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  • 101.
    Boman, K.
    et al.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Wirta, S. Bruce
    Novartis Sweden AB, Stockholm, Sweden..
    Costa-Scharplatz, M.
    Novartis Sweden AB, Stockholm, Sweden..
    Calado, F.
    Novartis Pharma AG, Basel, Switzerland..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Healthcare resource utilization associated with heart failure with preserved versus reduced ejection fraction: a retrospective population-based cohort study in Sweden2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, p. 346-346Article in journal (Other academic)
  • 102.
    Boman, K.
    et al.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Stålhammar, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Costa-Scharplatz, M.
    Novartis Sweden AB, Stockholm, Sweden..
    Wirta, S. Bruce
    Novartis Sweden AB, Stockholm, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Costs associated with heart failure with preserved versus reduced ejection fraction: a retrospective population-based cohort study in Sweden2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, p. 346-347Article in journal (Other academic)
  • 103. Bongiorni, Maria Grazia
    et al.
    Marinskis, Germanas
    Lip, Gregory Y H
    Svendsen, Jesper Hastrup
    Dobreanu, Dan
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    How European centres diagnose, treat, and prevent CIED infections: Results of an European Heart Rhythm Association survey2012In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 14, no 11, p. 1666-1669Article in journal (Refereed)
    Abstract [en]

    The purpose of our survey is to analyse the clinical approach used to prevent and treat cardiovascular implantable electronic device (CIED) infections in Europe. The survey involves high-volume implanting centres. According to the survey the incidence of CIED infections shows a slight decrease in most centres and is substantially under 2% in the majority of centres interviewed. However, there are still differences in terms of prophylactic antibiotic therapy: 8.9% of the centres administer oxacillin as preoperative treatment, 4.4% of them do not give any antibiotic therapy, all centres use some kind of skin antisepsis, but only 42.2% use chlorhexidine. In case of local infection, 43.5% of centres perform lead extraction as first approach. In the case of systemic infection or evidence of lead or valvular endocarditis, 95% of centres treat these conditions by extracting the leads, which indicates that the adherence to the lead extraction guidelines is quite good.

  • 104.
    Borg, Sabina
    et al.
    Linkoping Univ, Div Physiotherapy, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.
    Oberg, Birgitta
    Linkoping Univ, Div Physiotherapy, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
    Leosdottir, Margret
    Lund Univ, Dept Clin Sci Malmo, Fac Med, Malmo, Sweden;Skane Univ Hosp, Dept Cardiol, Malmo, Sweden.
    Lindholm, Daniel
    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.
    Nilsson, Lennart
    Linkoping Univ, Div Cardiovasc Med, Dept Med & Hlth Sci, Linkoping, Sweden.
    Back, Maria
    Linkoping Univ, Div Physiotherapy, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden;Sahlgrens Univ Hosp, Dept Occupat Therapy & Physiotherapy, Gothenburg, Sweden.
    Factors associated with non-attendance at exercise-based cardiac rehabilitation2019In: BMC SPORTS SCIENCE MEDICINE AND REHABILITATION, E-ISSN 2052-1847, Vol. 11, article id 13Article in journal (Refereed)
    Abstract [en]

    Background

    Despite its well-established positive effects, exercise-based cardiac rehabilitation (exCR) is underused in patients following an acute myocardial infarction (AMI). The aim of the study was to identify factors associated with non-attendance at exCR in patients post-AMI in a large Swedish cohort.

    Methods

    A total of 31,297 patients who have suffered an AMI, mean age 62.4 ± 4 years, were included from the SWEDEHEART registry during the years 2010–2016. Comparisons between attenders and non-attenders at exCR were done at baseline for the following variables: age, sex, body mass index, occupational status, smoking, previous diseases, type of index cardiac event and intervention, and left ventricular function. Distance of residence from the hospital and type of hospital were added as structural variables in logistic regression analyses, with non-attendance at exCR at one-year follow-up as dependent, and with individual and structural variables as independent variables.

    Results

    In total, 16,214 (52%) of the patients did not attend exCR. The strongest predictor for non-attendance was distance to the exCR centre (OR 1.75 [95% CI: 1.64–1.86]). Other predictors for non-attendance included smoking, history of stroke, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), AMI or diabetes, male sex, being retired vs. being employed, and being followed-up at a county hospital. Patients with ST-elevation myocardial infarction (STEMI) and those intervened with PCI or CABG were more likely to attend exCR.

    Conclusions

    A distance greater than 16 km was associated with increased probability of non-attendance at exCR, as were smoking, a higher burden of comorbidities, and male sex. A better understanding of individual and structural factors can support the development of future rehabilitation services.

  • 105. Boriani, Giuseppe
    et al.
    Fauchier, Laurent
    Aguinaga, Luis
    Beattie, James M
    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.
    Cohen, Ariel
    Dan, Gheorghe-Andrei
    Genovesi, Simonetta
    Israel, Carsten
    Joung, Boyoung
    Kalarus, Zbigniew
    Lampert, Rachel
    Malavasi, Vincenzo L
    Mansourati, Jacques
    Mont, Lluis
    Potpara, Tatjana
    Thornton, Andrew
    Lip, Gregory Y H
    European Heart Rhythm Association (EHRA) consensus document on management of arrhythmias and cardiac electronic devices in the critically ill and post-surgery patient, endorsed by endorsed by Heart Rhythm Society (HRS), Asia Pacific Heart Rhythm Society (APHRS), Cardiac Arrhythmia Society of Southern Africa (CASSA), and Latin American Heart Rhythm Society (LAHRS).2019In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 21, no 1, p. 7-8Article in journal (Refereed)
  • 106.
    Bosch, Jackie
    et al.
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;McMaster Univ, Sch Rehabil Sci, Hamilton Hlth Sci, Hamilton, ON, Canada.
    O'Donnell, Martin
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada;NUI Galway, Dept Med, Res Board Clin Res Facil, Galway, Ireland.
    Swaminathan, Balakumar
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Lonn, Eva Marie
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Sharma, Mikul
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Dagenais, Gilles
    Univ Laval, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ, Canada.
    Diaz, Rafael
    Inst Cardiovasc Rosario, Rosario, Santa Fe, Argentina.
    Khunti, Kamlesh
    Univ Leicester, Diabet Res Ctr, Leicester, Leics, England.
    Lewis, Basil S.
    Technion Israel Inst Technol, Ruth & Bruce Rappaport Sch Med, Lady Davis Carmel Med Ctr, Haifa, Israel.
    Avezum, Alvaro
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Keltai, Matyas
    Semmelweis Univ, Budapest, Hungary.
    Reid, Christopher
    Monash Univ, Melbourne, Vic, Australia.
    Toff, William D.
    Univ Leicester, Glenfield Hosp, Leicester Cardiovasc Biomed Res Unit, Dept Cardiovasc Sci, Leicester, Leics, England;Univ Leicester, Glenfield Hosp, Leicester Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, Leicester, Leics, England.
    Dans, Antonio
    Univ Philippines, Coll Med, Manila, Philippines.
    Leiter, Lawrence A.
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
    Sliwa, Karen
    Univ Cape Town, Soweto Cardiovasc Res Grp, Dept Med, Hatter Inst Cardiovasc Res Africa, Rondebosch, South Africa.
    Lee, Shun Fu
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Pogue, Janice M.
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Hart, Robert
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    McMaster Univ, Sch Rehabil Sci, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Effects of blood pressure and lipid lowering on cognition Results from the HOPE-3 study2019In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 92, no 13, p. E1435-E1446Article in journal (Refereed)
    Abstract [en]

    Objective: To assess whether long-term treatment with candesartan/hydrochlorothiazide, rosuvastatin, or their combination can slow cognitive decline in older people at intermediate cardiovascular risk.

    Methods: The Heart Outcomes Prevention Evaluation-3 (HOPE-3) study was a double-blind, randomized, placebo-controlled clinical trial using a 2 x 2 factorial design. Participants without known cardiovascular disease or need for treatment were randomized to candesartan (16 mg) plus hydrochlorothiazide (12.5 mg) or placebo and to rosuvastatin (10 mg) or placebo. Participants who were >= 70 years of age completed the Digit Symbol Substitution Test (DSST), the modified Montreal Cognitive Assessment, and the Trail Making Test Part B at baseline and study end.

    Results: Cognitive assessments were completed by 2,361 participants from 228 centers in 21 countries. Compared with placebo, candesartan/hydrochlorothiazide reduced systolic blood pressure by 6.0 mm Hg, and rosuvastatin reduced low-density lipoprotein cholesterol by 24.8 mg/dL. Participants were followed up for 5.7 years (median), and 1,626 completed both baseline and study-end assessments. Mean participant age was 74 years (SD +/- 3.5 years); 59% were women; 45% had hypertension; and 24% had >= 12 years of education. The mean difference in change in DSST scores was -0.91 (95% confidence interval [CI] -2.25 to 0.42) for candesartan/hydrochlorothiazide compared with placebo, -0.54 (95% CI -1.88 to 0.80) for rosuvastatin compared with placebo, and -1.43 (95% CI -3.37 to 0.50) for combination therapy vs double placebo. No significant differences were found for other measures.

    Conclusions: Long-term blood pressure lowering with candesartan plus hydrochlorothiazide, rosuvastatin, or their combination did not significantly affect cognitive decline in older people. ClinicalTrials.gov identifier: NCT00468923. Classification of evidence: This study provides Class II evidence that for older people, candesartan plus hydrochlorothiazide, rosuvastatin, or their combination does not significantly affect cognitive decline.

  • 107. Brilakis, Emmanouil
    et al.
    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.
    Meier, Bernhard
    Cools, Frank
    Claeys, Marc
    Cornel, Jan
    Aylward, Philip
    Lewis, Basil
    Weaver, Douglas
    Brandrup-Wognsen, Gunnar
    Stevens, Susanna
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Effect of Ticagrelor on the Outcomes of Patients With Prior Coronary Artery Bypass Graft Surgery: Insights From The PLATelet inhibition and patient Outcomes (PLATO) trial2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B215-B216Article in journal (Other academic)
  • 108. Brilakis, Emmanouil S.
    et al.
    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.
    Meier, Bernhard
    Cools, Frank
    Claeys, Marc J.
    Cornel, Jan H.
    Aylward, Philip
    Lewis, Basil S.
    Weaver, Douglas
    Brandrup-Wognsen, Gunnar
    Stevens, Susanna R.
    Himmelmann, Anders
    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.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Effect of ticagrelor on the outcomes of patients with prior coronary artery bypass graft surgery: Insights from the PLATelet inhibition and patient outcomes (PLATO) trial2013In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 166, no 3, p. 474-480Article in journal (Refereed)
    Abstract [en]

    Background Patients with prior coronary artery bypass graft surgery (CABG) who present with an acute coronary syndrome have a high risk for recurrent events. Whether intensive antiplatelet therapy with ticagrelor might be beneficial compared with clopidogrel is unknown. In this substudy of the PLATO trial, we studied the effects of randomized treatment dependent on history of CABG. Methods Patients participating in PLATO were classified according to whether they had undergone prior CABG. The trial's primary and secondary end points were compared using Cox proportional hazards regression. Results Of the 18,613 study patients, 1,133 (6.1%) had prior CABG. Prior-CABG patients had more high-risk characteristics at study entry and a 2-fold increase in clinical events during follow-up, but less major bleeding. The primary end point (composite of cardiovascular death, myocardial infarction, and stroke) was reduced to a similar extent by ticagrelor among patients with (19.6% vs 21.4%; adjusted hazard ratio [HR], 0.91 [0.67, 1.24]) and without (9.2% vs 11.0%; adjusted HR, 0.86 [0.77, 0.96]; P-interaction = .73) prior CABG. Major bleeding was similar with ticagrelor versus clopidogrel among patients with (8.1% vs 8.7%; adjusted HR, 0.89 [0.55, 1.47]) and without (11.8% vs 11.4%; HR, 1.08 [0.98, 1.20]; P-interaction =.46) prior CABG. Conclusions Prior-CABG patients presenting with acute coronary syndrome are a high-risk cohort for death and recurrent cardiovascular events but have a lower risk for major bleeding. Similar to the results in no-prior-CABG patients, ticagrelor was associated with a reduction in ischemic events without an increase in major bleeding.

  • 109. Brito, F. S. B. De Souza
    et al.
    Åkerblom, Axel A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wojdyla, D. W.
    Steg, P. G. S.
    Wallentin, Lars W.
    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.
    James, Stefan K. J.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Katus, H. A. K.
    Himmelmann, A. H.
    Becker, R. C. B.
    Lopes, R. D. L.
    Efficacy and safety of ticagrelor in patients with acute coronary syndrome and heart failure: insights from the platelet inhibition and patient outcomes (PLATO) trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 202-203Article in journal (Refereed)
  • 110. Brugada, Josep
    et al.
    Katritsis, Demosthenes G
    Arbelo, Elena
    Arribas, Fernando
    Bax, Jeroen J
    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.
    Calkins, Hugh
    Corrado, Domenico
    Deftereos, Spyridon G
    Diller, Gerhard-Paul
    Gomez-Doblas, Juan J
    Gorenek, Bulent
    Grace, Andrew
    Ho, Siew Yen
    Kaski, Juan-Carlos
    Kuck, Karl-Heinz
    Lambiase, Pier David
    Sacher, Frederic
    Sarquella-Brugada, Georgia
    Suwalski, Piotr
    Zaza, Antonio
    2019 ESC Guidelines for the management of patients with supraventricular tachycardiaThe Task Force for the management of patients with supraventricular tachycardia of the European Society of Cardiology (ESC).2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, article id ehz467Article in journal (Refereed)
  • 111.
    Brænne, Ingrid
    et al.
    University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck.
    Willenborg, Christina
    University of Lübeck, Institute for Cardiogeneticss.
    Tragante, Vinicius
    University Medical Center Utrecht, Division Heart and Lungs, Department of Cardiology.
    Kessler, Thorsten
    Technische Universität München, Deutsches Herzzentrum München.
    Zeng, Lingyao
    Technische Universität München, Deutsche s Herzzentrum München.
    Reiz, Benedikt
    University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck.
    Kleinecke, Mariana
    University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck.
    von Ameln, Simon
    Technische Universität München, Deutsches Herzzentrum München.
    Willer, Cristen J.
    University of Michigan, Dept of Biostatistics.
    Laakso, Markku
    University of Eastern Finland and Kuopio University Hospital, Internal Medicine, Institute of Clinical Medicine.
    Wild, Philipp S.
    University Medical Center Mainz, Preventive Cardiology and Preventive Medicine; University Medical Center Mainz, Center for Thrombosis and Hemostasis; DZHK (German Center for Cardiovascular Research), Partner Site RhineMain.
    Zeller, Tanja
    DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Hamburg-Eppendorf, Department of General and Interventional Cardiology .
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Franks, Paul W.
    Lund University, Skåne University Hospital Malmö, Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit .
    Salomaa, Veikko
    THL-National Institute for Health and Welfare, POB 30, Mannerheimintie 166, FI-00271, Helsinki.
    Dehghan, Abbas
    Erasmus University Medical Center, Department of Epidemiology.
    Meitinger, Thomas
    Erasmus University Medical Center, Department of Epidemiology; German Research Center for Environmental Health, Helmholtz Zentrum München, Institute of Human Genetics; DZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance; Technische Universität München, Institute of Human Genetics.
    Samani, Nilesh J.
    University of Leicester, Deparment of Cardiovascular Sciences; Glenfield Hospital, NIHR Leicester Cardiovascular Biomedical Research Unit.
    Asselbergs, Folkert W.
    University Medical Center Utrecht, Division Heart and Lungs, Department of Cardiology; University College London, Faculty of Population Health Science, Institute of Cardiovascular Science .
    Erdmann, Jeanette
    University of Lübeck, Institute for Cardiogeneticss; DZHK (German Research Center for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel; University Heart Center Lübeck.
    Schunkert, Heribert
    Technische Universität München, Deutsches Herzzentrum München; German Research Center for Environmental Health, Helmholtz Zentrum München, Institute of Human Genetics.
    A genomic exploration identifies mechanisms that may explain adverse cardiovascular effects of COX-2 inhibitors2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 10252Article in journal (Refereed)
    Abstract [en]

    Cyclooxygenase-2 inhibitors (coxibs) are characterized by multiple molecular off-target effects and increased coronary artery disease (CAD) risk. Here, we systematically explored common variants of genes representing molecular targets of coxibs for association with CAD. Given a broad spectrum of pleiotropic effects of coxibs, our intention was to narrow potential mechanisms affecting CAD risk as we hypothesized that the affected genes may also display genomic signals of coronary disease risk. A Drug Gene Interaction Database search identified 47 gene products to be affected by coxibs. We traced association signals in 200-kb regions surrounding these genes in 84,813 CAD cases and 202,543 controls. Based on a threshold of 1 x 10(-5) (Bonferroni correction for 3131 haplotype blocks), four gene loci yielded significant associations. The lead SNPs were rs7270354 (MMP9), rs4888383 (BCAR1), rs6905288 (VEGFA1), and rs556321 (CACNA1E). By additional genotyping, rs7270354 at MMP9 and rs4888383 at BCAR1 also reached the established GWAS threshold for genome-wide significance. The findings demonstrate overlap of genes affected by coxibs and those mediating CAD risk and points to further mechanisms, which are potentially responsible for coxib-associated CAD risk. The novel approach furthermore suggests that genetic studies may be useful to explore the clinical relevance of off-target drug effects.

  • 112.
    Buccheri, Sergio
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    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.
    Frobert, Ole
    Orebro Univ Hosp, Dept Cardiol, Orebro, Sweden.
    Gudnason, Thorarinn
    Landspitali Univ Hosp, Reykjavik, Iceland;Univ Iceland, Dept Cardiol, Reykjavik, Iceland;Univ Iceland, Cardiovasc Res Ctr, Reykjavik, Iceland.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindholm, Daniel P
    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.
    Maeng, Michael
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Olivecrona, Goran
    Lund Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    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.
    Assessing the Nationwide Impact of a Registry-Based Randomized Clinical Trial on Cardiovascular Practice The TASTE Trial in Perspective2019In: Circulation. Cardiovascular Interventions, ISSN 1941-7640, E-ISSN 1941-7632, Vol. 12, no 3, article id e007381Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Registry-based randomized clinical trials have emerged as useful tools to provide evidence on the comparative efficacy and safety of different therapeutic strategies. However, it remains unknown whether the results of registry-based randomized clinical trials have a sizable impact on daily clinical practice. We sought, therefore, to describe the temporal trends in thrombus aspiration (TA) use in Sweden before, during, and after dissemination of the TASTE trial (Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia) results.

    METHODS AND RESULTS: From January 1, 2006, to December 31, 2017, we included all consecutive patients with ST-segment-elevation myocardial infarction undergoing percutaneous revascularization in Sweden. All patients were registered in the Swedish Coronary Angiography and Angioplasty Registry. A total of 55 809 ST-segment-elevation myocardial infarction patients were included. TA use in Sweden substantially decreased after dissemination of TASTE results (from 39.8% to 11.8% during and after TASTE, respectively). Substantial variability in TA use across treating centers was observed before TASTE (TA use ranging from 0% to 70%), but after TASTE both the interhospital variability and the frequency of TA use were markedly reduced. A constant shift in medical practice was seen about 4 months after dissemination of the TASTE trial results. Time trends for all-cause mortality and definite stent thrombosis at 30 days were not associated with variations in TA use (P values >0.05 using the Granger test).

    CONCLUSIONS: In Sweden, the results of the TASTE trial were impactful in daily clinical practice and led to a relevant decrease in TA use in ST-segment-elevation myocardial infarction patients undergoing percutaneous revascularization.

  • 113.
    Buccheri, Sergio
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    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.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Olivecrona, Göran
    Hambraeus, Kristina
    Witt, Nils
    Lindholm, Daniel
    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.
    Erlinge, David
    Angerås, Oskar
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry.2018In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 14, no 5, p. e562-e569Article in journal (Refereed)
    Abstract [en]

    AIMS: The clinical performance of the SYNERGY drug-eluting stent (DES) in patients with acute myocardial infarction (MI) has not been investigated in detail. We sought to report on the outcomes after SYNERGY DES (Boston Scientific, Marlborough, MA, USA) implantation in patients with MI undergoing percutaneous revascularisation (PCI).

    METHODS AND RESULTS: We included all consecutive patients with MI undergoing PCI with the SYNERGY DES and newer-generation DES (n-DES group) in Sweden. From March 2013 to September 2016, a total of 36,292 patients, of whom 39.7% presented with ST-elevation MI, were included. As compared to patients in the n-DES group (n=31,403), patients in the SYNERGY group (n=4,889) were older and presented more often with left main or three-vessel disease involvement, as well as with restenotic lesions (p<0.001 for all parameters). The Kaplan-Meier estimates of ST at two years in the SYNERGY and n-DES groups were 0.69% and 0.81%, respectively (adjusted HR 1.00, 95% CI: 0.69-1.46; p=0.99). Clinically relevant restenosis was encountered in 1.48% and 1.25% of patients in the SYNERGY and n-DES groups, respectively (adjusted HR 1.05, 95% CI: 0.81-1.37; p=0.72). No differences in the risk of all-cause death and recurrent MI were found between the two groups after adjustment (adjusted HR 1.12, 95% CI: 0.98-1.28; p=0.10, and adjusted HR 0.95, 95% CI: 0.82-1.10; p=0.49, respectively).

    CONCLUSIONS: In a large and unselected cohort of patients with MI undergoing percutaneous revascularisation with the SYNERGY DES, stent performance and clinical outcomes did not differ compared with other n-DES up to two years.

  • 114.
    Bui, An H.
    et al.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Cannon, Christopher P.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Steg, Philippe Gabriel
    INSERM Unite 1148, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Dept Cardiol, Paris, France.;NHLI Imperial Coll, ICMS, Dept Cardiol, Royal Brompton Hosp, London, England..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Guo, Jianping
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Im, KyungAh
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelson, Eric L.
    Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    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.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Scirica, Benjamin M.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial2016In: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 9, no 2, article id e002951Article in journal (Refereed)
    Abstract [en]

    Background- Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. Methods and Results- In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by approximate to 5 months after ACS. Conclusions- NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event.

  • 115. Böhm, Michael
    et al.
    Ezekowitz, Michael D
    Connolly, Stuart J
    Eikelboom, John W
    Hohnloser, Stefan H
    Reilly, Paul A
    Schumacher, Helmut
    Brueckmann, Martina
    Schirmer, Stephan H
    Kratz, Mario T
    Yusuf, Salim
    Diener, Hans-Christoph
    Hijazi, Ziad
    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.
    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.
    Reply: Anticoagulant-Related Nephropathy2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 66, no 23, p. 2682-Article in journal (Refereed)
  • 116. C. ARDIoGRAMplusC4D, Consortium
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Large-scale association analysis identifies new risk loci for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 1, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.

  • 117. Calais, Fredrik
    et al.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Frobert, Ole
    Proximal coronary artery intervention: Stent thrombosis, restenosis and death2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 170, no 2, p. 227-232Article in journal (Refereed)
    Abstract [en]

    Background: Percutaneous coronary intervention (PCI) of lesions in the proximal left anterior descending coronary artery (LAD) may confer a worse prognosis compared with the proximal right coronary artery (RCA) and left circumflex coronary artery (LCX). Methods: From May 2005, to May 2011 we identified all PCIs for proximal, one-vessel coronary artery disease in the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). We evaluated restenosis, stent thrombosis (ST) and mortality in the LAD as compared to the RCA and LCX according to stent type, bare metal (BMS) or drug-eluting stents (DES). Results: 7840 single vessel proximal PCI procedures were identified. Mean follow-up time was 792 days. No differences in restenosis or ST were seen between the LAD and the RCA. The frequency of restenosis and ST was higher in the proximal LAD compared to the proximal LCX (restenosis: hazard ratio (HR) 2.28, confidence interval (CI) 1.56-3.34 p < 0.001; ST: HR 2.32, CI 1.11-4.85 p = 0.024). We found no difference in mortality related to coronary artery. In the proximal LAD, DES implantation was associated with a lower restenosis rate (HR 0.39, CI 0.27-0.55 < 0.001) and mortality (HR 0.58, CI 0.41-0.82 p = 0.002) compared with BMS. In the proximal RCA and LCX, DES use was not associated with lower frequency of clinical restenosis or mortality. Conclusions: Following proximal coronary artery intervention restenosis was more frequent in the LAD than in the LCX. Solely in the proximal LAD we found DES use to be associated with a lower risk of restenosis and death weighted against BMS.

  • 118.
    Calais, Fredrik
    et al.
    Univ Orebro, Fac Hlth, SE-70182 Orebro, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frobert, Ole
    Orebro Univ Hosp, Orebro, Sweden..
    Thrombus aspiration in patients with large anterior myocardial infarction: a TASTE trial substudy2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 66, no 15, p. B2-B2Article in journal (Other academic)
  • 119.
    Calais, Fredrik
    et al.
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden..
    Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 172, p. 129-134Article in journal (Refereed)
    Abstract [en]

    Background The TASTE trial did not demonstrate clinical benefit of thrombus aspiration (TA). High-risk patients might benefit from TA. Methods The TASTE trial was a multicenter, randomized, controlled, open-label trial obtaining end points from national registries. Patients (n = 7,244) with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) were randomly assigned 1: 1 to TA and PCI or to PCI alone. We assessed the 1-year clinical effect of TA in a subgroup with potentially large anterior STEMI: mid or proximal left anterior descending coronary artery infarct lesion, thrombolysis in myocardial infarction 0 to 2 flow, and symptom onset to PCI time = 5 hours. In this substudy, patient eligibility criteria corresponded to that of the INFUSE-AMI study. Results In total, 1,826 patients fulfilled inclusion criteria. All-cause mortality at 1 year of patients randomized to TA did not differ from those randomized to PCI only (hazard ratio [HR] 1.05, 95% CI 0.74-1.49, P = .77). Rates of rehospitalization for myocardial infarction, heart failure, and stent thrombosis did not differ between groups (HR 0.87, 95% CI 0.51-1.46, P = .59; HR 1.10 95% CI 0.77-1.58, P = .58; and HR 0.75, 95% CI 0.30-1.86, P = .53, respectively). This was also the case for the combined end point of all-cause mortality and rehospitalization for myocardial infarction, heart failure, or stent thrombosis (HR 1.00, 95% CI 0.79-1.26, P = .99). Conclusion In patients with STEMI and large area of myocardium at risk, TA did not affect outcome within 1 year.

  • 120.
    Cannon, Christopher P.
    et al.
    Baim Inst Clin Res, 930 Commonwealth Ave, Boston, MA 02215 USA.;Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lip, Gregory Y. H.
    Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Ellis, Stephen G.
    Cleveland Clin, Cleveland, OH 44106 USA..
    Kimura, Takeshi
    Kyoto Univ, Dept Cardiovasc Med, Kyoto, Japan..
    Maeng, Michael
    Aarhus Univ Hosp, Skejby, Denmark..
    Merkely, Bela
    Univ Heart & Vasc Ctr, Budapest, Hungary..
    Zeymer, Uwe
    Klinikum Stadt Ludwigshafen Rhein, Med Klin B, Ludwigshafen, Germany..
    Gropper, Savion
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Nordaby, Matias
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Kleine, Eva
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Harper, Ruth
    Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England..
    Manassie, Jenny
    Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England..
    Januzzi, James L.
    Baim Inst Clin Res, 930 Commonwealth Ave, Boston, MA 02215 USA.;Harvard Med Sch, Boston, MA USA.;Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA..
    ten Berg, Jurrien M.
    St Antonius Hosp, Nieuwegein, Netherlands..
    Steg, Gabriel
    Imperial Coll, London, England.;Univ Paris Diderot, French Alliance Cardiovasc Trials, F CRIN Network, DHU FIRE,INSERM,Unite 1148, Paris, France.;Hop Bichat Assistance Publ, Paris, France..
    Hohnloser, Stefan H.
    Goethe Univ Frankfurt, Dept Med, Div Cardiol, Frankfurt, Germany..
    Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 16, p. 1513-1524Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.

    METHODS In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y(12) inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y(12) inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (>= 80 years of age; >= 70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization.

    RESULTS The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups.

    CONCLUSIONS Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y(12) inhibitor than among those who received triple therapy with warfarin, a P2Y(12) inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events.

  • 121.
    Cannon, Christopher P.
    et al.
    Harvard Clin Res Inst, 930 Commonwealth Ave, Boston, MA 02215 USA.;Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Gropper, Savion
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Ellis, Stephen G.
    Cleveland Clin, Cleveland, OH 44106 USA..
    Kimura, Takeshi
    Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan..
    Lip, Gregory Y. H.
    Univ Birmingham, City Hosp, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Steg, Ph. Gabriel
    Univ Paris Diderot, Sorbonne Paris Cite, Hop Bichat, AP HP,Dept Hosp Univ FIRE,FACT,INSERM,U 1148, Paris, France.;ICMS Royal Brompton Hosp, NHLI Imperial Coll, London, England..
    ten Berg, Jurrien M.
    St Antonius Hosp, Nieuwegein, Netherlands..
    Manassie, Jenny
    Boehringer Ingelheim Ltd, Div Med, Bracknell, Berks, England..
    Kreuzer, Jorg
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med, Heidelberg, Germany..
    Blatchford, Jon
    Boehringer Ingelheim Ltd, Div Med, Bracknell, Berks, England..
    Massaro, Joseph M.
    Boston Univ, Sch Publ Hlth, Boston, MA USA..
    Brueckmann, Martina
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany..
    Ripoll, Ernesto Ferreiros
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hohnloser, Stefan H.
    Goethe Univ Frankfurt, Dept Cardiol, Frankfurt, Germany..
    Design and Rationale of the RE-DUAL PCI Trial: A Prospective, Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting2016In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 39, no 10, p. 555-564Article in journal (Refereed)
    Abstract [en]

    Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE-DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open-label, blinded-endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low-dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize similar to 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.

  • 122.
    Cannon, Christopher P.
    et al.
    Baim Inst Clin Res, Boston, MA, USA.
    Lip, Gregory Y. H.
    Univ Birmingham, Birmingham, England.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation: The authors reply2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 378, no 5, p. 485-486Article in journal (Other academic)
  • 123.
    Carlhed, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Quality Improvement in Acute Coronary Care: Combining the Use of an Interactive Quality Registry with a Quality Improvement Collaborative to Improve Clinical Outcome in Patients with Acute Myocardial Infarction2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The quality of care for Swedish patients with acute myocardial infarction (AMI) is continuously increasing. Nevertheless, a great potential for improvement still exists.

    The aim of the present study was to design and implement a systematic quality improvement (QI) collaborative in the area of AMI care, and to validate its usefulness primarily by analyzing its effect on hospital adherence to national guidelines. Also, the impact on patient morbidity and mortality was to be evaluated. The intervention was based on proven QI methodologies, as well as interactive use of a web-based quality registry with enhanced, powerful feedback functions.

    19 hospitals in the intervention group were matched to 19 similar control hospitals. In comparison with the control group, the intervention group showed significantly higher post-interventional improvements in 4 out of 5 analyzed quality indicators (significance shown for ACE-inhibitors, Clopidogrel, Heparin/LMWH, Coronary angiography, no significance for Lipid-lowering therapy).

    From baseline to the post-intervention measurement, the intervention hospitals showed significantly lower all-cause mortality and cardiovascular re-admission rates (events per 100 patient-years; -2,82, 95% CI -5,26 to -0,39; -9,31, 95% CI -15,48 to -3,14, respectively). No significant improvements were seen in the control group.

    The improved guideline adherence rates in the intervention hospitals were sustained for all indicators but one (ACE-inhibitors), this during a follow-up measurement three months after study support withdrawal. No effects were seen on any indicators other than those primarily targeted.

    In conclusion, by combining a systematic QI collaborative with the utilization of a national quality registry, significant improvements in quality of care for patients with AMI can be achieved.

  • 124.
    Carlhed, Rickard
    et al.
    Onkologi, Landstinget i Värmland.
    Bellman, Christina
    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.
    Bojestig, Mats
    Landstinget i Jönköping.
    Bojö, Leif
    Klinisk Fysiologi, Landstinget i Värmland.
    Peterson, Anette
    Landstinget i Jönköping.
    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.
    Quality improvement in coronary care: Analysis of sustainability and impact on adjacent clinical measures after a Swedish controlled, multicenter quality improvement collaborative2012In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 1, no 4, article id e000737Article in journal (Refereed)
    Abstract [en]

    Background Quality Improvement in Coronary Care, a Swedish multicenter, controlled quality-improvement (QI) collaborative, has shown significant improvements in adherence to national guidelines for acute myocardial infarction, as well as improved clinical outcome. The objectives of this report were to describe the sustainability of the improvements after withdrawal of study support and a consolidation period of 3 months and to report whether improvements were disseminated to treatments and diagnostic procedures other than those primarily targeted.

    Methods and Results Multidisciplinary teams from 19 Swedish hospitals were educated in basic QI methodologies. Another 19 matched hospitals were included as blinded controls. All evaluations were made on the hospital level, and data were obtained from a national quality registry, Swedish Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA). Sustainability indicators consisted of use of angiotensin-converting enzyme inhibitors, lipid-lowering therapy, clopidogrel, low-molecular weight heparin, and coronary angiography. Dissemination indicators were use of echocardiography, stress tests, and reperfusion therapy; time delays; and length of stay. At the reevaluation period of 6 months, the improvements at the QI intervention hospitals were sustained in all indicators but 1 (angiotensin-converting enzyme inhibitor). Between the 2 measurements, the control group improved significantly in all but 1 indicator (angiotensin-converting enzyme inhibitor). However, at the second measurement, the absolute adherence rates of the intervention hospitals were still numerically higher in all 5 indicators, and significantly so in 1 (clopidogrel). No significant changes were observed for the dissemination indicators.

    Conclusions The combination of a systematic QI collaborative with a national, interactive quality registry might lead to substantial and sustained improvements in the quality of acute myocardial infarction care. However, to achieve disseminated improvements in adjacent clinical measures, those adjacent measures probably should be made explicit before any QI intervention.

  • 125.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Feldreich, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Use of Proteomics To Investigate Kidney Function Decline over 5 Years2017In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 12, no 8, p. 1226-1235Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.

    CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.

  • 126.
    Carlsson, Axel C
    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.
    Juhlin, C Christofer
    Larsson, Tobias E
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Soluble tumor necrosis factor receptor 1 (sTNFR1) is associated with increased total mortality due to cancer and cardiovascular causes: Findings from two community based cohorts of elderly2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 237, no 1, p. 236-242Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Experimental evidence support soluble receptors for tumor necrosis factor alpha as important mediators of the underlying pathology leading to cardiovascular disease and cancer. However, prospective data concerning the relation between circulating soluble tumor necrosis factor receptor-1 (sTNFR1) and mortality in humans are lacking. We aimed to explore and validate the association between sTNFR1 and mortality, and to explore the influence of other established risk factors for mortality, including other inflammatory markers.

    METHODS: The association between serum sTNFR1and the risk for mortality was investigated in two community-based cohorts of elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n = 1005, mean age 70 years, median follow-up 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM, n = 775, mean age 77 years, median follow-up 8.1 years).

    RESULTS: In total, 101 participants in PIVUS and 274 in ULSAM died during follow-up. In multivariable Cox regression models adjusted for inflammation, lifestyle and established cardiovascular risk factors, one standard deviation (SD) higher sTNFR1 was associated with a hazard ratio (HR) for mortality of 1.37, 95% confidence interval (CI) 1.17-1.60, in PIVUS and HR 1.22, 95% CI 1.10-1.37 in ULSAM. Moreover, circulatingsTNFR1 was associated with cardiovascular mortality (HR per SD of sTNFR1, 1.24, 95% CI 1.07-1.44) and cancer mortality (HR per SD of sTNFR1, 1.32, 95% CI 1.11-1.57) in the ULSAM cohort. High levels of sTNFR1 identified individuals with increased risk of mortality among those with high as well as low levels of systemic inflammation.

    CONCLUSIONS: An association between circulating sTNFR1 and an increased risk for mortality was found and validated in two independent community-based cohorts. The future clinical role of sTNFR1 to identify high risk patients for adverse outcomes and mortality has yet to be determined.

  • 127.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, p. 359-365Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    METHOD AND RESULTS:

    At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m(2), n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m(2), n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m(2), n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    CONCLUSIONS:

    Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up.

  • 128. Carlsson, Marcus
    et al.
    Heiberg, Einar
    Ostenfeld, Ellen
    Steding-Ehrenborg, Katarina
    Kovács, Sándor J
    Flachskampf, Frank
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Arheden, Håkan
    Functional Contribution of Circumferential Versus Longitudinal Strain: Different Concepts Suggest Conflicting Results.2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 71, no 2, p. 254-255, article id S0735-1097(17)41601-9Article in journal (Refereed)
  • 129.
    Carrero, Juan J.
    et al.
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensevik, Karin
    Szummer, Karolina
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Evans, Marie
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Karolinska Inst, Clin Sci, Stockholm, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    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.
    Jernberg, Tomas
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Clinical Outcomes Associated With The Duration Of Dual Antiplatelet Therapy With Clopidogrel And Aspirin In Chronic Kidney Disease Patients With Acute Coronary Syndrome2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 1441-1441Article in journal (Other academic)
  • 130.
    Carrero, Juan-Jesus
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    Varenhorst, Christoph
    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.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Szummer, Karolina
    Karolinska Inst, Div Cardiol, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Evans, Marie
    Karolinska Inst, Div Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Jernberg, Tomas
    Karolinska Inst, Div Cardiol, Stockholm, Sweden..
    Long-term versus short-term dual antiplatelet therapy was similarly associated with a lower risk of death, stroke, or infarction in patients with acute coronary syndrome regardless of underlying kidney disease2017In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 91, no 1, p. 216-226Article in journal (Refereed)
    Abstract [en]

    Scarce and conflicting evidence exists on whether clopidogrel is effective and whether dual antiplatelet treatment (DAPT) is safe in patients with acute coronary syndrome and chronic kidney disease (CKD). To study this, we performed an observational, prospective, multicenter cohort study of 36,001 patients of the SWEDEHEART registry. The exposure was DAPT prolonged after 3 months versus DAPT stopped at 3 months in consecutive patients with acute coronary syndrome and known serum creatinine. DAPT duration with clopidogrel and aspirin was assessed by dispensed tablets. CKD stages were classified according to estimated glomerular filtration rate (eGFR). Study outcomes were 1) the composite of death, myocardial infarction, or ischemic stroke; 2) bleeding; or 3) the aggregate of these two outcomes within day 111 and 365 from discharge. A longer DAPT duration, as compared with 3-month DAPT, was associated with lower hazard ratios for outcome one in each CKD stratum (eGFR over 60, adjusted hazard ratio [95% confidence interval] 0.76 [0.67-0.85]; eGFR 60 and less, 0.84 [0.73-0.96], of which eGFR between 45 and 60, 0.85 [0.70-1.05], eGFR between 30 and 45, 0.78 [0.62-0.97]; eGFR 30 and less ml/min/1.73 m(2), 0.93 [0.70-1.24]. Bleeding (outcome 2) was in general more common in the longer DAPT group of each aforementioned CKD stratum. Aggregated outcome analysis (outcome 3) similarly favored longer DAPT in each stratum. There was no interaction between DAPT duration and CKD strata for any of the study outcomes. Thus, a prolonged as compared with three-month DAPT was similarly associated with a lower risk of death, stroke, or reinfarction regardless of underlying CKD.

  • 131.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden..
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmström, R. E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Clin Pharmacol, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Schwieler, J.
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Wettermark, B.
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example2018In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 103, no 3, p. 493-501Article in journal (Refereed)
    Abstract [en]

    Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different fromthose treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases froma well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.

  • 132.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Neovius, Martin
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmström, Rickard E.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Schwieler, Jonas
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Wettermark, Bjon
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    An Automatized Model for Sequential Monitoring of Effectiveness of New Drugs Using Dronedarone as Example2016In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 25, p. 504-504Article in journal (Refereed)
  • 133.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    An Automatized Model for Sequential Monitoring of Effectiveness of New Drugs using Dronedarone as ExampleManuscript (preprint) (Other academic)
  • 134.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Dronedarone and Hepatic Toxicity? A Model for Evaluation of Post-Marketing Safety of Drugs in Routine CareManuscript (preprint) (Other academic)
  • 135.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden..
    Wettermark, Bjorn
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Lofberg, Robert
    Karolinska Inst, Dept Med, Stockholm, Sweden.;IBD Unit Sophiahemmet, Stockholm, Sweden..
    Eriksson, Irene
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lordal, Mikael
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Digest Dis, Stockholm, Sweden..
    Healthcare Utilisation and Drug Treatment in a Large Cohort of Patients with Inflammatory Bowel Disease2016In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 10, no 5, p. 556-565Article in journal (Refereed)
    Abstract [en]

    Crohn's disease [CD] and ulcerative colitis [UC] are chronic diseases associated with a substantial utilisation of healthcare resources. We aimed to estimate the prevalence of inflammatory bowel disease [IBD], CD, and UC and to describe and compare healthcare utilisation and drug treatment in CD and UC patients. This was a cross-sectional study of all patients with a recorded IBD diagnosis in Stockholm County, Sweden. Data on outpatient visits, hospitalisations, surgeries, and drug treatment during 2013 were analysed. A total of 13 916 patients with IBD were identified, corresponding to an overall IBD prevalence of 0.65% [CD 0.27%, UC 0.35%, inflammatory bowel disease unclassified 0.04%]; 49% of all IBD patients were treated with IBD-related drugs. Only 3.6% of the patients received high-dose corticosteroids, whereas 32.4% were treated with aminosalicylates [CD 21.2%, UC 41.0%, p < 0.0001]. More CD patients were treated with biologicals compared with UC patients [CD 9.6%, UC 2.9%, p < 0.0001] and surgery was significantly more common among CD patients [CD 3.0%, UC 0.8%, p < 0.0001]. This study indicates that patients with CD are the group with the highest medical needs. Patients with CD utilised significantly more healthcare resources [including outpatient visits, hospitalisations, and surgeries] than UC patients. Twice as many CD patients received immunomodulators compared with UC patients and CD patients were treated with biologicals three times more often. These results highlight that CD remains a challenge and further efforts are needed to improve care in these patients.

  • 136.
    Chami, Nathalie
    et al.
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Chen, Ming-Huei
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Slater, Andrew J.
    GlaxoSmithKline, Genet Target Sci, Res Triangle Pk, Res Triangle Pk, NC 27709 USA.;OmicSoft Corp, Cary, NC 27513 USA..
    Eicher, John D.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Evangelou, Evangelos
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina 45110, Greece..
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA..
    Love-Gregory, Latisha
    Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA..
    Kacprowski, Tim
    Ernst Moritz Arndt Univ Greifswald, Dept Funct Gen, Interfaculty Inst Genet & Funct Gen, Univ Med, D-17475 Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany..
    Schick, Ursula M.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA..
    Nomura, Akihiro
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.;Kanazawa Univ, Grad Sch Med Sci, Div Cardiovasc Med, Kanazawa, Ishikawa 9200942, Japan..
    Giri, Ayush
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Div Epidemiol, Nashville, TN 37235 USA..
    Lessard, Samuel
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Pankratz, Nathan
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA..
    Yanek, Lisa R.
    Johns Hopkins Univ, Sch Med, Dept Med Div Gen Internal Med icine, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA..
    Pazoki, Raha
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Hill, W. David
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Burt, Amber
    Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA..
    Bartz, Traci M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Becker, Diane M.
    Johns Hopkins Univ, Sch Med, Dept Med Div Gen Internal Med icine, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Becker, Lewis C.
    Johns Hopkins Univ Sch Med, Dept Med, Div Cardiol & Gen Internal Med, Baltimore, MD 21205 USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA..
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA..
    Crosslin, David R.
    Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    Dube, Marie-Pierre
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA..
    Floyd, James S.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA..
    Gao, He
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England..
    Greinacher, Andreas
    Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Harris, Tamara B.
    NIA, Intramural Res Program, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Hayward, Caroline
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland.;Univ Tampere, Sch Med, Tampere 33014, Finland..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Hirschhorn, Joel N.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA..
    Hofman, Albert
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Dept Clin Physiol, Sch Med, Tampere 33014, Finland..
    Lange, Ethan
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA..
    Launer, Lenore J.
    NIA, Intramural Res Program, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Li, Jin
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 USA..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Linneberg, Allan
    Capital Region Denmark, Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark.;Rigshosp, Dept Clin Expt Res, DK-2100 Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mathias, Rasika A.
    Johns Hopkins Univ Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA.;Johns Hopkins Univ Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Melander, Olle
    Lund Univ, Dept Clin Sci, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mononen, Nina
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Nalls, Mike A.
    NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA..
    Nickerson, Deborah A.
    Univ Washington, Dept Genome Sci, Seattle, WA 98105 USA..
    Nikus, Kjell
    Univ Tampere, Sch Med, Tampere 33014, Finland.;Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland..
    O'Donnell, Chris J.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Vet Adm VA Healthcare, Cardiol Sect, Boston, MA 02118 USA.;Boston Vet Adm VA Healthcare, Ctr Populat Gen, Boston, MA 02118 USA..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Petersmann, Astrid
    Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany..
    Polfus, Linda
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland..
    Raitoharju, Emma
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Richard, Melissa
    Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA..
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Rivadeneira, Fernando
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands.;Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NL-3015 Rotterdam, Netherlands..
    Rotter, Jerome I.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Schmidt, Frank
    Ernst Moritz Arndt Univ Greifswald, Dept Funct Gen, Interfaculty Inst Genet & Funct Gen, Univ Med, D-17475 Greifswald, Germany..
    Smith, Albert Vernon
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Alzheimer Scotland Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Taylor, Kent D.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thuesen, Betina H.
    Capital Region Denmark, Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark..
    Torstenson, Eric S.
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Div Epidemiol, Nashville, TN 37235 USA..
    Tracy, Russell P.
    Univ Vermont Coll Med, Dept Pathol, Colchester, VT 05446 USA.;Univ Vermont Coll Med, Dept Lab Med, Colchester, VT 05446 USA.;Univ Vermont Coll Med, Dept Biochem, Colchester, VT 05446 USA..
    Tzoulaki, Ioanna
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina 45110, Greece..
    Zakai, Neil A.
    Univ Vermont Coll Med, Dept Med, Burlington, VT 05405 USA.;Univ Vermont Coll Med, Dept Pathol, Burlington, VT 05405 USA..
    Vacchi-Suzzi, Caterina
    SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA..
    van Duijn, Cornelia M.
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands..
    van Rooij, Frank J. A.
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands..
    Cushman, Mary
    Univ Vermont Coll Med, Dept Med, Burlington, VT 05405 USA.;Univ Vermont Coll Med, Dept Pathol, Burlington, VT 05405 USA..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN 37203 USA..
    Vergnaud, Anne-Claire
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Waterworth, Dawn M.
    Genet Target Sci, GlaxoSmithKline, King Of Prussia, PA 19406 USA..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.;Univ Auckland, Auckland 1142, New Zealand..
    Wilson, James G.
    Univ Mississippi Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA..
    Kathiresan, Sekar
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Faraday, Nauder
    Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA..
    Abumrad, Nada A.
    Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA..
    Edwards, Todd L.
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Div Epidemiol, Nashville, TN 37235 USA..
    Ganesh, Santhi K.
    Univ Michigan, Dept Internal Med, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48108 USA..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA..
    Johnson, Andrew D.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Reiner, Alexander P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Lettre, Guillaume
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, no 1, p. 8-21Article in journal (Refereed)
    Abstract [en]

    Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

  • 137.
    Chen, Yundai
    et al.
    Chinese PLA Gen Hosp 301 Hosp, Dept Cardiol, Beijing, Peoples R China..
    Li, Dandan
    Chinese PLA Gen Hosp 301 Hosp, Dept Hematol, Beijing, Peoples R China..
    Jing, Jing
    Chinese PLA Gen Hosp 301 Hosp, Dept Hematol, Beijing, Peoples R China..
    Yan, Hongbing
    Natl Ctr Cardiovasc Dis, Cardiovasc Inst, Beijing, Peoples R China.;FuWai Hosp, Beijing, Peoples R China..
    Liu, Jinghua
    Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China..
    Shen, Zhujun
    Beijing Union Med Coll Hosp, Dept Cardiol, Beijing, Peoples R China..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    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.
    Treatment Trends, Effectiveness, and Safety of Statins on Lipid Goal Attainment in Chinese Percutaneous Coronary Intervention Patients: a Multicenter, Retrospective Cohort Study2017In: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 39, no 9, p. 1827-1839Article in journal (Refereed)
    Abstract [en]

    Purpose: Limited data exist on the use of statins in Chinese patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). We therefore conducted this study to observe the usage trend and the effectiveness of statins on LDL-C goal attainment and other lipid parameters among PCI-treated patients.

    Methods: This multicenter, retrospective, observational, longitudinal cohort study was conducted in PCI-treated patients with CAD between July 1, 2011, and February 28, 2015. Primary study outcomes included statin treatment pattern after PCI and proportion of patients achieving target (LDL-C) levels 1 month after PCI and initiating statin therapy.

    Findings: Data were analyzed for 2708 patients (mean age, 59 [10] years; median body mass index, 25.6 [4.0] kg/m(2)). From baseline to the end of 1 month, atorvastatin and rosuvastatin were the most prescribed statins; 20 mg and 10 mg were the most prescribed doses and therefore chosen for efficacy comparisons. In patients without dose changes, LDL-C reduction with rosuvastatin 10 mg was significantly greater compared with atorvastatin 20 mg (-0.67 mmol/L [from 2.44 mmol/L to 1.77 mmol/L] vs 0.54 mmol/L [from 2.40 mmol/L to 1.86 mmol/L]; P = 0.008). However, there was no difference in HDL-C, triglyceride, or total cholesterol values between groups. Age and LDL-C levels at baseline were significantly associated with target LDL-C achievement.

  • 138.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    NOAK vid klaffsjukdom -: bara i särskilda fall2018In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 115, article id FA93Article in journal (Refereed)
  • 139.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Johnell, Matilda
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Evaluation of microparticles in whole blood by multicolour flow cytometry assay2013In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 73, no 3, p. 229-239Article in journal (Refereed)
    Abstract [en]

    Objective

    To develop and evaluate a multicolour flow cytometry method for analysis of microparticles (MPs) in fresh whole blood without any centrifugation steps or freezing/thawing procedure.

    Materials and methods

    Flow cytometry was performed using a FC500 MPL cytometer. The compensation in the protocol was performed based on the platelet population. Polystyrene microspheres 0.50–1.27 μm were used for size position, and the MP gate was set as particles 0.5–1.0 μm. Whole blood was incubated with annexin V and antibodies to tissue factor (TF), platelets (CD41 and CD62P), monocyte (CD14) and endothelial cells (CD144). For comparison, MPs from platelet free supernatant was used. The TF activity was evaluated by Calibrated Automated Thrombogram.

    Results

    Annexin V was used to distinguish true events from background noise. For standardization, each analysis included 10,000 events in the gate of platelets. There were 622(462–1001) MPannV+/10,000 platelets and of these, 66 (49–82)/10,000 platelets expressed TF. After correction for the individual platelet counts, the amount of circulating MPannV+ was 17.1 (12.1–24.9) × 109/L in whole blood, and of these, 10% (6–12%) expressed TF. The majority of the MPs expressed CD41, and 5.6% (2.2–6.9%) of these co-expressed TF. The amount of CD41 + MPannV+ tended to correlate to the TF activity in whole blood. There was no correlation between the MPannV+ in whole blood and MPs derived from platelet free supernatant. Patients with pulmonary arterial hypertension and stable coronary artery disease had increased concentrations of CD41 + MPannV+ in whole blood.

    Conclusion

    This multicolour flow cytometry assay in whole blood mimics the in vivo situation by avoiding several procedure steps interfering with the MP count. By standardized quantification of MPs a reference interval of MPs can be created.

  • 140.
    Christersson, Christina
    et al.
    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. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jönelid, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Thulin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    The change of the amount of circulating microparticles and their association to the general atherosclerotic burden after acute coronary syndrome2015In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, no S2, p. 214-214, article id OR312Article in journal (Other academic)
  • 141.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    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.
    The utility of coagulation activity for prediction of risk of mortality and cardiovascular events in guideline-treated myocardial infarction patients2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 4, p. 224-233Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite improved treatment of myocardial infarction (MI), real-world patients still suffer substantial risk for subsequent cardiovascular events. Little is known about coagulation activity shortly after MI and whether coagulation activity markers may identify patients at increased risk despite contemporary treatment.

    OBJECTIVE: To evaluate D-dimer concentration and thrombin generation potential shortly after discharge after MI and evaluate if these markers could predict the risk of future cardiovascular and bleeding events.

    METHODS: Unselected MI patients (n = 421) were included in the observational REBUS study (NCT01102933) and followed for two years. D-dimer concentrations, thrombin peak, and endogenous thrombin potential (ETP) were analyzed at inclusion (3-5 days after MI) and at early follow-up (after 2-3 weeks).

    RESULTS: Seventy-five patients (17.8%) experienced the composite endpoint (all-cause death, MI, congestive heart failure, or all-cause stroke), and 31 patients (7.4%) experienced a clinically relevant bleeding event. D-dimer concentrations at early follow-up were associated with the composite endpoint (HR [per SD increase] 1.51 [95% CI 1.22-1.87]) and with clinically relevant bleeding (HR [per SD increase] 1.80 [95% CI 1.32-2.44]). Thrombin generation potential was not significantly associated with either the composite endpoint or with clinically relevant bleeding. Higher thrombin peak and ETP at early follow-up were both inversely associated with stroke (HR [per SD increase] 0.50 [95% CI 0.30-0.81] and 0.43 [95% CI 0.22-0.83], respectively).

    CONCLUSION: In unselected MI patients treated according to contemporary guidelines, D-dimer measurements may identify patients at increased risk of new cardiovascular and bleeding events. The inverse association of thrombin generation potential and risk of stroke has to be further investigated.

  • 142.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The composition and daily variation of microparticles in whole blood in stable coronary artery disease2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 1Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The knowledge of circadian variation of microparticles (MPs) in stable coronary artery disease (SCAD) is limited. The aim of this study was to evaluate the daily variation of platelet-, endothelial- and monocyte-derived MPs in whole blood and their tissue factor expression (TF) in SCAD and whether these MPs were related to other endothelial and coagulation markers.

    MATERIALS AND METHODS: Serial blood samples from patients with SCAD were collected during one day. Flow cytometry was used to evaluate the amount of large MPs 0.5-1.0 μm, positive for annexin, and their expression of CD41, CD62P, CD144, CD14 and TF. The lag time and endogenous thrombin potential (ETP) was calculated by Calibrated Automated Thrombogram and soluble (s)P-selectin, sTF and vWF by ELISA.

    RESULTS: The majority of MPs in whole blood consisted of CD41 + MPs with no significant daily variation. In contrast, the concentration of CD62P + MPs described a daily variation with the lowest concentrations found in the evening (p = 0.031). CD62P + and CD144 + MPs had the highest expression of TF, 52.6% and 42.9%, respectively, and correlated to the endothelial activity evaluated by vWF. There was a circadian rhythm of lag time (p < 0.001) and ETP (p = 0.001). The CD62P+, CD14 + and CD144 + MPs correlated to the lag time.

    CONCLUSION: The different subsets of platelet-, endothelial- and monocyte-derived MPs do not present the same circadian variation and they differ in TF expression in SCAD. The MPs from activated platelets, endothelial cells and monocytes exist in low concentrations in whole blood but are related to the endothelial and coagulation activity found in SCAD.

  • 143.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Schollin, M.
    Alexander, J. H.
    Bersh, B. J.
    Horowitz, J.
    Hylek, E. M.
    Mohan, P.
    Granger, C. B.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Increased levels of D-dimer in atrial fibrillation identify patients with higher risk of thromboembolic events and death2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 969-969Article in journal (Other academic)
  • 144.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Thulin, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Microparticles during long-term follow-up after acute myocardial infarction: Association to atherosclerotic burden and risk of cardiovascular events2017In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, no 8, p. 1571-1581Article in journal (Refereed)
    Abstract [en]

    Microparticles (MPs) are formed from platelets (PMPs), endothelial cells (EMPs) and monocytes (MMPs), and in acute myocardial infarction (MI), there is an increase of MPs in the culprit artery. In this study MPs were evaluated in whole blood in 105 patients with MI at five time-points during a two-year follow-up (FU). Patients with non-ST elevated MI had higher concentrations of CD41+MPs compared to ST elevated MI patients (p=0.024). The concentrations of PMPs in whole blood increased during the time period (p<0.001), but no significant change over time was found for EMPs and MMPs. CD62P+MP counts were higher in MI patients with diabetes (p=0.020), and patients with hypertension had increased levels of CD14+MPs (p=0.004). The amount of CD62P+TF+MPs increased significantly during FU (p<0.001). Patients with atherosclerosis in three arterial beds, i.e. coronary, carotid and peripheral arteries, had lower concentrations of CD62P+TF+MPs (p=0.035) and CD144+TF+MPs (p=0.004) compared to patients with atherosclerosis in one or two arterial beds. Higher concentrations of CD62P+MPs early after MI were associated with an increased risk of cardiovascular events during FU, hazard ratio 3.32 (95 %C11.20-9.31). Only small variations in PMP, EMP and MMP concentrations were found during long-term FU after MI and their levels seem to reflect the underlying cardiovascular disease rather than the acute MI. PMPs expressing P-selectin might be a promising biomarker for predicting future cardiovascular events, but further studies are needed to confirm these results.

  • 145.
    Christersson, Christina
    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, 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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, J. H.
    Ansell, J.
    De Caterina, R.
    Gersh, B. J.
    Granger, C. B.
    Hanna, M.
    Horowitz, J. D.
    Huber, K.
    Husted, S.
    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.
    D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation: observations from the ARISTOTLE trial2014In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 12, no 9, p. 1401-1412Article in journal (Refereed)
    Abstract [en]

    BackgroundD-dimer is related to adverse outcomes in arterial and venous thromboembolic diseases. ObjectivesTo evaluate the predictive value of D-dimer level for stroke, other cardiovascular events, and bleeds, in patients with atrial fibrillation (AF) treated with oral anticoagulation with apixaban or warfarin; and to evaluate the relationship between the D-dimer levels at baseline and the treatment effect of apixaban vs. warfarin. MethodsIn the ARISTOTLE trial, 18201 patients with AF were randomized to apixaban or warfarin. D-dimer was analyzed in 14878 patients at randomization. The cohort was separated into two groups; not receiving vitaminK antagonist (VKA) treatment and receiving VKA treatment at randomization. ResultsHigher D-dimer levels were associated with increased frequencies of stroke or systemic embolism (hazard ratio [HR][Q4 vs. Q1]1.72, 95% confidence interval [CI]1.14-2.59, P=0.003), death (HR[Q4 vs. Q1]4.04, 95%CI3.06-5.33) and major bleeding (HR[Q4 vs. Q1]2.47, 95%CI1.77-3.45, P<0.0001) in the no-VKA group. Similar results were obtained in the on-VKA group. Adding D-dimer level to the CHADS(2) score improved the C-index from 0.646 to 0.655 for stroke or systemic embolism, and from 0.598 to 0.662 for death, in the no-VKA group. D-dimer level improved the HAS-BLED score for prediction of major bleeds, with an increase in the C-index from 0.610 to 0.641. There were no significant interactions between efficacy and safety of study treatment and D-dimer level. ConclusionIn anticoagulated patients with AF, the level of D-dimer is related to the risk of stroke, death, and bleeding, and adds to the predictive value of clinical risk scores. The benefits of apixaban were consistent, regardless of the baseline D-dimer level.

  • 146.
    Christersson, Christina
    et al.
    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, 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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H
    Alings, Marco
    De Caterina, Raffaele
    Gersh, Bernard J
    Granger, Christopher B
    Halvorsen, Sigrun
    Hanna, Michael
    Huber, Kurt
    Hylek, Elaine M
    Lopes, Renato D
    Oh, Byung-Hee
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Effect of apixaban compared with warfarin on coagulation markers in atrial fibrillation.2019In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 105, no 3, p. 235-242Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF).

    METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment.

    RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p<0.0001 for treatment differences for both). In patients on VKA at randomisation, F1+2 and D-dimer levels increased by 41% and 10%, respectively, with apixaban and decreased by 37% and 11%, respectively, with warfarin (p<0.0001 for treatment differences for both). sCD40L levels were slightly increased at 2 months, regardless of VKA or randomised treatment. Apixaban and warfarin also both reduced vWF antigen regardless of VKA treatment. The efficacy (stroke) and safety (bleeding) of apixaban compared with warfarin was similar irrespectively of biomarker levels at 2 months.

    CONCLUSIONS: Treatment with apixaban compared with warfarin for stroke prevention in patients with AF was associated with less reduction in thrombin generation and fibrin turnover. This effect of apixaban could contribute to the clinical results where apixaban was superior to warfarin both in stroke prevention and in reducing bleeding risk.

    TRIAL REGISTRATION NUMBER: NCT00412984.

  • 147. Chung, Sheng-Chia
    et al.
    Gedeborg, Rolf
    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 Surgical Sciences, Anaesthesiology and Intensive Care.
    Nicholas, Owen
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jeppsson, Anders
    Wolfe, Charles
    Heuschmann, Peter
    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.
    Deanfield, John
    Timmis, Adam
    Jernberg, Tomas
    Hemingway, Harry
    Acute myocardial infarction: a comparison of short-term survival in national outcome registries in Sweden and the UK2014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 383, no 9925, p. 1305-1312Article in journal (Refereed)
    Abstract [en]

    Background International research for acute myocardial infarction lacks comparisons of whole health systems. We assessed time trends for care and outcomes in Sweden and the UK. Methods We used data from national registries on consecutive patients registered between 2004 and 2010 in all hospitals providing care for acute coronary syndrome in Sweden and the UK. The primary outcome was all-cause mortality 30 days after admission. We compared effectiveness of treatment by indirect casemix standardisation. This study is registered with ClinicalTrials.gov, number NCT01359033. Findings We assessed data for 119 786 patients in Sweden and 391 077 in the UK. 30-day mortality was 7.6% (95% CI 7.4-7.7) in Sweden and 10.5% (10.4-10.6) in the UK. Mortality was higher in the UK in clinically relevant subgroups defined by troponin concentration, ST-segment elevation, age, sex, heart rate, systolic blood pressure, diabetes mellitus status, and smoking status. In Sweden, compared with the UK, there was earlier and more extensive uptake of primary percutaneous coronary intervention (59% vs 22%) and more frequent use of beta blockers at discharge (89% vs 78%). After casemix standardisation the 30-day mortality ratio for UK versus Sweden was 1.37 (95% CI 1.30-1.45), which corresponds to 11 263 (95% CI 9620-12 827) excess deaths, but did decline over time (from 1.47, 95% CI 1.38-1.58 in 2004 to 1.20, 1.12-1.29 in 2010; p=0.01). Interpretation We found clinically important differences between countries in acute myocardial infarction care and outcomes. International comparisons research might help to improve health systems and prevent deaths.

  • 148. Chung, Sheng-Chia
    et al.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gale, Chris P.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Deanfield, John
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Timmis, Adam
    Jernberg, Tomas
    Hemingway, Harry
    Comparison of hospital variation in acute myocardial infarction care and outcome between Sweden and United Kingdom: population based cohort study using nationwide clinical registries2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h3913Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To assess the between hospital variation in use of guideline recommended treatments and clinical outcomes for acute myocardial infarction in Sweden and the United Kingdom. DESIGN Population based longitudinal cohort study using nationwide clinical registries. SETTING AND PARTICIPANTS Nationwide registry data comprising all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART/RIKS-HIA, n=87; 119 786 patients) and the UK (NICOR/MINAP, n=242; 391 077 patients), 2004-10. MAIN OUTCOME MEASURES Between hospital variation in 30 day mortality of patients admitted with acute myocardial infarction. RESULTS Case mix standardised 30 day mortality from acute myocardial infarction was lower in Swedish hospitals (8.4%) than in UK hospitals (9.7%), with less variation between hospitals (interquartile range 2.6% v 3.5%). In both countries, hospital level variation and 30 day mortality were inversely associated with provision of guideline recommended care. Compared with the highest quarter, hospitals in the lowest quarter for use of primary percutaneous coronary intervention had higher volume weighted 30 day mortality for ST elevation myocardial infarction (10.7% v 6.6% in Sweden; 12.7% v 5.8% in the UK). The adjusted odds ratio comparing the highest with the lowest quarters for hospitals' use of primary percutaneous coronary intervention was 0.70 (95% confidence interval 0.62 to 0.79) in Sweden and 0.68 (0.60 to 0.76) in the UK. Differences in risk between hospital quarters of treatment for non-ST elevation myocardial infarction and secondary prevention drugs for all discharged acute myocardial infarction patients were smaller than for reperfusion treatment in both countries. CONCLUSION Between hospital variation in 30 day mortality for acute myocardial infarction was greater in the UK than in Sweden. This was associated with, and may be partly accounted for by, the higher practice variation in acute myocardial infarction guideline recommended treatment in the UK hospitals. High quality healthcare across all hospitals, especially in the UK, with better use of guideline recommended treatment, may not only reduce unacceptable practice variation but also deliver improved clinical outcomes for patients with acute myocardial infarction.

  • 149.
    Chung, Sheng-Chia
    et al.
    UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.;UCL, Inst Hlth Informat, London NW1 2DA, England..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Gale, Chris P.
    Univ Leeds, Cardiovasc Hlth Sci, Leeds, W Yorkshire, England..
    Timmis, Adam
    Barts Hlth London, Cardiovasc Biomed Res Unit, Natl Inst Hlth Res, London, England..
    Jernberg, Tomas
    Karolinska Inst, Dept Med, Sect Cardiol, Stockholm, Sweden..
    Hemingway, Harry
    UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.;UCL, Inst Hlth Informat, London NW1 2DA, England..
    Hospital Variation in AMI Outcome in UK and Sweden: Authors’ reply to Gupta2015In: BMJ-BRITISH MEDICAL JOURNAL, ISSN 1756-1833, Vol. 351, article id h5140Article in journal (Refereed)
  • 150.
    Collinson, Paul
    et al.
    St George Hosp, Dept Clin Blood Sci, London SW17 0RE, England.;St George Hosp, Dept Cardiol, London SW17 0RE, England.;Sch Med, London, England..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Type 2 myocardial infarction: the chimaera of cardiology?2015In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 101, no 21, p. 1697-1703Article, review/survey (Refereed)
    Abstract [en]

    The term type 2 myocardial infarction first appeared as part of the universal definition of myocardial infarction. It was introduced to cover a group of patients who had elevation of cardiac troponin but did not meet the traditional criteria for acute myocardial infarction although they were considered to have an underlying ischaemic aetiology for the myocardial damage observed. Since first inception, the term type 2 myocardial infarction has always been vague. Although attempts have been made to produce a systematic definition of what constitutes a type 2 myocardial infarction, it has been more often characterised by what it is not rather than what it is. Clinical studies that have used type 2 myocardial infarction as a diagnostic criterion have produced disparate incidence figures. The range of associated clinical conditions differs from study to study. Additionally, there are no agreed or evidence-based treatment strategies for type 2 myocardial infarction. The authors believe that the term type 2 myocardial infarction is confusing and not evidence-based. They consider that there is good reason to stop using this term and consider instead the concept of secondary myocardial injury that relates to the underlying pathophysiology of the primary clinical condition.

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