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  • 1401. Van Spall, Harriette G. C.
    et al.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yusuf, Salim
    Eikelboom, John W.
    Nieuwlaat, Robby
    Yang, Sean
    Kabali, Conrad
    Reilly, Paul A.
    Ezekowitz, Michael D.
    Connolly, Stuart J.
    Variation in Warfarin Dose Adjustment Practice Is Responsible for Differences in the Quality of Anticoagulation Control Between Centers and Countries An Analysis of Patients Receiving Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Trial2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 19, p. 2309-2316Article in journal (Refereed)
    Abstract [en]

    Background-The outcome of atrial fibrillation patients on warfarin partially depends on maintaining adequate time in therapeutic International Normalized Ratio range (TTR). Large differences in TTR have been reported between centers and countries. The association between warfarin dosing practice, TTR, and clinical outcomes was evaluated in Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial patients receiving warfarin. Methods and Results-RE-LY provided an algorithm for warfarin dosing, recommending no change for in-range, and 10% to 15% weekly dose changes for out-of-range International Normalized Ratio values. We determined whether dose adjustments were consistent with algorithm recommendations but could not verify whether providers used the algorithm. Using multilevel regression models to adjust for patient, center, and country characteristics, we assessed whether algorithm-consistent warfarin dosing could predict patient TTR and the composite outcome of stroke, systemic embolism, or major hemorrhage. We included 6022 nonvalvular atrial fibrillation patients from 912 centers in 44 countries. We found a strong association between the proportion of algorithm-consistent warfarin doses and mean country TTR (R-2 = 0.65). The degree of algorithm-consistency accounted for 87% of the between-center and 55% of the between-country TTR variation. Each 10% increase in center algorithm-consistent dosing independently predicted a 6.12% increase in TTR (95% confidence interval, 5.65-6.59) and an 8% decrease in rate of the composite clinical outcome (hazard ratio, 0.92; 95% confidence interval, 0.85-1.00). Conclusions-Adherence, intentional or not, to a simple warfarin dosing algorithm predicts improved TTR and accounts for considerable TTR variation between centers and countries. Systems facilitating algorithm-based warfarin dosing could optimize anticoagulation quality and improve clinical outcomes in atrial fibrillation on a global scale. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00262600. (Circulation. 2012; 126: 2309-2316.)

  • 1402.
    Vantler, M.
    et al.
    Univ Cologne, D-50931 Cologne, Germany..
    Jesus, J.
    Univ Cologne, D-50931 Cologne, Germany..
    Leppaenen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Chen, X.
    Univ Cologne, D-50931 Cologne, Germany..
    Gerhardt, M.
    Univ Cologne, D-50931 Cologne, Germany..
    Berghausen, E.
    Univ Cologne, D-50931 Cologne, Germany..
    Zierden, M.
    Univ Cologne, D-50931 Cologne, Germany..
    Baldus, S.
    Univ Cologne, D-50931 Cologne, Germany..
    Zhao, J. J.
    Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA USA..
    Rosenkranz, S.
    Univ Cologne, D-50931 Cologne, Germany..
    PI3Kalpha induced SMC migration and cell cycle progression is crucial for neointima formation following vascular injury2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 375-375Article in journal (Other academic)
  • 1403. Vantler, M.
    et al.
    Jesus, J.
    Leppaenen, Olli
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Chen, X.
    Ten Freyhaus, H.
    Caglayan, E.
    Blaschke, F.
    Zhao, J. J.
    Rosenkranz, S.
    Role of class IA PI 3-kinase isoforms in neointima formation following balloon angioplasty: only p110alpha is important2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 114-115Article in journal (Other academic)
  • 1404.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alfredsson, Joakim
    Angerås, Oskar
    Bohm, Felix
    Calais, Fredrik
    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.
    Koul, Sasha
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindholm, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Timing Of Pci In Patients With Non-St-Elevation Myocardial Infarction: A Swedeheart Study2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 44-44Article in journal (Other academic)
  • 1405.
    Varenhorst, Christoph
    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.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Braun, O. O.
    Storey, R. F.
    Mahaffey, K. W.
    Cannon, C.
    Himmelmann, A.
    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.
    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.
    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.
    Difference in causes of death between ticagrelor and clopidogrel in the PLATO trial2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 827-827Article in journal (Other academic)
  • 1406.
    Varenhorst, Christoph
    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.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Braun, Oscar Ö
    Storey, Robert F
    Mahaffey, Kenneth W
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cannon, Christopher P
    Scirica, Benjamin M
    Himmelmann, Anders
    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.
    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.
    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.
    Causes of mortality with ticagrelor compared with clopidogrel in acute coronary syndromes2014In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 100, no 22, p. 1762-1769Article in journal (Refereed)
    Abstract [en]

    Objective

    To describe specific causes of death and evaluate whether bleeding events and infection contributed to mortality in all ticagrelor-treated and clopidogrel-treated patients with acute coronary syndromes.

    Methods

    In the PLATelet inhibition and patient Outcomes (PLATO) trial, ticagrelor significantly reduced rates of vascular and total death compared with clopidogrel. In the 905 patients who died postenrolment in the PLATO trial (n=18 624), reviewers, blinded to study treatment, subclassified direct causes of death and evaluated whether infection or bleeding events contributed to fatal events.

    Results

    Among vascular deaths, there were significantly fewer sudden deaths (63 (0.7%) vs 98 (1.1%), p<0.01) but no significant difference in deaths caused by acute myocardial infarction (179 (1.9%) vs 194 (2.1%), p=0.43) or heart failure (31 (0.3%) vs 42 (0.5%), p=0.20) with ticagrelor compared with clopidogrel. For non-vascular deaths, there was no difference between treatments in deaths directly caused by infection. Although, patients treated with ticagrelor were at lower risk for death where infection was either a direct cause or contributed to death (51 (0.5%) vs 76 (0.8%), HR 0.67 (0.47 to 0.95), p<0.05) but not for bleeding (42 (0.5%) vs 42 (0.5%), HR 0.99 (0.65 to 1.53), p=0.98).

    Conclusions

    In this post hoc analysis, ticagrelor compared with clopidogrel reduced total and cardiovascular mortality, which appeared to be mainly mediated by a reduction in sudden death. Importantly, bleeding causing or contributing to death did not differ between treatments.

    Clinical trial registration number

    NCT00391872 (http://www.clinicaltrial.gov).

  • 1407.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Scirica, Benjamin M.
    Hogue, Charles W.
    Asenblad, Nils
    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.
    Storey, Robert F.
    Steg, Gabriel
    Horrow, Jay
    Mahaffey, Kenneth W.
    Becker, Richard C.
    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.
    Cannon, Christopher P.
    Brandrup-Wognsen, Gunnar
    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.
    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.
    Factors Contributing to the Lower Mortality With Ticagrelor Compared With Clopidogrel in Patients Undergoing Coronary Artery Bypass Surgery2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. 1623-1630Article in journal (Refereed)
    Abstract [en]

    Objectives This study investigated the differences in specific causes of post-coronary artery bypass graft surgery (CABG) deaths in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background In the PLATO trial, patients assigned to ticagrelor compared with clopidogrel and who underwent CABG had significantly lower total and cardiovascular mortality. Methods In the 1,261 patients with CABG performed within 7 days after stopping study drug, reviewers blinded to treatment assignment classified causes of death into subcategories of vascular and nonvascular, and specifically identified bleeding or infection events that either caused or subsequently contributed to death. Results Numerically more vascular deaths occurred in the clopidogrel versus the ticagrelor group related to myocardial infarction (14 vs. 10), heart failure (9 vs. 6), arrhythmia or sudden death (9 vs. 3), and bleeding, including hemorrhagic stroke (7 vs. 2). Clopidogrel was also associated with an excess of nonvascular deaths related to infection (8 vs. 2). Among factors directly causing or contributing to death, bleeding and infections were more common in the clopidogrel group compared with the ticagrelor group (infections: 16 vs. 6, p < 0.05, and bleeding: 27 vs. 9, p < 0.01, for clopidogrel and ticagrelor, respectively). Conclusions The mortality reduction with ticagrelor versus clopidogrel following CABG in the PLATO trial was associated with fewer deaths from cardiovascular, bleeding, and infection complications.

  • 1408.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bodegard, J.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Jerstrom, S.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Akesson, J.
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Brorsson, H.
    Statisticon AB, Uppsala, Sweden..
    Alfredsson, J.
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Fac Hlth Sci, Linkoping, Sweden..
    Albertsson, P.
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Karlsson, J. E.
    Ryhov Cty Hosp, Dept Internal Medicin, Jonkoping, Sweden..
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Dept Med Sci, Cardiol, Uppsala, Sweden..
    Effects of interactive patient support with a smartphone app on drug adherence and lifestyle changes in myocardial infarction patients2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 1 Supplement, p. 1202-1202Article in journal (Other academic)
  • 1409.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eriksson, Niclas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Barratt, Bryan J.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine.
    Becker, Richard C.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Katus, Hugo A.
    Husted, Steen
    Steg, Ph. Gabriel
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Voora, Deepak
    Teng, Renli
    Storey, Robert F.
    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.
    Effect of genetic variations on ticagrelor plasma levels and clinical outcomes2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 29, p. 1901-1912Article in journal (Refereed)
    Abstract [en]

    Aims Ticagrelor, a direct-acting P2Y(12)-receptor antagonist, is rapidly absorbed and partly metabolized to the major metabolite AR-C124910XX (ARC). To identify single-nucleotide polymorphisms (SNPs) associated with pharmacokinetics of ticagrelor and clinical outcomes, we performed a genome-wide association study (GWAS) in patients treated with ticagrelor in the PLATO trial. Methods and results A two-stage design was used for the GWAS with discovery (discovery phase: n = 1812) and replication cohorts (replication phase: n = 1941). The steady-state area under the curve (AUCss) values, estimated by the population pharmacokinetic (PK) models, were log transformed and analysed on a genome-wide scale using linear regression. SNPs were analysed against clinical events using Cox-regression in 4990 patients. An SNP (rs113681054) in SLCO1B1 was associated with levels of ticagrelor (P = 1.1 x 10(-6)) and ARC (P = 4.6 x 10(-13)). This SNP is in linkage disequilibrium with a functional variant (rs4149056) that results in decreased OATP1B1 transporter activity. Ticagrelor levels were also associated with two independent SNPs (rs62471956, P = 7.7 x 10(-15) and rs56324128, P = 9.7 x 10(-12)) in the CYP3A4 region. Further, ARC levels were associated with rs61361928 (P = 3.0 x 10(-14)) in UGT2B7. At all loci, the effects were small. None of the identified SNPs that affected ticagrelor PK were associated with the primary composite outcome (cardiovascular death myocardial infarction, and stroke), non-CABG-related bleeds or investigator-reported dyspnoea. Conclusion In patients with ACS, ticagrelor pharmacokinetics is influenced by three genetic loci (SLCO1B1, UGT2B7, and CYP3A4). However, the modest genetic effects on ticagrelor plasma levels did not translate into any detectable effect on efficacy or safety during ticagrelor treatment.

  • 1410.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hasvold, Pal
    AstraZeneca Nord Baltic, Sodertalje, Sweden.;AstraZeneca R&D, Molndal, Sweden..
    Johansson, Saga
    AstraZeneca R&D, Molndal, Sweden..
    Janzon, Magnus
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Albertsson, Per
    Univ Gothenburg, Sahlgrenska Acad, Gothenburg, Sweden..
    Leosdottir, Margret
    Lund Univ, Dept Cardiol, Skane Univ Hosp, Malmo, Sweden..
    Hambraeus, Kristina
    Falun Cty Hosp, Falun, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Solna Karolinska Univ Hosp, Karolinska Inst, Dept Med, Sect Cardiol, Stockholm, Sweden..
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Culprit and Nonculprit Recurrent Ischemic Events in Patients With Myocardial Infarction: Data From SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies)2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007174Article in journal (Refereed)
    Abstract [en]

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

  • 1411.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clin Res Ctr MTC, MTC, S-75237 Uppsala, Sweden.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clin Res Ctr MTC, MTC, S-75237 Uppsala, Sweden.
    Which antiplatelet agent for whom? Which patient populations benefit most from novel antiplatelet agents (ticagrelor, prasugrel)?2012In: Current Cardiology Reports, ISSN 1523-3782, E-ISSN 1534-3170, Vol. 14, no 4, p. 486-492Article in journal (Refereed)
    Abstract [en]

    Antiplatelet treatment is a cornerstone for patients with acute coronary syndromes treated invasively or conservatively to reduce the risk of early and late occurring ischemic complications and to improve survival. Compared to clopidogrel, the novel antiplatelet agents prasugrel and ticagrelor provide faster and more consistent inhibition of platelet aggregation and result in substantially improved clinical outcome in patients with acute coronary syndromes but also an increased bleeding risk. Therefore, balancing the rope between safety and efficacy of treatment is crucial for optimizing outcome. An understanding of the similarities but also differences in pharmacological effect, clinical trial design, and outcome is crucial for understanding which patient populations benefit the most from novel antiplatelet treatments. This review provides recommendations for their optimal use.

  • 1412.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Erlinge, David
    Braun, Oscar O.
    Brandt, John T.
    Winters, Kenneth J.
    Jakubowski, Joseph A.
    Olofsson, Sylvia
    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.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Assessment of P2Y(12) inhibition with the point-of-care device VerifyNow P2Y12 in patients treated with prasugrel or clopidogrel coadministered with aspirin2009In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 157, no 3, p. 562.e1-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Variability in response to thienopyridines has led to the development of point-of-care devices to assess adenosine diphosphate (ADP)-induced platelet aggregation. These tests need to be evaluated in comparison to reference measurements of P2Y(12) function during different thienopyridine treatments. METHODS: After a run-in on 75 mg aspirin, 110 subjects were randomized to double-blind treatment with clopidogrel 600 mg loading dose (LD)/75 mg maintenance dose (MD) or prasugrel 60 mg LD/10 mg MD. Antiplatelet effects were evaluated by VerifyNow P2Y12 (VN-P2Y12) device (Accumetrics, San Diego, CA), vasodilator-stimulated phosphoprotein (VASP) phosphorylation assay, and light transmission aggregometry (LTA). Prasugrel's and clopidogrel's active metabolite concentration were also determined. RESULTS: Dose- and time-dependent inhibition of P2Y(12) was evident with VN-P2Y12. There was strong correlation with VN-P2Y12 and VASP or LTA for all treatments through a wide range of P2Y(12) function. At high levels of P2Y(12) inhibition, platelet function measured by VN-P2Y12 was maximally inhibited and could not reflect further changes seen with VASP or LTA methods. Correlation was also observed between exposure to clopidogrel's active metabolite and VN-P2Y12 during MD and LD, whereas it was observed only with prasugrel MD. CONCLUSION: The VN-P2Y12 correlated strongly with inhibition of P2Y(12) function, as measured with either VASP or LTA. VN-P2Y12 also correlated to exposure to the active metabolite of prasugrel and clopidogrel up to levels associated with assumed saturation of the P2Y(12) receptor.

  • 1413.
    Varenhorst, Christoph
    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.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Sundstrom, Anders
    Hasvold, Pal
    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.
    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.
    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.
    Duration of dual antiplatelet treatment with clopidogrel and aspirin in patients with acute coronary syndrome2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 15, p. 969-978Article in journal (Refereed)
    Abstract [en]

    Aims Dual antiplatelet treatment (DAPT) is a cornerstone in the treatment of acute coronary syndrome(ACS) but the optimal treatment duration is unclear. We aimed to evaluate the effect of DAPT duration with clopidogrel and aspirin on the recurrence of ischaemic events and bleeding in a large, unselected ACS population. Methods and results We performed a prospective, observational cohort study of patients in Sweden (n= 56 440) admitted for ACS, with prescribed DAPT and hospitalized between January 2006 and July 2010. Patients were obtained from the SWEDEHEART register and data were merged with registers from the National Board of Health and Welfare. Depending on dispensed clopidogrel tablets, patients were divided into groups based on DAPT duration with clopidogrel and aspirin (3 months: 84-100 clopidogrel tablets (t);>3 months: >100 t; 6 months: 168-200 t; >6 months:>200 t). For the combined primary endpoint, defined as all-cause death, stroke, or re-infarction, only patients with an uneventful first 3-month period (no death, stroke, re-infarction, bleeding, stent thrombosis, or revascularization) were included. The incidence of the primary endpoint was 45 events per 1000 person-years in the >3 months DAPT group compared with 65 events per 1000 person-years in the >3 months DAPT group [ adjusted HR 0.84, 95% Cl (0.75; 0.95)]. Bleeding was more common in the >3 months treatment group (adjusted HR 1.56, 95% Cl (1.18; 2.07), but the number of events was small. For >6 vs >6 months DAPT, the adjusted HR for the combined endpoint was 0.75 with 95% Cl (0.59; 0.95). Conclusion In this contemporary, large real-life ACS population, DAPT for more than 3 months compared with a shorter duration was associated with a lower risk of death, stroke, or re-infarction.

  • 1414.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnston, Nina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    RE: Letter to the editor, Dr Cheng et al: "Smartphone apps and secondary prevention after myocardial infarction-How can long-term usage be improved?"2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 184, p. e2-e2Article in journal (Other academic)
  • 1415.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Koul, Sasha
    Department of Cardiology, Lund University.
    Erlinge, David
    Department of Cardiology, Lund University.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine. 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. 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, Internal Medicine. 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, Internal Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Relationship between Clopidogrel-Induced Platelet P2Y12 Inhibition and Stent Thrombosis or Myocardial Infarction after Percutaneous Coronary Intervention: A Case-Control Study2011In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 162, no 2, p. 363-371Article in journal (Refereed)
    Abstract [en]

    Aims: Platelet inhibition levels were investigated in patients with previous angiographically confirmed stent thrombosis (ST), myocardial infarction (MI) and controls.

    Methods and Results: Using The Swedish Coronary Angiography and Angioplasty Registry we identified patients with angiographically confirmed ST (n=48) or MI (n=30) while on dual antiplatelet therapy within 6 months of percutaneous coronary intervention (PCI) and matched control patients (n=78) with none of these events in the same setting. On-clopidogrel platelet reactivity was measured with VerifyNow™ P2Y12 and vasodilator stimulated phosphoprotein phosphorylation (VASP-P) assay.

    The mean P2Y12 reaction units (PRU) was higher (246.8 ± 75.9 vs. 200.0 ± 82.7, p=0.001) in ST patients compared to controls. The optimal cut-off for ST was ≥222 PRU (area under the curve 0.69, p<0.0001) in a receiver operating characteristics (ROC) analysis, which was identical to the cut-off level defined as the proportion of controls below the 30th percentile of P2Y12 inhibition distribution in patients with ST.  The cut-off level resulted in 70.2% sensitivity and 67.3% specificity. There was no significant difference in mean PRU but a higher device-reported % inhibition (45.1 ± 23.8 vs 32.1 ± 23.2, p=0.04) in patients with MI compared to controls. Results with the VASP-P assay were not related to the occurrence of ST or MI.

    Conclusion: Stent thrombosis was associated with high on-clopidogrel platelet reactivity measured with VerifyNow™. Spontaneous MI in stented patients on clopidogrel treatment was not. There was, however, a substantial overlap in clopidogrel platelet reactivity response between patients with and without on-treatment ST.

  • 1416.
    Varenhorst, Christoph
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lindholm, Martin
    Vasteras Cty Hosp, Dept Internal Med, Cardiol, Vasteras, Sweden.
    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.
    Olivecrona, Göran
    Lund Univ, Dept Cardiol, Lund, Sweden.
    Jensens, Ulf
    Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden.
    Nilsson, Johan
    Umea Univ, Heart Ctr, Dept Cardiol, Umea, Sweden.
    Carlsson, Jorg
    Linnaeus Univ, Fac Hlth & Life Sci, Kalmar, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Stent thrombosis rates the first year and beyond with new- and old-generation drug-eluting stents compared to bare metal stents2018In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 107, no 9, p. 816-823Article in journal (Refereed)
    Abstract [en]

    Old-generation drug-eluting coronary stents (o-DES) have despite being safe and effective been associated with an increased propensity of late stent thrombosis (ST). We evaluated ST rates in o-DES, new-generation DES (n-DES) and bare metal stents (BMS) the first year (< 1 year) and beyond 1 year (> 1 year). We evaluated all implantations with BMS, o-DES (Cordis Cypher, Boston Scientific Taxus Libert, and Medtronic Endeavor) and n-DES in the Swedish coronary angiography and angioplasty registry (SCAAR) between 1 January 2007 and 8 January 2014 (n = 207 291). All cases of ST (n = 2 268) until 31 December 2014 were analyzed. The overall risk of ST was lower in both n-DES and o-DES compared with BMS up to 1 year (n-DES versus BMS: adjusted risk ratio (RR) 0.48 (0.41-0.58) and o-DES versus BMS: 0.56 (0.46-0.67), both p < 0.001). From 1 year after stent implantation and onward, the risk for ST was higher in o-DES compared with BMS [adjusted RR, 1.82 (1.47-2.25], p < 0.001). N-DES were associated with similar low ST rates as BMS from 1 year and onward [adjusted RR 1.21 (0.94-1.56), p = 0.135]. New-generation DES were associated with lower ST rates in comparison to BMS during the first-year post-stenting. After 1 year, n-DES and BMS were associated with similar ST rates. This study was a retrospective observational study and as such did not require clinical trial database registration.

  • 1417.
    Varenhorst, Christoph
    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.
    Åkerblom, Axel
    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.
    Renlund, Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kunadian, V.
    Newcastle Univ, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England..
    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.
    Steg, P. G.
    Hop Bichat Claude Bernard, Dept Hosp Univ FIRE, Paris, France..
    Katus, H. A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Himmelmann, A.
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Aylward, P.
    Flinders Univ S Australia, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia.;Med Ctr, Adelaide, SA, Australia..
    Maurer, G.
    Med Univ Vienna, Vienna, Austria..
    Storey, R. F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Armstrong, P. W.
    Univ Alberta, Canadian VIGOUR Ctr, Edmonton, AB, Canada..
    Gibson, M.
    Harvard Med Sch, Dept Med, Beth Israel Deaconess Med Ctr, Boston, MA USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Successful reperfusion is associated with lower levels of markers of myocardial damage and dysfunction in ST-elevation but not in non-ST-elevation myocardial infarction: insights from the PLATO trial2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1282-1283Article in journal (Refereed)
  • 1418. Vargas, Kris G
    et al.
    Haller, Paul M
    Jäger, Bernhard
    Tscharre, Maximilian
    Binder, Ronald K
    Mueller, Christian
    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.
    Huber, Kurt
    Variations on classification of main types of myocardial infarction: a systematic review and outcome meta-analysis2019In: Clinical Research in Cardiology, ISSN 1861-0684, E-ISSN 1861-0692, Vol. 108, no 7, p. 749-762Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Classifying myocardial infarction into type 1 (T1MI) or type 2 (T2MI) remains a challenge in clinical practice. We aimed to identify factors contributing to variation in the classifications of MI into type 1 or type 2. In addition, pooled analyses of long-term mortality and reinfarction outcomes were performed.

    METHODS: We searched Medline, Embase and Web of Science through January 2018 for observational studies or clinical trials classifying patients as either T1MI or T2MI. Studies with baseline characteristics allowing a comparison between both groups were included. Inverse variance random-effects models were used to pool risk ratios (RR).

    RESULTS: Overall, 93,194 patients from 20 included observational studies were classified as T1MI and 9291 as T2MI; corresponding to 87.9% and 8.8% of all patients diagnosed with MI. Inclusion of ST-elevation MI patients was inconsistent among studies. Coronary angiography was performed in 77.7% and 31.5% of all patients with T1MI and T2MI, respectively. From a subgroup of 11 studies, percutaneous coronary intervention was performed in 79.2% of all patients classified as T1MI (range 44.2-93.0%) and 40.2% of all T2MI patients (range 0-87.5%). A meta-analysis of 6 studies (44,366 in total) on 2-year mortality showed worse outcome among T2MI patients (RR: 1.52, CI 1.07-2.17, P = 0.02; I2 = 92%). Risk of reinfarction at 1.6 years was higher among T2MI patients (RR: 1.68, CI 1.22-2.31, P = 0.001; I2 = 9%).

    CONCLUSIONS: Classification of T1MI and T2MI varies widely among studies. A standardized approach with clear definitions is needed to avoid misclassification and ensure appropriate patient management.

  • 1419.
    Vedin, Ola
    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.
    Should dental health now be considered a marker of coronary heart disease?2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 33, p. 2200-2201Article in journal (Other academic)
  • 1420.
    Vedin, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Budaj, Andrzej
    Denchev, Stephan
    Harrington, Robert A
    Koenig, Wolfgang
    Soffer, Joseph
    Sritara, Piyamitr
    Stebbins, Amanda
    Stewart, Ralph Ha
    Swart, Henk P
    Viigimaa, Margus
    Vinereanu, Dragos
    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.
    White, Harvey D
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Tooth loss is independently associated with poor outcomes in stable coronary heart disease.2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 8, p. 839-846Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: We investigated associations between self-reported tooth loss and cardiovascular outcomes in a global stable coronary heart disease cohort.

    METHODS: We examined 15,456 patients from 39 countries with stable coronary heart disease (prior myocardial infarction, prior revascularisation or multivessel coronary heart disease) in the STABILITY trial. At baseline, patients reported number of teeth (26-32 (all), 20-25, 15-19, 1-14 and no teeth) and were followed for 3.7 years. Cox regression models adjusted for cardiovascular risk factors and socioeconomic status, determined associations between tooth loss level (26-32 teeth: lowest level; no teeth: highest level) and cardiovascular outcomes.

    RESULTS: After adjustment, every increase in tooth loss level was associated with an increased risk of the primary outcome, the composite of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke (hazard ratio 1.06; 95% confidence interval 1.02-1.10), cardiovascular death (1.17; 1.10-1.24), all-cause death (1.16; 1.11-1.22) and non-fatal or fatal stroke (1.14; 1.04-1.24), but not with non-fatal or fatal myocardial infarction (0.99; 0.94-1.05). Having no teeth, compared to 26-32 teeth, entailed a significantly higher risk of the primary outcome (1.27 (1.08, 1.49)), cardiovascular death (1.85 (1.45, 2.37), all-cause death (1.81 (1.50, 2.20)) and stroke (1.67 (1.15, 2.39)).

    CONCLUSIONS: In this large global cohort of patients with coronary heart disease, self-reported tooth loss predicted adverse cardiovascular outcomes and all-cause death independent of cardiovascular risk factors and socioeconomic status.

  • 1421.
    Vedin, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Budaj, Andrzej
    Denchev, Stephan
    Harrington, Robert
    Uppsala Univ, Cardiol, Dept Med Sci, Uppsala, Sweden..
    Koenig, Wolfgang
    Soffer, Joseph
    Sritara, Piyamitr
    Stebbins, Amanda
    Stewart, Ralph
    Swart, Henk
    Viigimaa, Margus
    Vinereanu, Dragos
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    White, Harvey
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Tooth Loss Is Independently Associated With Adverse Outcome But Not Myocardial Infarction In Patients With Chronic Coronary Heart Disease2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 65, no 10, p. A1421-A1421Article in journal (Other academic)
  • 1422.
    Vedin, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Gallup, Dianne
    Neely, Megan L
    Stewart, Ralph
    Koenig, Wolfgang
    Budaj, Andrzej
    Sritara, Piyamitr
    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.
    White, Harvey D
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Periodontal disease in patients with chronic coronary heart disease: Prevalence and association with cardiovascular risk factors2015In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 22, no 6, p. 771-778Article in journal (Refereed)
    Abstract [en]

    Aim There are reported links between periodontal disease (PD) and cardiovascular (CV) risk but data are lacking, especially from populations with established coronary heart disease (CHD). This study describes self-reported indicators of PD and associations with CV risk factors in a global stable CHD population.

    Methods and results A total of 15,828 participants in the global STABILITY trial underwent a physical examination, blood sampling, and completed a lifestyle questionnaire. They reported remaining number of teeth (none, 114, 1520, 2125 or 2632 (all)) and frequency of gum bleeding (never/rarely, sometimes, often or always). Adjusted linear and logistic regression models assessed associations between tooth loss, gum bleeding, and socioeconomic and CV risk factors.

    A total of 40.9% of participants had <15 remaining teeth; 16.4% had no teeth; and 25.6% reported gum bleeding with large differences in prevalence among countries, regions and ethnic groups. Less tooth loss was associated with lower levels of glucose, low-density lipoprotein (LDL) cholesterol, systolic blood pressure, waist circumference and hs-CRP; higher estimated glomerular filtration rate; decreased odds for diabetes and smoking, and increased odds for higher education, alcohol consumption and work stress. Gum bleeding was associated with higher LDL cholesterol and systolic blood pressure; decreased odds for smoking, but increased odds for higher education, alcohol consumption and stress.

    Conclusion Self-reported indicators of PD were common in this chronic CHD population and were associated with an increasing socioeconomic and CV risk factor burden. However, causality between self-reported PD and CV risk and outcome needs further investigation.

  • 1423.
    Vedin, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Koenig, Wolfgang
    Stewart, Ralph
    White, Harvey
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Associations Between Tooth Loss And Prognostic Biomarkers And The Risk For Cardiovascular Events In Patients With Coronary Heart DiseaseManuscript (preprint) (Other academic)
  • 1424.
    Vedin, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Avezum, Alvaro
    Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil..
    Budaj, Andrzej
    Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland..
    Flather, Marcus D.
    Univ East Anglia, Norwich Med Sch, Norwich, Norfolk, England.;Norfolk & Norwich Univ Hosp, Norwich Med Sch, Norwich, Norfolk, England..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Koenig, Wolfgang
    Univ Ulm, Dept Internal Med Cardiol 2, Med Ctr, Ulm, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovascular Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Soffer, Joseph
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, King Of Prussia, PA USA..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Steg, Philippe Gabriel
    INSERM Unite 1148, Paris, France.;Dept Hosp Univ FIRE, Hop Bichat, AP HP, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;NHLI Imperial Coll, Royal Brompton Hosp, ICMS, London, England..
    Stewart, Ralph A. H.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    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.
    White, Harvey D.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Associations between tooth loss and prognostic biomarkers and the risk for cardiovascular events in patients with stable coronary heart disease2017In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 245, p. 271-276Article in journal (Refereed)
    Abstract [en]

    Background:

    Underlying mechanisms behind the hypothesized relationship between periodontal disease (PD) and coronary heart disease (CHD) have been insufficiently explored. We evaluated associations between self-reported tooth loss-a marker of PD- and prognostic biomarkers in 15,456 (97%) patients with stable CHD in the global STABILITY trial.

    Methods and results:

    Baseline blood samples were obtained and patients reported their number of teeth according to the following tooth loss levels: "26-32 (All)" [lowest level], "20-25", "15-19", "1-14", and "No Teeth" [highest level]. Linear and Cox regression models assessed associations between tooth loss levels and biomarker levels, and the relationship between tooth loss levels and outcomes, respectively.

    After multivariable adjustment, the relative biomarker increase between the highest and the lowest tooth loss level was: high-sensitivity C-reactive protein 1.21 (95% confidence interval, 1.14-1.29), interleukin 6 1.14 (1.10-1.18), lipoprotein-associated phospholipase A(2) activity 1.05 (1.03-1.06), growth differentiation factor 15 1.11 (1.08-1.14), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1.18 (1.11-1.25). No association was detected for high-sensitivity troponin T 1.02 (0.98-1.05). Some attenuation of the relationship between tooth loss and outcomes resulted from the addition of biomarkers to the multivariable analysis, of which NT-proBNP had the biggest impact.

    Conclusions:

    A graded and independent association between tooth loss and several prognostic biomarkers was observed, suggesting that tooth loss and its underlying mechanisms may be involved in multiple pathophysiological pathways also implicated in the development and prognosis of CHD. The association between tooth loss and cardiovascular death and stroke persisted despite comprehensive adjustment including prognostic biomarkers.

  • 1425.
    Vedin, Ola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Avezum, Alvaro
    Budaj, Andrzej
    Flather, Marcus
    Harrington, Robert
    Koenig, Wolfgang
    Soffer, Joseph
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Steg, Philippe
    Stewart, Ralph
    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.
    White, Harvey
    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.
    The Relationship Between Tooth Loss, Cardiovascular Biomarkers And Outcomes In Patients With Stable Coronary Heart Disease2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 1969-1969Article in journal (Other academic)
  • 1426.
    Vedin, Ola
    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.
    Lam, Carolyn S. P.
    Natl Heart Ctr Singapore, Singapore, Singapore.;Duke NUS Med Sch, Singapore, Singapore..
    Koh, Angela S.
    Natl Heart Ctr Singapore, Singapore, Singapore.;Duke NUS Med Sch, Singapore, Singapore..
    Benson, Lina
    Reg Canc Ctr Stockholm Gotland, Stockholm, Sweden..
    Teng, Tiew Hwa Katherine
    Natl Heart Ctr Singapore, Singapore, Singapore.;Univ Western Australia, Sch Populat Hlth, Perth, WA, Australia..
    Tay, Wan Ting
    Natl Heart Ctr Singapore, Singapore, Singapore..
    Braun, Oscar O.
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden..
    Savarese, Gianluigi
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Dahlstrom, Ulf
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lund, Lars H.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Significance of Ischemic Heart Disease in Patients With Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction: A Nationwide Cohort Study2017In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 10, no 6, article id e003875Article in journal (Refereed)
    Abstract [en]

    Background-The pathogenic role of ischemic heart disease (IHD) in heart failure (HF) with reduced ejection fraction (HFrEF; EF <40%) is well established, but its pathogenic and prognostic significance in HF with midrange (HFmrEF; EF 40%-50%) and preserved EF (HFpEF; EF >= 50%) has been much less explored.

    Methods and Results-We evaluated 42 987 patients from the Swedish Heart Failure Registry with respect to baseline IHD, outcomes (IHD, HF, cardiovascular events, and all-cause death), and EF change during a median follow-up of 2.2 years. Overall, 23% had HFpEF (52% IHD), 21% had HFmrEF (61% IHD), and 55% had HFrEF (60% IHD). After multivariable adjustment, associations with baseline IHD were similar for HFmrEF and HFrEF and lower in HFpEF (risk ratio, 0.91 [0.89-0.93] versus HFmrEF and risk ratio, 0.90 [0.88-0.92] versus HFrEF). The adjusted risk of IHD events was similar for HFmrEF versus HFrEF and lower in HFpEF (hazard ratio, 0.89 [0.84-0.95] versus HFmrEF and hazard ratio, 0.84 [0.80-0.90] versus HFrEF). After adjustment, prevalent IHD was associated with increased risk of IHD events and all other outcomes in all EF categories except all-cause mortality in HFpEF. Those with IHD, particularly new IHD events, were also more likely to change to a lower EF category and less likely to change to a higher EF category over time.

    Conclusions-HFmrEF resembled HFrEF rather than HFpEF with regard to both a higher prevalence of IHD and a greater risk of new IHD events. Established IHD was an important prognostic factor across all HF types.

  • 1427. Velagaleti, Raghava S.
    et al.
    Gona, Philimon
    Sundström, Johan
    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.
    Larson, Martin G.
    Siwik, Deborah
    Colucci, Wilson S.
    Benjamin, Emelia J.
    Vasan, Ramachandran S.
    Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality2010In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 30, no 11, p. 2283-2288Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE-: To evaluate if biomarkers reflecting left ventricular/vascular extracellular matrix remodeling are associated with cardiovascular disease (CVD) and death in the community. METHODS AND RESULTS-: In 922 Framingham Study participants (mean age, 58 years; 56% women), we related circulating concentrations of matrix metalloproteinase-9 (binary variable: detectable versus undetectable), log of tissue inhibitor of matrix metalloproteinase-1, and log of procollagen type III aminoterminal peptide (PIIINP) to incident CVD and death. On follow-up (mean, 9.9 years), 51 deaths and 81 CVD events occurred. Each SD increment of log of tissue inhibitor of matrix metalloproteinase-1 and log-PIIINP was associated with multivariable-adjusted hazards ratios of 1.72 (95% CI, 1.30 to 2.27) and 1.47 (95% CI, 1.11 to 1.96), respectively, for mortality risk. Log-PIIINP concentrations were also associated with CVD risk (hazard ratio [95% CI] per SD, 1.35 [1.05 to 1.74]). Death and CVD incidence rates were 2-fold higher in participants with both biomarkers higher than the median (corresponding hazard ratio [95% CI], 2.78 [1.43 to 5.40] and 1.77 [1.04 to 3.03], respectively) compared with those with either or both less than the median. The inclusion of both biomarkers improved the C-statistic (for predicting mortality) from 0.78 to 0.82 (P=0.03). Matrix metalloproteinase-9 was unrelated to either outcome. CONCLUSION-: Higher circulating tissue inhibitor of matrix metalloproteinase-1 and PIIINP concentrations are associated with mortality, and higher PIIINP is associated with incident CVD, in the community.

  • 1428.
    Velders, Matthijs A.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Abtan, Jeremie
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France..
    Angiolillo, Dominick J.
    Univ Florida, Coll Med Jacksonville, Dept Med, Jacksonville, FL USA..
    Ardissino, Diego
    Univ Parma, Azienda Osped, I-43100 Parma, Italy..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Hellkamp, Anne
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Husted, Steen
    Hosp Unit West, Dept Med, Holstebro Herning Holste, Denmark..
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Meier, Bernhard
    Univ Hosp Bern, CH-3010 Bern, Switzerland..
    Schulte, Phillip J.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.;Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France.;INSERM, Unite 1148, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6LY, England..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Safety and efficacy of ticagrelor and clopidogrel in primary percutaneous coronary intervention2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 8, p. 617-625Article in journal (Refereed)
    Abstract [en]

    Objective: The effects of ticagrelor in the subpopulation of patients with ST-elevation myocardial infarction (STEMI) were consistent with those observed in the overall Platelet Inhibition and Patient Outcomes (PLATO) study. However, this subgroup included patients initially or ultimately treated conservatively. The aim of this study is to compare treatment using ticagrelor with treatment using clopidogrel in patients with STEMI undergoing primary percutaneous coronary intervention (PCI).

    Methods: This post-hoc subgroup analysis compared ticagrelor with clopidogrel in 4949 PLATO patients with STEMI that were treated with primary PCI within 12h of admission. The primary endpoint was cardiovascular death, myocardial infarction or stroke. The safety endpoint consisted of any major bleeding. Secondary endpoints included stent thrombosis. The analysis was not adequately powered to establish significance of any treatment effects.

    Results: During a median of 286days, the primary endpoint occurred in 7.9% of ticagrelor-treated patients versus 8.6% of clopidogrel-treated patients (HR 0.91, 95% CI 0.75 to 1.12, p=0.38). Major bleeding occurred in 6.7% in ticagrelor-treated patients versus 6.8% of clopidogrel-treated patients (HR 0.97, 95% CI 0.77 to 1.22, p=0.79). No interactions were observed for the treatment effect of ticagrelor versus clopidogrel on the primary efficacy (p=0.40) and primary safety endpoints (p=0.15) as compared with the full PLATO population. Treatment with ticagrelor versus clopidogrel reduced the occurrence of definite stent thrombosis (HR 0.58, 95% CI 0.37 to 0.89, p=0.013).

    Conclusions: In the subset of patients with STEMI treated with primary PCI, ticagrelor compared with clopidogrel was safe, and efficacy outcomes were consistent with the overall PLATO trial.

  • 1429.
    Velders, Matthijs A
    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.
    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.
    Libungan, B
    Sarno, Giovanna
    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.
    Fröbert, Ole
    Carlsson, J
    Schalij, MJ
    Albertsson, P
    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.
    Response to the letter to the editor by Ariza-Solé et al2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 1, p. e5-Article in journal (Refereed)
  • 1430.
    Velders, Matthijs A.
    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.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Libungan, Berglind
    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.
    Frobert, Ole
    Carlsson, Jorg
    Schalij, Martin J.
    Albertsson, Per
    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.
    Prognosis of elderly patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention in 2001 to 2011: A report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) registry2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 167, no 5, p. 666-Article in journal (Refereed)
    Abstract [en]

    Background Elderly patients constitute a growing part of the population presenting with ST-elevation myocardial infarction (STEMI). The use of primary percutaneous coronary intervention (PCI) in this high-risk population remains poorly investigated. Methods Using the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), we identified consecutive patients with STEMI 80 years or older undergoing primary PCI during a 10-year period. Temporal trends in care and 1-year prognosis were investigated, and long-term outcome was compared with a reference group of patients with STEMI aged 70 to 79 years. Relative survival was calculated by dividing the observed survival rate with the expected survival rate of the general population. Adjusted end points were calculated using Cox regression. Results In total, 4,876 elderly patients with STEMI were included. During the study period, average age and presence of comorbidity increased, as well as the use of antithrombotic therapy. Procedural success remained constant. One-year mortality was exclusively reduced between the most recent vs the earliest cohort, whereas the risk of reinfarction, heart failure, stroke, and bleeding remained similar. The risk of death was higher for elderly patients early after PCI, after which the prognosis was slightly better compared with the general population. Long-term risk of adverse events increased markedly with age. Conclusions The prognosis of patients older than 80 years treated with primary PCI for STEMI was relatively unchanged during the 10-year inclusion period, despite changes in patient characteristics and treatment. Advanced age increased the risk of adverse events, but survivors of the early phase after PCI had a slightly improved prognosis compared with the general population.

  • 1431.
    Velders, Matthijs A.
    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.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Becker, Richard C.
    van Boven, Adrianus J.
    Himmelmann, Anders
    Husted, Steen
    Katus, Hugo A.
    Lindholm, Daniel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Morais, Joao
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Storey, Robert F.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Biomarkers for risk stratification of patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention: Insights from the Platelet Inhibition and Patient Outcomes trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 169, no 6, p. 879-889.e7Article in journal (Refereed)
    Abstract [en]

    Background The incremental prognostic value of admission measurements of biomarkers beyond clinical characteristics and extent of coronary artery disease (CAD) in patients treated with primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI) is unclear. Methods Centrally analyzed plasma for biomarker measurements was available in 5,385 of the STEMI patients treated with PPCI in the PLATO trial. Extent of CAD was graded by operators in association with PPCI. We evaluated the prognostic value of high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15) beyond clinical characteristics and extent of CAD using Cox proportional hazards analyses, C-index, and net reclassification improvement (NRI). Outcomes were cardiovascular death (CVD) and spontaneous myocardial infarction (MI). Results Angiographic data on extent of CAD improved the prediction of CVD compared to clinical risk factors alone, increasing the C-index from 0.760 to 0.778, total NRI of 0.31. Biomarker information provided additional prognostic value for CVD beyond clinical risk factors and extent of CAD, C-indices ranging from 0.792 to 0.795 for all biomarkers, but with a higher NRI for NT-proBNP. Extent of CAD and high-sensitivity cardiac troponin T were not associated with spontaneous MI. The prediction of spontaneous MI beyond clinical characteristics and extent of CAD (C-index 0.647) was improved by both NT-proBNP (C-index 0.663, NRI 0.22) and GDF-15 (C-index 0.652, NRI 0.05). Conclusions Biomarker measurement on admission is feasible and provides incremental risk stratification in patients with STEMI treated with PPCI, with NT-proBNP and GDF-15 being most valuable due to the association with both CVD and spontaneous MI.

  • 1432.
    Venetsanos, D.
    et al.
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    Lawesson, S. Sederholm
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Erlinge, D.
    Skane Univ Hosp, Lund, Sweden..
    Koul, S.
    Skane Univ Hosp, Lund, Sweden..
    Swahn, E.
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    Alfredsson, J.
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    Bivalirudin versus UFH with or without GP IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction undergoing primary PCI2016Conference paper (Refereed)
  • 1433.
    Venge, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cardiac Troponin Assay Classification by Both Clinical and Analytical Performance Characteristics: A Study on Outcome Prediction2013In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, no 6, p. 976-981Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cardiac troponin assays have been classified according to whether they measure the 99th percentile concentration of a healthy reference population with imprecision (expressed as CV) of <= 10%, between 10% and 20%, or >20%. Assays in these categories have been deemed "guideline acceptable," "clinically usable," or not acceptable," respectively. We compared four widely used "clinically usable" cardiac troponin I (cTnI) assays with an assay designated "not acceptable" for accuracy in predicting the clinical outcome of death. METHODS: Blood was collected from 259 men and 249 women, mean (SD) age 68.8 (17.8) and 70.2 (17.8) years, respectively, admitted to the emergency department for suspected myocardial infarction. We measured cTnI by the Access, Architect, i-Stat, Stratus CS, and VIDAS assays. Deaths in this population were recorded over a 31-month period. RESULTS: We found VIDAS cTnI assay measurement CVs of 10% and 20% at concentrations of 0.04 and 0.02 mu g/L, respectively. Comparing at the 10% CV cutoff concentration, VIDAS cTnI was less sensitive than the Access and Architect assays (P < 0.001) but more sensitive than i-Stat (P < 0.001) and Stratus CS (P < 0.001) in identifying patients with poor outcomes. At the 20% CV cutoff, the VIDAS assay was equivalent to the other assays in identifying patients with poor outcomes. CONCLUSIONS: For outcome prediction, the VIDAS cTnI assay was clinically equivalent or superior to other cTnI assays judged to be acceptable from a pure analytical standpoint. Thus, comparison of cardiac troponin assays should consider not only ana-lytical performance, but also clinical performance characteristics.

  • 1434.
    Venge, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    van Lippen, Lian
    Philips Handheld Diagnost, Eindhoven, Netherlands..
    Blaschke, Sabine
    Univ Med Ctr Gottingen, Interdisciplinary Emergency Care Unit, Gottingen, Germany..
    Christ, Michael
    Luzerner Kantonsspital, Emergency Dept, Luzern, Switzerland.;Paracelsus Med Univ, Nuernberg Gen Hosp, Dept Emergency & Crit Care Med, Nurnberg, Germany..
    Geier, Felicitas
    Paracelsus Med Univ, Nuernberg Gen Hosp, Dept Emergency & Crit Care Med, Nurnberg, Germany..
    Giannitsis, Evangelos
    Heidelberg Univ, Med Klin 3, Heidelberg, Germany..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hausfater, Pierre
    Hop La Pitie Salpetriere, AP HP, Emergency Dept, Paris, France.;UPMC Univ Paris 06, Sorbonne Univ, GRC BIOSFAST 14, Paris, France..
    Khellaf, Mehdi
    Hop Henri Mondor, Emergency Dept, Creteil, France..
    Mair, Johannes
    Innsbruck Med Univ, Dept Internal Med Cardiol & Angiol 3, Innsbruck, Austria..
    Pariente, David
    Hop La Pitie Salpetriere, AP HP, Emergency Dept, Paris, France..
    Scharnhorst, Volkher
    Catharina Ziekenhuis Eindhoven, Clin Lab, Eindhoven, Netherlands.;Tech Univ Eindhoven, Eindhoven, Netherlands..
    Semjonow, Veronique
    Philips Handheld Diagnost, Eindhoven, Netherlands..
    Equal clinical performance of a novel point-of-care cardiac troponin I (cTnI) assay with a commonly used high-sensitivity cTnI assay2017In: Clinica Chimica Acta, ISSN 0009-8981, E-ISSN 1873-3492, Vol. 469, p. 119-125Article in journal (Refereed)
    Abstract [en]

    Background: Efficient rule-out of acute myocardial infarction (MI) facilitates early disposition of chest pain patients in emergency departments (ED). Point-of-care (POC) cardiac troponin (cTn) may improve patient throughput. We compared the diagnostic accuracy of a novel cTnI test (Minicare cTnI, Philips), with current POC cTnI (I-Stat, Abbott) and high-sensitivity central laboratory cTnI (hs-cTnI; Architect, Abbott) assays.

    Methods: The clinical performance of the assays were compared in samples from 450 patients from a previous clinical evaluation of Minicare cTnI.

    Results: Minicare cTnI correlated with Architect hs-cTnI (r(2) = 0.85, p < 0.0001) and I-Stat cTnI (r(2) = 0.93, p < 0.0001). Areas under the receiver operating characteristics curves were 0.87-0.91 at admission (p = ns) and 0.96-0.97 3 h after admission (p = ns). The negative predictive values (NPV) at admission were 95% ((92-97%, 95% CI) for Minicare cTnI and increased to 99% (97-100%) at 2-4 h, and similar to Architect hs-cTnI (98%, 96-100%), but higher than I-Stat cTnI (95%, 92-97%; p < 0.01). Negative likelihood ratios (LR) after 2-4 h were 0.06 (0.02-0.17, 95% CI) for Minicare cTnI, 0.11 (0.05-0.24) for Architect hs-cTnI (p = 0.02) and 0.28 (0.18-0.43) for I-Stat cTnI (p < 0.0001). The clinical concordances between Minicare cTnI and Architect hs-cTnI were 92% (admission) and 95% (2-4 h), with lower concordances between Minicare cTnI and I-Stat cTnI (83% and 78%, respectively; p = 0.007).

    Conclusions: The Minicare cTnI POC assay may become useful for prompt and safe ruling-out of AMI in ED patients with suspected AMI using a guideline supported 0/3 h sampling protocol.

  • 1435.
    Venge, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Öhberg, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Flodin, Mats
    Uppsala University Hospital, Department of Clinical Chemistry and Pharmacology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Early and late outcome prediction of death in the emergency room setting by point-of-care and laboratory assays of cardiac troponin I2010In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 160, no 5, p. 835-841Article in journal (Refereed)
    Abstract [en]

    Background Point-of-care (POC) assays of cardiac troponins are common in the emergency department setting. The question raised was as follows: What is the clinical impact of the results of POC assays of cardiac troponins as compared with sensitive laboratory assays? Methods Patients admitted consecutively to the emergency department (N = 1,069) and on whom cardiac troponins were requested as part of their clinical work-up were included. Cardiac troponin I (cTnI) was measured by the POC assays-i-Stat (Abbott Diagnostics, Abbott Park, IL) and Stratus CS (Siemens Healthcare Diagnostics, Deerfield, IL)-and by the laboratory assays-Access AccuTnI (Beckman Coulter, Fullerton, CA) and Architect cTnI (Abbott Diagnostics). Results were related to early (14 days) and late outcome (median 3.3 months, range 0.1-35) as to death. Results The laboratory assays identified more patients (P<.001) with elevated levels than the two POC assays (39%-74% vs 20%-27%). Adopting the 99th percentiles upper reference limit, the Access AccuTnI identified 88% and Architect cTnI identified 81% of all patients who died of cardiovascular disease as compared with 50% and 54% for i-Stat and Stratus CS, respectively (P<.001). Negative predictive values for the laboratory assays were 97% as compared with 89% to 93% for the POC assays. Negative likelihood ratios were 0.25 (CI 0.15-0.041) and 0.59 to 0.68 (CI 0.47-0.79), respectively. Conclusions The current POC cTnI assays are less sensitive for outcome prediction of patients with myocardial injury. The clinical judgment of the patient with suspected myocardial ischemia should not solely rely on results from POC assays. If a clinical suspicion of myocardial injury remains despite negative cTnI results with the POC assays, such results should be complemented by results from sensitive laboratory assays.

  • 1436.
    Ventimiglia, Eugenio
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology. IRCCS, Osped San Raffaele, Div Expt Oncol, Unit Urol, Milan, Italy.
    Van Hemelrijck, Mieke
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res Tour, Guys Hosp, 3rd Floor, London SE1 9RT, England.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Stattin, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Garmo, Hans
    Kings Coll London, Sch Canc & Pharmaceut Sci, Translat Oncol & Urol Res Tour, Guys Hosp, 3rd Floor, London SE1 9RT, England;Uppsala Orebro, Reg Canc Ctr, Uppsala, Sweden.
    How to measure temporal changes in care pathways for chronic diseases using health care registry data2019In: BMC Medical Informatics and Decision Making, ISSN 1472-6947, E-ISSN 1472-6947, Vol. 19, article id 103Article in journal (Refereed)
    Abstract [en]

    Background: Disease trajectories for chronic diseases can span over several decades, with several time-dependent factors affecting treatment decisions. Thus, there is a need for long-term predictions of disease trajectories to inform patients and healthcare professionals on the long-term outcomes and provide information on the need of future health care. Here, we propose a state transition model to describe and predict disease trajectories up to 25 years after diagnosis in men with prostate cancer (PCa), as a proof of principle. Methods: States, state transitions, and transition probabilities were identified and estimated in Prostate Cancer data Base of Sweden (PCBaSeTraject), using nationwide population-based data from 118,743 men diagnosed with PCa. A state transition model in discrete time steps (i.e., 4 weeks) was developed and applied to capture all possible transitions (PCBaSeSim). Transition probabilities were estimated for changes in both treatment and comorbidity. These models combined yielded parameter estimates to run an individual-level simulation based on the state-transition model to obtain prediction estimates. Predicted estimates were then compared to real world data in PCBaSeTraject. Results: PCBaSeSim estimates for the cumulative incidence of first and second transitions, death from PCa and death from other causes were compared to observed transitions in PCBaSeTraject. A good agreement was found between simulated and observed estimates. Conclusions: We developed a reliable and accurate simulation tool, PCBaSeSim that provides information on disease trajectories for subjects with a chronic disease on an individual and population-based level.

  • 1437.
    Verdecchia, Paolo
    et al.
    Hosp Assisi, Dept Med, Assisi, Italy..
    Reboldi, Gianpaolo
    Univ Perugia, Dept Med, Perugia, Italy..
    Angeli, Fabio
    Hosp SM Misericordia, Dept Cardiol & Cardiovasc Pathophysiol, Perugia, Italy..
    Mazzotta, Giovanni
    Hosp Assisi, Dept Med, Assisi, Italy..
    Lip, Gregory Y. H.
    Univ Birmingham, Inst Cardiovasc Sci, City Hosp, Birmingham, W Midlands, England..
    Brueckmann, Martina
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany..
    Kleine, Eva
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ezekowitz, Michael D.
    Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA USA.;Coll Med, Wynnewood, PA USA.;Lankenau Med Ctr, Wynnewood, PA USA..
    Yusuf, Salim
    McMaster Univ, Hamilton, ON, Canada..
    Connolly, Stuart J.
    McMaster Univ, Hamilton, ON, Canada..
    Di Pasquale, Giuseppe
    Maggiore Hosp, Dept Cardiol, Bologna, Italy..
    Dabigatran vs. warfarin in relation to the presence of left ventricular hypertrophy in patients with atrial fibrillation-the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) study2018In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, no 2, p. 253-262Article in journal (Refereed)
    Abstract [en]

    Aim: We tested the hypothesis that left ventricular hypertrophy (LVH) interferes with the antithrombotic effects of dabigatran and warfarin in patients with atrial fibrillation (AF).

    Methods and results: This is a post-hoc analysis of the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) Study. We defined LVH by electrocardiography (ECG) and included patients with AF on the ECG tracing at entry. Hazard ratios (HR) for each dabigatran dose vs. warfarin were calculated in relation to LVH. LVH was present in 2353 (22.7%) out of 10 372 patients. In patients without LVH, the rates of primary outcome were 1.59%/ year with warfarin, 1.60% with dabigatran 110 mg (HR vs. warfarin 1.01, 95% confidence interval (CI) 0.75-1.36) and 1.08% with dabigatran 150 mg (HR vs. warfarin 0.68, 95% CI 0.49-0.95). In patients with LVH, the rates of primary outcome were 3.21%/ year with warfarin, 1.69% with dabigatran 110 mg (HR vs. warfarin 0.52, 95% CI 0.32-0.84) and 1.55% with 150 mg (HR vs. warfarin 0.48, 95% CI 0.29-0.78). The interaction between LVH status and dabigatran 110 mg vs. warfarin was significant for the primary outcome (P = 0.021) and stroke (P = 0.016). LVH was associated with a higher event rate with warfarin, not with dabigatran. In the warfarin group, the time in therapeutic range was significantly lower in the presence than in the absence of LVH.

    Conclusions: LVH was associated with a lower antithrombotic efficacy of warfarin, but not of dabigatran, in patients with AF. Consequently, the relative benefit of the lower dose of dabigatran compared to warfarin was enhanced in patients with LVH. The higher dose of dabigatran was superior to warfarin regardless of LVH status.

  • 1438. Verdecchia, Paolo
    et al.
    Reboldi, Gianpaolo
    Di Pasquale, Giuseppe
    Mazzotta, Giovanni
    Ambrosio, Giuseppe
    Yang, Sean
    Pogue, Janice
    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.
    Ezekowitz, Michael D.
    Connolly, Stuart J.
    Yusuf, Salim
    Prognostic Usefulness of Left Ventricular Hypertrophy by Electrocardiography in Patients With Atrial Fibrillation (from the Randomized Evaluation of Long-Term Anticoagulant Therapy Study)2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 4, p. 669-675Article in journal (Refereed)
    Abstract [en]

    It is unknown whether left ventricular hypertrophy (LVH) diagnosis by electrocardiography improves risk stratification in patients with atrial fibrillation (AF). We investigated the prognostic impact of LVH diagnosis by electrocardiography in a large sample of anticoagulated patients with AF included in the Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) Study. We defined electrographic LVH (ECG-LVH) by strain pattern or Cornell voltage (R wave in aVL plus S wave in V-3) >2.0 mV (women) or >2.4 mV (men). LVH prevalence was 22.7%. During a median follow-up of 2.0 years, 303 patients developed a stroke, 778 died (497 from cardiovascular causes), and 140 developed a myocardial infarction. LVH was associated with a greater risk of stroke (1.99% vs 1.32% per year, hazard ratio [BR] 1.51, 95% confidence interval [CI] 1.18 to 1.93, p <0.001), cardiovascular death (4.52% vs 1.80% per year, HR 2.56, 95% CI 2.14 to 3.06, p <0.0001), all-cause death (6.03% vs 3.11% per year, HR 1.95, 95% CI 1.68 to 2.26, p <0.0001), and myocardial infarction (1.11% vs 0.55% per year, HR 2.07, 95% CI 1.47 to 2.92, p <0.0001). In multivariate analysis, the prognostic value of LVH was additive to CHA(2)DS(2)-VASc score and other covariates. The category-free net reclassification index and integrated discrimination improvement increased significantly after adding LVH to multivariate models. In conclusion, our study demonstrates for the first time that ECG-LVH, a simple and easily accessible prognostic indicator, improves risk stratification in anticoagulated patients with AF.

  • 1439.
    Vessby, Bengt
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Gustafsson, Inga-Britt
    Tengblad, Siv
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Indices of fatty acid desaturase activity in healthy human subjects: effects of different types of dietary fat2013In: British Journal of Nutrition, ISSN 0007-1145, E-ISSN 1475-2662, Vol. 110, no 5, p. 871-879Article in journal (Refereed)
    Abstract [en]

    Delta 9-Desaturase (stearoyl-CoA desaturase 1, SCD-1) regulates the desaturation of SFA, mainly stearic and palmitic, to MUFA. Delta 6-Desaturase (D6D) and Delta 5-desaturase (D5D) are involved in the metabolism of linoleic and alpha-linolenic acid to polyunsaturated metabolites. The objective of the present study was to study the effects of different types of dietary fat on indices of fatty acid desaturase (FADS) activity (evaluated as product: precursor ratios) in plasma and skeletal muscle in human subjects. A high SCD-1 index has been related to obesity and metabolic disorders, while the D5D index is associated with insulin sensitivity. Fatty acid composition of serum and skeletal muscle lipids was analysed by GLC during a randomised, controlled, 3-month dietary intervention in healthy subjects. A comparison of the effects of a diet containing butter fat (SFA, n 17) with a diet containing monounsaturated fat (MUFA, n 17), keeping all other dietary components constant, showed a reduced SCD-1 activity index by 20% on the MUFA diet compared with the SFA diet assessed in serum cholesteryl esters. The D6D and D5D indices remained unaffected. Supplementation with long-chain n-3 fatty acids reduced the SCD-1 index by a similar magnitude while the D6D index decreased and the D5D index increased. It is concluded that changes in the type of fat in the diet affect the indices of FADS activity in serum and skeletal muscle in human subjects. The desaturase activity indices estimated from the serum lipid ester composition are significantly related to corresponding indices studied in skeletal muscle phospholipids.

  • 1440.
    Viberga, I
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Odlind, V
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Berglund, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    The impact of age and intrauterine contraception on the clinical course of pelvic inflammatory disease2006In: Gynecologic and Obstetric Investigation, ISSN 0378-7346, E-ISSN 1423-002X, Vol. 61, no 2, p. 65-71Article in journal (Refereed)
    Abstract [en]

    Background:The aim of the study was to investigate the clinical course of pelvic inflammatory disease (PID) and factors that could predict failed conservative treatment of PID. Additionally, the study aimed to examine the role of age and intrauterine device (IUD) use on the severity of PID. Method: Fifty-one women admitted to hospital with the diagnosis of acute PID were recruited. Of those, 17 patients were subsequently operated because of failed conservative treatment. All women underwent careful examination and completed a questionnaire at admission. Their clinical course was followed and the clinician responsible for the patient completed forms at admission and at discharge. Two groups were established retrospectively, those who were treated conservatively and those who underwent surgery. The outcome results were analyzed with regard to IUD use, duration of IUD use (≥5 or <5 years), and with regard to age below or above 35 years. All data were analyzed using the statistical package SAS. A p value <0.05 was considered significant. Results: Women who subsequently underwent surgical treatment were significantly older and significantly more frequently, current IUD users. There was no significant difference with regard to other socio-demographic characteristics. Women who subsequently underwent surgery had significantly more frequent complaints of severe abdominal pain, elevated body temperature, symptoms of peritoneal irritation, and appearance of adnexal mass. No differences were found between groups with regard to anaerobic microbiological findings, nor with regard to the finding of Actinomyces. IUD use and age ≥35 were found to be highly significant risk factors for surgery in patients with PID. Conclusion: Age over 35 years and IUD use, independently of each other, were factors strongly associated with an increased risk of surgery for PID as a result of failed conservative treatment.

  • 1441. Vichapat, Voralak
    et al.
    Garmo, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Holmqvist, Marit
    Liljegren, Göran
    Wärnberg, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Lambe, Mats
    Fornander, Tommy
    Adolfsson, Jan
    Lüchtenborg, Margreet
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Tumor stage affects risk and prognosis of contralateral breast cancer: results from a large Swedish-population-based study2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 28, p. 3478-3485Article in journal (Refereed)
    Abstract [en]

    PURPOSE

    The number of breast cancer survivors at risk of developing contralateral breast cancer (CBC) is increasing. However, ambiguity remains regarding risk factors and prognosis for women with CBC.

    PATIENTS AND METHODS

    In a cohort of 42,670 women with breast cancer in the Uppsala/Örebro and Stockholm regions in Sweden in 1992 to 2008, we assessed risk factors for and prognosis of metachronous CBC by using survival analysis. Breast cancer-specific survival for women with CBC was evaluated and compared with results for women with unilateral breast cancer (UBC) by using time-dependent Cox-regression modeling.

    RESULTS

    An increased risk for CBC was observed among women who had primary breast cancer with ≥ 10 involved lymph nodes compared with node-negative women (adjusted hazard ratio [HR], 1.8; 95% CI, 1.2 to 2.7). The prognosis was poorer in women with CBC than with UBC. The hazard of dying from breast cancer was especially high for women with a short interval time to CBC (adjusted HR, 2.3; 95% CI, 1.8 to 2.8 for CBC diagnosed ≤ 5 years v UBC) and gradually decreased with longer follow-up time but remained higher than the hazard originating from the primary tumor for ≥ 10 years.

    CONCLUSION

    Women with advanced-stage primary breast cancer had an increased risk of developing CBC. CBC is associated with an increased risk of dying from breast cancer throughout a long period of follow-up after the primary tumor. Our findings suggest that the event of CBC marks a new clinical situation in terms of investigations for metastases, treatment considerations, and follow-up strategy.

  • 1442.
    Victor, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Binnmyr, Jonas
    Karolinska Inst, Dept Clin Neurosci, Therapeut Immune Design Unit, Stockholm, Sweden.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rask-Andersen, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Elfman, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Levels of horse allergen Equ c 4 in dander and saliva from ten horse breeds2019In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 49, no 5, p. 701-711Article in journal (Refereed)
    Abstract [en]

    Background: Horses are an important source of allergens, but the distribution of horse allergens is poorly understood. Five horse allergens have been identified, Equ c 1-4 and 6. Equ c 4 seems to be an important allergen, with an IgE-binding frequency of 77% in horse-sensitized individuals.0000 Objectives: The aim of this study was to investigate levels of horse allergen Equ c 4 in dander, saliva and urine from ten horse breeds. Method: The study population included 170 horses (87 mares, 27 stallions, 56 geldings) from ten breeds. Horse dander, saliva and urine samples were collected. Levels of horse allergen Equ c 4 were quantified using a two-site sandwich ELISA (mAb 103 and 14G4) and were expressed as Equ c 4 U/mu g protein. Results: The horse allergen Equ c 4 was present in all dander and saliva samples from ten horse breeds, with high within-breed and inter-breed variations; GM values were 639 Equ c 4 U/mu g protein (range 5-15 264) for dander and 39.5 (4-263) for saliva. Equ c 4 was found in 19/21 urine samples. Adjusted for age, sex and changes over time, no differences between breeds could be seen in dander, while in saliva the North Swedish horse showed lower levels of Equ c 4 than any other breed. The levels of Equ c 4 protein in dander and saliva were significantly higher in samples from stallions compared to mares and geldings, independent of breed. Conclusions and Clinical Relevance: The results show a high variability in allergen levels of Equ c 4 in dander and saliva both within and between breeds. Significantly higher levels were found in stallions compared to mares and geldings, independent of breed. Results suggest that none of the horse breeds studied can be recommended for individuals allergic to Equ c 4.

  • 1443.
    Victor, Susanne
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Elfman, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    The horse allergen Equus caballus Equ C 4 in horse saliva2017In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 72, p. 727-727Article in journal (Other academic)
  • 1444.
    Vidal-Petiot, Emmanuelle
    et al.
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Cardiol Dept, 46 Rue Henri Huchard, F-75018 Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Dept Physiol, 46 Rue Henri Huchard, F-75018 Paris, France.;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France.;INSERM, U1149, Paris, France..
    Stebbins, Amanda
    Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Ardissino, Diego
    Univ Parma, Azienda Osped, Via Gramsci 14, I-43126 Parma, Italy..
    Aylward, Philip E.
    Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Cardiovasc Div, 70 Francis St, Boston, MA 02115 USA.;Harvard Clin Res Inst, Boston, MA USA..
    Corrales, Marco A. Ramos
    San Jose Satelite Hosp, Circunvalac Poniente 53, Naucalpan De Juarez 53100, Mexico..
    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.
    Lopez-Sendon, Jose Luis
    Hosp Univ La Paz, IdiPaz, Paseo Castellana 261,Planta 1, Madrid 28046, Spain..
    Stewart, Ralph A. H.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    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.
    White, Harvey D.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Cardiol Dept, 46 Rue Henri Huchard, F-75018 Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Dept Physiol, 46 Rue Henri Huchard, F-75018 Paris, France.;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France.;NHLI Imperial Coll, ICMS, Royal Brompton Hosp, London, England.;FACT, F CRIN Network, INSERM, U1148, Paris, France..
    Visit-to-visit variability of blood pressure and cardiovascular outcomes in patients with stable coronary heart disease. Insights from the STABILITY trial2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 37, p. 2813-2822Article in journal (Refereed)
    Abstract [en]

    Aims To study the relation between visit-to-visit variability of blood pressure (BP) and cardiovascular risk in patients with stable coronary heart disease. Methods and results In 15 828 patients from the STABILITY trial (darapladib vs. placebo in patients with established coronary heart disease), BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP, and minimum BP, from 5 measurements (baseline and months 1, 3, 6, and 12) during the first year after randomisation. Mean (SD) average BP during the first year of study was 131.0 (13.7) mmHg over 78.3 (8.3) mmHg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mmHg for systolic and 6.3 (3.0) mmHg for diastolic BP. During the subsequent median follow-up of 2.6 years, 1010 patients met the primary endpoint, a composite of time to cardiovascular death, myocardial infarction, or stroke. In Cox regression models adjusted for average BP during first year of study, baseline vascular disease, treatment, renal function and cardiovascular risk factors, the primary endpoint was associated with SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30, 95% CI 1.10-1.53, P = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38, 95% CI 1.18-1.62, P < 0.001). Peaks and troughs in BP were also independently associated with adverse events. Conclusion In patients with stable coronary heart disease, higher visit-to-visit variabilities of both systolic and diastolic BP are strong predictors of increased risk of cardiovascular events, independently of mean BP.

  • 1445. Vimaleswaran, Karani S
    et al.
    Cavadino, Alana
    Berry, Diane J
    Jorde, Rolf
    Dieffenbach, Aida Karina
    Lu, Chen
    Alves, Alexessander Couto
    Heerspink, Hiddo J Lambers
    Tikkanen, Emmi
    Eriksson, Joel
    Wong, Andrew
    Mangino, Massimo
    Jablonski, Kathleen A
    Nolte, Ilja M
    Houston, Denise K
    Ahluwalia, Tarunveer Singh
    van der Most, Peter J
    Pasko, Dorota
    Zgaga, Lina
    Thiering, Elisabeth
    Vitart, Veronique
    Fraser, Ross M
    Huffman, Jennifer E
    de Boer, Rudolf A
    Schöttker, Ben
    Saum, Kai-Uwe
    McCarthy, Mark I
    Dupuis, Josée
    Herzig, Karl-Heinz
    Sebert, Sylvain
    Pouta, Anneli
    Laitinen, Jaana
    Kleber, Marcus E
    Navis, Gerjan
    Lorentzon, Mattias
    Jameson, Karen
    Arden, Nigel
    Cooper, Jackie A
    Acharya, Jayshree
    Hardy, Rebecca
    Raitakari, Olli
    Ripatti, Samuli
    Billings, Liana K
    Lahti, Jari
    Osmond, Clive
    Penninx, Brenda W
    Rejnmark, Lars
    Lohman, Kurt K
    Paternoster, Lavinia
    Stolk, Ronald P
    Hernandez, Dena G
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    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, Clinical pharmacogenomics and osteoporosis.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Mellström, Dan
    Ljunggren, Östen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrinology and mineral metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Tzoulaki, Ioanna
    McLachlan, Stela
    Theodoratou, Evropi
    Tiesler, Carla M T
    Jula, Antti
    Navarro, Pau
    Wright, Alan F
    Polasek, Ozren
    Wilson, James F
    Rudan, Igor
    Salomaa, Veikko
    Heinrich, Joachim
    Campbell, Harry
    Price, Jacqueline F
    Karlsson, Magnus
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. 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.
    Bandinelli, Stefania
    Frayling, Timothy M
    Hartman, Catharina A
    Sørensen, Thorkild I A
    Kritchevsky, Stephen B
    Langdahl, Bente Lomholt
    Eriksson, Johan G
    Florez, Jose C
    Spector, Tim D
    Lehtimäki, Terho
    Kuh, Diana
    Humphries, Steve E
    Cooper, Cyrus
    Ohlsson, Claes
    März, Winfried
    de Borst, Martin H
    Kumari, Meena
    Kivimaki, Mika
    Wang, Thomas J
    Power, Chris
    Brenner, Hermann
    Grimnes, Guri
    van der Harst, Pim
    Snieder, Harold
    Hingorani, Aroon D
    Pilz, Stefan
    Whittaker, John C
    Järvelin, Marjo-Riitta
    Hyppönen, Elina
    Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study2014In: The Lancet Diabetes and Endocrinology, ISSN 2213-8587, E-ISSN 2213-8595, Vol. 2, no 9, p. 719-729Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk.

    METHODS: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium.

    FINDINGS: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002).

    INTERPRETATION: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study.

  • 1446. Vinereanu, Dragos
    et al.
    Lopes, Renato D
    Mulder, Hillary
    Gersh, Bernard J
    Hanna, Michael
    de Barros E Silva, Pedro G M
    Atar, Dan
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B
    Alexander, John H
    Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 12, p. 3266-3273Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Few data exist on the long-term outcomes of patients with spontaneous echo contrast (SEC), left atrial/left atrial appendage (LA/LAA) thrombus, and complex aortic plaque (CAP), in patients with atrial fibrillation receiving oral anticoagulation. We explored the relationship between these 3 echocardiographic findings and clinical outcomes, and the comparative efficacy and safety of apixaban and warfarin for each finding.

    METHODS: Patients from the ARISTOTLE trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) with SEC, LA/LAA thrombus, or CAP diagnosed by either transthoracic or transesophageal echocardiography were compared with patients with none of these findings on transesophageal echocardiography.

    RESULTS: A total of 1251 patients were included: 217 had SEC, 127 had LA/LAA thrombus, 241 had CAP, and 746 had none. The rates of stroke/systemic embolism were not significantly different among patients with and without these echocardiographic findings (hazard ratio, 0.96; 95% confidence interval, 0.25-3.60 for SEC; hazard ratio, 1.27; 95% confidence interval, 0.23-6.86 for LA/LAA thrombus; hazard ratio, 2.21; 95% confidence interval, 0.71-6.85 for CAP). Rates of ischemic stroke, myocardial infarction, cardiovascular death, and all-cause death were also not different between patients with and without these findings. For patients with either SEC or CAP, there was no evidence of a differential effect of apixaban over warfarin. For patients with LA/LAA thrombus, there was also no significant interaction, with the exception of all-cause death and any bleeding where there was a greater benefit of apixaban compared with warfarin among patients with no LA/LAA thrombus.

    CONCLUSIONS: In anticoagulated patients with atrial fibrillation and risk factors for stroke, echocardiographic findings do not seem to add to the risk of thromboembolic events.

    CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

  • 1447. Vinereanu, Dragos
    et al.
    Stevens, Susanna R.
    Alexander, John H.
    Al-Khatib, Sana M.
    Avezum, Alvaro
    Bahit, Cecilia
    Granger, Christopher B.
    Lopes, Renato D.
    Halvorsen, Sigrun
    Hanna, Michael
    Husted, Steen
    Hylek, Elaine M.
    Margulescu, Andrei D.
    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.
    Atar, Dan
    Efficacy and Safety of Apixaban in Patients With Atrial Fibrillation According to Sex: Results From the ARISTOTLE Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 22Article in journal (Other academic)
  • 1448. Vinereanu, Dragos
    et al.
    Stevens, Susanna R
    Alexander, John H
    Al-Khatib, Sana M
    Avezum, Alvaro
    Bahit, Marıa Cecilia
    Granger, Christopher B
    Lopes, Renato D
    Halvorsen, Sigrun
    Hanna, Michael
    Husted, Steen
    Hylek, Elaine M
    Mărgulescu, Andrei D
    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.
    Atar, Dan
    Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 46, p. 3268-+Article in journal (Refereed)
    Abstract [en]

    AIM: To assess clinical outcomes, efficacy, and safety according to sex during anticoagulation with apixaban compared with warfarin in patients with atrial fibrillation.

    METHODS AND RESULTS: Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) was a randomized, double-blind, placebo-controlled, multicentre trial that included 11 785 (64.7%) men and 6416 (35.3%) women with atrial fibrillation or flutter randomized to receive either warfarin or apixaban. The primary efficacy endpoint was stroke or systemic embolism; secondary efficacy endpoints were death from any cause and cardiovascular death. The primary safety endpoint was major bleeding; secondary safety endpoints were a composite of major bleeding and non-major clinically relevant bleeding. The risk of stroke or systemic embolism was similar in women vs. men [adjusted hazard ratio (adjHR): 0.91; 95% confidence interval (CI): 0.74-1.12; P = 0.38]. However, among patients with history of stroke or transient ischaemic attack, women had a lower risk of recurrent stroke compared with men (adjHR: 0.70; 95% CI: 0.50-0.97; P = 0.036). Women also had a lower risk of all-cause death (adjHR: 0.63; 95% CI: 0.55-0.73; P < 0.0001) and cardiovascular death (adjHR: 0.62; 95% CI: 0.51-0.75; P < 0.0001), and a trend towards less major bleeding (adjHR: 0.86; 95% CI: 0.74-1.01; P = 0.066) and major or non-major clinically relevant bleeding (adjHR: 0.89; 95% CI: 0.80-1.00; P = 0.049). The efficacy and safety benefits of apixaban compared with warfarin were consistent regardless of sex.

    CONCLUSION: In the ARISTOTLE trial, women had a similar rate of stroke or systemic embolism but a lower risk of mortality and less clinically relevant bleeding than men. The efficacy and safety benefits of apixaban compared with warfarin were consistent in men and women.

    TRIAL REGISTRATION: ARISTOTLE ClinicalTrials.gov number, NCT00412984.

  • 1449.
    Vinereanu, Dragos
    et al.
    Univ Med & Pharm Carol Davila, Cardiol, Bucharest, Romania;Univ & Emergency Hosp, Cardiol, Bucharest, Romania.
    Wang, Alice
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mulder, Hillary
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Jansky, Petr
    Univ Hosp Motol, Prague, Czech Republic.
    Lewis, Basil S.
    Lady Davis Carmel Med Ctr, Haifa, Israel.
    Gersh, Bernard J.
    Mayo Clin, Rochester, MN USA.
    Avezum, Alvaro
    Univ Sao Paulo, Dante Pazzanese Inst, Sao Paulo, Brazil.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    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.
    Granger, Clristopler B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Alexander, Jam H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease2018In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 104, no 15, p. 1292-1299Article in journal (Refereed)
    Abstract [en]

    Objective: To assess stroke/systemic embolism, major bleeding and other outcomes, and treatment effect of apixaban versus warfarin, in patients with atrial fibrillation (AF) and different types of valvular heart disease (VHD), using data from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial.

    Methods: There were 14 793 patients with known VHD status, categorised as having moderate or severe mitral regurgitation (MR) (n=3382), aortic regurgitation (AR) (n=842) or aortic stenosis (AS) (n=324); patients with moderate or severe mitral stenosis were excluded from the trial. Baseline characteristics, efficacy and safety outcomes were compared between each type and no significant VHD. Treatment effect was assessed using an adjusted model.

    Results: Patients with MR or AR had similar rates of stroke/systemic embolism and bleeding compared with patients without MR or AR, respectively. Patients with AS had significantly higher event rates (presented as rate per 100 patient-years of follow-up) of stroke/systemic embolism (3.47 vs 1.36; adjusted HR (adjHR) 2.21, 95% CI 1.35 to 3.63), death (8.30 vs 3.53; adjHR 1.92, 95% CI 1.41 to 2.61), major bleeding (5.31 vs 2.53; adjHR 1.80, 95% CI 1.19 to 2.75) and intracranial bleeding (1.29 vs 0.51; adjHR 2.54, 95% CI 1.08 to 5.96) than patients without AS. The superiority of apixaban over warfarin on stroke/systemic embolism was similar in patients with versus without MR (HR 0.69, 95% CI 0.46 to 1.04 vs HR 0.79, 95% CI 0.63 to 1.00; interaction P value 0.52), with versus without AR (HR 0.57, 95% CI 0.27 to 1.20 vs HR 0.78, 95% CI 0.63 to 0.96; interaction P value 0.52), and with versus without AS (HR 0.44, 95% CI 0.17 to 1.13 vs HR 0.79, 95% CI 0.64 to 0.97; interaction P value 0.19). For each of the primary and secondary efficacy and safety outcomes, there was no evidence of a different effect of apixaban over warfarin in patients with any VHD subcategory.

    Conclusions; In anticoagulated patients with AF, AS is associated with a higher risk of stroke/systemic embolism, bleeding and death. The efficacy and safety benefits of apixaban compared with warfarin were consistent, regardless of presence of MR, AR or AS.

  • 1450. Vranckx, P.
    et al.
    Tricoci, P.
    Huang, Z.
    Van de Werf, F.
    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.
    Aylward, P.
    Armstrong, P. W.
    Moliterno, D. J.
    Mahaffey, K. W.
    White, H. D.
    Clinical validation of BARC definitions of bleeding after an ACS in the TRACER trial2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 23-24Article in journal (Other academic)
26272829303132 1401 - 1450 of 1580
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