, Argentina.
    Descamps, Olivier
    Centre Hospital Jolimont, Belgium.
    Dieplinger, Hans
    Medical University of Innsbruck, Austria.
    Do, Can T.
    Bach Mai Hospital, Vietnam.
    Durst, Ronen
    Hadassah Hebrew University, Israel.
    Ezhov, Marat V.
    Russian Cardiol Research and Prod Centre, Russia.
    Fras, Zlatko
    University of Medical Centre Ljubljana, Slovenia; University of Ljubljana, Slovenia.
    Gaita, Dan
    University of Medical and Farm Victor Babes Timisoara, Romania.
    Gaspar, Isabel M.
    University of Lisbon, Portugal.
    Genest, Jaques
    McGill University, Canada.
    Harada-Shiba, Mariko
    National Cerebral and Cardiovasc Centre, Japan.
    Jiang, Lixin
    Fuwai Hospital, Peoples R China.
    Kayikcioglu, Meral
    Ege University, Turkey.
    Lam, Carolyn S. P.
    National Heart Centre Singapore, Singapore; Duke National University of Singapore, Singapore.
    Latkovskis, Gustavs
    University of Latvia, Latvia.
    Laufs, Ulrich
    University of Saarland, Germany.
    Liberopoulos, Evangelos
    University of Ioannina, Greece.
    Lin, Jie
    Capital Medical University, Peoples R China.
    Lin, Nan
    Imperial Coll London, England.
    Maher, Vincent
    Tallaght Hospital, Ireland.
    Majano, Nelson
    Hospital Mil Caracas, Venezuela.
    David Marais, A.
    University of Cape Town, South Africa; National Health Lab Serv, South Africa.
    Maerz, Winfried
    Heidelberg University, Germany.
    Mirrakhimov, Erkin
    Kyrgyz State Medical Acad, Kyrgyzstan.
    Miserez, Andre R.
    Diagene GmbH, Switzerland; University of Basel, Switzerland.
    Mitchenko, Olena
    Institute Cardiol AMS Ukraine, Ukraine; University of Teknol MARA, Malaysia.
    Nawawi, Hapizah
    Institute Pathol Lab and Forens Medical I PPerForM, Malaysia.
    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.
    Nordestgaard, Borge G.
    University of Copenhagen, Denmark.
    Paragh, Gyorgy
    University of Debrecen, Hungary.
    Petrulioniene, Zaneta
    Vilnius University, Lithuania.
    Pojskic, Belma
    Cantonal Hospital, Bosnia and Herceg.
    Reiner, Zeljko
    University of Zagreb, Croatia.
    Sahebkar, Amirhossein
    Mashhad University of Medical Science, Iran.
    Santos, Lourdes E.
    University of Philippines, Philippines.
    Schunkert, Heribert
    Technical University of Munich, Germany.
    Shehab, Abdullah
    UAE University, U Arab Emirates.
    Naceur Slimane, M.
    Fac Medical Monastir, Tunisia.
    Stoll, Mario
    Cardiovasc Health Commiss, Uruguay.
    Su, Ta-Chen
    National Taiwan University Hospital, Taiwan; National Taiwan University Hospital, Taiwan.
    Susekov, Andrey
    Russian Medical Academic Postgrad Educ, Russia.
    Tilney, Myra
    University of Malta, Malta.
    Tomlinson, Brian
    Chinese University of Hong Kong, Peoples R China.
    Tselepis, Alexandros D.
    University of Ioannina, Greece.
    Vohnout, Branislav
    Comenius University, Slovakia.
    Widen, Elisabeth
    University of Helsinki, Finland.
    Yamashita, Shizuya
    Rinku Gen Medical Centre, Japan; Osaka University, Japan.
    Catapano, Alberico L.
    University of Milan, Italy; Multimed IRCCS, Italy.
    Ray, Kausik K.
    Imperial Coll London, England.
    Pooling and expanding registries of familial hypercholesterolaemia to assess gaps in care and improve disease management and outcomes: Rationale and design of the global EAS Familial Hypercholesterolaemia Studies Collaboration2016In: Atherosclerosis Supplements, ISSN 1567-5688, E-ISSN 1878-5050, Vol. 22Article in journal (Refereed)
    Abstract [en]

    Background: The potential for global collaborations to better inform public health policy regarding major non-hypercholesterolaemia (FH), a common genetic disorder associated with premature cardiovascular disease, is yet to be reliably ascertained using similar approaches. The European Atherosclerosis Society FH Studies Collaboration (EAS FHSC) is a new initiative of international stakeholders which will help establish a global FH registry to generate large-scale, robust data on the burden of FH worldwide. Methods: The EAS FHSC will maximise the potential exploitation of currently available and future FH data (retrospective and prospective) by bringing together regional/national/international data sources with access to individuals with a clinical and/or genetic diagnosis of heterozygous or homozygous FH. A novel bespoke electronic platform and FH Data Warehouse will be developed to allow secure data sharing, validation, cleaning, pooling, harmonisation and analysis irrespective of the source or format. Standard statistical procedures will allow us to investigate cross-sectional associations, patterns of real-world practice, trends over time, and analyse risk and outcomes (e.g. cardiovascular outcomes, all-cause death), accounting for potential confounders and subgroup effects. Conclusions: The EAS FHSC represents an excellent opportunity to integrate individual efforts across the world to tackle the global burden of FH. The information garnered from the registry will help reduce gaps in knowledge, inform best practices, assist in clinical trials design, support clinical guidelines and policies development, and ultimately improve the care of FH patients. (C) 2016 Elsevier Ireland Ltd.

  • 409.
    Varenhorst, Christoph
    et al.
    Uppsala Clin Res Ctr, Sweden; Uppsala Univ, Sweden.
    Hasvold, Pal
    AstraZeneca Nord Baltic, Sweden; AstraZeneca RandD, Sweden.
    Johansson, Saga
    Uppsala Clin Res Ctr, Sweden; Uppsala Univ, Sweden; AstraZeneca RandD, Sweden.
    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.
    Albertsson, Per
    Univ Gothenburg, Sweden.
    Leosdottir, Margret
    Lund Univ, Sweden.
    Hambraeus, Kristina
    Falun Cty Hosp, Sweden.
    James, Stefan
    Uppsala Clinical Research Center, Uppsala, Sweden; Uppsala University, Uppsala, Sweden.
    Jernberg, Tomas
    Solna Karolinska Univ Hosp, Sweden.
    Svennblad, Bodil
    Uppsala Clin Res Ctr, Sweden.
    Lagerqvist, Bo
    Uppsala Clin Res Ctr, Sweden; Uppsala Univ, Sweden.
    Culprit and Nonculprit Recurrent Ischemic Events in Patients With Myocardial Infarction: Data From SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies)2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007174Article in journal (Refereed)
    Abstract [en]

    Background-Long-term disease progression after myocardial infarction (MI) is inadequately understood. We evaluated the pattern and angiographic properties (culprit lesion [CL]/non-CL [NCL]) of recurrent MI (re-MI) in a large real-world patient population. Methods and Results-Our observational study used prospectively collected data in 108 615 patients with first-occurrence MI enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) between July 1, 2006 and November 29, 2014. During follow-up (median, 3.2 years), recurrent hospitalization for MI occurred in 11 117 patients (10.2%). Of the patients who underwent coronary angiography for the index MI, a CL was identified in 44 332 patients. Of those patients, 3464 experienced an re-MI; the infarct originated from the NCL in 1243 patients and from the CL in 655 patients. In total, 1566 re-MIs were indeterminate events and could not be classified as NCL or CL re-MIs. The risk of re-MI within 8 years related to the NCL was 0.06 (95% confidence interval [CI], 0.05-0.06), compared with 0.03 (95% CI, 0.02-0.03) for the CL. There were no large differences in baseline characteristics of patients with subsequent NCL versus CL re-MIs. Independent predictors of NCL versus CL re-MI were multivessel disease (odds ratio, 2.29; 95% CI, 1.87-2.82), male sex (odds ratio, 1.36; 95% CI, 1.09-1.71), and a prolonged time between the index and re-MI (odds ratio, 1.16; 95% CI, 1.10-1.22). Conclusions-In a large cohort of patients with first-occurrence MI undergoing percutaneous coronary intervention, the risk of re-MI originating from a previously untreated lesion was twice higher than the risk of lesions originating from a previously stented lesion.

  • 410.
    Vavruch, Camilla
    et al.
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Lindström, Torbjörn
    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".
    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.
    Serum leptin levels are independently related to the incidence of ischemic heart disease in a prospective study of patients with type 2 diabetes2015In: Cardiovascular Diabetology, ISSN 1475-2840, E-ISSN 1475-2840, Vol. 14, no 62Article in journal (Refereed)
    Abstract [en]

    Background: New and clinically useful markers of cardiovascular risk are of essence in type 2 diabetes since ischemic heart disease is a major cause of death in these patients. Methods: We analyzed baseline data from 476 men and 244 women who participated in "Cardiovascular Risk factors in Patients with Diabetes -a Prospective study in Primary care" study. All participants had type 2 diabetes and were 55-66 years old at recruitment during year 2005 to 2008. Except for established traditional risk markers for vascular disease, we also estimated vascular complications non-invasively by performance of carotid-femoral pulse-wave velocity (PWV, with applanation-tonometry) and intima-media thickness of carotid arteries (IMT, with B-mode ultrasound). Patients were followed for incidence of ischemic heart disease mortality and morbidity until end of the year 2012, using the national Swedish Cause of Death and Hospitalization Registries. Results: During the follow-up period of a median of 6 years 47 men and 10 women died or were hospitalized for ischemic heart disease including myocardial infarction. Leptin levels were positively related to the hazard ratio (HR) in men (HR for each log 10 unit 4.9, CI 1.99 to 11.8) and women (HR 11.5, CI 1.47 to 89.7). Leptin predicted ischemic heart disease independently of age, HbA1c, BMI, systolic blood pressure and LDL-cholesterol/HDL-cholesterol ratio (men: HR 12.9 CI 3.2-53, women: HR 19.9, CI 1.2-327) This finding of increased risk related to high leptin levels was also statistically significant when carotid-femoral PWV and IMT were both added to the equations in men (hazard ratio 9.2 CI 2.1-41). Conclusions: Our data support the use of serum leptin in type 2 diabetes to add independent prognostic information in terms of ischemic heart disease when compared with traditional cardiovascular risk factors. In the men of the cohort this prognostic information was in addition also to data on IMT and PWV, two non-invasive measurements of the extent of vascular disease. The power to detect a similar relationship in women was less strong due to lower incidence of cardiovascular disease. Trial registration: ClinicalTrials. gov:

  • 411.
    Vedin, Ola
    et al.
    Uppsala University, Sweden; Uppsala Clin Research Centre, Sweden.
    Lam, Carolyn S. P.
    National Heart Centre Singapore, Singapore; Duke NUS Medical Sch, Singapore.
    Koh, Angela S.
    National Heart Centre Singapore, Singapore; Duke NUS Medical Sch, Singapore.
    Benson, Lina
    Regional Cancer Centre Stockholm Gotland, Sweden.
    Hwa Katherine Teng, Tiew
    National Heart Centre Singapore, Singapore; University of Western Australia, Australia.
    Ting Tay, Wan
    National Heart Centre Singapore, Singapore.
    Braun, Oscar O.
    Lund University, Sweden.
    Savarese, Gianluigi
    Karolinska Institute, Sweden; 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.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Significance of Ischemic Heart Disease in Patients With Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction A Nationwide Cohort Study2017In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 6, article id e003875Article in journal (Refereed)
    Abstract [en]

    Background-The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF amp;lt;40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%-50%) and preserved EF (HFpEF; EF amp;gt;= 50%) has been much less explored. Methods and Results-We evaluated 42 987 patients from the Swedish Heart Failure Registry with respect to baseline IHD, outcomes (IHD, HF, cardiovascular events, and all-cause death), and EF change during a median follow-up of 2.2 years. Overall, 23% had HFpEF (52% IHD), 21% had HFmrEF (61% IHD), and 55% had HFrEF (60% IHD). After multivariable adjustment, associations with baseline IHD were similar for HFmrEF and HFrEF and lower in HFpEF (risk ratio, 0.91 [0.89-0.93] versus HFmrEF and risk ratio, 0.90 [0.88-0.92] versus HFrEF). The adjusted risk of IHD events was similar for HFmrEF versus HFrEF and lower in HFpEF (hazard ratio, 0.89 [0.84-0.95] versus HFmrEF and hazard ratio, 0.84 [0.80-0.90] versus HFrEF). After adjustment, prevalent IHD was associated with increased risk of IHD events and all other outcomes in all EF categories except all-cause mortality in HFpEF. Those with IHD, particularly new IHD events, were also more likely to change to a lower EF category and less likely to change to a higher EF category over time. Conclusions-HFmrEF resembled HFrEF rather than HFpEF with regard to both a higher prevalence of IHD and a greater risk of new IHD events. Established IHD was an important prognostic factor across all HF types.

  • 412.
    Vegter, Eline L.
    et al.
    University of Medical Centre Groningen, Netherlands.
    Ovchinnikova, Ekaterina S.
    University of Medical Centre Groningen, Netherlands; University of Groningen, Netherlands.
    van Veldhuisen, Dirk J.
    University of Medical Centre Groningen, Netherlands.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Berezikov, Eugene
    University of Groningen, Netherlands.
    van der Meer, Peter
    University of Medical Centre Groningen, Netherlands.
    Voors, Adriaan A.
    University of Medical Centre Groningen, Netherlands.
    Low circulating microRNA levels in heart failure patients are associated with atherosclerotic disease and cardiovascular-related rehospitalizations2017In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 106, no 8, p. 598-609Article in journal (Refereed)
    Abstract [en]

    Objective Circulating microRNAs (miRNAs) have been implicated in both heart failure and atherosclerotic disease. The aim of this study was to examine associations between heart failure specific circulating miRNAs, atherosclerotic disease and cardiovascular-related outcome in patients with heart failure. Methods The levels of 11 heart failure-specific circulating miRNAs were compared in plasma of 114 heart failure patients with and without different manifestations of atherosclerotic disease. We then studied these miRNAs in relation to biomarkers associated to atherosclerosis and to cardiovascular-related rehospitalizations during 18 months of follow-up. Results At least one manifestation of atherosclerotic disease was found in 70 (61%) of the heart failure patients. A consistent trend was found between an increasing number of manifestations of atherosclerosis (peripheral arterial disease in specific), and lower levels of miR-18a-5p, miR27a-3p, miR-199a-3p, miR-223-3p and miR-652-3p (all P amp;lt; 0.05). Target prediction and network analyses identified several interactions between miRNA targets and biomarkers related to inflammation, angiogenesis and endothelial dysfunction. Lower miRNA levels were associated with higher levels of these atherosclerosis-related biomarkers. In addition, lower miRNA levels were significantly associated with rehospitalizations due to cardiovascular causes within 18 months, with let-7i-5p as strongest predictor [HR 2.06 (95% CI 1.29-3.28), C-index 0.70, P = 0.002]. Conclusions A consistent pattern of lower levels of circulating miRNAs was found in heart failure patients with atherosclerotic disease, in particular peripheral arterial disease. In addition, lower levels of miRNAs were associated with higher levels of biomarkers involved in atherosclerosis and an increased risk of a cardiovascular-related rehospitalization.

  • 413.
    Venetsanos, Dimitrios
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Improving management of STEMI patients treated with primary PCI: Pharmacotherapy, renal function estimation and gender perspective2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI.

    In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p<0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03).

    In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).

    In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment.

    In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI.

    MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03).

    Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients

    List of papers
    1. Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial.
    Open this publication in new window or tab >>Chewed ticagrelor tablets provide faster platelet inhibition compared to integral tablets: The inhibition of platelet aggregation after administration of three different ticagrelor formulations (IPAAD-Tica) study, a randomised controlled trial.
    2017 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 149, p. 88-94Article in journal (Refereed) Published
    Abstract [en]

    AIMS: To provide pharmacodynamic data of crushed and chewed ticagrelor tablets, in comparison with standard integral tablets.

    METHODS: Ninety nine patients with stable angina were randomly assigned, in a 3:1:1 fashion, to one of the following 180mg ticagrelor loading dose (LD) formulations: A) Integral B) Crushed or C) Chewed tablets. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60min after LD. High residual platelet reactivity (HRPR) was defined as >208 P2Y12 reaction units (PRU).

    RESULTS: There was no significant difference in PRU values at baseline. PRU 20min after LD were 237 (182-295), 112 (53-238) and 84 (29-129) and 60min after LD, 56 (15-150), 51 (18-85) and 9 (7-34) in integral, crushed and chewed ticagrelor LD, respectively (p<0.01 for both). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60min. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20min whereas no difference was observed at 60min. At 20min, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).

    CONCLUSION: With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared to standard integral tablets. We also show that administration of chewed tablets is feasible and provides faster inhibition than either crushed or integral tablets.

    CLINICAL TRIAL REGISTRATION: European Clinical Trial Database (EudraCT number 2014-002227-96).

    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-133985 (URN)10.1016/j.thromres.2016.10.013 (DOI)000391287300016 ()27773347 (PubMedID)
    Note

    Funding agencies: AstraZeneca

    Available from: 2017-01-17 Created: 2017-01-17 Last updated: 2017-11-29
    2. Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR
    Open this publication in new window or tab >>Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR
    Show others...
    2015 (English)In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 9, p. 1-8, article id e007835Article in journal (Refereed) Published
    Abstract [en]

    Objectives: To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting: Single centre, methodological study. Participants: 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures: Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens. statistics. Results: MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias -1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m(2) and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (. 0.83). CG showed the worst performance (correlation 0.73%, bias -1% to 3%, precision 22.5 mL/min 1.73 m(2) and P30 75%). The rG-CystC formula had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (kappa=0.87), whereas at discharge agreement was substantially lower (kappa=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions: In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.

    Place, publisher, year, edition, pages
    BMJ PUBLISHING GROUP, 2015
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-122794 (URN)10.1136/bmjopen-2015-007835 (DOI)000363484000021 ()26399570 (PubMedID)
    Available from: 2015-11-23 Created: 2015-11-23 Last updated: 2017-12-01
  • 414.
    Venetsanos, Dimitrios
    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.
    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.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    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.
    Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 9, p. 1-8, article id e007835Article in journal (Refereed)
    Abstract [en]

    Objectives: To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting: Single centre, methodological study. Participants: 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures: Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens. statistics. Results: MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias -1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m(2) and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (. 0.83). CG showed the worst performance (correlation 0.73%, bias -1% to 3%, precision 22.5 mL/min 1.73 m(2) and P30 75%). The rG-CystC formula had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (kappa=0.87), whereas at discharge agreement was substantially lower (kappa=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions: In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.

  • 415.
    Venetsanos, Dimitrios
    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
    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.
    Sederholm Lawesson, Sofia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Gustafsson, Kerstin
    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.
    Wallen, Hakan
    Karolinska Institute, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    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.
    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.
    Pretreatment with ticagrelor may offset additional inhibition of platelet and coagulation activation with bivalirudin compared to heparin during primary percutaneous coronary intervention2018In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 171, p. 38-44Article in journal (Refereed)
    Abstract [en]

    Background

    It remains unknown if bivalirudin compared to heparin confers any additional inhibition of platelet and coagulation activation during primary percutaneous coronary intervention(PPCI) after pretreatment with ticagrelor.

    Methods

    In this substudy of VALIDATE-SWEDEHEART trial, 103 patients pretreated with ticagrelor were randomized before PPCI to heparin or bivalirudin. Blood samples were collected before and 1 and 12 h after PPCI. We measured platelet reactivity (PR) using Multiplate, soluble P-selectin, thrombin-antithrombin complexes (TAT) and prothrombin fragments 1 + 2 (F1 + 2) as markers of platelet and coagulation activation.

    Results

    The median (IQR) time from ticagrelor administration to randomization was 63 (29) vs 60 (24) minutes, p = 0.28. ADP-induced PR did not significantly differ between groups over time (heparin vs bivalirudin, AUC 73 (62) vs 74 (68), p = 0.74, 32 (42) vs 43 (51), p = 0.38, 15 (15) vs 19 (15), p = 0.29, before, 1 and 12 h after PPCI). Soluble P-selectin did not significantly differ between groups. At 1 h TAT significantly increased with bivalirudin (3.0 (1.3) to 4.3 (4.2) ug/L; p < 0.01), but not with UFH (3.1 (2.1) to 3.5 (1.6) ug/L, p = 0.24). F1 + 2 increased in both groups but the rise was numerically higher with bivalirudin (170 (85) to 213 (126) pmol/L vs 168 (118) to 191 (103) pmol/L). At 12 h, a comparable significant increase in thrombin generation was observed in both groups.

    Conclusion

    In patients treated with ticagrelor, we found no major differences between bivalirudin and heparin in platelet aggregation or coagulation markers, which is in agreement with the neutral clinical results of the VALIDATE-SWEDEHEART study.

  • 416.
    Venetsanos, Dimitrios
    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.
    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.
    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.
    Cequier, Angel
    University of Barcelona, Spain.
    Chettibi, Mohamed
    CHU Frantz Fanon, Algeria.
    Goodman, Shaun G.
    University of Toronto, Canada.
    vant Hof, Arnoud W.
    Isala Clin, Netherlands.
    Montalescot, Gilles
    Sorbonne University, 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.
    Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial: a prespecified analysis2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, article id e015241Article in journal (Refereed)
    Abstract [en]

    Objectives To evaluate gender differences in outcomes in patents with ST-segment elevation myocardial infarction (STEMI) planned for primary percutaneous coronary intervention (PPCI). Settings A prespecified gender analysis of the multicentre, randomised, double-blind Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery. Participants Between September 2011 and October 2013, 1862 patients with STEMI and symptom duration amp;lt;6 hours were included. Interventions Patients were assigned to prehospital versus in-hospital administration of 180 mg ticagrelor. Outcomes The main objective was to study the association between gender and primary and secondary outcomes of the main study with a focus on the clinical efficacy and safety outcomes. Primary outcome: the proportion of patients who did not have 70% resolution of ST-segment elevation and did not meet the criteria for Thrombolysis In Myocardial Infarction (TIMI) flow 3 at initial angiography. Secondary outcome: the composite of death, MI, stent thrombosis, stroke or urgent revascularisation and major or minor bleeding at 30 days. Results Women were older, had higher TIMI risk score, longer prehospital delays and better TIMI flow in the infarct-related artery. Women had a threefold higher risk for all-cause mortality compared with men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 to 5.51). After adjustment, the difference was attenuated but remained statistically significant (HR 2.08, 95% CI 1.03 to 4.20). The incidence of major bleeding events was twofold to threefold higher in women compared with men. In the multivariable model, female gender was not an independent predictor of bleeding (Platelet Inhibition and Patient Outcomes major HR 1.45, 95% CI 0.73 to 2.86, TIMI major HR 1.28, 95% CI 0.47 to 3.48, Bleeding Academic Research Consortium type 3-5 HR 1.45, 95% CI 0.72 to 2.91). There was no interaction between gender and efficacy or safety of randomised treatment. Conclusion In patients with STEMI planned for PPCI and treated with modern antiplatelet therapy, female gender was an independent predictor of short-term mortality. In contrast, the higher incidence of bleeding complications in women could mainly be explained by older age and clustering of comorbidities.

  • 417.
    Venetsanos, Dimitrios
    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.
    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.
    Fröbert, O.
    Department of Cardiology, Örebro University, Sweden.
    Omerovic, E.
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Henareh, L.
    Department of Medicine, Karolinska Institute, Sweden.
    Robertsson, L.
    Department of Cardiology, Södra Älvsborgs Sjukhus, Sweden.
    Linder, R.
    Department of Cardiology, Danderyd Hospital, Sweden.
    Götberg, M.
    Department of Cardiology, Skåne University Hospital, Sweden.
    James, S.
    Department of Medical Sciences, Uppsala University, Sweden.
    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.
    Erlinge, D.
    Department of Cardiology, Skåne University Hospital, Sweden.
    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.
    Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A subgroup analysis of the VALIDATE-SWEDEHEART trial2019In: European Heart Journal. Acute Cardiovascular Care, ISSN 2048-8734, Vol. 8, no 6, p. 502-509Article in journal (Refereed)
    Abstract [en]

    Aims:

    Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.

    Methods:

    This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.

    Results:

    There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60–1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89–1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54–1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94–1.43) in men, pfor interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54–1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93–1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women.

    Conclusion:

    In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

  • 418.
    Venetsanos, Dimitrios
    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.
    Sederholm Lawesson, Sofia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    James, Stefan
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    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.
    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.
    Bivalirudin versus heparin with primary percutaneous coronary intervention2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 201, p. 9-16Article in journal (Refereed)
    Abstract [en]

    Background: Optimal adjunctive therapy in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI (PPCI) remains a matter of debate. Our aim was to compare the efficacy and safety of bivalirudin to unfractionated heparin (UFH), with or without glycoprotein IIb/IIIa inhibitors (GPI) in a large real-world population, using data from the Swedish national registry, SWEDEHEART. Method: From 2008 to 2014 we identified 23,800 STEMI patients presenting within 12 hours from symptom onset treated with PPCI and UFH +/- GPI or bivalirudin +/- GPI. Primary outcomes included 30-day all-cause mortality and major in-hospital bleeding. Multivariable regression models and propensity score modelling were utilized to study adjusted association between treatment and outcome. Results: Treatment with UFH +/- GPI was associated with similar risk of 30-day mortality compared to bivalirudin +/- GPI (5.3% vs 5.5%, adjusted HR 0.94; 95% CI 0.82-1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between UFH +/- GPI and bivalirudin +/- GPI. In contrast, treatment with UFH +/- GPI was associated with a significant higher risk of major in-hospital bleeding (adjusted OR 1.62; 95% CI 1.30-2.03). When including GPI use in the multivariable analysis, the difference was attenuated and no longer significant (adjusted OR 1.25; 95% CI 0.92-1.70). Conclusion: Bivalirudin +/- GPI was associated with significantly lower risk for major in hospital bleeding but no significant difference in 30-day or one year mortality, stent thrombosis or re-infarction compared with UFH +/- GPI. The bleeding reduction associated with bivalirudin could be explained by the greater GPI use with UFH. (C) 2018 Elsevier Inc. All rights reserved.

  • 419.
    Venetsanos, Dimitrios
    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.
    Sederholm Lawesson, Sofia
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Panayi, Georgios
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Todt, Tim
    Lund Univ, Sweden.
    Berglund, 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.
    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.
    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.
    Long-term efficacy of drug coated balloons compared with new generation drug-eluting stents for the treatment of de novo coronary artery lesions2018In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 92, no 5, p. E317-E326Article in journal (Refereed)
    Abstract [en]

    Background Studies comparing drug coated balloons (DCB) with new generation drug-eluting stents (nDES) for the treatment of de novo coronary artery lesions are lacking. Methods From 2009 to 2016, DCB or nDES used for treatment of de novo coronary lesions at our institution were included, in total 1,197 DEB and 6,458 nDES. We evaluated target lesions restenosis (TLR) and definite target lesion thrombosis (TLT). Propensity score modeling were utilized to study adjusted associations between treatment and outcomes. Results Median follow-up was 901days. DCB patients were older, with higher cardiovascular risk profile. Bailout stenting after DCB was performed in 8% of lesions. The cumulative rate of TLR and TLT was 7.0 vs. 4.9% and 0.2 vs. 0.8% for DCB vs. nDES, respectively. Before adjustment, DCB was associated with a higher risk of TLR [hazard ratio (HR) 1.44; 95% confidence interval (CI) 1.07-1.94] and a non-significantly lower risk of TLT (HR 0.30; 95% CI 0.07-1.24), compared to nDES. In the propensity matched population consisted of 1,197 DCB and 1,197 nDES, treatment with DCB was associated with similar risk for TLR (adjusted HR 1.05; 95% CI 0.72-1.53) but significantly lower risk for TLT (adjusted HR 0.18; 95% CI 0.04-0.82) compared to nDES. Conclusions Treatment with DCB was associated with a similar risk of TLR and a lower risk of definite TLT compared with nDES. In selected cases, DCB appears as a good alternative to nDES for the treatment of de novo coronary lesions.

  • 420.
    Venkata Ramanarao, Parasa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Forsslund, Helena
    Karolinska Inst, Sweden.
    Enger, Tobias
    Karolinska Inst, Sweden.
    Lorenz, Daniel
    Karolinska Inst, Sweden.
    Kullberg, Susanna
    Karolinska Inst, Sweden.
    Eklund, Anders
    Karolinska Inst, Sweden.
    Skold, Magnus
    Karolinska Inst, Sweden.
    Wahlstrom, Jan
    Karolinska Inst, Sweden.
    Grunewald, Johan
    Karolinska Inst, Sweden.
    Brighenti, Susanna
    Karolinska Inst, Sweden.
    Enhanced CD8(+) cytolytic T cell responses in the peripheral circulation of patients with sarcoidosis and non-Lofgrens disease2018In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 138, p. S38-S44Article in journal (Refereed)
    Abstract [en]

    Background: The role of CD4(+) T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8(+) cytolytic T cells (CTLs). Methods: CD8(+) CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8(+) T cells, using flow cytometry. Cytolytic function in blood lymphocytes was assessed using a standard 51Cr-release assay. Patients with Lofgrens syndrome (LS) and an acute disease onset, were compared to non-LS patients with an insidious onset. Results: Higher proportions of peripheral CD8(+) CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to healthy controls. Blood CTLs from non-LS patients had significantly higher expression of perforin, granzyme B and granulysin compared to matched BAL, while LS patients maintained lower levels of effector molecules in both compartments. Mitogen-stimulated peripheral lymphocytes from sarcoidosis patients, particularly from the non-LS group, showed a higher target cell lysis compared to controls. Conclusion: These results demonstrated enhanced peripheral CD8(+) CTL responses in sarcoidosis, especially in non-LS patients who have an increased risk of chronic disease. Further comprehensive clinical studies are warranted to increase our understanding of CD8(+) CTL responses in sarcoidosis.

  • 421.
    Verheijden Klompstra, Leonie
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    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. Univ Calif Irvine, CA 92717 USA.
    Self-efficacy Mediates the Relationship Between Motivation and Physical Activity Patients With Heart Failure2018In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 3, p. 211-216Article in journal (Refereed)
    Abstract [en]

    Motivation is necessary in patients with heart failure (HF) who are attempting to become more physically active but may not be sufficient to initiate physical activity. Self-efficacy might explain the relationship between motivation and physical activity. Objective: The aim of this study was to examine the role of exercise self-efficacy in the relationship between exercise motivation and physical activity in patients with HF. Methods: A total of 100 stable patients with HF (88% in New York Heart Association class IVIII; mean age, 67 +/- 13 years; 62% men) were studied. Self-efficacy was measured with the Exercise Self-Efficacy Scale; motivation, with the Exercise Motivation Index; and physical activity, with a self-report questionnaire. Logistic regression analyses were made to examine the mediation effect of exercise self-efficacy on the relationship between exercise motivation and physical activity. Result: Forty-two percent of the 100 patients reported engaging in less than 60 minutes per week of physical activity. Motivation predicted physical activity (b = 0.58, P amp;lt; .05), but after controlling for self-efficacy, the relationship between motivation and physical activity was no longer significant (b = 0.76, P = .06), indicating full mediation. Conclusion: Motivation to be physically active is important but not sufficient. In addition to a high level of motivation to be physically active, it is important that patients with HF have a high degree of self-efficacy.

  • 422.
    Vitale, Cristiana
    et al.
    IRCCS San Raffaele Pisana, Italy.
    Jankowska, Ewa
    Wroclaw Med Univ, Poland.
    Hill, Loreena
    Queens Univ, North Ireland.
    Piepoli, Massimo
    Guglielmo da Saliceto Hosp, Italy; Inst Life Sci, Italy.
    Doehner, Wolfram
    Wroclaw Med Univ, Poland.
    Anker, Stefan D.
    Charite Univ Med Berlin, Germany; Charite Univ Med Berlin, Germany.
    Lainscak, Mitja
    Gen Hosp Murska Sobota, Slovenia.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Univ Ljubljana, Slovenia.
    Ponikowski, Piotr
    Wroclaw Med Univ, Poland.
    Rosano, Giuseppe M. C.
    Seferovic, Petar
    Univ Med Ctr Belgrade, Serbia.
    Coats, Andrew J.
    Heart Failure Association/European Society of Cardiology position paper on frailty in patients with heart failure2019In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) and frailty are two distinct yet commonly associated conditions. The interplay between the two conditions is complex, due to overlaps in underlying mechanisms, symptoms and prognosis. The assessment of frailty in patients with HF is crucial, as it is associated with both unfavourable outcomes and reduced access and tolerance to treatments. However, to date a consensus definition of frailty in patients with HF remains lacking and the need for a validated assessment score, for identifying those HF patients with frailty, is high and timely. This position paper proposes a new definition of frailty for use by healthcare professionals in the setting of HF and creates a foundation for the design of a tailored and validated score for this common condition.

  • 423.
    Vorkapic, Emina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Folkesson, Maggie
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Magnell, Kerstin
    Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden.
    Bohlooly-Y, Mohammad
    Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden.
    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.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    ADAMTS-1 in abdominal aortic aneurysm2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0178729Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Extracellular matrix degradation is a hallmark of abdominal aortic aneurysm (AAA). Among proteases that are capable of degrading extracellular matrix are a disintegrin and metalloproteases with thrombospondin motifs (ADAMTS). Pathogenesis of these proteases in AAA has not been investigated until date.

    METHODS AND RESULTS: Human aneurysmal and control aortas were collected and analyzed with RT-PCR measuring the ADAMTS-1, 4,5,6,8,9,10,13,17 and ADAMTSL-1. Expression of a majority of the investigated ADAMTS members on mRNA level was decreased in aneurysm compared to control aorta. ADAMTS-1 was one of the members that was reduced most. Protein analysis using immunohistochemistry and western blot for localization and expression of ADAMTS-1 revealed that ADAMTS-1 was present predominantly in areas of SMCs and macrophages in aneurysmal aorta and higher expressed in AAA compared to control aortas. The role of ADAMTS-1 in AAA disease was further examined using ADAMTS-1 transgenic/apoE-/- mice with the experimental angiotensin II induced aneurysmal model. Transgenic mice overexpressing ADAMTS-1 showed to be similar to ADAMTS-1 wild type mice pertaining collagen, elastin content and aortic diameter.

    CONCLUSION: Several of the ADAMTS members, and especially ADAMTS-1, are down regulated at mRNA level in AAA, due to unknown mechanisms, at the same time ADAMTS-1 protein is induced. The cleavage of its substrates, don't seem to be crucial for the pathogenesis of AAA but rather more important in the development of thoracic aortic aneurysm and atherosclerosis as shown in previous studies.

  • 424.
    Vánky, Farkas
    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.
    Hultkvist, 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.
    Svedjeholm, Rolf
    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.
    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.
    Is the present definition of mycardial infarction in transcatheter aortic valve implantation relevant for the postprocedulal outcome?2015Conference paper (Other academic)
    Abstract [en]

    Background: The association between biomarkers and adverse procedural outcome has been established. However, the additive prognostic importance of signs and symptoms according to the Valve Academic Research Consortium (VARC)-2 criteria for periprocedural myocardial infarction (MI) are more uncertain.

    Aim: To evaluate the relevance of the individual components of the VARC-2 criteria for periprocedural myocardial infarction (MI) in transcatheter aortic valve implantation (TAVI).Methods: A total of 125 consecutive TAVI patients were prospectively included in this study. Biomarkers for MI were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records.

    Results: The criteria of elevated biomarkers and of signs or symptoms were found in 27 ( 22%) and 32 ( 26%) of the patients, respectively. According to VARC-2 definition, 12 (10%) had MI. VARC-2 definition of MI, Troponin T (TnT) >600 ng/L, and presence of signs or symptoms correlated with 6 month mortality, prolonged ICU stay, elevation of N-terminal prohormone brain natriuretic peptide, and renal impairment. No signs or symptoms were found in 7 (4 4%) of the patients who fulfilled the criterion of elevated TnT>600 ng/L. In the group with positive TnT criterion, there were no significant differences between those with and without signs or symptoms in respect to levels of TnT (1014 [585-1720] ng/L versus 704 [515-905] ng/L, p=0.17) or creatine kinase-MB ( 36 [25-52] μg/L versus 29 [25-39] μg/L, p=0.32). In the multiple logistic regression model, TnT>600 ng/L turned out as the only independent variable associated with 6-month mortality, OR 7.89 (95% CI 2.21-28.1, p = 0.001).

    Conclusion: Myocardial injury in TAVI, measured with TnT, correlates well with adverse procedural outcome. The additional requirement of signs or symptoms for the diagnosis of MI results in omission of a considerable number of clinically significant MI.

  • 425.
    Wahman, K
    et al.
    Department of Neurobiology, Care Sciences and Society (NVS), Division of neurorehabilitation, Karolinska Institutet, 139 89 Stockholm, Sweden..
    Nash, MS
    Department of Neurobiology, Care Sciences and Society (NVS), Division of neurorehabilitation, Karolinska Institutet, 139 89 Stockholm, Sweden.
    Lewis, JE
    Department of Neurobiology, Care Sciences and Society (NVS), Division of neurorehabilitation, Karolinska Institutet, 139 89 Stockholm, Sweden.
    Seiger, A
    Department of Neurobiology, Care Sciences and Society (NVS), Division of neurorehabilitation, Karolinska Institutet, 139 89 Stockholm, Sweden.
    Levi, Richard
    Department of Neurobiology, Care Sciences and Society (NVS), Division of neurorehabilitation, Karolinska Institutet, 139 89 Stockholm, Sweden.
    Increased cardiovascular disease risk in Swedish persons with paraplegia: The Stockholm spinal cord injury study.2010In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 42, no 5, p. 489-492Article in journal (Refereed)
    Abstract [en]

    Objective: Comparison of prevalence of cardiovascular disease risks in persons with chronic traumatic paraplegia with those in the general population.andlt;br /andgt;Design: Cross-sectional comparative study.andlt;br /andgt;Subjects: A total of 135 individuals, age range 18-79 years, with chronic (andgt; or = 1 year) traumatic paraplegia.andlt;br /andgt;Methods: The prevalences of diabetes mellitus, dyslipidaemia, hypertension, overweight, and smoking, were assessed in the study population and were compared with an age- and gender-matched sample of the general population in the region under study. History of myocardial infarction and medication for dyslipidaemia, hypertension, and diabetes mellitus were also recorded. chi2 tests were used to compare the paraplegic cohort with the general population sample.andlt;br /andgt;Results: Significantly more persons with paraplegia reported a history of myocardial infarction (5.9%) than those in the comparison group (0.7%). The prevalences of diabetes mellitus (5.9%), dyslipidaemia (11.1%), and hypertension (14.1%) were also significantly higher in the paraplegic group, as were drug treatment for these disorders.andlt;br /andgt;Conclusion: Persons with paraplegia report increased prevalences of diabetes mellitus, hypertension, and dyslipidaemia, in particular, compared with the general population. Population-based screening and therapeutic counter-measures for these conditions may therefore be particularly indicated for this patient group.

  • 426.
    Wahman, Kerstin
    et al.
    Department of Neurobiology, Care Sciences and Society, Division of Neurorehabilitation, Karolinska Institutet.
    Nash, Mark S
    University of Miami Miller School of Medicine, Miami, Florida, USA.
    Westgren, Ninni
    Spinalis Spinal Cord Injury Rehabilitation Unit, Karolinska University Hospital, Stockholm, Sweden.
    Lewis, John E
    University of Miami Miller School of Medicine, Miami, Florida, USA.
    Seiger, Ake
    Department of Neurobiology, Care Sciences and Society, Division of Neurorehabilitation, Karolinska Institutet.
    Levi, Richard
    Department of Neurobiology, Care Sciences and Society, Division of Neurorehabilitation, Karolinska Institutet.
    Cardiovascular disease risk factors in persons with paraplegia: the Stockholm spinal cord injury study.2010In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 42, no 3, p. 272-278Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine cardiovascular disease risk factors and risk clusters in Swedish persons with traumatic wheelchair-dependent paraplegia.

    DESIGN: Prospective examination.

    SUBJECTS: A total of 135 individuals aged 18-79 years with chronic (>or= 1 year) post-traumatic paraplegia.

    METHODS: Cardiovascular disease risk factors; dyslipidemia, impaired fasting glucose, hypertension, overweight, smoking, and medication usage for dyslipidemia, hypertension, and diabetes mellitus, were analyzed according to authoritative guidelines. Stepwise regression tested the effects of age, gender, and injury characteristics on cardiovascular disease risks.

    RESULTS: High-prevalence risk factors were dyslipidemia (83.1%), hypertension (39.3%), and overweight (42.2%) with pervasive clustering of these risks. Being older was related to increased cardiovascular disease risk, except for dyslipidemia. Hypertension was more common in low-level paraplegia. Prevalence of impaired fasting glucose was lower than previously reported after paraplegia. A high percentage of persons being prescribed drug treatment for dyslipidemia and hypertension failed to reach authoritative targets for cardiovascular disease risk reduction.

    CONCLUSION: Swedish persons with paraplegia are at high risk for dyslipidemia, hypertension, and overweight. Impaired fasting glucose was not as common as reported in some previous studies. Pharmacotherapy for dyslipidemia and hypertension often failed to achieve recommended targets. Population-based screening and therapeutic countermeasures to these cardiovascular disease risks are indicated.

  • 427.
    Waldreus, Nana
    et al.
    Karolinska Inst, Sweden.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Australian Catholic Univ, Australia.
    Ivarsson, Bodil
    Lund Univ, Sweden; Skane Univ Hosp, Sweden; Med Serv, 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.
    Arestedt, Kristofer
    Linnaeus Univ, Sweden.
    Kjellstrom, Barbro
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Development and Validation of a Questionnaire to Measure Patients Experiences of Health Care in Pulmonary Arterial Hypertension Outpatient Clinics2019In: Heart, Lung and Circulation, ISSN 1443-9506, E-ISSN 1444-2892, Vol. 28, no 7, p. 1074-1081Article in journal (Refereed)
    Abstract [en]

    Background Measuring the patients experience of care at an outpatient clinic can provide feedback about the quality of health care and if needed, can be support for quality improvements. To date, there is no patient reported experience measurement (PREM) developed targeting patients at the pulmonary arterial hypertension (PAH) outpatient clinics. Therefore, the aim was to develop and evaluate the psychometric properties of a PREM scale to be used for patients at PAH-outpatient clinics. Methods The development and psychometric evaluation of the PREM for patients at PAH outpatient clinics followed two stages: (I) development of the PAH Clinic PREM (PAHC-PREM) scale based on interviews with patients; and (II) psychometric evaluation of the PAHC-PREM scale including data quality, factor structure (construct validity), criterion validity and internal consistency. Results A sample of 156 patients at PAH outpatient clinics completed the PAHC-PREM scale (median age 69 years, 57% women). Unidimensionality of the PAHC-PREM scale was supported by parallel analysis. A single factor explained 67% of the variance. Inter-item and item-total correlations were satisfactory (0.46-0.88 and 0.64-0.91, respectively). Internal consistency reliability with ordinal coefficient alpha was good (0.93). Conclusions The PAHC-PREM scale was demonstrated to have good psychometric properties and is now ready to be used to measure quality of health care experience from patients at PAH-outpatient clinics.

    The full text will be freely available from 2020-08-10 07:57
  • 428.
    Waldréus, Nana
    Linköping University, Department of Social and Welfare Studies, Division of Health, Activity and Care. Linköping University, Faculty of Medicine and Health Sciences.
    Thirst in Patients with Heart Failure: Description of thirst dimensions and associated factors with thirst2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Introduction: Nurses and other health care professionals meet patients with heart failure (HF) who report they are thirsty. Thirst is described by the patients as a concern, and it is distressing. Currently there are no standardized procedures to identify patients with increased thirst or to help a patient to manage troublesome thirst and research in the area of thirst is scarce. In order to prevent and relieve troublesome thirst more knowledge is needed on how thirst is experienced and what factors cause increased thirst.

    Aim: The aim of this thesis was to describe the thirst experience of patients with HF and describe the relationship of thirst with physiologic, psychologic and situational factors. The goal was to contribute to the improvement of the care by identifying needs and possible approaches to prevent and relieve thirst in patients with HF.

    Methods: The studies in this thesis used a cross-sectional design (Study I) and prospective observational designs (II-IV). Studies include data from patients with HF who were admitted to the emergency department for deterioration in HF (I, IV) or visited an outpatient HF clinic for worsening of HF symptoms (III); others were patients who were following up after HF hospitalization (II), and patients with no HF diagnosis who sought care at the emergency department for other illness (I). Patients completed questionnaires on thirst intensity, thirst distress, HF self-care behaviour, feeling depressive and feeling anxious. Data on sociodemographic, clinical characteristics, pharmacological treatment and prescribed fluid restriction were retrieved from hospital medical records and by asking the patients. Data were also collected from blood, urine and saliva samples to measure biological markers of dehydration, HF severity and stress.

    Results: Thirst was prevalent in 1 out of 5 patients (II) and 63% of patients with worsening of HF symptoms experienced moderate to severe thirst distress at hospital admission (IV). Patients at an outpatient HF clinic who reported thirst at the first visit were more often thirsty at the follow-up visits compared to patients who did not report thirst at the first visit (II). Thirst intensity was significantly higher in patients hospitalized with decompensated HF compared to patients with no HF (median 75 vs. 25 mm, visual analogue scale [VAS] 0-100 mm; P < 0.001) (I). During optimization of pharmacological treatment of HF, thirst intensity increased in 67% of the patients. Thirst intensity increased significantly more in patients in the high thirst intensity group compared to patients in the low thirst intensity group (median +18 mm vs. -3 mm; P < 0.001) (III). Patients who were admitted to the hospital with high thirst distress continued to have high thirst distress over time (IV). A large number of patients were bothered by thirst and feeling dry in the mouth when they were thirsty (III, IV). Patients with a fluid restriction had high thirst distress over time and patients who were feeling depressed had high thirst intensity over time (IV). Thirst was associated with fluid restriction (III-IV), a higher serum urea (IIIII), and depressive symptoms (II).

    Conclusions: A considerable amount of patients with HF experiences thirst intensity and thirst distress. Patients who reported thirst at the first follow-up more often had thirst at the subsequent follow-ups. The most important factors related to thirst intensity or thirst distress were a fluid restriction, a higher plasma urea, and depressive symptoms. Nurses should ask patients with HF if they are thirsty and measure the thirst intensity and thirst distress, and ask if thirst is bothering them. Each patient should be critically evaluated if a fluid restriction really is needed, if the patient might be dehydrated or needs to be treated for depression.

    List of papers
    1. Thirst in the elderly with and without heart failure
    Open this publication in new window or tab >>Thirst in the elderly with and without heart failure
    2011 (English)In: Archives of gerontology and geriatrics (Print), ISSN 0167-4943, E-ISSN 1872-6976, Vol. 53, no 2, p. 174-178Article in journal (Refereed) Published
    Abstract [en]

    Elderly patients with heart failure (HF) may be troubled by thirst, despite the fact that elderly have an impaired ability to sense thirst. The present study was undertaken to compare the intensity of thirst in patients with and without HF and to evaluate how this symptom relates to the health-related quality of life and indices of the fluid balance. Forty-eight patients (mean age 80 years) admitted to hospital with worsening HF (n = 23) or with other acute illness (n = 25) graded their thirst and estimated their health-related quality of life (HRQoL). Serum sodium was measured and urine samples were assessed for color and electrolyte content. The HF patients reported significantly more intensive thirst (median = 75 mm) compared with those in the control group (median = 25 mm; p less than 0.0001). There was no statistically significant relationship between thirst and HRQoL, which was low overall. Serum sodium and urine color did not differ significantly between the groups, but the urine of the HF patients had a lower sodium concentration and osmolality. We conclude that elderly patients with worsening HF have considerably increased thirst and, hence, intense thirst should be regarded as a symptom of HF.

    Place, publisher, year, edition, pages
    Elsevier, 2011
    Keywords
    Thirst of elderly; Aged heart failure patients; Quality of life; Dehydration
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-69768 (URN)10.1016/j.archger.2010.10.003 (DOI)000292547000044 ()
    Available from: 2011-08-10 Created: 2011-08-08 Last updated: 2017-12-08Bibliographically approved
    2. Thirst Trajectory and Factors Associated With Persistent Thirst in Patients With Heart Failure
    Open this publication in new window or tab >>Thirst Trajectory and Factors Associated With Persistent Thirst in Patients With Heart Failure
    Show others...
    2014 (English)In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 20, no 9, p. 689-695Article in journal (Refereed) Published
    Abstract [en]

    Background: Thirst is often increased in patients with heart failure (HF) and can cause distress during the course of the condition. The aim of the present study was to describe the trajectory of thirst during an 18-month period and to identify variables associated with persistent thirst in patients with HF. Methods and Results: Data were collected from 649 patients with HF with the use of the Revised Heart Failure Compliance Scale at 1, 6, 12, and 18 months after a period of hospital treatment for worsening HF. Thirst trajectory was described for the 4 follow-up visits and logistic regression analysis was used to identify factors independently associated with persistent thirst. In total, 33% (n = 212) of the patients reported thirst on greater than= 1 occasions and 34% (n = 46) continued to have thirst at every follow-up visit. Nineteen percent (n = 121) of the patients had persistent thirst. Patients with persistent thirst were more often younger and male and had more HF symptoms. Higher body mass index and serum urea also increased the risk of persistent thirst. Conclusions: Patients with HF who were thirsty at the 1-month follow-up were more often also thirsty at subsequent visits. Assessment of thirst is warranted in clinical practice because one-fifth of patients suffer from persistent thirst.

    Place, publisher, year, edition, pages
    Elsevier, 2014
    Keywords
    Thirst; heart failure; trajectory; persistent thirst
    National Category
    Clinical Medicine Sociology
    Identifiers
    urn:nbn:se:liu:diva-111268 (URN)10.1016/j.cardfail.2014.06.352 (DOI)000341799300010 ()24951934 (PubMedID)
    Available from: 2014-10-15 Created: 2014-10-14 Last updated: 2019-06-27Bibliographically approved
    3. Changes in Thirst Intensity During Optimization of Heart Failure Medical Therapy by Nurses at the Outpatient Clinic.
    Open this publication in new window or tab >>Changes in Thirst Intensity During Optimization of Heart Failure Medical Therapy by Nurses at the Outpatient Clinic.
    Show others...
    2016 (English)In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 31, no 5, p. E17-E24Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Thirst can be aggravated in patients with heart failure (HF), and optimization of HF medication can have positive impact on thirst.

    OBJECTIVES: The aims of this study were to describe changes in thirst intensity and to determine factors associated with high thirst intensity during optimization of HF medication.

    METHODS AND RESULTS: Patients with HF (N = 66) who were referred to an HF clinic for up-titration of HF medication were included. Data were collected during the first visit to the clinic and at the end of the treatment program. Data were dichotomized by the median visual analog scale score for thirst, dividing patients into 2 groups: low thirst intensity (0-20 mm) and high thirst intensity (>20 mm on a visual analog scale of 0-100 mm). In total, 67% of the patients reported a higher thirst intensity after the HF up-titration program. There was no difference in thirst intensity between the patients who reached target doses and those who did not. Plasma urea level (odds ratio, 1.33; 95% confidence interval, 1.07-1.65) and fluid restriction (odds ratio, 6.25; 95% confidence interval, 1.90-20.5) were independently associated with high thirst intensity in patients with HF.

    CONCLUSIONS: Thirst intensity increased in two-thirds of the patients during a time period of optimization of HF medication. Fluid restriction and plasma urea levels were associated with high thirst intensity.

    Place, publisher, year, edition, pages
    Lippincott Williams & Wilkins, 2016
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-125914 (URN)10.1097/JCN.0000000000000319 (DOI)000382251400003 ()26696035 (PubMedID)
    Note

    Funding agencies: Mats Klebergs Stiftelse; Lindhes Advokatbyra

    Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2019-06-27Bibliographically approved
  • 429.
    Waldréus, Nana
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Social and Welfare Studies, Division of Nursing Science.
    Hahn, Robert G
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Department of Research, Södertälje Sjukhus, Södertälje, Sweden.
    Lyngå, Patrik
    Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset, Stockholm, Sweden.
    van der Wal, Martje H L
    Department of Cardiology, University of Groningen, University Medical Center Groningen, the Netherlands.
    Hägglund, Ewa
    Karolinska Institutet, Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Changes in Thirst Intensity During Optimization of Heart Failure Medical Therapy by Nurses at the Outpatient Clinic.2016In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 31, no 5, p. E17-E24Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Thirst can be aggravated in patients with heart failure (HF), and optimization of HF medication can have positive impact on thirst.

    OBJECTIVES: The aims of this study were to describe changes in thirst intensity and to determine factors associated with high thirst intensity during optimization of HF medication.

    METHODS AND RESULTS: Patients with HF (N = 66) who were referred to an HF clinic for up-titration of HF medication were included. Data were collected during the first visit to the clinic and at the end of the treatment program. Data were dichotomized by the median visual analog scale score for thirst, dividing patients into 2 groups: low thirst intensity (0-20 mm) and high thirst intensity (>20 mm on a visual analog scale of 0-100 mm). In total, 67% of the patients reported a higher thirst intensity after the HF up-titration program. There was no difference in thirst intensity between the patients who reached target doses and those who did not. Plasma urea level (odds ratio, 1.33; 95% confidence interval, 1.07-1.65) and fluid restriction (odds ratio, 6.25; 95% confidence interval, 1.90-20.5) were independently associated with high thirst intensity in patients with HF.

    CONCLUSIONS: Thirst intensity increased in two-thirds of the patients during a time period of optimization of HF medication. Fluid restriction and plasma urea levels were associated with high thirst intensity.

  • 430.
    Walfridsson, Ulla
    et al.
    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.
    Steen Hansen, Peter
    Private Hosp Molholm, Denmark.
    Charitakis, Emmanouil
    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.
    Almroth, Henrik
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonsson, Anders
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Karlsson, Lars
    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.
    Liuba, Ioan
    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.
    Ayou, Romeo Samo
    Skaraborgs Hosp, Sweden.
    Poci, Dritan
    Univ Hosp Orebro, Sweden.
    Holmqvist, Fredrik
    Skane Univ Hosp, Sweden.
    Kongstad, Ole
    Skane Univ Hosp, Sweden.
    Walfridsson, Håkan
    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.
    Gender and age differences in symptoms and health-related quality of life in patients with atrial fibrillation referred for catheter ablation2019In: Pacing and Clinical Electrophysiology, ISSN 0147-8389, E-ISSN 1540-8159, Vol. 42, no 11, p. 1431-1439Article in journal (Refereed)
    Abstract [en]

    Background

    Primary indication for catheter ablation of atrial fibrillation (AF) is to reduce symptoms and improve health‐related quality of life (HRQoL). There are data showing differences between the genders and between younger and older patients. To evaluate this, we studied a large Scandinavian cohort of patients referred for catheter ablation of AF.

    Methods

    Consecutive patients filled out the ASTA questionnaire, assessing symptoms, HRQoL, and perception of arrhythmia, prior to ablation. Patients were recruited from four Swedish and one Danish tertiary center.

    Results

    A total of 2493 patients (72% men) filled out the ASTA questionnaire. Women experienced eight of the nine ASTA scale symptoms more often than men. Patients <65 years reported four symptoms more often, only tiredness was more frequent in those ≥65 years (P = .007). Women and patients <65 years experienced more often palpitations and regarding close to fainting and this was more common among women, no age differences were seen. Women and men scored differently in 10 of the 13 HRQoL items. Only negative impact on sexual life was more common in men (P < .001). Older patients reported more negative influence in four of the HRQoL items and the younger in one; ability to concentrate.

    Conclusions

    Women experienced a more pronounced symptom burden and were more negatively affected in all HRQoL concerns, except for the negative impact on sexual life, where men reported more influence of AF. Differences between age groups were less pronounced. Disease‐specific patient‐reported outcomes measures (PROMs) add important information where gender differences should be considered in the care.

  • 431.
    Wallentin, Lars
    et al.
    Uppsala University, Sweden.
    Lindhagen, Lars
    Uppsala University, Sweden.
    Arnstrom, Elisabet
    Uppsala University, Sweden.
    Husted, Steen
    Hospital Unit West, Denmark.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. 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.
    Paaske Johnsen, Soren
    Aarhus University Hospital, Denmark.
    Kontny, Frederic
    Stavanger University Hospital, Norway; Drammen Heart Centre, Norway.
    Kempf, Tibor
    Hannover Medical Sch, Germany.
    Levin, Lars-Åke
    Linköping University, Department of Medical and Health Sciences, Division of Health Care Analysis. Linköping University, Faculty of Medicine and Health Sciences.
    Lindahl, Bertil
    Uppsala University, Sweden.
    Stridsberg, Mats
    Uppsala University, Sweden.
    Stahle, Elisabeth
    Uppsala University, Sweden.
    Venge, Per
    Uppsala University, Sweden.
    Wollert, Kai C.
    Hannover Medical Sch, Germany.
    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.
    Lagerqvist, Bo
    Uppsala University, Sweden.
    Early invasive versus non-invasive treatment in patients with non-ST-elevation acute coronary syndrome (FRISC-II): 15 year follow-up of a prospective, randomised, multicentre study2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10054, p. 1903-1911Article in journal (Refereed)
    Abstract [en]

    Background The FRISC-II trial was the first randomised trial to show a reduction in death or myocardial infarction with an early invasive versus a non-invasive treatment strategy in patients with non-ST-elevation acute coronary syndrome. Here we provide a remaining lifetime perspective on the effects on all cardiovascular events during 15 years follow-up. Methods The FRISC-II prospective, randomised, multicentre trial was done at 58 Scandinavian centres in Sweden, Denmark, and Norway. Between June 17, 1996, and Aug 28, 1998, we randomly assigned (1:1) 2457 patients with non-ST-elevation acute coronary syndrome to an early invasive treatment strategy, aiming for revascularisation within 7 days, or a non-invasive strategy, with invasive procedures at recurrent symptoms or severe exercise-induced ischaemia. Plasma for biomarker analyses was obtained at randomisation. For long-term outcomes, we linked data with national health-care registers. The primary endpoint was a composite of death or myocardial infarction. Outcomes were compared as the average postponement of the next event, including recurrent events, calculated as the area between mean cumulative count-of-events curves. Analyses were done by intention to treat. Findings At a minimum of 15 years follow-up on Dec 31, 2014, data for survival status and death were available for 2421 (99%) of the initially recruited 2457 patients, and for other events after 2 years for 2182 (89%) patients. During follow-up, the invasive strategy postponed death or next myocardial infarction by a mean of 549 days (95% CI 204-888; p= 0.0020) compared with the non-invasive strategy. This effect was larger in non-smokers (mean gain 809 days, 95% CI 402-1175; p(interaction) = 0.0182), patients with elevated troponin T (778 days, 357-1165; p (interaction) = 0.0241), and patients with high concentrations of growth differentiation factor-15 (1356 days, 507-1650; p (interaction) = 0.0210). The difference was mainly driven by postponement of new myocardial infarction, whereas the early difference in mortality alone was not sustained over time. The invasive strategy led to a mean of 1128 days (95% CI 830-1366) postponement of death or next readmission to hospital for ischaemic heart disease, which was consistent in all subgroups (pamp;lt; 0.0001). Interpretation During 15 years of follow-up, an early invasive treatment strategy postponed the occurrence of death or next myocardial infarction by an average of 18 months, and the next readmission to hospital for ischaemic heart disease by 37 months, compared with a non-invasive strategy in patients with non-ST-elevation acute coronary syndrome. This remaining lifetime perspective supports that an early invasive treatment strategy should be the preferred option in most patients with non-ST-elevation acute coronary syndrome.

  • 432.
    Wang, Chunliang
    Linköping University, Department of Medicine and Health Sciences, Radiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Computer Assisted Coronary CT Angiography Analysis: Disease-centered Software Development2009Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    The substantial advances of coronary CTA have resulted in a boost of use of this new technique in the last several years, which brings a big challenge to radiologists by the increasing number of exams and the large amount of data for each patient. The main goal of this study was to develop a computer tool to facilitate coronary CTA analysis by combining knowledge of medicine and image processing.Firstly, a competing fuzzy connectedness tree algorithm was developed to segment the coronary arteries and extract centerlines for each branch. The new algorithm, which is an extension of the “virtual contrast injection” method, preserves the low density soft tissue around the coronary, which reduces the possibility of introducing false positive stenoses during segmentation.Secondly, this algorithm was implemented in open source software in which multiple visualization techniques were integrated into an intuitive user interface to facilitate user interaction and provide good over¬views of the processing results. Considerable efforts were put on optimizing the computa¬tional speed of the algorithm to meet the clinical requirements.Thirdly, an automatic seeding method, that can automatically remove rib cage and recognize the aortic root, was introduced into the interactive segmentation workflow to further minimize the requirement of user interactivity during post-processing. The automatic procedure is carried out right after the images are received, which saves users time after they open the data. Vessel enhance¬ment and quantitative 2D vessel contour analysis are also included in this new version of the software. In our preliminary experience, visually accurate segmentation results of major branches have been achieved in 74 cases (42 cases reported in paper II and 32 cases in paper III) using our software with limited user interaction. On 128 branches of 32 patients, the average overlap between the centerline created in our software and the manually created reference standard was 96.0%. The average distance between them was 0.38 mm, lower than the mean voxel size. The automatic procedure ran for 3-5 min as a single-thread application in the background. Interactive processing took 3 min in average with the latest version of software. In conclusion, the presented software provides fast and automatic coron¬ary artery segmentation and visualization. The accuracy of the centerline tracking was found to be acceptable when compared to manually created centerlines.

    List of papers
    1. Coronary Artery Segmentation and Skeletonization Based on Competing Fuzzy Connectedness Tree
    Open this publication in new window or tab >>Coronary Artery Segmentation and Skeletonization Based on Competing Fuzzy Connectedness Tree
    2007 (English)In: Medical Image Computing and Computer-Assisted Intervention – MICCAI 2007: 10th International Conference, Brisbane, Australia, October 29 - November 2, 2007, Proceedings, Part I / [ed] Nicholas Ayache, Sébastien Ourselin, Anthony Maeder, Springer Berlin/Heidelberg, 2007, Vol. 4791, p. 311-318Conference paper, Published paper (Refereed)
    Abstract [en]

    We propose a new segmentation algorithm based on competing fuzzy connectedness theory, which is then used for visualizing coronary arteries in 3D CT angiography (CTA) images. The major difference compared to other fuzzy connectedness algorithms is that an additional data structure, the connectedness tree, is constructed at the same time as the seeds propagate. In preliminary evaluations, accurate result have been achieved with very limited user interaction. In addition to improving computational speed and segmentation results, the fuzzy connectedness tree algorithm also includes automated extraction of the vessel centerlines, which is a promising approach for creating curved plane reformat (CPR) images along arteries’ long axes.

    Place, publisher, year, edition, pages
    Springer Berlin/Heidelberg, 2007
    Series
    Lecture Notes in Computer Science, ISSN 0302-9743, E-ISSN 1611-3349 ; 4791
    Keywords
    segmentation - fuzzy connectedness tree - centerline extraction - skeletonization - coronary artery - CT angiography
    National Category
    Radiology, Nuclear Medicine and Medical Imaging Computer Vision and Robotics (Autonomous Systems)
    Identifiers
    urn:nbn:se:liu:diva-17816 (URN)10.1007/978-3-540-75757-3_38 (DOI)000250916000038 ()978-3-540-75756-6 (ISBN)
    Conference
    10th International Conference on Medical Image Computing and Computer-Assisted Intervention, Brisbane, Australia, October 29 - November 2, 2007
    Note

    The original publication is available at www.springerlink.com: Chunliang Wang and Örjan Smedby, Coronary Artery Segmentation and Skeletonization Based on Competing Fuzzy Connectedness Tree, 2007, Medical Image Computing and Computer-Assisted Intervention, (4791), 311-318. http://dx.doi.org/10.1007/978-3-540-75757-3_38 Copyright: Springer-verlag http://www.springerlink.com/

    Available from: 2009-04-21 Created: 2009-04-21 Last updated: 2018-02-07Bibliographically approved
    2. An interactive software module for visualizing coronary arteries in CT angiography
    Open this publication in new window or tab >>An interactive software module for visualizing coronary arteries in CT angiography
    2008 (English)In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, Vol. 3, no 1-2, p. 11-18Article in journal (Refereed) Published
    Abstract [en]

    A new software module for coronary artery segmentation and visualization in CT angiography (CTA) datasets is presented, which aims to interactively segment coronary arteries and visualize them in 3D with maximum intensity projection (MIP) and volume rendering (VRT).

    Materials and Methods:  The software was built as a plug-in for the open-source PACS workstation OsiriX. The main segmentation function is based an optimized “virtual contrast injection” algorithm, which uses fuzzy connectedness of the vessel lumen to separate the contrast-filled structures from each other. The software was evaluated in 42 clinical coronary CTA datasets acquired with 64-slice CT using isotropic voxels of 0.3–0.5 mm.

    Results:  The median processing time was 6.4 min, and 100% of main branches (right coronary artery, left circumflex artery and left anterior descending artery) and 86.9% (219/252) of visible minor branches were intact. Visually correct centerlines were obtained automatically in 94.7% (321/339) of the intact branches.

    Conclusion:  The new software is a promising tool for coronary CTA post-processing providing good overviews of the coronary artery with limited user interaction on low-end hardware, and the coronary CTA diagnosis procedure could potentially be more time-efficient than using thin-slab technique.

    Place, publisher, year, edition, pages
    Heidelberg/Berlin: Springer, 2008
    Keywords
    Coronary vessels - Tomography, spiral computed - Algorithms - Radiographic image interpretation, computer-assisted
    National Category
    Radiology, Nuclear Medicine and Medical Imaging Cardiac and Cardiovascular Systems Computer Vision and Robotics (Autonomous Systems)
    Identifiers
    urn:nbn:se:liu:diva-17817 (URN)10.1007/s11548-008-0160-6 (DOI)
    Note

    The original publication is available at www.springerlink.com: Chunliang Wang, Hans Frimmel, Anders Persson and Örjan Smedby, An interactive software module for visualizing coronary arteries in CT angiography, 2008, International Journal of Computer Assisted Radiology and Surgery, (3), 1-2, 11-18. http://dx.doi.org/10.1007/s11548-008-0160-6 Copyright: Springer Science Business Media http://www.springerlink.com/

    Available from: 2009-04-21 Created: 2009-04-21 Last updated: 2018-01-13Bibliographically approved
    3. Integrating automatic and interactive method for coronary artery segmentation: let PACS workstation think ahead
    Open this publication in new window or tab >>Integrating automatic and interactive method for coronary artery segmentation: let PACS workstation think ahead
    2010 (English)In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, E-ISSN 1861-6429, Vol. 5, no 3, p. 275-285Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To provide an efficient method to extract useful information from the increasing amount of coronary CTA.

    Methods: A quantitative coronary CTA analysis tool was built on OsiriX, which integrates both fully automatic and interactive methods for coronary artery extraction. The computational power of an ordinary PC is exploited by running the non-supervised coronary artery segmentation and centerline tracking in the background as soon as the images are received. When the user opens the data, the software provides a real-time interactive analysis environment.

    Results: The average overlap between the centerline created in our software and the reference standard was 96.0%. The average distance between them was 0.38 mm. The automatic procedure runs for 3-5 min as a single-thread application in background. Interactive processing takes 3 min in average.

    Conclusion: In preliminary experiments, the software achieved higher efficiency than the former interactive method, and reasonable accuracy compared to manual vessel extraction.

    Keywords
    Coronary CT angiography, automatic vessel extraction, vessel segmentation, centerline tracking
    National Category
    Radiology, Nuclear Medicine and Medical Imaging Cardiac and Cardiovascular Systems Computer Vision and Robotics (Autonomous Systems)
    Identifiers
    urn:nbn:se:liu:diva-17818 (URN)10.1007/s11548-009-0393-z (DOI)000289288800008 ()
    Note

    The original publication is available at www.springerlink.com: Chunliang Wang and Örjan Smedby, Integrating automatic and interactive method for coronary artery segmentation: let PACS workstation think ahead, 2011, International Journal of Computer Assisted Radiology and Surgery, (5), 3, 275-285. http://dx.doi.org/10.1007/s11548-009-0393-z Copyright: Springer Science Business Media http://www.springerlink.com/

    Available from: 2009-04-21 Created: 2009-04-21 Last updated: 2018-01-13Bibliographically approved
  • 433.
    Wang, Chunliang
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Frimmel, Hans
    Institutionen för informationteknologi, Uppsala universitet, Sweden.
    Persson, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    An interactive software module for visualizing coronary arteries in CT angiography2008In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, Vol. 3, no 1-2, p. 11-18Article in journal (Refereed)
    Abstract [en]

    A new software module for coronary artery segmentation and visualization in CT angiography (CTA) datasets is presented, which aims to interactively segment coronary arteries and visualize them in 3D with maximum intensity projection (MIP) and volume rendering (VRT).

    Materials and Methods:  The software was built as a plug-in for the open-source PACS workstation OsiriX. The main segmentation function is based an optimized “virtual contrast injection” algorithm, which uses fuzzy connectedness of the vessel lumen to separate the contrast-filled structures from each other. The software was evaluated in 42 clinical coronary CTA datasets acquired with 64-slice CT using isotropic voxels of 0.3–0.5 mm.

    Results:  The median processing time was 6.4 min, and 100% of main branches (right coronary artery, left circumflex artery and left anterior descending artery) and 86.9% (219/252) of visible minor branches were intact. Visually correct centerlines were obtained automatically in 94.7% (321/339) of the intact branches.

    Conclusion:  The new software is a promising tool for coronary CTA post-processing providing good overviews of the coronary artery with limited user interaction on low-end hardware, and the coronary CTA diagnosis procedure could potentially be more time-efficient than using thin-slab technique.

  • 434.
    Wang, Chunliang
    et al.
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Moreno, Rodrigo
    Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences.
    Smedby, Örjan
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Center for Medical Image Science and Visualization, CMIV. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Diagnostics, Department of Radiology in Linköping.
    Vessel Segmentation Using Implicit Model-Guided Level Sets2012Conference paper (Refereed)
    Abstract [en]

    This paper proposes an automatic segmentation method of vasculature that combines level-sets with an implicit 3D model of the vessels. First, a 3D vessel model from a set of initial centerlines is generated. This model is incorporated in the level set propagation to regulate the growth of the vessel contour. After evolving the level set, new centerlines are extracted and the diameter of vessels is re-estimated in order to generate a new vessel model. The propagation and re-modeling steps are repeated until convergence. The organizers of the 3D Cardiovascular Imaging: a MICCAI segmentation challenge report the following results for the 24 testing datasets. The sensitivity and PPV are 0.26, 0.40 for QCA and 0.05 and 0.22 for CTA. As for quantitation, the absolute and RMS dierences for QCA are 29.7% and 34.1% and the weighted kappa for CTA are -0.37. As for lumen segmentation, the dice are 0.68 and 0.69 for healthy and diseased vessel segments respectively. Performance for QCA and lumen segmentation are close to the reported by the organizers for three human observers.

  • 435.
    Wang, Chunliang
    et al.
    Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smedby, Örjan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Radiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medical Imaging, Department of Radiology in Linköping.
    Integrating automatic and interactive method for coronary artery segmentation: let PACS workstation think ahead2010In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, E-ISSN 1861-6429, Vol. 5, no 3, p. 275-285Article in journal (Refereed)
    Abstract [en]

    Purpose: To provide an efficient method to extract useful information from the increasing amount of coronary CTA.

    Methods: A quantitative coronary CTA analysis tool was built on OsiriX, which integrates both fully automatic and interactive methods for coronary artery extraction. The computational power of an ordinary PC is exploited by running the non-supervised coronary artery segmentation and centerline tracking in the background as soon as the images are received. When the user opens the data, the software provides a real-time interactive analysis environment.

    Results: The average overlap between the centerline created in our software and the reference standard was 96.0%. The average distance between them was 0.38 mm. The automatic procedure runs for 3-5 min as a single-thread application in background. Interactive processing takes 3 min in average.

    Conclusion: In preliminary experiments, the software achieved higher efficiency than the former interactive method, and reasonable accuracy compared to manual vessel extraction.

  • 436.
    Ward, Liam
    Linköping University, Department of Clinical and Experimental Medicine, Division of Children's and Women's health. Linköping University, Faculty of Medicine and Health Sciences.
    Sex differences in atherosclerosis and exercise effects2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Cardiovascular disease (CVD) is the leading cause of death globally, with atherosclerosis being the main cause of cardiovascular diseases. Atherosclerosis is an inflammatory disease of the blood vessel wall, which over time will cause thickening and hardening of the vessel wall. Atherosclerosis can result in catastrophic vascular events, such as myocardial infarction and stroke. There are distinct sex differences in CVD mortality at different ages, before menopause women have a lower mortality of CVD in comparison to men, which equalises after menopause. In addition to sex differences in the incidence of CVD, there are also distinct sex differences in the phenotype of atherosclerotic plaques, with men generally developing more severe and vulnerable plaques that are at risk of rupture.

    This thesis aimed to investigate the sex differences in atherosclerosis, in particular how the proteome and pathophysiology differs. In addition, we sought to investigate the potential benefit of an exercise programme, in reducing CVD risks, using a randomised controlled trial including postmenopausal women.

    Sex differences in atherosclerosis were first investigated via proteomic analysis of human carotid endarterectomy samples. Initially, five intraplaque biopsies were taken from distinct atheroma regions, including; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Protein extracts from these biopsies were subjected to analysis by mass spectrometry. The novel sampling method was successful in reducing the effect of plaque heterogeneity, a limitation in previous proteomic studies of atherosclerosis, and a number of previously unreported proteins were identified in human carotid atheroma. In addition to this, with the inclusion of multivariate statistical modelling, it was found that 43 proteins significantly discriminated the carotid atheroma between men and women. These proteins were grouped by function, and it was found that atheroma from men was associated with the increased abundance of inflammatory response proteins, including phospholipase-A2 membrane associated and lysozyme C, and atheroma from women was associated with increased abundance of blood coagulation, complement activation, and transport proteins, notably including; antithrombin-III, coagulation factor XII, and afamin. In addition, differences were also ii observed in the abundance of iron metabolism related proteins. These sex differences were further expanded upon from a pathophysiological perspective. Immunohistochemistry stainings of ferritin and transferrin receptor 1 were found significantly increased in the atheroma from men. Moreover, the levels of plasma haemoglobin were also significantly increased in men and were associated with the development of more vulnerable and severe plaque types. The more vulnerable and severe plaque types were also associated with significantly greater macrophage infiltration. In summary, these results are indicative of men developing atheroma with greater inflammation that are more vulnerable, due to increased iron and inflammatory proteins and macrophage infiltration, whereas atheroma from women develop with less inflammation and a more stable phenotype.

    The randomised controlled clinical trial aimed at investigating the effects of resistance training (RT), over a 15-week period, in postmenopausal women. Plasma samples were obtained at week-0 and week-15 of the study period, and analyses were performed primarily using a series of immunoassays. Results showed that women participating in RT, with good compliance, were associated with significant decreases in plasma levels of ferritin, lipids, and inflammatory adipokines. These results suggest that the use of regular RT may be a beneficial intervention in reducing the levels of body iron, lipids, and inflammation, all of which are risk factors for the development of CVD. However, validation studies are required in a larger cohort of postmenopausal women, in addition to the inclusion or complementary studies in middle-aged men.

    In summary, the works included in this thesis further expand on the current knowledge of sex differences in atherosclerosis, and also provides information on the potential of an exercise intervention to beneficially reduces the effects of known risk factors of CVD.

    List of papers
    1. Distinctive proteomic profiles among different regions of human carotid plaques in men and women
    Open this publication in new window or tab >>Distinctive proteomic profiles among different regions of human carotid plaques in men and women
    Show others...
    2016 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 6, no 26231Article in journal (Refereed) Published
    Abstract [en]

    The heterogeneity of atherosclerotic tissue has limited comprehension in proteomic and metabolomic analyses. To elucidate the functional implications, and differences between genders, of atherosclerotic lesion formation we investigated protein profiles from different regions of human carotid atherosclerotic arteries; internal control, fatty streak, plaque shoulder, plaque centre, and fibrous cap. Proteomic analysis was performed using 2-DE with MALDI-TOF, with validation using nLC-MS/MS. Protein mapping of 2-DE identified 52 unique proteins, including 15 previously unmapped proteins, of which 41 proteins were confirmed by nLC-MS/MS analysis. Expression levels of 18 proteins were significantly altered in plaque regions compared to the internal control region. Nine proteins showed site-specific alterations, irrespective of gender, with clear associations to extracellular matrix remodelling. Five proteins display gender-specific alterations with 2-DE, with two alterations validated by nLC-MS/MS. Gender differences in ferritin light chain and transthyretin were validated using both techniques. Validation of immunohistochemistry confirmed significantly higher levels of ferritin in plaques from male patients. Proteomic analysis of different plaque regions has reduced the effects of plaque heterogeneity, and significant differences in protein expression are determined in specific regions and between genders. These proteomes have functional implications in plaque progression and are of importance in understanding gender differences in atherosclerosis.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2016
    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:liu:diva-129495 (URN)10.1038/srep26231 (DOI)000376554600001 ()27198765 (PubMedID)
    Note

    Funding Agencies|Swedish Heart Lung Foundation; Linkoping University Hospital Research foundation; Swedish Institute; China Scholarship Council

    Available from: 2016-06-20 Created: 2016-06-20 Last updated: 2019-04-17
    2. Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma
    Open this publication in new window or tab >>Proteomics and multivariate modelling reveal sex-specific alterations in distinct regions of human carotid atheroma
    2018 (English)In: Biology of Sex Differences, ISSN 2042-6410, Vol. 9, article id 54Article in journal (Refereed) Published
    Abstract [en]

    BackgroundAtherosclerotic lesions are comprised of distinct regions with different proteomic profiles. Men and women develop differences in lesion phenotype, with lesions from women generally being more stable and less prone to rupture. We aimed to investigate the differences in proteomic profiles between sexes, including distinct lesion regions, to identify altered proteins that contribute to these differences observed clinically.MethodsCarotid endarterectomy samples (ten men/ten women) were obtained, and intraplaque biopsies from three distinct regions (internal control, fatty streak and plaque) were analysed by tandem-mass spectrometry. Multivariate statistical modelling, using orthogonal partial least square-discriminant analysis, was used to discriminate the proteomes between men and women.ResultsMultivariate discriminant modelling revealed proteins from 16 functional groups that displayed sex-specific associations. Additional statistics revealed ten proteins that display region-specific alterations when comparing sexes, including proteins related to inflammatory response, response to reactive oxygen species, complement activation, transport and blood coagulation. Transport protein afamin and blood coagulation proteins antithrombin-III and coagulation factor XII were significantly increased in plaque region from women. Inflammatory response proteins lysozyme C and phospholipase A2 membrane-associated were significantly increased in plaque region from men. Limitations with this study are the small sample size, limited patient information and lack of complementary histology to control for cell type differences between sexes.ConclusionsThis pilot study, for the first time, utilises a multivariate proteomic approach to investigate sexual dimorphism in human atherosclerotic tissue, and provides an essential proteomic platform for further investigations to help understand sexual dimorphism and plaque vulnerability in atherosclerosis.

    Place, publisher, year, edition, pages
    BMC, 2018
    Keywords
    Afamin; Atherosclerosis; Lysozyme C; Mass spectrometry; Serine protease inhibitors; Vulnerability
    National Category
    Medical Genetics
    Identifiers
    urn:nbn:se:liu:diva-153822 (URN)10.1186/s13293-018-0217-3 (DOI)000454616000001 ()30594242 (PubMedID)
    Note

    Funding Agencies|Swedish Heart Lung Foundation; Torsten and Ragnar Soderbergs Foundation; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjanarinnor Foundation; Linkoping University Hospital Research Fund

    Available from: 2019-01-11 Created: 2019-01-11 Last updated: 2019-05-02
    3. Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
    Open this publication in new window or tab >>Carotid Atheroma From Men Has Significantly Higher Levels of Inflammation and Iron Metabolism Enabled by Macrophages
    Show others...
    2018 (English)In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, no 2, p. 419-425Article in journal (Refereed) Published
    Abstract [en]

    Background and Purpose-Men differ from women in the manifestation of atherosclerosis and iron metabolism. Intraplaque hemorrhage and hemoglobin (Hb) catabolism by macrophages are associated with atherosclerotic lesion instability. The study aims were to investigate sex differences in (1) lesion severity in relation to blood Hb, (2) iron homeostasis in human carotid plaques, and (3) macrophage polarization within atheroma. Methods-The carotid artery samples from 39 men and 23 women were immunostained with cell markers for macrophages, smooth muscle cells, ferritin, and TfR1 (transferrin receptor 1), which were further analyzed according to sex in relation to iron, Hb, and lipids in circulation. Additionally, samples of predefined regions from human carotid atherosclerotic lesions, including internal controls, were used for proteomic analysis by mass spectrometry. Results-Male patients, compared with women, had larger necrotic cores and more plaque rupture, which were associated with higher levels of Hb. Atheroma of male patients had significantly higher levels of Hb in circulation and CD68 macrophages, ferritin, and TfR1 in lesions. CD68 macrophages were significantly correlated with ferritin and TfR1. Plaques from male patients comparatively possessed higher levels of inflammatory macrophage subsets, CD86 (M1) and CD163 (M2), but lower levels of STF (serotransferrin) and HPX (hemopexin). Conclusions-Male patients with carotid atheroma had more advanced and ruptured lesions associated with significantly higher levels of inflammatory macrophage infiltration and high iron stores in the blood and in their plaques. These findings help to understand sex differences and iron metabolism in atherosclerosis and factors related to atheroma progression.

    Place, publisher, year, edition, pages
    LIPPINCOTT WILLIAMS & WILKINS, 2018
    Keywords
    atherosclerosis; ferritins; hemoglobins; hemopexin; macrophages; male
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-144876 (URN)10.1161/STROKEAHA.117.018724 (DOI)000422928000035 ()29284736 (PubMedID)
    Note

    Funding Agencies|Swedish Heart-Lung Foundation; Torsten and Ragnar Soderbergs Foundation; Stroke Foundation; Olle Engkvist Foundation; Swedish Gamla Tjanarinnor Foundation; Linkoping University; Linkoping University Hospital Research Fund

    Available from: 2018-02-09 Created: 2018-02-09 Last updated: 2019-05-02
  • 437.
    Warme, Anna
    et al.
    Univ Gothenburg, Sweden; Skaraborg Hosp, Sweden.
    Hadimeri, Ursula
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Skaraborg Hosp, Sweden.
    Hadimeri, Henrik
    Univ Gothenburg, Sweden; Skaraborg Hosp, Sweden.
    Nasic, Salmir
    Skaraborg Hosp, Sweden.
    Stegmayr, Bernd
    Umea Univ, Sweden.
    High doses of erythropoietin stimulating agents may be a risk factor for AV-fistula stenosis2019In: Clinical hemorheology and microcirculation, ISSN 1386-0291, E-ISSN 1875-8622, Vol. 71, no 1, p. 53-57Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A native AV-fistula (AVF) for access in hemodialysis (HD) is preferable. Stenosis, a major hurdle, is associated with older age and diabetes mellitus. PURPOSE: This case-control study aimed to clarify if any medical and/or laboratory factors, that can be altered, could be associated to AVF stenosis. METHODS: 33 patients with a patent AVF without need of intervention during a two year period (Controls) were matched by diagnosis and age with 33 patients (Cases), that had at least one radiological invasive examination/intervention due to suspected AVF malfunction (case-control mode 2:1). RESULTS: Cases had higher weekly doses of Erythropoietin-Stimulating Agent (ESA) than Controls both before intervention (mean 8312 +/- 7119 U/w versus 4348 +/- 3790, p = 0.005) and after the intervention (7656 +/- 6795, versus 4477 +/- 3895, p = 0.018). Before intervention serum phosphate was higher in Cases while there was no significant difference in blood hemoglobin, weekly standard Kt/V, parathyroid hormone, calcium, albumin, C-reactive protein, smoking habits, BMI or other medication. CONCLUSION: Higher doses of ESA were administered in patients with AVF stenosis. Since ESA may cause local hypertrophic effects on the vascular endothelium, we should prescribe lower doses of ESA in patients at risk. Further studies should clarify such connection.

  • 438.
    White, H.D.
    et al.
    Green Lane Cardiovascular Services, Auckland City Hospital, 5 Park Road, Grafton, Auckland, 1142, New Zealand.
    Gabriel, Steg Ph.
    FACT (French Alliance for Cardiovascular Trials), F-CRIN network, Département Hospitalo-Universitaire FIRE, AP-HP, Hôpital Bichat, Université Paris-Diderot, Sorbonne Paris-Cité, INSERM U-1148, 46 rue Henri Huchard, Paris, 75018, France; National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, Sydney Street, London, SW3 6NP, United Kingdom.
    Szarek, M.
    Department of Epidemiology and Biostatistics, SUNY Downstate Medical Center School of Public Health, 450 Clarkson Avenue, Brooklyn, NY 11203, United States.
    Bhatt, D.L.
    Brigham and Women’s Hospital Heart and Vascular Center, Harvard Medical School, 75 Francis Street, Boston, MA 02115, United States.
    Bittner, V.A.
    Division of Cardiovascular Disease, University of Alabama at Birmingham, 701 19th Street South - LHRB 310, Birmingham, AL 35294, United States.
    Diaz, R.
    Estudios Cardiológicos Latinoamérica, Instituto Cardiovascular de Rosario, Paraguay 160, Rosario, Santa Fe, Argentina.
    Edelberg, J.M.
    Sanofi, 55 Corporate Drive, Bridgewater, NJ 08807, United States.
    Erglis, A.
    Latvian Centre of Cardiology, Pauls Stradins Clinical University Hospital, University of Latvia, Pilsonu Street 13, Riga, LV1002, Latvia.
    Goodman, S.G.
    Canadian VIGOUR Centre, 2-132 Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB T6G 2E1, Canada; St. Michael’s Hospital, University of Toronto, 30 Bond Street, Toronto, ON M5B 1W8, Canada.
    Hanotin, C.
    Sanofi, 54-56 Rue la Boétie, Paris, 75008, France.
    Harrington, R.A.
    Stanford Center for Clinical Research, Department of Medicine, 300 Pasteur Drive, S-102, Stanford, CA 94305, United States.
    Wouter, Jukema J.
    Department of Cardiology, Leiden University Medical Center, 2300 RC, Leiden, Netherlands.
    Lopes, R.D.
    Duke Clinical Research Institute, 200 Morris Street, Durham, NC 27710, United States.
    Mahaffey, K.W.
    Department of Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Grant S-102, Stanford, CA 94305, United States.
    Moryusef, A.
    Sanofi, 55 Corporate Drive, Bridgewater, NJ 08807, United States.
    Pordy, R.
    Regeneron Pharmaceuticals, 777 Old Saw Mill River Road, Tarrytown, NY 10591, United States.
    Roe, M.T.
    Duke Clinical Research Institute, 200 Morris Street, Durham, NC 27710, United States.
    Sritara, P.
    Department of Medicine, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Rama VI Road10400, Thailand.
    Tricoci, P.
    CSL Behring, 1100 N Miami Blvd Ste 613, Durham, NC 27703, United States.
    Zeiher, A.M.
    Department of Medicine III, Goethe University, Theodor-Stern-Kai 7, Frankfurt am Main, 60590, Germany.
    Schwartz, G.G.
    Division of Cardiology, University of Colorado School of Medicine, 1700 N. Wheeling Street, Aurora, CO 80045, United States.
    ODYSSEY, OUTCOMES Investigators
    Effects of alirocumab on types of myocardial infarction: Insights from the ODYSSEY OUTCOMES trial2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 33, p. 2801-2809Article in journal (Refereed)
    Abstract [en]

    Aims The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (=1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

  • 439.
    Wijkman, Magnus
    et al.
    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.
    Sandberg, Klas
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping. Region Östergötland, Local Health Care Services in East Östergötland, Department of Rehabilitation in Norrköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy.
    Kleist, Marie
    Region Östergötland, Local Health Care Services in East Östergötland, Department of Rehabilitation in Norrköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Falk, Lars
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Dermatology and Venerology. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    Enthoven, Paul
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in West Östergötland, Research & Development Unit in Local Health Care.
    The exaggerated blood pressure response to exercise in the sub-acute phase after stroke is not affected by aerobic exercise.2018In: The Journal of Clinical Hypertension, ISSN 1524-6175, E-ISSN 1751-7176, Journal of Clinical Hypertension, Vol. 20, p. 56-64Article in journal (Refereed)
    Abstract [en]

    The prevalence of an exaggerated exercise blood pressure (BP) response is unknown in patients with subacute stroke, and it is not known whether an aerobic exercise program modulates this response. The authors randomized 53 patients (27 women) with subacute stroke to 12 weeks of twice-weekly aerobic exercise (n = 29) or to usual care without scheduled physical exercise (n = 24). At baseline, 66% of the patients exhibited an exaggerated exercise BP response (peak systolic BP ≥210 mm Hg in men and ≥190 mm Hg in women) during a symptom-limited ergometer exercise test. At follow-up, patients who had been randomized to the exercise program achieved higher peak work rate, but peak systolic BP remained unaltered. Among patients with a recent stroke, it was common to have an exaggerated systolic BP response during exercise. This response was not altered by participation in a 12-week program of aerobic exercise.

  • 440.
    Wiklander, Kerstin
    et al.
    Chalmers, Sweden; University of Gothenburg, Sweden.
    Erichsen Andersson, Annette
    University of Gothenburg, Sweden.
    Källman, Ulrika
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. South Alvsborg Hospital, Sweden.
    An investigation of the ability to produce a defined "target pressure using the PressCise compression bandage2016In: International Wound Journal, ISSN 1742-4801, E-ISSN 1742-481X, Vol. 13, no 6, p. 1336-1343Article in journal (Refereed)
    Abstract [en]

    Compression therapy is the cornerstone in the prevention and treatment of leg ulcers related to chronic venous insufficiency. The application of optimal high pressure is essential for a successful outcome, but the literature has reported difficulty applying the intended pressure, even among highly skilled nurses. The PressCise bandage has a novel design, with both longitudinal and horizontal reference points for correct application. In the current experimental study, the results for the general linear model, where the data set is treated optimally, showed that all 95% confidence intervals of the expected values for pressure were, at most, 5 mmHg from the target value of 50 mmHg, independent of the position on the leg and the state of activity. Moreover, even nurses with limited experience were consistently able to reach the targeted pressure goal. Future studies are needed to determine how well the bandage works on legs of different shapes, the optimal way of using the bandage (day only or both day and night) and whether the bandage should be combined with an outer bandage layer. In addition, special attention should be paid to subjective patient experiences in relation to the treatment as pain, discomfort and bulk are factors that can compromise patients willingness to adhere to the treatment protocol and thereby prolong the healing process.

  • 441.
    Willeit, Peter
    et al.
    Med Univ Innsbruck, Austria; Univ Cambridge, England.
    Ridker, Paul M.
    Harvard Med Sch, MA USA.
    Nestel, Paul J.
    Baker Heart and Diabet Inst, Australia.
    Simes, John
    Univ Sydney, Australia.
    Tonkin, Andrew M.
    Monash Univ, Australia.
    Pedersen, Terje R.
    Oslo Univ Hosp, Norway; Univ Oslo, Norway.
    Schwartz, Gregory G.
    VA Med Ctr, CO USA; Univ Colorado, CO USA.
    Olsson, Anders
    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.
    Colhoun, Helen M.
    MRC Inst Genet and Mol Med, Scotland.
    Kronenberg, Florian
    Med Univ Innsbruck, Austria.
    Drechsler, Christiane
    Univ Hniv Hosp Wurzburg, Germany.
    Wanner, Christoph
    Univ Hosp Wurzburg, Germany.
    Mora, Samia
    Harvard Med Sch, MA USA.
    Lesogor, Anastasia
    Novartis Pharma AG, Switzerland.
    Tsimikas, Sotirios
    Univ Calif San Diego, CA 92093 USA.
    Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials2018In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, no 10155, p. 1311-1320Article in journal (Refereed)
    Abstract [en]

    Background Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established cardiovascular disease or on statin therapy is uncertain. Methods Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal coronary heart disease, stroke, or revascularisation procedures. HRs for cardiovascular events were estimated within each trial across predefined lipoprotein(a) groups (15 to amp;lt;30 mg/dL, 30 to amp;lt;50 mg/dL, and amp;gt;= 50 mg/dL, vs amp;lt;15 mg/dL), before pooling estimates using multivariate random-effects meta-analysis. Findings Analyses included data for 29 069 patients with repeat lipoprotein(a) measurements (mean age 62 years [SD 8]; 8064 [28%] women; 5751 events during 95 576 person-years at risk). Initiation of statin therapy reduced LDL cholesterol (mean change -39% [95% CI -43 to -35]) without a significant change in lipoprotein(a). Associations of baseline and on-statin treatment lipoprotein(a) with cardiovascular disease risk were approximately linear, with increased risk at lipoprotein(a) values of 30 mg/dL or greater for baseline lipoprotein(a) and 50 mg/dL or greater for on-statin lipoprotein(a). For baseline lipoprotein(a), HRs adjusted for age and sex (vs amp;lt;15 mg/dL) were 1.04 (95% CI 0.91-1.18) for 15 mg/dL to less than 30 mg/dL, 1.11 (1.00-1.22) for 30 mg/dL to less than 50 mg/dL, and 1.31 (1.08-1.58) for 50 mg/dL or higher; respective HRs for on-statin lipoprotein(a) were 0.94 (0.81-1.10), 1.06 (0. 94-1.21), and 1.43 (1.15-1.76). HRs were almost identical after further adjustment for previous cardiovascular disease, diabetes, smoking, systolic blood pressure, LDL cholesterol, and HDL cholesterol. The association of on-statin lipoprotein(a) with cardiovascular disease risk was stronger than for on-placebo lipoprotein(a) (interaction p=0.010) and was more pronounced at younger ages (interaction p=0.008) without effect-modification by any other patient-level or study-level characteristics. Interpretation In this individual-patient data meta-analysis of statin-treated patients, elevated baseline and on-statin lipoprotein(a) showed an independent approximately linear relation with cardiovascular disease risk. This study provides a rationale for testing the lipoprotein(a) lowering hypothesis in cardiovascular disease outcomes trials. Copyright (C) 2018 Elsevier Ltd. All rights reserved.

  • 442.
    Wirestam, Lina
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Frodlund, Martina
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Enocsson, Helena
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Skogh, Thomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Wetterö, Jonas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Sjöwall, Christopher
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Rheumatology.
    Osteopontin is associated with disease severity and antiphospholipid syndrome in well characterised Swedish cases of SLE2017In: Lupus Science and Medicine, ISSN 2053-8790, E-ISSN 1625-9823, Vol. 4, no 1, p. 7article id 000225Article in journal (Refereed)
    Abstract [en]

    Objective The variety of disease phenotypes among patients with SLE challenges the identification of new biomarkers reflecting disease activity and/or organ damage. Osteopontin (OPN) is an extracellular matrix protein with immunomodulating properties. Although raised levels have been reported, the pathogenic implications and clinical utility of OPN as a biomarker in SLE are far from clear. Thus, the aim of this study was to characterise OPN in SLE.

    Methods Sera from 240 well-characterised adult SLE cases classified according to the American College of Rheumatology (ACR) and/or the Systemic Lupus International Collaborating Clinics (SLICC) criteria, and 240 population-based controls were immunoassayed for OPN. The SLE Disease Activity Index 2000 (SLEDAI-2K) was used to evaluate disease activity and the SLICC/ACR Damage Index (SDI) to detect damage accrual.

    Results Serum OPN levels were in average raised fourfold in SLE cases compared with the controls (p<0.0001). OPN correlated with SLEDAI-2K, especially in patients with a disease duration of <12 months (r=0.666, p=0.028). OPN was highly associated with SDI (p<0.0001), especially in the renal (p<0.0001), cardiovascular (p<0.0001) and malignancy (p=0.012) domains. Finally, OPN associated with coherent antiphospholipid syndrome (APS; p=0.009), and both clinical and laboratory criteria of APS had significant positive impact on OPN levels.

    Conclusions In this cross-sectional study, circulating OPN correlates with disease activity in recent-onset SLE, reflects global organ damage and associates with APS. Longitudinal studies to dissect whether serum OPN also precedes and predicts future organ damage are most warranted.

  • 443.
    Wittboldt, Susanna
    et al.
    Sahlgrenska University Hospital.
    Cider, Åsa
    Sahlgrenska University Hospital, University of Gothenburg.
    Bäck, Maria
    Linköping University, Department of Medical and Health Sciences, Division of Physiotherapy. Linköping University, Faculty of Medicine and Health Sciences.
    Reliability of two questionnaires on physical function in patients with stable coronary artery disease.2016In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 15, no 2, p. 142-149Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Exercise-based cardiac rehabilitation is highly recommended for patients with coronary artery disease, as it improves physical fitness and reduces mortality and morbidity. Physical fitness per se does not always correlate with the patient's physical function. For this reason, additional measurements of physical function could be included in cardiac rehabilitation programmes to further tailor interventions to suit the individual patient. As a result, reliable measurements to assess physical function are required for patients with coronary artery disease.

    AIM: The aim of this study was to evaluate the reliability of the Patient-Specific Functional Scale (PSFS) and the Disability Rating Index (DRI) in patients with stable coronary artery disease.

    MATERIAL: Fifty-one patients (11 women), age 63.9 (SD 7.6) years, with stable coronary artery disease and coronary-angiographic changes indicating an elective percutaneous coronary intervention, were recruited at the Cardiology Department at Sahlgrenska University Hospital, Gothenburg.

    METHODS: The reliability tests included stability over time, evaluated with a test-retest procedure using the intraclass correlation coefficient (ICC), and internal consistency, measured with Cronbach's alpha and item-total correlation coefficients.

    RESULTS: Both questionnaires were stable over time (DRI, ICC=0.74, and PSFS, ICC=0.72). The internal consistency for the DRI was good, with a Cronbach's alpha value of > 0.85 for all items. The item-total correlation coefficients presented acceptable values of > 0.40, apart from two items.

    CONCLUSION: We have provided introductory support for the reliability of the DRI and PSFS questionnaires in patients with stable CAD. These questionnaires can be used to assess physical function and to evaluate the effect of interventions in addition to measuring physical fitness.

  • 444.
    Wuopio, Jonas
    et al.
    Mora Cty Hosp, Sweden.
    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, Primary Care Center, Primary Health Care Center Ödeshög.
    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. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lind, Lars
    Uppsala Univ, Sweden.
    Ruge, Toralph
    Karolinska Univ Hosp, Sweden.
    Carlsson, Axel C.
    Karolinska Inst, Sweden.
    Larsson, Anders
    Uppsala Univ, Sweden.
    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.
    Arnlov, Johan
    Karolinska Inst, Sweden; Dalarna Univ, Sweden.
    The association between circulating endostatin and a disturbed circadian blood pressure pattern in patients with type 2 diabetes2018In: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 27, no 4, p. 215-221Article in journal (Refereed)
    Abstract [en]

    Background: Endostatin, cleaved from collagen XVIII in the extracellular matrix, is a promising circulating biomarker for cardiovascular damage. It possesses anti-angiogenic and anti-fibrotic functions and has even been suggested to be involved in blood pressure regulation. Less is known if endostatin levels relate to circadian blood pressure patterns. In the present paper we studied the association between circulating levels of endostatin and nocturnal dipping in blood pressure.Methods: We used the CARDIPP-study, a cohort of middle aged, type 2 diabetics (n=593, 32% women), with data on both 24-hour and office blood pressure, serum-endostatin, cardiovascular risk factors, and incident major cardiovascular events. Nocturnal dipping was defined as a amp;gt;10% difference between day- and night-time blood pressures.Results: Two-hundred four participants (34%) were classified as non-dippers. The mean endostatin levels were significantly higher in non-dippers compared to dippers (meanstandard deviation: 62.6 +/- 1.8 mu g/l vs. 58.7 +/- 1.6 mu g/l, respectively, p=.007). Higher serum levels of endostatin were associated with a diminished decline in nocturnal blood pressure adjusted for age, sex, HbA1c, mean systolic day blood pressure, hypertension treatment, glomerular filtration rate, and prevalent cardiovascular disease (regression coefficient per SD increase of endostatin -0.01, 95% CI, -0.02-(-0.001), p=.03). Structural equation modelling analyses suggest that endostatin mediates 7% of the association between non-dipping and major cardiovascular events.Conclusion: We found an independent association between higher circulating levels of endostatin and a reduced difference between day- and night-time systolic blood pressure in patients with type 2 diabetes. Yet endostatin mediated only a small portion of the association between non-dipping and cardiovascular events arguing against a clinical utility of our findings.

  • 445.
    Zajac, Jacub
    et al.
    Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eriksson, Jonatan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Dyverfeldt, Petter
    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).
    Bolger, Ann F.
    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. Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carl-Johan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). 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.
    Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles2015In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 41, no 4, p. 1021-1029Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess turbulent kinetic energy (TKE) within the left ventricle (LV) of healthy subjects using novel 4D flow MRI methods and to compare TKE values to those from a spectrum of patients with dilated cardiomyopathy (DCM).

    Methods: 4D flow and morphological MRI-data were acquired in 11 healthy subjects and 9 patients with different degrees of diastolic dysfunction. TKELV was calculated within the LV at each diastolic time frame. At peak early (E) and late (A) diastolic filling, the TKELV was compared to transmitral peak velocity, LV diameter and mitral annular diameter.

    Results: In the majority of all subjects, peaks in TKELV could be observed at E and A. Peak TKELV at E was not different between the groups, and correlated with mitral annular dimensions. Peak TKELV at A was higher in DCM patients compared to healthy subjects, and was related to LV diameter and transmitral velocity.

    Conclusions: In normal LVs, TKE values are low. Values are highest during early diastole, and diminish with increasing LV size. In a heterogeneous group of DCM patients, late diastolic TKE values are higher than in healthy subjects. Kinetic energy loss due to elevated late diastolic TKE may reflect inefficient flow in dilated LVs.

  • 446.
    Zajac, Jakub
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Assessment of Ventricular Function in Normal and Failing Hearts Using 4D Flow CMR2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Heart failure is a common disorder and a major cause of illness and death in the population, creating an enormous health-care burden. It is a complex condition, representing the end-point of many cardiovascular diseases. In general heart failure progresses slowly over time and once it is diagnosed it has a poor prognosis which is comparable with that of many types of cancer.

    The heart has an ability to adapt in response to long lasting increases in hemodynamic demand; the heart conforms its shape and size in order to maintain adequate cardiac output. This process is called remodeling and can be triggered by pathologies such as hypertension or valvular disease. When the myocardial remodeling is maintained chronically it becomes maladaptive and is associated with an increased risk of heart failure.

    In many cases, heart failure is associated with left bundle branch block (LBBB). This electrical disturbance leads to dyssynchronous left ventricular (LV) contraction and relaxation which may contribute to cardiac dysfunction and ultimately heart failure. Mechanical dyssynchrony can be treated with cardiac resynchronization therapy (CRT). However, many heart failure patients do not demonstrate clinical improvement despite CRT.

    Blood flow plays an important role in the normal development of the fetal heart. However, flow-induced forces may also induce changes in the heart cells that could lead to pathological remodeling in the adult heart. Until recently, measurement tools have been inadequate in describing the complex three-dimensional and time-varying characteristics of blood flow within the beating heart.

    4D (3D + time) flow cardiovascular magnetic resonance (CMR) enables acquisition of three-dimensional, three-directional, time-resolved velocity data from which visualization and quantification of the blood flow patterns over a complete cardiac cycle can be performed. In this thesis, novel 4D Flow CMR based methods are used to study the intraventricular blood flow in healthy subjects and heart failure patients with and without ventricular dyssynchrony in order to gain new knowledge of the ventricular function.

    Different flow components were assessed in normal heart ventricles. It was found that inflowing blood that passes directly to outflow during the same heartbeat (the Direct Flow component) was larger and possessed more kinetic energy (KE) than other flow components. Diastolic flow through the normal heart appears to create favorable conditions for effective systolic ejection. This organized blood flow pattern within the normal LV is altered in heart failure patients and is associated with decreased preservation of KE which might be unfavorable for efficient LV ejection. Inefficient flow of blood through the heart may influence diastolic wall stress, and thus contribute to pathological myocardial remodeling.

    In dyssynchronous LVs of heart failure patients with LBBB, Direct Flow showed even more reduced preservation of KE compared to similarly remodeled LVs without LBBB. Furthermore, in LBBB patients, LV filling hemodynamic forces, acting on the myocardium, were more orthogonal to the main flow direction compared to patients without LBBB. Deviation of LV flow forces and reduction of KE preservation and may reflect impairment of LV diastolic function and less efficient ensuing ejection related to dyssynchrony in these failing ventricles.

    Blood flow patterns were also studied with respect to fluctuations of the velocity of the flow (turbulent flow) in normal and failing LVs. In failing hearts, turbulent kinetic energy (TKE) was higher during diastole than in healthy subjects. TKE is a cause of energy loss and can thus be seen as a measure of flow inefficiency.

    Elucidating the transit of multidimensional blood flow through the heart chambers is fundamental in understanding the physiology of the heart and to detect abnormalities in cardiac function. The 4D Flow CMR parameters presented in this thesis can be utilized to detect altered intracardiac blood flow and may be used as markers of deteriorating cardiac function, pathological remodeling and mechanical dyssynchrony in heart failure.

    List of papers
    1. 4-D blood flow in the human right ventricle
    Open this publication in new window or tab >>4-D blood flow in the human right ventricle
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    2011 (English)In: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 301, no 6, p. H2344-H2350Article in journal (Refereed) Published
    Abstract [en]

    Right ventricular (RV) function is a powerful prognostic indicator in many forms of heart disease, but its assessment remains challenging and inexact. RV dysfunction may alter the normal patterns of RV blood flow, but those patterns have been incompletely characterized. We hypothesized that, based on anatomic differences, the proportions and energetics of RV flow components would differ from those identified in the left ventricle (LV) and that the portion of the RV inflow passing directly to outflow (Direct Flow) would be prepared for effective systolic ejection as a result of preserved kinetic energy (KE) compared with other RV flow components. Three-dimensional, time-resolved phase-contrast velocity, and balanced steady-state free-precession morphological data were acquired in 10 healthy subjects using MRI. A previously validated method was used to separate the RV and LV end-diastolic volumes into four flow components and measure their volume and KE over the cardiac cycle. The RV Direct Flow: 1) followed a smoothly curving route that did not extend into the apical region of the ventricle; 2) had a larger volume and possessed a larger presystolic KE (0.4 +/- 0.3 mJ) than the other flow components (P andlt; 0.001 and P andlt; 0.01, respectively); and 3) represented a larger part of the end-diastolic blood volume compared with the LV Direct Flow (P andlt; 0.01). These findings suggest that diastolic flow patterns distinct to the normal RV create favorable conditions for ensuing systolic ejection of the Direct Flow component. These flow-specific aspects of RV diastolic-systolic coupling provide novel perspectives on RV physiology and may add to the understanding of RV pathophysiology.

    Place, publisher, year, edition, pages
    American Physiological Society, 2011
    Keywords
    cardiac disease, interventricular function, kinetic energy, phase-contrast magnetic resonance imaging, pump physiology
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-74161 (URN)10.1152/ajpheart.00622.2011 (DOI)000298325200020 ()
    Note
    Funding Agencies|Swedish Research Council||Swedish Heart-Lung Foundation||Emil and Wera Cornell Foundation||Available from: 2012-01-20 Created: 2012-01-20 Last updated: 2017-12-08
    2. Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
    Open this publication in new window or tab >>Turbulent Kinetic Energy in Normal and Myopathic Left Ventricles
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    2015 (English)In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 41, no 4, p. 1021-1029Article in journal (Refereed) Published
    Abstract [en]

    Purpose: To assess turbulent kinetic energy (TKE) within the left ventricle (LV) of healthy subjects using novel 4D flow MRI methods and to compare TKE values to those from a spectrum of patients with dilated cardiomyopathy (DCM).

    Methods: 4D flow and morphological MRI-data were acquired in 11 healthy subjects and 9 patients with different degrees of diastolic dysfunction. TKELV was calculated within the LV at each diastolic time frame. At peak early (E) and late (A) diastolic filling, the TKELV was compared to transmitral peak velocity, LV diameter and mitral annular diameter.

    Results: In the majority of all subjects, peaks in TKELV could be observed at E and A. Peak TKELV at E was not different between the groups, and correlated with mitral annular dimensions. Peak TKELV at A was higher in DCM patients compared to healthy subjects, and was related to LV diameter and transmitral velocity.

    Conclusions: In normal LVs, TKE values are low. Values are highest during early diastole, and diminish with increasing LV size. In a heterogeneous group of DCM patients, late diastolic TKE values are higher than in healthy subjects. Kinetic energy loss due to elevated late diastolic TKE may reflect inefficient flow in dilated LVs.

    Place, publisher, year, edition, pages
    Wiley-Blackwell, 2015
    Keywords
    Magnetic resonance imaging, blood flow, turbulent flow, cardiac function, diastolic dysfunction, heart failure
    National Category
    Medical Engineering Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-99957 (URN)10.1002/jmri.24633 (DOI)000351521700019 ()
    Note

    Contract grant sponsor: Swedish Heart-Lung Foundation; Contract grant sponsor: Swedish Research Council; Contract grant sponsor: European Research Council.

    Available from: 2013-10-24 Created: 2013-10-24 Last updated: 2017-12-06Bibliographically approved
    3. Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block
    Open this publication in new window or tab >>Left ventricular hemodynamic forces as a marker of mechanical dyssynchrony in heart failure patients with left bundle branch block
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    2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 2971Article in journal (Refereed) Published
    Abstract [en]

    Left bundle branch block (LBBB) causes left ventricular (LV) dyssynchrony which is often associated with heart failure. A significant proportion of heart failure patients do not demonstrate clinical improvement despite cardiac resynchronization therapy (CRT). How LBBB-related effects on LV diastolic function may contribute to those therapeutic failures has not been clarified. We hypothesized that LV hemodynamic forces calculated from 4D flow MRI could serve as a marker of diastolic mechanical dyssynchrony in LBBB hearts. MRI data were acquired in heart failure patients with LBBB or matched patients without LBBB. LV pressure gradients were calculated from the Navier-Stokes equations. Integration of the pressure gradients over the LV volume rendered the hemodynamic forces. The findings demonstrate that the LV filling forces are more orthogonal to the main LV flow direction in heart failure patients with LBBB compared to those without LBBB during early but not late diastole. The greater the conduction abnormality the greater the discordance of LV filling force with the predominant LV flow direction (r(2) = 0.49). Such unique flow-specific measures of mechanical dyssynchrony may serve as an additional tool for considering the risks imposed by conduction abnormalities in heart failure patients and prove to be useful in predicting response to CRT.

    Place, publisher, year, edition, pages
    NATURE PUBLISHING GROUP, 2017
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:liu:diva-138889 (URN)10.1038/s41598-017-03089-x (DOI)000402879800027 ()28592851 (PubMedID)
    Note

    Funding Agencies|Swedish Heart Lung foundation [20140398]; Swedish Research Council [2014-6191]; European Research Council [310612]

    Available from: 2017-06-27 Created: 2017-06-27 Last updated: 2018-04-17
  • 447.
    Zhou, Zien
    et al.
    Univ New South Wales, Australia; Shanghai Jiao Tong Univ, Peoples R China.
    Lindley, Richard I.
    George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Rådholm, Karin
    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 Ödeshög. George Inst Global Hlth, Australia; Univ Sydney, Australia.
    Jenkins, Bronwyn
    Royal North Shore Hosp, Australia.
    Watson, John
    Univ New South Wales, Australia.
    Perkovic, Vlado
    Univ New South Wales, Australia; Univ Sydney, Australia; Royal North Shore Hosp, Australia.
    Mahaffey, Kenneth W.
    Stanford Univ, CA 94305 USA.
    de Zeeuw, Dick
    Univ Groningen, Netherlands.
    Fulcher, Greg
    Univ Sydney, Australia; Royal North Shore Hosp, Australia.
    Shaw, Wayne
    Janssen Res and Dev LLC, NJ USA.
    Oh, Richard
    Janssen Res and Dev LLC, NJ USA.
    Desai, Mehul
    Janssen Res and Dev LLC, NJ USA.
    Matthews, David R.
    Univ Oxford, England; Univ Oxford, England.
    Neal, Bruce
    Univ New South Wales, Australia; Univ New South Wales, Australia; Univ Sydney, Australia; Imperial Coll London, England.
    Canagliflozin and Stroke in Type 2 Diabetes Mellitus Results From the Randomized CANVAS Program Trials2019In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 50, no 2, p. 396-404Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without cerebrovascular disease (stroke or transient ischemic attack) at baseline from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program. Methods-The CANVAS Program, comprising 2 similarly designed and conducted clinical trials, randomly assigned 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk to canagliflozin or placebo. Its primary outcome was a composite of major adverse cardiovascular events. The main outcome of interest for this report was fatal or nonfatal stroke. Additional exploratory outcomes were stroke subtypes and other vascular outcomes defined according to standard criteria. Results-There were 1 958 (19%) participants with prior stroke or transient ischemic attack at baseline. These individuals were older, more frequently women, and had higher rates of heart failure, atrial fibrillation, and microvascular disease (all Pamp;lt;0.001) compared with those without such a history. There were 309 participants with stroke events during followup (123 had prior stroke or transient ischemic attack at baseline and 186 did not), at a rate of 7.93/1000 patient-years among those assigned canagliflozin and 9.62/1000 patient-years among placebo (hazard ratio, 0.87; 95% CI, 0.691.09). Analysis of stroke subtypes found no effect on ischemic stroke (n=253, hazard ratio, 0.95; 95% CI, 0.74-1.22), a significant reduction for hemorrhagic stroke (n=30, hazard ratio, 0.43; 95% CI, 0.20-0.89) and no effect on undetermined stroke (n=29, hazard ratio, 1.04; 95% CI, 0.48-2.22). Effects on other cardiovascular outcomes were comparable among participants with and without stroke or transient ischemic attack at baseline. Conclusions-There were too few events in the CANVAS Program to separately define the effects of canagliflozin on stroke, but benefit is more likely than harm. The observed possible protective effect for hemorrhagic stroke was based on small numbers but warrants further investigation.

  • 448.
    Ängerud, Karin H
    et al.
    Umeå University, Sweden.
    Sederholm Lawesson, Sofia
    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.
    Isaksson, Rose-Marie
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Department of Research, Norrbotten County Council, Sweden.
    Thylén, Ingela
    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.
    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.
    Differences in symptoms, first medical contact and pre-hospital delay times between patients with ST- and non-ST-elevation myocardial infarction2019In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 8, no 3, p. 201-207Article in journal (Refereed)
    Abstract [en]

    AIM: In ST-elevation myocardial infarction, time to reperfusion is crucial for the prognosis. Symptom presentation in myocardial infarction influences pre-hospital delay times but studies about differences in symptoms between patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction are sparse and inconclusive. The aim was to compare symptoms, first medical contact and pre-hospital delay times in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction.

    METHODS AND RESULTS: This multicentre, observational study included 694 myocardial infarction patients from five hospitals. The patients filled in a questionnaire about their pre-hospital experiences within 24 h of hospital admittance. Chest pain was the most common symptom in ST-elevation myocardial infarction and non-ST-elevation myocardial infarction (88.7 vs 87.0%, p=0.56). Patients with cold sweat (odds ratio 3.61, 95% confidence interval 2.29-5.70), jaw pain (odds ratio 2.41, 95% confidence interval 1.04-5.58), and nausea (odds ratio 1.70, 95% confidence interval 1.01-2.87) were more likely to present with ST-elevation myocardial infarction, whereas the opposite was true for symptoms that come and go (odds ratio 0.58, 95% confidence interval 0.38-0.90) or anxiety (odds ratio 0.52, 95% confidence interval 0.29-0.92). Use of emergency medical services was higher among patients admitted with ST-elevation myocardial infarction. The pre-hospital delay time from symptom onset to first medical contact was significantly longer in non-ST-elevation myocardial infarction (2:05 h vs 1:10 h, p=0.001).

    CONCLUSION: Patients with ST-elevation myocardial infarction differed from those with non-ST-elevation myocardial infarction regarding symptom presentation, ambulance utilisation and pre-hospital delay times. This knowledge is important to be aware of for all healthcare personnel and the general public especially in order to recognise symptoms suggestive of ST-elevation myocardial infarction and when to decide if there is a need for an ambulance.

  • 449.
    Åhman, Rasmus
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Forsberg Siverhall, Pontus
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Snygg, Johan
    Sahlgrens Univ Hosp, Sweden.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences.
    Enlund, Gunnar
    Uppsala Univ Hosp, Sweden.
    Björnström, Karin
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Chew, Michelle
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Anaesthesiology and Intensive Care in Linköping.
    Determinants of mortality after hip fracture surgery in Sweden: a registry-based retrospective cohort study2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 15695Article in journal (Refereed)
    Abstract [en]

    Surgery for hip fractures is associated with high mortality and morbidity. The causes of poor outcome are not fully understood and may be related to other factors than the surgery itself. The relative contributions of patient, surgical, anaesthetic and structural factors have seldom been studied together. This study, a retrospective registry-based cohort study of 14 932 patients undergoing hip fracture surgery in Sweden from 1st of January 2014 to 31st of December 2016, aimed to identify important predictors of mortality post-surgery. The independent predictive power of our included variables was examined using Cox proportional hazards modeling with all-cause mortality at longest follow-up as the outcome. Twelve independent variables were considered as interrelated exposures and their individual adjusted effect within a single model were evaluated. Kaplan-Meier curves were also generated. Crude mortality rates were 8.2% at 30 days (95% CI 7.7-8.6%) and 23.6% at 365 days (95% CI 22.9-24.2%). Of the 12 factors entered into the Cox regression analysis, age (aHR1.06, p amp;lt; 0.001), male gender (aHR 1.45, p amp;lt; 0.001), ASA-PS-class (ASA 1amp;2 reference; ASA 3 aHR 2.12; ASA 4 aHR 4.79; ASA 5 aHR 12.57 respectively, p amp;lt; 0.001) and PACU-LOS (aHR 1.01, p amp;lt; 0.001) were significantly associated with mortality at longest follow-up (up to 3 years). University hospital status was protective (aHR 0.83, p amp;lt; 0.001) in the same model. Age, gender and ASA-PS-class were strong predictors of mortality after surgery for hip fractures in Sweden. University hospital status and length of stay in the postoperative care unit were also identified as modifiable risk factors after multivariable adjustment and require confirmation in future studies.

  • 450.
    Åström Aneq, Meriam
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Arytmogen högerkammarkardiomyopati2016In: Idrott och hjärtat / [ed] Mats Börjesson, Mikael Dellborg, Studentlitteratur, 2016, Vol. 1, p. 141-150Chapter in book (Other academic)
678910 401 - 450 of 452
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