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  • 151. Attar, Rubina
    et al.
    Wu, Angie
    Wojdyla, Daniel
    Jensen, Svend Eggert
    Andell, Pontus
    Mahaffey, Kenneth W
    Roe, Matthew T
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Vemulapalli, Sreekanth
    Alexander, John H
    Lopes, Renato D
    Ohman, E Magnus
    Hernandez, Adrian F
    Patel, Manesh R
    Jones, W Schuyler
    Outcomes After Acute Coronary Syndrome in Patients With Diabetes Mellitus and Peripheral Artery Disease (from the TRACER, TRILOGY-ACS, APPRAISE-2, and PLATO Clinical Trials).2022In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 178, p. 11-17, article id S0002-9149(22)00579-3Article in journal (Refereed)
    Abstract [en]

    Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.

  • 152.
    Attelind, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Swedish Med Prod Agcy, Dept Drug Safety, Uppsala, Sweden..
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala Univ Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Sundstroem, Anders
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Identification of risk factors for adverse drug reactions in a pharmacovigilance database2023In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 32, no 12, p. 1431-1438Article in journal (Refereed)
    Abstract [en]

    Introduction In addition to identifying new safety signals, pharmacovigilance databases could be used to identify potential risk factors for adverse drug reactions (ADRs).Objective To evaluate whether data mining in a pharmacovigilance database can be used to identify known and possible novel risk factors for ADRs, for use in pharmacovigilance practice.Method Exploratory data mining was performed within the Swedish national database of spontaneously reported ADRs. Bleeding associated with direct oral anticoagulants (DOACs)-rivaroxaban, apixaban, edoxaban, and dabigatran-was used as a test model. We compared demographics, drug treatment, and clinical features between cases with bleeding (N = 965) and controls who had experienced other serious ADRs to DOACs (N = 511). Statistical analysis was performed by unadjusted and age adjusted logistic regression models, and the random forest based machine-learning method Boruta.Results In the logistic regression, 13 factors were significantly more common among cases of bleeding compared with controls. Eleven were labelled or previously proposed risk factors. Cardiac arrhythmia (e.g., atrial fibrillation), hypertension, mental impairment disorders (e.g., dementia), renal and urinary tract procedures, gastrointestinal ulceration and perforation, and interacting drugs remained significant after adjustment for age. In the Boruta analysis, high age, arrhythmia, hypertension, cardiac failure, thromboembolism, and pharmacodynamically interacting drugs had a larger than random association with the outcome. High age, cardiac arrhythmia, hypertension, cardiac failure, and pharmacodynamically interacting drugs had odds ratios for bleeding above one, while thromboembolism had an odds ratio below one.Conclusions We demonstrated that data mining within a pharmacovigilance database identifies known risk factors for DOAC bleeding, and potential risk factors such as dementia and atrial fibrillation. We propose that the method could be used in pharmacovigilance for identification of potential ADR risk factors that merit further evaluation.

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  • 153.
    Attelind, Sofia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hallberg, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Hamberg, Anna-Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Granger, Christopher B.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Alexander, John H.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Genetic determinants of apixaban plasma levels and their relationship to bleeding and thromboembolic events2022In: Frontiers in Genetics, E-ISSN 1664-8021, Vol. 13, article id 982955Article in journal (Refereed)
    Abstract [en]

    Apixaban is a direct oral anticoagulant, a factor Xa inhibitor, used for the prevention of ischemic stroke in patients with atrial fibrillation. Despite using recommended dosing a few patients might still experience bleeding or lack of efficacy that might be related to inappropriate drug exposure. We conducted a genome-wide association study using data from 1,325 participants in the pivotal phase three trial of apixaban with the aim to identify genetic factors affecting the pharmacokinetics of apixaban. A candidate gene analysis was also performed for pre-specified variants in ABCB1, ABCG2, CYP3A4, CYP3A5, and SULT1A1, with a subsequent analysis of all available polymorphisms within the candidate genes. Significant findings were further evaluated to assess a potential association with clinical outcome such as bleeding or thromboembolic events. No variant was consistently associated with an altered apixaban exposure on a genome-wide level. The candidate gene analyses showed a statistically significant association with a well-known variant in the drug transporter gene ABCG2 (c.421G > T, rs2231142). Patients carrying this variant had a higher exposure to apixaban [area under the curve (AUC), beta = 151 (95% CI 59-243), p = 0.001]. On average, heterozygotes displayed a 5% increase of AUC and homozygotes a 17% increase of AUC, compared with homozygotes for the wild-type allele. Bleeding or thromboembolic events were not significantly associated with ABCG2 rs2231142. This large genome-wide study demonstrates that genetic variation in the drug transporter gene ABCG2 is associated with the pharmacokinetics of apixaban. However, the influence of this finding on drug exposure was small, and further studies are needed to better understand whether it is of relevance for ischemic and bleeding events.

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  • 154.
    Aulin, Julia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Biomarkers of inflammation in atrial fibrillation2021Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Atrial fibrillation (AF) is common and associated with increased risk of stroke, heart failure (HF) and mortality. Inflammation is linked to AF.

    The overall aim of this thesis was to investigate inflammatory activity and cardiovascular outcomes and mortality in patients with AF on effective oral anticoagulation. Levels of the inflammatory biomarkers interleukin 6 (IL-6), C-reactive protein (CRP) and fibrinogen at study entry and serial changes of IL-6 over time were investigated and related to stroke or systemic embolism, mortality and other cardiovascular events, including major bleeding. Associations between IL-6, CRP and biomarkers of cardiorenal dysfunction (NT-proBNP, troponin, GDF-15 and cystatin C) and HF hospitalisation, recurrent HF hospitalisations and mortality, were also investigated in patients with AF stratified for HF symptoms and reduced or preserved ejection fraction.

    The study populations consisted of patients with AF included in the biomarker substudies of the large multicentre randomised controlled trials RE-LY (n=6,187) and ARISTOTLE (n=14,954) with a median follow-up of 2.0 and 1.9 years, respectively. Repeated IL-6 measurements were available at study entry and at any postbaseline time point at 3, 6 and 12 months in RE-LY (n=2,559), and at study entry and at 2 months in ARISTOTLE (n=4,830). For HF stratification, patients in ARISTOTLE with information on HF symptoms and left ventricular function at study entry and with IL-6, CRP, NT-proBNP, troponin T, GDF-15 and cystatin C available at randomisation (n=11,818) were included.

    Higher level of IL-6, but not of CRP, was significantly associated with higher risk of mortality in Cox models adjusted for established clinical risk factors and other cardiovascular biomarkers. The level of any of the studied inflammatory biomarkers was not independently associated with any other cardiovascular outcome, including stroke or systemic embolism or major bleeding, in presence of other strong cardiovascular biomarkers. Levels of IL-6 were stable over time and persistent inflammatory activity was associated with increased risk of mortality, independent of clinical risk factors and other prognostic biomarkers. All biomarkers (IL-6, CRP, NT-proBNP, troponin T, GDF-15 and cystatin C) were associated with higher risk of HF hospitalisation and mortality regardless of HF symptoms and reduced or preserved ejection fraction.

    In conclusion, in anticoagulated patients with AF, higher level of IL-6, but not of CRP, was associated with higher risk of mortality, independent of clinical risk factors and other cardiovascular biomarkers. IL-6 levels were stable over time and provided incremental information on the risk of mortality irrespective of when measured. IL-6 may therefore serve as a risk marker for fatal outcomes. Biomarkers improved the identification of patients with AF at risk of HF in addition to clinical and echocardiography data.

    List of papers
    1. Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation
    Open this publication in new window or tab >>Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation
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    2015 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 170, no 6, p. 1151-1160Article in journal (Refereed) Published
    Abstract [en]

    Background Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. Methods Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. Results Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism (P =.0041), major bleedings (P =.0001), vascular death (P<.0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) (P<.0001). CRP was independently related to myocardial infarction (P =.0047), vascular death (P =.0004), and the composite thromboembolic outcome (P =.0001). When further adjusted for cardiac (troponin andN-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death (P<.0001), major bleeding (P<.0170) and the composite thromboembolic outcome (P<.0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 (P =.0017) when adding IL-6 to the clinically used CHA(2)DS(2)-VASc risk score with net reclassification improvement of 28%. Conclusion In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-276878 (URN)10.1016/j.ahj.2015.09.018 (DOI)000368255700012 ()
    Funder
    AstraZenecaGlaxoSmithKline (GSK)
    Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2021-04-12Bibliographically approved
    2. Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation
    Open this publication in new window or tab >>Biomarkers of inflammation and risk of cardiovascular events in anticoagulated patients with atrial fibrillation
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    2016 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 7, p. 508-517Article in journal (Refereed) Published
    Abstract [en]

    Objective: Atrial fibrillation (AF) is a risk factor for stroke and mortality and the prothrombotic state has been linked to inflammation. In this study we evaluated the relationship between inflammatory biomarkers at baseline and future risk of cardiovascular events in the Apixaban for Reduction In Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

    Methods: The ARISTOTLE trial randomised 18 201 patients with AF to apixaban or warfarin. Interleukin 6 (IL-6) and C reactive protein (CRP) were analysed in plasma obtained at randomisation from 14 954 participants, and median follow-up was 1.9 years. Association between quartile groups of IL-6 and CRP and outcomes were analysed by Cox regression adjusted for clinical risk factors and other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).

    Results: The IL-6 median level was 2.3 ng/L (IQR 1.5-3.9), median CRP level was 2.2 mg/L (1.0-4.8). IL-6 and CRP were significantly associated with all-cause mortality independent of clinical risk factors and other biomarkers (HR (95% CI) 1.93 (1.57 to 2.37) and 1.49 (1.24 to 1.79), respectively, Q4 vs Q1). IL-6 was associated with myocardial infarction, cardiovascular mortality, and major bleeding beyond clinical risk factors but not in the presence of cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C). Neither inflammatory biomarker was associated with stroke/systemic embolism. Risk prediction for stroke, death and major bleeding was not improved by IL-6 or CRP when added to clinical risk factors and the other cardiovascular biomarkers (NT-proBNP, troponin, GDF-15, cystatin C).

    Conclusions: In patients with AF on anticoagulation, after accounting for clinical risk factors and other biomarkers, biomarkers of inflammation were significantly associated with an increased risk of mortality. However, there were no associations with the risk of stroke or major bleeding.

    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-293014 (URN)10.1136/heartjnl-2015-308887 (DOI)000373308500006 ()26839066 (PubMedID)
    Available from: 2016-05-12 Created: 2016-05-11 Last updated: 2021-04-12Bibliographically approved
    3. Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials.
    Open this publication in new window or tab >>Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials.
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    2020 (English)In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 18, no 9, p. 2287-2295Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).

    OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.

    METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression.

    RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.

    CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.

    Keywords
    anticoagulants, atrial fibrillation, inflammation, interleukin-6, mortality, stroke
    National Category
    Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-430329 (URN)10.1111/jth.14947 (DOI)000556558300001 ()32510737 (PubMedID)
    Available from: 2021-01-08 Created: 2021-01-08 Last updated: 2021-05-07Bibliographically approved
    4. Biomarkers predict risk for heart failure in patients with atrial fibrillation: Insights from the ARISTOTLE trial
    Open this publication in new window or tab >>Biomarkers predict risk for heart failure in patients with atrial fibrillation: Insights from the ARISTOTLE trial
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    (English)Manuscript (preprint) (Other academic)
    Keywords
    Atrial fibrillation, heart failure, biomarkers, left ventricular function, oral anticoagulation
    National Category
    Medical and Health Sciences Clinical Medicine Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:uu:diva-439906 (URN)
    Available from: 2021-04-12 Created: 2021-04-12 Last updated: 2021-04-12
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  • 155.
    Aulin, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gersh, B. J.
    Hanna, M.
    Horowitz, J. D.
    Hylek, E. M.
    Lopes, R. D.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Interleukin-6 and C-reactive protein and risk for cardiovascular events and death in anticoagulated patients with atrial fibrillation2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 1115-1116Article in journal (Refereed)
  • 156.
    Aulin, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hijazi, Ziad
    Lindbäck, Johan
    Alexander, John
    Gersh, Bernard
    Granger, Christopher
    Hanna, Michael
    Horowitz, John
    Hylek, Elaine
    Lopes, Renato
    McMurray, John
    Oldgren, Jonas
    Siegbahn, Agneta
    Wallentin, Lars
    Biomarkers predict risk for heart failure in patients with atrial fibrillation: Insights from the ARISTOTLE trialManuscript (preprint) (Other academic)
  • 157.
    Aulin, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H.
    Duke Clin Res Inst, Duke Hlth, Durham, NC USA..
    Gersh, Bernard J.
    Mayo Clin, Coll Med & Sci, Rochester, MN USA..
    Granger, Christopher B.
    Duke Clin Res Inst, Duke Hlth, Durham, NC USA..
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Horowitz, John
    Univ Adelaide, Basil Hetzel Inst, Adelaide, SA, Australia..
    Lopes, Renato D.
    Duke Clin Res Inst, Duke Hlth, Durham, NC USA..
    McMurray, John J. V.
    Univ Glasgow, BHF Cardiovasc Res Ctr, Glasgow, Scotland..
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). 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, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Biomarkers and heart failure events in patients with atrial fibrillation in the ARISTOTLE trial evaluated by a multi-state model2022In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 251, p. 13-24Article in journal (Refereed)
    Abstract [en]

    Background

    Atrial fibrillation (AF) and heart failure (HF) often coexist. We investigated the prognostic impact of biomarkers on the development of HF and death in patients with AF and different left ventricular systolic function considering the influence of competing events.

    Methods

    The study included 11,818 patients with AF from the ARISTOTLE trial who at entry had information on history of HF, an estimate of left ventricular function and plasma samples for determination of biomarkers representing cardiorenal dysfunction (NT-proBNP, troponin T, cystatin C) and inflammation (GDF-15, IL-6, CRP). Patients were categorized into: (I) HF with reduced ejection fraction (HFrEF, n = 2,048), (II) HF with preserved ejection fraction (HFpEF, n = 2,520), and (III) No HF (n = 7,250). Biomarker associations with HF hospitalization and death were analyzed using a multi-state model accounting also for repeated events.

    Results

    Baseline levels of NT-proBNP, troponin T, cystatin C, GDF-15, IL-6, and CRP were highest in HFrEF and lowest in No HF. During median 1.9 years follow-up, 546 patients were hospitalized at least once for HF and 819 died. Higher levels of all investigated biomarkers were associated with both outcomes (all P < .0001), with highest event rates in HFrEF and lowest in No HF. The associations remained after adjustments and were more pronounced for first than for recurrent events.

    Conclusions

    In anticoagulated patients with AF, biomarkers indicating cardiorenal dysfunction and inflammation improve the identification of patients at risk of developing HF or worsening of already existing HF. These biomarkers might be useful for targeting novel HF therapies in patients with AF.

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  • 158.
    Aulin, Julia
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). 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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Alexander, John H
    Connolly, Stuart J
    Ezekowitz, Michael D
    Gersh, Bernard J
    Granger, Christopher B
    Horowitz, John
    Hylek, Elaine M
    Lopes, Renato D
    Yusuf, Salim
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Serial measurement of interleukin-6 and risk of mortality in anticoagulated patients with atrial fibrillation: Insights from ARISTOTLE and RE-LY trials.2020In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 18, no 9, p. 2287-2295Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The inflammatory biomarker interleukin-6 (IL-6) is associated with mortality in atrial fibrillation (AF).

    OBJECTIVE: To investigate if repeated IL-6 measurements improve the prognostication for stroke or systemic embolism, major bleeding, and mortality in anticoagulated patients with AF.

    METHODS: IL-6 levels by ELISA were measured at study entry and at 2 months in 4830 patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial with 1.8 years median follow-up. In the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, IL-6 was measured at study entry, 3, 6, and 12 months in 2559 patients with 2.0 years median follow-up. Associations between a second IL-6 measurement and outcomes, adjusted for baseline IL-6, clinical variables, and other cardiovascular biomarkers, were analyzed by Cox regression.

    RESULTS: Median IL-6 levels were 2.0 ng/L (interquartile range [IQR] 1.30-3.20) and 2.10 ng/L (IQR 1.40-3.40) at the two time-points in ARISTOTLE, and, in RE-LY, 2.5 ng/L (IQR 1.6-4.3), 2.5 ng/L (IQR 1.6-4.2), 2.4 ng/L (IQR 1.6, 3.9), and 2.4 ng/L (IQR 1.5, 3.9), respectively. IL-6 was associated with mortality; hazard ratios per 50% higher IL-6 at 2 or 3 months, respectively, were 1.32 (95% confidence interval, 1.23-1.41; P < .0001) in ARISTOTLE, and 1.11 (1.01-1.22, P = .0290) in RE-LY; with improved C index from 0.74 to 0.76 in ARISTOTLE, but not in the smaller RE-LY cohort. There were no consistent associations with second IL-6 and stroke or systemic embolism, or major bleeding.

    CONCLUSIONS: Persistent systemic inflammatory activity, assessed by repeated IL-6 measurements, is associated with mortality independent of established clinical risk factors and other strong cardiovascular biomarkers in anticoagulated patients with AF.

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  • 159.
    Auricchio, Angelo
    et al.
    ivision of Cardiology, Fondazione Cardiocentro Ticino, Lugano, Switzerland.
    Gasparini, Maurizio
    Department of Cardiology, Humanitas Research Hospital IRCCS, Rozzano, Italy.
    Linde, Cecilia
    Heart and Vascular Theme, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden.
    Dobreanu, Dan
    Institute of Cardiovascular Disease and Transplant, University of Medicine and Pharmacy, Tîrgu Mureș, Romania.
    Cano, Óscar
    Electrophysiology Section, Cardiology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain.
    Sterlinski, Maciej
    Heart Rhythm Department, Institute of Cardiology, Warsaw, Poland.
    Bogale, Nigussie
    Department of Cardiology, Stavanger University Hospital, Stavanger, Norway.
    Stellbrink, Christoph
    Department of Cardiology, Klinikum Bielefeld, Bielefeld, Germany.
    Refaat, Marwan M
    Division of Cardiology, Department of Internal Medicine, Faculty of Medicine and Medical Center, American University of Beirut, Beirut, Lebanon.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Lober, Christiane
    Department of Statistics, IHF GmbH, Ludwigshafen, Germany.
    Dickstein, Kenneth
    Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; Institute of Internal Medicine, University of Bergen, Bergen, Norway.
    Normand, Camilla
    Department of Cardiology, Stavanger University Hospital, Stavanger, Norway; Institute of Internal Medicine, University of Bergen, Bergen, Norway.
    Sex-Related Procedural Aspects and Complications in CRT Survey II: A Multicenter European Experience in 11,088 Patients2019In: JACC: Clinical Electrophysiology, ISSN 2405-500X, E-ISSN 2405-5018, Vol. 5, no 9, p. 1048-1058Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study sought to compare sex difference for procedural aspects and complications in the European Society of Cardiology CRT Survey II, exploring whether adverse events were related to the type of CRT device implanted.

    BACKGROUND: Sex-related differences in procedural aspects and complications in patients undergoing cardiac resynchronization therapy (CRT) implantation has not been explored in a real-life population.

    METHODS: A post-hoc analysis of procedural data and complications in different sexes and factors associated with events was performed from data collected in the European Society of Cardiology CRT Survey II.

    RESULTS: Of all patients (n = 11,088) included, 24.3% were women. The mean age (70 years of age) of male and female recipients was similar. Female patients more frequently had an idiopathic cardiomyopathy (67.4% vs. 44.1%) and fewer comorbidities, including atrial fibrillation (34.8% vs. 42.8%), diabetes (29.1% vs. 32.1%), chronic obstructive lung disease (10.3% vs. 12.6%), and renal failure (28.7% vs. 31.9%), compared with men. More women compared with men had a pacemaker (56.6% vs. 46.3%) and much less often an implantable cardioverter-defibrillator (CRT-D) (19.0% vs. 34.7%) implant. Periprocedural event rate was the highest in women with CRT with defibrillator (7.1% vs. 4.8% in men), followed by women with a CRT with pacing (5.5% vs. 4.4% in men). The higher periprocedural event rate in CRT-D women was attributable primarily to the occurrence of pneumothorax (1.4%), coronary sinus dissection (2.1%), and pericardial tamponade (0.3%). The rate of in-hospital major adverse events (6.0%) and complications necessitating reoperation (4.0%) was not different among sex and device type.

    CONCLUSIONS: Women are more likely to experience adverse procedure-related events during CRT implantation. Thus, preventive strategies should be employed to minimize complication rate.

  • 160. Aurora, Lindsey
    et al.
    McCord, James
    Nowak, Richard
    Giannitsis, Evangelos
    Christenson, Robert
    DeFilippi, Christopher
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Christ, Michael
    Body, Richard
    Jacobsen, Gordon
    Mueller, Christian
    Prognostic Utility of a Modified HEART Score When Different Troponin Cut Points Are Used.2021In: Critical Pathways in Cardiology, ISSN 1535-282X, E-ISSN 1535-2811, Vol. 20, no 3, p. 134-139Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although the recommended cut point for cardiac troponin (cTn) is the 99th percentile, many institutions use cut points that are multiples higher than the 99th percentile for diagnosing acute myocardial infarction (AMI). Prior studies have shown that patients with a HEART score (HS) ≤ 3 and normal serial cTn values (modified HS) are at low risk for adverse events. This study aimed to evaluate the prognostic utility of the HS when various cTn cut points are used.

    METHODS: This was a substudy of High Sensitivity Cardiac Troponin T assay for RAPID Rule-out of Acute Myocardial Infarction (TRAPID-AMI), a multicenter, international trial evaluating a rapid rule-out AMI study using high-sensitivity cardiac troponin T (hs-cTnT). One-thousand two-hundred eighty-two patients were evaluated for AMI from 12 centers in Europe, United States, and Australia from 2011 to 2013. Blood samples of hs-cTnT were collected at presentation and 2 hours, and each patient had a HS calculated. The US Food and Drug Administration approved 99th percentile for hs-cTnT (19 ng/L) was used.

    RESULTS: There were 213 (17%) AMIs. Within 30 days, there were an additional 2 AMIs and 8 deaths. The adverse event rates at 30 days (death/AMI) for a HS ≤ 3 and nonelevated hs-cTnT over 2 hours using increasing hs-cTnT cut points ranged from 0.6% to 5.1%.

    CONCLUSIONS: Using the recommended 99th percentile cut point for hs-cTnT, the combination of a HS ≤ 3 with nonelevated hs-cTnT values over 2 hours identifies a low-risk cohort who can be considered for discharge from the emergency department without further testing. The prognostic utility of this strategy is greatly lessened as higher hs-cTnT cut points are used.

  • 161.
    Avdic, Daniel
    et al.
    CINC-Health Economics Research Center, Universitat Duisburg-Essen - Campus Essen, Essen, Germany.
    Hägglund, Pathric
    Swedish Institute for Social Research, Stockholm University, Stockholm, Sweden .
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johansson, Per
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Statistics.
    Sex differences in sickness absence and the morbidity-mortality paradox: a longitudinal study using Swedish administrative registers2019In: BMJ Open, E-ISSN 2044-6055, Vol. 9, no 8, article id e024098Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To analyse whether gender-specific health behaviour can be an explanation for why women outlive men, while having worse morbidity outcomes, known as the morbidity-mortality or gender paradox.

    SETTING: The working population in Sweden.

    PARTICIPANTS: Thirty per cent random sample of Swedish women and men aged 40-59 with a hospital admission in the 1993-2004 period were included. The sample for analysis consists of 233 274 individuals (115 430 men and 117 844 women) and in total 1 867 013 observations on sickness absence.

    INTERVENTION: Hospital admission across 18 disease categories.

    MAIN OUTCOME MEASURES: The main outcome measures were sickness absence (morbidity) and mortality. Longitudinal data at the individual level allow us to study how sickness absence changed after a hospital admission in men and women using a difference-in-differences regression analysis. Cox regression models are used to study differences in mortality after the admission.

    RESULTS: Women increased their sickness absence after a hospital admission by around five more days per year than men (95% CI 5.25 to 6.22). At the same time, men had higher mortality in the 18 diagnosis categories analysed. The pattern of more sickness absence in women was the same across 17 different diagnosis categories. For neoplasm, with a 57% higher risk of death for men (54.18%-59.89%), the results depended on the imputation method of sickness for those deceased. By using the premortality means of sickness absence, men had an additional 14.47 (-16.30- -12.64) days of absence, but with zero imputation women had an additional 1.6 days of absence (0.05-3.20). Analyses with or without covariates revealed a coherent picture.

    CONCLUSIONS: The pattern of increased sickness absence (morbidity) and lower mortality in women provides evidence on the more proactive and preventive behaviour of women than of men, which could thus explain the morbidity-mortality paradox.

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  • 162.
    Avezum, Alvaro
    et al.
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    de Figueiredo Oliveira, Gustavo Bernardes
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Diaz, Rafael
    Estudios Clin Latinoamer, Rosario, Santa Fe, Argentina.
    Gonzalez Hermosillo, Jesus Antonio
    Inst Nacl Cardiol Ignacio Chavez, Rosario, Santa Fe, Argentina.
    Oldgren, Jonas
    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.
    Ripoll, Ernesto Ferreiros
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
    Noack, Herbert
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
    Piegas, Leopoldo Soares
    Hosp Coracao, Sao Paulo, Brazil.
    Connolly, Stuart J.
    Hamilton Hlth Sci, Hamilton, ON, Canada;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Efficacy and safety of dabigatran versus warfarin from the RE-LY trial2018In: Open heart, E-ISSN 2053-3624, Vol. 5, no 1, article id 000800Article in journal (Refereed)
    Abstract [en]

    Background Current data for atrial fibrillation (AF) and stroke are predominantly derived from North American and European patients. Although the burden of AF is high in Latin America (LA), little is known about current management of AF in the region. Methods We aimed to assess the consistency of efficacy and safety outcomes associated with dabigatran etexilate (DE) versus warfarin in patients with AF in LA from the RE-LY (Randomised Evaluation of Long-Term Anticoagulant Therapy) trial. Data from 956 LA patients and 17 157 non-LA patients were included in this analysis.chi(2) test and Cox proportional regression analysis were performed. The primary efficacy outcome included all strokes or systemic embolism (SE). Main safety outcome was major bleeding. Results LA patients were more often female, had higher proportion of permanent AF and lower creatinine clearance, among other characteristics. Vitamin K antagonist use at randomisation and time in therapeutic range were lower in LA than in non-LA patients (44% vs 63%, p<0.001; and 61.3 +/- 22.6% vs 64.6 +/- 19.6%, p=0.015, respectively). Efficacy endpoints were 0.91% versus 1.68% for DE 150 mg twice daily versus warfarin, respectively. Stroke/SE risk was lower in LA patients treated with DE 150 mg twice daily compared with warfarin, although not significant (HR 0.54; 95% CI 0.18 to 1.62). The annual stroke/SE rates for DE 110 mg twice daily versus warfarin were 1.82 versus 1.68, also not significantly different (HR 1.09; CI 0.44 to 2.67). There were no treatment-by-region interactions for either dose of DE on efficacy and safety outcomes. Conclusion Despite differences in the clinical profile and AF management, the efficacy and safety benefits of dabigatran over warfarin in LA patients relative to non-LA patients are consistent with those observed in the main RE-LY trial.

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  • 163.
    Avis, Suzanne R.
    et al.
    Royal North Shore Hosp, Cardiovasc Discovery Grp, Kolling Inst, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Fac Med & Hlth, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Tasmania, Coll Hlth & Med, Tasmanian Sch Med, Sydney Campus,Glover St, Lilyfield, NSW 2040, Australia..
    Vernon, Stephen T.
    Royal North Shore Hosp, Cardiovasc Discovery Grp, Kolling Inst, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Fac Med & Hlth, Level 12,Bldg 6, St Leonards, NSW 2065, Australia..
    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, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    Figtree, Gemma A.
    Royal North Shore Hosp, Cardiovasc Discovery Grp, Kolling Inst, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Univ Sydney, Royal North Shore Hosp, Northern Clin Sch, Fac Med & Hlth, Level 12,Bldg 6, St Leonards, NSW 2065, Australia.;Royal North Shore Hosp, Dept Cardiol, Reserve Rd, St Leonards, NSW 2065, Australia..
    Coronary artery disease in the absence of traditional risk factors: a call for action2021In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 42, no 37, p. 3822-3824Article in journal (Other academic)
  • 164. Axelman, Elena
    et al.
    Henig, Israel
    Crispel, Yonatan
    Attias, Judith
    Li, Jin-Ping
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Brenner, Benjamin
    Vlodavsky, Israel
    Nadir, Yona
    Novel peptides that inhibit heparanase activation of the coagulation system2014In: Thrombosis and Haemostasis, ISSN 0340-6245, E-ISSN 2567-689X, Vol. 112, no 3, p. 466-477Article in journal (Refereed)
    Abstract [en]

    Heparanase is implicated in cell invasion, tumour metastasis and angiogenesis. It forms a complex and enhances the activity of the blood coagulation initiator tissue factor (IF). We describe new peptides derived from the solvent accessible surface of TF pathway inhibitor 2 (TFPI-2) that inhibit the heparanase procoagulant activity. Peptides were evaluated in vitro by measuring activated coagulation factor X levels and co-immunoprecipitation. Heparanase protein and/or lipopolysaccharide (LPS) were injected intra-peritoneally and inhibitory peptides were injected subcutaneously in mouse models. Plasma was analysed by ELISA for thrombin-antithrombin complex (TAT), D-dimer as markers of coagulation activation, and interleukin 6 as marker of sepsis severity. Peptides 5, 6, 7, 21 and 22, at the length of 11-14 amino acids, inhibited heparanase procoagulant activity but did not affect IF activity. Injection of newly identified peptides 5, 6 and 7 significantly decreased or abolished TAT plasma levels when heparanase or LPS were pre-injected, and inhibited clot formation in an inferior vena cava thrombosis model. To conclude, the solvent accessible surface of TFPI-2 first Kunitz domain is involved in TF/heparanase complex inhibition. The newly identified peptides potentially attenuate activation of the coagulation system induced by heparanase or LPS without predisposing to significant bleeding tendency.

  • 165.
    Axelsson, Erik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ljungvall, Ingrid
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Bhoumik, Priyasma
    Novartis Inst BioMed Res, Translat Med, Basel, Switzerland.;Swiss Fed Inst Technol, Sci & IT Serv, Basel Campus, Basel, Switzerland..
    Conn, Laura Bas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Murén, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ohlsson, Åsa
    Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Uppsala, Sweden..
    Olsen, Lisbeth Hoier
    Univ Copenhagen, Dept Vet & Anim Sci, Copenhagen, Denmark..
    Engdahl, Karolina
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Hagman, Ragnvi
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Hanson, Jeanette
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Kryvokhyzha, Dmytro
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pettersson, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Grenet, Olivier
    Novartis Inst BioMed Res, Translat Med, Basel, Switzerland..
    Moggs, Jonathan
    Novartis Inst BioMed Res, Translat Med, Basel, Switzerland..
    Del Rio-Espinola, Alberto
    Novartis Inst BioMed Res, Translat Med, Basel, Switzerland..
    Epe, Christian
    Elanco Anim Hlth, Greenfield, IN USA.;Boehringer Ingelheim Anim Hlth, Ingelheim, Germany..
    Taillon, Bruce
    Elanco Anim Hlth, Greenfield, IN USA..
    Tawari, Nilesh
    Elanco Anim Hlth, Greenfield, IN USA..
    Mane, Shrinivas
    Elanco Anim Hlth, Greenfield, IN USA..
    Hawkins, Troy
    Elanco Anim Hlth, Greenfield, IN USA..
    Hedhammar, Åke
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Gruet, Philippe
    Novartis Anim Hlth, St Aubin, Switzerland..
    Häggström, Jens
    Swedish Univ Agr Sci, Dept Clin Sci, Uppsala, Sweden..
    Lindblad-Toh, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Broad Inst MIT & Harvard, Cambridge, MA 02142 USA..
    The genetic consequences of dog breed formation-Accumulation of deleterious genetic variation and fixation of mutations associated with myxomatous mitral valve disease in cavalier King Charles spaniels2021In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 17, no 9, article id e1009726Article in journal (Refereed)
    Abstract [en]

    Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a similar to 10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heartderived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.

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  • 166.
    Aziz, Faisal
    et al.
    Penn State Hlth Heart & Vasc Inst, Integrated Vasc Surg Program, Hershey, PA USA..
    Behrendt, Christian-Alexander
    Univ Med Ctr Hamburg Eppendorf, Hamburg, Germany.;GermanVasc, Hamburg, Germany..
    Sullivan, Kaity
    Soc Vasc Surg, Chicago, IL USA..
    Beck, W. Adam
    Univ Alabama Birmingham, Div Vasc Surg & Endovasc Therapy, Birmingham, AL USA..
    Beiles, C. Barry
    Australian & New Zealand Soc Vasc Surg, Australasian Vasc Audit, Melbourne, Vic, Australia..
    Boyle, R. Jon
    Univ Cambridge, Cambridge, Cambs, England.;Vasc Soc Great Britain & Ireland, Lichfield, Staffs, England..
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Benson, A. Ruth
    Univ Hosp Coventry & Warwickshire, Coventry, W Midlands, England..
    Wohlauer, V. Max
    Univ Colorado, Vasc Surg, Denver, CO 80202 USA.;Vasc Surg COVID 19 Collaborat, Aurora, CO USA..
    Khashram, Manar
    Univ Auckland, Dept Surg, Auckland, New Zealand..
    Jorgensen, Jens Eldrup
    Tufts Univ, Sch Med, Boston, MA 02111 USA.;Soc Vasc Surg, Patient Safety Org, Rosemont, IL 60018 USA..
    Lemmon, W. Gary
    Soc Vasc Surg, Patient Safety Org, Rosemont, IL 60018 USA.;Indiana Univ, 1801 N Senate Blvd,D-3500, Indianapolis, IN 46202 USA..
    The impact of COVID-19 pandemic on vascular registries and clinical trials2021In: Seminars in Vascular Surgery, ISSN 0895-7967, E-ISSN 1558-4518, Vol. 34, no 2, p. 28-36Article, review/survey (Refereed)
    Abstract [en]

    Quality improvement programs and clinical trial research experienced disruption due to the coronavirus disease 2019 (COVID-19) pandemic. Vascular registries showed an immediate impact with significant declines in second-quarter vascular procedure volumes witnessed across Europe and the United States. To better understand the magnitude and impact of the pandemic, organizations and study groups sent grass roots surveys to vascular specialists for needs assessment. Several vascular registries responded quickly by insertion of COVID-19 variables into their data collection forms. More than 80% of clinical trials have been reported delayed or not started due to factors that included loss of enrollment from patient concerns or mandated institutional shutdowns, weighing the risk of trial participation on patient safety. Preliminary data of patients undergoing vascular surgery with active COVID-19 infection show inferior outcomes (morbidity) and increased mortality. Disease specific vascular surgery study collaboratives about COVID-19 were created for the desire to study the disease in a more focused manner than possible through registry outcomes. This review describes the pandemic effect on multiple VASCUNET registries including Germany (GermanVasc), Sweden (SwedVasc), United Kingdom (UK National Vascular Registry), Australia and New Zealand (bi-national Australasian Vascular Audit), as well as the United States (Society for Vascular Surgery Vascular Quality Initiative). We will highlight the continued collaboration of VASCUNET with the Vascular Quality Initiative in the International Consortium of Vascular Registries as part of the Medical Device Epidemiology Network coordinated registry network. Vascular registries must remain flexible and responsive to new and future real-world problems affecting vascular patients.

  • 167.
    Azzam, Ahmed Y.
    et al.
    Nested Knowledge, St Paul, MN 55117 USA..
    Ghozy, Sherief
    Mayo Clin, Dept Radiol, Rochester, MN USA.;Univ Oxford, Nuffield Dept Primary Care Hlth Sci, Oxford, England.;Univ Oxford, Dept Continuing Educ, EBHC Program, Oxford, England..
    Elswedy, Adam
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC.
    Azab, Mohammed A.
    Univ Utah, Clin Neurosci Ctr, Dept Neurosurg, Salt Lake City, UT 84132 USA..
    Kallmes, Kevin M.
    Nested Knowledge, St Paul, MN 55117 USA.;Super Med Experts, St Paul, MN USA..
    Dmytriw, Adam A.
    Harvard Med Sch, Massachusetts Gen Hosp, Neuroendovasc Program, Boston, MA USA..
    Kadirvel, Ramanathan
    Mayo Clin, Dept Radiol, Rochester, MN USA.;Mayo Clin, Dept Neurol Surg, Rochester, MN USA..
    Kallmes, David F.
    Mayo Clin, Dept Radiol, Rochester, MN USA..
    Carotid endarterectomy versus carotid stenting for asymptomatic carotid stenosis: Evaluating the overlapping meta-analyses of randomized controlled trials2023In: EUROPEAN JOURNAL OF RADIOLOGY OPEN, ISSN 2352-0477, Vol. 10, article id 100460Article in journal (Refereed)
    Abstract [en]

    Background: Asymptomatic carotid stenosis is associated with increased risk of ischemic stroke. The management of asymptomatic carotid stenosis ranges from open surgical approaches, minimally invasive endovascular in-terventions, and medical therapeutics. However, the research synthesis comparing these interventions, as shown by the scattered and overlapping published meta-analysis, has been inconsistent and non-comprehensive.

    Methods: Using previously-employed methods, we searched for and compared published meta-analyses comparing carotid endarterectomy and carotid stenting. A comprehensive search was conducted for all rele-vant studies published until November 13th, 2021, using the following databases: PubMed/MEDLINE, Scopus, Web of Science, Cochrane Library, OVID, and Google Scholar.

    Results: Five meta-analysis studies were included in this review. In summary, clinical findings were: carotid endarterectomy reduced the rate of ischemic stroke and stroke-related mortality, but led to a higher rate of intraoperative cranial nerve injury. There was no significant difference between carotid endarterectomy and carotid stenting in ipsilateral stroke and myocardial infarction events.

    Conclusions: The clinical findings favor the carotid endarterectomy over the carotid stenting in terms of stroke incidence (overall and minor events) and stroke-related mortality rates. However, the carotid stenting was su-perior to the carotid endarterectomy in the events of cranial nerve injury during the intervention.

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  • 168.
    Back, Anna-Karin
    et al.
    Örebro Univ, Fac Hlth Sci, Dept Radiol, Örebro, Sweden..
    Savvopoulos, Christos
    Örebro Univ, Fac Med & Hlth, Dept Radiol, Örebro, Sweden..
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Gryback, Per
    Karolinska Inst, Karolinska Univ Hosp, Dept Nucl Med, Dept Mol Med & Surg, Stockholm, Sweden..
    Geijer, Hakan
    Örebro Univ, Fac Med & Hlth, Dept Radiol, Örebro, Sweden..
    Renography with a semiautomated algorithm for diuretic decision 7 min postradiopharmaceutical administration: a feasibility study2020In: Nuclear medicine communications, ISSN 0143-3636, E-ISSN 1473-5628, Vol. 41, no 10, p. 1018-1025Article in journal (Refereed)
    Abstract [en]

    Objective The F+10 method for diuretic renography (diuretics given 10 min after the radiopharmaceutical) could be a time-conserving method. This method involves a 30-min dynamic acquisition where diuretics are administered only when necessary by the Nuclear Medicine technologist performing the examination. The purpose of this study was to assess the method's performance and to discover the optimal threshold of residual activity for a diuretic administration 7 min into the F+10 renography by reprocessing raw data from prior performed examinations with 20-min acquisitions without diuretics. Methods Retrospectively, raw data from 320 original examinations of adult patients performed from 2013 to 2015 were reprocessed into 7-min series and categorized as requiring diuretic or not. The diuretic decisions made by an expert panel were used as a reference. A receiver-operating characteristic curve was drawn to assess the optimal cutoff value for the residual renal activity. Sensitivity, specificity, positive and negative predictive values, as well as the Youden J index were calculated. Result The experts classified 50% (160 examinations) as in need of diuretics. The receiver-operating characteristic curve demonstrated the theoretical optimal cutoff value at 7 min to be 94% of maximum activity (sensitivity 0.93, specificity 0.81, Youden J index 0.73). A clinically acceptable threshold is suggested to be 85% (sensitivity 0.99, specificity 0.59, Youden J index 0.58). Conclusion Tc-99m-mercaptoacetyltriglycine renography with the F+10 method and the threshold 85% for diuretic decision 7 min into the renography is a feasible and acceptable method in clinical practice.

  • 169.
    Back, Maria
    et al.
    Sahlgrens Univ Hosp, Dept Occupat Therapy & Physiotherapy, Gothenburg, Sweden.;Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Linköping Univ, Dept Med & Hlth Sci, Div Physiotherapy, Linköping, Sweden.;Sahlgrens Univ Hosp, Dept Physiotherapy, Vita Straket 13, S-41345 Gothenburg, Sweden..
    Leosdottir, Margret
    Skane Univ Hosp, Dept Cardiol, Malmö, Sweden.;Lund Univ, Dept Clin Sci Malmö, Malmö, Sweden..
    Ekstrom, Mattias
    Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Hambraeus, Kristina
    Falun Cent Hosp, Dept Cardiol, Falun, Sweden..
    Ravn-Fischer, Annica
    Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Oberg, Birgitta
    Linköping Univ, Dept Med & Hlth Sci, Div Physiotherapy, Linköping, Sweden..
    Östlund, Ollie
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR).
    The remote exercise SWEDEHEART study-Rationale and design of a multicenter registry-based cluster randomized crossover clinical trial (RRCT)2023In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 262, p. 110-118Article in journal (Refereed)
    Abstract [en]

    Background: Despite proven benefits of exercise-based cardiac rehabilitation (EBCR), few patients with myocardial infarction (MI) participate in and complete these programs.

    Study design and objectives: The Remote Exercise SWEDEHEART study is a large multicenter registry-based cluster randomized crossover clinical trial with a planned enrollment of 1500 patients with a recent MI. Patients at intervention centers will be offered supervised EBCR, either delivered remotely, center-based or as a combination of both modes, as self -preferred choice. At control centers, patients will be offered supervised center-based EBCR, only. The duration of each time period (intervention/control) for each center will be 15 months and then cross-over occurs. The primary aim is to evaluate if remotely delivered EBCR, offered as an alternative to center-based EBCR, can increase participation in EBCR sessions. The proportion completers in each group will be presented in a supportive responder analysis. The key secondary aim is to investigate if remote EBCR is as least as effective as center-based EBCR, in terms of physical fitness and patient-reported outcome measures. Follow-up of major adverse cardiovascular events (cardiovascular-and all-cause mortality, recurrent hospitalization for acute coronary syndrome, heart failure hospitalization, stroke, and coronary revascularization) will be performed at 1 and 3 years. Safety monitoring of serious adverse events will be registered, and a cost-effectiveness analysis will be conducted to estimate the cost per quality-adjusted life-year (QALY) associated with the intervention compared with control.

    Conclusions: The cluster randomized crossover clinical trial Remote Exercise SWEDEHEART study is evaluating if par-ticipation in EBCR sessions can be increased, which may contribute to health benefits both on a group level and for individual patients including a more equal access to health care.Trial registration The study is registered at

    ClinicalTrials.gov (Identifier: NCT04260958) (Am Heart J 2023;262:110-118.)

  • 170. Badimon, Lina
    et al.
    Hernández Vera, Rodrigo
    Padró, Teresa
    Vilahur, Gemma
    Antithrombotic therapy in obesity2013In: Thrombosis and Haemostasis, ISSN 0340-6245, E-ISSN 2567-689X, Vol. 110, no 4, p. 681-688Article in journal (Refereed)
    Abstract [en]

    Clinical management of obese subjects to reduce their risk of suffering cardiovascular events is complex. Obese patients typically require preventive strategies, life-style modifications, and multi-drug therapy to address obesity-induced co-morbidities. Data regarding the effects of excess weight on the pharmacokinetics of most drugs is scarce as these individuals are often excluded from clinical trials. However, the physiological alterations observed in obese patients and their lower response to some antiplatelet agents and anticoagulants have suggested that dosage regimes need to be adjusted for these subjects. In this review we will briefly discuss platelet alterations that can contribute to increased thrombotic risk, analyse existing data regarding the effects of obesity on drug pharmacokinetics focusing on antiplatelet agents and anticoagulants, and we will describe the beneficial effects of weight loss on thrombosis.

  • 171. Badimon, Lina
    et al.
    Hernández Vera, Rodrigo
    Vilahur, Gemma
    Atherothrombotic risk in obesity2013In: Hämostaseologie, ISSN 0720-9355, Vol. 33, no 4, p. 259-268Article in journal (Refereed)
    Abstract [en]

    A link between obesity and coronary artery disease development has been repeatedly proposed, possibly in part due to the development of a proinflammatory and prothrombotic state in obese subjects. Adipocytes secrete numerous hormones and cytokines (adipokines) which influence gene expression and cell functions in endothelial cells, arterial smooth muscle cells, and monocytes/macrophages favouring the development of an atherosclerotic vulnerable plaque. Moreover, the release of such biologically active molecules also promotes endothelial function impairment, disturbs the haemostatic and fibrinolytic systems, and produces alterations in platelet function affecting the initiation, progression, and stabilization of thrombus formation upon atherosclerotic plaque rupture. In this review we will discuss the pathophysiological mechanisms by which obesity contributes to increase atherothrombosis paying special attention to its effects over thrombosis.

  • 172.
    Baensch, Dietmar
    et al.
    Univ Hosp Rostock, Dept Internal Med 1, Div Cardiol, Heart Ctr Rostock, D-18057 Rostock, Germany..
    Bonnemeier, Hendrik
    Univ Hosp Schleswig Holstein, Dept Internal Med Cardiol & Angiol 3, Kiel, Germany..
    Brandt, Johan
    Skane Univ Hosp, Arrhythmia Dept, Lund, Sweden..
    Bode, Frank
    Univ Hosp Schleswig Holstein, Med Clin Cardiol Angiol & Intens Care Med 2, Lubeck, Germany..
    Svendsen, Jesper Hastrup
    Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Ctr Heart, Copenhagen, Denmark.;Univ Copenhagen, Danish Arrhythmia Res Ctr, Copenhagen, Denmark..
    Taborsky, Milos
    Fac Hosp Olomouc, Dept Internal Med Cardiol 1, Olomouc, Czech Republic..
    Kuster, Stefan
    DRK Hosp Molln Ratzeburg, Dept Internal Med, Cardiol, Ratzeburg, Germany..
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Felk, Angelika
    Biotronik, Berlin, Germany..
    Hauser, Tino
    Biotronik, Berlin, Germany..
    Suling, Anna
    Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, Hamburg, Germany..
    Wegscheider, Karl
    Univ Med Ctr Hamburg Eppendorf, Dept Med Biometry & Epidemiol, Hamburg, Germany..
    Intra-operative defibrillation testing and clinical shock efficacy in patients with implantable cardioverter-defibrillators: the NORDIC ICD randomized clinical trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 37, p. 2500-2507Article in journal (Refereed)
    Abstract [en]

    Aims This trial was designed to test the hypothesis that shock efficacy during follow-up is not impaired in patients implanted without defibrillation (DF) testing during first implantable cardioverter-defibrillator (ICD) implantation. Methods and results Between February 2011 and July 2013, 1077 patients were randomly assigned (1 : 1) to first time ICD implantation with (n = 540) or without (n = 537) DF testing. The intra-operative DF testing was standardized across all participating centres, and all ICD shocks were programmed to 40 J irrespective of DF test results. The primary end point was the average first shock efficacy (FSE) for all true ventricular tachycardia and fibrillation (VT/VF) episodes during follow-up. The secondary end points included procedural data, serious adverse events, and mortality. During a median follow-up of 22.8 months, the model-based FSE was found to be non-inferior in patients with an ICD implanted without a DF test, with a difference in FSE of 3.0% in favour of the no DF test [confidence interval (CI) -3.0 to 9.0%, Pnon-inferiority <0.001 for the pre-defined non-inferiority margin of 210%). A total of 112 procedure-related serious adverse events occurred within 30 days in 94 patients (17.6%) tested compared with 89 events in 74 patients (13.9%) not tested (P = 0.095). Conclusion Defibrillation efficacy during follow-up is not inferior in patients with a 40 J ICD implanted without DF testing. Defibrillation testing during first time ICD implantation should no longer be recommended for routine left-sided ICD implantation.

  • 173.
    Bagge, Louise
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Surgical ablation for the treatment of atrial fibrillation in different patient populations: A study of clinical outcomes including rhythm, quality of life, atrial function and safety2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Patients with atrial fibrillation (AF) have markedly reduced quality of life (QoL) and catheter ablation has become a useful tool in the rhythm control therapy. However, because of the poor outcome for patients with persistent AF, new surgical ablation strategies for rhythm control are emerging.

    The aims of this thesis were to evaluate QoL, the main indication for rhythm control, after three different types of surgical ablation for AF, two stand-alone epicardial AF ablation procedures and one concomitant procedure during mitral valve surgery (MVS), and to perform a long-term follow-up of one of the techniques with regard to rhythm outcome, left atrial function, exercise capacity and safety.

    As the first center in the Nordic countries to adopt the video-assisted epicardial pulmonary vein isolation and ganglionated plexi ablation combined with left atrial appendage excision (LAA), the  freedom from AF at one year follow-up was found to be 71% and associated with improved exercise capacity, QoL and symptoms as well as preserved left atrial function and size. The most common complication was bleeding events (14%). After 10 years, the improved symptoms and QoL remained, reaching comparable levels of the general Swedish population, despite a marked decline in the rate of freedom from AF (36%). 4 strokes appeared during follow-up despite LAA excision in 3 of these patients.

    In order to improve the rhythm outcome for patients with longstanding persistent AF a box-lesion was added to the procedure. At one year follow-up, both symptoms and QoL improved and was indistinguishable from those in the Swedish general population.

    Finally, concomitant AF ablation during MVS did not improve QoL compared to MVS alone in a double blinded randomized controlled trial. Moreover, no difference was seen between patients in AF or sinus rhythm at one year follow-up, irrespective of the allocated therapy, indicating that their preoperative symptoms were mainly related to their valve disease.

    In conclusion, the stand-alone procedures using surgical ablation was found to be effective but at the expense of procedural complications. In contrast, the concomitant surgical AF ablation did not improve QoL, a finding that raises concerns regarding current recommendations for this procedure. 

    List of papers
    1. Epicardial off-pump pulmonary vein isolation and vagal denervation improve long-term outcome and quality of life in patients with atrial fibrillation
    Open this publication in new window or tab >>Epicardial off-pump pulmonary vein isolation and vagal denervation improve long-term outcome and quality of life in patients with atrial fibrillation
    Show others...
    2009 (English)In: Journal of Thoracic and Cardiovascular Surgery, ISSN 0022-5223, E-ISSN 1097-685X, Vol. 137, no 5, p. 1265-1271Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: The limited information available on thoracoscopic pulmonary vein isolation combined with ganglionated plexi ablation and the lack of studies regarding its effect on quality of life and physical capacity urged us to study its acute and long-term results in patients with atrial fibrillation. METHODS: Forty-three patients (mean age 57.1 years) with symptomatic atrial fibrillation referred for thoracoscopic off-pump epicardial pulmonary vein isolation and ganglionated plexi ablation using radiofrequency energy were included. RESULTS: The physical capacity improved significantly at 6-month follow-up compared with baseline (mean +/- standard deviation, 165.2 +/- 65 Watt versus 155.9 +/- 57 Watt, P = .02). Quality of life (Short Form-36 health survey) significantly improved 12 months after surgery compared with baseline in all subscales except for bodily pain. The symptom severity questionnaire score decreased significantly from mean 15.2 +/- 4.0 points to 10.7 +/- 4.8 points (P = .02). Overall, 25 of 33 patients (76%) followed up for 12 months had no symptomatic atrial fibrillation recurrences or atrial fibrillation episodes on 24-hour Holter recordings. The corresponding figures were 79% (19/24) for patients with paroxysmal atrial fibrillation, 100% (2/2) for persistent atrial fibrillation, and 57% (4/7) for permanent atrial fibrillation. The most common complication was bleeding events (9%) during pulmonary vein dissection. CONCLUSIONS: Epicardial off-pump pulmonary vein isolation combined with ganglionated plexi ablation improved quality of life, symptoms, and exercise capacity and therefore may be considered for patients with atrial fibrillation who fail endocardial pulmonary vein ablation or as a first-line procedure if left atrial appendage exclusion is warranted.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-103119 (URN)10.1016/j.jtcvs.2008.12.017 (DOI)000265299000034 ()19380002 (PubMedID)
    Available from: 2009-05-14 Created: 2009-05-14 Last updated: 2022-01-28Bibliographically approved
    2. Left atrial function after epicardial pulmonary vein isolation in patients with atrial fibrillation
    Open this publication in new window or tab >>Left atrial function after epicardial pulmonary vein isolation in patients with atrial fibrillation
    Show others...
    2017 (English)In: Journal of Interventional Cardiac Electrophysiology, ISSN 1383-875X, E-ISSN 1572-8595, Vol. 50, no 2, p. 195-201Article in journal (Refereed) Published
    Keywords
    left atrial function; epicardial; atrial fibrillation; left atrial size; minimally invasive; pulmonary vein isolation; vagal denervation; ganglionated plexi
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:uu:diva-338090 (URN)10.1007/s10840-017-0290-2 (DOI)000416448400007 ()29127542 (PubMedID)
    Funder
    Swedish Research Council, 2014-36708-117759-70Swedish Heart Lung Foundation, 20150751
    Available from: 2018-01-07 Created: 2018-01-07 Last updated: 2022-04-29Bibliographically approved
    3. Quality of life is not improved after mitral valve surgery combined with epicardial left atrial cryoablation as compared with mitral valve surgery alone: a substudy of the double blind randomized SWEDish Multicentre Atrial Fibrillation study (SWEDMAF)
    Open this publication in new window or tab >>Quality of life is not improved after mitral valve surgery combined with epicardial left atrial cryoablation as compared with mitral valve surgery alone: a substudy of the double blind randomized SWEDish Multicentre Atrial Fibrillation study (SWEDMAF)
    Show others...
    2018 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, no FI_3, p. f343-f350Article in journal (Refereed) Published
    Abstract [en]

    Aims

    Concomitant surgical ablation of atrial fibrillation (AF) in patients undergoing mitral valve surgery (MVS) has almost become routine despite lack of convincing information about improved quality-of-life (QOL) and clinical benefit. Quality-of-life was therefore assessed after MVS with or without epicardial left atrial cryoablation.

    Methods and results

    Sixty-five patients with permanent AF randomized to MVS with or without left atrial cryoablation, in the double-blinded multicentre SWEDMAF trial, replied to the Short Form 36 QOL survey at 6 and 12 months follow-up. The QOL scores at 12 month follow-up did not differ significantly between patients undergoing MVS combined with cryoablation vs. those undergoing MVS alone regarding Physical Component Summary mean 42.8 (95% confidence interval 38.3–47.3) vs. mean 44.0 (40.1–47.7), P = 0.700 or Mental Component Summary mean 53.1 (49.7–56.4) vs. mean 48.4 (44.6–52.2), P = 0.075. All patients, irrespective of allocated procedure, reached the same QOL after surgery as an age-matched Swedish general population. The Physical Component Summary in patients with sinus rhythm did also not differ from those in AF at 12 months; mean 45.4 (42.0–48.7) vs. mean 40.5 (35.5–45.6), P = 0.096) nor was there a difference in Mental Component Summary; mean 51.0 (48.0–54.1) vs. mean 49.6 (44.6–54.5), P = 0.581).

    Conclusion

    Left atrial cryoablation added to MVS does not improve health-related QOL in patients with permanent AF, a finding that raises concerns regarding recommendations made for this combined procedure.

    Keywords
    concomitant surgical ablation; mitral valve surgery; atrial fibrillation; quality of life; ablation;
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:uu:diva-338091 (URN)10.1093/europace/eux253 (DOI)000454047100014 ()29016835 (PubMedID)
    Funder
    Swedish Heart Lung Foundation, 20150751Swedish Research Council, 2014-36708-117759-70
    Available from: 2018-01-07 Created: 2018-01-07 Last updated: 2020-08-11Bibliographically approved
    4. 10 years follow-up of video-assisted epicardial pulmonary vein isolation and vagal denervation in patients with atrial fibrillation
    Open this publication in new window or tab >>10 years follow-up of video-assisted epicardial pulmonary vein isolation and vagal denervation in patients with atrial fibrillation
    (English)In: Article in journal (Other academic) Submitted
    Keywords
    Atrial fibrillation; epicardial; pulmonary vein isolation; qualiy of life; minimally invasive; vagal denervation; ganglionated plexi
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:uu:diva-338092 (URN)
    Available from: 2018-01-07 Created: 2018-01-07 Last updated: 2018-02-14
    5. A Prospective Study of the Effects of Thoracoscopic Epicardial Left Atrial Ablation on Symptoms and Quality of Life: A comparison with the normal Swedish population and other severe disease states
    Open this publication in new window or tab >>A Prospective Study of the Effects of Thoracoscopic Epicardial Left Atrial Ablation on Symptoms and Quality of Life: A comparison with the normal Swedish population and other severe disease states
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keywords
    Atrial fibrillation; quality of life; thoracoscopic; epicardial; left atrial ablation;
    National Category
    Cardiac and Cardiovascular Systems
    Research subject
    Cardiology
    Identifiers
    urn:nbn:se:uu:diva-338093 (URN)
    Available from: 2018-01-07 Created: 2018-01-07 Last updated: 2020-08-11
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  • 174.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Jidéus, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Lönnerholm, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Left atrial function after epicardial pulmonary vein isolation in patients with atrial fibrillation2017In: Journal of Interventional Cardiac Electrophysiology, ISSN 1383-875X, E-ISSN 1572-8595, Vol. 50, no 2, p. 195-201Article in journal (Refereed)
    Download full text (pdf)
    fulltext
  • 175.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Surgical ablation for atrial fibrillation in mitral valve disease: impact of the maze procedure-authors' response2018In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, no FI_3, p. f458-f459Article in journal (Refereed)
  • 176.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Jansson, Victoria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    10 years follow-up of video-assisted epicardial pulmonary vein isolation and vagal denervation in patients with atrial fibrillationIn: Article in journal (Other academic)
  • 177.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Probst, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Quality of Life Is Not Significantly Improved by Adding Epicardial Left Atrial Cryoablation to Mitral Valve Surgery Than if Performed Alone2017In: Cardiovascular Electrophysiology, ISSN 1045-3873, E-ISSN 1540-8167, Vol. 28, no 5, p. 589-590, article id MA19Article in journal (Other academic)
  • 178.
    Bagge, Louise
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Probst, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Jensen, Steen M
    Faculty of Medicine, Department of Public Health and Clinical Medicine (Heart centre) Umeå University, SE-901 87 Umeå, Sweden.
    Blomström, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Thelin, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Holmgren, Anders
    Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology, Umeå University, SE-901 87 Umeå, Sweden.
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Quality of life is not improved after mitral valve surgery combined with epicardial left atrial cryoablation as compared with mitral valve surgery alone: a substudy of the double blind randomized SWEDish Multicentre Atrial Fibrillation study (SWEDMAF)2018In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, no FI_3, p. f343-f350Article in journal (Refereed)
    Abstract [en]

    Aims

    Concomitant surgical ablation of atrial fibrillation (AF) in patients undergoing mitral valve surgery (MVS) has almost become routine despite lack of convincing information about improved quality-of-life (QOL) and clinical benefit. Quality-of-life was therefore assessed after MVS with or without epicardial left atrial cryoablation.

    Methods and results

    Sixty-five patients with permanent AF randomized to MVS with or without left atrial cryoablation, in the double-blinded multicentre SWEDMAF trial, replied to the Short Form 36 QOL survey at 6 and 12 months follow-up. The QOL scores at 12 month follow-up did not differ significantly between patients undergoing MVS combined with cryoablation vs. those undergoing MVS alone regarding Physical Component Summary mean 42.8 (95% confidence interval 38.3–47.3) vs. mean 44.0 (40.1–47.7), P = 0.700 or Mental Component Summary mean 53.1 (49.7–56.4) vs. mean 48.4 (44.6–52.2), P = 0.075. All patients, irrespective of allocated procedure, reached the same QOL after surgery as an age-matched Swedish general population. The Physical Component Summary in patients with sinus rhythm did also not differ from those in AF at 12 months; mean 45.4 (42.0–48.7) vs. mean 40.5 (35.5–45.6), P = 0.096) nor was there a difference in Mental Component Summary; mean 51.0 (48.0–54.1) vs. mean 49.6 (44.6–54.5), P = 0.581).

    Conclusion

    Left atrial cryoablation added to MVS does not improve health-related QOL in patients with permanent AF, a finding that raises concerns regarding recommendations made for this combined procedure.

  • 179. Bahit, M C
    et al.
    Lopes, R D
    Clare, R M
    Newby, L K
    Pieper, K S
    van der Werf, F
    Armstrong, P W
    Mahaffey, K W
    Harrington, R H
    Diaz, R
    Ohman, E M
    White, H D
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, C B
    Heart failure complicating non-ST-segment elevation acute coronary syndrome: timing, predictors, and clinical outcomes2013In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 1, no 3, p. 223-229Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study sought to describe the occurrence and timing of heart failure (HF), associated clinical factors, and 30-day outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). BACKGROUND: Little is known about HF-complicating NSTE-ACS. METHODS: Using pooled patient-level data from 7 clinical trials from 1994 to 2008, we describe the occurrence and timing of HF, associated clinical factors, and 30-day outcomes in NSTE-ACS patients. HF at presentation was defined as Killip classes II to III; patients with Killip class IV or cardiogenic shock were excluded. New in-hospital cases of HF included new pulmonary edema. After adjusting for baseline variables, we created logistic regression models to identify clinical factors associated with HF at presentation and to determine the association between HF and 30-day mortality. RESULTS: Of 46,519 NSTE-ACS patients, 4,910 (10.6%) had HF at presentation. Of the 41,609 with no HF at presentation, 1,194 (2.9%) developed HF during hospitalization. A total of 40,415 (86.9%) had no HF at any time. Patients presenting with or developing HF during hospitalization were older, more often female, and had a higher risk of death at 30 days than patients without HF (adjusted odds ratio [OR]: 1.74; 95% confidence interval: 1.35 to 2.26). Older age, higher presenting heart rate, diabetes, prior myocardial infarction (MI), and enrolling MI were significantly associated with HF during hospitalization. CONCLUSIONS: In this large cohort of NSTE-ACS patients, presenting with or developing HF during hospitalization was associated with an increased risk of 30-day mortality. Research targeting new strategies to prevent and manage HF in this high-risk population is needed.

  • 180.
    Bahit, M. C.
    et al.
    INECO Neurociencias, Rosario, Santa Fe, Argentina..
    Lopes, R. D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Wojdyla, D. M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    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.
    Hanna, M.
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Vinereanu, D.
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Goto, S.
    Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan..
    Alexander, J. H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    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.
    Granger, C. B.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA..
    Less non-major bleeding with apixaban versus warfarin among patients with atrial fibrillation: insights from the ARISTOTLE trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 338-339Article in journal (Other academic)
  • 181.
    Bahit, M. Cecilia
    et al.
    INECO Neurociencias Orono, Rosario, Santa Fe, Argentina.
    Granger, Christopher B.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Alexander, John H.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Mulder, Hillary
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Wojdyla, Daniel M.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA.
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan.
    Xavier, Denis
    St Johns Med Coll, Bangalore, Karnataka, India.
    Verheugt, Freek W. A.
    OLVG, Dept Cardiol, Amsterdam, Netherlands.
    Lanas, Fernando
    Univ La Frontera, Temuco, Chile.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, Renato D.
    Duke Clin Res Inst, 200 West Morris St, Durham, NC 27701 USA.
    Regional variation in clinical characteristics and outcomes in patients with atrial fibrillation: Findings from the ARISTOTLE trial2020In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 302, p. 53-58Article in journal (Refereed)
    Abstract [en]

    Background: Variation in patient characteristics and practice patterns may influence outcomes at a regional level.

    Methods: We assessed differences in demographics, practice patterns, outcomes, and the effect of apixaban compared with warfarin in ARISTOTLE (n = 18,201) by prespecified regions: North America, Latin America, Europe, and Asia Pacific. The primary outcomes were stroke/systemic embolism and major bleeding.

    Results: Compared with other regions, patients from Asia Pacific were younger, more women were enrolled in Latin America. Coronary artery disease was more prevalent in Europe and Asia Pacific had the highest rate of prior stroke and renal impairment. Over 50% of patients in North America were taking >= 9 drugs at randomization, compared with 10% in Latin America. North America had the highest rates of temporary study drug discontinuation and procedures. Time in therapeutic range (INR 2.0-3.0) on warfarin was highest in North America and lowest in Asia Pacific. After adjustment and compared with Europe, patients in Asia Pacific had 2-fold higher risk of stroke/systemic embolism and 3-fold higher risk of intracranial hemorrhage. Patients in Latin America had 2-fold increased risk of all-cause death compared with Europe. The benefits of apixaban compared with war-farin were consistent across regions; there was a pronounced reduction in major bleeding in patients from Asia Pacific compared with other regions (p-interaction = 0.03).

    Conclusions: Patients with AF enrolled in prespecified regions in ARISTOTLE had differences in clinical baseline characteristics and practice patterns. After adjustment, patients in Asia Pacific and Latin America had worse outcomes than patients from other regions. The relative benefits of apixaban compared with warfarin were consistent across regions with an even greater treatment effect in the reduction of bleeding in patients from Asia Pacific. 

  • 182.
    Bahit, M. Cecilia
    et al.
    INECO, Neurociencias Orono Rosario, Santa Fe, NM, Argentina..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wojdyla, Daniel M.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Verheugt, Freek
    Onze Lieve Vrouwe Gasthuis OLVG, Heartctr, Amsterdam, Netherlands..
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa, Japan..
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Non-major bleeding with apixaban versus warfarin in patients with atrial fibrillation2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 8, p. 623-628Article in journal (Refereed)
    Abstract [en]

    Objective We describe the incidence, location and management of non-major bleeding, and assess the association between non-major bleeding and clinical outcomes in patients with atrial fibrillation (AF) receiving anticoagulation therapy enrolled in Apixaban for Reduction in Stroke and other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE). Methods We included patients who received >= 1 dose of study drug (n= 18 140). Non-major bleeding was defined as the first bleeding event considered to be clinically relevant non-major (CRNM) or minor bleeding, and not preceded by a major bleeding event. Results Non-major bleeding was three times more common than major bleeding (12.1% vs 3.8%). Like major bleeding, non-major bleeding was less frequent with apixaban (6.4 per 100 patient-years) than warfarin (9.4 per 100 patient-years) (adjusted HR 0.69, 95% CI 0.63 to 0.75). The most frequent sites of non-major bleeding were haematuria (16.4%), epistaxis (14.8%), gastrointestinal (13.3%), haematoma (11.5%) and bruising/ecchymosis (10.1%). Medical or surgical intervention was similar among patients with non-major bleeding on warfarin versus apixaban (24.7% vs 24.5%). A change in antithrombotic therapy (58.6% vs 50.0%) and permanent study drug discontinuation (5.1% (61) vs 3.6% (30), p=0.10) was numerically higher with warfarin than apixaban. CRNM bleeding was independently associated with an increased risk of overall death (adjusted HR 1.70, 95% CI 1.32 to 2.18) and subsequent major bleeding (adjusted HR 2.18, 95% CI 1.56 to 3.04). Conclusions In ARISTOTLE, non-major bleeding was common and substantially less frequent with apixaban than with warfarin. CRNM bleeding was independently associated with a higher risk of death and subsequent major bleeding. Our results highlight the importance of any severity of bleeding in patients with AF treated with anticoagulation therapy and suggest that non-major bleeding, including minor bleeding, might not be minor.

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  • 183.
    Bahls, Martin
    et al.
    Univ Med Greifswald, Dept Internal Med B, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany..
    Lorenz, Matthias W.
    Goethe Univ, Dept Neurol, Frankfurt, Germany..
    Doerr, Marcus
    Univ Med Greifswald, Dept Internal Med B, Ferdinand Sauerbruch Str, D-17475 Greifswald, Germany.;German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany..
    Gao, Lu
    Univ Cambridge, Inst Publ Hlth, MRC Biostat Unit, Univ Forvie Site, Cambridge, England..
    Kitagawa, Kazuo
    Tokyo Womens Med Univ, Dept Neurol, Tokyo, Japan..
    Tuomainen, Tomi-Pekka
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Agewall, Stefan
    Univ Oslo, Inst Clin Sci, Oslo, Norway.;Oslo Univ Hosp Ulleval, Dept Cardiol, Oslo, Norway..
    Berenson, Gerald
    Tulane Univ, Sch Med, Dept Med Pediat Biochem Epidemiol, 1430 Tulane Ave, New Orleans, LA 70112 USA.;Tulane Univ, Sch Publ Hlth & Trop Med, Dept Med Pediat Biochem Epidemiol, New Orleans, LA USA..
    Catapano, Alberico L.
    IRCSS Multimed, Milan, Italy.;Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy..
    Norata, Giuseppe D.
    Univ Milan, Dept Pharmacol & Biomol Sci, Milan, Italy.;Bassini Hosp, SISA Ctr Study Atherosclerosis, Cinisello Balsamo, Italy..
    Bots, Michiel L.
    Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands..
    van Gilst, Wiek
    Univ Med Ctr Groningen, Dept Expt Cardiol, Groningen, Netherlands..
    Asselbergs, Folkert W.
    Univ Med Ctr Utrecht, Dept Cardiol, Utrecht, Netherlands.;UCL, Inst Cardiovasc Sci, London, England.;UCL, Hlth Data Res UK, London, England.;UCL, Inst Hlth Informat, London, England..
    Brouwers, Frank P.
    Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands..
    Uthoff, Heiko
    Univ Hosp Basel, Dept Angiol, Basel, Switzerland..
    Sander, Dirk
    Benedictus Hosp Tutzing, Dept Neurol, Tutzing, Germany..
    Poppert, Holger
    Tech Univ Munich, Dept Neurol, Munich, Germany..
    Olsen, Michael Hecht
    Univ Southern Denmark, Holbaek Hosp, Dept Internal Med, Odense, Denmark.;Univ Southern Denmark, Inst Reg Hlth Res, Odense, Denmark..
    Empana, Jean Philippe
    Univ Paris, INSERM U970, Paris Cardiovasc Res Ctr, Paris, France..
    Schminke, Ulf
    Univ Med Greifswald, Dept Neurol, Greifswald, Germany..
    Baldassarre, Damiano
    IRCCS, Ctr Cardiol Monzino, Milan, Italy.;Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy..
    Veglia, Fabrizio
    IRCCS, Ctr Cardiol Monzino, Milan, Italy..
    Franco, Oscar H.
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Univ Bern, ISPM, Bern, Switzerland..
    Kavousi, Maryam
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands..
    de Groot, Eric
    Imagelabonline & Cardiovasc, Erichem, Netherlands..
    Mathiesen, Ellisiv B.
    UiT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.;Univ Hosp North Norway, Dept Neurol, Tromso, Norway..
    Grigore, Liliana
    Bassini Hosp, Ctr Sisa Studio Aterosclerosi, Cinisello Balsamo, Italy..
    Polak, Joseph F.
    Tufts Univ, Sch Med, Tufts Med Ctr, Boston, MA 02111 USA..
    Rundek, Tatjana
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Stehouwer, Coen D. A.
    Maastricht Univ, Med Ctr, Dept Internal Med, Maastricht, Netherlands.;Maastricht Univ, Med Ctr, Cardiovasc Res Inst Maastricht CARIM, Maastricht, Netherlands..
    Skilton, Michael R.
    Univ Sydney, Boden Collaborat Obes Nutr Exercise & Eating Diso, Sydney, NSW, Australia..
    Hatzitolios, Apostolos, I
    Aristotle Univ Thessaloniki, Propedeut Dept Internal Med, AHEPA Hosp, Thessaloniki, Greece..
    Savopoulos, Christos
    Aristotle Univ Thessaloniki, Propedeut Dept Internal Med, AHEPA Hosp, Thessaloniki, Greece..
    Ntaios, George
    Univ Thessaly, Fac Med, Sch Hlth Sci, Dept Internal Med, Larisa, Greece..
    Plichart, Matthieu
    Bassini Hosp, Ctr Sisa Studio Aterosclerosi, Cinisello Balsamo, Italy.;Hop Broca, AP HP, Paris, France..
    McLachlan, Stela
    Univ Edinburgh, Usher Inst, Edinburgh, Midlothian, Scotland..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Willeit, Peter
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria.;Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Steinmetz, Helmuth
    Goethe Univ, Dept Neurol, Frankfurt, Germany..
    Desvarieux, Moise
    Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.;INSERM, UMR 1153, Ctr Rech Epidemiol & Stat Paris Sorbonne Cite CRE, METHODS Core, Paris, France..
    Ikram, M. Arfan
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Erasmus MC, Dept Neurol, Rotterdam, Netherlands.;Erasmus MC, Dept Radiol, Rotterdam, Netherlands..
    Johnsen, Stein Harald
    UiT Arctic Univ Norway, Dept Clin Med, Tromso, Norway.;Univ Hosp North Norway, Dept Neurol, Tromso, Norway..
    Schmidt, Caroline
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden..
    Willeit, Johann
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Ducimetiere, Pierre
    Univ Paris Sud Xi, Le Kremlin Bicetre, France..
    Price, Jackie F.
    Univ Edinburgh, Usher Inst, Edinburgh, Midlothian, Scotland..
    Bergstrom, Goran
    Sahlgrens Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Clin Physiol, Reg Vastra Gotaland, Gothenburg, Sweden..
    Kauhanen, Jussi
    Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland..
    Kiechl, Stefan
    Med Univ Innsbruck, Dept Neurol, Innsbruck, Austria..
    Sitzer, Matthias
    Goethe Univ, Dept Neurol, Frankfurt, Germany.;Klinikum Herford, Dept Neurol, Herford, Germany..
    Bickel, Horst
    Tech Univ Munich, Dept Psychiat & Psychotherapy, Munich, Germany..
    Sacco, Ralph L.
    Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA..
    Hofman, Albert
    Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA..
    Voelzke, Henry
    German Ctr Cardiovasc Res DZHK, Partner Site Greifswald, Greifswald, Germany.;Univ Med Greifswald, Inst Community Med, SHIP Clin Epidemiol Res, Greifswald, Germany..
    Thompson, Simon G.
    Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge, England..
    Progression of conventional cardiovascular risk factors and vascular disease risk in individuals: insights from the PROG-IMT consortium2020In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 27, no 3, p. 234-243Article in journal (Refereed)
    Abstract [en]

    Aims Averaged measurements, but not the progression based on multiple assessments of carotid intima-media thickness, (cIMT) are predictive of cardiovascular disease (CVD) events in individuals. Whether this is true for conventional risk factors is unclear. Methods and results An individual participant meta-analysis was used to associate the annualised progression of systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol with future cardiovascular disease risk in 13 prospective cohort studies of the PROG-IMT collaboration (n = 34,072). Follow-up data included information on a combined cardiovascular disease endpoint of myocardial infarction, stroke, or vascular death. In secondary analyses, annualised progression was replaced with average. Log hazard ratios per standard deviation difference were pooled across studies by a random effects meta-analysis. In primary analysis, the annualised progression of total cholesterol was marginally related to a higher cardiovascular disease risk (hazard ratio (HR) 1.04, 95% confidence interval (CI) 1.00 to 1.07). The annualised progression of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol was not associated with future cardiovascular disease risk. In secondary analysis, average systolic blood pressure (HR 1.20 95% CI 1.11 to 1.29) and low-density lipoprotein cholesterol (HR 1.09, 95% CI 1.02 to 1.16) were related to a greater, while high-density lipoprotein cholesterol (HR 0.92, 95% CI 0.88 to 0.97) was related to a lower risk of future cardiovascular disease events. Conclusion Averaged measurements of systolic blood pressure, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol displayed significant linear relationships with the risk of future cardiovascular disease events. However, there was no clear association between the annualised progression of these conventional risk factors in individuals with the risk of future clinical endpoints.

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  • 184.
    Bainey, Kevin R.
    et al.
    Univ Alberta, Mazankowski Alberta Heart Inst, Edmonton, AB, Canada..
    Engstrm, Thomas
    Univ Copenhagen, Rigshosp, Heart Ctr, Copenhagen, Denmark..
    Smits, Pieter C.
    Maasstad Ziekenhuis, Dept Cardiol, Rotterdam, Netherlands..
    Gershlick, Anthony H.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England.;Univ Hosp Leicester NHS Natl Hlth Serv Trust, Glenfield Hosp, NIHR Natl Inst Heath Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England..
    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.
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England..
    Wood, David A.
    Univ British Columbia, Ctr Cardiovasc Innovat, Vancouver, BC, Canada..
    Mehran, Roxana
    Mt Sinai Sch Med, Zena & Michael A Weiner Cardiovasc Inst, New York, NY USA..
    Cairns, John A.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Mehta, Shamir R.
    McMaster Univ, Populat Hlth Res Inst, Hamilton Hlth Sci, 237 Barton St E, Hamilton, ON L8L 2X2, Canada..
    Complete vs Culprit-Lesion-Only Revascularization for ST-Segment Elevation Myocardial Infarction A Systematic Review and Meta-analysis2020In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 5, no 8, p. 881-888Article, review/survey (Refereed)
    Abstract [en]

    IMPORTANCE Recently, the Complete vs Culprit-Only Revascularization to Treat Multi vessel Disease After Early PCI (percutaneous coronary intervention) for STEMI (ST-segment elevation myocardial infarction [MI]) (COMPLETE) trial showed that angiography-guided PCI of the nonculprit lesion with the goal of complete revascularization reduced cardiovascular (CV) death or new MI compared with PCI of the culprit lesion only in STEMI. Whether complete revascularization also reduces CV mortality is uncertain. Moreover, whether the association of complete revascularization with hard clinical outcomes is consistent when fractional flow reserve (FFR)- and angiography-guided strategies are used is unknown. OBJECTIVE To determine through a systematic review and meta-analysis (1) whether complete revascularization is associated with decreased CV mortality and (2) whether heterogeneity in the association occurs when FFR- and angiography-guided PCI strategies for nonculprit lesions are performed. DATA SOURCES A systematic search of MEDLINE, Embase, ISI Web of Science, and CENTRAL (Cochrane Central Register of Controlled Trials) from database inception to September 30, 2019, was performed. Conference proceedings were also reviewed from January 1, 2002, to September 30, 2019. STUDY SELECTION English-language randomized clinical trials comparing complete revascularization vs culprit-lesion-only PCI in patients with STEMI and multivessel disease were included. DATA EXTRACTION AND SYNTHESIS The combined odds ratio (OR) was calculated with the random-effects model using the Mantel-Haenszel method (sensitivity with fixed-effects model). Heterogeneity was measured using the I-2 statistic. Publication bias was evaluated using the inverted funnel plot approach. Data were analyzed from October 2019 to January 2020. MAIN OUTCOMES AND MEASURES Cardiovascular death and the composite of CV death or new MI. RESULTS Ten randomized clinical trials involving 7030 unique patients were included. The weighted mean follow-up time was 29.5 months. Complete revascularization was associated with reduced CV death compared with culprit-lesion-only PCI (80 of 3191 [2.5%] vs 106 of 3406 [3]%1 OR, 0.69 [95% CI, 0.48-0.99]; P =.05; fixed-effects model OR, 0.74 [95% CI, 0.55-0.99]; P =.04). All-cause mortality occurred in 153 of 3426 patients (4.5%) in the complete revascularization group vs 177 of 3604 (4.9%) in the culprit-lesion-only group (OR, 0.84 [95% [I, 0.67-1.05]; P =.13; I-2 = 0%). Complete revascularization was associated with a reduced composite of CV death or new MI (192 of 2616 [7.3%] vs 266 of 2586 [10.3%]; OR, 0.69 [95% [I, 0.55-0.87]; P =.001; fixed-effects model OR, 0.69 [95% [I, 0.57-0.84]; P <.001), with no heterogeneity in this outcome when complete revascularization was performed using an FFR-guided strategy (OR, 0.78 [95% CI, 0.43-1.44]) or an angiography-guided strategy (OR, 0.61 [95% CI, 0.38-0.97]; P =.52 for interaction). CONCLUSIONS AND RELEVANCE In patients with STEMI and multivessel disease, complete revascularization was associated with a reduction in CV mortality compared with culprit-lesion-only PCI. There was no differential association with treatment between FFR- and angiography-guided strategies on major CV outcomes.

  • 185. Bakhai, A
    et al.
    Ferrieres, J
    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.
    Iniguez, A
    Mohacsi, A
    Pavlides, G
    Belger, M
    Norrbacka, K
    Sartral, M
    Treatment, outcomes, costs, and quality of life of women and men with acute coronary syndromes who have undergone percutaneous coronary intervention: results from the antiplatelet therapy observational registry2013In: Postgraduate medicine, ISSN 0032-5481, E-ISSN 1941-9260, Vol. 125, no 2, p. 100-107Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Treatment, outcomes, costs, and quality of life after percutaneous coronary intervention (PCI) were compared between women and men with acute coronary syndromes (ACS) using data from the Antiplatelet Therapy Observational Registry (APTOR). METHODS: Fourteen European countries participated in this noninterventional, prospective, observational cohort registry, which enrolled patients with ACS who underwent PCI from 2007 to 2009. The 12-month outcomes included bleeding, cardiovascular events, and mortality. Quality of life was measured using the EQ-5D (EuroQol Group) health index and the visual analog scale. RESULTS: The APTOR registry included 4546 patients, of whom 1047 (23%) were women and 3499 (77%) were men. The women were older (mean age, 67 vs 61 years) and had higher rates of diabetes mellitus and hypertension. A greater proportion of the men were smokers (40% vs 30%). Approximately 70% of the patients underwent PCI on the day of the qualifying ACS event. Women and men received similar medications at the time of PCI, hospital discharge, and 12-month follow-up visit. Bleeding, cardiovascular events, and mortality occurred at higher rates in women than in men, but the differences were not statistically significant. At 12 months post-PCI, women reported lower quality-of-life scores on the EQ-5D health index and the visual analog scale than did men. The mean total cost of care was pound6252 (euro7189) for women and pound5841 (euro6717) for men; the differences may be driven by resource use after discharge from the hospital. CONCLUSION: Women with ACS tended to be older and had more comorbidities than men, but both sexes experienced similar outcomes after 1 year. This study indicated no differences in treatment between sexes.

  • 186. Bakhai, Ameet
    et al.
    Palaka, Eirini
    Linde, Cecilia
    Bennett, Hayley
    Furuland, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine.
    Qin, Lei
    McEwan, Phil
    Ewans, Marc
    Development of a health economic model to evaluate the potential benefits of optimal serum potassium management in patients with heart failure.2018In: Journal of Medical Economics, ISSN 1369-6998, E-ISSN 1941-837X, Vol. 21, no 12, p. 1172-1182Article in journal (Refereed)
    Abstract [en]

    Aims: Patients with heart failure are at increased risk of hyperkalemia, particularly when treated with renin-angiotensin-aldosterone system inhibitor (RAASi) agents. This study developed a model to quantify the potential health and economic value associated with sustained potassium management and optimal RAASi therapy in heart failure patients.

    Materials and methods: A patient-level, fixed-time increment stochastic simulation model was designed to characterize the progression of heart failure through New York Heart Association functional classes, and predict associations between serum potassium levels, RAASi use, and consequent long-term outcomes. Following internal and external validation exercises, model analyses sought to quantify the health and economic benefits of optimizing both serum potassium levels and RAASi therapy in heart failure patients. Analyses were conducted using a UK payer perspective, independent of costs and utilities related to pharmacological potassium management.

    Results: Validation against multiple datasets demonstrated the predictive capability of the model. Compared to those who discontinued RAASi to manage serum potassium, patients with normokalemia and ongoing RAASi therapy benefited from longer life expectancy (+1.38 years), per-patient quality-adjusted life year gains (+0.53 QALYs), cost savings (110) pound, and associated net monetary benefit (10,679 pound at 20,000 pound per QALY gained) over a lifetime horizon. The predicted value of sustained potassium management and ongoing RAASi treatment was largely driven by reduced mortality and hospitalization risks associated with optimal RAASi therapy.

    Limitations: Several modeling assumptions were made to account for a current paucity of published literature; however, ongoing refinement and validation of the model will ensure its continued accuracy as the clinical landscape of hyperkalemia evolves.

    Conclusions: Predictions generated by this novel modeling approach highlight the value of sustained potassium management to avoid hyperkalemia, enable RAASi therapy, and improve long-term health economic outcomes in patients with heart failure.

  • 187. Balabanski, Tosho
    et al.
    Brugada, Josep
    Arbelo, Elena
    Laroche, Cécile
    Maggioni, Aldo
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kautzner, Josef
    Tavazzi, Luigi
    Tritto, Massimo
    Kulakowski, Piotr
    Kalejs, Oskars
    Forster, Tamas
    Villalobos, Federico Segura
    Dagres, Nikolaos
    Impact of monitoring on detection of arrhythmia recurrences in the ESC-EHRA EORP atrial fibrillation ablation long-term registry2019In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 21, no 12, p. 1802-1808Article in journal (Refereed)
    Abstract [en]

    AIMS: Monitoring of patients after ablation had wide variations in the ESC-EHRA atrial fibrillation ablation long-term (AFA-LT) registry. We aimed to compare four different monitoring strategies after catheter AF ablation.

    METHODS AND RESULTS: The ESC-EHRA AFA-LT registry included 3593 patients who underwent ablation. Arrhythmia monitoring during follow-up was performed by 12-lead electrocardiogram (ECG), Holter ECG, trans-telephonic ECG monitoring (TTMON), or an implanted cardiac monitoring (ICM) system. Patients were selected to a given monitoring group according to the most extensive ECG tool used in each of them. Comparison of the probability of freedom from recurrences was performed by censored log-rank test and presented by Kaplan-Meier curves. The rhythm monitoring methods were used among 2658 patients: ECG (N = 578), Holter ECG (N = 1874), TTMON (N = 101), and ICM (N = 105). A total of 767 of 2658 patients (28.9%) had AF recurrences during follow-up. Censored log-rank test discovered a lower probability of freedom from relapses, which was detected with ICM compared to TTMON, ECG, and Holter ECG (P < 0.001). The rate of freedom from AF recurrences was 50.5% among patients using the ICM while it was 65.4%, 70.6%, and 72.8% using the TTMON, ECG, and Holter ECG, respectively.

    CONCLUSION: Comparing all main electrocardiographic monitoring methods in a large patient sample, our results suggest that post-ablation recurrences of AF are significantly underreported by TTMON, ECG, and Holter ECG. The ICM estimates AF ablation recurrences most reliably and should be a preferred mode of monitoring for trials evaluating novel AF ablation techniques.

  • 188.
    Balaz, P.
    et al.
    Inst Clin & Expt Med, Vasc & Transplant Surg Dept, Prague, Czech Republic.;Charles Univ Prague, Fac Med 3, Fac Hosp Kralovske Vinohrady, Vasc Surg Unit,Dept Surg, Prague, Czech Republic..
    Wohlfahrt, P.
    St Annes Univ Hosp, Int Clin Res Ctr, Brno, Czech Republic.;Inst Clin & Expt Med, Dept Prevent Cardiol, Prague, Czech Republic.;Charles Univ Prague, Fac Med 1, Ctr Cardiovasc Prevent, Prague, Czech Republic.;Thomayer Hosp, Prague, Czech Republic..
    Rokosny, S.
    Inst Clin & Expt Med, Vasc & Transplant Surg Dept, Prague, Czech Republic..
    Maly, S.
    Inst Clin & Expt Med, Vasc & Transplant Surg Dept, Prague, Czech Republic..
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Is It Worthwhile Treating Occluded Cold Stored Venous Allografts by Thrombolysis?2016In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 52, no 3, p. 370-376Article in journal (Refereed)
    Abstract [en]

    Objectives: Thrombolysis has been reported to be suboptimal in occluded vein grafts and cryopreserved allografts, and there are no data on the efficacy of thrombolysis in occluded cold stored venous allografts. The aim was to evaluate early outcomes, secondary patency and limb salvage rates of thrombolysed cold stored venous allograft bypasses and to compare the outcomes with thrombolysis of autologous bypasses. Methods: This was a single center study of consecutive patients with acute and non-acute limb ischemia between September 1, 2000, and January 1, 2014, with occlusion of cold stored venous allografts, and between January 1, 2012, and January 1, 2014, with occlusion of autologous bypass who received intra-arterial thrombolytic therapy. Results: Sixty-one patients with occlusion of an infrainguinal bypass using a cold stored venous allograft (n = 35) or an autologous bypass (n = 26) underwent percutaneous intra-arterial thrombolytic therapy. The median duration of thrombolysis was 20 h (IQR 18-24) with no difference between the groups (p = .14). The median follow up was 18.5 months (IQR 11.0-52.0). Secondary patency rates of thrombolysed bypass at 6 and 12 months were 44 +/- 9% and 32 +/- 9% in patients with a venous allograft bypass and 46 +/- 10% and 22 +/- 8% with an autologous bypass, with no difference between groups (p = .40). Limb salvage rates at 1, 6, and 12 months after thrombolysis in the venous allograft group were 83 +/- 7%, 72 8% and 63 +/- 9%, and in the autologous group 91 +/- 6%, 76 +/- 9%, and 65 +/- 13%, with no difference between groups (p = .69). Conclusions: Long-term results of thrombolysis of venous allograft bypasses are similar to those of autologous bypasses. Occluded cold stored venous allograft can be successfully re-opened in most cases with a favorable effect on limb salvage.

  • 189. Balaz, Peter
    et al.
    Björck, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    True aneurysm in autologous hemodialysis fistulae: definitions, classification and indications for treatment2015In: Journal of Vascular Access, ISSN 1129-7298, E-ISSN 1724-6032, Vol. 16, no 6, p. 446-453Article, review/survey (Refereed)
    Abstract [en]

    INTRODUCTION: Definition, etiology, classification and indication for treatment of the arteriovenous access (AVA) aneurysm are poorly described in medical literature. The objectives of the paper are to complete this information gap according to the extensive review of the literature.

    METHODS: A literature search was performed of the articles published between April 1, 1967, and March 1, 2014. The databases searched included Medline and the Cochrane Database of Systematic Reviews. The eligibility criteria in this review studies the need to assess the association of aneurysms and pseudoaneurysms with autologous AVA. Aneurysms and pseudoaneurysms involving prosthetic AVA were not included in this literature review. From a total of 327 papers, 54 non-English papers, 40 case reports and 167 papers which did not meet the eligibility criteria were removed. The remaining 66 papers were reviewed.

    RESULTS: Based on the literature the indication for the treatment of an AVA aneurysm is its clinical presentation related to the patient's discomfort, bleeding prevention and inadequate access flow. A new classification system of AVA aneurysm, which divides it into the four types, was also suggested.

    CONCLUSIONS: AVA aneurysm is characterized by an enlargement of all three vessel layers with a diameter of more than 18 mm and can be presented in four types according to the presence of stenosis and/or thrombosis. The management of an AVA aneurysm depends on several factors including skin condition, clinical symptoms, ease of cannulation and access flow. The diameter of the AVA aneurysm as a solo parameter is not an indication for the treatment.

  • 190.
    Balboa Ramilo, Amanda
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Becirovic Agic, Mediha
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Petri, Marcelo Heron
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wanhainen, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery. Umeå Univ, Dept Surg & Perioperat Sci, Surg, Umeå, Sweden..
    Wågsäter, Dick
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The tyrosine kinase inhibitor Bosutinib does not inhibit angiotensin II-induced abdominal aortic aneurysm: Validation of the importance of PDGFR and c-Kit tyrosine kinases by Imatinib2022In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 340, p. 68-69Article in journal (Refereed)
  • 191.
    Baldanzi, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Hammar, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Lindberg, Eva
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Elmståhl, Sölve
    Department of Clinical Sciences in Malmö, Division of Geriatric Medicine, Lund University, Sweden; CRC, Skåne University Hospital, Malmö, Sweden.
    Theorell-Haglöw, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Lung- allergy- and sleep research. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Evening chronotype is associated with elevated biomarkers of cardiometabolic risk in the EpiHealth cohort: a cross-sectional study2022In: Sleep, ISSN 0161-8105, E-ISSN 1550-9109, Vol. 45, no 2, article id zsab226Article in journal (Refereed)
    Abstract [en]

    Study objectives: Individuals with evening chronotype have a higher risk of cardiovascular and metabolic disorders, although the underlying mechanisms are not well understood. In a population- based cohort, we aimed to investigate the association between chronotype and 242 circulating proteins from three panels of established or candidate biomarkers of cardiometabolic processes. 

    Methods: In 2,471 participants (49.7% men, mean age 61.2±8.4 SD years) from the EpiHealth cohort, circulating proteins were analyzed with a multiplex proximity extension technique. Participants self- reported their chronotype on a five-level scale from extreme morning to extreme evening chronotype. With the intermediate chronotype set as the reference, each protein was added as the dependent variable in a series of linear regression models adjusted for confounders. Next, the chronotype coefficients were jointly tested and the resulting p-values adjusted for multiple testing using false discovery rate (5%). For the associations identified, we then analyzed the marginal effect of each chronotype category. 

    Results: We identified 17 proteins associated with chronotype. Evening chronotype was positively associated with proteins previously linked to insulin resistance and cardiovascular risk, namely retinoic acid receptor protein 2, fatty acid-binding protein adipocyte, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 (PAI-1). Additionally, PAI-1 was inversely associated with the extreme morning chronotype. 

    Conclusions: In this population-based study, proteins previously related with cardiometabolic risk were elevated in the evening chronotypes. These results may guide future research in the relation between chronotype and cardiometabolic disorders. 

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  • 192.
    Baldi, Enrico
    et al.
    Univ Pavia, Dept Mol Med, Sect Cardiol, I-27100 Pavia, Italy.;Fdn IRCCS Policlin San Matteo, Cardiac Intens Care Unit, Arrhythmia & Electrophysiol & Expt Cardiol, I-27100 Pavia, Italy.;Italian Resuscitat Council, I-40128 Bologna, Italy..
    Grieco, Niccolo B.
    Italian Resuscitat Council, I-40128 Bologna, Italy.;Osped Niguarda Ca Granda, Cardiol Dept, I-20162 Milan, Italy..
    Ristagno, Giuseppe
    Italian Resuscitat Council, I-40128 Bologna, Italy.;Univ Milan, Dept Pathophysiol & Transplantat, I-20122 Milan, Italy..
    Alihodzic, Hajriz
    Univ Tuzla, Publ Inst Hlth Ctr Dr Mustafa Sehovic, Emergency Med Serv, Tuzla 75000, Bosnia & Herceg.;Univ Tuzla, Fac Med, Tuzla 75000, Bosnia & Herceg..
    Canon, Valentine
    Univ Lille, CHU Lille, ULR 2694 METRICS Evaluat Technol Sante & Prat Med, F-59000 Lille, France.;French Natl Out Hosp Cardiac Arrest Registry Regi, F-59000 Lille, France..
    Birkun, Alexei
    VI Vernadsky Crimean Fed Univ, Med Acad, UA-95000 Simferopol, Ukraine..
    Cresta, Ruggero
    Federaz Cantonale Ticinese Servizi Ambulanza FCTS, Qual & Res Div, CH-6500 Bellinzona, Switzerland.;Fdn Ticino Cuore, CH-6900 Lugano, Switzerland..
    Cimpoesu, Diana
    Grigore T Popa Univ Med & Pharm, Fac Med, Emergency Dept, Iasi 700115, Romania..
    Clarens, Carlo
    Luxembourg Resuscitat Council, L-2680 Luxembourg, Luxembourg..
    Ganter, Julian
    Univ Heart Ctr Freiburg, Fac Med, Dept Cardiovasc Surg, D-79085 Freiburg, Germany..
    Markota, Andrej
    Slovenian Resuscitat Council, Slovenian Soc Emergency Med, Ljubljana 1000, Slovenia.;Univ Med Ctr Maribor, Med Intens Care Unit, Maribor 2000, Slovenia..
    Mols, Pierre
    Univ Libre Bruxelles, CHU St Pierre, Serv Urgences & SMUR, B-1000 Brussels, Belgium..
    Nikolaidou, Olympia
    EMS Natl Ctr Emergency Care, Thessaloniki 546, Greece..
    Quinn, Martin
    Natl Univ Ireland, Out Hosp Cardiac Arrest Registry Steering Grp, Galway H91 CF50, Ireland..
    Raffay, Violetta
    European Univ Cyprus, Dept Med, CY-2404 Nicosia, Cyprus.;Serbian Resuscitat Council, Novi Sad 21102, Serbia..
    Ortiz, Fernando Rosell
    Serv Urgencias Med 061 La Rioja, Logrono 26007, Spain..
    Salo, Ari
    Univ Helsinki, Dept Emergency Med & Serv, Helsinki 00530, Finland.;Helsinki Univ Hosp, Helsinki 00530, Finland..
    Stieglis, Remy
    Univ Amsterdam, Med Ctr, Dept Cardiol, Locat AMC, NL-1105 Amsterdam, Netherlands..
    Strömsöe, Anneli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Center for Clinical Research Dalarna. Dalarna Univ, Sch Educ Hlth & Social Studies, S-79188 Falun, Sweden.;Reg Dalarna, Dept Prehosp Care, S-79129 Falun, Sweden..
    Tjelmeland, Ingvild
    Oslo Univ Hosp, Div Prehosp Serv, N-0372 Oslo, Norway.;Univ Oslo, Fac Med, Inst Clin Med, N-0372 Oslo, Norway.;Univ Hosp Schleswig Holstein, Inst Emergency Med, D-24105 Kiel, Germany..
    Trenkler, Stefan
    Safarik Univ, Med Fac, Dept Anaesthesiol & Intens Med, Kosice 04011, Slovakia..
    Wnent, Jan
    Univ Hosp Schleswig Holstein, Inst Emergency Med, D-24105 Kiel, Germany.;Univ Hopspital Schleswig Holstein, Dept Anesthesiol, Campus Kiel, D-24105 Kiel, Germany.;Univ Namibia, Sch Med, Windhoek 10005, Namibia..
    Grasner, Jan-Thorsten
    Univ Hosp Schleswig Holstein, Inst Emergency Med, D-24105 Kiel, Germany.;Univ Hopspital Schleswig Holstein, Dept Anesthesiol, Campus Kiel, D-24105 Kiel, Germany..
    Bottiger, Bernd W.
    Univ Hosp, Dept Anaesthesiol & Intens Care Med, D-50931 Cologne, Germany.;Med Fac Cologne, D-50931 Cologne, Germany.;European Resuscitat Council ERC, B-2845 Niel, Belgium..
    Savastano, Simone
    Italian Resuscitat Council, I-40128 Bologna, Italy.;Fdn IRCCS Policlin San Matteo, Div Cardiol, I-27100 Pavia, Italy..
    The Automated External Defibrillator: Heterogeneity of Legislation, Mapping and Use across Europe. New Insights from the ENSURE Study2021In: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 10, no 21, article id 5018Article in journal (Refereed)
    Abstract [en]

    Introduction: The rapid use of an automated external defibrillator (AED) is crucial for increased survival after an out-of-hospital cardiac arrest (OHCA). Many factors could play a role in limiting the chance of an AED use. We aimed to verify the situation regarding AED legislation, the AED mapping system and first responders (FRs) equipped with an AED across European countries.

    Methods: We performed a survey across Europe entitled "European Study about AED Use by Lay Rescuers " (ENSURE), asking the national coordinators of the European Registry of Cardiac Arrest (EuReCa) program to complete it.

    Results: Nineteen European countries replied to the survey request for a population covering 128,297,955 inhabitants. The results revealed that every citizen can use an AED in 15 countries whereas a training certificate was required in three countries. In one country, only EMS personnel were allowed to use an AED. An AED mapping system and FRs equipped with an AED were available in only 11 countries. The AED use rate was 12-59% where AED mapping and FR systems were implemented, which was considerably higher than in other countries (0-7.9%), reflecting the difference in OHCA survival.

    Conclusions: Our survey highlighted a heterogeneity in AED legislation, AED mapping systems and AED use in Europe, which was reflected in different AED use and survival.

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  • 193.
    Ballin, Marcel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical geriatrics. Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden.
    Neovius, Martin
    Department of Medicine, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
    Ortega, Francisco B.
    Department of Physical Education and Sports, Faculty of Sport Sciences, Sport and Health University Research Institute, University of Granada, Granada, Spain;Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland;CIBER de Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Granada, Spain.
    Henriksson, Pontus
    Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
    Nordström, Anna
    Rehabilitation and Pain Centre, Uppsala University Hospital, Uppsala, Sweden; School of Sport Sciences, UiT the Arctic University of Norway, Tromsø, Norway; Department of Health Sciences, The Swedish Winter Sport Research Centre, Mid Sweden University, Östersund, Sweden.
    Berglind, Daniel
    Centre for Epidemiology and Community Medicine, Region Stockholm, Stockholm, Sweden;Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Nordström, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical geriatrics.
    Ahlqvist, Viktor H.
    Department of Global Public Health, Karolinska Institutet, Stockholm, Sweden.
    Genetic and Environmental Factors and Cardiovascular Disease Risk in Adolescents2023In: JAMA Network Open, E-ISSN 2574-3805, Vol. 6, no 11, article id e2343947Article in journal (Refereed)
    Abstract [en]

    Importance  Cardiovascular risk factors in youth have been associated with future cardiovascular disease (CVD), but conventional observational studies are vulnerable to genetic and environmental confounding.

    Objective  To examine the role of genetic and environmental factors shared by full siblings in the association of adolescent cardiovascular risk factors with future CVD.

    Design, Setting, and Participants  This is a nationwide cohort study with full sibling comparisons. All men who underwent mandatory military conscription examinations in Sweden between 1972 and 1995 were followed up until December 31, 2016. Data analysis was performed from May 1 to November 10, 2022.

    Exposures  Body mass index (BMI), cardiorespiratory fitness, blood pressure, handgrip strength, and a combined risk z score in late adolescence.

    Main Outcomes and Measures  The primary outcome was fatal or nonfatal CVD, as recorded in the National Inpatient Register or the Cause of Death Register before 2017.

    Results  A total of 1 138 833 men (mean [SD] age, 18.3 [0.8] years), of whom 463 995 were full brothers, were followed up for a median (IQR) of 32.1 (26.7-37.7) years, during which 48 606 experienced a CVD outcome (18 598 among full brothers). All risk factors were associated with CVD, but the effect of controlling for unobserved genetic and environmental factors shared by full siblings varied. In the sibling analysis, hazard ratios for CVD (top vs bottom decile) were 2.10 (95% CI, 1.90-2.32) for BMI, 0.77 (95% CI, 0.68-0.88) for cardiorespiratory fitness, 1.45 (95% CI, 1.32-1.60) for systolic blood pressure, 0.90 (95% CI, 0.82-0.99) for handgrip strength, and 2.19 (95% CI, 1.96-2.46) for the combined z score. The percentage attenuation in these hazard ratios in the sibling vs total cohort analysis ranged from 1.1% for handgrip strength to 40.0% for cardiorespiratory fitness. Consequently, in the sibling analysis, the difference in cumulative CVD incidence at age 60 years (top vs bottom decile) was 7.2% (95% CI, 5.9%-8.6%) for BMI and 1.8% (95% CI, 1.0%-2.5%) for cardiorespiratory fitness. Similarly, in the sibling analysis, hypothetically shifting everyone in the worst deciles of BMI to the middle decile would prevent 14.9% of CVD at age 60 years, whereas the corresponding number for cardiorespiratory fitness was 5.3%.

    Conclusions and Relevance  In this Swedish national cohort study, cardiovascular risk factors in late adolescence, especially a high BMI, were important targets for CVD prevention, independently of unobserved genetic and environmental factors shared by full siblings. However, the role of adolescent cardiorespiratory fitness in CVD may have been overstated by conventional observational studies.

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  • 194.
    Banefelt, Jonas
    et al.
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Lindh, Maria
    Quantify Res, Hantverkargatan 8, S-11221 Stockholm, Sweden..
    Svensson, Maria K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Renal Medicine. Amgen AB Sweden, Gustav III S Blvd 54, S-16974 Solna, Sweden.
    Eliasson, Björn
    Univ Gothenburg, Sahlgrenska Univ Hosp, Dept Med, S-41345 Gothenburg, Sweden..
    Tai, Ming-Hui
    Amgen Inc, 1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA..
    Statin dose titration patterns and subsequent major cardiovascular events in very high-risk patients: estimates from Swedish population-based registry data2020In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 6, no 4, p. 323-331Article in journal (Refereed)
    Abstract [en]

    Clinical studies have demonstrated the efficacy of intensive statin therapy in lowering low-density lipoprotein cholesterol and cardiovascular (CV) events. Our objective was to examine statin titration patterns and the association between titration patterns and subsequent CV events in very high-risk patients. Using Swedish national population-based registry data, we identified 192 435 patients with very high risk of atherosclerotic CV disease initiated on moderate-intensity statin therapy between 2006 and 2013. Outcomes of interest were titration to high-intensity therapy and the major adverse cardiovascular events (MACE) composite (myocardial infarction, ischaemic stroke, and CV death) outcome. Cumulative incidence of MACE was assessed by titration status 1-year post-treatment initiation in patients adherent to treatment during the first year, using a 12-week cutoff from initiation to define early, delayed and no up-titration to high-intensity statins. Cox regression analysis was used to estimate adjusted hazard ratios (HRs). In 144 498 eligible patients, early titration was associated with significantly lower risk of MACE in the subsequent 2 years compared to no up-titration (HR 0.76, P < 0.01]. Delayed up-titration was associated with a smaller reduction (HR 0.88, P = 0.08). The majority of patients did not up-titrate. Early up-titration to high-intensity statins was independently associated with lower risk of subsequent CV events compared to no up-titration. Delayed up-titration was not associated with the same benefit. Despite the higher risk associated with no up-titration, few patients at very high CV risk who started treatment on moderate-intensity up-titrated to high intensity, indicating a potential need for more aggressive lipid management of these patients in clinical practice.

  • 195.
    Bao, Xue
    et al.
    Nanjing Univ, Nanjing Drum Tower Hosp, Dept Cardiol, Affiliated Hosp,Med Sch, 321 Zhongshan Rd, Nanjing 210008, Peoples R China.;Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Xu, Biao
    Nanjing Univ, Nanjing Drum Tower Hosp, Dept Cardiol, Affiliated Hosp,Med Sch, 321 Zhongshan Rd, Nanjing 210008, Peoples R China..
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Engström, Gunnar
    Lund Univ, Dept Clin Sci, Malmö, Sweden..
    Carotid ultrasound and systematic coronary risk assessment 2 in the prediction of cardiovascular events2023In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 30, no 10, p. 1007-1014Article in journal (Refereed)
    Abstract [en]

    Aims

    Subclinical carotid atherosclerosis adds predictive value to traditional risk factors for cardiovascular diseases (CVDs). Systematic Coronary Risk Assessment 2 (SCORE2), an algorithm composed of traditional risk factors, is a state-of-the-art to estimate the 10-year risk of first-onset CVDs. We aim to investigate whether and how subclinical carotid atherosclerosis affects the performance of SCORE2.

    Methods and results

    Carotid plaque presence and intima media thickness (IMT) were measured with ultrasound. The SCORE2 was calculated in 4588 non-diabetic participants aged 46–68 years. The incremental value for predicting CVD events of adding carotid plaque or IMT to SCORE2 was evaluated using C-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). The predicted 10-year CVD risk by SCORE2 and the observed event rate were compared between participants with and without carotid plaque. Adding plaque or IMT to SCORE2 significantly improved performance for predicting CVDs. The improvements in C-statistics, IDI, and NRI of adding plaque to SCORE2 for events occurring during the first 10 years were 2.20%, 0.70%, and 46.1%, respectively (all P < 0.0001). The SCORE2 over-predicted the 10-year CVD risk in those without carotid plaque (3.93% observed vs. 5.89% predicted, P < 0.0001) while under-predicted the risk in those with carotid plaque (9.69% observed vs. 8.12% predicted, P = 0.043).

    Conclusion

    Carotid ultrasound adds predictive performance to SCORE2 for assessment of CVD risk. Using SCORE2 without considering carotid atherosclerosis could under- or over-estimate the risk.

  • 196.
    Barbu, Andreea
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Jansson, Leif
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sandberg, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quach, My
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Palm, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    The use of hydrogen gas clearance for blood flow measurements in single endogenous and transplanted pancreatic islets2015In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 97, p. 124-129Article in journal (Refereed)
    Abstract [en]

    The blood perfusion of pancreatic islets is regulated independently from that of the exocrine pancreas, and is of importance for multiple aspects of normal islet function, and probably also during impaired glucose tolerance. Single islet blood flow has been difficult to evaluate due to technical limitations. We therefore adapted a hydrogen gas washout technique using microelectrodes to allow such measurements. Platinum micro-electrodes monitored hydrogen gas clearance from individual endogenous and transplanted islets in the pancreas of male Lewis rats and in human and mouse islets implanted under the renal capsule of male athymic mice. Both in the rat endogenous pancreatic islets as well as in the intra-pancreatically transplanted islets, the vascular conductance and blood flow values displayed a highly heterogeneous distribution, varying by factors 6-10 within the same pancreas. The blood flow of human and mouse islet grafts transplanted in athymic mice was approximately 30% lower than that in the surrounding renal parenchyma. The present technique provides unique opportunities to study the islet vascular dysfunction seen after transplantation, but also allows for investigating the effects of genetic and environmental perturbations on islet blood flow at the single islet level in vivo. (C) 2014 The Authors. Published by Elsevier Inc.

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  • 197.
    Baron, Tomasz
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Berglund, 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 Public Health and Caring Sciences, Geriatrics.
    Hedin, Eva-Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia.
    Flachskampf, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Test-retest reliability of new and conventional echocardiographic parameters of left ventricular systolic function2019In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 108, no 4, p. 355-365Article in journal (Refereed)
    Abstract [en]

    Background: Reliability of left ventricular function measurements depends on actual biological conditions, repeated registrations and their analyses.

    Objective: To investigate test–retest reliability of speckle-tracking-derived strain measurements and its determinants compared to the conventional parameters, such as ejection fraction (EF), LV volumes and mitral annular plane systolic excursion (MAPSE).

    Methods: In 30 patients with a wide range of left ventricular function (mean EF 46.4 ± 16.4%, range 14–73%), standard echo views were acquired independently in a blinded fashion by two different echocardiographers in immediate sequence and analyzed off-line by two independent readers, creating 4 data sets per patient. Test–retest reliability of studied parameters was calculated using the smallest detectable change (SDC) and a total, inter-acquisition and inter-reader intra-class correlation coefficient (ICC).

    Results: The smallest detectable change normalized to the mean absolute value of the measured parameter (SDCrel) was lowest for MAPSE (10.7%). SDCrel for EF was similar to GLS (14.2 and 14.7%, respectively), while SDCrel for CS was much higher (35.6%). The intra-class correlation coefficient was excellent (> 0.9) for all measures of the left ventricular function. Intra-patient inter-acquisition reliability (ICCacq) was significantly better than inter-reader reliability (ICCread) (0.984 vs. 0.950, p = 0.03) only for EF, while no significant difference was observed for any other LV function parameter. Mean intra-subject standard deviations were significantly correlated to the mean values for CS and LV volumes, but not for the other studied parameters.

    Conclusions: In a test–retest setting, both with normal and impaired left ventricular function, the smallest relative detectable change of EF, GLS and MAPSE was similar (11–15%), but was much higher for CS (35%). Surprisingly, reliability of GLS was not superior to that of EF. Acquisition and reader to a similar extent influenced the reliability of measurements of all left ventricular function measures except for ejection fraction, where the reliability was more dependent on the reader than on the acquisition.

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  • 198.
    Baron, Tomasz
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Disciplinary Domain of Medicine and Pharmacy, research centers etc., Uppsala Clinical Research Center (UCR). 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, Clinical Physiology.
    Bergsten, Johannes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Albåge, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Lundin, Lennart
    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, Clinical Physiology.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Flachskampf, Frank A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Cardiac Imaging in Carcinoid Heart Disease2021In: JACC Cardiovascular Imaging, ISSN 1936-878X, E-ISSN 1876-7591, Vol. 14, no 11, p. 2240-2253Article in journal (Refereed)
    Abstract [en]

    Carcinoid disease is caused by neuroendocrine tumors, most often located in the gut, and leads in approximately 20% of cases to specific, severe heart disease, most prominently affecting right-sided valves. If cardiac disease occurs, it determines the patient's prognosis more than local growth of the tumor. Surgical treatment of carcinoid-induced valve disease has been found to improve survival in observational studies. Cardiac imaging is crucial for both diagnosis and management of carcinoid heart disease; in the past, imaging was accomplished largely by echocardiography, but more recently, imaging for carcinoid heart disease has increasingly become multimodal and warrants awareness of the particular diagnostic challenges of this disease. This paper reviews the pathophysiology and manifestations of carcinoid heart disease in light of the different imaging modalities.

  • 199.
    Baron, Tomasz
    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.
    Beskow, Anna H.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala Biobank, Uppsala, Sweden.
    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.
    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.
    Biobank linked to SWEDEHEART quality registry-routine blood sample collection opens new opportunities for cardiovascular research2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 12-15Article in journal (Refereed)
    Abstract [en]

    High-quality biobanking within routine health services, through the use of existing health-care practices and infrastructure, with respect to safety and integrity of patients in line with the Swedish Biobank Act, enables large-scale collection of biological material at reasonable costs. Complementing the extensive information on myocardial infarction patients from a national registry gives unique opportunities for research focusing on better understanding of cardiovascular disease occurrence and prognosis, developing of new diagnostic methods, and personalized treatments with greater efficacy and fewer side effects.

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    fulltext
  • 200.
    Baron, Tomasz
    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, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Beskow, Anna
    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, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. 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, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biobank kopplad till Swedeheart en resurs för framtida forskning: Erfarenheter av insamling av blodprov i hjärtsjukvården i Uppsala2013In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 110, p. CF43-Article in journal (Refereed)
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