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  • 401.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Östlund, Olof Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, J. H.
    Duke Univ, Med Ctr, Durham, NC 27706 USA..
    Granger, C. B.
    Duke Univ, Med Ctr, Durham, NC 27706 USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stewart, R. A. H.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1, New Zealand..
    White, H. D.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1, New Zealand..
    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.
    External validation of the biomarker-based ABC-stroke risk score for atrial fibrillation2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 710-711Article in journal (Other academic)
  • 402.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Stora studier av NOAK visar på gott och säkert strokeskydd: {Large studies of NOAC shows good and safe stroke protection}2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 37Article in journal (Refereed)
  • 403.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, S. J.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, J. W.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, M. D.
    Jefferson Med Coll, Wynnewood, PA USA.;Ctr Heart, Wynnewood, PA USA..
    Reilly, P. A.
    Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Yusuf, S.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Growth differentiation factor 15 is an independent marker of risk of major bleeding in atrial fibrillation: insights from the RE-LY trial2016Conference paper (Refereed)
  • 404.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart J
    Eikelboom, John W
    Ezekowitz, Michael D
    Reilly, Paul A
    Yusuf, Salim
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial2017In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 190, p. 94-103, article id S0002-8703(17)30172-2Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial.

    METHODS: GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment.

    RESULTS: GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores.

    CONCLUSIONS: In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment.

  • 405.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart J.
    Ezekowitz, Michael D.
    Hohnloser, Stefan H.
    Reilly, Paul A.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Yusuf, Salim
    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.
    Importance of Persistent Elevation of Cardiac Biomarkers in Atrial Fibrillation: a RE-LY Substudy2014In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 100, no 15, p. 1193-1200Article in journal (Other academic)
    Abstract [en]

    Objectives To evaluate the prognostic importance of transient or persistent elevations of cardiac troponin-I (cTnI) and N-terminal-B-type natriuretic peptide (NT-proBNP) in atrial fibrillation (AF). Methods Plasma samples were obtained at randomisation and after 3 months in 2514 patients with AF in the RE-LY trial; median follow-up was 2.0 years. Patients were grouped based on levels at the two time points according to detectable cTnI levels (>= 0.01 mu g/L) or NT-proBNP levels above median (>= 778 ng/L). These groups were related to occurrence of stroke or cardiovascular events evaluated with Cox models adjusting for established risk factors. Results The proportion of patients with detectable cTnI levels at both time points was 48.5%, at one time point 28.5% and at neither time point 21.0%. Patients with detectable cTnI at both time points had substantially higher rates of stroke compared with those with transient elevations and those with no elevation at either time point (p<0.005, effect of cTnI). Persistent elevation of either or both cardiac biomarkers at baseline and 3 months was associated with a higher risk for cardiovascular events and mortality (p<0.0001). Prognostic prediction improved most with the use of repeated measurements of both cardiac biomarkers simultaneously (p<0.05) and achieved C-statistic 0.644 for stroke compared with 0.611 for CHADS2-score. Conclusions Persistent elevation of troponin and NT-proBNP indicates a worse prognosis than transient elevations or no elevations of either marker. Prognostication of stroke, death and thromboembolic events is improved by the use of repeated determinations of cardiac biomarkers.

  • 406.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart J.
    Ezekowitz, Michael D.
    Hohnloser, Stefan H.
    Reilly, Paul A.
    Vinereanu, Dragos
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yusuf, Salim
    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.
    Cardiac Biomarkers Are Associated With an Increased Risk of Stroke and Death in Patients With Atrial Fibrillation: A Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Substudy2012In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, no 13, p. 1605-1616Article in journal (Refereed)
    Abstract [en]

    Background—Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association to cardiovascular events in atrial fibrillation (AF) patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial.

    Methods and Results—Biomarkers at randomization were analyzed in 6189 patients. Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS2 and CHA2DS2-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010 to 0.019 μg/L, n=2006; 0.020 to 0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to 1402; >1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group (hazard ratio [HR], 1.99 [95% CI, 1.17–3.39]; P=0.0040), and to NT-proBNP with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile groups, (HR, 2.40 [95% CI, 1.41–4.07]; P=0.0014). Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group (HR, 4.38 [95% CI, 3.05–6.29]; P<0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR, 6.73 [3.95–11.49]; P<0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72, P<0.0001, for a composite of thromboembolic events.

    Conclusions—Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality. Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables.

  • 407.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Connolly, Stuart
    Eikelboom, John
    Ezekowitz, Michael
    Granger, Christopher
    Hylek, Elaine
    Lopes, Renato
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Yusuf, Salim
    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.
    External Validation Of The Biomarker-Based ABC-Bleeding Risk Score For Atrial Fibrillation2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 893-893Article in journal (Other academic)
  • 408.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Lindbäck, Johan
    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..
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, John W.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, Michael D.
    Thomas Jefferson Med Coll & Heart Ctr, Wynnewood, PA USA..
    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.
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Lopes, Renato D.
    Duke Med, Duke Clin Res Inst, Durham, NC USA..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    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.
    The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10035, p. 2302-2311Article in journal (Refereed)
    Abstract [en]

    Background: The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation.

    Methods: We developed and internally validated a new biomarker-based risk score for major bleeding in 14 537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov, numbers NCT00412984 and NCT00262600, respectively.

    Findings: The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers [GDF-15, cTnT-hs, and haemoglobin], and clinical history [previous bleeding]) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0.68 [95% CI 0.66-0.70] vs 0.61 [0.59-0.63] vs 0.65 [0.62-0.67], respectively; ABC-bleeding vs HAS-BLED p< 0.0001 and ABC-bleeding vs ORBIT p= 0.0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0.71 [95% CI 0.68-0.73] vs 0.62 [0.59-0.64] for HAS-BLED vs 0.68 [0.65-0.70] for ORBIT; ABC-bleeding vs HAS-BLED p< 0.0001 and ABC-bleeding vs ORBIT p= 0.0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores.

    Interpretation: The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation.

  • 409.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Alexander, John H.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Eikelboom, John W.
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Ezekowitz, Michael D.
    Thomas Jefferson Med Coll, Wynnewood, PA USA.;Ctr Heart, Wynnewood, PA USA..
    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.
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Lopes, Renato D.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada..
    Granger, Christopher B.
    Duke Hlth, Duke Clin Res Inst, Durham, NC USA..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    A biomarker-based risk score to predict death in patients with atrial fibrillation: the ABC (age, biomarkers, clinical history) death risk score2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 6, p. 477-485Article in journal (Refereed)
    Abstract [en]

    Aims: In atrial fibrillation (AF), mortality remains high despite effective anticoagulation. A model predicting the risk of death in these patients is currently not available. We developed and validated a risk score for death in anticoagulated patients with AF including both clinical information and biomarkers.

    Methods and results: The new risk score was developed and internally validated in 14 611 patients with AF randomized to apixaban vs. warfarin for a median of 1.9 years. External validation was performed in 8548 patients with AF randomized to dabigatran vs. warfarin for 2.0 years. Biomarker samples were obtained at study entry. Variables significantly contributing to the prediction of all-cause mortality were assessed by Cox-regression. Each variable obtained a weight proportional to the model coefficients. There were 1047 all-cause deaths in the derivation and 594 in the validation cohort. The most important predictors of death were N-terminal pro B-type natriuretic peptide, troponin-T, growth differentiation factor-15, age, and heart failure, and these were included in the ABC (Age, Biomarkers, Clinical history)-death risk score. The score was well-calibrated and yielded higher c-indices than a model based on all clinical variables in both the derivation (0.74 vs. 0.68) and validation cohorts (0.74 vs. 0.67). The reduction in mortality with apixaban was most pronounced in patients with a high ABC-death score.

    Conclusion: A new biomarker-based score for predicting risk of death in anticoagulated AF patients was developed, internally and externally validated, and well-calibrated in two large cohorts. The ABC-death risk score performed well and may contribute to overall risk assessment in AF.

  • 410.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. psala, Sweden.;Uppsala Clin Res Ctr, Uppsala, Sweden..
    The ABC risk score for patients with atrial fibrillation Reply2016In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 388, no 10055, p. 1980-1981Article in journal (Refereed)
  • 411.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Granger, Christopher B
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Biomarkers in atrial fibrillation: a clinical review2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 20, p. 1475-1480Article in journal (Refereed)
    Abstract [en]

    Assessment of atrial fibrillation (AF)-associated stroke risk is at present mainly based on clinical risk scores such as CHADS2 and CHA2DS2-VASc, although these scores provide only modest discrimination of risk for individual patients. Biomarkers derived from the blood may help refine risk assessment in AF for stroke outcomes and for mortality. Recent studies of biomarkers in AF have shown that they can substantially improve risk stratification. Cardiac biomarkers, such as troponin and natriuretic peptides, significantly improve risk stratification in addition to current clinical risk stratification models. Similar findings have recently been described for markers of renal function, coagulation, and inflammation in AF populations based on large randomized prospective clinical trials or large community-based cohorts. These new findings may enable development of novel tools to improve clinical risk assessment in AF. Biomarkers in AF may also improve the understanding of the pathophysiology of AF further as well as potentially elucidate novel treatment targets. This review will highlight novel associations of biomarkers and outcomes in AF as well as recent progress in the use of biomarkers for risk stratification.

  • 412.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Ulrika
    Connolly, Stuart J.
    Yusuf, Salim
    Ezekowitz, Michael D.
    Hohnloser, Stefan H.
    Reilly, Paul A.
    Vinereanu, Dragos
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Response to Letter Regarding Article, "Cardiac Biomarkers Are Associated With an Increased Risk of Stroke and Death in Patients With Atrial Fibrillation: A Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) Substudy"2013In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 127, no 2, p. E278-E279Article in journal (Refereed)
  • 413.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Andersson, Ulrika
    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.
    Alexander, John H.
    Atar, Dan
    Gersh, Bernard J.
    Mohan, Puneet
    Harjola, Veli-Pekka
    Horowitz, John
    Husted, Steen
    Hylek, Elaine M.
    Lopes, Renato D.
    McMurray, John J. V.
    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.
    High-Sensitivity Troponin I for Risk Assessment in Patients With Atrial Fibrillation Insights From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 129, no 6, p. 625-634Article in journal (Refereed)
    Abstract [en]

    Background High-sensitivity troponin-I (hs-TnI) measurement improves risk assessment for cardiovascular events in many clinical settings, but the added value in atrial fibrillation patients has not been described. Methods and Results At randomization, hs-TnI was analyzed in 14 821 atrial fibrillation patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial comparing apixaban with warfarin. The associations between hs-TnI concentrations and clinical outcomes were evaluated by using adjusted Cox analysis. The hs-TnI assay detected troponin (1.3 ng/L) in 98.5% patients, 50% had levels >5.4, 25% had levels >10.1, and 9.2% had levels 23 ng/L (the 99th percentile in healthy individuals). During a median of 1.9 years follow-up, annual rates of stroke or systemic embolism ranged from 0.76% in the lowest hs-TnI quartile to 2.26% in the highest quartile (>10.1 ng/L). In multivariable analysis, hs-TnI was significantly associated with stroke or systemic embolism, adjusted hazard ratio 1.98 (1.42-2.78), P=0.0007. hs-TnI was also significantly associated with cardiac death; annual rates ranged from 0.40% to 4.24%, hazard ratio 4.52 (3.05-6.70), P<0.0001, in the corresponding groups, and for major bleeding hazard ratio 1.44 (1.11-1.86), P=0.0250. Adding hs-TnI levels to the CHA(2)DS(2)VASc score improved c-statistics from 0.629 to 0.653 for stroke or systemic embolism, and from 0.591 to 0.731 for cardiac death. There were no significant interactions with study treatment. Conclusions Troponin-I is detected in 98.5% and elevated in 9.2% of atrial fibrillation patients. The hs-TnI level is independently associated with a raised risk of stroke, cardiac death, and major bleeding and improves risk stratification beyond the CHA(2)DS(2)VASc score. The benefits of apixaban in comparison with warfarin are consistent regardless of hs-TnI levels.

  • 414.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher
    Duke Clinical Research Institute, Durham, NC, US.
    Alexander, John H
    Duke Clinical Research Institute, Durham, NC, US.
    Atar, Dan
    Department of Cardiology, Oslo University Hospital Ulleval and Faculty of Medicine, Institute for Clinical Medicine, University of Oslo, Norway.
    Gersh, Bernard
    Mayo Clinic College of Medicine, Rochester, MN, US.
    Hanna, Michael
    Bristol-Myers Squibb, Princeton, NJ, US.
    Harjola, Veli-Pekka
    Horowitz, John D
    Hylek, Elaine M
    Lopes, Renato D
    McMurray, John JV
    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.
    Comparison of Cardiac Troponins I and T Measured with High-Sensitivity Methods for Evaluation of Prognosis in Atrial Fibrillation: An ARISTOTLE Substudy2015In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 61, no 2, p. 368-378Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Although cardiac troponin is associated with outcomes in atrial fibrillation (AF), the complementary prognostic information provided by cardiac troponin I (cTnI) and cTnT is unknown. This study investigated the distribution, determinants, and prognostic value of cTnI and cTnT concentrations in patients with AF.

    METHODS:

    At the time of randomization, we analyzed cTnI and cTnT concentrations of 14 806 AF patients in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial using high-sensitivity assays. Correlations (Spearman), determinants (multiple analysis of variance), and outcomes (adjusted Cox models and c-statistics) were investigated.

    RESULTS:

    Concentrations of cTnI and cTnT were correlated (r = 0.70) and measurable in most participants [cTnI 98.5% (median 5.4 ng/L, ≥99th percentile in 9.2%) and cTnT 93.5% (median 10.9 ng/L, ≥99th percentile in 34.4%)]. Renal impairment was the most important factor affecting the concentrations of both troponins. cTnI increase was more associated with heart failure, vascular disease, and persistent/permanent AF, and cTnT with age, male sex, and diabetes. Over a median 1.9 years of follow-up, patients with both troponins above the median had significantly higher risk for stroke/systemic embolism [hazard ratio (HR) 1.72 (95% CI 1.31-2.27)], cardiac death [3.14 (2.35-4.20)], and myocardial infarction [2.99 (1.78-5.03)] than those with both troponins below median (all P < 0.005). Intermediate risks were observed when only 1 troponin was above the median. When combined with clinical information, each marker provided similar prognostication and had comparable c-statistics.

    CONCLUSIONS:

    cTnI and cTnT concentrations are moderately correlated and measurable in plasma of most AF patients. The risk of stroke and cardiovascular events is highest when both troponins are above median concentrations. Each troponin provides comparable prognostic information when combined with clinical risk factors.

  • 415.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Verdecchia, P.
    Hosp Assisi, Dept Med, Assisi, Italy..
    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.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Reboldi, M. G.
    Univ Perugia, Dept Internal Med, Perugia, Italy..
    Di Pasquale, G.
    Maggiore Hosp, Dept Cardiol, Bologna, Italy..
    Mazzotta, G.
    Hosp Assisi, Dept Med, Assisi, Italy..
    Angeli, F.
    Hosp Santa Maria Della Misericordia, Cardiol & Cardiovasc Pathophysiol, Perugia, Italy..
    Ezekowitz, M. D.
    Thomas Jefferson Med Coll & Heart Ctr, Wynnewood, PA USA..
    Connolly, S. J.
    McMaster Univ, Hamilton, ON, Canada..
    Yusuf, S.
    McMaster Univ, Hamilton, ON, Canada..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cardiac biomarkers and left ventricular hypertrophy in relation to outcomes in patients with atrial fibrillation: experiences from the RELY trial2016In: EUROPEAN HEART JOURNAL, ISSN 0195-668X, Vol. 37, p. 47-47Article in journal (Refereed)
  • 416.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Verdecchia, Paolo
    Hosp Assisi, Dept Med, Assisi, Italy.
    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. Uppsala Univ, Dept Med Sci, Cardiol, Uppsala, Sweden;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Reboldi, Gianpaolo
    Univ Perugia, Dept Med, Perugia, Italy.
    Di Pasquale, Giuseppe
    Maggiore Hosp, Dept Cardiol, Bologna, Italy.
    Mazzotta, Giovanni
    Hosp Assisi, Dept Med, Assisi, Italy.
    Angeli, Fabio
    Univ Perugia, Dept Cardiol & Cardiovasc Pathophysiol, Perugia, Italy.
    Eikelboom, John W.
    Ezekowitz, Michael D.
    Thomas Jefferson Med Coll & Heart Ctr, Wynnewood, PA USA.
    Connolly, Stuart J.
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    Populat Hlth Res Inst, Hamilton, ON, Canada.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cardiac Biomarkers and Left Ventricular Hypertrophy in Relation to Outcomes in Patients With Atrial Fibrillation: Experiences From the RE-LY Trial2019In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 8, no 2, article id e010107Article in journal (Refereed)
    Abstract [en]

    Background

    Cardiac biomarkers and left ventricular hypertrophy (LVH) are related to the risk of stroke and death in patients with atrial fibrillation. We investigated the interrelationship between LVH and cardiac biomarkers and their independent associations with outcomes.

    Methods and Results

    Plasma samples were obtained at baseline in 5275 patients with atrial fibrillation in the RE‐LY (Randomized Evaluation of Long‐Term Anticoagulation Therapy) trial. NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), cardiac troponin I and T, and growth differentiation factor‐15 were determined using high‐sensitivity (hs) assays. LVH was defined by ECG. Cox models were adjusted for baseline characteristics, LVH, and biomarkers. LVH was present in 1257 patients. During a median follow‐up of 2.0 years, 165 patients developed a stroke and 370 died. LVH was significantly (P<0.0001) associated with higher levels of all biomarkers in linear regression analyses adjusting for baseline characteristics. Geometric mean ratios (95% CIs) were as follows: NT‐proBNP, 1.32 (1.25–1.38); hs cardiac troponin I, 1.67 (1.57–1.78); hs troponin T, 1.38 (1.32–1.44); and growth differentiation factor‐15, 1.09 (1.05–1.12). For stroke, the hazard ratios (95% CIs) per 50% increase were as follows: NT‐proBNP, 1.09 (1.00–1.19); hs cardiac troponin I, 1.09 (1.03–1.15); hs troponin T, 1.14 (1.06–1.24); and growth differentiation factor‐15, 1.22 (1.08–1.38) (all P<0.05). For death, hazard ratios (95% CIs) were as follows: NT‐proBNP, 1.24 (1.17–1.31); hs cardiac troponin I, 1.13 (1.10–1.17); hs troponin T, 1.28 (1.23–1.34); and growth differentiation factor‐15, 1.31 (1.22–1.42) (all P<0.0001). LVH was not significantly associated with stroke or death after adjustment for biomarkers.

    Conclusions

    Cardiac biomarkers are significantly associated with LVH. The prognostic value of biomarkers for stroke and death is not affected by LVH. The prognostic information of LVH is attenuated in the presence of cardiac biomarkers.

  • 417.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Natriuretic peptide should be used as a routine tool for evaluation of patients with atrial fibrillation2018In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 105, no 5, p. 353-354Article in journal (Other academic)
  • 418.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Renal Function in Atrial Fibrillation A Multifaceted Dilemma2016In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 134, no 1, p. 48-51Article in journal (Other academic)
  • 419.
    Hijazi, Ziad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Ezekowitz, Justin
    Gersh, Bernard J
    Hanna, Michael
    Hohnloser, Stefan
    Horowitz, John
    Huber, Kurt
    Hylek, Elaine M
    Lopes, Renato D
    McMurray, John J V
    Granger, Christopher B
    N-Terminal Pro-B-Type Natriuretic Peptide for Risk Assessment in Patients With Atrial Fibrillation: Insights from the ARISTOTLE trial2013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 22, p. 2274-2284Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    This study sought to assess the prognostic value of N-terminal pro–B-type natriuretic peptide (NT-proBNP) in patients with atrial fibrillation (AF) enrolled in the ARISTOTLE (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation) trial, and the treatment effect of apixaban according to NT-proBNP levels.

    BACKGROUND:

    Natriuretic peptides are associated with mortality and cardiovascular events in several cardiac diseases.

    METHODS:

    In the ARISTOTLE trial, 18,201 patients with AF were randomized to apixaban or warfarin. Plasma samples at randomization were available from 14,892 patients. The association between NT-proBNP concentrations and clinical outcomes was evaluated using Cox proportional hazard models, after adjusting for established cardiovascular risk factors.

    RESULTS:

    Quartiles of NT-proBNP were Q1:≤363, Q2:364-713, Q3:714-1250 and Q4:>1250 ng/L. During 1.8 years the annual rates of stroke or systemic embolism ranged from 0.74% in the bottom NT-proBNP quartile to 2.21% in the top quartile, adjusted hazard ratio (HR) 2.35 (95% CI 1.62-3.40, p<0.0001. Annual rates of cardiac death ranged from 0.86% in Q1 to 4.14% in Q4, adjusted HR 2.50 (1.81-3.45), p<0.0001. Adding NT-proBNP levels to the CHA2DS2VASc score improved C-statistics from 0.62 to 0.65 (p=0.0009) for stroke or systemic embolism and from 0.59 to 0.69 for cardiac death (p<0.0001). Apixaban reduced stroke, mortality, and bleeding regardless of the NT-proBNP level.

    CONCLUSIONS:

    NT-proBNP levels are often elevated in AF and independently associated with an increased risk of stroke and mortality. NT-proBNP improves risk stratification beyond the CHA2DS2VASc score and might be a novel tool for improved stroke prediction in AF. The efficacy of apixaban compared with warfarin is independent of the NT-proBNP level. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE].

  • 420.
    Hjort, Marcus
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Baron, Tomasz
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jernberg, Tomas
    Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet.
    Tornvall, Per
    Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet.
    Eggers, Kai M.
    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.
    Prognosis in relation to high-sensitivity cardiac troponin T levels in patients with myocardial infarction and non-obstructive coronary arteries2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 200, p. 60-66Article in journal (Refereed)
    Abstract [en]

    Background: Myocardial infarction (MI) with non-obstructive coronary arteries (MINOCA) is a recently recognized condition where biomarkers and prognosis are less well studied than in MI with obstructive coronary artery disease (MI-CAD). We therefore aimed to investigate the one-year prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) levels in MINOCA in comparison to MI-CAD.

    Methods: In this registry-based cohort study, we used data frompatientswith a discharge diagnosis ofMI, admitted between 2009 and 2013 to Swedish hospitals using the hs-cTnT assay. Only patients without previously known coronary artery disease were considered. Patients with and without coronary stenosis N50% were regarded to haveMI-CAD andMINOCA, respectively. Assessed outcomes included all-cause mortality, cardiovascular (CV) mortality and major CV events (MACE), defined as the composite of CV death or admissions for nonfatal MI, heart failure (HF) or ischemic stroke.

    Results: The study cohort consisted of 1639 MINOCA and 17,304 MI-CAD patients. In adjusted analyses, hs-cTnT (ln) in MINOCA patients predicted all-cause mortality (HR 1.32 [95% CI 1.11-1.56]), CVmortality (HR 2.11 [95% CI 1.51-2.96]) and MACE (HR 1.44 [95% CI 1.20-1.72]). Hs-cTnT (ln) also predicted readmissions for HF (HR 1.51 [95% CI 1.51-2.96]) but not non-fatal MI or stroke. Interaction analyses suggested that hs-cTnT (ln) was at least as prognostic in patients with MINOCA compared to MI-CAD.

    Conclusions: Hs-cTnT levels inMINOCA patients are strong and independent predictors of adverse outcome. Consideration of hs-cTnT levels is important for risk assessment of MINOCA patients.

  • 421.
    Ho, C. L. B.
    et al.
    Univ Tasmania, Hobart, Tas, Australia..
    Doust, J.
    Bond Univ, Gold Coast, Qld, Australia..
    Jackson, R.
    Univ Auckland, Auckland, New Zealand..
    McManus, R. J.
    Univ Oxford, Oxford OX1 2JD, England..
    Reid, C. M.
    Monash Univ, Clayton, Vic, Australia.;Curtin Univ, Perth, WA 6845, Australia..
    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.
    Nelson, M. R.
    Univ Tasmania, Hobart, Tas, Australia..
    Should You Leave A Legacy?: Potential Effects Of Delayed Blood Pressure Lowering Pharmacotherapy In Individuals Stratified By Absolute Cardiovascular Disease Risk2016In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 67, no 5, p. E17-E18Article in journal (Other academic)
  • 422.
    Hochman, Judith S.
    et al.
    Cardiovascular Clinical Research Center, New York University School of Medicine, New York, New York.
    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.
    Jeffries, Neal
    NHLBI, Bldg 10, Bethesda, MD 20892 USA.
    Baseline Characteristics and Risk Profiles of Participants in the ISCHEMIA Randomized Clinical Trial2019In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 4, no 3, p. 273-286Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE

    It is unknown whether coronary revascularization, when added to optimal medical therapy, improves prognosis in patients with stable ischemic heart disease (SIHD) at increased risk of cardiovascular events owing to moderate or severe ischemia.

    OBJECTIVE

    To describe baseline characteristics of participants enrolled and randomized in the International Study of Comparative Health Effectiveness With Medical and Invasive Approaches (ISCHEMIA) trial and to evaluate whether qualification by stress imaging or nonimaging exercise tolerance test (ETT) influenced risk profiles.

    DESIGN, SETTING, AND PARTICIPANTS

    The ISCHEMIA trial recruited patients with SIHD with moderate or severe ischemia on stress testing. Blinded coronary computed tomography angiography was performed in most participants and reviewed by a core laboratory to exclude left main stenosis of at least 50% or no obstructive coronary artery disease (CAD) (< 50% for imaging stress test and < 70% for ETT). The study included 341 enrolling sites (320 randomizing) in 38 countries and patients with SIHD and moderate or severe ischemia on stress testing. Data presented were extracted on December 17, 2018.

    MAIN OUTCOMES AND MEASURES

    Enrolled, excluded, and randomized participants' baseline characteristics. No clinical outcomes are reported.

    RESULTS

    A total of 8518 patients were enrolled, and 5179 were randomized. Common reasons for exclusion were core laboratory determination of insufficient ischemia, unprotected left main stenosis of at least 50%, or no stenosis that met study obstructive CAD criteria on study coronary computed tomography angiography. Randomized participants had a median age of 64 years, with 1168 women (22.6%), 1726 nonwhite participants (33.7%), 748 Hispanic participants (15.5%), 2122 with diabetes (41.0%), and 4643 with a history of angina (89.7%). Among the 3909 participants randomized after stress imaging, core laboratory assessment of ischemia severity (in 3901 participants) was severe in 1748 (44.8%), moderate in 1600 (41.0%), mild in 317 (8.1%) and none or uninterpretable in 236 (6.0%), Among the 1270 participants who were randomized after nonimaging ETT, core laboratory determination of ischemia severity (in 1266 participants) was severe (an eligibility criterion) in 1051 (83.0%), moderate in 101 (8.0%), mild in 34 (2.7%) and none or uninterpretable in 80 (6.3%). Among the 3912 of 5179 randomized participants who underwent coronary computed tomography angiography, 79.0% had multivessel CAD (n = 2679 of 3390) and 86.8% had left anterior descending (LAD) stenosis (n = 3190 of 3677) (proximal in 46.8% [ n = 1749 of 3739]). Participants undergoing ETT had greater frequency of 3-vessel CAD, LAD, and proximal LAD stenosis than participants undergoing stress imaging.

    CONCLUSIONS AND RELEVANCE

    The ISCHEMIA trial randomized an SIHD population with moderate or severe ischemia on stress testing, of whom most had multivessel CAD.

  • 423.
    Hofmann, Robin
    et al.
    Karolinska Inst, Div Cardiol, Dept Clin Sci & Educ, Sodersjukhuset, Sjukhusbacken 10, S-11883 Stockholm, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Response to letter regarding article, 'Oxygen therapy in ST-elevation myocardial infarction'2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 2, p. 215-215Article in journal (Other academic)
    Abstract [en]

    This commentary refers to 'Oxygen therapy in ST-elevation myocardial infarction', by Y. Xin et al., on page 213.

  • 424.
    Hofmann, Robin
    et al.
    Karolinska Inst, Div Cardiol, Dept Clin Sci & Educ, Södersjukhuset, Stockholm, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Routine Oxygen Supplementation in Acute Cardiovascular Disease: The End of a Paradigm?2018In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, no 4, p. 320-322Article in journal (Other academic)
  • 425.
    Hofmann, Robin
    et al.
    Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Div Cardiol, Sjukhusbacken 10, S-11883 Stockholm, Sweden..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Cardiol, Stockholm, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Clin Sci, Cardiol, Lund, Sweden..
    Witt, Nils
    Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Div Cardiol, Sjukhusbacken 10, S-11883 Stockholm, Sweden..
    Arefalk, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Frick, Mats
    Soder Sjukhuset, Karolinska Inst, Dept Clin Sci & Educ, Div Cardiol, Sjukhusbacken 10, S-11883 Stockholm, Sweden..
    Alfredsson, Joakim
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Dept Cardiol, Linkoping, Sweden..
    Nilsson, Lennart
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden.;Linkoping Univ, Dept Cardiol, Linkoping, Sweden..
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Omerovic, Elmir
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Kellerth, Thomas
    Orebro Univ Hosp, Dept Cardiol, Orebro, Sweden..
    Sparv, David
    Lund Univ, Dept Clin Sci, Cardiol, Lund, Sweden..
    Ekelund, Ulf
    Lund Univ, Dept Clin Sci, Emergency Med, Lund, Sweden..
    Linder, Rickard
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Cardiol, Stockholm, Sweden..
    Ekstrom, Mattias
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Cardiol, Stockholm, Sweden..
    Lauermann, Jorg
    Ryhov Hosp, Dept Internal Med, Div Cardiol, Jonkoping, Sweden..
    Haaga, Urban
    Karlstad Cent Hosp, Dept Cardiol, Karlstad, Sweden..
    Pernow, John
    Karolinska Univ Hosp, Dept Cardiol, Solna, Sweden.;Karolinska Inst, Dept Med, Solna, Sweden..
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Herlitz, Johan
    Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden.;Univ Boras, Dept Hlth Sci, Boras, Sweden..
    Svensson, Leif
    Soder Sjukhuset, Karolinska Inst, Ctr Resuscitat Sci, Stockholm, Sweden.;Karolinska Inst, Dept Med, Solna, Sweden..
    Oxygen Therapy in Suspected Acute Myocardial Infarction2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 13, p. 1240-1249Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The clinical effect of routine oxygen therapy in patients with suspected acute myocardial infarction who do not have hypoxemia at baseline is uncertain. METHODS In this registry-based randomized clinical trial, we used nationwide Swedish registries for patient enrollment and data collection. Patients with suspected myocardial infarction and an oxygen saturation of 90% or higher were randomly assigned to receive either supplemental oxygen (6 liters per minute for 6 to 12 hours, delivered through an open face mask) or ambient air. RESULTS A total of 6629 patients were enrolled. The median duration of oxygen therapy was 11.6 hours, and the median oxygen saturation at the end of the treatment period was 99% among patients assigned to oxygen and 97% among patients assigned to ambient air. Hypoxemia developed in 62 patients (1.9%) in the oxygen group, as compared with 254 patients (7.7%) in the ambient-air group. The median of the highest troponin level during hospitalization was 946.5 ng per liter in the oxygen group and 983.0 ng per liter in the ambient-air group. The primary end point of death from any cause within 1 year after randomization occurred in 5.0% of patients (166 of 3311) assigned to oxygen and in 5.1% of patients (168 of 3318) assigned to ambient air (hazard ratio, 0.97; 95% confidence interval [CI], 0.79 to 1.21; P = 0.80). Rehospitalization with myocardial infarction within 1 year occurred in 126 patients (3.8%) assigned to oxygen and in 111 patients (3.3%) assigned to ambient air (hazard ratio, 1.13; 95% CI, 0.88 to 1.46; P = 0.33). The results were consistent across all predefined subgroups. CONCLUSIONS Routine use of supplemental oxygen in patients with suspected myocardial infarction who did not have hypoxemia was not found to reduce 1-year all-cause mortality.

  • 426. Hofmann, Robin
    et al.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Leif
    Witt, Nils
    Frick, Mats
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Östlund, Ollie
    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.
    Ekelund, Ulf
    Erlinge, David
    Herlitz, Johan
    Jernberg, Tomas
    DETermination of the role of OXygen in suspected Acute Myocardial Infarction trial2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 167, no 3, p. 322-328Article in journal (Refereed)
    Abstract [en]

    Background The use of supplemental oxygen in the setting of suspected acute myocardial infarction (AMI) is recommended in international treatment guidelines and established in prehospital and hospital clinical routine throughout the world. However, to date there is no conclusive evidence from adequately designed and powered trials supporting this practice. Existing data are conflicting and fail to clarify the role of supplemental oxygen in AMI. Methods A total of 6,600 normoxemic (oxygen saturation [SpO2] >= 90%) patients with suspected AMI will be randomly assigned to either supplemental oxygen 6 L/min delivered by Oxymask (MedCore Sweden AB, Kista, Sweden) for 6 to 12 hours in the treatment group or room air in the control group. Patient inclusion and randomization will take place at first medical contact, either before hospital admission or at the emergency department. The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry will be used for online randomization, allowing inclusion of a broad population of all-comers. Follow-up will be carried out in nationwide health registries and Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies. The primary objective is to evaluate whether oxygen reduces 1-year all-cause mortality. Secondary end points include 30-day mortality, major adverse cardiac events, and health economy. Prespecified subgroups include patients with confirmed AMI and certain risk groups. In a 3-month pilot study, the study concept was found to be safe and feasible. Conclusion The need to clarify the uncertainty of the role of supplemental oxygen therapy in the setting of suspected AMI is urgent. The DETO2X-AMI trial is designed and powered to address this important issue and may have a direct impact on future recommendations.

  • 427.
    Hofmann, Robin
    et al.
    Karolinska Inst, Stockholm, Sweden..
    Svensson, Leif
    Karolinska Inst, Stockholm, Sweden..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala Univ, Uppsala, Sweden..
    Oxygen Therapy in Suspected Acute Myocardial Infarction REPLY2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 378, no 2, p. 201-202Article in journal (Refereed)
  • 428.
    Hofmann, Robin
    et al.
    Karolinska Inst, Div Cardiol, Dept Clin Sci & Educ, Soder Sjukhuset, Sjukhusbacken 10, S-11883 Stockholm, Sweden.
    Witt, Nils
    Karolinska Inst, Div Cardiol, Dept Clin Sci & Educ, Soder Sjukhuset, Sjukhusbacken 10, S-11883 Stockholm, Sweden.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Cardiol, Morbygardsvagen 5, S-18288 Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden.
    Herlitz, Johan
    Univ Boras, Dept Hlth Sci, S-50190 Boras, Sweden;Sahlgrens Univ Hosp, Dept Cardiol, S-41345 Gothenburg, Sweden.
    Alfredsson, Joakim
    Linkoping Univ, Dept Med & Hlth Sci, Sandbacksgatan 7, S-58183 Linkoping, Sweden;Linkoping Univ Hosp, Dept Cardiol, S-58185 Linkoping, Sweden.
    Linder, Rikard
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Cardiol, Morbygardsvagen 5, S-18288 Stockholm, Sweden.
    Omerovic, Elmir
    Sahlgrens Univ Hosp, Dept Cardiol, S-41345 Gothenburg, Sweden.
    Angeras, Oskar
    Sahlgrens Univ Hosp, Dept Cardiol, S-41345 Gothenburg, Sweden.
    Venetsanos, Dimitrios
    Linkoping Univ, Dept Med & Hlth Sci, Sandbacksgatan 7, S-58183 Linkoping, Sweden;Linkoping Univ Hosp, Dept Cardiol, S-58185 Linkoping, Sweden.
    Kellerth, Thomas
    Orebro Univ Hosp, Dept Cardiol, S-70185 Orebro, Sweden.
    Sparv, David
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden.
    Lauermann, Jorg
    Ryhov Hosp, Dept Internal Med, Div Cardiol, Sjukhusgatan, S-55305 Jonkoping, Sweden.
    Barmano, Neshro
    Ryhov Hosp, Dept Internal Med, Div Cardiol, Sjukhusgatan, S-55305 Jonkoping, Sweden.
    Verouhis, Dinos
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, S-17176 Solna, Sweden;Karolinska Univ Hosp, Dept Cardiol, S-17176 Stockholm, Sweden.
    Östlund, Olof Petter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Svensson, Leif
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, S-17176 Solna, Sweden;Karolinska Inst, Ctr Resuscitat Sci, Soder Sjukhuset, Jagargatan 20, S-11883 Stockholm, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oxygen therapy in ST-elevation myocardial infarction2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 29, p. 2730-2739Article in journal (Refereed)
    Abstract [en]

    Aims

    To determine whether supplemental oxygen in patients with ST-elevation myocardial infarction (STEMI) impacts on procedure-related and clinical outcomes.

    Methods and results The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized patients with suspected myocardial infarction (MI) to receive oxygen at 6 L/min for 6-12 h or ambient air. In this pre-specified analysis, we included only STEMI patients who underwent percutaneous coronary intervention (PCI). In total, 2807 patients were included, 1361 assigned to receive oxygen, and 1446 assigned to ambient air. The pre-specified primary composite endpoint of all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis at 1 year occurred in 6.3% (86 of 1361) of patients allocated to oxygen compared to 7.5% (108 of 1446) allocated to ambient air [hazard ratio (HR) 0.85, 95% confidence interval (95% CI) 0.64-1.13; P = 0.27]. There was no difference in the rate of death from any cause (HR 0.86, 95% CI 0.61-1.22; P = 0.41), rate of rehospitalization for MI (HR 0.92, 95% CI 0.57-1.48; P = 0.73), rehospitalization for cardiogenic shock (HR 1.05, 95% CI 0.21-5.22; P = 0.95), or stent thrombosis (HR 1.27, 95% CI 0.46-3.51; P = 0.64). The primary composite endpoint was consistent across all subgroups, as well as at different time points, such as during hospital stay, at 30 days and the total duration of follow-up up to 1356 days.

    Conclusions Routine use of supplemental oxygen in normoxemic patients with STEMI undergoing primary PCI did not significantly affect 1-year all-cause death, rehospitalization with MI, cardiogenic shock, or stent thrombosis.

  • 429. Hohnloser, Stefan H.
    et al.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Thomas, Laine
    Alexander, John H.
    Amerena, John
    Hanna, Michael
    Keltai, Matyas
    Lanas, Fernando
    Lopes, Renato D.
    Lopez-Sendon, Jose
    Granger, Christopher B.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Efficacy of apixaban when compared with warfarin in relation to renal function in patients with atrial fibrillation: insights from the ARISTOTLE trial2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no 22, p. 2821-2830Article in journal (Refereed)
    Abstract [en]

    Aims

    Atrial fibrillation (AF) is common among patients with impaired renal function. Apixaban, a novel oral anticoagulant with partial renal excretion, was compared with warfarin and reduced the rate stroke, death and bleeding in the ARISTOTLE trial. We evaluated these outcomes in relation to renal function.

    Methods and results

    Baseline glomerular filtration rate (GFR) was estimated using the Cockcroft–Gault and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations as well as cystatin C measurements. According to baseline Cockcroft–Gault, there were 7518 patients (42%) with an estimated GFR (eGFR) of >80 mL/min, 7587 (42%) between >50 and 80 mL/min, and 3017 (15%) with an eGFR of ≤50 mL/min. The rate of cardiovascular events and bleeding was higher at impaired renal function (≤80 mL/min). Apixaban was more effective than warfarin in preventing stroke or systemic embolism and reducing mortality irrespective of renal function. These results were consistent, regardless of methods for GFR estimation. Apixaban was associated with less major bleeding events across all ranges of eGFRs. The relative risk reduction in major bleeding was greater in patients with an eGFR of ≤50 mL/min using Cockcroft–Gault {hazard ratio (HR) 0.50 [95% confidence interval (CI) 0.38–0.66], interaction P = 0.005} or CKD-EPI equations [HR 0.48 (95% CI 0.37–0.64), interaction P = 0.003].

    Conclusion

    In patients with AF, renal impairment was associated with increased risk of cardiovascular events and bleeding. When compared with warfarin, apixaban treatment reduced the rate of stroke, death, and major bleeding, regardless of renal function. Patients with impaired renal function seemed to have the greatest reduction in major bleeding with apixaban.

  • 430. Holmes, Michael V.
    et al.
    Dale, Caroline E.
    Zuccolo, Luisa
    Silverwood, Richard J.
    Guo, Yiran
    Ye, Zheng
    Prieto-Merino, David
    Dehghan, Abbas
    Trompet, Stella
    Wong, Andrew
    Cavadino, Alana
    Drogan, Dagmar
    Padmanabhan, Sandosh
    Li, Shanshan
    Yesupriya, Ajay
    Leusink, Maarten
    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.
    Hubacek, Jaroslav A.
    Pikhart, Hynek
    Swerdlow, Daniel I.
    Panayiotou, Andrie G.
    Borinskaya, Svetlana A.
    Finan, Chris
    Shah, Sonia
    Kuchenbaecker, Karoline B.
    Shah, Tina
    Engmann, Jorgen
    Folkersen, Lasse
    Eriksson, Per
    Ricceri, Fulvio
    Melander, Olle
    Sacerdote, Carlotta
    Gamble, Dale M.
    Rayaprolu, Sruti
    Ross, Owen A.
    McLachlan, Stela
    Vikhireva, Olga
    Sluijs, Ivonne
    Scott, Robert A.
    Adamkova, Vera
    Flicker, Leon
    Van Bockxmeer, Frank M.
    Power, Christine
    Marques-Vidal, Pedro
    Meade, Tom
    Marmot, Michael G.
    Ferro, Jose M.
    Paulos-Pinheiro, Sofia
    Humphries, Steve E.
    Talmud, Philippa J.
    Leach, Irene Mateo
    Verweij, Niek
    Linneberg, Allan
    Skaaby, Tea
    Doevendans, Pieter A.
    Cramer, Maarten J.
    Van der Harst, Pim
    Klungel, Olaf H.
    Dowling, Nicole F.
    Dominiczak, Anna F.
    Kumari, Meena
    Nicolaides, Andrew N.
    Weikert, Cornelia
    Boeing, Heiner
    Ebrahim, Shah
    Gaunt, Tom R.
    Price, Jackie F.
    Lannfelt, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Peasey, Anne
    Kubinova, Ruzena
    Pajak, Andrzej
    Malyutina, Sofia
    Voevoda, Mikhail I.
    Tamosiunas, Abdonas
    Maitland-van der Zee, Anke H.
    Norman, Paul E.
    Hankey, Graeme J.
    Bergmann, Manuela M.
    Hofman, Albert
    Franco, Oscar H.
    Cooper, Jackie
    Palmen, Jutta
    Spiering, Wilko
    de Jong, Pim A.
    Kuh, Diana
    Hardy, Rebecca
    Uitterlinden, Andre G.
    Ikram, M. Arfan
    Ford, Ian
    Hyppoenen, Elina
    Almeida, Osvaldo P.
    Wareham, Nicholas J.
    Khaw, Kay-Tee
    Hamsten, Anders
    Husemoen, Lise Lotte N.
    Tjonneland, Anne
    Tolstrup, Janne S.
    Rimm, Eric
    Beulens, Joline W. J.
    Verschuren, W. M. Monique
    Onland-Moret, N. Charlotte
    Hofker, Marten H.
    Wannamethee, S. Goya
    Whincup, Peter H.
    Morris, Richard
    Vicente, Astrid M.
    Watkins, Hugh
    Farrall, Martin
    Jukema, J. Wouter
    Meschia, James
    Cupples, L. Adrienne
    Sharp, Stephen J.
    Fornage, Myriam
    Kooperberg, Charles
    LaCroix, Andrea Z.
    Dai, James Y.
    Lanktree, Matthew B.
    Siscovick, David S.
    Jorgenson, Eric
    Spring, Bonnie
    Coresh, Josef
    Li, Yun R.
    Buxbaum, Sarah G.
    Schreiner, Pamela J.
    Ellison, R. Curtis
    Tsai, Michael Y.
    Patel, Sanjay R.
    Redline, Susan
    Johnson, Andrew D.
    Hoogeveen, Ron C.
    Rotter, Jerome I.
    Boerwinkle, Eric
    de Bakker, Paul I. W.
    Kivimaki, Mika
    Asselbergs, Folkert W.
    Sattar, Naveed
    Lawlor, Debbie A.
    Whittaker, John
    Smith, George Davey
    Mukamal, Kenneth
    Psaty, Bruce M.
    Wilson, James G.
    Lange, Leslie A.
    Hamidovic, Ajna
    Hingorani, Aroon D.
    Nordestgaard, Borge G.
    Bobak, Martin
    Leon, David A.
    Langenberg, Claudia
    Palmer, Tom M.
    Reiner, Alex P.
    Keating, Brendan J.
    Dudbridge, Frank
    Casas, Juan P.
    Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data2014In: BMJ-BRIT MED J, ISSN 1756-1833, Vol. 349, p. g4164-Article in journal (Refereed)
    Abstract [en]

    Objective To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Design Mendelian randomisation meta-analysis of 56 epidemiological studies. Participants 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Main outcome measures Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Results Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P= 0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). Conclusions Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health.

  • 431. Holmqvist, Fredrik
    et al.
    Kesek, Milos
    Englund, Anders
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Karlsson, Lars O.
    Kennebäck, Göran
    Poçi, Dritan
    Samo-Ayou, Romeo
    Sigurjónsdóttir, Runa
    Ringborn, Michael
    Herczku, Csaba
    Carlson, Jonas
    Fengsrud, Espen
    Tabrizi, Fariborz
    Höglund, Niklas
    Lönnerholm, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kongstad, Ole
    Jönsson, Anders
    Insulander, Per
    A decade of catheter ablation of cardiac arrhythmias in Sweden: ablation practices and outcomes2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 10, p. 820-830Article in journal (Refereed)
    Abstract [en]

    Aims: Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing 'real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported.

    Methods and Results: Consecutive patients (≥18 years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26 642 patients (57 ± 15 years, 62% men), undergoing a total of 34 428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11 916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7 years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P < 0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3 years). The rate of reported adverse events was low (n = 595, 1.7%). Death in the immediate period following ablation was rare (n = 116, 0.34%).

    Conclusion: Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.

  • 432. Holmqvist, Marie
    et al.
    Mantel, Angla
    Jernberg, Tomas
    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.
    Wallberg-Jonsson, Solveig
    Askling, Johan
    Angiographic Pattern Among Rheumatoid Arthritis Patients Who Are Hospitalized Due to Acute Coronary Syndrome2014In: Arthritis & Rheumatology, ISSN 2326-5191, Vol. 66, no S10, p. S606-S606, article id 1376Article in journal (Other academic)
  • 433. Horowitz, J. D.
    et al.
    De Caterina, R.
    Heresztyn, T.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, R.
    Hylek, E.
    Mohan, P.
    Hanna, M.
    Granger, C. B.
    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.
    ADMA and SDMA predict outcomes in patients with chronic atrial fibrillation: an ARISTOTLE substudy2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 1040-1041Article in journal (Other academic)
  • 434.
    Horowitz, John D.
    et al.
    Univ Adelaide, Queen Elizabeth Hosp, Basil Hetzel Inst, Cardiol Unit, Adelaide, SA, Australia.
    De Caterina, Raffaele
    G Monasterio Fdn, Pisa, Italy;Univ G dAnnunzio, Chieti, Italy.
    Heresztyn, Tamila
    Univ Adelaide, Queen Elizabeth Hosp, Basil Hetzel Inst, Cardiol Unit, Adelaide, SA, Australia.
    Alexander, John H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Andersson, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lopes, Renato D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Steg, Philippe Gabriel
    INSERM, Unite 698, Paris, France;Univ Paris Diderot, Sorbonne Paris Cite, Paris, France;Hop Bichat Claude Bernard, Dept Hosp Univ FIRE, Paris, France;Royal Brompton Hosp, NHLI Imperial Coll, ICMS, London, England;AP HP, Paris, France.
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA.
    Mohan, Puneet
    Bristol Myers Squibb, Princeton, NJ USA.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA.
    Jansky, Petr
    Univ Hosp Motol, Cardiovasc Ctr, Prague, Czech Republic.
    Granger, Christopher B.
    Duke Univ, Med Ctr, 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.
    Asymmetric and Symmetric Dimethylarginine Predict Outcomes in Patients With Atrial Fibrillation: An ARISTOTLE Substudy2018In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 72, no 7, p. 721-733Article in journal (Refereed)
    Abstract [en]

    BACKGROUND There is little mechanistic information on factors predisposing atrial fibrillation (AF) patients to thromboembolism or bleeding, but generation of nitric oxide (NO) might theoretically contribute to both. OBJECTIVES The authors tested the hypothesis that plasma levels of the methylated arginine derivatives asymmetric and symmetric dimethylarginine (ADMA/SDMA), which inhibit NO generation, might be associated with outcomes in AF. METHODS Plasma samples were obtained from 5,004 patients with AF at randomization to warfarin or apixaban in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. ADMA and SDMA concentrations were measured by high-performance liquid chromatography. Relationships to clinical characteristics were evaluated by multivariable analyses. Associations with major outcomes, during a median of 1.9 years follow-up, were evaluated by adjusted Cox proportional hazards models. RESULTS Both ADMA and SDMA plasma concentrations at study entry increased significantly with patients' age, female sex, renal impairment, permanent AF, or congestive heart failure. ADMA and SDMA increased (p < 0.001) with both increased CHA2DS2-VASc and HAS-BLED scores, but decreased in the presence of diabetes. On multivariable analysis adjusting for established risk factors and treatment, tertile groups of ADMA concentrations were significantly associated with stroke/systemic embolism (p = 0.034), and death (p < 0.0001), whereas tertile groups of SDMA were associated with major bleeding and death (p < 0.001 for both). Incorporating ADMA and SDMA into CHA2DS2-VASc or HAS-BLED predictive models improved C-indices for those outcomes. Neither ADMA nor SDMA predicted differential responses to warfarin or apixaban. CONCLUSIONS In anticoagulated patients with AF, elevated ADMA levels are weakly associated with thromboembolic events, elevated SDMA levels with bleeding events and both are strongly associated with increased mortality. These findings suggest that disturbances of NO function modulate both thrombotic and hemorrhagic risk in anticoagulated patients with AF. (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation [ARISTOTLE]; NCT00412984)

  • 435. Huber, Kurt
    et al.
    Bates, Eric R.
    Valgimigli, Marco
    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.
    Kristensen, Steen Dalby
    Anderson, Jeffrey L.
    Lopez Sendon, Jose Luis
    Tubaro, Marco
    Granger, Christopher B.
    Bode, Christoph
    Ohman, Erik Magnus
    Steg, Philippe Gabriel
    Antiplatelet and anticoagulation agents in acute coronary syndromes: What is the current status and what does the future hold?2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 5, p. 611-621Article in journal (Refereed)
    Abstract [en]

    Mortality and morbidity in acute coronary syndromes (ACSs), caused principally by plaque erosion or rupture leading to thrombus formation and myocardial ischemia, have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization. Aspirin is the foundation antiplatelet agent. New P2Y(12) receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy, and cangrelor or vorapaxar, a thrombin receptor inhibitor, may be of value in specific settings. Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux. Moreover, some patients (such as those who have chronic atrial fibrillation) require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist. New oral anticoagulants have been shown to be at least as effective as vitamin K antagonists in atrial fibrillation and led to fewer bleeding complications. Finally, the combination of aspirin, clopidogrel, and low-dose rivaroxaban has recently been approved by the European Medicines Agency (but not the Food and Drug Administration) for secondary prevention after ACS. Several strategies have been developed to balance the potential benefit of antithrombotic therapy against the risk of bleeding complications, for example, radial access in coronary angiography or restricted use of combination therapy, and others are under investigation, such as discontinuation of aspirin. This overview summarizes the current status of antithrombotic therapy in ACS and describes strategies currently explored to optimize its benefit/risk ratio.

  • 436.
    Humphries, K. H.
    et al.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada.;BC Ctr Improved Cardiovasc Hlth, Vancouver, BC, Canada..
    Izadnegandar, M.
    BC Ctr Improved Cardiovasc Hlth, Vancouver, BC, Canada..
    Sedlak, T.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Saw, J.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Johnston, Nina
    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.
    Schenck-Gustafsson, K.
    Karolinska Univ Hosp, Dept Med, Cardiac Unit, Solna, Sweden.;Karolinska Univ Hosp, Ctr Gender Med, Solna, Sweden.;Karolinska Inst, Solna, Sweden..
    Shah, R. U.
    Univ Utah, Sch Med, Div Cardiovasc Med, Salt Lake City, UT USA..
    Regitz-Zagrosek, V.
    Charite Univ Med Berlin, Inst Gender Med GIM, Partner Site, Berlin, Germany.;Charite Univ Med Berlin, Ctr Cardiovasc Res CCR, Partner Site, Berlin, Germany.;DZHK, Partner Site, Berlin, Germany..
    Grewal, J.
    Univ British Columbia, Div Cardiol, Vancouver, BC, Canada..
    Vaccarino, V.
    Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.;Emory Univ, Sch Med, Dept Med, Atlanta, GA USA..
    Wei, J.
    Cedars Sinai Heart Inst, Barbra Streisand Womens Heart Ctr, Los Angeles, CA USA..
    Merz, C. N. Bairey
    Cedars Sinai Heart Inst, Barbra Streisand Womens Heart Ctr, Los Angeles, CA USA..
    Sex differences in cardiovascular disease: Impact on care and outcomes2017In: Frontiers in neuroendocrinology (Print), ISSN 0091-3022, E-ISSN 1095-6808, Vol. 46, p. 46-70Article, review/survey (Refereed)
  • 437. Husted, Steen
    et al.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Becker, Richard C.
    Horrow, Jay
    Katus, Hugo
    Storey, Robert F.
    Cannon, Christopher P.
    Heras, Magda
    Lopes, Renato D.
    Morais, Joao
    Mahaffey, Kenneth W.
    Bach, Richard G.
    Wojdyla, Daniel
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ticagrelor Versus Clopidogrel in Elderly Patients With Acute Coronary Syndromes A Substudy From the Prospective Randomized PLATelet Inhibition and Patient Outcomes (PLATO) Trial2012In: Circulation. Cardiovascular Quality and Outcomes, ISSN 1941-7713, E-ISSN 1941-7705, Vol. 5, no 5, p. 680-688Article in journal (Refereed)
    Abstract [en]

    Background-Elderly patients with acute coronary syndrome are at high risk of recurrent ischemic events and death, and for both antithrombotic therapy and catheter-based complications. This prespecified analysis investigates the effect and treatment-related complications of ticagrelor versus clopidogrel in elderly patients (>= 75 years of age) with acute coronary syndrome compared with those < 75 years of age. Methods and Results-The association between age and the primary composite outcome, as well as major bleeding were evaluated in the PLATelet inhibition and patient Outcomes (PLATO) trial using Cox proportional hazards. Similar models were used to evaluate the interaction of age with treatment effects. Hazard ratios were adjusted for baseline characteristics. The clinical benefit of ticagrelor over clopidogrel was not significantly different between patients aged >= 75 years of age (n=2878) and those < 75 years of age (n=15744) with respect to the composite of cardiovascular death, myocardial infarction, or stroke (interaction P=0.56), myocardial infarction (P=0.33), cardiovascular death (P=0.47), definite stent thrombosis (P=0.81), or all-cause mortality (P=0.76). No increase in PLATO-defined overall major bleeding with ticagrelor versus clopidogrel was observed in patients aged >= 75 years (hazard ratio, 1.02; 95% confidence interval, 0.82-1.27) or patients aged < 75 years (hazard ratio, 1.04; 95% confidence interval, 0.94-1.15). Dyspnea and ventricular pauses were more common during ticagrelor than clopidogrel treatment, with no evidence of an age-by-treatment interaction. Conclusions-The significant clinical benefit and overall safety of ticagrelor compared with clopidogrel in acute coronary syndrome patients in the PLATO cohort were not found to depend on age. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872. (Circ Cardiovasc Qual Outcomes. 2012;5:680-688.)

  • 438. Husted, Steen
    et al.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bach, Richard G.
    Becker, Richard C.
    Budaj, Andrzej
    Heras, Magda
    Himmelmann, Anders
    Horrow, Jay
    Katus, Hugo A.
    Lassila, Riita
    Morais, Joao
    Nicolau, Jose C.
    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.
    Steg, Ph. Gabriel
    Storey, Robert F.
    Wojdyla, Daniel
    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.
    The efficacy of ticagrelor is maintained in women with acute coronary syndromes participating in the prospective, randomized, PLATelet inhibition and patient Outcomes (PLATO) trial2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no 23, p. 1541-1550Article in journal (Refereed)
    Abstract [en]

    Aims The aim of this study was to assess the relationship between sex and clinical outcomes and treatment-related complications in patients with ST-elevation or non-ST-elevation acute coronary syndromes (ACS) randomized to treatment with ticagrelor or clopidogrel in the PLATelet inhibition and patient Outcomes (PLATO) trial. Methods The associations between sex subgroup and the primary composite outcomes, secondary outcomes, and major bleeding endpoints as well as interaction of sex subgroup with treatment effects were analysed using Cox proportional-hazards models. Results Sex was not significantly associated with the probability of the primary composite endpoint [adjusted hazard ratio (HR): 1.02 (0.91-1.16)], or other adverse cardiovascular endpoints. Ticagrelor was similarly more effective than clopidogrel in reducing rates of the primary endpoint in women 11.2 vs. 13.2% [adjusted HR: 0.88 (0.74-1.06)] and men 9.4 vs. 11.1% [adjusted HR: 0.86 (0.76-0.97)] (interaction P-value 0.78), all-cause death in women 5.8 vs. 6.8% [adjusted HR: 0.90 (0.69-1.16)] and men 4.0 vs. 5.7% [adjusted HR: 0.80 (0.67-0.96)] (interaction P-value 0.49), and definite stent thrombosis in women 1.2 vs. 1.4% [adjusted HR: 0.71 (0.36-1.38)] and men 1.4 vs. 2.1% [adjusted HR: 0.63 (0.45-0.89)] (interaction P-value 0.78). The treatments did not differ for PLATO-defined overall major bleeding complications in women [adjusted HR: 1.01 (0.83-1.23)] or men [adjusted HR: 1.10 (0.98-1.24)]. Sex had no significant association with these outcomes (interactions P = 0.43-0.88). Conclusion Female sex is not an independent risk factor for adverse clinical outcomes in moderate-to-high risk ACS patients. Ticagrelor has a similar efficacy and safety profile in men and women.

  • 439.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sandin, Fredrik
    Holmberg, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.2015In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 51, no 4, p. 558-568Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We studied the association between taking part in a long distance ski race and cancer incidence to address the hypothesis that a lifestyle involving a high degree of physical activity (PA) lowers cancer incidence with a pattern that is different by cancer site.

    METHODS: Cancer incidence was estimated in a large cohort of skiers (n=185,412) participating in the Vasaloppet long distance ski race in Sweden 1989-2010 and non-participants in the ski race, randomly selected from the Swedish general population (n=184,617). Data include race finishing times as a measurement of physical fitness. Hazard ratios (HRs) and net probability of cancer over twenty years of follow-up were estimated for all invasive cancer, and separately for prostate, breast, colo-rectal and lung cancer, and groups of cancers with presumed relation to lifestyle.

    FINDINGS: Participating in Vasaloppet was associated with a relative risk reduction for all invasive cancer of 6% (95% confidence interval 2-9%) and a relative risk reduction of 32% (95% confidence interval 28-37%) of cancer sites where there is epidemiological evidence that smoking, bodyweight, regular PA and consumption of fruit and vegetables are aetiological factors. For skin cancer the risk was increased, as for prostate cancer. Skiers with shorter finishing times had lower incidence of cancer.

    INTERPRETATION: This study indicates that it is unrealistic to reduce overall population cancer incidence drastically with life style. However, cancers that are epidemiologically associated with life style factors were significantly reduced by what presumably is a blend of non-smoking, normal body weight, sound dietary habits and PA. Our data thus provide additional support for present days' recommendations about life style prevention. Higher health awareness is associated with attendance to screening, which may explain our results for prostate cancer.

    FUNDING: University fund, independent funds from an insurance company and a private foundation.

  • 440.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Mora Hosp, Dept Internal Med, S-79285 Mora, Sweden.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Dalarna Univ, Sch Hlth & Social Studies, S-79188 Falun, Sweden;Karolinska Inst, Dept Neurobiol Care Sci & Soc, Div Family Med & Primary Care, S-17177 Stockholm, Sweden.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Wester, Per
    Umea Univ, Dept Publ Hlth & Clin Sci, S-90185 Umea, Sweden;Danderyd Hosp, Karolinska Inst, Dept Clin Sci, S-18288 Stockholm, Sweden.
    Hellberg, Dan
    Ctr Clin Res, S-79182 Falun, Sweden.
    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.
    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.
    Survival and incidence of cardiovascular diseases in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population2018In: European Heart Journal - Quality of Care and Clinical Outcomes, ISSN 2058-5225, E-ISSN 2058-1742, Vol. 4, no 2, p. 91-97Article in journal (Refereed)
    Abstract [en]

    We studied the relationship between taking part in a long-distance ski race and incidence of cardiovascular diseases (CVDs) to address the hypothesis that lifestyle lowers the incidence. A cohort of 399 630 subjects in Sweden, half were skiers in the world's largest ski race, and half were non-skiers. Non-skiers were frequency matched for sex, age, and year of race. Individuals with severe diseases were excluded. The endpoints were death, myocardial infarction, or stroke. The subjects were followed up for a maximum of 21.8 years and median of 9.8 years. We identified 9399 death, myocardial infarction, or stroke events among non-skiers and 4784 among the Vasaloppet skiers. The adjusted hazard ratios (HRs) comparing skiers and non-skiers were 0.52 [95% confidence interval (CI) 0.49-0.54] for all-cause mortality, 0.56 (95% CI 0.52-0.60) for myocardial infarction and 0.63 (95% CI 0.58-0.67) for stroke and for all three outcomes 0.56 (95% CI 0.54-0.58). The results were consistent across subgroups: age, sex, family status, education, and race year. For skiers, a doubling of race time was associated with a higher age-adjusted risk of 19%, and male skiers had a doubled risk than female skiers, with a HR 2.06 (95% CI 1.89-2.41). The outcome analyses revealed no differences in risk of atrial fibrillation between skiers and non-skiers. This large cohort study provides additional support for the hypothesis that individuals with high level of physical activity representing a healthy lifestyle, as evident by their participation in a long-distance ski race, have a lower risk of CVD or death.

  • 441.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Arnlov, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Cardiac Arrest in a Long-Distance Ski Race (Vasaloppet) in Sweden2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 15, p. 1431-1432Article in journal (Refereed)
  • 442.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Medicinkliniken Mora Landstinget Dalarna.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna, Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum för klinisk forskning, Dalarna, Falun.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Risk of recurrent ischaemic events after myocardial infarction in long-distance ski race participants2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 3, p. 282-290Article in journal (Refereed)
    Abstract [en]

    AIMS: To study whether a high level of physical activity prior to myocardial infarction (MI) also protects against recurrent MI (re-MI) or death.

    METHODS AND RESULTS: A longitudinal study of a primary cohort consisting of 204,038 skiers with a proved substantially high level of physical activity in the world's largest long-distance ski race, Vasaloppet, and 499,543 non-skiers selected from the Swedish population. Individuals with severe diseases at baseline were excluded. In the nationwide clinical register, Swedeheart, we identified 7092 individuals with a first MI incident between 1989 and 2010. Of these, 1039 (0.5%) were skiers and 6053 (1.2%) were non-skiers. One hundred and sixty-three (15.7%) skiers and 1352 (22.3%) non-skiers suffered a re-MI or died during follow-up (median 4.44 years), corresponding to an incidence rate of 38.9 (95% confidence interval (CI) 33.2-45.4)/1000 person-years and 55.6 (95% CI 52.7-58.7)/1000 person-years, respectively. Severity of MI in both groups was the same. For skiers compared to non-skiers the unadjusted hazard ratio (HR) for re-MI was 0.66 (95% CI 0.52-0.82). For death or re-MI, HR was 0.70 (95% CI 0.59-0.82) with consistent results in subgroups based on race year, age, gender, education level, marital status. After adjustment for also smoking, diabetes, hypertension and cardiovascular medication, HR was 0.80 (95% CI 0.67-0.97).

    CONCLUSIONS: This large cohort study supports the hypothesis that patients with MI and with prior physical activity and healthy lifestyle, as evidenced by their participation in a long-distance ski race, have a lower risk of subsequent re-MI or death.

  • 443.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    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.
    Reply to" Airway Remodeling and Cardiac Arrest in Long-Distance Ski Races" Journal of the American College of Cardiology, Volume 61, Issue 3, 22 January 2013, Pages 388-3892013In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, no 3, p. 389-Article in journal (Other academic)
  • 444.
    Hållmarker, Ulf
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Högskolan Dalarna Falun.
    Hellberg, Dan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology. Centrum klinisk forskning Dalarna Falun.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wester, Per
    Medicin och folhälsa Umeå Universitet.
    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.
    Risk of Recurrent Stroke and Death After First Stroke in Long‐Distance Ski Race Participants2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002469Article in journal (Refereed)
    Abstract [en]

    Background Physical activity is of benefit for primary prevention of cardiovascular diseases, but it appears to increase the risk for atrial fibrillation. We aimed to study a cohort of patients following a first stroke in individuals with previous high physical activity, compare them to the general population with respect to recurrent stroke and death, and relate these to atrial fibrillation.

    Methods and Results From the participants of the Vasaloppet, the world's largest ski‐race, and matched individuals from the general population (n=708 604), we identified 5964 patients hospitalized with a first‐time stroke between 1994 and 2010. Individuals with severe diseases were excluded. One half percent of skiers and 1% of nonskiers were hospitalized due to stroke. The incidence rate was 8.3 per 100 person‐years among skiers and 11.1 among nonskiers. The hazard ratio (HR) for recurrent stroke or death between the 2 groups was 0.76 (95% CI 0.67 to 0.86). The result was consistent in subgroups. The HR for death was 0.66 (95% CI 0.56 to 0.78) and for recurrent stroke 0.82 (95% CI 0.70 to 0.96). After adjustment for smoking and socioeconomic factors, the HR for death was consistent at 0.70 (95% CI 0.56 to 0.87) while the HR for recurrent stroke was not statistically significant. Outcomes for skiers with atrial fibrillation tended to show a lower risk than for nonskiers.

    Conclusions This large cohort study supports the hypothesis that patients with a stroke and with prior regular physical activity have a lower risk of death, while their risk for recurrent stroke is similar to that of nonskiers. The skiers had a higher incidence of atrial fibrillation, but still no increased risk of recurring stroke.

  • 445. Ibanez, Borja
    et al.
    Halvorsen, Sigrun
    Roffi, Marco
    Bueno, Héctor
    Thiele, Holger
    Vranckx, Pascal
    Neumann, Franz-Josef
    Windecker, Stephan
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Integrating the results of the CULPRIT-SHOCK trial in the 2017 ESC ST-elevation myocardial infarction guidelines: viewpoint of the task force2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 48, p. 4239-4242Article in journal (Other academic)
  • 446.
    Ibanez, Borja
    et al.
    Ctr Nacl Invest Cardiovasc Carlos III CNIC, Clin Res, Melchor Fernandez Almagro 3, Madrid 28029, Spain..
    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.
    Agewall, Stefan
    Antunes, Manuel J.
    Bucciarelli-Ducci, Chiara
    Bueno, Hector
    Caforio, Alida L. P.
    Crea, Filippo
    Goudevenos, John A.
    Halvorsen, Sigrun
    Hindricks, Gerhard
    Kastrati, Adnan
    Lenzen, Mattie J.
    Prescott, Eva
    Roffi, Marco
    Valgimigli, Marco
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Vranckx, Pascal
    Widimsky, Petr
    2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation2018In: Kardiologia polska, ISSN 0022-9032, E-ISSN 1897-4279, Vol. 76, no 2, p. 229-313Article in journal (Refereed)
  • 447. Ibanez, Borja
    et al.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Agewall, Stefan
    Antunes, Manuel J.
    Bucciarelli-Ducci, Chiara
    Bueno, Hector
    Caforio, Alida L. P.
    Crea, Filippo
    Goudevenos, John A.
    Halvorsen, Sigrun
    Hindricks, Gerhard
    Kastrati, Adnan
    Lenzen, Mattie J.
    Prescott, Eva
    Roffi, Marco
    Valgimigli, Marco
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Vranckx, Pascal
    Widimsky, Petr
    2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC)2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 2, p. 119-177Article in journal (Refereed)
  • 448.
    Inohara, Taku
    et al.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Pieper, Karen
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Wojdyla, Daniel M.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Patel, Manesh R.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Jones, William Schuyler
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Tricoci, Pierluigi
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA;Stanford Ctr Clin Res, Stanford, CA 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. Uppsala Univ, Cardiol, Dept Med Sci, Uppsala, Sweden;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
    Alexander, John H.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Lopes, Renato D.
    Duke Univ, Med Ctr, 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.
    Oilman, Erik Magnus
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Roe, Matthew T.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Vemulapalli, Sreekanth
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
    Incidence, timing, and type of first and recurrent ischemic events in patients with and without peripheral artery disease after an acute coronary syndrome2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 201, p. 25-32Article in journal (Refereed)
    Abstract [en]

    Background: Patients with peripheral artery disease (PAD) are known to have an increased risk of ischemic cardiovascular events. However, the influence of concomitant PAD on first and subsequent recurrent ischemic events after an acute coronary syndrome (ACS) remains poorly characterized. Methods: We analyzed the combined data set from 4 randomized trials (PLATO, APPRAISE-2, TRA-CER, and TRILOGY ACS) in ACS for a follow-up length of 1 year. Using multivariable regression, we examined the association between PAD and major adverse cardiovascular events, a composite of cardiovascular death, myocardial infarction, and stroke. Among patients with a nonfatal first event, we evaluated the incidence and type of a second recurrent event. Results: A total of 4,098 of 48,094 (8.5%) post-ACS patients had a history of PAD. The unadjusted frequency of major adverse cardiovascular events was 2-fold higher in patients with PAD (14.3% vs 7.5%) over a median (25th-75th) follow-up of 353 (223-365) days with an adjusted hazard ratio of 1.63 (95% CI: 1.48-1.78; P <.001). The frequency of recurrent ischemic eventsamong those patients with a first, nonfatal event was higher among those with PAD (40.0% vs 27.7%). The relative frequency of each event type (cardiovascular death, noncardiovascular death, myocardial infarction, or stroke) within first and subsequent ischemic events was similar regardless of PAD status at baseline. Conclusions: Patients with PAD have a significantly higher risk of first and recurrent ischemic events in the post-ACS setting. These findings highlight the opportunity for improved treatments in patients with PAD who experience an ACS.

  • 449.
    Jaffe, Allan S.
    et al.
    Mayo Clin, Rochester, MN 55902 USA..
    Collinson, Paul O.
    St Georges Hosp & Med Sch, London, England..
    Hamm, Christian W.
    Kerckhoff Heart Ctr, Bad Nauheim, Germany.;Univ Giessen, Giessen, Germany..
    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.
    Mills, Nicholas L.
    Univ Edinburgh, Edinburgh, Midlothian, Scotland..
    Thygesen, Kristian
    Aarhus Univ Hosp, Aarhus, Denmark..
    Sometimes earlier may not be better2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 44, p. 3316-3318Article in journal (Refereed)
  • 450. Jaffe, AS
    et al.
    Moeckel, M
    Giannitsis, E
    Huber, K
    Mair, J
    Mueller, C
    Plebani, M
    Thygesen, K
    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.
    In search for the Holy Grail: Suggestions for studies to define delta changes to diagnose or exclude acute myocardial infarction: a position paper from the study group on biomarkers of the Acute Cardiovascular Care Association2014In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, Vol. 3, no 4, p. 313-316Article in journal (Refereed)
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