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  • 151. Connolly, Stuart J.
    et al.
    Reilly, Paul A.
    Pogue, Janice
    Eikelboom, John
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Ezekowitz, Michael D.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Yusuf, Salim
    Randomized Comparison of the Effects of Two Doses of Dabigatran Etexilate on Clinical Outcomes Over 4.3 Years: Results of the Rely-Able Double-Blind Randomized Trial2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 23, p. 2793-2793Article in journal (Other academic)
  • 152. Connolly, Stuart J.
    et al.
    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.
    Eikelboom, John
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Reilly, Paul A.
    Brueckmann, Martina
    Pogue, Janice
    Alings, Marco
    Amerena, John V.
    Avezum, Alvaro
    Baumgartner, Iris
    Budaj, Andrzej J.
    Chen, Jyh-Hong
    Dans, Antonio L.
    Darius, Harald
    Di Pasquale, Giuseppe
    Ferreira, Jorge
    Flaker, Greg C.
    Flather, Marcus D.
    Franzosi, Maria Grazia
    Golitsyn, Sergey P.
    Halon, David A.
    Heidbuchel, Hein
    Hohnloser, Stefan H.
    Huber, Kurt
    Jansky, Petr
    Kamensky, Gabriel
    Keltai, Matyas
    Kim, Sung Soon
    Lau, Chu-Pak
    Le Heuzey, Jean-Yves
    Lewis, Basil S.
    Liu, Lisheng
    Nanas, John
    Omar, Razali
    Pais, Prem
    Pedersen, Knud E.
    Piegas, Leopoldo S.
    Raev, Dimitar
    Smith, Pal J.
    Talajic, Mario
    Tan, Ru San
    Tanomsup, Supachai
    Toivonen, Lauri
    Vinereanu, Dragos
    Xavier, Denis
    Zhu, Jun
    Wang, Susan Q.
    Duffy, Christine O.
    Themeles, Ellison
    Yusuf, Salim
    The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 128, no 3, p. 237-243Article in journal (Refereed)
    Abstract [en]

    Background During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. Methods and Results Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. Conclusions During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death. 

  • 153. Connolly, Stuart J.
    et al.
    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.
    Yusuf, Salim
    Additional Events in the RE-LY Trial2014In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 371, no 15, p. 1464-1465Article in journal (Refereed)
  • 154. Cornel, Jan H.
    et al.
    Becker, Richard C.
    Goodman, Shaun G.
    Husted, Steen
    Katus, Hugo
    Santoso, Anwar
    Steg, Gabriel
    Storey, Robert F.
    Vintila, Marius
    Sun, Jie L.
    Horrow, Jay
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Harrington, Robert
    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.
    Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial2012In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 164, no 3, p. 334-342Article in journal (Refereed)
    Abstract [en]

    Background Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.

    Methods Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.

    Results Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).

    Conclusions In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.

  • 155. Cornel, Jan H.
    et al.
    Lopes, Renato D.
    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.
    Stevens, Susanna R.
    Neely, Megan L.
    Liaw, Danny
    Miller, Julie
    Mohan, Puneet
    Amerena, John
    Raev, Dimitar
    Huo, Yong
    Urina-Triana, Miguel
    Cazorla, Alex Gallegos
    Vinereanu, Dragos
    Fridrich, Viliam
    Harrington, Robert A.
    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.
    Alexander, John H.
    Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes: Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial2015In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 169, no 4, p. 531-538Article in journal (Refereed)
    Abstract [en]

    Background Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. Methods High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Results Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. Conclusions In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.

  • 156. Cornel, Jan H.
    et al.
    Tricoci, Pierluigi
    Lokhnygina, Yuliya
    Moliterno, David J.
    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.
    Armstrong, Paul W.
    Aylward, Philip E.
    Clare, Robert M.
    Chen, Edmond
    Leonardi, Sergio
    de Werf, Frans Van
    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.
    Strony, John
    Mahaffey, Kenneth W.
    Harrington, Robert A.
    Glycoprotein IIb/IIIa Receptor Inhibitors in Combination With Vorapaxar, a Platelet Thrombin Receptor Antagonist, Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes (from the TRACER Trial)2015In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 115, no 10, p. 1325-1332Article in journal (Refereed)
    Abstract [en]

    We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIn/IIIa group; adjusted FIR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.

  • 157.
    Costa, Francesco
    et al.
    Univ Messina, Dept Clin & Expt Med, Policlin G Martino, Messina, Italy;Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Van Klaveren, David
    Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands;Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA 02111 USA.
    Feres, Fausto
    Ist Dante Pazzanese Cardiol, Sao Paulo, Brazil.
    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.
    Raber, Lorenz
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Pilgrim, Thomas
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Hong, Myeong-Ki
    Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Seoul, South Korea;Yonsei Univ, Severance Biomed Sci Inst, Coll Med, Seoul, South Korea.
    Kim, Hyo-Soo
    Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea.
    Colombo, Antonio
    Ist Sci San Raffaele, Intervent Cardiol Unit, Milan, Italy;EMO GVM Ctr Cuore Columbus, Intervent Cardiol Unit, Milan, Italy.
    Steg, Philippe Gabriel
    AP HP, FACT, Paris, France;Univ Paris Diderot, Bichat Hosp, Paris, France.
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA;Harvard Med Sch, Boston, MA USA.
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA;Cardiovasc Res Fdn, New York, NY USA.
    Windecker, Stephan
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Steyerberg, Ewout W.
    Leiden Univ, Med Ctr, Dept Med Stat & Bioinformat, Leiden, Netherlands.
    Valgimigli, Marco
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.
    Dual Antiplatelet Therapy Duration Based on Ischemic and Bleeding Risks After Coronary Stenting2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 73, no 7, p. 741-754Article in journal (Refereed)
    Abstract [en]

    BACKGROUND

    Complex percutaneous coronary intervention (PCI) is associated with higher ischemic risk, which can be mitigated by long-term dual antiplatelet therapy (DAPT). However, concomitant high bleeding risk (HBR) may be present, making it unclear whether short-or long-term DAPT should be prioritized.

    OBJECTIVES

    This study investigated the effects of ischemic (by PCI complexity) and bleeding (by PRECISE-DAPT [PREdicting bleeding Complications in patients undergoing stent Implantation and SubsequEnt Dual AntiPlatelet Therapy] score) risks on clinical outcomes and on the impact of DAPT duration after coronary stenting.

    METHODS

    Complex PCI was defined as $ 3 stents implanted and/or $ 3 lesions treated, bifurcation stenting and/or stent length > 60 mm, and/or chronic total occlusion revascularization. Ischemic and bleeding outcomes in high ($ 25) or nonhigh (< 25) PRECISE-DAPT strata were evaluated based on randomly allocated duration of DAPT.

    RESULTS

    Among 14,963 patients from 8 randomized trials, 3,118 underwent complex PCI and experienced a higher rate of ischemic, but not bleeding, events. Long-term DAPT in non-HBR patients reduced ischemic events in both complex (absolute risk difference:-3.86%; 95% confidence interval:-7.71 to thorn0.06) and noncomplex PCI strata (absolute risk difference:-1.14%; 95% confidence interval:-2.26 to-0.02), but not among HBR patients, regardless of complex PCI features. The bleeding risk according to the Thrombolysis In Myocardial Infarction scale was increased by long-term DAPT only in HBR patients, regardless of PCI complexity.

    CONCLUSIONS

    Patients who underwent complex PCI had a higher risk of ischemic events, but benefitted from long-term DAPT only if HBR features were not present. These data suggested that when concordant, bleeding, more than ischemic risk, should inform decision-making on the duration of DAPT.

  • 158.
    Costa, Francesco
    et al.
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.;Erasmus Univ, Med Ctr, Rotterdam, Netherlands.;Univ Messina, Policlin G Martino, Dept Clin & Expt Med, Messina, Italy..
    van Klaveren, David
    Erasmus Univ, Med Ctr, Rotterdam, Netherlands.;Tufts Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Heg, Dik
    Univ Bern, Inst Social & Prevent Med, Bern, Switzerland..
    Raber, Lorenz
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Feres, Fausto
    Ist Dante Pazzanese Cardiol, Sao Paulo, Brazil..
    Pilgrim, Thomas
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Hong, Myeong-Ki
    Yonsei Univ, Coll Med, Severance Cardiovasc Hosp, Seoul, South Korea.;Yonsei Univ, Coll Med, Severance Biomed Sci Inst, Seoul, South Korea..
    Kim, Hyo-Soo
    Seoul Natl Univ Hosp, Dept Internal Med, Seoul, South Korea..
    Colombo, Antonio
    EMO GVM Ctr Cuore Columbus, Milan, Italy.;Ist Sci San Raffaele, Intervent Cardiol Dept, Milan, Italy..
    Steg, Philippe Gabriel
    Hop Xavier Bichat, AP HP, Dept Cardiol, Paris, France..
    Zanchin, Thomas
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Palmerini, Tullio
    Univ Bologna, Dipartimento Cardiotoracovasc, Bologna, Italy..
    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.
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Stone, Gregg W.
    Columbia Univ, Med Ctr, New York Presbyterian Hosp, New York, NY USA.;Cardiovasc Res Fdn, New York, NY USA..
    Windecker, Stephan
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Steyerberg, Ewout W.
    Erasmus Univ, Med Ctr, Rotterdam, Netherlands..
    Valgimigli, Marco
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland.;Erasmus Univ, Med Ctr, Rotterdam, Netherlands..
    Derivation and validation of the predicting bleeding complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials2017In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 389, no 10073, p. 1025-1034Article in journal (Refereed)
    Abstract [en]

    Background: Dual antiplatelet therapy (DAPT) with aspirin plus a P2Y(12) inhibitor prevents ischaemic events after coronary stenting, but increases bleeding. Guidelines support weighting bleeding risk before the selection of treatment duration, but no standardised tool exists for this purpose.

    Methods: A total of 14 963 patients treated with DAPT after coronary stenting-largely consisting of aspirin and clopidogrel and without indication to oral anticoagulation-were pooled at a single-patient level from eight multicentre randomised clinical trials with independent adjudication of events. Using Cox proportional hazards regression, we identified predictors of out-of-hospital Thrombosis in Myocardial Infarction (TIMI) major or minor bleeding stratified by trial, and developed a numerical bleeding risk score. The predictive performance of the novel score was assessed in the derivation cohort and validated in patients treated with percutaneous coronary intervention from the PLATelet inhibition and patient Outcomes (PLATO) trial (n=8595) and BernPCI registry (n=6172). The novel score was assessed within patients randomised to different DAPT durations (n=10 081) to identify the effect on bleeding and ischaemia of a long (12-24 months) or short (3-6 months) treatment in relation to baseline bleeding risk.

    Findings: The PRECISE-DAPT score (age, creatinine clearance, haemoglobin, white-blood-cell count, and previous spontaneous bleeding) showed a c-index for out-of-hospital TIMI major or minor bleeding of 0.73 (95% CI 0.61-0.85) in the derivation cohort, and 0.70 (0.65-0.74) in the PLATO trial validation cohort and 0.66 (0.61-0.71) in the BernPCI registry validation cohort. A longer DAPT duration significantly increased bleeding in patients at high risk (score >= 25), but not in those with lower risk profiles (p(interaction)=0.007), and exerted a significant ischaemic benefit only in this latter group.

    Interpretation: The PRECISE-DAPT score is a simple five-item risk score, which provides a standardised tool for the prediction of out-of-hospital bleeding during DAPT. In the context of a comprehensive clinical evaluation process, this tool can support clinical decision making for treatment duration.

  • 159. Cowper, Patricia A
    et al.
    Pan, Wenqin
    Anstrom, Kevin J
    Kaul, Padma
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Davidson-Ray, Linda
    Nikolic, Elisabet
    Janzon, Magnus
    Levin, Lars-Åke
    Cannon, Christopher P
    Harrington, Robert A
    Mark, Daniel B
    Economic Analysis of Ticagrelor Therapy From a U.S. Perspective: Results From the PLATO Study2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 65, no 5, p. 465-476Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Based on results of the PLATO (Platelet Inhibition and Patient Outcomes) trial comparing ticagrelor with clopidogrel therapy, the U.S. Food and Drug Administration approved ticagrelor in 2011 for reducing thrombotic cardiovascular events in patients with acute coronary syndrome (ACS) with the proviso that it be taken with low-dose aspirin.

    OBJECTIVES: This study sought to assess the cost and cost effectiveness of ticagrelor therapy relative to clopidogrel in treating ACS patients from the perspective of the U.S. health care system.

    METHODS: We estimated within-trial resource use and costs using U.S. low-dose aspirin patients in PLATO (n = 547). Quality-adjusted life expectancy was estimated using the total PLATO population (n = 18,624), combined with baseline risk and long-term survival data from an external ACS patient cohort. Study drugs were valued at current costs. Cost effectiveness was assessed, as was the sensitivity of results to sampling and methodological uncertainties.

    RESULTS: One year of ticagrelor therapy, relative to that of generic clopidogrel, cost $29,665/quality-adjusted life-year gained, with 99% of bootstrap estimates falling under a $100,000 willingness-to-pay threshold. Results were robust to extensive sensitivity analyses, including variations in clopidogrel cost, exclusion of costs in extended years of life, and a recalibrated estimate of survival reflecting a lower underlying mortality risk in the United States.

    CONCLUSIONS: For PLATO-eligible ACS patients, a U.S. perspective comparison of the current standard of dual antiplatelet therapy of aspirin with clopidogrel versus aspirin plus ticagrelor showed that the ticagrelor regimen increased life expectancy at an incremental cost well within accepted benchmarks of good value for money. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872).

  • 160.
    Crona, Joakim
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Experimental Surgery.
    Fanola, Irina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindholm, Daniel P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Antonodimitrakis, Pantelis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Öberg, Kjell
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Eriksson, Barbro
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Tumor Biology.
    Granberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Endocrine Oncology.
    Effect of Temozolomide in Patients with Metastatic Bronchial Carcinoids2013In: Neuroendocrinology, ISSN 0028-3835, E-ISSN 1423-0194, Vol. 98, no 2, p. 151-155Article in journal (Refereed)
    Abstract [en]

    Introduction: Metastatic bronchial carcinoids are rare neoplasms, where efforts of medical treatment so far have been disappointing. A previous study from our center indicated that temozolomide might be of value. Materials and Methods: All patients with progressive metastatic bronchial carcinoid treated with tennozolomide as monotherapy at our center between 2004 and 2010 (n = 31) were included in this retrospective study. 14 tumors were classified as typical and 15 as atypical carcinoids, whereas 2 tumors could not be classified. Temozolomide was given on 5 consecutive days every 4 weeks. Toxicity was evaluable in 28 of 31 patients, and 22 patients were evaluable by RECIST 1.1. Results: There were no complete responses. A partial response was seen in 3 patients (14%), stable disease in 11(52%) and progressive disease in 7 patients (33%). Median progression-free survival was 5.3 months and median overall survival was 23.2 months from the start of temozolomide. Toxcities grade 3-4 were noted in 4 patients, thrombocytopenia (n =3) and leukopenia (n = 1). Conclusion: Temozolomide as monotherapy shows activity in metastatic bronchial carcinoids. Regimens combining tennozolomide with other agents (e.g. capecitabine and/or bevacizumab, everolimus, radiolabeled somatostatin analogues) should be further studied in these patients. Copyright (C) 2013 S. Karger AG, Basel

  • 161.
    Dagenais, Gilles R.
    et al.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Jung, Hyejung
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Lonn, Eva
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bogaty, Peter M.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Dehghan, Mahshid
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    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.
    Avezum, Alvaro
    Univ Santo Amaro, Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Jansky, Petr
    Univ Hosp Motol, Prague, Czech Republic.
    Keltai, Matyas
    Semmelweis Univ, Budapest, Hungary.
    Leiter, Lawrence A.
    Univ Toronto, Li Ka Shing Knowledge Inst, St Michaels Hosp, Toronto, ON, Canada;Univ Toronto, Dept Med, Toronto, ON, Canada;Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada.
    Lopez-Jaramillo, Patricio
    Univ Santander UDES, Med Sch, Res Dept, FOSCAL, Bucaramanga, Colombia.
    Toff, William D.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Bosch, Jackie
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 15, article id e008918Article in journal (Refereed)
    Abstract [en]

    Background-It is not clear whether the effects of lipid-lowering or antihypertensive medications are influenced by adherence to healthy lifestyle factors. We assessed the effects of both drug interventions in subgroups by the number of healthy lifestyle factors in participants in the HOPE-3 (Heart Outcomes Prevention Evaluation) trial. Methods and Results-In this primary prevention trial, 4 healthy lifestyle factors (nonsmoking status, physical activity, optimal body weight, and healthy diet) were recorded in 12 521 participants who were at intermediate risk of cardiovascular disease (CVD) and were randomized to rosuvastatin, candesartan/hydrochlorothiazide, their combination, or matched placebos. Median follow-up was 5.6 years. The outcome was a composite of CVD events. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. Participants with >= 2 healthy lifestyle factors had a lower rate of CVD compared with those with fewer factors (HR: 0.85; 95% CI, 0.73-1.00). Rosuvastatin reduced CVD events in participants with >= 2 healthy lifestyle factors (HR: 0.74; 95% CI, 0.62-0.90) and in participants with <2 factors (HR: 0.79; 95% CI, 0.61-1.01). Consistent results were observed with combination therapy (>= 2 factors: HR: 0.74; 95% CI, 0.57-0.97; <2 factors: HR: 0.61; 95% CI, 0.43-0.88). Candesartan/hydrochlorothiazide tends to reduce CVD only in participants with <2 healthy lifestyle factors (HR: 0.78; 95% CI, 0.61-1.00). Conclusions-Healthy lifestyles are associated with lower CVD. Rosuvastatin alone and combined with candesartan/hydrochlorothiazide is beneficial regardless of healthy lifestyle status; however, the benefit of antihypertensive treatment appears to be limited to patients with less healthy lifestyles.

  • 162. Dal-Ré, Rafael
    et al.
    Avendaño-Solà, Cristina
    Bloechl-Daum, Brigitte
    de Boer, Anthonius
    Eriksson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Centre for Research Ethics and Bioethics.
    Fuhr, Uwe
    Holm, Søren
    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.
    Mentz, Robert J
    Perucca, Emilio
    Rosendaal, Frits R
    Treweek, Shaun
    Low risk pragmatic trials do not always require participants' informed consent2019In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 364, article id l1092Article in journal (Other academic)
  • 163. Damman, Peter
    et al.
    de Winter, Robbert J
    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.
    Fox, Keith A
    Letter by Damman et al regarding articles, "Long-term cardiovascular mortality after procedure-related or spontaneous myocardial infarction in patients with non-ST-segment elevation acute coronary syndrome: a collaborative analysis of individual patient data from the FRISC II, ICTUS, and RITA-3 Trials (FIR)" and "American College of Cardiology/American Heart Association/European Society of Cardiology/World Heart Federation universal definition of myocardial infarction classification system and the risk of cardiovascular death: Observations From the TRITON-TIMI 38 Trial (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition With Prasugrel-Thrombolysis in Myocardial Infarction 38)”2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 126, no 9, p. E136-E137Article in journal (Refereed)
  • 164.
    Damman, Peter
    et al.
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Holmvang, Lene
    Copenhagen Univ Hosp, Ctr Heart, Copenhagen, Denmark.
    Tijssen, Jan G P
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Clayton, Tim C
    London Sch Hyg & Trop Med, London WC1, England.
    Pocock, Stuart J
    London Sch Hyg & Trop Med, London WC1, England.
    Windhausen, Fons
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Hirsch, Alexander
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Fox, Keith A A
    Royal Infirm, Dept Med & Radiol Sci, Edinburgh, Midlothian, Scotland.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    de Winter, Robbert J
    Univ Amsterdam, Acad Med Ctr, Dept Cardiol, NL-1105 AZ Amsterdam, Netherlands.
    Usefulness of the Admission Electrocardiogram to Predict Long-Term Outcomes After Non-ST-Elevation Acute Coronary Syndrome (from the FRISC II, ICTUS, and RITA-3 [FIR] Trials)2012In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 109, no 1, p. 6-12Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to evaluate the independent prognostic value of qualitative and quantitative admission electrocardiographic (ECG) analysis regarding long-term outcomes after non-ST-segment elevation acute coronary syndromes (NSTE-ACS). From the Fragmin and Fast Revascularization During Instability in Coronary Artery Disease (FRISC II), Invasive Versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of Unstable Angina 3 (RITA-3) patient-pooled database, 5,420 patients with NSTE-ACS with qualitative ECG data, of whom 2,901 had quantitative data, were included in this analysis. The main outcome was 5-year cardiovascular death or myocardial infarction. Hazard ratios (HRs) were calculated with Cox regression models, and adjustments were made for established outcome predictors. The additional discriminative value was assessed with the category-less net reclassification improvement and integrated discrimination improvement indexes. In the 5,420 patients, the presence of ST-segment depression (≥1 mm; adjusted HR 1.43, 95% confidence interval [CI] 1.25 to 1.63) and left bundle branch block (adjusted HR 1.64, 95% CI 1.18 to 2.28) were independently associated with long-term cardiovascular death or myocardial infarction. Risk increases were short and long term. On quantitative ECG analysis, cumulative ST-segment depression (≥5 mm; adjusted HR 1.34, 95% CI 1.05 to 1.70), the presence of left bundle branch block (adjusted HR 2.15, 95% CI 1.36 to 3.40) or ≥6 leads with inverse T waves (adjusted HR 1.22, 95% CI 0.97 to 1.55) was independently associated with long-term outcomes. No interaction was observed with treatment strategy. No improvements in net reclassification improvement and integrated discrimination improvement were observed after the addition of quantitative characteristics to a model including qualitative characteristics. In conclusion, in the FRISC II, ICTUS, and RITA-3 NSTE-ACS patient-pooled data set, admission ECG characteristics provided long-term prognostic value for cardiovascular death or myocardial infarction. Quantitative ECG characteristics provided no incremental discrimination compared to qualitative data.

  • 165.
    Damman, Peter
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Koul, Sasha
    Eriksson, Peter
    Erlinge, David
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Treatment Patterns and Outcomes in Patients Undergoing Percutaneous Coronary Intervention Treated With Prasugrel or Clopidogrel (from the Swedish Coronary Angiography and Angioplasty Registry [SCAAR])2014In: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 113, no 1, p. 64-69Article in journal (Refereed)
    Abstract [en]

    Large real-world registry data are important for understanding the current use and outcomes of novel therapies. The aim of this study was to assess treatment patterns and outcomes in patients who underwent percutaneous coronary intervention (PCI) with prasugrel or clopidogrel. Consecutive patient data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for 2010 and 2011 were used. The study population consisted of all patients with acute coronary syndromes (ACS) and those without ACS who underwent PCI and were treated with prasugrel (with or without a clopidogrel loading dose) or solely with clopidogrel. Outcomes included were 30-day mortality and in-hospital bleeding. In 2010 and 2011, 23,994 patients were treated with clopidogrel during hospitalization for their first PCI during the study period, while 2,142 patients were treated with prasugrel. Prasugrel was mainly used in patients with ST-segment elevation myocardial infarction. Hemorrhagic risk factors such as older age, female gender, and previous stroke were more common in the clopidogrel-treated patients. However, Mehran bleeding risk scores were higher in prasugrel-treated patients. In the ACS group, lower mortality was observed in the prasugrel group compared with the clopidogrel group. Mortality was comparable in patients who underwent elective angiography and PCI. In-hospital bleeding was lower in prasugrel-treated patients. In conclusion, in this real world population of patients who underwent urgent or elective PCI, prasugrel was used mainly in patients with ACS, while it was avoided in patients with characteristics indicating increased bleeding risk. Mortality and bleeding rates were lower with prasugrel than clopidogrel, probably because of patient selection.

  • 166. Danad, Ibrahim
    et al.
    Uusitalo, Valtteri
    Kero, Tanja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Saraste, Antti
    Raijmakers, Pieter G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Lammertsma, Adriaan A.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Heymans, Martijn W.
    Kajander, Sami A.
    Pietilae, Mikko
    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.
    Sörensen, Jens
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Knaapen, Paul
    Knuuti, Juhani
    Quantitative Assessment of Myocardial Perfusion in the Detection of Significant Coronary Artery Disease Cutoff Values and Diagnostic Accuracy of Quantitative [O-15]H2O PET Imaging2014In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 64, no 14, p. 1464-1475Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Recent studies have demonstrated improved diagnostic accuracy for detecting coronary artery disease (CAD) when myocardial blood flow (MBF) is quantified in absolute terms, but there are no uniformly accepted cutoff values for hemodynamically significant CAD. OBJECTIVES The goal of this study was to determine cutoff values for absolute MBF and to evaluate the diagnostic accuracy of quantitative [O-15]H2O positron emission tomography (PET). METHODS A total of 330 patients underwent both quantitative [O-15]H2O PET imaging and invasive coronary angiography in conjunction with fractional flow reserve measurements. A stenosis >90% and/or fractional flow reserve <= 0.80 was considered obstructive; a stenosis <30% and/or fractional flow reserve >0.80 was nonobstructive. RESULTS Hemodynamically significant CAD was diagnosed in 116 (41%) of 281 patients who fulfilled study criteria for CAD. Resting perfusion was 1.00 +/- 0.25 and 0.92 +/- 0.23 ml/min/g in regions supplied by nonstenotic and significantly stenosed vessels, respectively (p < 0.001). During stress, perfusion increased to 3.26 +/- 1.04 ml/min/g and 1.73 +/- 0.67 ml/min/g, respectively (p < 0.001). The optimal cutoff values were 2.3 and 2.5 for hyperemic MBF and myocardial flow reserve, respectively. For MBF, these cutoff values showed a sensitivity, specificity, and accuracy for detecting significant CAD of 89%, 84%, and 86%, respectively, at a per-patient level and 87%, 85%, and 85% at a per-vessel level. The corresponding myocardial flow reserve values were 86%, 72%, and 78% (per patient) and 80%, 82%, and 81% (per vessel). Age and sex significantly affected diagnostic accuracy of quantitative PET. CONCLUSIONS Quantitative MBF measurements with the use of [O-15]H2O PET provided high diagnostic performance, but both sex and age should be taken into account.

  • 167. Danaei, Goodarz
    et al.
    Fahimi, Saman
    Lu, Yuan
    Zhou, Bin
    Hajifathalian, Kaveh
    Di Cesare, Mariachiara
    Lo, Wei-Cheng
    Reis-Santos, Barbara
    Cowan, Melanie J.
    Shaw, Jonathan E.
    Bentham, James
    Lin, John K.
    Bixby, Honor
    Magliano, Dianna
    Bovet, Pascal
    Miranda, J. Jaime
    Khang, Young-Ho
    Stevens, Gretchen A.
    Riley, Leanne M.
    Ali, Mohammed K.
    Ezzati, Majid
    Abdeen, Ziad A.
    Kadir, Khalid Abdul
    Abu-Rmeileh, Niveen M.
    Acosta-Cazares, Benjamin
    Aekplakorn, Wichai
    Aguilar-Salinas, Carlos A.
    Ahmadvand, Alireza
    Al Nsour, Mohannad
    Alkerwi, Ala'a
    Amouyel, Philippe
    Andersen, Lars Bo
    Anderssen, Sigmund A.
    Andrade, Dolores S.
    Anjana, Ranjit Mohan
    Aounallah-Skhiri, Hajer
    Aris, Tahir
    Arlappa, Nimmathota
    Arveiler, Dominique
    Assah, Felix K.
    Avdicova, Maria
    Balakrishna, Nagalla
    Bandosz, Piotr
    Barbagallo, Carlo M.
    Barcelo, Alberto
    Batieha, Anwar M.
    Baur, Louise A.
    Ben Romdhane, Habiba
    Bernabe-Ortiz, Antonio
    Bhargava, Santosh K.
    Bi, Yufang
    Bjerregaard, Peter
    Bjorkelund, Cecilia
    Blake, Margaret
    Blokstra, Anneke
    Bo, Simona
    Boehm, Bernhard O.
    Boissonnet, Carlos P.
    Brajkovich, Imperia
    Breckenkamp, Juergen
    Brewster, Lizzy M.
    Brian, Garry R.
    Bruno, Graziella
    Bugge, Anna
    de Leon, Antonio Cabrera
    Can, Gunay
    Candido, Ana Paula C.
    Capuano, Vincenzo
    Carvalho, Maria J.
    Casanueva, Felipe F.
    Caserta, Carmelo A.
    Castetbon, Katia
    Chamukuttan, Snehalatha
    Chaturvedi, Nishi
    Chen, Chien-Jen
    Chen, Fangfang
    Chen, Shuohua
    Cheng, Ching-Yu
    Chetrit, Angela
    Chiou, Shu-Ti
    Cho, Yumi
    Chudek, Jerzy
    Cifkova, Renata
    Claessens, Frank
    Concin, Hans
    Cooper, Cyrus
    Cooper, Rachel
    Costanzo, Simona
    Cottel, Dominique
    Cowell, Chris
    Crujeiras, Ana B.
    D'Arrigo, Graziella
    Dallongeville, Jean
    Dankner, Rachel
    Dauchet, Luc
    de Gaetano, Giovanni
    De Henauw, Stefaan
    Deepa, Mohan
    Dehghan, Abbas
    Dhana, Klodian
    Di Castelnuovo, Augusto F.
    Djalalinia, Shirin
    Doua, Kouamelan
    Drygas, Wojciech
    Du, Yong
    Egbagbe, Eruke E.
    Eggertsen, Robert
    El Ati, Jalila
    Elosua, Roberto
    Erasmus, Rajiv T.
    Erem, Cihangir
    Ergor, Gul
    Eriksen, Louise
    la Penaa, Jorge Escobedo-De
    Fall, Caroline H.
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Fernandez-Berges, Daniel
    Ferrari, Marika
    Ferreccio, Catterina
    Finn, Joseph D.
    Foger, Bernhard
    Foo, Leng Huat
    Fouad, Heba M.
    Francis, Damian K.
    Franco, Maria do Carmo
    Franco, Oscar H.
    Frontera, Guillermo
    Furusawa, Takuro
    Gaciong, Zbigniew
    Galbarczyk, Andrzej
    Garnett, Sarah P.
    Gaspoz, Jean-Michel
    Gasull, Magda
    Gates, Louise
    Geleijnse, Johanna M.
    Ghasemain, Anoosheh
    Giampaoli, Simona
    Gianfagna, Francesco
    Giovannelli, Jonathan
    Gross, Marcela Gonzalez
    Rivas, Juan P. Gonzalez
    Gorbea, Mariano Bonet
    Gottrand, Frederic
    Grant, Janet F.
    Grodzicki, Tomasz
    Grontved, Anders
    Gruden, Grabriella
    Gu, Dongfeng
    Guan, Ong Peng
    Guerrero, Ramiro
    Guessous, Idris
    Guimaraes, Andre L.
    Gutierrez, Laura
    Hardy, Rebecca
    Kumar, Rachakulla Hari
    He, Jiang
    Heidemann, Christin
    Hihtaniemi, Ilpo Tapani
    Ho, Sai Yin
    Ho, Suzanne C.
    Hofman, Albert
    Russo, Andrea R. V.
    Hormiga, Claudia M.
    Horta, Bernardo L.
    Houti, Leila
    Hussieni, Abdullatif S.
    Huybrechts, Inge
    Hwalla, Nahla
    Iacoviello, Licia
    Iannone, Anna G.
    Ibrahim, Mohsen M.
    Ikeda, Nayu
    Ikram, M. Arfan
    Irazola, Vilma E.
    Islam, Muhammad
    Iwasaki, Masanori
    Jacobs, Jeremy M.
    Jafar, Tazeen
    Jasienska, Grazyna
    Jiang, Chao Qiang
    Jonas, Jost B.
    Joshi, Pradeep
    Kafatos, Anthony
    Kalter-Leibovici, Ofra
    Kasaeian, Amir
    Katz, Joanne
    Kaur, Prabhdeep
    Kavousi, Maryam
    Kelishadi, Roya
    Kengne, Andre P.
    Kersting, Mathilde
    Khader, Yousef Saleh
    Kiechl, Stefan
    Kim, Jeongseon
    Kiyohara, Yutaka
    Kolsteren, Patrick
    Korrovits, Paul
    Koskinen, Seppo
    Kratzer, Wolfgang
    Kromhout, Daan
    Kula, Krzysztof
    Kurjata, Pawel
    Kyobutungi, Catherine
    Lachat, Carl
    Laid, Youcef
    Lam, Tai Hing
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Laxmaiah, Avula
    Leclercq, Catherine
    Lee, Jeannette
    Lee, Jeonghee
    Lehtimaki, Terho
    Lekhraj, Rampal
    Leon-Munoz, Luz M.
    Li, Yanping
    Lim, Wei-Yen
    Lima-Costa, M. Fernanda
    Lin, Hsien-Ho
    Lin, Xu
    Lissner, Lauren
    Lorbeer, Roberto
    Lozano, Jose Eugenio
    Lundqvist, Annamari
    Lytsy, Per
    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, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Ma, Guansheng
    Machado-Coelho, George L. L.
    Machi, Suka
    Maggi, Stefania
    Makdisse, Marcia
    Rao, Kodavanti Mallikharjuna
    Manios, Yannis
    Manzato, Enzo
    Margozzini, Paula
    Marques-Vidal, Pedro
    Martorell, Reynaldo
    Masoodi, Shariq R.
    Matsha, Tandi E.
    Mbanya, Jean Claude N.
    McFarlane, Shelly R.
    McGarvey, Stephen T.
    McLachlan, Stela
    McNulty, Breige A.
    Mediene-Benchekor, Sounnia
    Meirhaeghe, Aline
    Menezes, Ana Maria B.
    Merat, Shahin
    Meshram, Indrapal I.
    Mi, Jie
    Miquel, Juan Francisco
    Mohamed, Mostafa K.
    Mohammad, Kazem
    Mohan, Viswanathan
    Yusoff, Muhammad Fadhli Mohd
    Moller, Niels C.
    Molnar, Denes
    Mondo, Charles K.
    Moreno, Luis A.
    Morgan, Karen
    Moschonis, George
    Mossakowska, Malgorzata
    Mostafa, Aya
    Mota, Jorge
    Muiesan, Maria L.
    Muller-Nurasyid, Martina
    Mursu, Jaakko
    Nagel, Gabriele
    Namesna, Jana
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Navarrete-Munoz, Eva Maria
    Ndiaye, Ndeye Coumba
    Nervi, Flavio
    Nguyen, Nguyen D.
    Nieto-Martinez, Ramfi S. E.
    Ning, Guang
    Ninomiya, Toshiharu
    Noale, Marianna
    Noto, Davide
    Ochoa-Aviles, Angelica M.
    Oh, Kyungwon
    Onat, Altan
    Osmond, Clive
    Otero, Johanna A.
    Palmieri, Luigi
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Parsaeian, Mahboubeh
    Peixoto, Sergio Viana
    Pereira, Alexandre C.
    Peters, Annette
    Peykari, Niloofar
    Pilav, Aida
    Pitakaka, Freda
    Piwonska, Aleksandra
    Piwonski, Jerzy
    Plans-Rubio, Pedro
    Porta, Miquel
    Portegies, Marileen L. P.
    Poustchi, Hossein
    Pradeepa, Rajendra
    Price, Jacqueline F.
    Punab, Margus
    Qasrawi, Radwan F.
    Qorbani, Mostafa
    Raitakari, Olli
    Rao, Sudha Ramachandra
    Ramachandran, Ambady
    Ramos, Rafel
    Rampal, Sanjay
    Rathmann, Wolfgang
    Redon, Josep
    Reganit, Paul Ferdinand M.
    Rigo, Fernando
    Robinson, Sian M.
    Robitaille, Cynthia
    Rodriguez, Laura A.
    Rodriguez-Artalejo, Fernando
    Rodriguez-Perez, Maria del Cristo
    Rojas-Martinez, Rosalba
    Romaguera, Dora
    Rosengren, Annika
    Rubinstein, Adolfo
    Rui, Ornelas
    Ruiz-Betancourt, Blanca Sandra
    Rutkowski, Marcin
    Sabanayagam, Charumathi
    Sachdev, Harshpal S.
    Saidi, Olfa
    Sakarya, Sibel
    Salanave, Benoit
    Salonen, Jukka T.
    Salvetti, Massimo
    Sanchez-Abanto, Jose
    Nunes, Renata
    Santos, Rute
    Sardinha, Luis B.
    Scazufca, Marcia
    Schargrodsky, Herman
    Scheidt-Nave, Christa
    Shibuya, Kenji
    Shin, Youchan
    Shiri, Rahman
    Siantar, Rosalynn
    Sibai, Abla M.
    Simon, Mary
    Simons, Judith
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    Snijder, Marieke B.
    Solfrizzi, Vincenzo
    Sonestedt, Emily
    Soumare, Aicha
    Staessen, Jan A.
    Steene-Johannessen, Jostein
    Stehle, Peter
    Stein, Aryeh D.
    Stessman, Jochanan
    Stockl, Doris
    Stokwiszewski, Jakub
    Strufaldi, Maria Wany
    Sun, Chien-An
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Suriyawongpaisal, Paibul
    Sy, Rody G.
    Tai, E. Shyong
    Tarawneh, Mohammed
    Tarqui-Mamani, Carolina B.
    Thijs, Lutgarde
    Tolstrup, Janne S.
    Topbas, Murat
    Torrent, Maties
    Traissac, Pierre
    Trinh, Oanh T. H.
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Turley, Maria L.
    Tzourio, Christophe
    Ueda, Peter
    Ukoli, Flora M.
    Ulmer, Hanno
    Valdivia, Gonzalo
    Van Valkengoed, Irene G. M.
    Vanderschueren, Dirk
    Vanuzzo, Diego
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Veronesi, Giovanni
    Verschuren, Monique
    Vioque, Jesus
    Virtanen, Jyrki
    Visvikis-Siest, Sophie
    Viswanathan, Bharathi
    Vollenweider, Peter
    Voutilainen, Sari
    Wade, Alisha N.
    Wagner, Aline
    Walton, Janette
    Mohamud, Wan Nazaimoon Wan
    Wang, Ming-Dong
    Wang, Ya Xing
    Wannamethee, S. Goya
    Weerasekera, Deepa
    Whincup, Peter H.
    Widhalm, Kurt
    Wiecek, Andrzej
    Wilks, Rainford J.
    Willeit, Johann
    Wojtyniak, Bogdan
    Wong, Tien Yin
    Woo, Jean
    Woodward, Mark
    Wu, Aleksander Giwercman
    Wu, Frederick C.
    Wu, Shou Ling
    Xu, Haiquan
    Yang, Xiaoguang
    Ye, Xingwang
    Yoshihara, Akihiro
    Younger-Coleman, Novie O.
    Zambon, Sabina
    Zargar, Abdul Hamid
    Zdrojewski, Tomasz
    Zhao, Wenhua
    Zheng, Yingfeng
    Effects of diabetes definition on global surveillance of diabetes prevalence and diagnosis: a pooled analysis of 96 population-based studies with 331288 participants2015In: LANCET DIABETES & ENDOCRINOLOGY, ISSN 2213-8587, Vol. 3, no 8, p. 624-637Article in journal (Refereed)
    Abstract [en]

    Background Diabetes has been defined on the basis of different biomarkers, including fasting plasma glucose (FPG), 2-h plasma glucose in an oral glucose tolerance test (2hOGTT), and HbA(1c). We assessed the effect of different diagnostic definitions on both the population prevalence of diabetes and the classification of previously undiagnosed individuals as having diabetes versus not having diabetes in a pooled analysis of data from population-based health examination surveys in different regions. Methods We used data from 96 population-based health examination surveys that had measured at least two of the biomarkers used for defining diabetes. Diabetes was defined using HbA(1c) (HbA(1c) >= 6 . 5% or history of diabetes diagnosis or using insulin or oral hypoglycaemic drugs) compared with either FPG only or FPG-or-2hOGTT definitions (FPG >= 7 . 0 mmol/L or 2hOGTT >= 11 . 1 mmol/L or history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated diabetes prevalence, taking into account complex survey design and survey sample weights. We compared the prevalences of diabetes using different definitions graphically and by regression analyses. We calculated sensitivity and specificity of diabetes diagnosis based on HbA1c compared with diagnosis based on glucose among previously undiagnosed individuals (ie, excluding those with history of diabetes or using insulin or oral hypoglycaemic drugs). We calculated sensitivity and specificity in each survey, and then pooled results using a random-effects model. We assessed the sources of heterogeneity of sensitivity by meta-regressions for study characteristics selected a priori. Findings Population prevalence of diabetes based on FPG- or-2hOGTT was correlated with prevalence based on FPG alone (r= 0 . 98), but was higher by 2-6 percentage points at different prevalence levels. Prevalence based on HbA(1c) was lower than prevalence based on FPG in 42 . 8% of age-sex-survey groups and higher in another 41 . 6%; in the other 15 . 6%, the two definitions provided similar prevalence estimates. The variation across studies in the relation between glucose-based and HbA(1c)-based prevalences was partly related to participants' age, followed by natural logarithm of per person gross domestic product, the year of survey, mean BMI, and whether the survey population was national, subnational, or from specific communities. Diabetes defined as HbA(1c) 6 . 5% or more had a pooled sensitivity of 52 . 8% (95% CI 51 . 3-54 . 3%) and a pooled specificity of 99 . 74% (99 . 71-99 . 78%) compared with FPG 7 . 0 mmol/L or more for diagnosing previously undiagnosed participants; sensitivity compared with diabetes defined based on FPG-or-2hOGTT was 30 . 5% (28 . 7-32 . 3%). None of the preselected study-level characteristics explained the heterogeneity in the sensitivity of HbA(1c) versus FPG. Interpretation Different biomarkers and definitions for diabetes can provide different estimates of population prevalence of diabetes, and differentially identify people without previous diagnosis as having diabetes. Using an HbA(1c)-based definition alone in health surveys will not identify a substantial proportion of previously undiagnosed people who would be considered as having diabetes using a glucose-based test.

  • 168. Danchin, N.
    et al.
    Battler, A.
    Bueno, H.
    Hamm, C.
    Fox, K. A. A.
    Lindhal, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Schiele, F.
    Tendera, M.
    Tubaro, M.
    Vrints, C.
    The importance of global economic level on AMI outcomes: Data from the Euro Heart Survey 2009 AMI snapshot2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl 1, p. 950-950Article in journal (Other academic)
  • 169. Dans, Antonio L
    et al.
    Connolly, Stuart J
    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.
    Yang, Sean
    Nakamya, Juliet
    Brueckmann, Martina
    Ezekowitz, Michael
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Eikelboom, John W
    Reilly, Paul A
    Yusuf, Salim
    Concomitant Use of Antiplatelet Therapy with Dabigatran or Warfarin in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY®) Trial2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 127, no 5, p. 634-640Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    RE-LY showed that dabigatran etexilate 150 mg bid (DE150) was superior, and 110 mg bid (DE110) non-inferior to warfarin in preventing stroke and systemic embolism (SSE) in patients with atrial fibrillation (AF). In this subgroup analysis, we assess the efficacy and safety of dabigatran in patients who did and didn't receive concomitant antiplatelets METHODS AND RESULTS: All comparisons used a cox proportional hazards model with adjustments made for risk factors for bleeding. A time dependent analysis was performed when comparing patients with concomitant antiplatelets to those without. 6952 of 18,113 patients (38.4%) received concomitant ASA or clopidogrel at some time during the study. DE110 was non-inferior to warfarin in reducing SSE, whether patients received antiplatelets (HR=0.93; 95%CI: 0.70-1.25) or not (HR=0.87; 95%CI: 0.66-1.15; interaction p=0.738). There were less major bleeds than warfarin in both subgroups (HR=0.82; 95%CI: 0.67-1.00 for patients who used antiplatelets; HR=0.79; 95% CI: 0.64-0.96 for patients who didn't; interaction p=0.794). DE 150 reduced the primary outcome of SSE compared to warfarin. This effect seemed attenuated among patients who used antiplatelets (HR=0.80, 95%CI: 0.59-1.08) compared to those who didn't (HR=0.52, 95%CI: 0.38-0.72; p for interaction=0.058). Major bleeding was similar to warfarin regardless of antiplatelet use (HR=0.93, 95%CI: 0.76-1.12 for patients who used antiplatelets; HR=0.94, 95%CI: 0.78-1.15 for patients who didn't; p for interaction=0.875). In the time dependent analysis, concomitant use of a single antiplatelet seemed to increase the risk of major bleeding (HR=1.60; 95% CI: 1.42, 1.82). Dual antiplatelet seemed to increased this even more (HR=2.31; 95% CI: 1.79, 2.98). The absolute risks were lowest on DE110 compared to DE150 or warfarin.

    CONCLUSIONS:

    Concomitant antiplatelet drugs appeared to increase the risk for major bleeding in RE-LY without affecting the advantages of dabigatran over warfarin. Choosing between DE110 and DE150 requires a careful assessment of characteristics that influence the balance between benefit and harm.

  • 170. D'Ascenzo, Fabrizio
    et al.
    Bollati, Mario
    Clementi, Fabrizio
    Castagno, Davide
    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.
    de la Torre Hernandez, Jose M
    Ten Berg, Juriën M
    Brodie, Bruce R
    Urban, Philip
    Jensen, Lisette Okkels
    Sardi, Gabriel
    Waksman, Ron
    Lasala, John M
    Schulz, Stefanie
    Stone, Gregg W
    Airoldi, Flavio
    Colombo, Antonio
    Lemesle, Gilles
    Applegate, Robert J
    Buonamici, Piergiovanni
    Kirtane, Ajay J
    Undas, Anetta
    Sheiban, Imad
    Gaita, Fiorenzo
    Sangiorgi, Giuseppe
    Modena, Maria Grazia
    Frati, Giacomo
    Biondi-Zoccai, Giuseppe
    Incidence and predictors of coronary stent thrombosis: Evidence from an international collaborative meta-analysis including 30 studies, 221,066 patients, and 4276 thromboses2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 2, p. 575-584Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Stent thrombosis remains among the most feared complications of percutaneous coronary intervention (PCI) with stenting. However, data on its incidence and predictors are sparse and conflicting. We thus aimed to perform a collaborative systematic review on incidence and predictors of stent thrombosis.

    METHODS:

    PubMed was systematically searched for eligible studies from the drug-eluting stent (DES) era (1/2002-12/2010). Studies were selected if including ≥2000 patients undergoing stenting or reporting on ≥25 thromboses. Study features, patient characteristics, and incidence of stent thrombosis were abstracted and pooled, when appropriate, with random-effect methods (point estimate [95% confidence intervals]), and consistency of predictors was formally appraised.

    RESULTS:

    A total of 30 studies were identified (221,066 patients, 4276 thromboses), with DES used in 87%. After a median of 22months, definite, probable, or possible stent thrombosis had occurred in 2.4% (2.0%; 2.9%), with acute in 0.4% (0.2%; 0.6%), subacute in 1.1% (1.0%; 1.3%), late in 0.5% (0.4%; 0.6%), and very late in 0.6% (0.4%; 0.8%). Similar figures were computed for studies reporting only on DES. From a total of 47 candidate variables, definite/probable stent thrombosis was more commonly and consistently predicted by early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length, with acute coronary syndrome at admission, diabetes, smoking status, and bifurcation/ostial disease also proving frequent predictors, but less consistently.

    CONCLUSIONS:

    Despite numerous possible risk factors, the most common and consistent predictors of stent thrombosis are early antiplatelet therapy discontinuation, extent of coronary disease, and stent number/length.

  • 171. Davidson, Thomas
    et al.
    Husberg, Magnus
    Janzon, Magnus
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Levin, Lars-Åke
    Cost-effectiveness of dabigatran compared with warfarin for patients with atrial fibrillation in Sweden2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 3, p. 177-183Article in journal (Refereed)
    Abstract [en]

    Aims

    Patients with atrial fibrillation have a significantly increased risk of thromboembolic events such as ischaemic stroke, and patients are therefore recommended to be treated with anticoagulation treatment. The most commonly used anticoagulant consists of vitamin K antagonist such as warfarin. A new oral anticoagulation treatment, dabigatran, has recently been approved for stroke prevention among patients with atrial fibrillation. The purpose of this study was to estimate the cost-effectiveness of dabigatran as preventive treatment of stroke and thromboembolic events compared with warfarin in 65-year-old patients with atrial fibrillation in Sweden.

    Methods and results

    A decision analytic simulation model was used to estimate the long-term (20-year) costs and effects of the different treatments. The outcome measures are the number of strokes prevented, life years gained, and quality-adjusted life years (QALYs) gained. Costs and effect data are adjusted to a Swedish setting. Patients below 80 years of age are assumed to start with dabigatran 150 mg twice a day and switch to 110 mg twice a day at the age of 80 years due to higher bleeding risk. The price of dabigatran in Sweden is €2.82 (Swedish kronor 25.39) per day for both doses. The cost per QALY gained for dabigatran compared with warfarin is estimated at €7742, increasing to €12 449 if dabigatran is compared with only well-controlled warfarin treatment.

    Conclusion

    Dabigatran is a cost-effective treatment in Sweden, as its incremental cost-effectiveness ratio is below the normally accepted willingness to pay limit.

  • 172. De Caterina, R
    et al.
    Husted, S
    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.
    Andreotti, F
    Arnesen, H
    Bachmann, F
    Baigent, C
    Huber, K
    Jespersen, J
    Kristensen, S D
    Lip, G Y H
    Morais, J
    Rasmussen, L H
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Verheugt, F W A
    Weitz, J I
    General mechanisms of coagulation and targets of anticoagulants (Section I): Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease2013In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 109, no 4, p. 569-579Article in journal (Refereed)
    Abstract [en]

    Contrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. "Classical" anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.

  • 173.
    De Caterina, Raffaele
    et al.
    Univ G DAnnunzio, Inst Cardiol, Chieti, Italy.;Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy..
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Al-Khatib, Sana M.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Bahit, M. Cecilia
    INECO Neurociencias Orono, Rosario, Santa Fe, Argentina..
    Goto, Shinya
    Tokai Univ, Sch Med, Isehara, Kanagawa 25911, Japan..
    Hanna, Michael
    Bristol Myers Squibb Co, 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, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Hohnloser, Stefan
    Goethe Univ Frankfurt, Frankfurt, Germany..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA 02215 USA..
    Lanas, Fernando
    Univ La Frontera, Temuco, Chile..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Lopez-Sendon, Jose
    Hosp Univ La Paz, IdiPaz Madrid, Madrid, Spain..
    Renda, Giulia
    Univ G DAnnunzio, Inst Cardiol, Chieti, Italy.;Univ G DAnnunzio, Ctr Excellence Aging, Chieti, Italy..
    Horowitz, John
    Queen Elizabeth Hosp, Adelaide, SA, Australia..
    Granger, Christopher B.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 175, p. 175-183Article in journal (Refereed)
    Abstract [en]

    Aims History of bleeding strongly influences decisions for anticoagulation in atrial fibrillation (AF). We analyzed outcomes in relation to history of bleeding and randomization in ARISTOTLE trial patients. Methods and results The on-treatment safety population included 18,140 patients receiving at least 1 dose of study drug (apixaban) or warfarin. Centrally adjudicated outcomes in relation to bleeding history were analyzed using a Cox proportional hazards model adjusted for randomized treatment and established risk factors. Efficacy end points were analyzed on the randomized (intention to treat) population. A bleeding history was reported at baseline in 3,033 patients (16.7%), who more often were male, with a history of prior stroke/transient ischemic attack/systemic embolism and diabetes; higher CHADS2 scores, age, and body weight; and lower creatinine clearance and mean systolic blood pressure. Major (but not intracranial) bleeding occurred more frequently in patients with versus without a history of bleeding (adjusted hazard ratio 1.35, 95% CI 1.14-1.61). There were no significant interactions between bleeding history and treatment for stroke/systemic embolism, hemorrhagic stroke, death, or major bleeding, with fewer outcomes with apixaban versus warfarin for all of these outcomes independent of the presence/absence of a bleeding history. Conclusion In patients with AF in a randomized clinical trial of oral anticoagulants, a history of bleeding is associated with several risk factors for stroke and portends a higher risk of major-but not intracranial-bleeding, during anticoagulation. However, the beneficial effects of apixaban over warfarin for stroke, hemorrhagic stroke, death, or major bleeding remains consistent regardless of history of bleeding.

  • 174.
    De Caterina, Raffaele
    et al.
    Univ G DAnnunzio, Chieti, Italy.;Fdn Toscana G Monasterio, Pisa, Italy..
    Husted, Steen
    Univ Aarhus, Aarhus, Denmark..
    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.
    Andreotti, Felicita
    Univ Cattolica Sacro Cuore, I-00168 Rome, Italy..
    Arnesen, Harald
    Oslo Univ Hosp Ulleval, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Bachmann, Fedor
    Univ Lausanne, Lausanne, Switzerland..
    Baigent, Colin
    Univ Oxford, Oxford, England..
    Collet, Jean-Philippe
    Grp Hosp Pitie Salpetriere, INSERM, UMRS ICAN 1166, F-75634 Paris, France..
    Halvorsen, Sigrun
    Oslo Univ Hosp Ulleval, Oslo, Norway.;Univ Oslo, Oslo, Norway..
    Huber, Kurt
    Wilhelminenhosp, Vienna, Austria..
    Jespersen, Jorgen
    Univ Southern Denmark, Esbjerg, Denmark..
    Kristensen, Steen Dalby
    Aarhus Univ Hosp, DK-8000 Aarhus, Denmark..
    Lip, Gregory Y. H.
    Univ Birmingham, City Hosp, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Morais, Joao
    Hosp Santo Andre, Leiria, Portugal..
    Rasmussen, Lars Hvilsted
    Aalborg Univ, Aalborg, Denmark..
    Ricci, Fabrizio
    Univ G DAnnunzio, Chieti, Italy.;Fdn Toscana G Monasterio, Pisa, Italy..
    Sibbing, Dirk
    Univ Munich, Klinikum Univ Munchen, Med Klin & Poliklin 1, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Storey, Robert F.
    Univ Sheffield, Sheffield, S Yorkshire, England..
    ten Berg, Jurrien
    St Antonius Hosp, Nieuwegein, Netherlands..
    Verheugt, Freek W. A.
    Onze Lieve Vrouw Hosp, Amsterdam, Netherlands..
    Weitz, Jeffrey I.
    McMaster Univ, Hamilton, ON, Canada.;Thrombosis & Atherosclerosis Res Inst, Hamilton, ON, Canada..
    Oral anticoagulants in coronary heart disease (Section IV) Position paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease2016In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 115, no 4, p. 685-711Article in journal (Refereed)
    Abstract [en]

    Until recently, vitamin K antagonists (VKAs) were the only available oral anticoagulants evaluated for long-term treatment of patients with coronary heart disease (CHD), particularly after an acute coronary syndrome (ACS). Despite efficacy in this setting, VKAs are rarely used because they are cumbersome to administer. Instead, the more readily manageable antiplatelet agents are the mainstay of prevention in ACS patients. This situation has the potential to change with the introduction of non-VKA oral anticoagulants (NOACs), which are easier to administer than VKAs because they can be given in fixed doses without routine coagulation monitoring. The NOACs include dabigatran, which inhibits thrombin, and apixaban, rivaroxaban and edoxaban, which inhibit factor Xa. Apixaban and rivaroxaban were evaluated in phase III trials for prevention of recurrent ischaemia in ACS patients, most of whom were also receiving dual antiplatelet therapy with aspirin and clopidogrel. Although at the doses tested rivaroxaban was effective and apixaban was not, both agents increased major bleeding. The role for the NOACs in ACS management, although promising, is therefore complicated, because it is uncertain how they compare with newer antiplatelet agents, such as prasugrel, ticagrelor or vorapaxar, and because their safety in combination with these other drugs is unknown. Ongoing studies are also now evaluating the use of NOACs in non-valvular atrial fibrillation patients, where their role is established, with coexistent ACS or coronary stenting. Focusing on CHD, we review the results of clinical trials with the NOACs and provide a perspective on their future incorporation into clinical practice.

  • 175. De Caterina, Raffaele
    et al.
    Husted, Steen
    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. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Andreotti, Felicita
    Arnesen, Harald
    Bachmann, Fedor
    Baigent, Colin
    Huber, Kurt
    Jespersen, Jorgen
    Kristensen, Steen Dalby
    Lip, Gregory Y. H.
    Morais, Joao
    Rasmussen, Lars Hvilsted
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Verheugt, Freek W. A.
    Weitz, Jeffrey I.
    Parenteral anticoagulants in heart disease: Current status and perspectives (Section II) Position Paper of the ESC Working Group on Thrombosis - Task Force on Anticoagulants in Heart Disease2013In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 109, no 5, p. 769-786Article in journal (Refereed)
    Abstract [en]

    Anticoagulants are a mainstay of cardiovascular therapy, and parenteral anticoagulants have widespread use in cardiology, especially in acute situations. Parenteral anticoagulants include unfractionated heparin, low-molecular-weight heparins, the synthetic pentasaccharides fondaparinux, idraparinux and idrabiotaparinux, and parenteral direct thrombin inhibitors. The several shortcomings of unfractionated heparin and of low-molecular-weight heparins have prompted the development of the other newer agents. Here we review the mechanisms of action, pharmacological properties and side effects of parenteral anticoagulants used in the management of coronary heart disease treated with or without percutaneous coronary interventions, cardioversion for atrial fibrillation, and prosthetic heart valves and valve repair. Using an evidence-based approach, we describe the results of completed clinical trials, highlight ongoing research with currently available agents, and recommend therapeutic options for specific heart diseases.

  • 176. De Caterina, Raffaele
    et al.
    Husted, Steen
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andreotti, Felicita
    Arnesen, Harald
    Bachmann, Fedor
    Baigent, Colin
    Huber, Kurt
    Jespersen, Jorgen
    Kristensen, Steen Dalby
    Lip, Gregory Y. H.
    Morais, Joao
    Rasmussen, Lars Hvilsted
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Verheugt, Freek W. A.
    Weitz, Jeffrey I.
    Vitamin K antagonists in heart disease: Current status and perspectives (Section III)2013In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 110, no 6, p. 1087-1107Article in journal (Refereed)
    Abstract [en]

    Oral anticoagulants are a mainstay of cardiovascular therapy, and for over 60 years vitamin K antagonists (VKAs) were the only available agents for long-term use. VKAs interfere with the cyclic inter-conversion of vitamin K and its 2,3 epoxide, thus inhibiting gamma-carboxylation of glutamate residues at the amino-termini of vitamin K-dependent proteins, including the coagulation factors (F) II (prothrombin), VII, IX and X, as well as of the anticoagulant proteins C, S and Z. The overall effect of such interference is a dose-dependent anticoagulant effect, which has been therapeutically exploited in heart disease since the early 1950s. In this position paper, we review the mechanisms of action, pharmacological properties and side effects of VKAs, which are used in the management of cardiovascular diseases, including coronary heart disease (where their use is limited), stroke prevention in atrial fibrillation, heart valves and/or chronic heart failure. Using an evidence-based approach, we describe the results of completed clinical trials, highlight areas of uncertainty, and recommend therapeutic options for specific disorders. Although VKAs are being increasingly replaced in most patients with non-valvular atrial fibrillation by the new oral anticoagulants, which target either thrombin or FXa, the VKAs remain the agents of choice for patients with atrial fibrillation in the setting of rheumatic valvular disease and for those with mechanical heart valves.

  • 177. De Palma, Rodney
    et al.
    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.
    Jueni, Peter
    Cuisset, Thomas
    Will this trial change my practice?: ACCOAST - early loading with a novel P2Y12 inhibitor in patients with an acute coronary syndrome2014In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 10, no 3, p. 408-410Article in journal (Other academic)
  • 178. Di Angelantonio, Emanuele
    et al.
    Gao, Pei
    Khan, Hassan
    Butterworth, Adam S.
    Wormser, David
    Kaptoge, Stephen
    Seshasai, Sreenivasa Rao Kondapally
    Thompson, Alex
    Sarwar, Nadeem
    Willeit, Peter
    Ridker, Paul M.
    Barr, Elizabeth L. M.
    Khaw, Kay-Tee
    Psaty, Bruce M.
    Brenner, Hermann
    Balkau, Beverley
    Dekker, Jacqueline M.
    Lawlor, Debbie A.
    Daimon, Makoto
    Willeit, Johann
    Njolstad, Inger
    Nissinen, Aulikki
    Brunner, Eric J.
    Kuller, Lewis H.
    Price, Jackie F.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Knuiman, Matthew W.
    Feskens, Edith J. M.
    Verschuren, W. M. M.
    Wald, Nicholas
    Bakker, Stephan J. L.
    Whincup, Peter H.
    Ford, Ian
    Goldbourt, Uri
    Gomez-de-la-Camara, Agustin
    Gallacher, John
    Simons, Leon A.
    Rosengren, Annika
    Sutherland, Susan E.
    Bjorkelund, Cecilia
    Blazer, Dan G.
    Wassertheil-Smoller, Sylvia
    Onat, Altan
    Ibanez, Alejandro Marin
    Casiglia, Edoardo
    Jukema, J. Wouter
    Simpson, Lara M.
    Giampaoli, Simona
    Nordestgaard, Borge G.
    Selmer, Randi
    Wennberg, Patrik
    Kauhanen, Jussi
    Salonen, Jukka T.
    Dankner, Rachel
    Barrett-Connor, Elizabeth
    Kavousi, Maryam
    Gudnason, Vilmundur
    Evans, Denis
    Wallace, Robert B.
    Cushman, Mary
    D'Agostino, Ralph B., Sr.
    Umans, Jason G.
    Kiyohara, Yutaka
    Nakagawa, Hidaeki
    Sato, Shinichi
    Gillum, Richard F.
    Folsom, Aaron R.
    van der Schouw, Yvonne T.
    Moons, Karel G.
    Griffin, Simon J.
    Sattar, Naveed
    Wareham, Nicholas J.
    Selvin, Elizabeth
    Thompson, Simon G.
    Danesh, John
    Glycated Hemoglobin Measurement and Prediction of Cardiovascular Disease2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 311, no 12, p. 1225-1233Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The value of measuring levels of glycated hemoglobin (HbA(1c)) for the prediction of first cardiovascular events is uncertain. OBJECTIVE To determine whether adding information on HbA(1c) values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS Analysis of individual-participant data available from 73 prospective studies involving 294 998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (>= 7.5%) risk. RESULTS During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20 840 incident fatal and nonfatal CVD outcomes (13 237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA(1c) values and CVD risk. The association between HbA(1c) values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA(1c) was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA(1c) assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE In a study of individuals without known CVD or diabetes, additional assessment of HbA(1c) values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

  • 179. Di Angelantonio, Emanuele
    et al.
    Kaptoge, Stephen
    Wormser, David
    Willeit, Peter
    Butterworth, Adam S.
    Bansal, Narinder
    O'Keeffe, Linda M.
    Gao, Pei
    Wood, Angela M.
    Burgess, Stephen
    Freitag, Daniel F.
    Pennells, Lisa
    Peters, Sanne A.
    Hart, Carole L.
    Haheim, Lise Lund
    Gillum, Richard F.
    Nordestgaard, Borge G.
    Psaty, Bruce M.
    Yeap, Bu B.
    Knuiman, Matthew W.
    Nietert, Paul J.
    Kauhanen, Jussi
    Salonen, Jukka T.
    Kuller, Lewis H.
    Simons, Leon A.
    van der Schouw, Yvonne T.
    Barrett-Connor, Elizabeth
    Selmer, Randi
    Crespo, Carlos J.
    Rodriguez, Beatriz
    Verschuren, W. M. Monique
    Salomaa, Veikko
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    van der Harst, Pim
    Bjorkelund, Cecilia
    Wilhelmsen, Lars
    Wallace, Robert B.
    Brenner, Hermann
    Amouyel, Philippe
    Barr, Elizabeth L. M.
    Iso, Hiroyasu
    Onat, Altan
    Trevisan, Maurizio
    D'Agostino, Ralph B., Sr.
    Cooper, Cyrus
    Kavousi, Maryam
    Welin, Lennart
    Roussel, Ronan
    Hu, Frank B.
    Sato, Shinichi
    Davidson, Karina W.
    Howard, Barbara V.
    Leening, Maarten
    Rosengren, Annika
    Dorr, Marcus
    Deeg, Dorly J. H.
    Kiechl, Stefan
    Stehouwer, Coen D. A.
    Nissinen, Aulikki
    Giampaoli, Simona
    Donfrancesco, Chiara
    Kromhout, Daan
    Price, Jackie F.
    Peters, Annette
    Meade, Tom W.
    Casiglia, Edoardo
    Lawlor, Debbie A.
    Gallacher, John
    Nagel, Dorothea
    Franco, Oscar H.
    Assmann, Gerd
    Dagenais, Gilles R.
    Jukema, J. Wouter
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Woodward, Mark
    Brunner, Eric J.
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Whitsel, Eric A.
    Njolstad, Inger
    Hedblad, Bo
    Wassertheil-Smoller, Sylvia
    Engstrom, Gunnar
    Rosamond, Wayne D.
    Selvin, Elizabeth
    Sattar, Naveed
    Thompson, Simon G.
    Danesh, John
    Association of Cardiometabolic Multimorbidity With Mortality: The Emerging Risk Factors Collaboration2015In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 314, no 1, p. 52-60Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing.

    OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.

    DESIGN, SETTING, AND PARTICIPANTS Age-and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689 300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128 843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499 808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).

    MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy.

    RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.

    CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

  • 180.
    Di Cesare, Mariachiara
    et al.
    Univ London Imperial Coll Sci Technol & Med, London, England.;Middlesex Univ, London N17 8HR, England..
    Bentham, James
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Stevens, Gretchen A.
    WHO, CH-1211 Geneva, Switzerland..
    Zhou, Bin
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Danaei, Goodarz
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Lu, Yuan
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Bixby, Honor
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Cowan, Melanie J.
    WHO, CH-1211 Geneva, Switzerland..
    Riley, Leanne M.
    WHO, CH-1211 Geneva, Switzerland..
    Hajifathalian, Kaveh
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Fortunato, Lea
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Taddei, Cristina
    Univ Florence, Florence, Italy..
    Bennett, James E.
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ikeda, Nayu
    Natl Inst Hlth & Nutr, Tokyo 162, Japan..
    Khang, Young-Ho
    Seoul Natl Univ, Seoul, South Korea..
    Kyobutungi, Catherine
    African Populat & Hlth Res Ctr, Nairobi, Kenya..
    Laxmaiah, Avula
    Indian Council Med Res, New Delhi, India..
    Li, Yanping
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Lin, Hsien-Ho
    Natl Taiwan Univ, Taipei 10764, Taiwan..
    Miranda, J. Jaime
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Mostafa, Aya
    Ain Shams Univ, Cairo, Egypt..
    Turley, Maria L.
    Minist Hlth, Wellington, New Zealand..
    Paciorek, Christopher J.
    Univ Calif Berkeley, Berkeley, CA 94720 USA..
    Gunter, Marc
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ezzati, Majid
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Abdeen, Ziad A.
    Al Quds Univ, Jerusalem, Israel..
    Hamid, Zargar Abdul
    Ctr Diabet & Endocrine Care, Bengaluru, India..
    Abu-Rmeileh, Niveen M.
    Birzeit Univ, Bir Zayt, Israel..
    Acosta-Cazares, Benjamin
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Adams, Robert
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Aekplakorn, Wichai
    Mahidol Univ, Bangkok 10700, Thailand..
    Aguilar-Salinas, Carlos A.
    Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Rio Grande, Mexico..
    Ahmadvand, Alireza
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Ahrens, Wolfgang
    Leibniz Inst Prevent Res & Epidemiol BIPS, Leibniz, Germany..
    Ali, Mohamed M.
    World Hlth Org Reg Off Eastern Mediterranean, Giza, Egypt..
    Alkerwi, Ala'a
    Luxembourg Inst Hlth, Luxembourg, Luxembourg..
    Alvarez-Pedrerol, Mar
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Aly, Eman
    World Hlth Org Reg Off Eastern Mediterranean, Giza, Egypt..
    Amouyel, Philippe
    Lille Univ & Hosp, Lille, France..
    Amuzu, Antoinette
    London Sch Hyg & Trop Med, London, England..
    Andersen, Lars Bo
    Univ Southern Denmark, Lyngby, Denmark..
    Anderssen, Sigmund A.
    Norwegian Sch Sport Sci, Oslo, Norway..
    Andrade, Dolores S.
    Univ Cuenca, Cuenca, Ecuador..
    Anjana, Ranjit Mohan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Aounallah-Skhiri, Hajer
    Natl Inst Publ Hlth, Tunis, Tunisia..
    Ariansen, Inger
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Aris, Tahir
    Minist Hlth, Kuala Lumpur, Malaysia..
    Arlappa, Nimmathota
    Indian Council Med Res, New Delhi, India..
    Arveiler, Dominique
    Strasbourg Univ & Hosp, Strasbourg, France..
    Assah, Felix K.
    Univ Yaounde I, Yaounde, Cameroon..
    Avdicova, Maria
    Reg Author Publ Hlth, Banska Bystrica, Slovakia..
    Azizi, Fereidoun
    Shahid Beheshti Univ Med Sci, Tehran, Iran..
    Babu, Bontha V.
    Indian Council Med Res, New Delhi, India..
    Balakrishna, Nagalla
    Indian Council Med Res, New Delhi, India..
    Bandosz, Piotr
    Med Univ Gdansk, Gdansk, Poland..
    Banegas, Jose R.
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    Barbagallo, Carlo M.
    Univ Palermo, I-90133 Palermo, Italy..
    Barcelo, Alberto
    Pan Amer Hlth Org, El Paso, TX USA..
    Barkat, Amina
    Univ Mohammed V Rabat, Rabat, Morocco..
    Barros, Mauro V.
    Univ Pernambuco, Petrolina, PE, Brazil..
    Bata, Iqbal
    Dalhousie Univ, Halifax, NS B3H 3J5, Canada..
    Batieha, Anwar M.
    Jordan Univ Sci & Technol, Amman, Jordan..
    Batista, Rosangela L.
    Univ Fed Maranhao, Sao Luis, Brazil..
    Baur, Louise A.
    Univ Sydney, Sydney, NSW 2006, Australia..
    Beaglehole, Robert
    Univ Auckland, Auckland 1, New Zealand..
    Ben Romdhane, Habiba
    Univ Tunis El Manar, Tunis, Tunisia..
    Benet, Mikhail
    Univ Med Sci, Havana, Cuba..
    Bernabe-Ortiz, Antonio
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Bernotiene, Gailute
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Bettiol, Heloisa
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Bhagyalaxmi, Aroor
    BJ Med Coll, New Delhi, India..
    Bharadwaj, Sumit
    Chirayu Med Coll, Bhopal, India..
    Bhargava, Santosh K.
    Sunder Lal Jain Hosp, New Delhi, India..
    Bhatti, Zaid
    Aga Khan Univ, Lahore, Pakistan..
    Bhutta, Zulfiqar A.
    Aga Khan Univ, Lahore, Pakistan..
    Bi, HongSheng
    Shandong Univ Tradit Chinese Med, Jinan, Peoples R China..
    Bi, Yufang
    Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China..
    Bjerregaard, Peter
    Univ Southern Denmark, Lyngby, Denmark..
    Bjertness, Espen
    Univ Oslo, N-0316 Oslo, Norway..
    Bjertness, Marius B.
    Univ Oslo, N-0316 Oslo, Norway..
    Bjorkelund, Cecilia
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Blake, Margaret
    NatCen Social Res, London, England..
    Blokstra, Anneke
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Bo, Simona
    Univ Turin, I-10124 Turin, Italy..
    Bobak, Martin
    UCL, London WC1E 6BT, England..
    Boddy, Lynne M.
    Liverpool John Moores Univ, Liverpool L3 5UX, Merseyside, England..
    Boehm, Bernhard O.
    Nanyang Technol Univ, Singapore 639798, Singapore..
    Boeing, Heiner
    German Inst Human Nutr, Berlin, Germany..
    Boissonnet, Carlos P.
    CEMIC, Buenos Aires, DF, Argentina..
    Bongard, Vanina
    Toulouse Univ, Sch Med, Toulouse, France..
    Bovet, Pascal
    Minist Hlth, Victoria, Seychelles.;Univ Lausanne, CH-1015 Lausanne, Switzerland..
    Braeckman, Lutgart
    Univ Ghent, B-9000 Ghent, Belgium..
    Bragt, Marjolijn C. E.
    FrieslandCampina, Singapore, Singapore..
    Brajkovich, Imperia
    Cent Univ Venezuela, Caracas, Venezuela..
    Branca, Francesco
    WHO, CH-1211 Geneva, Switzerland..
    Breckenkamp, Juergen
    Univ Bielefeld, Bielefeld, Germany..
    Brenner, Hermann
    German Canc Res Ctr, Berlin, Germany..
    Brewster, Lizzy M.
    Univ Amsterdam, NL-1012 WX Amsterdam, Netherlands..
    Brian, Garry R.
    Fred Hollows Fdn New Zealand, Auckland, New Zealand..
    Bruno, Graziella
    Univ Turin, I-10124 Turin, Italy..
    Bueno-de-Mesquita, H. B(as)
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Bugge, Anna
    Univ Southern Denmark, Lyngby, Denmark..
    Burns, Con
    Cork Inst Technol, Cork, Ireland..
    Cabrera de Leon, Antonio
    Univ La Laguna, E-38207 San Cristobal la Laguna, Spain..
    Cacciottolo, Joseph
    Univ Malta, Msida, Malta..
    Cama, Tilema
    Minist Hlth, Nukualofa, Tonga..
    Cameron, Christine
    Canadian Fitness & Lifestyle Res Inst, Toronto, ON, Canada..
    Camolas, Jose
    Hosp Santa Maria, CHLN, Lisbon, Portugal..
    Can, Gunay
    Istanbul Univ, Istanbul, Turkey..
    Candido, Ana Paula C.
    Univ Fed Juiz de Fora, Juiz De Fora, Brazil..
    Capuano, Vincenzo
    Cardiol Mercato S Severino, Mercato San Severino, Italy..
    Cardoso, Viviane C.
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Carvalho, Maria J.
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Casanueva, Felipe F.
    Univ Santiago de Compostela, Santiago De Compostela, Spain..
    Casas, Juan-Pablo
    UCL, London WC1E 6BT, England..
    Caserta, Carmelo A.
    Assoc Calabrese Epatol, Rome, Italy..
    Castetbon, Katia
    French Inst Hlth Surveillance, Lyon, France..
    Chamukuttan, Snehalatha
    India Diabet Res Fdn, New Delhi, India..
    Chan, Angelique W.
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Chan, Queenie
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Chaturvedi, Himanshu K.
    Natl Inst Med Stat, New Delhi, India..
    Chaturvedi, Nishi
    UCL, London WC1E 6BT, England..
    Chen, Chien-Jen
    Acad Sinica, Taipei, Taiwan..
    Chen, Fangfang
    Capital Inst Pediat, Beijing, Peoples R China..
    Chen, Huashuai
    Duke Univ, Durham, NC 27706 USA..
    Chen, Shuohua
    Kailuan Gen Hosp, Beijing, Peoples R China..
    Chen, Zhengming
    Univ Oxford, Oxford OX1 2JD, England..
    Cheng, Ching-Yu
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Chetrit, Angela
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Chiolero, Arnaud
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Chiou, Shu-Ti
    Minist Hlth & Welf, Taipei, Taiwan..
    Chirita-Emandi, Adela
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Cho, Yumi
    Korea Ctr Dis Control & Prevent, Seoul, South Korea..
    Christensen, Kaare
    Univ Southern Denmark, Lyngby, Denmark..
    Chudek, Jerzy
    Med Univ Silesia, Katowice, Poland..
    Cifkova, Renata
    Charles Univ Prague, Prague, Czech Republic..
    Claessens, Frank
    Katholieke Univ Leuven, Louvain, Belgium..
    Clays, Els
    Univ Ghent, B-9000 Ghent, Belgium..
    Concin, Hans
    Agcy Prevent & Social Med, Vienna, Austria..
    Cooper, Cyrus
    Univ Southampton, Southampton SO9 5NH, Hants, England..
    Cooper, Rachel
    UCL, London WC1E 6BT, England..
    Coppinger, Tara C.
    Cork Inst Technol, Cork, Ireland..
    Costanzo, Simona
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Cottel, Dominique
    Inst Pasteur, Lille, France..
    Cowell, Chris
    Westmead Univ Sydney, Sydney, NSW, Australia..
    Craig, Cora L.
    Canadian Fitness & Lifestyle Res Inst, Toronto, ON, Canada..
    Crujeiras, Ana B.
    CIBEROBN, Madrid, Spain..
    D'Arrigo, Graziella
    CNR, Rome, Italy..
    d'Orsi, Eleonora
    Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Dallongeville, Jean
    Inst Pasteur, Lille, France..
    Damasceno, Albertino
    Eduardo Mondlane Univ, Maputo, Mozambique..
    Damsgaard, Camilla T.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Dankner, Rachel
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Dauchet, Luc
    Lille Univ Hosp, Lille, France..
    De Backer, Guy
    Univ Ghent, B-9000 Ghent, Belgium..
    De Bacquer, Dirk
    Univ Ghent, B-9000 Ghent, Belgium..
    de Gaetano, Giovanni
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    De Henauw, Stefaan
    Univ Ghent, B-9000 Ghent, Belgium..
    De Smedt, Delphine
    Univ Ghent, B-9000 Ghent, Belgium..
    Deepa, Mohan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Deev, Alexander D.
    Natl Res Ctr Prevent Med, Moscow, Russia..
    Dehghan, Abbas
    Erasmus MC, Rotterdam, Netherlands.;Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Delisle, Helene
    Univ Montreal, Montreal, PQ H3C 3J7, Canada..
    Delpeuch, Francis
    Inst Rech Dev, Lyon, France..
    Dhana, Klodian
    Erasmus MC, Rotterdam, Netherlands..
    Di Castelnuovo, Augusto F.
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Dias-da-Costa, Juvenal Soares
    Univ Vale Rio dos Sinos, Sao Leopoldo, RS, Brazil..
    Diaz, Alejandro
    Natl Council Sci & Tech Res, Buenos Aires, DF, Argentina..
    Djalalinia, Shirin
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Do, Ha T. P.
    Natl Inst Nutr, Hanoi, Vietnam..
    Dobson, Annette J.
    Univ Queensland, Brisbane, Qld 4072, Australia..
    Donfrancesco, Chiara
    Ist Super Sanita, Rome, Italy..
    Doering, Angela
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Doua, Kouamelan
    Minist Sante & Lutte Sida, Yamoussoukro, Cote Ivoire..
    Drygas, Wojciech
    Cardinal Wyszynski Inst Cardiol, Warsaw, Poland..
    Egbagbe, Eruke E.
    Univ Benin, Coll Med Sci, Benin, Nigeria..
    Eggertsen, Robert
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Ekelund, Ulf
    Norwegian Sch Sport Sci, Oslo, Norway..
    El Ati, Jalila
    Natl Inst Nutr & Food Technol, Tunis, Tunisia..
    Elliott, Paul
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Engle-Stone, Reina
    Univ Calif Davis, Davis, CA USA..
    Erasmus, Rajiv T.
    Univ Stellenbosch, ZA-7600 Stellenbosch, South Africa..
    Erem, Cihangir
    Karadeniz Tech Univ, Trabzon, Turkey..
    Eriksen, Louise
    Univ Southern Denmark, Lyngby, Denmark..
    Escobedo-de la Pena, Jorge
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Evans, Alun
    Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland..
    Faeh, David
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Fall, Caroline H.
    Univ Southampton, Southampton SO9 5NH, Hants, England.;Univ Tehran Med Sci, Tehran, Iran..
    Farzadfar, Farshad
    Felix-Redondo, Francisco J.
    Ferguson, Trevor S.
    Univ W Indies, Kingston, Jamaica..
    Fernandez-Berges, Daniel
    Ferrante, Daniel
    Minist Hlth, Buenos Aires, DF, Argentina..
    Ferrari, Marika
    Council Agr Res & Econ, Rome, Italy..
    Ferreccio, Catterina
    Ferrieres, Jean
    Toulouse Univ, Sch Med, Toulouse, France..
    Finn, Joseph D.
    Univ Manchester, Manchester M13 9PL, Lancs, England..
    Fischer, Krista
    Univ Tartu, Tartu, Estonia..
    Monterubio Flores, Eric
    Inst Nacl Salud Publ, Mexico City, DF, Mexico..
    Foeger, Bernhard
    Agcy Prevent & Social Med, Vienna, Austria..
    Foo, Leng Huat
    Univ Sains Malaysia, Shah Alam, Malaysia..
    Forslund, Ann-Sofie
    Univ Lulea, S-97187 Lulea, Sweden..
    Fortmann, Stephen P.
    Stanford Univ, Stanford, CA 94305 USA..
    Fouad, Heba M.
    Francis, Damian K.
    Franco, Maria do Carmo
    Franco, Oscar H.
    Erasmus MC, Rotterdam, Netherlands.;Univ Fed Sao Paulo, Sao Paulo, Brazil..
    Frontera, Guillermo
    Fuchs, Flavio D.
    Fuchs, Sandra C.
    Univ Fed Rio Grande do Sul, BR-90046900 Porto Alegre, RS, Brazil..
    Fujita, Yuki
    Kinki Univ, Fac Med, Higashiosaka, Osaka 577, Japan..
    Furusawa, Takuro
    Kyoto Univ, Kyoto 6068501, Japan..
    Gaciong, Zbigniew
    Med Univ Warsaw, Warsaw, Poland..
    Gafencu, Mihai
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Gareta, Dickman
    Garnett, Sarah P.
    Univ Sydney, Sydney, NSW 2006, Australia..
    Gaspoz, Jean-Michel
    Univ Hosp Geneva, Geneva, Switzerland..
    Gasull, Magda
    Gates, Louise
    Geleijnse, Johanna M.
    Wageningen Univ, NL-6700 AP Wageningen, Netherlands..
    Ghasemian, Anoosheh
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Giampaoli, Simona
    Ist Super Sanita, Rome, Italy..
    Gianfagna, Francesco
    Univ Insubria, Varese, Italy..
    Giovannelli, Jonathan
    Lille Univ Hosp, Lille, France..
    Giwercman, Aleksander
    Lund Univ, S-22100 Lund, Sweden..
    Goldsmith, Rebecca A.
    Gonzalez Gross, Marcela
    Univ Politecn Madrid, E-28040 Madrid, Spain..
    Gonzalez Rivas, Juan P.
    Andes Clin Cardiometab Studies, Caracas, Venezuela..
    Bonet Gorbea, Mariano
    Natl Inst Hyg Epidemiol & Microbiol, Havana, Cuba..
    Gottrand, Frederic
    Univ Lille 2, F-59800 Lille, France..
    -Iversen, Sidsel Graff
    Norwegian Inst Publ Hlth, Oslo, Norway..
    Grafnetter, Dusan
    Inst Clin & Expt Med, Prague, Czech Republic..
    Grajda, Aneta
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Grammatikopoulou, Maria G.
    Alexander Technol Educ Inst, Athens, Greece..
    Gregor, Ronald D.
    Dalhousie Univ, Halifax, NS B3H 3J5, Canada..
    Grodzicki, Tomasz
    Jagiellonian Univ, Coll Med, PL-31007 Krakow, Poland..
    Grontved, Anders
    Univ Southern Denmark, Lyngby, Denmark..
    Gruden, Grabriella
    Univ Turin, I-10124 Turin, Italy..
    Grujic, Vera
    Inst Publ Hlth Vojvodina, Belgrade, Serbia..
    Gu, Dongfeng
    Natl Ctr Cardiovasc Dis, Beijing, Peoples R China..
    Guan, Ong Peng
    Singapore Eye Res Inst, Singapore, Singapore..
    Gudnason, Vilmundur
    Iceland Heart Assoc, Kopavogur, Iceland..
    Guerrero, Ramiro
    Univ Icesi, Cali, Colombia..
    Guessous, Idris
    Univ Hosp Geneva, Geneva, Switzerland..
    Guimaraes, Andre L.
    Gulliford, Martin C.
    Kings Coll London, London WC2R 2LS, England..
    Gunnlaugsdottir, Johanna
    Guo, Xiu H.
    Capital Med Univ, Beijing, Peoples R China..
    Guo, Yin
    Capital Med Univ, Beijing, Peoples R China..
    Gupta, Prakash C.
    Healis Sekhsaria Inst Publ Hlth, New Delhi, India..
    Gureje, Oye
    Univ Ibadan, Ibadan, Nigeria..
    Gurzkowska, Beata
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Gutierrez, Laura
    Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina..
    Gutzwiller, Felix
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Halkjaer, Jytte
    Danish Canc Soc Res Ctr, Lyngby, Denmark..
    Hardy, Rebecca
    UCL, London WC1E 6BT, England..
    Kumar, Rachakulla Hari
    Indian Council Med Res, New Delhi, India..
    Hayes, Alison J.
    Univ Sydney, Sydney, NSW 2006, Australia.;Tulane Univ, New Orleans, LA 70118 USA..
    He, Jiang
    Hendriks, Marleen Elisabeth
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Hernandez Cadena, Leticia
    Natl Inst Publ Hlth, Mexicali, Baja California, Mexico..
    Heshmat, Ramin
    Hihtaniemi, Ilpo Tapani
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Ho, Sai Yin
    Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Ho, Suzanne C.
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Hobbs, Michael
    Univ Western Australia, Nedlands, WA 6009, Australia..
    Hofman, Albert
    Erasmus MC, Rotterdam, Netherlands..
    Hormiga, Claudia M.
    Horta, Bernardo L.
    Univ Fed Pelotas, Pelotas, Brazil..
    Houti, Leila
    Univ Oran 1, Oran, Algeria..
    Htay, Thein Thein
    Htet, Aung Soe
    Univ Oslo, N-0316 Oslo, Norway..
    Htike, Maung Maung Than
    Minist Hlth, Naypyidaw, Myanmar..
    Hu, Yonghua
    Peking Univ, Hlth Sci Ctr, Beijing, Peoples R China..
    Hussieni, Abdullatif S.
    Birzeit Univ, Bir Zayt, Israel..
    Huu, Chinh Nguyen
    Huybrechts, Inge
    Int Agcy Res Canc, Lyon, France..
    Hwalla, Nahla
    Amer Univ Beirut, Beirut, Lebanon..
    Iacoviello, Licia
    IRCCS Ist Neurol Mediterraneo Neuromed, Rome, Italy..
    Iannone, Anna G.
    Cardiol Mercato S Severino, Mercato San Severino, Italy..
    Ibrahim, M. Mohsen
    Cairo Univ, Cairo, Egypt..
    Ikram, M. Arfan
    Erasmus MC, Rotterdam, Netherlands..
    Irazola, Vilma E.
    Islam, Muhammad
    Aga Khan Univ, Lahore, Pakistan..
    Iwasaki, Masanori
    Niigata Univ, Niigata 95021, Japan..
    Jackson, Rod T.
    Univ Auckland, Auckland 1, New Zealand..
    Jacobs, Jeremy M.
    Hadassah Univ, Med Ctr, Tel Aviv, Israel..
    Jafar, Tazeen
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Jamil, Kazi M.
    Kuwait Inst Scientifi c Res, Kuwait, Kuwait..
    Jamrozik, Konrad
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Jasienska, Grazyna
    Jiang, Chao Qiang
    Guangzhou 12th Hosp, Guangzhou, Guangdong, Peoples R China..
    Joffres, Michel
    Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada..
    Johansson, Mattias
    Jonas, Jost B.
    Heidelberg Univ, Heidelberg, Germany..
    Jorgensen, Torben
    Joshi, Pradeep
    World Hlth Org Country Off, New Delhi, India..
    Juolevi, Anne
    Natl Inst Hlth & Welf, Espoo, Finland..
    Jurak, Gregor
    Univ Ljubljana, Ljubljana 61000, Slovenia..
    Juresa, Vesna
    Univ Zagreb, Zagreb 41000, Croatia..
    Kaaks, Rudolf
    German Canc Res Ctr, Berlin, Germany..
    Kafatos, Anthony
    Univ Crete, Iraklion, Greece..
    Kalter-Leibovici, Ofra
    Gertner Inst Epidemiol & Hlth Policy Res, Tel Aviv, Israel..
    Kapantais, Efthymios
    Hellen Med Assoc Obes, Iraklion, Greece..
    Kasaeian, Amir
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Katz, Joanne
    Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Kaur, Prabhdeep
    Natl Inst Epidemiol, Madras, Tamil Nadu, India..
    Kavousi, Maryam
    Erasmus MC, Rotterdam, Netherlands..
    Keil, Ulrich
    Univ Munster, Munster, Germany..
    Boker, Lital Keinan
    Univ Haifa, IL-31999 Haifa, Israel..
    Kelishadi, Roya
    Kemper, Han H. C. G.
    Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands..
    Kengne, Andre P.
    South African Med Res Council, Johannesburg, South Africa..
    Kersting, Mathilde
    Res Inst Child Nutr FKE, Munich, Germany..
    Key, Timothy
    Univ Oxford, Oxford OX1 2JD, England..
    Khader, Yousef Saleh
    Jordan Univ Sci & Technol, Amman, Jordan..
    Khalili, Davood
    Shahid Beheshti Univ Med Sci, Tehran, Iran..
    Khaw, Kay-Tee H.
    Univ Cambridge, Cambridge CB2 1TN, England..
    Khouw, Ilse M. S. L.
    FrieslandCampina, Singapore, Singapore..
    Kiechl, Stefan
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Killewo, Japhet
    Univ Hlth & Allied Sci, Tanza, Tanzania..
    Kim, Jeongseon
    Natl Canc Ctr, Seoul, South Korea..
    Kiyohara, Yutaka
    Kyushu Univ, Fukuoka 812, Japan..
    Klimont, Jeannette
    Stat Austria, Vienna, Austria..
    Kolle, Elin
    Norwegian Sch Sport Sci, Oslo, Norway..
    Kolsteren, Patrick
    Inst Trop Med, Brussels, Belgium..
    Korrovits, Paul
    Tartu Univ Clin, Tartu, Estonia..
    Koskinen, Seppo
    Kouda, Katsuyasu
    Kinki Univ, Fac Med, Higashiosaka, Osaka 577, Japan..
    Koziel, Slawomir
    Polish Acad Sci, Anthropol Unit, Wroclaw, Poland..
    Kratzer, Wolfgang
    Univ Hosp Ulm, Ulm, Germany..
    Krokstad, Steinar
    Norwegian Univ Sci & Technol, Oslo, Norway..
    Kromhout, Daan
    Wageningen Univ, NL-6700 AP Wageningen, Netherlands..
    Kruger, Herculina S.
    North West Univ, Johannesburg, South Africa..
    Kula, Krzysztof
    Med Univ Lodz, Lodz, Poland..
    Kulaga, Zbigniew
    Childrens Mem Hlth Inst, Warsaw, Poland..
    Kumar, R. Krishna
    Amrita Inst Med Sci, Kochi, India..
    Kusuma, Yadlapalli S.
    All India Inst Med Sci, New Delhi 110029, India..
    Kuulasmaa, Kari
    Laamiri, Fatima Zahra
    Univ Mohammed V Rabat, Rabat, Morocco..
    Laatikainen, Tiina
    Lachat, Carl
    Univ Ghent, B-9000 Ghent, Belgium..
    Laid, Youcef
    Lam, Tai Hing
    Landrove, Orlando
    Lanska, Vera
    Lappas, Georg
    Sahlgrens Acad, Stockholm, Sweden..
    Laugsand, Lars E.
    Norwegian Univ Sci & Technol, Oslo, Norway..
    Bao, Khanh Le Nguyen
    Le, Tuyen D.
    Natl Inst Nutr, Hanoi, Vietnam..
    Leclercq, Catherine
    Food & Agr Org, Rome, Italy..
    Lee, Jeannette
    Natl Univ Singapore, Singapore 117548, Singapore..
    Lee, Jeonghee
    Natl Canc Ctr, Seoul, South Korea..
    Lehtimaki, Terho
    Tampere Univ Hosp, Tampere, Finland..
    Lekhraj, Rampal
    Univ Putra Malaysia, Serdang 43400, Malaysia..
    Leon-Munoz, Luz M.
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    Lim, Wei-Yen
    Natl Univ Singapore, Singapore 117548, Singapore..
    Fernanda Lima-Costa, M.
    Fundacao Oswaldo Cruz, Rene Rachou Res Inst, Rio De Janeiro, Brazil..
    Lin, Xu
    Univ Chinese Acad Sci, Beijing, Peoples R China..
    Linneberg, Allan
    Res Ctr Prevent & Hlth, Aalborg, Denmark..
    Lissner, Lauren
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Litwin, Mieczyslaw
    Childrens Mem Hlth Inst, Lodz, Poland..
    Liu, Jing
    Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Lorbeer, Roberto
    Univ Med Greifswald, Greifswald, Germany..
    Lotufo, Paulo A.
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Eugenio Lozano, Jose
    Consejeria Sanidad Junta Castilla & Leon, Leon, Spain..
    Luksiene, Dalia
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Lundqvist, Annamari
    Natl Inst Hlth & Welf, Tampere, Finland..
    Lunet, Nuno
    Univ Porto, Sch Med, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ma, Guansheng
    Peking Univ, Beijing 100871, Peoples R China..
    Machi, Suka
    Jikei Univ, Sch Med, Tokyo, Japan..
    Maggi, Stefania
    CNR, Pisa, Italy..
    Magliano, Dianna J.
    Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia..
    Makdisse, Marcia
    Hosp Israelita Albert Einstein, Sao Paulo, Brazil..
    Malekzadeh, Reza
    Univ Tehran Med Sci, Tehran, Iran..
    Malhotra, Rahul
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Rao, Kodavanti Mallikharjuna
    Indian Council Med Res, New Delhi, India..
    Manios, Yannis
    Harokopio Univ Athens, Athens, Greece..
    Mann, Jim I.
    Univ Otago, Otaru, Hokkaido, Japan..
    Manzato, Enzo
    Univ Padua, I-35100 Padua, Italy..
    Margozzini, Paula
    Pontificia Univ Catolica Chile, Santiago, Chile..
    Markey, Oonagh
    Univ Reading, Reading RG6 2AH, Berks, England..
    Marques-Vidal, Pedro
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Marrugat, Jaume
    Martin-Prevel, Yves
    Inst Rech Dev, Lyon, France..
    Martorell, Reynaldo
    Emory Univ, Atlanta, GA 30322 USA..
    Masoodi, Shariq R.
    Sherikashmir Inst Med Sci, Jammu, India..
    Matsha, Tandi E.
    Cape Peninsula Univ Technol, Cape Town, South Africa..
    Mazur, Artur
    Univ Rzeszow, Rzeszow, Poland..
    Mbanya, Jean Claude N.
    Univ Yaounde I, Yaounde, Cameroon..
    McFarlane, Shelly R.
    McGarvey, Stephen T.
    Brown Univ, Providence, RI 02912 USA..
    McKee, Martin
    London Sch Hyg & Trop Med, London, England..
    McLachlan, Stela
    Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland..
    McLean, Rachael M.
    McNulty, Breige A.
    Univ Coll Dublin, Dublin, Ireland..
    Yusof, Safiah Md
    Univ Teknol MARA, Serdang, Malaysia..
    Mediene-Benchekor, Sounnia
    Meirhaeghe, Aline
    Meisinger, Christa
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Mendes, Larissa L.
    Univ Fed Juiz de Fora, Juiz De Fora, Brazil..
    Menezes, Ana Maria B.
    Mensink, Gert B. M.
    Robert Koch Inst, Berlin, Germany..
    Meshram, Indrapal I.
    Indian Council Med Res, New Delhi, India..
    Metspalu, Andres
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Mi, Jie
    Capital Inst Pediat, Beijing, Peoples R China..
    Michaelsen, Kim F.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Mikkel, Kairit
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Miller, Jody C.
    Francisco Miquel, Juan
    Jaime Miranda, J.
    Univ Peruana Cayetano Heredia, Lima, Peru..
    Misigoj-Durakovic, Marjeta
    Univ Zagreb, Zagreb 41000, Croatia..
    Mohamed, Mostafa K.
    Ain Shams Univ, Cairo, Egypt..
    Mohammad, Kazem
    Univ Tehran Med Sci, Tehran, Iran..
    Mohammadifard, Noushin
    Isfahan Cardiovasc Res Ctr, Esfahan, Iran..
    Mohan, Viswanathan
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Yusoff, Muhammad Fadhli Mohd
    Minist Hlth, Kuala Lumpur, Malaysia..
    Molbo, Drude
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Moller, Niels C.
    Univ Southern Denmark, Lyngby, Denmark..
    Molnar, Denes
    Univ Pecs, Pecs, Hungary..
    Mondo, Charles K.
    Mulago Hosp, Kampala, Uganda..
    Monterrubio, Eric A.
    Monyeki, Kotsedi Daniel K.
    Univ Limpopo, Limpopo, South Africa..
    Moreira, Leila B.
    Morejon, Alain
    Univ Med Sci, Havana, Cuba..
    Moreno, Luis A.
    Univ Zaragoza, E-50009 Zaragoza, Spain..
    Morgan, Karen
    RCSI Dublin, Dublin, Ireland..
    Mortensen, Erik Lykke
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Moschonis, George
    Harokopio Univ Athens, Athens, Greece..
    Mossakowska, Malgorzata
    Mota, Jorge
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Motlagh, Mohammad Esmaeel
    Ahvaz Jundishapur Univ Med Sci, Tehran, Iran..
    Motta, Jorge
    Gorgas Mem Inst Publ Hlth, Panama City, Panama..
    Mu, Thet Thet
    Muiesan, Maria Lorenza
    Univ Brescia, I-25121 Brescia, Italy..
    Mueller-Nurasyid, Martina
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Murphy, Neil
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Mursu, Jaakko
    Univ Eastern Finland, Joensuu, Finland..
    Murtagh, Elaine M.
    Mary Immaculate Coll, Limerick, Ireland..
    Musa, Kamarul Imran
    Univ Sains Malaysia, Kota Baharu, Malaysia..
    Musil, Vera
    Univ Zagreb, Zagreb 41000, Croatia..
    Nagel, Gabriele
    Univ Ulm, D-89069 Ulm, Germany..
    Nakamura, Harunobu
    Namesna, Jana
    Reg Author Publ Hlth, Banska Bystrica, Slovakia..
    Nang, Ei Ei K.
    Nangia, Vinay B.
    Suraj Eye Inst, Nagpur, Maharashtra, India..
    Nankap, Martin
    Helen Keller Int, Yaounde, Cameroon..
    Narake, Sameer
    Maria Navarrete-Munoz, Eva
    Nenko, Ilona
    Neovius, Martin
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Nervi, Flavio
    Neuhauser, Hannelore K.
    Nguyen, Nguyen D.
    Univ Pharm & Med Ho Chi Minh City, Ho Chi Minh City, Vietnam..
    Nguyen, Quang Ngoc
    Nieto-Martinez, Ramfis E.
    Ning, Guang
    Shanghai Jiao Tong Univ, Sch Med, Shanghai 200030, Peoples R China..
    Ninomiya, Toshiharu
    Nishtar, Sania
    Heartfile, Karachi, Pakistan..
    Noale, Marianna
    Norat, Teresa
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Noto, Davide
    Univ Palermo, I-90133 Palermo, Italy..
    Al Nsour, Mohannad
    Eastern Mediterranean Publ Hlth Network, Amman, Jordan..
    O'Reilly, Dermot
    Ochoa-Aviles, Angelica M.
    Univ Cuenca, Cuenca, Ecuador..
    Oh, Kyungwon
    Korea Ctr Dis Control & Prevent, Seoul, South Korea..
    Olayan, Iman H.
    Kuwait Inst Sci Res, Kuwait, Kuwait..
    Anselmo Olinto, Maria Teresa
    Univ Vale Rio dos Sinos, Sao Leopoldo, RS, Brazil..
    Oltarzewski, Maciej
    Omar, Mohd A.
    Minist Hlth, Kuala Lumpur, Malaysia..
    Ordunez, Pedro
    Pan Amer Hlth Org, El Paso, TX USA..
    Ortiz, Ana P.
    Univ Puerto Rico, San Juan, PR USA..
    Osler, Merete
    Osmond, Clive
    MRC Lifecourse Epidemiol Unit, Southampton, Hants, England..
    Ostojic, Sergej M.
    Univ Novi Sad, Novi Sad 21000, Serbia..
    Otero, Johanna A.
    Overvad, Kim
    Aarhus Univ, DK-8000 Aarhus C, Denmark..
    Paccaud, Fred Michel
    Padez, Cristina
    Univ Coimbra, P-3000 Coimbra, Portugal..
    Pajak, Andrzej
    Palli, Domenico
    Palloni, Alberto
    Univ Madison Wisconsin, Madison, WI USA..
    Palmieri, Luigi
    Ist Super Sanita, Rome, Italy..
    Panda-Jonas, Songhomitra
    Panza, Francesco
    Univ Bari, I-70121 Bari, Italy..
    Parnell, Winsome R.
    Parsaeian, Mahboubeh
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Pednekar, Mangesh S.
    Peeters, Petra H.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Peixoto, Sergio Viana
    Pereira, Alexandre C.
    Heart Inst InCor, Sao Paulo, Brazil..
    Perez, Cynthia M.
    Peters, Annette
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Peykari, Niloofar
    Noncommunicable Dis Res Ctr, Tehran, Iran..
    Pham, Son Thai
    Pigeot, Iris
    Leibniz Inst Prevent Res & Epidemiol BIPS, Leibniz, Germany..
    Pikhart, Hynek
    UCL, London WC1E 6BT, England..
    Pilav, Aida
    Fed Minist Hlth, Sarajevo, Bosnia & Herceg..
    Pilotto, Lorenza
    Pistelli, Francesco
    Univ Hosp Pisa, Pisa, Italy..
    Pitakaka, Freda
    Univ New S Wales, Sydney, NSW 2052, Australia..
    Piwonska, Aleksandra
    Cardinal Wyszynski Inst Cardiol, Warsaw, Poland..
    Piwonski, Jerzy
    Plans-Rubio, Pedro
    Poh, Bee Koon
    Publ Hlth Agcy Catalonia, Catalonia, Spain..
    Porta, Miquel
    Portegies, Marileen L. P.
    Erasmus MC, Rotterdam, Netherlands..
    Poulimeneas, Dimitrios
    Pradeepa, Rajendra
    Madras Diabet Res Fdn, Madras, Tamil Nadu, India..
    Prashant, Mathur
    Indian Council Med Res, New Delhi, India..
    Price, Jacqueline F.
    Univ Edinburgh, Edinburgh EH8 9YL, Midlothian, Scotland..
    Puiu, Maria
    Victor Babes Univ Med & Pharm, Cluj Napoca, Romania..
    Punab, Margus
    Tartu Univ Clin, Tartu, Estonia..
    Qasrawi, Radwan F.
    Al Quds Univ, Jerusalem, Israel..
    Qorbani, Mostafa
    Alborz Univ Med Sci, Golestan, Iran..
    Bao, Tran Quoc
    Radic, Ivana
    Inst Publ Hlth Vojvodina, Vojvodina, Serbia..
    Radisauskas, Ricardas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Rahman, Mahmudur
    Inst Epidemiol Dis Control & Res, Dhaka, Bangladesh..
    Raitakari, Olli
    Turku Univ Hosp, FIN-20520 Turku, Finland..
    Raj, Manu
    Rao, Sudha Ramachandra
    Ramachandran, Ambady
    India Diabet Res Fdn, New Delhi, India..
    Ramke, Jacqueline
    Univ New S Wales, Sydney, NSW 2052, Australia..
    Ramos, Rafel
    Rampal, Sanjay
    Univ Malaya, Serdang, Malaysia..
    Rasmussen, Finn
    Redon, Josep
    Univ Valencia, E-46003 Valencia, Spain..
    Reganit, Paul Ferdinand M.
    Univ Philippines, Quezon City 1101, Philippines..
    Ribeiro, Robespierre
    Riboli, Elio
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Rigo, Fernando
    Hlth Ctr San Agustin, Madrid, Spain..
    de Wit, Tobias Floris Rinke
    PharmAccess Fdn, Groningen, Netherlands..
    Ritti-Dias, Raphael M.
    Rivera, Juan A.
    Robinson, Sian M.
    Univ Southampton, Southampton SO9 5NH, Hants, England..
    Robitaille, Cynthia
    Publ Hlth Agcy Canada, Montreal, PQ, Canada..
    Rodriguez-Artalejo, Fernando
    Univ Autonoma Madrid, E-28049 Madrid, Spain..
    del Cristo Rodriguez-Perez, Maria
    Canarian Hlth Serv, Madrid, Spain..
    Rodriguez-Villamizar, Laura A.
    Univ Ind Santander, Santander, Colombia..
    Rojas-Martinez, Rosalba
    Rojroongwasinkul, Nipa
    Mahidol Univ, Bangkok 10700, Thailand..
    Romaguera, Dora
    CIBEROBN, Madrid, Spain..
    Ronkainen, Kimmo
    Rosengren, Annika
    Gothenburg Univ, S-41124 Gothenburg, Sweden..
    Rouse, Ian
    Fiji Natl Univ, Nasinu, Fiji..
    Rubinstein, Adolfo
    Inst Clin Effectiveness & Hlth Policy, Buenos Aires, DF, Argentina..
    Ruehli, Frank J.
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Rui, Ornelas
    Univ Madeira, Funchal, Portugal..
    Sandra Ruiz-Betancourt, Blanca
    Inst Mexicano Seguro Social, Rio Grande, Mexico..
    Russo Horimoto, Andrea R. V.
    Rutkowski, Marcin
    Med Univ Gdansk, Gdansk, Poland..
    Sabanayagam, Charumathi
    Singapore Eye Res Inst, Singapore, Singapore..
    Sachdev, Harshpal S.
    Sitaram Bhartia Inst Sci & Res, New Delhi, India..
    Saidi, Olfa
    Fac Med Tunis, Tunis, Tunisia..
    Salanave, Benoit
    French Inst Hlth Surveillance, Lyon, France..
    Salazar Martinez, Eduardo
    Salomaa, Veikko
    Salonen, Jukka T.
    Univ Helsinki, FIN-00014 Helsinki, Finland..
    Salvetti, Massimo
    Univ Brescia, I-25121 Brescia, Italy..
    Sanchez-Abanto, Jose
    Natl Inst Hlth, Lima, Peru..
    Sandjaja,
    Sans, Susana
    Catalan Dept Hlth, Madrid, Spain..
    Santos, Diana A.
    Univ Lisbon, P-1699 Lisbon, Portugal..
    Santos, Osvaldo
    dos Santos, Renata Nunes
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Santos, Rute
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Sardinha, Luis B.
    Univ Lisbon, P-1699 Lisbon, Portugal..
    Sarrafzadegan, Nizal
    Saum, Kai-Uwe
    German Canc Res Ctr, Berlin, Germany..
    Savva, Savvas C.
    Res & Educ Inst Child Hlth, Nicosia, Cyprus..
    Scazufca, Marcia
    Univ Sao Paulo, BR-05508 Sao Paulo, Brazil..
    Rosario, Angelika Schaffrath
    Schargrodsky, Herman
    Hosp Italiano Buenos Aires, Buenos Aires, DF, Argentina..
    Schienkiewitz, Anja
    Schmidt, Ida Maria
    Rigshosp, Copenhagen, Denmark..
    Schneider, Ione J.
    Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Schultsz, Constance
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Schutte, Aletta E.
    MRC North West Univ, Johannesburg, South Africa..
    Sein, Aye Aye
    Minist Hlth, Bangkok, Thailand..
    Senbanjo, Idowu O.
    Lagos State Univ, Coll Med, Lagos, Nigeria..
    Sepanlou, Sadaf G.
    Digest Dis Res Inst, Tehran, Iran..
    Shalnova, Svetlana A.
    Natl Res Ctr Prevent Med, Moscow, Russia..
    Shaw, Jonathan E.
    Shibuya, Kenji
    Univ Tokyo, Tokyo 1138654, Japan..
    Shin, Youchan
    Shiri, Rahman
    Finnish Inst Occupat Hlth, Espoo, Finland..
    Siantar, Rosalynn
    Sibai, Abla M.
    Silva, Antonio M.
    Univ Fed Maranhao, Sao Luis, Brazil.;Univ Fed Santa Catarina, BR-88040900 Florianopolis, SC, Brazil..
    Santos Silva, Diego Augusto
    Simon, Mary
    India Diabet Res Fdn, New Delhi, India..
    Simons, Judith
    St Vincents Hosp, Melbourne, Vic, Australia..
    Simons, Leon A.
    Sjostrom, Michael
    Slowikowska-Hilczer, Jolanta
    Med Univ Lodz, Lodz, Poland..
    Slusarczyk, Przemyslaw
    Smeeth, Liam
    London Sch Hyg & Trop Med, London, England..
    Smith, Margaret C.
    Univ Oxford, Oxford OX1 2JD, England..
    Snijder, Marieke B.
    So, Hung-Kwan
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Sobngwi, Eugene
    Univ Yaounde I, Yaounde, Cameroon..
    Soderberg, Stefan
    Umea Univ, S-90187 Umea, Sweden..
    Soekatri, Moesijanti Y. E.
    Hlth Polytech Inst, Bandung, Indonesia..
    Solfrizzi, Vincenzo
    Univ Bari, I-70121 Bari, Italy..
    Sonestedt, Emily
    Lund Univ, S-22100 Lund, Sweden..
    Sorensen, Thorkild I. A.
    Univ Copenhagen, DK-1168 Copenhagen, Denmark..
    Soric, Maroje
    Univ Zagreb, Zagreb 41000, Croatia..
    Jerome, Charles Sossa
    Soumare, Aicha
    Univ Bordeaux, Bordeaux, France..
    Staessen, Jan A.
    Univ Leuven, Leuven, Belgium..
    Starc, Gregor
    Stathopoulou, Maria G.
    INSERM, F-75654 Paris 13, France..
    Staub, Kaspar
    Univ Zurich, CH-8006 Zurich, Switzerland..
    Stavreski, Bill
    Heart Fdn, Sydney, NSW, Australia..
    Steene-Johannessen, Jostein
    Norwegian Sch Sport Sci, Oslo, Norway..
    Stehle, Peter
    Univ Bonn, Bonn, Germany..
    Stein, Aryeh D.
    Emory Univ, Atlanta, GA 30322 USA..
    Stergiou, George S.
    Sotiria Hosp, Athina, Greece..
    Stessman, Jochanan
    Stieber, Jutta
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Stoeckl, Doris
    Helmholtz Zentrum mUNCHEN, Munich, Germany..
    Stocks, Tanja
    Stokwiszewski, Jakub
    Natl Inst Hyg, Natl Inst Publ Hlth, Warsaw, Poland..
    Stratton, Gareth
    Swansea Univ, Swansea, W Glam, Wales..
    Strufaldi, Maria Wany
    Sun, Chien-An
    Fu Jen Catholic Univ, Taipei, Taiwan..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sung, Yn-Tz
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Sunyer, Jordi
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Suriyawongpaisal, Paibul
    Mahidol Univ, Bangkok 10700, Thailand..
    Swinburn, Boyd A.
    Univ Auckland, Auckland 1, New Zealand..
    Sy, Rody G.
    Univ Philippines, Quezon City 1101, Philippines..
    Szponar, Lucjan
    Natl Food & Nutr Inst, Warsaw, Poland..
    Tai, E. Shyong
    Natl Univ Singapore, Singapore 117548, Singapore..
    Tammesoo, Mari-Liis
    Univ Tartu, Ulikooli 18, EE-50090 Tartu, Estonia..
    Tamosiunas, Abdonas
    Lithuanian Univ Hlth Sci, Kaunas, Lithuania..
    Tang, Line
    Res Ctr Prevent & Hlth, Odense, Denmark..
    Tang, Xun
    Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China..
    Tanser, Frank
    Univ KwaZulu Natal, Durban, South Africa..
    Tao, Yong
    Peking Univ, Beijing 100871, Peoples R China..
    Tarp, Jakob
    Univ Southern Denmark, Lyngby, Denmark..
    Tarqui-Mamani, Carolina B.
    Natl Inst Hlth, Lima, Peru..
    Taylor, Anne
    Univ Adelaide, Adelaide, SA 5005, Australia..
    Tchibindat, Felicite
    UNICEF, Yaounde, Cameroon..
    Thijs, Lutgarde
    Thuesen, Betina H.
    Tjonneland, Anne
    Danish Canc Soc Res Ctr, Odense, Denmark..
    Tolonen, Hanna K.
    Tolstrup, Janne S.
    Univ Southern Denmark, Lyngby, Denmark..
    Topbas, Murat
    Karadeniz Tech Univ, Ankara, Turkey..
    Topor-Madry, Roman
    Jagiellonian Univ, Coll Med, PL-31007 Krakow, Poland..
    Torrent, Maties
    Traissac, Pierre
    Inst Rech Dev, Lyon, France..
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA.;Alexander Technol Educ Inst, Athens, Greece..
    Trinh, Oanh T. H.
    Trivedi, Atul
    Govt Med Coll, New Delhi, India..
    Tshepo, Lechaba
    Sefako Makgatho Hlth Sci Univ, Johannesburg, South Africa..
    Tulloch-Reid, Marshall K.
    Tuomainen, Tomi-Pekka
    Tuomilehto, Jaakko
    Dasman Diabet Inst, Kuwait, Kuwait. Minist Hlth, Hamilton, New Zealand..
    Tynelius, Per
    Karolinska Inst, S-10401 Stockholm, Sweden..
    Tzotzas, Themistoklis
    Hellen Med Assoc Obes, Athens, Greece..
    Tzourio, Christophe
    Univ Bordeaux, Bordeaux, France..
    Ueda, Peter
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    Ukoli, Flora A. M.
    Meharry Med Coll, Nashville, TN USA..
    Ulmer, Hanno
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Unal, Belgin
    Dokuz Eylul Univ, TR-35210 Alsancak, Turkey..
    Valdivia, Gonzalo
    Vale, Susana
    Univ Porto, Rua Campo Alegre 823, P-4100 Oporto, Portugal..
    Valvi, Damaskini
    Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA..
    van der Schouw, Yvonne T.
    Univ Med Ctr Utrecht, Utrecht, Netherlands..
    Van Herck, Koen
    Univ Ghent, B-9000 Ghent, Belgium..
    Minh, Hoang Van
    van Valkengoed, Irene G. M.
    Univ Amsterdam, Acad Med Ctr, NL-1012 WX Amsterdam, Netherlands..
    Vanderschueren, Dirk
    Katholieke Univ Leuven, Louvain, Belgium..
    Vanuzzo, Diego
    Ctr Prevenz Cardiovasc Udine, Udine, Italy..
    Vatten, Lars
    Vega, Tomas
    Velasquez-Melendez, Gustavo
    Univ Fed Minas Gerais, Belo Horizonte, MG, Brazil..
    Veronesi, Giovanni
    Univ Insubria, Varese, Italy..
    Verschuren, W. M. Monique
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Viegi, Giovanni
    Viet, Lucie
    Natl Inst Publ Hlth & Environm, Amsterdam, Netherlands..
    Viikari-Juntura, Eira
    Finnish Inst Occupat Hlth, Helsinki, Finland..
    Vineis, Paolo
    Univ London Imperial Coll Sci Technol & Med, London, England..
    Vioque, Jesus
    Univ Miguel Hernandez, Madrid, Spain..
    Virtanen, Jyrki K.
    Visvikis-Siest, Sophie
    INSERM, F-75654 Paris 13, France..
    Viswanathan, Bharathi
    Minist Hlth, Victoria, Seychelles..
    Vollenweider, Peter
    Univ Lausanne Hosp, Lausanne, Switzerland..
    Voutilainen, Sari
    Vrijheid, Martine
    Ctr Res Environm Epidemiol, Madrid, Spain..
    Wade, Alisha N.
    Univ Witwatersrand, ZA-2050 Johannesburg, South Africa..
    Wagner, Aline
    Univ Strasbourg, Strasbourg, France..
    Walton, Janette
    Univ Coll Cork, Cork, Ireland..
    Mohamud, Wan Nazaimoon Wan
    Inst Med Res, Serdang, Malaysia..
    Wang, Ming-Dong
    Wang, Qian
    Xinjiang Med Univ, Xinjiang, Peoples R China..
    Wang, Ya Xing
    Beijing Tongren Hosp, Beijing, Peoples R China..
    Wannamethee, S. Goya
    UCL, London WC1E 6BT, England..
    Wareham, Nicholas
    Univ Cambridge, Cambridge CB2 1TN, England..
    Weerasekera, Deepa
    Minist Hlth, Hamilton, New Zealand..
    Whincup, Peter H.
    Univ London, London WC1E 7HU, England..
    Widhalm, Kurt
    Med Univ Vienna, Vienna, Austria..
    Widyahening, Indah S.
    Univ Indonesia, Bandung, Indonesia..
    Wiecek, Andrzej
    Med Univ Silesia, Katowice, Poland..
    Wilks, Rainford J.
    Willeit, Johann
    Med Univ Innsbruck, A-6020 Innsbruck, Austria..
    Wojtyniak, Bogdan
    Wong, Jyh Eiin
    Univ Kebangsaan Malaysia, Bangi 43600, Malaysia..
    Wong, Tien Yin
    Duke NUS Grad Med Sch, Singapore, Singapore..
    Woo, Jean
    Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China..
    Woodward, Mark
    Univ Sydney, Sydney, NSW 2006, Australia.;Univ Oxford, Oxford OX1 2JD, England..
    Wu, Frederick C.
    Univ Manchester, Manchester M13 9PL, Lancs, England..
    Wu, JianFeng
    Shandong Univ Tradit Chinese Med, Jinan, Peoples R China..
    Wu, Shou Ling
    Kailuan Gen Hosp, Beijing, Peoples R China..
    Xu, Haiquan
    Minist Agr, Inst Food & Nutr Dev, Beijing, Peoples R China..
    Xu, Liang
    Capital Med Univ, Beijing, Peoples R China..
    Yamborisut, Uruwan
    Mahidol Univ, Bangkok 10700, Thailand..
    Yan, Weili
    Fudan Univ, Shanghai, Peoples R China..
    Yang, Xiaoguang
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Yardim, Nazan
    Minist Hlth, Ankara, Turkey..
    Ye, Xingwang
    Univ Chinese Acad Sci, Beijing, Peoples R China..
    Yiallouros, Panayiotis K.
    Cyprus Univ Technol, Limassol, Cyprus..
    Yoshihara, Akihiro
    Niigata Univ, Niigata 95021, Japan..
    You, Qi Sheng
    Younger-Coleman, Novie O.
    Yusoff, Ahmad F.
    Minist Hlth, Kuala Lumpur, Malaysia..
    Zainuddin, Ahmad A.
    Univ Teknol MARA, Serdang, Malaysia..
    Zambon, Sabina
    Univ Padua, I-35100 Padua, Italy..
    Zdrojewski, Tomasz
    Med Univ Gdansk, Gdansk, Poland..
    Zeng, Yi
    Duke Univ, Durham, NC 27706 USA.;Peking Univ, Beijing 100871, Peoples R China..
    Zhao, Dong
    Capital Med Univ, Beijing Anzhen Hosp, Beijing, Peoples R China..
    Zhao, Wenhua
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Zheng, Yingfeng
    Singapore Eye Res Inst, Singapore, Singapore..
    Zhou, Maigeng
    Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China..
    Zhu, Dan
    Inner Mongolia Med Univ, Inner Mongolia, Peoples R China..
    Zimmermann, Esther
    Bispebjerg Hosp, Copenhagen, Denmark.;Frederiksberg Univ Hosp, Frederiksberg, Denmark..
    Zuniga Cisneros, Julio
    Gorgas Mem Inst Publ Hlth, Panama City, Panama..
    Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10026, p. 1377-1396Article in journal (Refereed)
    Abstract [en]

    Background Underweight and severe and morbid obesity are associated with highly elevated risks of adverse health outcomes. We estimated trends in mean body-mass index (BMI), which characterises its population distribution, and in the prevalences of a complete set of BMI categories for adults in all countries.

    Methods We analysed, with use of a consistent protocol, population-based studies that had measured height and weight in adults aged 18 years and older. We applied a Bayesian hierarchical model to these data to estimate trends from 1975 to 2014 in mean BMI and in the prevalences of BMI categories (<18.5 kg/m(2) [underweight], 18.5 kg/m(2) to <20 kg/m(2), 20 kg/m(2) to <25 kg/m(2), 25 kg/m(2) to <30 kg/m(2), 30 kg/m(2) to <35 kg/m(2), 35 kg/m(2) to <40 kg/m(2), = 40 kg/m(2) [morbid obesity]), by sex in 200 countries and territories, organised in 21 regions. We calculated the posterior probability of meeting the target of halting by 2025 the rise in obesity at its 2010 levels, if post-2000 trends continue.

    Findings We used 1698 population-based data sources, with more than 19.2 million adult participants (9.9 million men and 9.3 million women) in 186 of 200 countries for which estimates were made. Global age-standardised mean BMI increased from 21.7 kg/m(2) (95% credible interval 21.3-22.1) in 1975 to 24.2 kg/m(2) (24.0-24.4) in 2014 in men, and from 22.1 kg/m(2) (21.7-22.5) in 1975 to 24.4 kg/m(2) (24.2-24.6) in 2014 in women. Regional mean BMIs in 2014 for men ranged from 21.4 kg/m(2) in central Africa and south Asia to 29.2 kg/m(2) (28.6-29.8) in Polynesia and Micronesia; for women the range was from 21.8 kg/m(2) (21.4-22.3) in south Asia to 32.2 kg/m(2) (31.5-32.8) in Polynesia and Micronesia. Over these four decades, age-standardised global prevalence of underweight decreased from 13.8% (10.5-17.4) to 8.8% (7.4-10.3) in men and from 14.6% (11.6-17.9) to 9.7% (8.3-11.1) in women. South Asia had the highest prevalence of underweight in 2014, 23.4% (17.8-29.2) in men and 24.0% (18.9-29.3) in women. Age-standardised prevalence of obesity increased from 3.2% (2.4-4.1) in 1975 to 10.8% (9.7-12.0) in 2014 in men, and from 6.4% (5.1-7.8) to 14.9% (13.6-16.1) in women. 2.3% (2.0-2.7) of the world's men and 5.0% (4.4-5.6) of women were severely obese (ie, have BMI = 35 kg/m(2)). Globally, prevalence of morbid obesity was 0.64% (0.46-0.86) in men and 1.6% (1.3-1.9) in women.

    Interpretation If post-2000 trends continue, the probability of meeting the global obesity target is virtually zero. Rather, if these trends continue, by 2025, global obesity prevalence will reach 18% in men and surpass 21% in women; severe obesity will surpass 6% in men and 9% in women. Nonetheless, underweight remains prevalent in the world's poorest regions, especially in south Asia.

  • 181. Di Cori, Andrea
    et al.
    Auricchio, Angelo
    Regoli, François
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Butter, Christian
    Dagres, Nikolaos
    Deharo, Jean-Claude
    Maggioni, Aldo P
    Kutarski, Andrzej
    Kennergren, Charles
    Laroche, Cécile
    Rinaldi, Christopher A
    Dovellini, Emilio Vincenzo
    Golzio, Pier Giorgio
    Thøgersen, Anna Margrethe
    Bongiorni, Maria Grazia
    Clinical impact of antithrombotic therapy in transvenous lead extraction complications: a sub-analysis from the ESC-EORP EHRA ELECTRa (European Lead Extraction ConTRolled) Registry.2019In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 21, no 7, p. 1096-1105Article in journal (Refereed)
    Abstract [en]

    AIMS: A sub-analysis of the ESC-EHRA European Lead Extraction ConTRolled (ELECTRa) Registry to evaluate the clinical impact of antithrombotic (AT) on transvenous lead extraction (TLE) safety and efficacy.

    METHODS AND RESULTS: ELECTRa outcomes were compared between patients without AT therapy (No AT Group) and with different pre-operative AT regimens, including antiplatelets (AP), anticoagulants (AC), or both (AP + AC). Out of 3510 pts, 2398 (68%) were under AT pre-operatively. AT patients were older with more comorbidities (P < 0.0001). AT subgroups, defined as AP, AC, or AP + AC, were 1096 (31.2%), 985 (28%), and 317 (9%), respectively. Regarding AP patients, 1413 (40%) were under AP, 1292 (91%) with a single AP, interrupted in 26% about 3.8 ± 3.7 days before TLE. In total, 1302 (37%) patients were under AC, 881 vitamin K antagonist (68%), 221 (17%) direct oral anticoagulants, 155 (12%) low weight molecular heparin, and 45 (3.5%) unfractionated heparin. AC was 'interrupted without bridging' in 696 (54%) and 'interrupted with bridging' in 504 (39%) about 3.3 ± 2.3 days before TLE, and 'continued' in 87 (7%). TLE success rate was high in all subgroups. Only overall in-hospital death (1.4%), but not the procedure-related one, was higher in the AT subgroups (P = 0.0500). Age >65 years and New York Heart Association Class III/IV, but not AT regimens, were independent predictors of death for any cause. Haematomas were more frequent in AT subgroups, especially in AC 'continued' (P = 0.025), whereas pulmonary embolism in the No-AT (P < 0.01).

    CONCLUSIONS: AT minimization is safe in patients undergoing TLE. AT does not seem to predict death but identifies a subset of fragile patients with a worse in-hospital TLE outcome.

  • 182. Di Mario, C
    et al.
    Syrseloudis, D
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Viceconte, N
    Wijns, W
    STEMI guidelines: from formulation to implementation2013In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 8, p. 11-17Article in journal (Refereed)
  • 183.
    Diamanti, Klev
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Visvanathar, Robin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Pereira, Maria J
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Cavalli, Marco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Kumar, Chanchal
    Translational Science & Experimental Medicine, Early Cardiovascular, Renal and Metabolism, R&D BioPharmaceuticals, AstraZeneca; Karolinska Institute/AstraZeneca Integrated CardioMetabolic Centre (KI/AZ ICMC), Department of Medicine.
    Stanko, Stanko
    Pharmaceutical Technology & Development, AstraZeneca AB; Department of Medicine, Sahlgrenska University Hospital, Gothenburg.
    Ingelsson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Fall, Tove
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lind, Lars
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. 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, Faculty of Medicine, Department of Surgical Sciences, Radiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Eriksson, Jan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical diabetology and metabolism.
    Kullberg, Joel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Wadelius, Claes
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Komorowski, Jan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Integration of whole-body PET/MRI with non-targeted metabolomics provides new insights into insulin sensitivity of various tissuesManuscript (preprint) (Other academic)
    Abstract [en]

    Background: Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific alterations is challenging and requires a multi-omics approach. In this study, we aimed at discovering associations of metabolites from subcutaneous adipose tissue (SAT) and plasma with the volume, the fat fraction (FF) and the insulin sensitivity (Ki) of specific tissues using [18F]FDG PET/MRI.

    Materials and Methods: In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body-mass-index (BMI) we calculated associations between parameters of whole-body FDG PET/MRI during clamp and non-targeted metabolomics profiling for SAT and blood plasma. We also used a rule-based classifier to identify a large collection of prevalent patterns of co-dependent metabolites that characterize non-diabetes (ND) and T2D.

    Results: The plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Ki in visceral adipose tissue (VAT) and SAT, was positively associated with several species of lysophospholipids while the opposite applied to branched-chain amino acids (BCAA) and their intermediates. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. On the contrary, bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Finally, we presented a transparent machine-learning model that predicted ND or T2D in “unseen” data with an accuracy of 78%.

    Conclusions: Novel associations of several metabolites from SAT and plasma with the FF, volume and insulin senstivity of various tissues throughout the body were discovered using PET/MRI and a new integrative multi-omics approach. A promising computational model that predicted ND and T2D with high certainty, suggested novel non-linear interdependencies of metabolites.

  • 184.
    Dimberg, Axel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Alström, Ulrica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Higher Preoperative Plasma Thrombin Potential in Patients Undergoing Surgery for Aortic Stenosis Compared to Surgery for Stable Coronary Artery Disease2018In: Clinical and applied thrombosis/hemostasis, ISSN 1076-0296, E-ISSN 1938-2723, Vol. 24, no 8, p. 1282-1290Article in journal (Refereed)
    Abstract [en]

    Aortic stenosis (AS) and coronary artery disease (CAD) influence the coagulation system, potentially affecting hemostasis during cardiac surgery. Our aim was to evaluate 2 preoperative global hemostasis assays, plasma thrombin potential and thromboelastometry, in patients with severe aortic valve stenosis compared to patients with CAD. A secondary aim was to test whether the assays were associated with postoperative bleeding. Calibrated automated thrombogram (CAT) in platelet-poor plasma and rotational thromboelastometry (ROTEM) in whole blood were analyzed in patients scheduled for elective surgery due to severe AS (n = 103) and stable CAD (n = 68). Patients with AS displayed higher plasma thrombin potential, both thrombin peak with median 252 nmol/L (interquartile range 187-319) and endogenous thrombin potential (ETP) with median 1552 nmol/L/min (interquartile range 1340-1838), when compared to patients with CAD where thrombin peak was median 174 nmol/L (interquartile range 147-229) and ETP median 1247 nmol/L/min (interquartile range 1034-1448; both P < .001). Differences persisted after adjustment for age, gender, comorbidity, and antithrombotic treatment. Differences observed in thromboelastometry between the groups did not persist after adjustment for baseline characteristics. Bleeding amount showed no relationship with plasma thrombin potential but weakly to thromboelastometry (R-2 = .064, P = .001). Patients with AS exhibited preoperatively increased plasma thrombin potential compared to patients with CAD. Plasma thrombin potential was not predictive for postoperative bleeding in patients scheduled for elective surgery.

  • 185. Do, Ron
    et al.
    Willer, Cristen J.
    Schmidt, Ellen M.
    Sengupta, Sebanti
    Gao, Chi
    Peloso, Gina M.
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kanoni, Stavroula
    Ganna, Andrea
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Chen, Jin
    Buchkovich, Martin L.
    Mora, Samia
    Beckmann, Jacques S.
    Bragg-Gresham, Jennifer L.
    Chang, Hsing-Yi
    Demirkan, Ayse
    Den Hertog, Heleen M.
    Donnelly, Louise A.
    Ehret, Georg B.
    Esko, Tonu
    Feitosa, Mary F.
    Ferreira, Teresa
    Fischer, Krista
    Fontanillas, Pierre
    Fraser, Ross M.
    Freitag, Daniel F.
    Gurdasani, Deepti
    Heikkila, Kauko
    Hyppoenen, Elina
    Isaacs, Aaron
    Jackson, Anne U.
    Johansson, Åsa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johnson, Toby
    Kaakinen, Marika
    Kettunen, Johannes
    Kleber, Marcus E.
    Li, Xiaohui
    Luan, Jian'an
    Lyytikainen, Leo-Pekka
    Magnusson, Patrik K. E.
    Mangino, Massimo
    Mihailov, Evelin
    Montasser, May E.
    Mueller-Nurasyid, Martina
    Nolte, Ilja M.
    O'Connell, Jeffrey R.
    Palmer, Cameron D.
    Perola, Markus
    Petersen, Ann-Kristin
    Sanna, Serena
    Saxena, Richa
    Service, Susan K.
    Shah, Sonia
    Shungin, Dmitry
    Sidore, Carlo
    Song, Ci
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Strawbridge, Rona J.
    Surakka, Ida
    Tanaka, Toshiko
    Teslovich, Tanya M.
    Thorleifsson, Gudmar
    Van den Herik, Evita G.
    Voight, Benjamin F.
    Volcik, Kelly A.
    Waite, Lindsay L.
    Wong, Andrew
    Wu, Ying
    Zhang, Weihua
    Absher, Devin
    Asiki, Gershim
    Barroso, Ines
    Been, Latonya F.
    Bolton, Jennifer L.
    Bonnycastle, Lori L.
    Brambilla, Paolo
    Burnett, Mary S.
    Cesana, Giancarlo
    Dimitriou, Maria
    Doney, Alex S. F.
    Doering, Angela
    Elliott, Paul
    Epstein, Stephen E.
    Eyjolfsson, Gudmundur Ingi
    Gigante, Bruna
    Goodarzi, Mark O.
    Grallert, Harald
    Gravito, Martha L.
    Groves, Christopher J.
    Hallmans, Goran
    Hartikainen, Anna-Liisa
    Hayward, Caroline
    Hernandez, Dena
    Hicks, Andrew A.
    Holm, Hilma
    Hung, Yi-Jen
    Illig, Thomas
    Jones, Michelle R.
    Kaleebu, Pontiano
    Kastelein, John J. P.
    Khaw, Kay-Tee
    Kim, Eric
    Klopp, Norman
    Komulainen, Pirjo
    Kumari, Meena
    Langenberg, Claudia
    Lehtimaki, Terho
    Lin, Shih-Yi
    Lindstrom, Jaana
    Loos, Ruth J. F.
    Mach, Francois
    McArdle, Wendy L.
    Meisinger, Christa
    Mitchell, Braxton D.
    Mueller, Gabrielle
    Nagaraja, Ramaiah
    Narisu, Narisu
    Nieminen, Tuomo V. M.
    Nsubuga, Rebecca N.
    Olafsson, Isleifur
    Ong, Ken K.
    Palotie, Aarno
    Papamarkou, Theodore
    Pomilla, Cristina
    Pouta, Anneli
    Rader, Daniel J.
    Reilly, Muredach P.
    Ridker, Paul M.
    Rivadeneira, Fernando
    Rudan, Igor
    Ruokonen, Aimo
    Samani, Nilesh
    Scharnagl, Hubert
    Seeley, Janet
    Silander, Kaisa
    Stancakova, Alena
    Stirrups, Kathleen
    Swift, Amy J.
    Tiret, Laurence
    Uitterlinden, Andre G.
    van Pelt, L. Joost
    Vedantam, Sailaja
    Wainwright, Nicholas
    Wijmenga, Cisca
    Wild, Sarah H.
    Willemsen, Gonneke
    Wilsgaard, Tom
    Wilson, James F.
    Young, Elizabeth H.
    Zhao, Jing Hua
    Adair, Linda S.
    Arveiler, Dominique
    Assimes, Themistocles L.
    Bandinelli, Stefania
    Bennett, Franklyn
    Bochud, Murielle
    Boehm, Bernhard O.
    Boomsma, Dorret I.
    Borecki, Ingrid B.
    Bornstein, Stefan R.
    Bovet, Pascal
    Burnier, Michel
    Campbell, Harry
    Chakravarti, Aravinda
    Chambers, John C.
    Chen, Yii-Der Ida
    Collins, Francis S.
    Cooper, Richard S.
    Danesh, John
    Dedoussis, George
    de Faire, Ulf
    Feranil, Alan B.
    Ferrieres, Jean
    Ferrucci, Luigi
    Freimer, Nelson B.
    Gieger, Christian
    Groop, Leif C.
    Gudnason, Vilmundur
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hamsten, Anders
    Harris, Tamara B.
    Hingorani, Aroon
    Hirschhorn, Joel N.
    Hofman, Albert
    Hovingh, G. Kees
    Hsiung, Chao Agnes
    Humphries, Steve E.
    Hunt, Steven C.
    Hveem, Kristian
    Iribarren, Carlos
    Jarvelin, Marjo-Riitta
    Jula, Antti
    Kahonen, Mika
    Kaprio, Jaakko
    Kesaniemi, Antero
    Kivimaki, Mika
    Kooner, Jaspal S.
    Koudstaal, Peter J.
    Krauss, Ronald M.
    Kuh, Diana
    Kuusisto, Johanna
    Kyvik, Kirsten O.
    Laakso, Markku
    Lakka, Timo A.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindgren, Cecilia M.
    Martin, Nicholas G.
    Maerz, Winfried
    McCarthy, Mark I.
    McKenzie, Colin A.
    Meneton, Pierre
    Metspalu, Andres
    Moilanen, Leena
    Morris, Andrew D.
    Munroe, Patricia B.
    Njolstad, Inger
    Pedersen, Nancy L.
    Power, Chris
    Pramstaller, Peter P.
    Price, Jackie F.
    Psaty, Bruce M.
    Quertermous, Thomas
    Rauramaa, Rainer
    Saleheen, Danish
    Salomaa, Veikko
    Sanghera, Dharambir K.
    Saramies, Jouko
    Schwarz, Peter E. H.
    Sheu, Wayne H-H
    Shuldiner, Alan R.
    Siegbahn, Agneta
    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, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Spector, Tim D.
    Stefansson, Kari
    Strachan, David P.
    Tayo, Bamidele O.
    Tremoli, Elena
    Tuomilehto, Jaakko
    Uusitupa, Matti
    van Duijn, Cornelia M.
    Vollenweider, Peter
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wareham, Nicholas J.
    Whitfield, John B.
    Wolffenbuttel, Bruce H. R.
    Altshuler, David
    Ordovas, Jose M.
    Boerwinkle, Eric
    Palmer, Colin N. A.
    Thorsteinsdottir, Unnur
    Chasman, Daniel I.
    Rotter, Jerome I.
    Franks, Paul W.
    Ripatti, Samuli
    Cupples, L. Adrienne
    Sandhu, Manjinder S.
    Rich, Stephen S.
    Boehnke, Michael
    Deloukas, Panos
    Mohlke, Karen L.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Abecasis, Goncalo R.
    Daly, Mark J.
    Neale, Benjamin M.
    Kathiresan, Sekar
    Common variants associated with plasma triglycerides and risk for coronary artery disease2013In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 45, no 11, p. 1345-+Article in journal (Refereed)
    Abstract [en]

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.

  • 186. Dobreanu, Dan
    et al.
    Dagres, Nikolaos
    Svendsen, Jesper Hastrup
    Marinskis, Germanas
    Bongiorni, Maria Grazia
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Approach to cardiac resyncronization therapy2012In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 14, no 9, p. 1359-1362Article in journal (Refereed)
    Abstract [en]

    AIMS:

    The purpose of this EP Wire is to compare indications, techniques, implant strategy, and follow-up regarding cardiac resynchronization therapy (CRT) in several countries across Europe.

    METHODS AND RESULTS:

    Forty-one centres, members of the EHRA-EP Research Network, responded to this survey and completed the questions. Thirty-two per cent of the responding centres always use CRT in heart failure (HF) patients with New York Heart Association functional class II and QRS width >120 ms, and 55% of the responding centres demand additional criteria when indicating CRT, most often QRS width >150 ms (49%) and echocardiographic criteria of asynchrony (34%). Only 10% of centres indicate CRT in all HF patients with QRS >120 ms and right bundle branch block, and 51% demand additional criteria, most frequently echocardiographic asynchrony parameters. The vast majority of centres also indicate CRT in patients with atrial fibrillation and standard criteria for CRT. In 24% of the centres, biventricular pacemaker (CRT-P) is implanted in all situations, unless there is an indication for secondary prevention of sudden cardiac death, while 10% always choose to implant a biventricular defibrillator (CRT-D). There are no clear evidence-based recommendations concerning the implant procedure and follow-up in patients treated with CRT; therefore, the chosen strategies vary widely from one centre to another.

    CONCLUSION:

    This EP Wire survey shows a wide variation not only as far as CRT indications are concerned, but especially in techniques, implant strategy, and follow-up across the European countries.

  • 187.
    Dondo, T. B.
    et al.
    Univ Leeds, Div Epidemiol & Biostat, LICAMM, Leeds, W Yorkshire, England..
    Hall, M.
    Univ Leeds, Div Epidemiol & Biostat, LICAMM, Leeds, W Yorkshire, England..
    West, R.
    Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England..
    Jernberg, T.
    Karolinska Univ Hosp, Cardiol Sect, Dept Med, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bueno, H.
    Univ Hosp 12 Octubre, Inst Invest I 12, Madrid, Spain.;Univ Hosp 12 Octubre, Dept Cardiol, Madrid, Spain..
    Deanfield, J. E.
    UCL, Natl Inst Cardiovasc Outcomes Res, London, England..
    Hemingway, H.
    UCL, Farr Inst, London, England..
    Timmis, A. D.
    Barts Hlth NHS Trust, Natl Inst Hlth Biomed Res Unit, London, England..
    Gale, C. P.
    Univ Leeds, Div Epidemiol & Biostat, LICAMM, Leeds, W Yorkshire, England..
    Beta blocker use and mortality in hospital survivors of acute myocardial infarction without heart failure2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 1253-1253Article in journal (Other academic)
  • 188.
    Dondo, Tatendashe B.
    et al.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, MRC, Bioinformat Ctr, Level 11,Worsley Bldg, Leeds LS2 9JT, W Yorkshire, England..
    Hall, Marlous
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, MRC, Bioinformat Ctr, Level 11,Worsley Bldg, Leeds LS2 9JT, W Yorkshire, England..
    West, Robert M.
    Univ Leeds, Leeds Inst Hlth Sci, Leeds, W Yorkshire, England..
    Jernberg, Tomas
    Karolinska Univ Hosp, Karolinska Inst, Dept Cardiol, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bueno, Hector
    Ctr Nacl Invest Cardiovasc, Madrid, Spain.;Hosp Univ 12 Octubre, Inst Invest i 12, Madrid, Spain.;Hosp Univ 12 Octubre, Cardiol Dept, Madrid, Spain.;Univ Complutense Madrid, Fac Med, Madrid, Spain..
    Danchin, Nicolas
    Hop Europeen Georges Pompidou, Dept Cardiol, Paris, France.;AP HP, Paris, France.;Univ Paris 05, Paris, France..
    Deanfield, John E.
    UCL, Natl Inst Cardiovasc Outcomes Res, London, England..
    Hemingway, Harry
    UCL, London, England.;Farr Inst Hlth Informat Res, London, England..
    Fox, Keith A. A.
    Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland..
    Timmis, Adam D.
    Barts Heart Ctr, Biomed Res Unit, Natl Inst Hlth, London, England..
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, MRC, Bioinformat Ctr, Level 11,Worsley Bldg, Leeds LS2 9JT, W Yorkshire, England.;York Teaching Hosp NHS Fdn Trust, Dept Cardiol, York, N Yorkshire, England..
    beta-Blockers and Mortality After Acute Myocardial Infarction in Patients Without Heart Failure or Ventricular Dysfunction2017In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 69, no 22, p. 2710-2720Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: For acute myocardial infarction (AMI) without heart failure (HF), it is unclear if beta-blockers are associated with reduced mortality.

    OBJECTIVES: The goal of this study was to determine the association between beta-blocker use and mortality in patients with AMI without HF or left ventricular systolic dysfunction (LVSD).

    METHODS: This cohort study used national English and Welsh registry data from the Myocardial Ischaemia National Audit Project. A total of 179,810 survivors of hospitalization with AMI without HF or LVSD, between January 1, 2007, and June 30, 2013 (final follow-up: December 31, 2013), were assessed. Survival-time inverse probability weighting propensity scores and instrumental variable analyses were used to investigate the association between the use of beta-blockers and 1-year mortality.

    RESULTS: Of 91,895 patients with ST-segment elevation myocardial infarction and 87,915 patients with non-ST-segment elevation myocardial infarction, 88,542 (96.4%) and 81,933 (93.2%) received beta-blockers, respectively. For the entire cohort, with> 163,772 person-years of observation, there were 9,373 deaths (5.2%). Unadjusted 1-year mortality was lower for patients who received beta-blockers compared with those who did not (4.9% vs. 11.2%; p < 0.001). However, after weighting and adjustment, there was no significant difference in mortality between those with and without beta-blocker use (average treatment effect [ATE] coefficient: 0.07; 95% confidence interval [CI]: -0.60 to 0.75; p = 0.827). Findings were similar for ST-segment elevation myocardial infarction (ATE coefficient: 0.30; 95% CI: -0.98 to 1.58; p = 0.637) and non-ST-segment elevation myocardial infarction (ATE coefficient: -0.07; 95% CI: -0.68 to 0.54; p = 0.819).

    CONCLUSIONS: Among survivors of hospitalization with AMI who did not have HF or LVSD as recorded in the hospital, the use of beta-blockers was not associated with a lower risk of death at any time point up to 1 year.

  • 189. Douketis, J D
    et al.
    Healey, J S
    Brueckmann, M
    Eikelboom, J W
    Ezekowitz, M D
    Fraessdorf, M
    Noack, H
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Reilly, P
    Spyropoulos, A C
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Clinical Research Center.
    Connolly, S J
    Perioperative bridging anticoagulation during dabigatran or warfarin interruption among patients who had an elective surgery or procedure: Substudy of the RE-LY trial2015In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 113, no 3, p. 625-632Article in journal (Refereed)
    Abstract [en]

    In patients with atrial fibrillation (AF) who require interruption of dabigatran or warfarin for an elective surgery/procedure, the risks and benefits of perioperative bridging anticoagulation is uncertain. We accessed the database from RE-LY, a randomised trial comparing dabigatran with warfarin for stroke prevention in AF, to assess the potential benefits and risks of bridging. In patients who had a first interruption of dabigatran or warfarin for an elective surgery/procedure, we compared the risk for major bleeding (MB), stroke or systemic embolism (SSE) and any thromboembolism (TE) in patients who were bridged or not bridged during the period of seven days before until 30 days after surgery/procedure. We used multivariable Cox regression to adjust for potential confounders. Bridging was used more during warfarin interruption than dabigatran interruption (27.5 % vs 15.4 %; p< 0.001). With dabigatran interruption, bridged patients had more MB (6.5 % vs. 1.8 %, P< 0.001) than those not bridged but bridged and not bridged groups did not differ for any TE (1.2 % vs 0.6 %, p=0.16) and SSE (0.5 % vs 0.3 %, p=0.46). With warfarin interruption, bridged patients had more MB (6.8 % vs 1.6 %, p< 0.001) and any TE (1.8 % vs 0.3 %, p=0.007) than those not bridged but bridged and not bridged groups did not differ for SSE (0.5 % vs 0.2 %, p=0.321). In conclusion, in patients who interrupted dabigatran or warfarin for a surgery/procedure in the RE-LY trial, use of bridging anticoagulation appeared to increase the risk for major bleeding irrespective of dabigatran or warfarin interruption.

  • 190. Douketis, J.
    et al.
    Healey, J. S.
    Brueckmann, M.
    Fraessdorf, M.
    Spyropoulos, A.
    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.
    Oldgren, J.
    Reilly, P.
    Ezekowitz, M.
    Connolly, S.
    Yusuf, S.
    Bleeding and thromboembolic outcomes in warfarin-and dabigatran-treated patients in the RE-LY trial who required an urgent surgery or procedure2015In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, no S2, p. 393-394, article id PO362-MONArticle in journal (Other academic)
  • 191.
    Douketis, James D.
    et al.
    McMaster Univ, Dept Med, Hamilton, ON, Canada..
    Healey, Jeff S.
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Brueckmann, Martina
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.;Mannheim Univ Heidelberg, Fac Med, Heidelberg, Germany..
    Fraessdorf, Mandy
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany..
    Spyropoulos, Alex C.
    Hofstra North Shore Long Isl Jewish Sch Med, Manhasset, NY USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Reilly, Paul
    Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA..
    Ezekowitz, Michael D.
    Jefferson Med Coll, Wynnewood, PA USA..
    Connolly, Stuart J.
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Yusuf, Salim
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, John W.
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Urgent surgery or procedures in patients taking dabigatran or warfarin: Analysis of perioperative outcomes from the RE-LY trial2016In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 139, p. 77-81Article, review/survey (Refereed)
    Abstract [en]

    Background: There is concern about the management of anticoagulated patients with atrial fibrillation (AF) who require an urgent surgery/procedure, especially in those who are receiving a direct oral anticoagulant such as dabigatran. Methods: We accessed the database from RE-LY, a randomized trial comparing dabigatran (110 mg and 150 mg twice daily) with warfarin for stroke prevention in AF, to assess patients who had an urgent and elective surgery/procedure. We compared the risk for thromboembolism, major bleeding and mortality according to treatment allocation (dabigatran 110 mg or 150 mg, or warfarin) or surgery/procedure type (urgent or elective). Outcomes were assessed from day-7 to day 30 after a surgery/procedure. Results: 353 patients (2.0% of study population) had an urgent surgery/procedure and 4168 patients (23.1% of study population) had an elective surgery/procedure. In patients on dabigatran 110 mg, dabigatran 150 mg and warfarin who had an urgent surgery/procedure: rates of thromboembolism were 16.1%, 7.4%, and 10.5%; rates of major bleeding were 17.0%, 17.6%, and 22.9%; rates of mortality were 6.3%, 1.5%, and 2.9%, respectively (P > 0.50 for all comparisons). Rates of these outcomes were multi-fold higher in patients having an urgent rather than an elective surgery/procedure (P < 0.5 for all comparisons). Conclusion: In anticoagulated patients with atrial fibrillation who require an urgent surgery/procedure, the risks for thromboembolism, major bleeding and mortality did not differ depending on treatment with dabigatran or warfarin, but rates of these outcomes were multi-fold higher than in patients having an elective surgery/procedure.

  • 192.
    Ducrocq, G.
    et al.
    Hop Bichat Claude Bernard, AP HP, F-75877 Paris 18, France..
    Schulte, P. J.
    Duke Clin Res Inst, Durham, NC USA..
    Budaj, A.
    Grochowski Hosp, Warsaw, Poland..
    Cornel, J. H.
    Med Ctr Alkmaar, Alkmaar, Netherlands..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Himmelmann, A.
    AstraZeneca Res & Dev, Molndal, Sweden..
    Husted, S.
    Holstebro Hosp, Holstebro, Denmark..
    Storey, R. F.
    Univ Sheffield, 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, P. G.
    Hop Bichat Claude Bernard, F-75877 Paris 18, France..
    Balancing the risk of ischaemic and bleeding events in ACS2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 860-861Article in journal (Other academic)
  • 193. Ducrocq, G.
    et al.
    Schulte, P. J.
    Cannon, C. P.
    Becker, R. C.
    Harrington, R. A.
    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.
    Himmelmann, A.
    Sorbets, E.
    Wallentin, L.
    Steg, P. G.
    Prognostic implications of major bleeding on mortality in ACS patients: An analysis of the PLATO trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 724-724Article in journal (Refereed)
  • 194. Ducrocq, Gregory
    et al.
    Schulte, P J
    Becker, R C
    Cannon, C P
    Harrington, R A
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Himmelmann, A
    Lassila, R
    Storey, R F
    Sorbets, E
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Steg, P G
    Association of spontaneous and procedure-related bleeds with short- and long-term mortality after acute coronary syndromes:: an analysis from the PLATO trial2015In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 11, no 7, p. 737-745Article in journal (Refereed)
    Abstract [en]

    Aims: We sought to describe the differential effect of bleeding events in acute coronary syndromes (ACS) on short- and long-term mortality according to their type and severity.

    Methods and results: The PLATO trial randomised 18,624 ACS patients to clopidogrel or ticagrelor. Post-randomisation bleeding events were captured according to bleeding type (spontaneous or procedure-related), with PLATO, TIMI, and GUSTO definitions. The association of bleeding events with subsequent short-term (<30 days) and long-term (>30 days) all-cause mortality was assessed using time-dependent Cox proportional hazard models. A model was fitted to compare major and minor bleeding for mortality prediction. Of 18,624 patients, 2,189 (11.8%) had at least one PLATO major bleed (mean follow-up 272.2±123.5 days). Major bleeding was associated with higher short-term mortality (adjusted hazard ratio [HR] 9.28; 95% confidence interval [CI]: 7.50-11.48) but not with long-term mortality (adjusted HR 1.28; 95% CI: 0.93-1.75). Spontaneous bleeding was associated with short-term (adjusted HR 14.59; 95% CI: 11.14-19.11) and long-term (adjusted HR 3.38; 95% CI: 2.26-5.05) mortality. Procedure-related bleeding was associated with short-term mortality (adjusted HR 5.29; 95% CI: 4.06-6.87): CABG-related and non-coronary-procedure-related bleeding were associated with a higher short-term mortality, whereas PCI or angiography-related bleeding was not associated with either short- or long-term mortality. Similar results were obtained using the GUSTO and TIMI bleeding definitions.

    Conclusions: Major bleeding is associated with high subsequent mortality in ACS. However, this association is much stronger in the first 30 days and is strongest for spontaneous (vs. procedure-related) bleeding.

  • 195.
    Ducrocq, Gregory
    et al.
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;INSERM, Unite 1148, Paris, France..
    Schulte, Phillip J.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.;Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA..
    Budaj, Andrzej
    Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland..
    Cornel, Jan H.
    Noordwest Ziekenhuisgrp, Dept Cardiol, Alkmaar, Netherlands..
    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.
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Hunted, Steen
    Hosp Unit Wwst, Med Dept, Herning Holstebro, Denmark..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.;Baim Inst Clin Res Boston, Boston, MA USA..
    Becker, Richard C.
    Univ Cincinnati, Coll Med, Heart Lung & Vasc Inst, Div Cardiovasc Hlth & Dis, Cincinnati, OH USA..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Sorbets, Enunanuel
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;INSERM, Unite 1148, Paris, France.;Hop Avicenne, AP HP, Bobigny, France.;Univ Paris 13, Bobigny, France..
    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.
    Steg, Philippe Gabriel
    FACT, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.;INSERM, Unite 1148, Paris, France.;NHLI Imperial Coll, Royal Brampton Hosp, ICMS, London, England..
    Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 186, p. 91-99Article in journal (Refereed)
    Abstract [en]

    Background: Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality.

    Methods: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events.

    Results: A total of 822 patients (4.4%) had >= 1 spontaneous ischemic event; 485 patients (2.6%), >= 1 spontaneous PLATO major bleed, 282 (1.5%), >= 1 spontaneous TIMI major bleed; and 207 (1.1%), >= 1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% Cls) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05)

    Conclusions: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.

  • 196.
    Durheim, Michael T.
    et al.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA..
    Cyr, Derek D.
    Duke Clin Res Inst, Durham, NC USA..
    Lopes, Renato D.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Thomas, Laine E.
    Duke Clin Res Inst, Durham, NC USA..
    Tsuang, Wayne M.
    Cleveland Clin, Dept Pulm Med, Cleveland, OH 44106 USA..
    Gersh, Bernard J.
    Coll Med, Mayo Clin, Div Cardiovasc Dis, Rochester, MN 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, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Granger, Christopher B.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Palmer, Scott M.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Pulm Allergy & Crit Care Med, Durham, NC USA..
    Al-Khatib, Sana M.
    Duke Clin Res Inst, Durham, NC USA.;Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA..
    Chronic obstructive pulmonary disease in patients with atrial fibrillation: Insights from the ARISTOTLE trial2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 202, p. 589-594Article in journal (Refereed)
    Abstract [en]

    Background: Comorbid chronic obstructive pulmonary disease (COPD) is associated with poor outcomes among patients with cardiovascular disease. The risks of stroke and mortality associated with COPD among patients with atrial fibrillation are not well understood. Methods: We analyzed patients from ARISTOTLE, a randomized trial of 18,201 patients with atrial fibrillation comparing the effects of apixaban versus warfarin on the risk of stroke or systemic embolism. Using Cox proportional hazards models, we assessed the associations between comorbid COPD and risk of stroke or systemic embolism and of mortality, adjusting for treatment allocation, smoking history and other risk factors. Results: COPD was present in 1950 (10.8%) of 18,134 patients with data on pulmonary disease history. After multivariable adjustment, COPD was not associated with risk of stroke or systemic embolism (adjusted HR 0.85 [95% CI 0.60, 1.21], p = 0.356). However, COPD was associated with a higher risk of all-cause mortality (adjusted HR 1.60 [95% CI 1.36, 1.88], p < 0.001) and both cardiovascular and non-cardiovascular mortality. The benefit of apixaban over warfarin on stroke or systemic embolism was consistent among patients with and without COPD (HR 0.92 [95% CI 0.52, 1.63] versus 0.78 [95% CI 0.65, 0.95], interaction p = 0.617). Conclusions: COPD was independently associated with increased risk of cardiovascular and non-cardiovascular mortality among patients with atrial fibrillation, but was not associated with risk of stroke or systemic embolism. The effect of apixaban on stroke or systemic embolism in COPD patients was consistent with its effect in the overall trial population.

  • 197. Déry, Jean-Pierre
    et al.
    Mahaffey, Kenneth W
    Tricoci, Pierluigi
    White, Harvey D
    Podder, Mohua
    Westerhout, Cynthia M
    Moliterno, David J
    Harrington, Robert A
    Chen, Edmond
    Strony, John
    Van de Werf, Frans
    Ziada, Khaled M
    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.
    Aylward, Philip E
    Armstrong, Paul W
    Rao, Sunil V
    Arterial access site and outcomes in patients undergoing percutaneous coronary intervention with and without vorapaxar2016In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 88, no 2, p. 163-173Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: We evaluated outcomes associated with transradial vs. transfemoral approaches and vorapaxar in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) in the TRACER trial.

    BACKGROUND: Vorapaxar reduces ischemic events but increases the risk of major bleeding.

    METHODS: We compared 30-day and 2-year major adverse cardiac events (MACE: cardiovascular death, myocardial infarction, stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization) and noncoronary artery bypass graft (CABG)-related bleedings in 2,192 transradial and 4,880 transfemoral patients undergoing PCI after adjusting for confounding variables, including propensity for transradial access.

    RESULTS: Overall, 30-day GUSTO moderate/severe and non-CABG TIMI major/minor bleeding occurred less frequently in transradial (0.9% vs. 2.0%, P = 0.001) vs. transfemoral (1.1% vs. 2.5%, P = 0.005) patients. A similar reduction was seen at 2 years (3.3% vs. 4.7%, P = 0.008; 3.3% vs. 4.9%, P < 0.001, respectively). Transradial was associated with an increased risk of ischemic events at 30 days (OR 1.38, 95% CI 1.11-1.72; P = 0.004), driven primarily by increased periprocedural myocardial infarctions. At 2 years, rates of MACE were comparable (HR 1.14, 95% CI 0.98-1.33; P = 0.096). Although bleeding rates were higher with vorapaxar in transfemoral vs. transradial patients, there was no significant treatment interaction. Also, the access site did not modulate the association between vorapaxar and MACE.

    CONCLUSIONS: Transradial access was associated with lower bleeding rates and similar long-term ischemic outcomes, suggesting transradial access is safer than transfemoral access among ACS patients receiving potent antiplatelet therapies. Because of the nonrandomized allocation of arterial access, these results should be considered exploratory. © 2015 Wiley Periodicals, Inc.

  • 198.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lundin, Elin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Melki, Vilyam
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    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.
    Nyman, Rickard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Percutaneous Closure in Transfemoral Aortic Valve Implantation: A Single-Centre Experience2015In: Cardiovascular and Interventional Radiology, ISSN 0174-1551, E-ISSN 1432-086X, Vol. 38, no 6, p. 1438-1443Article in journal (Refereed)
    Abstract [en]

    PURPOSE: To report the experience of a percutaneous closure device used for transfemoral transcatheter aortic valve implantation (TAVI) in an unselected patient and operator population.

    MATERIALS AND METHODS: Eighty-two consecutive patients (32 women, 50 men) who underwent transfemoral TAVI between September 2009 and February 2014 at our hospital were retrospectively reviewed for percutaneous closure device (PCD) failure, vascular complications, and bleeding. The diameter and calcification of the common femoral artery (CFA) and the thickness of the subcutaneous fat layer in the groin were assessed on computed tomography images.

    RESULTS: The incidences of PCD failure and minor and major vascular complications were 19.5 % (n = 16/82), 19.5 % (n = 16/82), and 7 % (n = 6/82) respectively. 8.5 % (n = 7/82) had a minor perioperative bleeding, 6 % (n = 5/82) had a major bleeding, and none had any life-threatening bleeding. When PCD failed, haemostasis was obtained with fascia suturing, covered stent placement, or with surgical cutdown. Thirty-day mortality and 1-year all-cause mortality were 8.5 % (n = 7/82) and 19.5 % (n = 16/82), respectively. In a multiple regression analysis, the CFA diameter and the presence of severe calcification were independently related to PCD failure (correlation coefficient = -0.24, p = 0.027 and correlation coefficient = 0.23, p = 0.036, respectively).

    CONCLUSION: PCD failure was related to a small CFA diameter and to a severely calcified CFA. Failure could largely be managed with minimally invasive techniques such as covered stents or fascia suturing.

  • 199.
    Ebeling Barbier, Charlotte
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Themudo, Raquel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Bjerner, Tomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Johansson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ahlström, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Radiology.
    Cardiac Troponin I Associated with the Development of Unrecognized Myocardial Infarctions Detected with MRI2014In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 60, no 10, p. 1327-1335Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Late enhancement MRI (LE-MRI) and cardiac troponin I (cTnI) are sensitive methods to detect subclinical myocardial injury. We sought to investigate the relation between plasma concentrations of cTnI measured with a high-sensitivity assay (hs-cTnI) and the development of unrecognized myocardial infarctions (UMIs) detected with LE-MRI.

    METHODS:

    After approval from the ethics committee and written informed consent were obtained, LE-MRI was performed on 248 randomly selected community-living 70-year-old volunteers and hs-cTnI was determined with a highly sensitive premarket assay. Five years later these individuals were invited to a second LE-MRI, and 176 of them (82 women, 94 men), who did not have a hospital diagnosis of MI, constitute the present study population. LE-MR images were analyzed by 2 radiologists independently and in a consensus reading, blinded to any information on previous disease or assessments.

    RESULTS:

    New or larger UMIs were detected in 37 participants during follow-up. Plasma concentrations of hs-cTnI at 70 years of age, which were mainly within what is considered to be the reference interval, were related to new or larger UMIs at 75 years of age with an odds ratio of 1.98 per 1 unit increase in ln-transformed cTnI (95% CI, 1.17-3.35; P = 0.010). Plasma concentrations of hs-cTnI at 70 years of age were associated with the volumes of the UMIs detected at 75 years of age (P = 0.028).

    CONCLUSIONS:

    hs-cTnI in 70-year-old community-living women and men was associated with the development of MRI-detected UMIs within 5 years.

  • 200. Edfors, R.
    et al.
    Szummer, K.
    Evans, M.
    Carrero-Roig, J-J
    Spaak, J.
    James, Stefan
    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.
    Jernberg, T.
    Renal function and outcome in patients with stable coronary artery disease undergoing coronary angiography. Data from 6 years of consecutive patients in a nationwide registry2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 718-718Article in journal (Other academic)
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