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  • 451.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Anti-platelet and anti-thrombotic therapy in diabetic patients with ACS2013In: Diabetes in Heart Disease - a companion to Braunwald Heart Disease / [ed] McGuire DK, Marx N, Elsevier, 2013Chapter in book (Other academic)
  • 452.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Enoxaparin for anticoagulation in patients undergoing percutaneous coronary intervention2012In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 344, p. e712-Article in journal (Refereed)
  • 453.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Evidenced-Based Antithrombotic Therapy for Acute Coronary Syndromes2013In: Diabetes, ISSN 0012-1797, E-ISSN 1939-327X, Vol. 62, no 3, p. 709-710Article in journal (Refereed)
  • 454.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    How far will the FIREHAWK stent fly?2018In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 392, no 10153, p. 1091-1092Article in journal (Other academic)
  • 455.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Non-Vitamin K Antagonist Preferred in Patients With Nonvalvular Atrial Fibrillation and Indication for Aspirin Therapy2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 11, p. 1130-1131Article in journal (Other academic)
  • 456.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Registry studies and post marketing surveillance.2012In: Percutaneous Interventional Cardiovascular Medicine - the PCR-EAPCI textbook / [ed] Naber CK, Baumbach A, Vahanian A, Europa digital publishing , 2012Chapter in book (Other academic)
  • 457.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stroke: a rare but devastating procedural complication of PCI2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 25, p. 1571-1572Article in journal (Other academic)
    Abstract [en]

    This editorial refers to 'Stroke followingpercutaneous coronary intervention: type-specific incidence, outcomes, and determinants seenby theBritishCardiovascular Intervention Society 2007-2012'(dagger), by C.S. Kwok et al., on page 1618.

  • 458.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    ST-segment elevation myocardial infarction2013In: The ESC textbook of Intensive and Acute Cardiac Care - 2nd edition / [ed] Tubaro M, Vranckx P., Oxford University Press, 2013Chapter in book (Other academic)
  • 459.
    James, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Fröbert, Ole
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Cardiovascular registries: a novel platform for randomised clinical trials2012In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 98, no 18, p. 1329-1331Article in journal (Refereed)
  • 460.
    James, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Improving long-term outcomeafter myocardial infarction2012In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 380, no 9850, p. 1290-1291Article in journal (Other academic)
  • 461.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Importance of post-approval real-word evidence2018In: European Heart Journal - Cardiovascular Pharmacotherapy, ISSN 2055-6837, E-ISSN 2055-6845, Vol. 4, no 1, p. 10-11Article in journal (Other academic)
  • 462.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bellavia, Andrea
    Orsini, Nicola
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Cannon, Christopher
    Harrington, Robert
    Himmelmann, Anders
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Time Based Measures Of Treatment Effect: Reassessment Of Ticagrelor Versus Clopidogrel In The Plato Study2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 548-548Article in journal (Other academic)
  • 463.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Timmer, Jorik R.
    Ottervanger, Jan Paul
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Armstrong, Paul
    Califf, Robert
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Simoons, Maarten L.
    Usefulness of biomarkers for predicting long-term mortality in patients with diabetes mellitus and non-ST-elevation acute coronary syndromes (A GUSTO IV substudy)2006In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 97, no 2, p. 167-172Article in journal (Refereed)
    Abstract [en]

    The present study evaluated whether biomarkers of ischemia, inflammation, myocardial damage, and dysfunction are equally useful in patients who have diabetes mellitus (DM) for prediction of cardiac events in non-ST-elevation acute coronary syndrome (ACS). DM was present in 1,677 of 7,800 patients (21.5%) who had non-ST-elevation ACS and were included in the Fourth Global Utilization of Strategies To Open Occluded Arteries (GUSTO IV) trial. Creatinine, N-terminal pro-B-type natriuretic peptide (NT-pro-BNP), troponin T, C-reactive protein, and interleukin-6 were analyzed in serum samples that were obtained at a median of 9.5 hours from symptom onset. One-year mortality rates were 13.5% among patients who had DM (n = 227) and 6.9% among those who did not (n = 418, p < 0.001). The median level of NT-pro-BNP was 2 times as high in patients who had DM, whereas troponin T levels did not differ by DM status. Mortality increased with ascending quartiles of NT-pro-BNP, with 1-year mortality rates of 3.9% (n = 11) in the bottom quartile and 29% (n = 103) in the top quartile. In multivariable analyses, factors that were predictive of 1-year mortality in patients who did not have DM were also significant for those who did. Presence of ST depression > 0.5 mm had the highest odds ratio of 2.3 (95% confidence interval 1.2 to 4.6). NT-pro-BNP levels > 669 ng/L (odds ratio 2.0, 95% confidence interval 1.1 to 3.6) and interleukin-6 levels > 10 ng/L (odds ratio 1.9, 95% confidence interval 1.2 to 3.0) were significant biomarker predictors. In conclusion, DM confers a high long-term mortality in non-ST-elevation ACS. Despite a larger proportion of ST depression and increased levels of NT-pro-BNP and interleukin-6 at admission, these factors provide independent prognostic information that may improve risk stratification and guidance of treatment.

  • 464.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Pieper, Karen S.
    Cannon, Christopher P.
    Storey, Robert F.
    Becker, Richard C.
    Steg, Philippe Gabriel
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Harrington, Robert A.
    Ticagrelor in Patients With Acute Coronary Syndromes and Stroke Interpretation of Subgroups in Clinical Trials2013In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, no 5, p. 1477-1479Article in journal (Other academic)
  • 465.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Armstrong, P
    Barnathan, E
    Califf, R
    Lindahl, B
    Simoons, M
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Activation of the inflammation, coagulation, and fibrinolysis systems, without influence of abciximab infusion in patients with non-ST–elevation acute coronary syndromes treated with dalteparin: a GUSTO IV substudy2004In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 147, no 2, p. 267-274Article in journal (Refereed)
    Abstract [en]

    Background

    In acute coronary syndromes, the inflammation and the coagulation systems are activated, implying an impaired outcome. In addition to platelet inhibition, recent evidence suggests that the glycoprotein IIb/IIIa receptor inhibitor abciximab attenuates inflammation and coagulation activity.

    Methods

    The Swedish Global Utilization of Strategies To open Occluded arteries-IV (GUSTO-IV) substudy included 404 patients with non-ST–elevation acute coronary syndromes. In addition to aspirin and dalteparin, all patients were randomized to receive abciximab infusion for 24 hours or 48 hours or corresponding placebo without early coronary revascularization. Plasma samples were obtained at baseline and 24, 48, and 72 hours.

    Results

    The median levels of the coagulation markers thrombin/antithrombin complex and soluble fibrin increased significantly from 3.1 to 3.7 ug/L (baseline to peak; P <.001) and from 20 to 23 nmol/L (P <.001), respectively. The fibrinolysis marker, tissue plasminogen-activator, also increased its median levels, from 11.7 to 17.5 ug/L (P <.001), whereas the median level of plasminogen-activator-inhibitor was unchanged. The inflammatory markers interleukin-6, C-reactive protein, and fibrinogen also increased their median levels (5.4–7.8 ng/L, P <.001; 4.4–8.7 mg/L, P <.001; 3.3–3.9 g/L, P <.001). However, there were no differences in median levels or in changes of median levels of any marker at any point between the placebo group and any of the abciximab groups.

    Conclusions

    In non-ST–elevation acute coronary syndrome, there was a simultaneous activation of the inflammation, coagulation, and fibrinolysis systems, despite aspirin and dalteparin treatment. Prolonged treatment with abciximab had no influence of the activation of these systems.

    Unstable coronary artery disease (CAD) intricately involves inflammatory mediators in the development of an atherosclerotic plaque and in thrombus formation by platelet aggregation.1 Acute phase elevation of inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and fibrinogen are important predictors of the short- and long-term prognosis in unstable CAD.2, 3 and 4 Activation of the coagulation and fibrinolysis systems, as demonstrated with elevated markers of thrombin generation, thrombin activity, and fibrin turnover, also have been found in the acute phase of unstable CAD and are associated with an adverse outcome.5, 6 and 7 Glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors potently inhibit platelet aggregation and reduce the incidence of ischemic events in patients undergoing percutaneuos coronary interventions8, 9 and 10 and in patients with unstable CAD.11 The GP IIb/IIIa inhibitor abciximab, in addition to its antithrombotic effect, also suppresses the rise in levels of inflammatory markers after percutaneous coronary interventions.12 This anti-inflammatory effect might be related to abciximab's cross-reaction with other integrin receptors.13 Furthermore, by inhibiting platelet aggregation, abciximab might also attenuate the coagulation and fibrinolysis activation as shown in vitro and in vivo.14 and 15

    The Global Utilization of Strategies To Open occluded arteries in acute coronary syndromes (GUSTO IV-ACS) trial unexpectedly failed to show any benefit of abciximab treatment in a high risk ACS population not undergoing early coronary revascularization.16 In the GUSTO IV-ACS low-molecular weight heparin substudy,17 dalteparin was used as the anticoagulant. Dalteparin, which is an inhibitor of the coagulation cascade, mainly by inhibition of factor Xa and less of factor IIa, has previously been shown to reduce the generation and activity of thrombin in unstable coronary disease.18 There is evidence that a combination of abciximab and a low-molecular-weight heparin have additive effects on the lag-time to platelet aggregation,19 and there are several theoretical advantages with the combination treatment. There was still no significant reduction in clinical events with abciximab in combination with dalteparin.17 The aim of this Swedish substudy of GUSTO IV-ACS was to evaluate the influence of abciximab infusion on markers on inflammation, coagulation, and fibrinolysis in patients with unstable CAD treated with aspirin and subcutaneous dalteparin.

  • 466.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Spertus, John A.
    Evidence-based treatments for STEMI: are we doing enough?2013In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 382, no 9892, p. 576-579Article in journal (Other academic)
  • 467.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Storey, Robert F.
    Khurmi, Nardev S.
    Husted, Steen
    Keltai, Matyas
    Mahaffey, Kenneth W.
    Maya, Juan
    Morais, Joao
    Lopes, Renato D.
    Nicolau, Jose C.
    Pais, Prem
    Raev, Dimitar
    Lopez-Sendon, Jose L.
    Stevens, Susanna R.
    Becker, Richard C.
    Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and a History of Stroke or Transient Ischemic Attack2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 23, p. 2914-2921Article in journal (Refereed)
    Abstract [en]

    Background-Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages.

    Methods and Results-We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively).

    Conclusions-Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.

  • 468.
    James, Stefan K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Storey, Robert F.
    Pieper, Karen S.
    Cannon, Christopher P.
    Becker, Richard C.
    Steg, Philippe Gabriel
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Harrington, Robert A.
    Response to Letter Regarding Article, "Ticagrelor in Patients With Acute Coronary Syndromes and Stroke: Interpretation of Subgroups in Clinical Trials"2013In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 44, no 8, p. E95-E96Article in journal (Refereed)
  • 469.
    James, Stefan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Armstrong, P
    Barnathan, E
    Califf, R
    Topol, E
    Simoons, Maarten L
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    N-Terminal Pro–Brain Natriuretic Peptide and Other Risk Markers for the Separate Prediction of Mortality and Subsequent Myocardial Infarction in Patients With Unstable Coronary Artery Disease: A Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV Substudy2003In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 108, no 3, p. 275-281Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients. METHODS AND RESULTS: NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile. CONCLUSIONS: The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.

  • 470.
    Janiec, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Dimberg, Axel
    Nazari Shafti, Timo Z
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindblom, Rickard P F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erratum to: "No improvements in long-term outcome after coronary artery bypass grafting with arterial grafts as a second conduit2018In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 53, no 5, article id 1098Article in journal (Refereed)
  • 471.
    Janiec, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Department of Cardiothoracic Surgery and Anaesthesia, Uppsala University Hospital, Uppsala, Sweden.
    Dimberg, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. epartment of Cardiothoracic Surgery and Anaesthesia, Uppsala University Hospital, Uppsala, Sweden.
    Nazari Shafti, Timo Z
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Department of Cardiology and Clinical Physiology, Uppsala University Hospital, Uppsala, Sweden.
    Lindblom, Rickard P.F.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery. Department of Cardiothoracic Surgery and Anaesthesia, Uppsala University Hospital, Uppsala, Sweden.
    No improvements in long-term outcome after coronary artery bypass grafting with arterial grafts as a second conduit: a Swedish nationwide registry study2018In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 53, no 2, p. 448-454Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Coronary artery bypass grafting using saphenous vein grafts (SVGs) in addition to the left internal mammary artery (IMA) graft is vitiated by poor long-term patency of the vein grafts. Hypothetically, the increased use of arterial grafts could confer even better outcomes. Our goal was to evaluate results after coronary artery bypass grafting in Sweden, where arterial grafts were used as a second conduit.

    METHODS: Within the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we identified patients who had coronary artery bypass grafting from 2001 to 2015 using the IMA and the SVG, the radial artery (RA) or the additional IMA [bilateral IMA (BIMA)] as a second conduit. Deaths, postoperative incidence of coronary angiography and need for reintervention were recorded, and multivariable adjusted hazard ratios were calculated for different types of grafts.

    RESULTS: The study population comprised 45 319 cases of IMA + SVG, 1225 cases of IMA + RA and 1697 cases of BIMA. The mean follow-up time (SD) was 9.2 (4.2) years for IMA + SVG, 11.2 (4.0) years for IMA + RA grafts and 9.2 (5.2) years for the BIMA graft. The adjusted hazard ratio for death was (95% confidence interval) 1.06 (0.95-1.18) for IMA + RA and 1.21 (1.10-1.33) for BIMA grafts compared with IMA + SVG. The adjusted hazard ratio for the first angiographic examination was (95% confidence interval) 0.89 (0.78-1.01) for IMA + RA and 1.07 (0.96-1.20) for BIMA grafts. The adjusted hazard ratio for the need for reintervention was (95% confidence interval) 0.88 (0.74-1.04) for IMA + RA and 1.14 (0.98-1.32) for BIMA grafts.

    CONCLUSIONS: Patients who had arterial grafts as second conduits did not demonstrate a better outcome in any of the studied end-points. Radial artery grafts seem to be preferable to BIMA grafts as an alternative to an SVG.

  • 472.
    Janiec, Mikael
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Shafti, Timo Z. Nazari
    Deutsch Herzzentrum Berlin, Dept Cardiothorac & Vasc Surg, Berlin, Germany;Berlin Inst Hlth, Berlin, Germany.
    Dimberg, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindblom, Rickard P F
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Graft failure and recurrence of symptoms after coronary artery bypass grafting2018In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 52, no 3, p. 113-119Article in journal (Refereed)
    Abstract [en]

    Objectives: Saphenous vein grafts (SVGs) most often used in coronary artery bypass grafting (CABG) are subject to graft disease and have poor long-term patency, however the clinical implication of this is not completely known. We aim to assess the influence of graft failure on the postoperative recurrence of coronary artery disease (CAD) symptoms in relation to the contribution from progression of atherosclerosis in the native coronary vessels.

    Design: Within the SWEDEHEART registry we identified 46,663 CABG cases between 2001 and 2015 with patient age 40-80 years where single internal mammary artery (IMA) anastomosis (IMA), single IMA with one (1SVG) or multiple SVG anastomoses (2+ SVG) had been performed. Clinical characteristics as well as mortality and postoperative incidence of coronary angiography were recorded and multivariable adjusted hazard ratios were calculated. Indications for the angiographies and occurrence of graft failure were also registered.

    Results: The adjusted hazard ratio for death was similar for the three groups. The adjusted hazard ratio for being submitted to angiography as compared to 2+ SVG was (95% CI) 1.24 (1.06-1.46) for IMA and 1.21 (1.15-1.28) for 1SVG. Failed grafts were found at the first postoperative angiography with preceding CAD symptoms in 21.4% of patients in the IMA group, 41.6% in the 1SVG group and 61.1% in the 2+ SVG group.

    Conclusions: A substantial amount of angiographies occur in patients without any graft failure and a large part of postoperative recurrence of CAD symptoms and are likely attributed to IMA failure or progression of atherosclerosis in the native coronary arteries.

  • 473. Janzon, M.
    et al.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cannon, C. P.
    Storey, R. F.
    Mellstrom, C.
    Nicolau, J. C.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Henriksson, M.
    Health economic analysis of ticagrelor in patients with acute coronary syndromes intended for non-invasive therapy2015In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 2, p. 119-125Article in journal (Refereed)
    Abstract [en]

    Objective To investigate the cost effectiveness of ticagrelor versus clopidogrel in patients with acute coronary syndromes (ACS) in the Platelet Inhibition and Patient Outcomes (PLATO) study who were scheduled for non-invasive management. Methods A previously developed cost effectiveness model was used to estimate long-term costs and outcomes for patients scheduled for non-invasive management. Healthcare costs, event rates and health-related quality of life under treatment with either ticagrelor or clopidogrel over 12 months were estimated from the PLATO study. Long-term costs and health outcomes were estimated based on data from PLATO and published literature sources. To investigate the importance of different healthcare cost structures and life expectancy for the results, the analysis was carried out from the perspectives of the Swedish, UK, German and Brazilian public healthcare systems. Results Ticagrelor was associated with lifetime quality-adjusted life-year (QALY) gains of 0.17 in Sweden, 0.16 in the UK, 0.17 in Germany and 0.13 in Brazil compared with generic clopidogrel, with increased healthcare costs of (sic)467, (sic)551, (sic)739 and (sic)574, respectively. The cost per QALY gained with ticagrelor was (sic)2747, (sic)3395, (sic)4419 and (sic)4471 from a Swedish, UK, German and Brazilian public healthcare system perspective, respectively. Probabilistic sensitivity analyses indicated that the cost per QALY gained with ticagrelor was below conventional threshold values of cost effectiveness with a high probability. Conclusions Treatment of patients with ACS scheduled for 12 months' non-invasive management with ticagrelor is associated with a cost per QALY gained below conventional threshold values of cost effectiveness compared with generic clopidogrel.

  • 474. Jernberg, Tomas
    et al.
    Hambraeus, Kristina
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Rück, Andreas
    Friberg, Örjan
    Carlsson, Marcus
    Bäck, Maria
    Johansson, Pelle
    Replik till Åke Thörn och Bengt Järhult: seriös diskussion om kvalitetsregister välkomnas2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, article id DFSSArticle in journal (Refereed)
  • 475.
    Jernberg, Tomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Natriuretic peptides in unstable coronary artery disease2004In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 25, no 17, p. 1486-1493Article in journal (Other academic)
    Abstract [en]

    Patients with unstable coronary artery disease (CAD), i.e., unstable angina or non-ST-elevation myocardial infarction, vary widely in clinical presentation, prognosis and response to treatment. To select appropriate therapy, early risk stratification has become increasingly important. This review focuses on the emerging role of natriuretic peptides in the early assessment of patients with unstable CAD. We conclude that levels of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are strongly associated to mortality and the risk of future congestive heart failure, and carry important prognostic information independent from previously known risk factors in unstable CAD. There are some data indicating that these markers can also be helpful in the selection of appropriate therapy in these patients but further studies are needed. Before a routine use of BNP or NT-proBNP in unstable CAD can be recommended, the cost-effectiveness of adding these new markers to the currently routine markers and their impact on selection of treatment needs further evaluation.

  • 476.
    Jernberg, Tomas
    et al.
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Cardiol, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alfredsson, Joakim
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Berglund, Ellinor
    Karolinska Inst, Ctr Resuscitat Sci, Dept Med, Stockholm, Sweden.
    Bergstroem, Olle
    Vaxjo Hosp, Dept Med, Vaxjo, Sweden.
    Engstrom, Anders
    Kalmar Reg Hosp, Div Cardiol, Dept Med, Kalmar, Sweden.
    Erlinge, David
    Lund Univ, Dept Clin Sci, Cardiol, Lund, Sweden.
    Herlitz, Johan
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Cardiol, Gothenburg, Sweden;Univ Boras, Dept Hlth Sci, Boras, Sweden.
    Jumatate, Raluca
    Kristianstad Hosp, Dept Med, Kristianstad, Sweden.
    Kellerth, Thomas
    Orebro Univ Hosp, Dept Cardiol, Orebro, Sweden.
    Lauermann, Jorg
    Ryhov Hosp, Div Cardiol, Dept Internal Med, Jonkoping, Sweden.
    Lindmark, Krister
    Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
    Lingman, Markus
    Halland Hosp, Dept Med, Halmstad, Sweden;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.
    Ljung, Lina
    Karolinska Inst, Sodersjukhuset, Div Cardiol, Dept Clin Sci & Educ, Sjukhusbacken 10, S-11883 Stockholm, Sweden.
    Nilsson, Carina
    Ljungby Hosp, Dept Med, Ljungby, Sweden.
    Omerovic, Elmir
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Pernow, John
    Karolinska Inst, Div Cardiol, Dept Med, Solna, Sweden;Karolinska Univ Hosp, Stockholm, Sweden.
    Ravn-Fischer, Annica
    Univ Gothenburg, Dept Mol & Clin Med, Gothenburg, Sweden;Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Cardiol, Gothenburg, Sweden.
    Sparv, David
    Lund Univ, Dept Clin Sci, Cardiol, Lund, Sweden.
    Yndigegn, Troels
    Lund Univ, Dept Clin Sci, Cardiol, Lund, Sweden.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hofmann, Robin
    Karolinska Inst, Sodersjukhuset, Div Cardiol, Dept Clin Sci & Educ, Sjukhusbacken 10, S-11883 Stockholm, Sweden.
    Long-Term Effects of Oxygen Therapy on Death or Hospitalization for Heart Failure in Patients With Suspected Acute Myocardial Infarction2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 138, no 24, p. 2754-2762Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In the DETO2X-AMI trial (Determination of the Role of Oxygen in Suspected Acute Myocardial Infarction), we compared supplemental oxygen with ambient air in normoxemic patients presenting with suspected myocardial infarction and found no significant survival benefit at 1 year. However, important secondary end points were not yet available. We now report the prespecified secondary end points cardiovascular death and the composite of all-cause death and hospitalization for heart failure. METHODS: In this pragmatic, registry-based randomized clinical trial, we used a nationwide quality registry for coronary care for trial procedures and evaluated end points through the Swedish population registry (mortality), the Swedish inpatient registry (heart failure), and cause of death registry (cardiovascular death). Patients with suspected acute myocardial infarction and oxygen saturation of >= 90% were randomly assigned to receive either supplemental oxygen at 6 L/min for 6 to 12 hours delivered by open face mask or ambient air. RESULTS: A total of 6629 patients were enrolled. Acute heart failure treatment, left ventricular systolic function assessed by echocardiography, and infarct size measured by high-sensitive cardiac troponin T were similar in the 2 groups during the hospitalization period. All-cause death or hospitalization for heart failure within 1 year after randomization occurred in 8.0% of patients assigned to oxygen and in 7.9% of patients assigned to ambient air (hazard ratio, 0.99; 95% CI, 0.84-1.18; P=0.92). During long-term follow-up (median [range], 2.1 [1.0-3.7] years), the composite end point occurred in 11.2% of patients assigned to oxygen and in 10.8% of patients assigned to ambient air (hazard ratio, 1.02; 95% CI, 0.88-1.17; P=0.84), and cardiovascular death occurred in 5.2% of patients assigned to oxygen and in 4.8% assigned to ambient air (hazard ratio, 1.07; 95% CI, 0.87-1.33; P=0.52). The results were consistent across all predefined subgroups. CONCLUSIONS: Routine use of supplemental oxygen in normoxemic patients with suspected myocardial infarction was not found to reduce the composite of all-cause mortality and hospitalization for heart failure, or cardiovascular death within 1 year or during long-term follow-up.

  • 477.
    Jobs, Elisabeth
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Ingelsson, Erik
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jobs, Magnus
    University of Dalarna.
    Nerpin, Elisabet
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Iggman, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Basu, Samar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Oxidative Stress and Inflammation.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lars, Lind
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Serum cathepsin S is associated with decreased insulin sensitivity and the development of diabetes type 2 in a community-based cohort of elderly men2013In: Diabetes Care, ISSN 0149-5992, E-ISSN 1935-5548, Vol. 36, no 1, p. 163-165Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    To investigate associations between serum cathepsin S, impaired insulin sensitivity, defective insulin secretion, and diabetes risk in a community-based sample of elderly men without diabetes.

    RESEARCH DESIGN AND METHODS:

    Serum cathepsin S, insulin sensitivity (euglycemic-hyperinsulinemic clamp), and insulin secretion (early insulin response during an oral glucose tolerance test) were measured in 905 participants of the Uppsala Longitudinal Study of Adult Men (mean age, 71 years). Thirty participants developed diabetes during 6 years of follow-up.

    RESULTS:

    After adjustment for age, anthropometric variables, and inflammatory markers, higher cathepsin S was associated with decreased insulin sensitivity (regression coefficient per SD increase -0.09 [95% CI -0.14 to -0.04], P = 0.001), but no association with early insulin response was found. Moreover, higher cathepsin S was associated with a higher risk for developing diabetes (odds ratio per SD increase 1.48 [1.08-2.01], P = 0.01).

    CONCLUSIONS:

    Cathepsin S activity appears to be involved in the early dysregulation of glucose and insulin metabolism.

  • 478. Johansson, B.
    et al.
    Engstrom, K. -G
    Dellborg, M.
    Kronvall, T.
    Kvidal, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Mattsson, E.
    Thilen, U.
    Functional class, symptoms, medications, arrhythmia devices and quality of life in adults with congenital aortic valve disease. Data from the national registry of congenital heart disease2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 375-375Article in journal (Other academic)
  • 479.
    Johansson, Jakob
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Hammerby, Rutger
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Rubertsson, Sten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Adrenaline administration during cardiopulmonary resuscitation: poor adherence to clinical guidelines2004In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 48, no 7, p. 909-913Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Adrenaline does not appear to improve the outcome after cardiac arrest in clinical trials in spite of beneficial effects in experimental studies. The objective of this study was to determine whether adrenaline was administered in accordance with advanced cardiac life support (ACLS) guidelines during adult cardiopulmonary resuscitation (CPR). METHODS: From 15 January to 31 December 2000, all patients at Uppsala University Hospital in whom CPR was attempted were registered prospectively. The duration of CPR was documented in the register and the total dose of adrenaline was retrieved retrospectively from patient records. From these data the average interval between adrenaline doses was calculated. RESULTS: Data for evaluation of the between-dose interval of adrenaline was available in 53 of 107 registered cardiac arrests. In 68% (36/53) the average between-dose interval was longer than the 3-5 min recommended in the guidelines, and 8% (4/53) received no adrenaline. The median interval between adrenaline doses during CPR was 6.5 min (25th-75th percentile: 5.1-10.4). Adherence to guidelines was lower in out-of-hospital cardiac arrest than in in-hospital cardiac arrest (P = 0.01). CONCLUSIONS: In the majority of cases adrenaline did not appear to be administered according to current ACLS guidelines.

  • 480.
    Johansson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Becker, Richard C.
    Storey, Robert F.
    Himmelmann, Anders
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Axelsson, Tomas
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Barratt, Bryan J.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Katus, Hugo A.
    Steg, Philippe Gabriel
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    NLRC4 Inflammasome Is an Important Regulator of Interleukin-18 Levels in Patients With Acute Coronary Syndromes Genome-Wide Association Study in the PLATelet inhibition and patient Outcomes Trial (PLATO)2015In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, E-ISSN 1942-3268, Vol. 8, no 3, p. 498-506Article in journal (Refereed)
    Abstract [en]

    Background Interleukin 18 (IL-18) promotes atherosclerotic plaque formation and is increased in patients with acute coronary syndromes. However the relative contribution of genetic variants to the IL-18 levels has not been fully determined. Methods and Results Baseline plasma IL-18 levels were measured in 16633 patients with acute coronary syndrome, of whom 9340 had genetic data that passed genotype quality control. A 2-stage genome-wide association study was performed, followed by combined analyses using >10 million genotyped or imputed genetic markers. Single nucleotide polymorphisms at 3 loci (IL18, NLRC4, and MROH6) were identified (P<3.15x10(-8)) in the discovery cohort (n=3777) and replicated in the remaining patients (n=5563). In the pooled data (discovery+replication cohort), 7 independent associations, in 5 chromosomal regions, were associated with IL-18 levels (minimum P=6.99x10(-72)). Six single nucleotide polymorphisms are located in predicted promoter regions of which one disrupts a transcription factor binding site. One single nucleotide polymorphism in NLRC4 is a rare missense variant, predicted to be deleterious to the protein. Altogether, the identified genetic variants explained 8% of the total variation in IL-18 levels in the cohort. Conclusions Our results show that genetic variants play an important role in determining IL-18 levels in patients with acute coronary syndrome and we have identified genetic variants located in the IL-18 gene (IL18) or close to genes that are involved in procaspase-1 activation (NLRC4 and CARD16, CARD17, and CARD18). These associations also highlight the importance of the NLRC4 inflammasome for IL-18 production in acute coronary syndrome patients.

  • 481.
    Johansson, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindholm, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Axelsson, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Barratt, Bryan J.
    AstraZeneca R&D, Alderley Pk SK10 4TF, Cheshire, England..
    Becker, Richard C.
    Acad Hlth Ctr, Div Cardiovasc Hlth & Dis, Heart Lung & Vasc Inst, Cincinnati, OH 45267 USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, S-43150 Molndal, Sweden..
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, D-69120 Heidelberg, Germany..
    Steg, Philippe Gabriel
    INSERM, Unite 1148, F-75019 Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75018 Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, F-75013 Paris, France.;Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6NP, England..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2RX, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Genome-wide association and Mendelian randomization study of NT-proBNP in patients with acute coronary syndrome2016In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 25, no 7, p. 1447-1456Article in journal (Refereed)
    Abstract [en]

    N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a strong predictor of mortality in coronary artery disease and is widely employed as a prognostic biomarker. However, a causal relationship between NT-proBNP and clinical endpoints has not been established. We have performed a genome-wide association and Mendelian randomization study of NT-proBNP. We used a discovery set of 3740 patients from the PLATelet inhibition and patient Outcomes (PLATO) trial, which enrolled 18 624 patients with acute coronary syndrome (ACS). A further set of 5492 patients, from the same trial, was used for replication. Genetic variants at two novel loci (SLC39A8 and POC1B/GALNT4) were associated with NT-proBNP levels and replicated together with the previously known NPPB locus. The most significant SNP (rs198389, pooled P = 1.07 x 10(-15)) in NPPB interrupts an E-box consensus motif in the gene promoter. The association in SLC39A8 is driven by a deleterious variant (rs13107325, pooled P = 5.99 x 10(-10)), whereas the most significant SNP in POC1B/GALNT4 (rs11105306, pooled P = 1.02 x 10(-16)) is intronic. The SLC39A8 SNP was associated with higher risk of cardiovascular (CV) death (HR = 1.39, 95% CI: 1.08-1.79, P = 0.0095), but the other loci were not associated with clinical endpoints. We have identified two novel loci to be associated with NT-proBNP in patients with ACS. Only the SLC39A8 variant, but not the NPPB variant, was associated with a clinical endpoint. Due to pleotropic effects of SLC39A8, these results do not suggest that NT-proBNP levels have a direct effect on mortality in ACS patients. PLATO Clinical Trial Registration: ; NCT00391872.

  • 482.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bergdahl, Ellinor
    Samnegard, Ann
    Kenttä, Linda
    Holm, Anna
    Petursson, Petur
    Bäck, Magnus
    [ST-elevation myocardial infarction and dual antiplatelet therapy: new guidelines].2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id E7UIArticle in journal (Refereed)
    Abstract [sv]

    This report summarizes some of the most important changes and new recommendations from the ESC ST-elevation myocardial infarction and double antiplatelet therapy guidelines for 2017, which are of interest for physicians managing patients with coronary artery disease.

  • 483.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bodegard, Johan
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Jerström, Susanna
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Åkesson, Johanna
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Brorsson, Hilja
    Statisticon AB, Uppsala, Sweden..
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Fac Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Fac Hlth Sci, Linkoping, Sweden..
    Albertsson, Per A.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Karlsson, Jan-Erik
    Linkoping Univ, Fac Hlth Sci, Dept Med & Hlth Sci, Dept Internal Med,Cty Council Jonkoping, Linkoping, Sweden..
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effects of interactive patient smartphone support app on drug adherence and lifestyle changes in myocardial infarction patients: a randomized study2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 178, p. 85-94Article in journal (Refereed)
    Abstract [en]

    Background Patients with myocardial infarction (MI) seldom reach recommended targets for secondary prevention. This study evaluated a smartphone application ("app") aimed at improving treatment adherence and cardiovascular lifestyle in MI patients. Design Multicenter, randomized trial. Methods A total of 174 ticagrelor-treated MI patients were randomized to either an interactive patient support tool (active group) or a simplified tool (control group) in addition to usual post-MI care. Primary end point was a composite nonadherence score measuring patient-registered ticagrelor adherence, defined as a combination of adherence failure events (2 missed doses registered in 7-day cycles) and treatment gaps (4 consecutive missed doses). Secondary end points included change in cardiovascular risk factors, quality of life (European Quality of Life-5 Dimensions), and patient device satisfaction (System Usability Scale). Results Patient mean age was 58 years, 81% were men, and 21% were current smokers. At 6 months, greater patient registered drug adherence was achieved in the active vs the control group (nonadherence score: 16.6 vs 22.8 [P = .025]). Numerically, the active group was associated with higher degree of smoking cessation, increased physical activity, and change in quality of life; however, this did not reach statistical significance. Patient satisfaction was significantly higher in the active vs the control group (system usability score: 87.3 vs 78.1 [P = .001]). Conclusions In MI patients, use of an interactive patient support tool improved patient self-reported drug adherence and may be associated with a trend toward improved cardiovascular lifestyle changes and quality of life. Use of a disease-specific interactive patient support tool may be an appreciated, simple, and promising complement to standard secondary prevention.

  • 484.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bornefalk-Hermansson, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, Karin
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Goodman, Shaun G
    Yan, Andrew T
    Bierman, Arlene S
    Do clinical factors explain persistent sex disparities in the use of acute reperfusion therapy in STEMI in Sweden and Canada?2013In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 2, no 4, p. 350-358Article in journal (Refereed)
    Abstract [en]

    AIMS:

    This study examined clinical factors associated with sex differences in the use of acute reperfusion therapy (fibrinolysis or primary percutaneous coronary intervention) in ST-elevation myocardial infarction (STEMI) patients, and the interaction between sex and these factors in Sweden and Canada.

    METHODS:

    Patients with STEMI in Sweden (n=32,676 from the Register of Information and Knowledge about Swedish Heart Intensive Care Admissions) were compared with similar patients in Canada (n=3375 from the Canadian Global Registry of Acute Coronary Events) for the period 2004-2008.

    RESULTS:

    Unadjusted vs. age-adjusted odds ratios (OR) for no reperfusion (women vs. men) were for Sweden 1.57 (95% CI 1.49-1.64) vs. 1.14 (95% CI 1.08-1.20), and for Canada 1.61 (95% CI 1.39-1.87) vs. OR 1.18 (95% CI 1.01-1.39). Sex differences persisted after multivariable adjustments (including prehospital delay, atypical symptoms, diabetes), factors for which no interaction with sex was found. Among women <60 years, adjusting for atypical symptoms in Canada and angiographic data in Sweden made the greatest contribution to explaining observed sex differences.

    CONCLUSIONS:

    In both countries, acute reperfusion therapy in STEMI was used less often in women than in men. Factors associated with these sex differences appear to differ between older and younger women. Targeted interventions are needed to optimize care for women with STEMI, as well as sex- and age-stratified reporting of quality indicators to assess their effectiveness.

  • 485.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stridsberg, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemical endocrinology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biochemical indicators of cardiac and renal function in a healthy elderly population2004In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 37, no 3, p. 210-216Article in journal (Refereed)
    Abstract [en]

    Objectives:

    To examine the distributions of NT-proBNP and cystatin C and their relation to age, gender, and other physiological factors in an apparently healthy elderly population.

    Method:

    NT-proBNP and cystatin C were analyzed in 407 and 408 healthy individuals, median age: 65 (range 40–76).

    Results:

    Increasing age, female gender and CRP were independently associated to higher NT-proBNP levels. Age, body mass index, and CRP level were independently associated to the cystatin C level. In women and men, ≤65 years, the 97.5th percentile value for NT-proBNP was 268 ng/l and 184 ng/l, in those older, 391 ng/l and 269 ng/l. For those ≤65 years the 97.5th percentile value for cystatin C was 1.12 mg/l, and for those older 1.21 mg/l.

    Conclusion:

    In a healthy elderly population, NT-proBNP is influenced by age and gender, whereas cystatin C is influenced by age but not by gender. Both markers seem to be associated to the CRP level.

  • 486.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jönelid, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schenck-Gustafsson, Karin
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effect of Gender on Patients With ST-Elevation and Non-ST-Elevation Myocardial Infarction Without Obstructive Coronary Artery Disease2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 12, p. 1661-1666Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to compare the prognoses of patients with ST-segment elevation myocardial infarction (STEMI) and those with non-ST-segment elevation myocardial infarction (NSTEMI) without obstructive coronary artery disease (CAD) and the risk associated with gender for future cardiovascular events. The study population was selected from 95,849 patients who underwent coronary angiography for myocardial infarction from 2005 to 2010 and registered in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Outcome analyses, including all-cause death, myocardial infarction, congestive heart failure, stroke, and revascularization, were performed in 2,268 patients with STEMI and 10,904 with NSTEMI without obstructive CAD (<50% stenosis). Hazard ratios and 95% confidence intervals comparing women with men were calculated for events, adjusting for cardiovascular risk factors and age. Nonobstructive CAD was found in 7% of patients with STEMI (6% men, 10% women) and in 17% of those with NSTEMI (11% men, 28% women). During a median follow-up of 2.6 years, 8% of patients with STEMI and 5% of those with NSTEMI died. Gender-associated differences in risk were observed in patients with NSTEMI, with adjusted hazard ratios lower in women than men for mortality (hazard ratio 0.90, 95% confidence interval 0.50 to 0.73) and congestive heart failure (hazard ratio 0.61, 95% confidence interval 0.52 to 0.72). In the 2 groups, women underwent less revascularization. In conclusion, nonobstructive CAD was more common in patients with NSTEMI than those with STEMI, as well as in women compared with men. Long-term mortality in patients with nonobstructive CAD was higher after STEMI than NSTEMI. The gender differences in outcomes suggest gender differences in the underlying pathogenesis of myocardial infarction without obstructive CAD.

  • 487.
    Johnston, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Schenck-Gustafsson, Karin
    Karolinska Univ Hosp, Stockholm, Sweden.
    Spontaneous coronary artery dissection: A need for raised awareness among healthcare professionals evaluating pregnant and post-partum women with chest pain2017In: Maturitas, ISSN 0378-5122, E-ISSN 1873-4111, Vol. 104, p. 123-124Article in journal (Other academic)
  • 488.
    Jolly, Sanjit S.
    et al.
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dzavik, Vladimir
    Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada..
    Cairns, John A.
    Univ British Columbia, Vancouver, BC, Canada..
    Mahmoud, Karim D.
    Erasmus MC, Ctr Thorax, Dept Cardiol, Rotterdam, Netherlands..
    Zijlstra, Felix
    Erasmus MC, Ctr Thorax, Dept Cardiol, Rotterdam, Netherlands..
    Yusuf, Salim
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Olivecrona, Göran K.
    Lund Univ, Skane Univ Hosp Lund, Lund, Sweden..
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gao, Peggy
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alazzoni, Ashraf
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Kedev, Sasko
    Sts Cyril & Methodius Univ, Univ Clin Cardiol, Skopje, Macedonia..
    Stankovic, Goran
    Univ Belgrade, Fac Med, Clin Ctr Serbia, Belgrade, Serbia.;Univ Belgrade, Fac Med, Dept Cardiol, Belgrade, Serbia..
    Meeks, Brandi
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, Orebro, Sweden..
    Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, no 2, p. 143-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Thrombus aspiration during percutaneous coronary intervention (PCI) for the treatment of ST-segment-elevation myocardial infarction (STEMI) has been widely used; however, recent trials have questioned its value and safety. In this meta-analysis, we, the trial investigators, aimed to pool the individual patient data from these trials to determine the benefits and risks of thrombus aspiration during PCI in patients with ST-segment-elevation myocardial infarction. METHODS: Included were large (n >= 1000), randomized, controlled trials comparing manual thrombectomy and PCI alone in patients with ST-segment-elevation myocardial infarction. Individual patient data were provided by the leadership of each trial. The prespecified primary efficacy outcome was cardiovascular mortality within 30 days, and the primary safety outcome was stroke or transient ischemic attack within 30 days. RESULTS: The 3 eligible randomized trials (TAPAS [Thrombus Aspiration During Percutaneous Coronary Intervention in Acute Myocardial Infarction], TASTE [Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia], and TOTAL [Trial of Routine Aspiration Thrombectomy With PCI Versus PCI Alone in Patients With STEMI]) enrolled 19 047 patients, of whom 18 306 underwent PCI and were included in the primary analysis. Cardiovascular death at 30 days occurred in 221 of 9155 patients (2.4%) randomized to thrombus aspiration and 262 of 9151 (2.9%) randomized to PCI alone (hazard ratio, 0.84; 95% confidence interval, 0.70-1.01; P=0.06). Stroke or transient ischemic attack occurred in 66 (0.8%) randomized to thrombus aspiration and 46 (0.5%) randomized to PCI alone (odds ratio, 1.43; 95% confidence interval, 0.98-2.10; P=0.06). There were no significant differences in recurrent myocardial infarction, stent thrombosis, heart failure, or target vessel revascularization. In the subgroup with high thrombus burden (TIMI [Thrombolysis in Myocardial Infarction] thrombus grade >= 3), thrombus aspiration was associated with fewer cardiovascular deaths (170 [2.5%] versus 205 [3.1%]; hazard ratio, 0.80; 95% confidence interval, 0.65-0.98; P=0.03) and with more strokes or transient ischemic attacks (55 [0.9%] versus 34 [0.5%]; odds ratio, 1.56; 95% confidence interval, 1.02-2.42, P=0.04). However, the interaction P values were 0.32 and 0.34, respectively. CONCLUSIONS: Routine thrombus aspiration during PCI for ST-segment-elevation myocardial infarction did not improve clinical outcomes. In the high thrombus burden group, the trends toward reduced cardiovascular death and increased stroke or transient ischemic attack provide a rationale for future trials of improved thrombus aspiration technologies in this high-risk subgroup.

  • 489.
    Jolly, Sanjit S.
    et al.
    McMaster Univ, Hamilton, ON, Canada.;Hamilton Hlth Sci, Populat Hlth Res Inst, Hamilton, ON, Canada. Uppsala Univ, Dept Med Sci, Uppsala, Sweden..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dzavik, Vladimir
    Univ Hlth Network, Peter Munk Cardiac Ctr, Toronto, ON, Canada..
    Cairns, John A.
    Univ British Columbia, Vancouver, BC, Canada..
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Sodra Grev Rosengatan, Orebro, Sweden..
    Response by Jolly et al to Letters Regarding Article, "Thrombus Aspiration in ST-Segment-Elevation Myocardial Infarction: An Individual Patient Meta-Analysis: Thrombectomy Trialists Collaboration"2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, no 22, p. E1103-E1104Article in journal (Refereed)
  • 490. Jones, Schuyler
    et al.
    Tricoci, Pierluigi
    Huang, Zhen
    Moliterno, David J.
    Harrington, Robert A.
    Sinnaeve, Peter
    Strony, John
    Van de Werf, Frans
    White, Harvey D.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Armstrong, Paul W.
    Aylward, Philip E.
    Chen, Edmond
    Patel, Manesh R.
    Mahaffey, Kenneth W.
    Vorapaxar in Non-ST-Segment Elevation Acute Coronary Syndrome Patients With Peripheral Artery Disease: Results From TRACER2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 491. Jones, William Schuyler
    et al.
    Tricoci, Pierluigi
    Huang, Zhen
    Moliterno, David J
    Harrington, Robert A
    Sinnaeve, Peter R
    Strony, John
    Van de Werf, Frans
    White, Harvey D
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Armstrong, Paul W
    Aylward, Philip E
    Chen, Edmond
    Patel, Manesh R
    Mahaffey, Kenneth W
    Vorapaxar in patients with peripheral artery disease and acute coronary syndrome:: Insights from Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER)2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 4, p. 588-596Article in journal (Refereed)
    Abstract [en]

    Background In the TRACER trial, vorapaxar, a protease-activated receptor-1 antagonist, plus standard care in non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients did not significantly reduce the primary composite end point but reduced a key secondary end point and significantly increased bleeding. History of peripheral artery disease (PAD) was a risk-enrichment inclusion criterion. We investigated the efficacy and safety of vorapaxar in NSTE ACS patients with documented PAD. Methods TRACER was a double-blind, randomized trial comparing vorapaxar with placebo in 12,944 patients with NSTE ACS. Results In total, 936 (7.2%) patients had a history of PAD. Ischemic events occurred more frequently among patients with PAD (25.3%) versus no PAD (12.2%, P < .001), and Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding was more common in PAD (9.1%) versus no PAD (5.0%, P = .004). Similar rates of the composite end point (cardiovascular death, myocardial infarction, or stroke) occurred in patients with PAD treated with vorapaxar and placebo (21.7% vs 24.8%, P interaction = .787). Patients with PAD treated with vorapaxar, when compared with placebo, also had a numerical reduction in peripheral revascularization procedures (8.1% vs 9.0%, P = .158) and a lower extremity amputation rate (0.9% vs 1.5%, P = .107). Vorapaxar increased Global Use of Strategies to Open Occluded Coronary Arteries moderate/severe bleeding similarly in patients with PAD (hazard ratio 1.47, 95% CI 0.89-2.45) and without (hazard ratio 1.48, 95% CI 1.22-1.79; P interaction = .921). Conclusions Patients with NSTEACS and PAD were at increased risk for ischemic events. Lower rates of ischemic end points, peripheral revascularization, and amputation with vorapaxar did not reach statistical significance but warrant further investigation. Vorapaxar increased bleeding in both patients with and without PAD at a similar magnitude of risk.

  • 492.
    Joseph, Philip
    et al.
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Pare, Guillaume
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Yusuf, Salim
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Wang, Jia
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, Michael
    Jefferson Med Coll, Wynnewood, PA USA..
    Eikelboom, John
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Reilly, Paul
    Boehringer Ingelheim Pharmaceut, Dept Clin Dev & Clin Biostat, Ridgefield, CT USA..
    Themeles, Ellison
    McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dabigatran etexilate and reduction in serum apolipoprotein B2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 1, p. 57-62Article in journal (Refereed)
    Abstract [en]

    Objective Carboxylesterases, which convert dabigatran etexilate to its active form, dabigatran, have also been shown to influence lipoprotein metabolism, although any pleotropic effects of the drug based on this possible mechanism has not been evaluated. We examined the effects of dabigatran etexilate on serum lipoprotein markers in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study. Methods 2513 participants from the RE-LY randomised control trial with baseline and 3-month apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) measurements were included. We prospectively compared the effects of dabigatran 110mg twice daily, dabigatran 150mg twice daily and warfarin on changes in ApoB and ApoA1 concentrations using a mixed model analysis. Results From baseline to 3months, a significant reduction in ApoB concentration was observed with low-dose dabigatran (-0.057 (95% CI -0.069 to -0.044) g/L, p<0.001) and high-dose dabigatran (-0.065 (95% CI -0.078 to -0.053) g/L, p<0.001) but not warfarin (-0.006g/L (95% CI -0.018 to 0.007) g/L, p=0.40). Compared with warfarin, ApoB reduction was significantly greater with both doses of dabigatran (p<0.001 for both groups). Reductions in ApoA1 concentrations did not statistically differ with either dose of dabigatran when compared with warfarin. Conclusions Dabigatran is associated with a significant (approximate to 7%) reduction in ApoB concentration, suggesting a novel effect of this drug on lipoprotein metabolism. Further studies are needed to determine the mechanism of this observed effect, and its impact on clinical outcomes.

  • 493.
    Journath, Gunilla
    et al.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Cardiol Unit, Stockholm, Sweden..
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Pettersson, Billie
    Amgen Inc, Thousand Oaks, CA 91320 USA..
    Lothgren, Mickael
    Amgen Europe GmbH, Zug, Switzerland..
    Predicted impact of lipid lowering therapy on cardiovascular and economic outcomes of Swedish atherosclerotic cardiovascular disease guideline2017In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, article id 224Article in journal (Refereed)
    Abstract [en]

    Background: The effects on cardiovascular disease (CVD) by treatment recommendations on prevention of atherosclerotic CVD remain to be evaluated. The objectives were to assess treatment gap for low density lipoprotein cholesterol (LDL-C) according to guidelines, potential impact on CVD outcomes, and possible avoided economic costs, in post myocardial infarction (MI) patients, if target LDL-C levels of <= 1.8 mmol/L would be achieved. Methods: All patients registered in the Swedish Secondary Prevention after Heart Intensive care Admission register, with one-year post-MI follow-up during 2013 were selected. The REACH risk prediction and a calibrated model for recurrent cardiovascular events and death were used to estimate unadjusted risk prediction based on the REACH equation henceforth called base case, and calibrated CVD outcomes based on gender-specific risk factors. The predicted impact of the LDL-C reduction on the risk of CVD was based on the Cholesterol Treatment Trialists' Collaboration findings. Results: A sample of n = 5904 patients (74% men) with a mean age of 64 years were included. Around 70% did not reach LDL-C target = 1.8 mmol/L. Over a 10-year period, 820-2262 events were predicted to occur in those who did not reach target corresponding to 20%-55% risk of CVD events. To achieve LDL-C target, the mean LDL-C had to be reduced by 0.73 mmol/L (29%). If this LDL-C reduction was achieved, 195-544 life years, 132-343 CVD events, and 7.9-20.9 million Swedish crowns (MSEK) of direct costs, and 19.3-51.0 MSEK of total costs would be avoided. Conclusion: Lowering of LDL cholesterol to achieve target levels according to guidelines for post-MI patients may lead to fewer cardiovascular events and avoidance of event costs.

  • 494. Justice, Anne E.
    et al.
    Giedraitis, Vilmantas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Gustafsson, Stefan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindgren, Cecilia M.
    Protein-coding variants implicate novel genes related to lipid homeostasis contributing to body-fat distribution2019In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 51, no 3, p. 452-469Article in journal (Refereed)
    Abstract [en]

    Body-fat distribution is a risk factor for adverse cardiovascular health consequences. We analyzed the association of body-fat distribution, assessed by waist-to-hip ratio adjusted for body mass index, with 228,985 predicted coding and splice site variants available on exome arrays in up to 344,369 individuals from five major ancestries (discovery) and 132,177 European-ancestry individuals (validation). We identified 15 common (minor allele frequency, MAF ≥5%) and nine low-frequency or rare (MAF <5%) coding novel variants. Pathway/gene set enrichment analyses identified lipid particle, adiponectin, abnormal white adipose tissue physiology and bone development and morphology as important contributors to fat distribution, while cross-trait associations highlight cardiometabolic traits. In functional follow-up analyses, specifically in Drosophila RNAi-knockdowns, we observed a significant increase in the total body triglyceride levels for two genes (DNAH10 and PLXND1). We implicate novel genes in fat distribution, stressing the importance of interrogating low-frequency and protein-coding variants.

  • 495.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ankle brachial index most important to identify polyvascular disease in patients with non-ST elevation or ST-elevation myocardial infarction2016In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 30, p. 55-60Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atherosclerosis is a systemic disease. In patients with acute myocardial infarction (MI) the extent of polyvascular disease (PvD) is largely unknown. In this study we investigate the prevalence and clinical characteristics predictive of PvD in patients with non-ST-elevation (NSTEMI) and ST-elevation (STEMI) MI.

    METHOD: 375 patients with acute MI included in the REBUS (Relevance of Biomarkers for Future Risk of Thromboembolic Events in Unselected Post-myocardial Infarction Patients) study were examined. Atherosclerotic changes were assessed in three arterial beds by coronary angiography, carotid ultrasound and ankle brachial index (ABI). Results compared findings of atherosclerosis in three arterial beds to fewer than 3 beds. PvD was defined as atherosclerosis in all three arterial beds.

    RESULTS: A medical history of MI, peripheral artery disease (PAD) or stroke was reported at admission in 17.9%, 2.1% and 3.7% of the patients, respectively. After evaluation, abnormal ABI was found in 20.3% and carotid artery atherosclerosis in 54.9% of the patients. In the total population, PvD was found in 13.8% of patients with no significant differences observed between NSTEMI and STEMI patients. Age (p<0.001), diabetes (p=0.039), previous PAD (p=0.009) and female gender (p=0.016) were associated with PvD. ABI was the most important predictor of PvD with a positive predictive value of 68.4% (95% CI 57.7-79.2%) and specificity of 92.4% (95% CI 89.5-95.4%).

    CONCLUSIONS: PvD is underdiagnosed in patients suffering from MI, both NSTEMI and STEMI. ABI is a useful and simple measurement that appears predictive of widespread atherosclerosis in these patients.

  • 496.
    Jönelid, Birgitta
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kragsterman, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andrén, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Low Walking Impairment Questionnaire score after a recent myocardial infarction identifies patients with polyvascular disease2019In: JRSM Cardiovascular Disease, ISSN 2048-0040, Vol. 8, p. 1-9Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate whether the Walking Impairment Questionnaire score could identify patients with polyvascular disease in a population with recent myocardial infarction and their association with cardiovascular events during two-year follow-up.

    Design: A prospective observational study.

    Setting: Patients admitted to the acute coronary care unit, the Department of Cardiology, Uppsala University Hospital.

    Participants: Patients admitted with acute Non-STEMI- or STEMI-elevation myocardial infarction.

    Main outcome measures: The Walking Impairment Questionnaire, developed as a self-administered instrument to assess walking distance, speed, and stair climbing in patients with peripheral artery disease, predicts future cardiovascular events and mortality. Two hundred and sixty-three patients with recent myocardial infarction answered Walking Impairment Questionnaire. Polyvascular disease was defined as abnormal findings in the coronary- and carotid arteries and an abnormal ankle-brachial index. The calculated score for each of all three categories were divided into quartiles with the lowest score in first quartile.

    Results: The lowest (worst) quartile in all three Walking Impairment Questionnaire categories was associated with polyvascular disease, fully adjusted; distance, odds ratio (OR) 5.4 (95% confidence interval (CI) 1.8-16.1); speed, OR 7.4 (95% CI 1.5-36.5); stair climbing, OR 8.4 (95% CI 1.0-73.6). In stair climbing score, patients with the lowest (worst) score had a higher risk for the composite cardiovascular endpoint compared to the highest (best) score; hazard ratio 5.3 (95% CI 1.5-19.0). The adherence to medical treatment was high (between 81.7% and 99.2%).

    Conclusions: The Walking Impairment Questionnaire is a simple tool to identify myocardial infarction patients with more widespread atherosclerotic disease and although well treated medically, stair climbing predicts cardiovascular events.

  • 497.
    Jönsson, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Agic, Mediha Becriovic
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Isackson, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Tveitarås, Maria K.
    Department of Biomedicine, University of Bergen, Bergen, Norway.
    Skogstrand, Trude
    Department of Biomedicine, University of Bergen, Bergen, Norway.
    Narfström, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Karlsen, Tine V.
    Department of Biomedicine, University of Bergen, Bergen, Norway.
    Lidén, Åsa
    Department of Biomedicine, University of Bergen, Bergen, Norway.
    Leh, Sabine
    Department of Pathology, Haukeland University Hospital Bergen, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
    Ericsson, Madelene
    Department of Medical Biosciences, umeå University, Umeå, Sweden.
    Nilsson, Stefan K.
    Department of Medical Biosciences, umeå University, Umeå, Sweden.
    Reed, Rolf K.
    Department of Biomedicine, University of Bergen, Bergen, and Centre for Cancer Biomarkers (CCBIO), University of Bergen, Norway.
    Hultström, Michael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Angiotensin II and salt-induced decompensation in Balb/CJ mice is aggravated by fluid retention related to low oxidative stress2019In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 5, p. F914-F933Article in journal (Refereed)
    Abstract [en]

    Balb/CJ mice are more sensitive to treatment with angiotensin II (ANG II) and high-salt diet compared with C57BL/6J mice. Together with higher mortality, they develop edema, signs of heart failure, and acute kidney injury. The aim of the present study was to identify differences in renal gene regulation that may affect kidney function and fluid balance, which could contribute to decompensation in Balb/CJ mice after ANG II + salt treatment. Male Balb/CJ and C57BL/6J mice were divided into the following five different treatment groups: control, ANG II, salt, ANG II + salt. and ANG II + salt + N-acetylcysteine. Gene expression microarrays were used to explore differential gene expression after treatment and between the strains. Published data from the Mouse Genome Database were used to identify the associated genomic differences. The glomerular filtration rate (GFR) was measured using inulin clearance, and fluid balance was measured using metabolic cages. Gene ontology enrichment analysis of gene expression microarrays identified glutathione transferase (antioxidant system) as highly enriched among differentially expressed genes. Balb/CJ mice had similar GFR compared with C57BL/6J mice but excreted less Na+ and water, although net fluid and electrolyte balance did not differ, suggesting that Balb/CJ mice may be inherently more prone to decompensation. Interestingly, C57BL/6J mice had higher urinary oxidative stress despite their relative protection from decompensation. In addition, treatment with the antioxidant N-acetylcysteine decreased oxidative stress in C57BL/6J mice, reduced urine excretion, and increased mortality. Balb/CJ mice are more sensitive than C57BL/6J to ANG II + salt, in part mediated by lower oxidative stress, which favors fluid and Na+ retention.

  • 498. Kahan, Thomas
    et al.
    Forslund, Lennart
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Björkander, Inge
    Billing, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Diabetes Nursing Research.
    Eriksson, Sven V
    Näsman, Per
    Rehnqvist, Nina
    Hjemdahl, Paul
    Risk prediction in stable angina pectoris2013In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 43, no 2, p. 141-151Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Although stable angina pectoris often carries a favourable prognosis, it remains important to identify patients with an increased risk of cardiovascular (CV) complications. Many new markers of disease activity and prognosis have been described. We evaluated whether common and easily accessible markers in everyday care provide sufficient prognostic information.

    MATERIALS AND METHODS:

    The Angina Pectoris Prognosis Study in Stockholm treated 809 patients (248 women) with stable angina pectoris with metoprolol or verapamil double blind during a median follow-up of 3·4 years, with a registry-based extended follow-up after 9·1 years. Clinical and mechanistic variables, including lipids and glucose, renal function, ambulatory and exercise-induced ischaemia, heart rate variability, cardiac and vascular ultrasonography, and psychosocial variables were included in an integrated analysis. Main outcome measures were nonfatal myocardial infarction (MI) and CV death combined.

    RESULTS:

    In all, 139 patients (18 women) suffered a main outcome. Independent predictive variables were (odds ratio [95% confidence intervals]), age (1·04 per year [1·00;1·08], P = 0·041), female sex (0·33 [0·16;0·69], P = 0·001), fasting blood glucose (1.29 per mM [1.14; 1.46], P < 0·001), serum creatinine (1·02 per μM [1·00;1·03], P < 0·001) and leucocyte counts (1·21 per 106 cells/L [1·06;1·40], P = 0·008). Smoking habits, lipids and hypertension or a previous MI provided limited additional information. Impaired fasting glucose was as predictive as manifest diabetes and interacted adversely with serum creatinine. Sexual problems were predictive among men.

    CONCLUSIONS:

    Easily accessible clinical and demographic variables provide a good risk prediction in stable angina pectoris. Impaired glucose tolerance and an elevated serum creatinine are particularly important.

  • 499.
    Kalkan, A.
    et al.
    AstraZeneca, Sodertalje, Sweden..
    Bodegard, J.
    AstraZeneca, Sodertalje, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ostgren, C.
    Linkoping Univ, S-58183 Linkoping, Sweden..
    Nilsson, P. M.
    Lund Univ, Malmo, Sweden..
    Johansson, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Ekman, M.
    AstraZeneca, Sodertalje, Sweden..
    Healthcare utilisation and costs following initiation of insulin treatment in type 2 diabetes: a long-term follow-up in clinical practice2015In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 58, no Suppl. 1, p. S482-S483Article in journal (Other academic)
  • 500. Kang, Hyun-Jae
    et al.
    Clare, Robert M.
    Gao, Runlin
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Himmelmann, Anders
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lim, Soo Teik
    Santoso, Anwar
    Yu, Cheuk-Man
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Becker, Richard C.
    Ticagrelor versus clopidogrel in Asian patients with acute coronary syndrome: A retrospective analysis from the Platelet Inhibition and Patient Outcomes (PLATO) Trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 169, no 6, p. 899-+Article in journal (Refereed)
    Abstract [en]

    Background In the PLATO trial, ticagrelor was superior to clopidogrel in reducing cardiovascular events among patients with acute coronary syndrome (ACS) at the expense of increased nonfatal bleeding. Because Asian patients, when compared with non-Asian patients, are believed to be more susceptible to bleeding, we evaluated the effects of ticagrelor compared with clopidogrel in Asian (n = 1,106) and non-Asian (n = 17,515) patients with acute coronary syndrome enrolled in the PLATO study. Methods and Results Interaction between Asian/non-Asian and primary efficacy end point (a composite of vascular death, myocardial infarction, and stroke) and net clinical benefit (composite of primary efficacy end point and coronary artery bypass graft [CABG] surgery or non-CABG-related major bleeding) were evaluated with a Cox proportional hazards model. Baseline demographics and comorbidities were different between Asians and non-Asians. The overall cardiovascular event rates were higher in Asians, but bleeding rates were similar. Despite these observed differences, the effects of ticagrelor versus clopidogrel were not significantly different between Asians and non-Asians with respect to the primary efficacy outcome (hazard ratio for Asians vs non-Asians, 0.84 [95% CI 0.61-1.17] vs 0.85 [95% CI 0.77-0.93], P = .974), net clinical benefit (0.85 [95% CI 0.65-1.11] vs 0.93 [95% CI 0.86-0.99], P = .521), or individual efficacy end points. There was no significant interaction for bleeding (PLATO major bleeding, 1.02 [95% CI 0.70-1.49] vs 1.04 [95% CI 0.95-1.14], P = .938) and other related adverse events with ticagrelor compared with clopidogrel between Asians and non-Asians. Conclusions We observed consistency of effects in Asian patients receiving ticagrelor and clopidogrel in the PLATO study. The relatively modest number of Asian patients in this analysis supports further investigation of larger cohorts to confirm our observations.

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