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  • 1.
    Ahmad, Tariq
    et al.
    Yale Univ, CT USA; Yale Univ, CT USA.
    Lund, Lars H.
    Karolinska Inst, Sweden; Karolinska Univ Hosp, Sweden.
    Rao, Pooja
    Qure Ai, India.
    Ghosh, Rohit
    Qure Ai, India.
    Warier, Prashant
    Qure Ai, India.
    Vaccaro, Benjamin
    Yale Univ, CT USA; Yale Univ, CT USA.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    OConnor, Christopher M.
    Duke Univ, NC USA.
    Felker, G. Michael
    Duke Univ, NC USA.
    Desai, Nihar R.
    Yale Univ, CT USA; Yale Univ, CT USA.
    Machine Learning Methods Improve Prognostication, Identify Clinically Distinct Phenotypes, and Detect Heterogeneity in Response to Therapy in a Large Cohort of Heart Failure Patients2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 8, article id e008081Article in journal (Refereed)
    Abstract [en]

    Background-Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials. We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response. Methods and Results-The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information. We applied random forest modeling to identify predictors of 1-year survival. Cluster analysis was performed and validated using serial bootstrapping. Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity-matched clusters. Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012. Random forest modeling demonstrated excellent calibration and discrimination for survival (C-statistic=0.83) whereas left ventricular ejection fraction did not (C-statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1-year survival: 80%, 81%, 83%, and 84%). Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1-year survival. There were significant interactions between propensity-matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin-converting enzyme inhibitors, )i-blockers, and nitrates, Pamp;lt;0.001, all). Conclusions-Machine learning algorithms accurately predicted outcomes in a large data set of HF patients. Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics. Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.

  • 2.
    Alabas, Oras A.
    et al.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England..
    Gale, Chris P.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England.;York Teaching Hosp NHS Fdn Trust, Dept Cardiol, York, N Yorkshire, England..
    Hall, Marlous
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Bioinformat Ctr, MRC, Leeds, W Yorkshire, England..
    Rutherford, Mark J.
    Univ Leicester, Dept Hlth Sci, Leicester, Leics, England..
    Szummer, Karolina
    Dept Med, Huddinge, Sweden..
    Lawesson, Sofia Sederholm
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Danderyds Hosp, Dept Clin Sci, Stockholm, Sweden..
    Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007123Article in journal (Refereed)
    Abstract [en]

    Background - This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction.

    Methods and Results - A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]).

    Conclusions - Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

  • 3.
    Alabas, Oras A.
    et al.
    University of Leeds, England.
    Gale, Chris P.
    University of Leeds, England; York Teaching Hospital NHS Fdn Trust, England.
    Hall, Marlous
    University of Leeds, England.
    Rutherford, Mark J.
    University of Leicester, England.
    Szummer, Karolina
    Department Med, Sweden.
    Sederholm Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Alfredsson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Bertil
    Uppsala University, Sweden; Uppsala University, Sweden.
    Jernberg, Tomas
    Karolinska Institute, Sweden.
    Sex Differences in Treatments, Relative Survival, and Excess Mortality Following Acute Myocardial Infarction: National Cohort Study Using the SWEDEHEART Registry2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e007123Article in journal (Refereed)
    Abstract [en]

    Background-This study assessed sex differences in treatments, all-cause mortality, relative survival, and excess mortality following acute myocardial infarction. Methods and Results-A population-based cohort of all hospitals providing acute myocardial infarction care in Sweden (SWEDEHEART [Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies]) from 2003 to 2013 was included in the analysis. Excess mortality rate ratios (EMRRs), adjusted for clinical characteristics and guideline-indicated treatments after matching by age, sex, and year to background mortality data, were estimated. Although there were no sex differences in all-cause mortality adjusted for age, year of hospitalization, and comorbidities for ST-segment-elevation myocardial infarction (STEMI) and non-STEMI at 1 year (mortality rate ratio: 1.01 [95% confidence interval (CI), 0.96-1.05] and 0.97 [95% CI, 0.95-.99], respectively) and 5 years (mortality rate ratio: 1.03 [95% CI, 0.99-1.07] and 0.97 [95% CI, 0.95-.99], respectively), excess mortality was higher among women compared with men for STEMI and non-STEMI at 1 year (EMRR: 1.89 [95% CI, 1.66-2.16] and 1.20 [95% CI, 1.16-1.24], respectively) and 5 years (EMRR: 1.60 [95% CI, 1.48-1.72] and 1.26 [95% CI, 1.21-1.32], respectively). After further adjustment for the use of guideline-indicated treatments, excess mortality among women with non-STEMI was not significant at 1 year (EMRR: 1.01 [95% CI, 0.97-1.04]) and slightly higher at 5 years (EMRR: 1.07 [95% CI, 1.02-1.12]). For STEMI, adjustment for treatments attenuated the excess mortality for women at 1 year (EMRR: 1.43 [95% CI, 1.26-1.62]) and 5 years (EMRR: 1.31 [95% CI, 1.19-1.43]). Conclusions-Women with acute myocardial infarction did not have statistically different all-cause mortality, but had higher excess mortality compared with men that was attenuated after adjustment for the use of guideline-indicated treatments. This suggests that improved adherence to guideline recommendations for the treatment of acute myocardial infarction may reduce premature cardiovascular death among women.

  • 4.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Roe, Matthew T
    Duke Clinical Research Institute, Durham, NC.
    Balancing the risks and benefits of long-term antiplatelet therapies for cardiovascular disease: clinical, research, and regulatory implications.2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 3, article id e001897Article in journal (Other academic)
  • 5. Andell, Pontus
    et al.
    Erlinge, David
    Smith, J. Gustav
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    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.
    Koul, Sasha
    beta-Blocker Use and Mortality in COPD Patients After Myocardial Infarction: A Swedish Nationwide Observational Study2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 4, article id e001611Article in journal (Refereed)
    Abstract [en]

    Background-Patients with myocardial infarction (MI) and concomitant chronic obstructive pulmonary disease (COPD) constitute a high-risk group with increased mortality. beta-Blocker therapy has been shown to reduce mortality, prevent arrhythmias, and delay heart failure development after an MI in broad populations. However, the effect of beta-blockers in COPD patients is less well established and they may also be less treated due to fear of adverse reactions. We investigated beta-blocker prescription at discharge in patients with COPD after MI. ethods and Results-Patients hospitalized for MI between 2005 and 2010 were identified from the nationwide Swedish SWEDEHEART registry. Patients with COPD who were alive and discharged after an MI were selected as the study population. In this cohort, patients who were discharged with beta-blockers were compared to patients not discharged with beta-blockers. The primary end point was all-cause mortality. A total of 4858 patients were included, of which 4086 (84.1%) were discharged with a beta-blocker while 772 (15.9%) were not. After adjusting for potential confounders including baseline characteristics, comorbidities, and in-hospital characteristics, patients discharged with a beta-blocker had lower all-cause mortality (hazard ratio 0.87, 95% CI 0.78 to 0.98) during the total follow-up time (maximum 7.2 years). In the subgroup of patients with a history of heart failure, the corresponding hazard ratio was 0.77 (95% CI 0.63 to 0.95). Conclusions-Patients with COPD discharged with beta-blockers after an MI had a lower all-cause mortality compared to patients not prescribed beta-blockers. The results indicate that MI patients with COPD may benefit from beta-blockers.

  • 6.
    Andell, Pontus
    et al.
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, 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.
    Cannon, Christopher P.
    Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA.;Harvard Clin Res Inst, Boston, MA USA..
    Cyr, Derek D.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Molndal, Sweden..
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Keltai, Matyas
    Semmelweis Univ, Hungarian Inst Cardiol, H-1085 Budapest, Hungary..
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Santoso, Anwar
    Univ Indonesia, Natl Cardiovasc Ctr, Harapan Kita Hosp, Dept Cardiol,Vasc Med,Fac Med, Jakarta, Indonesia. INSERM, U1148, Paris, France. Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France. Univ Paris Diderot, Sorbonne Paris Cite, Paris, France. Royal Brompton Hosp, ICMS, NHLI Imperial Coll, London SW3 6LY, England..
    Steg, Gabriel
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2TN, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, S-22185 Lund, Sweden..
    Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and Chronic Obstructive Pulmonary Disease: An Analysis From the Platelet Inhibition and Patient Outcomes (PLATO) Trial2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 10, article id e002490Article in journal (Refereed)
    Abstract [en]

    Background-Patients with chronic obstructive pulmonary disease (COPD) experiencing acute coronary syndromes (ACS) are at high risk for clinical events. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor versus clopidogrel reduced the primary endpoint of death from vascular causes, myocardial infarction, or stroke after ACS, but increased the incidence of dyspnea, which may lead clinicians to withhold ticagrelor from COPD patients. Methods and Results-In 18 624 patients with ACS randomized to treatment with ticagrelor or clopidogrel, history of COPD was recorded in 1085 (5.8%). At 1 year, the primary endpoint occurred in 17.7% of patients with COPD versus 10.4% in those without COPD (P<0.001). The 1-year event rate for the primary endpoint in COPD patients treated with ticagrelor versus clopidogrel was 14.8% versus 20.6% (hazard ratio [HR]=0.72; 95% confidence interval [CI]: 0.54 to 0.97), for death from any cause 8.4% versus 12.4% (HR=0.70; 95% CI: 0.47 to 1.04), and for PLATO-defined major bleeding rates at 1 year 14.6% versus 16.6% (HR=0.85; 95% CI: 0.61 to 1.17). Dyspnea occurred more frequently with ticagrelor (26.1% vs. 16.3%; HR=1.71; 95% CI: 1.28 to 2.30). There was no differential increase in the relative risk of dyspnea compared to non-COPD patients (HR=1.85). No COPD status-by-treatment interactions were found, showing consistency with the main trial results. Conclusions-In this post-hoc analysis, COPD patients experienced high rates of ischemic events. Ticagrelor versus clopidogrel reduced and substantially decreased the absolute risk of ischemic events (5.8%) in COPD patients, without increasing overall major bleeding events. The benefit-risk profile supports the use of ticagrelor in patients with ACS and concomitant COPD.

  • 7.
    Angeras, Oskar
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Haraldsson, Inger
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Redfors, Bjorn
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Frobert, Ole
    Orebro Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Petursson, Petur
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Albertsson, Per
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Ioanes, Dan
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Odenstedt, Jacob
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Olsson, Hans
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden..
    Witt, Nils
    South Hosp Stockholm, Dept Cardiol, Stockholm, Sweden..
    Ruck, Andreas
    Karolinska Univ Hosp, Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Millgard, Jonas
    Sunderby Hosp, Dept Cardiol, Sunderbyn, Sweden..
    Nilsson, Johan
    Umea Univ Hosp, Dept Cardiol, Heart Ctr, Umea, Sweden..
    Persson, Jonas
    Danderyd Hosp, Dept Cardiol, Stockholm, Sweden..
    Soderbom, Mans
    Univ Gothenburg, Dept Econ, Gothenburg, Sweden..
    Wedel, Hans
    Univ Gothenburg, Hlth Metr, Sahlgrenska Acad, Gothenburg, Sweden..
    Erlinge, David
    Lund Univ, Dept Cardiol, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ramunddal, Truls
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Omerovic, Elmir
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Impact of Thrombus Aspiration on Mortality, Stent Thrombosis, and Stroke in Patients With ST-Segment-Elevation Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007680Article in journal (Refereed)
    Abstract [en]

    Background-Thrombus aspiration is still being used in a substantial number of patients despite 2 large randomized clinical trials showing no favorable effect of routine thrombus aspiration during primary percutaneous coronary intervention in patients with STsegment- elevation myocardial infarction. The aim of this observational study was to evaluate the impact of thrombus aspiration on mortality, stent thrombosis, and stroke using all available data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). Methods and Results-We identified 42 829 consecutive patients registered in SCAAR between January 2005 and September 2014 who underwent percutaneous coronary intervention for ST-segment-elevation myocardial infarction. Thrombus aspiration was used in 25% of the procedures. We used instrumental variable analysis with administrative healthcare region as the treatmentpreference instrumental variable to evaluate the effect of thrombus aspiration on mortality, stent thrombosis, and stroke. Thrombus aspiration was not associated with mortality at 30 days (risk reduction: -1.2; 95% confidence interval [CI], -5.4 to 3.0; P=0.57) and 1 year (risk reduction: -2.4; 95% CI, -7.6 to 3.0; P=0.37). Thrombus aspiration was associated with a lower risk of stent thrombosis both at 30 days (risk reduction: -2.7; 95% CI, -4.1 to -1.4; P<0.001) and 1 year (risk reduction: -3.5; 95% CI, -5.3 to -1.7; P<0.001). In-hospital stroke and neurologic complications did not differ between groups (risk reduction: 0.1; 95% CI, -0.8 to 1.1; P=0.76). Conclusions-Mortality was not different between the groups. Thrombus aspiration was associated with decreased risk of stent thrombosis. Our study provides important evidence for the external validity of previous randomized studies regarding mortality.

  • 8.
    Angerås, Oskar
    et al.
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Haraldsson, Inger
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Redfors, Björn
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Petursson, Petur
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Albertsson, Per
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ioanes, Dan
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Odenstedt, Jacob
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Hans
    Department of Cardiology, Karlstad Hospital, Karlstad, Sweden.
    Witt, Nils
    Department of Cardiology, South Hospital Stockholm, Stockholm, Sweden.
    Rück, Andreas
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Millgård, Jonas
    Department of Cardiology, Sunderby Hospital, Sunderbyn, Sweden.
    Nilsson, Johan
    Department of Cardiology, Heart Centre, Umeå University Hospital, Umeå, Sweden.
    Persson, Jonas
    Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden.
    Söderbom, Måns
    Department of Economics, University of Gothenburg, Gothenburg, Sweden.
    Wedel, Hans
    Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Erlinge, David
    Department of Cardiology, Lund University, Lund, Sweden.
    James, Stefan
    Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ramunddal, Truls
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Omerovic, Elmir
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Impact of Thrombus Aspiration on Mortality, Stent Thrombosis, and Stroke in Patients With ST-Segment-Elevation Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007680Article in journal (Refereed)
    Abstract [en]

    Background: Thrombus aspiration is still being used in a substantial number of patients despite 2 large randomized clinical trials showing no favorable effect of routine thrombus aspiration during primary percutaneous coronary intervention in patients with STsegment- elevation myocardial infarction. The aim of this observational study was to evaluate the impact of thrombus aspiration on mortality, stent thrombosis, and stroke using all available data from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR).

    Methods and Results: We identified 42 829 consecutive patients registered in SCAAR between January 2005 and September 2014 who underwent percutaneous coronary intervention for ST-segment-elevation myocardial infarction. Thrombus aspiration was used in 25% of the procedures. We used instrumental variable analysis with administrative healthcare region as the treatmentpreference instrumental variable to evaluate the effect of thrombus aspiration on mortality, stent thrombosis, and stroke. Thrombus aspiration was not associated with mortality at 30 days (risk reduction: -1.2; 95% confidence interval [CI], -5.4 to 3.0; P=0.57) and 1 year (risk reduction: -2.4; 95% CI, -7.6 to 3.0; P=0.37). Thrombus aspiration was associated with a lower risk of stent thrombosis both at 30 days (risk reduction: -2.7; 95% CI, -4.1 to -1.4; P<0.001) and 1 year (risk reduction: -3.5; 95% CI, -5.3 to -1.7; P<0.001). In-hospital stroke and neurologic complications did not differ between groups (risk reduction: 0.1; 95% CI, -0.8 to 1.1; P=0.76).

    Conclusions: Mortality was not different between the groups. Thrombus aspiration was associated with decreased risk of stent thrombosis. Our study provides important evidence for the external validity of previous randomized studies regarding mortality.

  • 9.
    Arpegard, Johannes
    et al.
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden..
    Magnusson, Patrik K. E.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Chen, Xu
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    Ridefelt, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Pedersen, Nancy L.
    Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden..
    De Faire, Ulf
    Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Svensson, Per
    Karolinska Inst, Dept Med Solna, Stockholm, Sweden.;Karolinska Univ Hosp Solna, Dept Emergency Med, Stockholm, Sweden..
    Cystatin C Predicts Incident Cardiovascular Disease in Twins2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 6, article id e003085Article in journal (Refereed)
    Abstract [en]

    Background - Cystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors.

    Methods and Results - The predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox-regression model during a median follow-up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow-up were identified and within-pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47-1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25-1.70), ASCVD hazard ratio 1.26, 95% CI (1.13-1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01-1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co-twin (1.11 +/- 0.3 mg/L versus 1.06 +/- 0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co-twins (76.1 +/- 16.9 mu mol/L versus 79.4 +/- 20.3 mu mol/L).

    Conclusions - Variation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end-organ damage and small-vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease-discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important.

  • 10.
    Ban, Lu
    et al.
    Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom; Division of Rheumatology, Orthopaedics and Dermatology, Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom.
    Sprigg, Nikola
    Stroke, Division of Neuroscience, University of Nottingham, Nottingham, United Kingdom.
    Abdul Sultan, Alyshah
    Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom; Arthritis Research UK Primary Care Centre, Research Institute for Primary Care & Health Sciences, Keele University, Keele, United Kingdom.
    Nelson-Piercy, Catherine
    Women's Health Academic Centre, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
    Bath, Philip M
    Women's Health Academic Centre, Guy's and St. Thomas' NHS Foundation Trust, London, United Kingdom.
    Ludvigsson, Jonas F.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Stephansson, Olof
    Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Tata, Laila J
    Division of Epidemiology & Public Health, University of Nottingham, Nottingham, United Kingdom.
    Incidence of First Stroke in Pregnant and Nonpregnant Women of Childbearing Age: A Population-Based Cohort Study From England2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 4, article id e004601Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Pregnant women may have an increased risk of stroke compared with nonpregnant women of similar age, but the magnitude and the timing of such risk are unclear. We examined the risk of a first stroke event in women of childbearing age and compared the risk during pregnancy and in the early postpartum period with the background risk outside these periods.

    METHODS AND RESULTS: We conducted an open cohort study of 2 046 048 women aged 15 to 49 years between April 1, 1997, and March 31, 2014, using linked primary (Clinical Practice Research Datalink) and secondary (Hospital Episode Statistics) care records in England. Risk of first stroke was assessed by calculating the incidence rate of stroke in antepartum, peripartum (2 days before until 1 day after delivery), and early (first 6 weeks) and late (second 6 weeks) postpartum periods compared with nonpregnant time using a Poisson regression model with adjustment for maternal age, socioeconomic group, and calendar time. A total of 2511 women had a first stroke. The incidence rate of stroke was 25.0 per 100 000 person-years (95% CI 24.0-26.0) in nonpregnant time. The rate was lower antepartum (10.7 per 100 000 person-years, 95% CI 7.6-15.1) but 9-fold higher peripartum (161.1 per 100 000 person-years, 95% CI 80.6-322.1) and 3-fold higher early postpartum (47.1 per 100 000 person-years, 95% CI 31.3-70.9). Rates of ischemic and hemorrhagic stroke both increased peripartum and early postpartum.

    CONCLUSIONS: Although the absolute risk of first stroke is low in women of childbearing age, healthcare professionals should be aware of a considerable increase in relative risk during the peripartum and early postpartum periods.

  • 11.
    Bandak, Ghassan
    et al.
    Johns Hopkins Univ, Dept Med, Div Nephrol, Baltimore, MD USA..
    Sang, Yingying
    Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Gasparini, Alessandro
    Karolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Chang, Alex R.
    Geisinger Hlth Syst, Div Nephrol, Danville, PA USA..
    Ballew, Shoshana H.
    Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Evans, Marie
    Karolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Arnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Dalarna Univ, Sch Hlth & Social Studies, Falun, Sweden..
    Lund, Lars H.
    Karolinska Inst, Unit Cardiol, Dept Med, Stockholm, Sweden..
    Inker, Lesley A.
    Tufts Med Ctr, Div Nephrol, Boston, MA USA..
    Coresh, Josef
    Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Carrero, Juan-Jesus
    Karolinska Inst, Div Renal Med, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Grams, Morgan E.
    Johns Hopkins Univ, Dept Med, Div Nephrol, Baltimore, MD USA.;Johns Hopkins Univ, Dept Epidemiol, Bloomberg Sch Publ Hlth, Baltimore, MD USA..
    Hyperkalemia After Initiating Renin-Angiotensin System Blockade: The Stockholm Creatinine Measurements (SCREAM) Project2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 7, article id e005428Article in journal (Refereed)
    Abstract [en]

    Background: Concerns about hyperkalemia limit the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding potassium-monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE-I/ARB initiation and developed and validated a hyperkalemia susceptibility score.

    Methods and Results: We evaluated 69 426 new users of ACE-I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow-up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity-matched new ACE-I/ARB users to 20 186 new beta-blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new beta-blocker and ACEI/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m(2) were risks higher among ACE-I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium-sparing diuretics in new ACE-I/ARB users; this score accurately predicted 1-year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840-0.869) and in a validation cohort from the US-based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794-0.841), with good calibration.

    Conclusions: Hyperkalemia within the first year of ACE-I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m(2), but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.

  • 12. Bandak, Ghassan
    et al.
    Sang, Yingying
    Gasparini, Alessandro
    Chang, Alex R
    Ballew, Shoshana H
    Evans, Marie
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Lund, Lars H
    Inker, Lesley A
    Grams, Morgan E
    Hyperkalemia after initiating renin-angiotensin system blockade: The Stockholm creatinine measurements (SCREAM) project2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 7, article id e005428Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Concerns about hyperkalemia limit the use of angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs), but guidelines conflict regarding potassium-monitoring protocols. We quantified hyperkalemia monitoring and risks after ACE-I/ARB initiation and developed and validated a hyperkalemia susceptibility score.

    METHODS AND RESULTS: We evaluated 69 426 new users of ACE-I/ARB therapy in the Stockholm Creatinine Measurements (SCREAM) project with medication initiation from January 1, 2007 to December 31, 2010, and follow-up for 1 year thereafter. Three fourths (76%) of SCREAM patients had potassium checked within the first year. Potassium >5 and >5.5 mmol/L occurred in 5.6% and 1.7%, respectively. As a comparison, we propensity-matched new ACE-I/ARB users to 20 186 new β-blocker users in SCREAM: 64% had potassium checked. The occurrence of elevated potassium levels was similar between new β-blocker and ACE-I/ARB users without kidney disease; only at estimated glomerular filtration rate <60 mL/min per 1.73 m(2) were risks higher among ACE-I/ARB users. We developed a hyperkalemia susceptibility score that incorporated estimated glomerular filtration rate, baseline potassium level, sex, diabetes mellitus, heart failure, and the concomitant use of potassium-sparing diuretics in new ACE-I/ARB users; this score accurately predicted 1-year hyperkalemia risk in the SCREAM cohort (area under the curve, 0.845, 95% CI: 0.840-0.869) and in a validation cohort from the US-based Geisinger Health System (N=19 524; area under the curve, 0.818, 95% CI: 0.794-0.841), with good calibration.

    CONCLUSIONS: Hyperkalemia within the first year of ACE-I/ARB therapy was relatively uncommon among people with estimated glomerular filtration rate >60 mL/min per 1.73 m(2), but rates were much higher with lower estimated glomerular filtration rate. Use of the hyperkalemia susceptibility score may help guide laboratory monitoring and prescribing strategies.

  • 13. Bang, Casper N.
    et al.
    Greve, Anders M.
    Rossebø, Anne B.
    Ray, Simon
    Egstrup, Kenneth
    Boman, Kurt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Nienaber, Christoph
    Okin, Peter M.
    Devereux, Richard B.
    Wachtell, Kristian
    Antihypertensive treatment with β-blockade in patients with asymptomatic aortic stenosis and association with cardiovascular events2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 12, article id e006709Article in journal (Refereed)
    Abstract [en]

    Background: Patients with aortic stenosis (AS) often have concomitant hypertension. Antihypertensive treatment with a beta-blocker (Bbl) is frequently avoided because of fear of depression of left ventricular function. However, it remains unclear whether antihypertensive treatment with a Bbl is associated with increased risk of cardiovascular events in patients with asymptomatic mild to moderate AS.

    Methods and results: We did a post hoc analysis of 1873 asymptomatic patients with mild to moderate AS and preserved left ventricular ejection fraction in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. Propensity-matched Cox regression and competing risk analyses were used to assess risk ratios for all-cause mortality, sudden cardiac death, and cardiovascular death. A total of 932 (50%) patients received Bbl at baseline. During a median follow-up of 4.3 +/- 0.9 years, 545 underwent aortic valve replacement, and 205 died; of those, 101 were cardiovascular deaths, including 40 sudden cardiovascular deaths. In adjusted analyses, Bbl use was associated with lower risk of all-cause mortality (hazard ratio 0.5, 95% confidence interval 0.3-0.7, P<0.001), cardiovascular death (hazard ratio 0.4, 95% confidence interval 0.2-0.7, P<0.001), and sudden cardiac death (hazard ratio 0.2, 95% confidence interval 0.1-0.6, P=0.004). This was confirmed in competing risk analyses (all P<0.004). No interaction was detected with AS severity (all P>0.1).

    Conclusions: In post hoc analyses Bbl therapy did not increase the risk of all-cause mortality, sudden cardiac death, or cardiovascular death in patients with asymptomatic mild to moderate AS. A prospective study may be warranted to determine if Bbl therapy is in fact beneficial.

  • 14.
    Batra, Gorav
    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.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andell, Pontus
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden.; Skane Univ Hosp, Lund, Sweden..
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, Lund, Sweden.; Skane Univ Hosp, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Spaak, Jonas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    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.
    Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are associated with improved outcome but do not prevent new-onset atrial fibrillation after acute myocardial infarction2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 3, article id e005165Article in journal (Refereed)
    Abstract [en]

    Background Treatment with renin‐angiotensin system (RAS) inhibitors might restrain the structural/electrical remodeling associated with atrial fibrillation (AF). Limited evidence exists regarding the potential benefits of RAS inhibition post‐acute myocardial infarction (AMI) in patients with AF. This study sought to assess the association between RAS inhibition and all‐cause mortality and new‐onset AF in patients with/without congestive heart failure (CHF) post‐AMI.

    Methods and Results Patients hospitalized for AMI between 2006 and 2012 were identified in Swedish registries. Patients were stratified in 4 subgroups; patients with CHF and AF (n=11 489); patients with CHF without AF (n=31 676); patients with AF without CHF (n=10 066); and patients without both CHF and AF (n=59 417). Patients exposed to RAS inhibition were compared to nontreated. Three‐year risk of all‐cause mortality and new‐onset AF was assessed using adjusted Cox regression analyses. At discharge, 83 291 (73.9%) patients received RAS inhibition. RAS inhibition was associated with lower 3‐year risk of all‐cause mortality in CHF patients with AF, adjusted hazard ratio (HR) with 95% CI 0.75 (0.70–0.81), CHF patients without AF, HR 0.65 (0.60–0.69), AF patients without CHF, HR 0.82 (0.75–0.90), and in patients without CHF and AF, HR 0.76 (0.72–0.81), respectively. RAS inhibition was not associated with lower 3‐year risk of new‐onset AF in patients without AF but with/without CHF; HR 0.96 (0.84–1.10) and 1.12 (1.02–1.22), respectively.

    Conclusions RAS inhibition post‐AMI was associated with lower risk of all‐cause mortality. In patients with/without CHF, RAS inhibition was not associated with lower incidence of new‐onset AF.

  • 15.
    Björkenheim, Anna
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Brandes, Axel
    Department of Cardiology, Odense University Hospital, Odense, Denmark.
    Magnuson, Anders
    Chemnitz, Alexander
    Department of Cardiology, Odense University Hospital, Odense, Denmark.
    Edvardsson, Nils
    Sahlgrenska Academy, Sahlgrenska University Hospital, Göteborg, Sweden.
    Poçi, Dritan
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Patient-Reported Outcomes in Relation to Continuously Monitored Rhythm Before and During 2 Years After Atrial Fibrillation Ablation Using a Disease-Specific and a Generic Instrument2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 5, article id e008362Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Atrial fibrillation (AF) ablation improves patient-reported outcomes, irrespective of mode of intermittent rhythm monitoring. We evaluated the use of an AF-specific and a generic patient-reported outcomes instrument during continuous rhythm monitoring 2 years after AF ablation.

    METHODS AND RESULTS: Fifty-four patients completed the generic 36-Item Short-Form Health Survey and the AF-specific AF6 questionnaires before and 6, 12, and 24 months after AF ablation. All patients underwent continuous ECG monitoring via an implantable loop recorder. The generic patient-reported outcomes scores were compared with those of a Swedish age- and sex-matched population. After ablation, both summary scores reached normative levels at 24 months, while role-physical and vitality remained lower than norms. Responders to ablation (AF burden <0.5%) reached the norms in all individual 36-Item Short-Form Health Survey domains, while nonresponders (AF burden >0.5%) reached norms only in social functioning and mental component summary. All AF6 items and the sum score showed moderate to large improvement in both responders and nonresponders, although responders showed significantly greater improvement in all items except item 1 from before to 24 months after ablation. Higher AF burden was independently associated with poorer physical component summary and AF6 sum score.

    CONCLUSIONS: The AF-specific AF6 questionnaire was more sensitive to changes related to AF burden than the generic 36-Item Short-Form Health Survey. Patients improved as documented by both instruments, but a higher AF burden after ablation was associated with poorer AF-specific patient-reported outcomes and poorer generic physical but not mental health. Our results support the use of an AF-specific instrument, alone or in combination with a generic instrument, to assess the effect of ablation.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00697359.

  • 16. Bonamy, Anna-Karin Edstedt
    et al.
    Mohlkert, Lilly-Ann
    Hallberg, Jenny
    Liuba, Petru
    Fellman, Vineta
    Domellöf, Magnus
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Norman, Mikael
    Blood Pressure in 6-Year-Old Children Born Extremely Preterm2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 8, article id e005858Article in journal (Refereed)
    Abstract [en]

    Background-Advances in perinatal medicine have increased infant survival after very preterm birth. Although this progress is welcome, there is increasing concern that preterm birth is an emerging risk factor for hypertension at young age, with implications for the lifetime risk of cardiovascular disease. Methods and Results-We measured casual blood pressures (BPs) in a population-based cohort of 6-year-old survivors of extremely preterm birth (< 27 gestational weeks; n=171) and in age-and sex-matched controls born at term (n=172). Measured BP did not differ, but sex, age-, and height-adjusted median z scores were 0.14 SD higher (P=0.02) for systolic BP and 0.10 SD higher (P=0.01) for diastolic BP in children born extremely preterm than in controls. Among children born extremely preterm, shorter gestation, higher body mass index, and higher heart rate at follow-up were all independently associated with higher BP at 6 years of age, whereas preeclampsia, smoking in pregnancy, neonatal morbidity, and perinatal corticosteroid therapy were not. In multivariate regression analyses, systolic BP decreased by 0.10 SD (P=0.08) and diastolic BP by 0.09 SD (P=0.02) for each week-longer gestation. Conclusions-Six-year-old children born extremely preterm have normal but slightly higher BP than their peers born at term. Although this finding is reassuring for children born preterm and their families, follow-up at older age is warranted.

  • 17.
    Carlhed, Rickard
    et al.
    Onkologi, Landstinget i Värmland.
    Bellman, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Bojestig, Mats
    Landstinget i Jönköping.
    Bojö, Leif
    Klinisk Fysiologi, Landstinget i Värmland.
    Peterson, Anette
    Landstinget i Jönköping.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Quality improvement in coronary care: Analysis of sustainability and impact on adjacent clinical measures after a Swedish controlled, multicenter quality improvement collaborative2012In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 1, no 4, article id e000737Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 18.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ruge, Toralph
    Kjøller, Erik
    Hilden, Jørgen
    Kolmos, Hans Jørn
    Sajadieh, Ahmad
    Kastrup, Jens
    Jensen, Gorm Boje
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Nowak, Christoph
    Jakobsen, Janus Christian
    Winkel, Per
    Gluud, Christian
    Ärnlöv, Johan
    10-Year Associations between Tumor Necrosis Factor Receptors 1 and 2 and Cardiovascular Events in Patients with Stable Coronary Heart Disease: A CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) Trial Substudy.2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008299Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

    METHODS AND RESULTS: CLARICOR (Effect of Clarithromycin on Mortality and Morbidity in Patients With Ischemic Heart Disease) is a randomized clinical trial comparing clarithromycin with placebo in patients with stable coronary heart disease. The primary outcome was a composite of nonfatal acute myocardial infarction, unstable angina pectoris, cerebrovascular disease, and all-cause mortality. Patients were followed up for 10 years; discovery sample, those assigned placebo (1204 events in n=1998); and replication sample, those assigned clarithromycin (1220 events in n=1979). We used Cox regression adjusted for C-reactive protein level, established cardiovascular risk factors, kidney function, and cardiovascular drugs. After adjustments, higher serum levels of TNFR1 and TNFR2 were associated with the composite outcome in the discovery sample (hazard ratio per SD increase, 1.13; 95% confidence interval, 1.05-1.22; P=0.001 for TNFR1; hazard ratio, 1.16; 95% confidence interval, 1.08-1.24; P<0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

    CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

  • 19. Carlsson, Axel C
    et al.
    Ruge, Toralph
    Kjøller, Erik
    Hilden, Jørgen
    Kolmos, Hans Jørn
    Sajadieh, Ahmad
    Kastrup, Jens
    Jensen, Gorm Boje
    Larsson, Anders
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska institutet.
    10-year associations between tumor necrosis factor receptors 1 and 2 and cardiovascular events in patients with stable coronary heart disease: a CLARICOR (effect of clarithromycin on mortality and morbidity in patients with ischemic heart disease) trial substudy2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008299Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We aimed to assess the associations and predictive powers between the soluble receptors for tumor necrosis factor (TNF)-α (TNFR1 and TNFR2) and cardiovascular outcomes in patients with stable coronary heart disease.

    METHODS AND RESULTS: <0.001 for TNFR2). The associations were similar in the replication sample. The associations with the composite outcome were mainly driven by acute myocardial infarction, cardiovascular mortality, and noncardiovascular mortality. The addition of TNFR1 and TNFR2 to established cardiovascular risk factors improved prediction only modestly (<1%).

    CONCLUSIONS: Increased concentrations of circulating TNFR1 and TNFR2 were associated with increased risks of cardiovascular events and mortality in patients with stable coronary heart disease. Yet, the utility of measuring TNFR1 and TNFR2 to improve risk prediction in these patients appears limited.

    CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00121550.

  • 20.
    Charitakis, Emmanouil
    et al.
    Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Walfridsson, Håkan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alehagen, Urban
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Short‐Term Influence of Radiofrequency Ablation on NT‐proBNP, MR‐proANP, Copeptin, and MR‐proADM in Patients With Atrial Fibrillation: Data From the Observational SMURF Study2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 9Article in journal (Refereed)
    Abstract [en]

    Background There is limited knowledge on the short‐term influence of radiofrequency ablation (RFA) of atrial fibrillation (AF) on 2 cardiac biomarkers; the N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and the midregional fragment of the N‐terminal of pro‐ANP (MR‐proANP) and 2 extracardiac biomarkers; the c‐terminal provasopressin (copeptin) and the midregional portion of proadrenomedullin (MR‐proADM). There are also limited data concerning cardiac production of the latter two.

    Methods and Results We studied 192 consecutive patients eligible for RFA of AF referred to the University Hospital, Linköping, Sweden. NT‐proBNP, MR‐proANP, copeptin, and MR‐proADM levels were measured in peripheral blood, the coronary sinus (CS), and the left atrium before ablation, and in peripheral blood immediately and the day after RFA. The level of NT‐proBNP decreased the day after RFA in participants in AF at the time of RFA, compared to the participants in sinus rhythm who showed a slight increase (P<0.001). Furthermore, regardless of the actual rhythm, the level of MR‐proANP showed an increase immediately after RFA (P<0.001), followed by a decrease the day after ablation (P<0.001). Copeptin level showed a 6‐fold increase immediately after RFA compared to baseline (P<0.001), whereas MR‐proADM level increased the day after RFA (P<0.001). Levels of copeptin and MR‐proADM were not higher in the CS compared to peripheral blood.

    Conclusions RFA of AF is a strong stimulus with a significant and direct impact on different neurohormonal systems. We found no sign of a cardiac release of MR‐proADM or copeptin.

  • 21.
    Dagenais, Gilles R.
    et al.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Jung, Hyejung
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Lonn, Eva
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Bogaty, Peter M.
    Lava Univ, Quebec Heart & Lung Univ Inst, Quebec City, PQ, Canada.
    Dehghan, Mahshid
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Avezum, Alvaro
    Univ Santo Amaro, Dante Pazzanese Inst Cardiol, Sao Paulo, Brazil.
    Jansky, Petr
    Univ Hosp Motol, Prague, Czech Republic.
    Keltai, Matyas
    Semmelweis Univ, Budapest, Hungary.
    Leiter, Lawrence A.
    Univ Toronto, Li Ka Shing Knowledge Inst, St Michaels Hosp, Toronto, ON, Canada;Univ Toronto, Dept Med, Toronto, ON, Canada;Univ Toronto, Dept Nutr Sci, Toronto, ON, Canada.
    Lopez-Jaramillo, Patricio
    Univ Santander UDES, Med Sch, Res Dept, FOSCAL, Bucaramanga, Colombia.
    Toff, William D.
    Univ Leicester, Dept Cardiovasc Sci, Leicester, Leics, England;NIHR Leicester Biomed Res Ctr, Leicester, Leics, England.
    Bosch, Jackie
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Yusuf, Salim
    McMaster Univ, Hamilton Gen Hosp, Populat Hlth Res Inst, Hamilton, ON, Canada.
    Effects of Lipid-Lowering and Antihypertensive Treatments in Addition to Healthy Lifestyles in Primary Prevention: An Analysis of the HOPE-3 Trial2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 15, article id e008918Article in journal (Refereed)
    Abstract [en]

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

  • 22.
    Ekblom, Örjan
    et al.
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology.
    Ek, Amanda
    Swedish School of Sport and Health Sciences, GIH, Department of Sport and Health Sciences, Åstrand Laboratory of Work Physiology, Björn Ekblom's research group.
    Cider, Åsa
    University of Gothenburg.
    Hambraeus, Kristina
    Falun Hospital.
    Börjesson, Mats
    University of Gothenburg.
    Increased Physical Activity Post-Myocardial Infarction Is Related to Reduced Mortality; Results From the SWEDEHEART Registry2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 24, article id e010108Article in journal (Refereed)
    Abstract [en]

    Background

    With increasing survival rates among patients with myocardial infarction (MI), more demands are placed on secondary prevention. While physical activity (PA) efforts to obtain a sufficient PA level are part of secondary preventive recommendations, it is still underutilized. Importantly, the effect of changes in PA after MI is largely unknown. Therefore, we sought to investigate the effect on survival from changes in PA level, post‐MI.

    Methods and Results

    Data from Swedish national registries were combined, totaling 22 227 patients with MI. PA level was self‐reported at 6 to 10 weeks post‐MI and 10 to 12 months post‐MI. Patients were classified as constantly inactive, increased activity, reduced activity, and constantly active. Proportional hazard ratios were calculated. During 100 502 person‐years of follow‐up (mean follow‐up time 4.2 years), a total of 1087 deaths were recorded. Controlling for important confounders (including left ventricular function, type of MI, medication, smoking, participation in cardiac rehabilitation program, quality of life, and estimated kidney function), we found lower mortality rates among constantly active (hazard ratio: 0.29, 95% confidence interval: 0.21–0.41), those with increased activity (0.41, 95% confidence interval: 0.31–0.55), and those with reduced activity (hazard ratio: 0.56, 95% confidence interval: 0.45–0.69) during the first year post‐MI, compared with those being constantly inactive. Stratified analyses indicated strong effect of PA level among both sexes, across age, MI type, kidney function, medication, and smoking status.

    Conclusions

    The present article shows that increasing the PA level, compared with staying inactive the first year post‐MI, was related to reduced mortality.

  • 23.
    Emilsson, Louise
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Vårdcentralen Värmlands Nysäter, Värmland County, Sweden; Department of Medicine, School of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Andersson, Bert
    Institute of Medicine, Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Elfström, Peter
    Department of Neonatology, Astrid Lindgren Children's Hospital Danderyd, Stockholm, Sweden; Karolinska University Hospital, Stockholm, Sweden.
    Green, Peter H. R.
    Department of Medicine, Columbia University College of Physicians and Surgeons, New York NY, USA.
    Ludvigsson, Jonas F.
    Department of Pediatrics, Örebro University Hospital, Örebro, Sweden; the Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden; Karolinska Institutet, Stockholm, Sweden.
    Risk of idiopathic dilated cardiomyopathy in 29 000 patients with celiac disease2012In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 1, no 3, article id e001594Article in journal (Refereed)
    Abstract [en]

    Background: Dilated cardiomyopathy (DCM) is a rare disease of largely unknown origin. Previous studies have suggested an increased prevalence of celiac disease (CD) in patients with DCM. These studies, however, were based on a maximum of 5 patients with both CD and DCM. In the present large Swedish population-based cohort study, we examined the risk of idiopathic DCM in patients with CD determined by small-intestinal histopathology.

    Methods and Results: From 2006 to 2008, we collected duodenal/jejunal biopsy data on CD (equal to villous atrophy, Marsh stage 3, n=29 071 unique individuals) from (all) 28 pathology departments in Sweden. These individuals were compared with 144 429 reference individuals matched for age, sex, calendar year, and county. Data on DCM were obtained through the National Patient Register and confirmed by patient charts and echocardiography data. During follow-up, 17 patients with CD and 52 reference individuals developed idiopathic DCM. Thus, patients with CD were at an increased risk of idiopathic DCM (hazard ratio, 1.73; 95% confidence interval, 1.00 to 3.00), although the risk estimate failed to attain statistical significance (P=0.052).

    Conclusion: This nationwide study found a moderately but not statistically significantly increased risk of idiopathic DCM in patients with biopsy-verified CD.

  • 24. Frobert, Ole
    et al.
    Calais, Fredrik
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    ST-Elevation Myocardial Infarction, Thrombus Aspiration, and Different Invasive Strategies. A TASTE Trial Substudy2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 6, article id e001755Article in journal (Refereed)
    Abstract [en]

    Background-The clinical effect of thrombus aspiration in ST-elevation myocardial infarction may depend on the type of aspiration catheter and stenting technique. Methods and Results-The multicenter, prospective, randomized, open-label trial Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE) did not demonstrate a clinical benefit of thrombus aspiration compared to percutaneous coronary intervention alone. We assessed the effect of type of aspiration device, stent type, direct stenting, and postdilatation on outcomes at 1 year. There was no difference in all-cause mortality, between the 3 most frequently used aspiration catheters (Eliminate [Terumo] 5.4%, Export [Medtronic] 5.0%, Pronto [Vascular Solutions] 4.5%) in patients randomized to thrombus aspiration. There was no difference in mortality between directly stented patients randomized to thrombus aspiration compared to patients randomized to percutaneous coronary intervention only (risk ratio 1.08, 95% CI 0.70 to 1.67, P=0.73). Similarly, there was no difference in mortality between the 2 randomized groups for patients receiving drug-eluting stents (risk ratio 0.89, 95% CI 0.63 to 1.26, P=0.50) or for those treated with postdilation (risk ratio 0.72, 95% CI 0.49 to 1.07, P=0.11). Furthermore, there was no difference in rehospitalization for myocardial infarction or stent thrombosis between the randomized arms in any of the subgroups. Conclusions-In patients with ST-elevation myocardial infarction randomized to thrombus aspiration, the type of aspiration catheter did not affect outcome. Stent type, direct stenting, or postdilation did not affect outcome irrespective of treatment with thrombus aspiration and percutaneous coronary intervention or percutaneous coronary intervention alone.

  • 25.
    Fröbert, Ole
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Calais, Fredrik
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    James, Stefan K.
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Lagerqvist, Bo
    Department of Medical Sciences, Cardiology, Uppsala University, Uppsala, Sweden; Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    ST-Elevation Myocardial Infarction, Thrombus Aspiration, and Different Invasive Strategies: A TASTE Trial Substudy2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 6, article id e001755Article in journal (Refereed)
    Abstract [en]

    Background: The clinical effect of thrombus aspiration in ST-elevation myocardial infarction may depend on the type of aspiration catheter and stenting technique.

    Methods and Results: The multicenter, prospective, randomized, open-label trial Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia (TASTE) did not demonstrate a clinical benefit of thrombus aspiration compared to percutaneous coronary intervention alone. We assessed the effect of type of aspiration device, stent type, direct stenting, and postdilatation on outcomes at 1 year. There was no difference in all-cause mortality, between the 3 most frequently used aspiration catheters (Eliminate [Terumo] 5.4%, Export [Medtronic] 5.0%, Pronto [Vascular Solutions] 4.5%) in patients randomized to thrombus aspiration. There was no difference in mortality between directly stented patients randomized to thrombus aspiration compared to patients randomized to percutaneous coronary intervention only (risk ratio 1.08, 95% CI 0.70 to 1.67, P=0.73). Similarly, there was no difference in mortality between the 2 randomized groups for patients receiving drug-eluting stents (risk ratio 0.89, 95% CI 0.63 to 1.26, P=0.50) or for those treated with postdilation (risk ratio 0.72, 95% CI 0.49 to 1.07, P=0.11). Furthermore, there was no difference in rehospitalization for myocardial infarction or stent thrombosis between the randomized arms in any of the subgroups.

    Conclusions: In patients with ST-elevation myocardial infarction randomized to thrombus aspiration, the type of aspiration catheter did not affect outcome. Stent type, direct stenting, or postdilation did not affect outcome irrespective of treatment with thrombus aspiration and percutaneous coronary intervention or percutaneous coronary intervention alone.

  • 26.
    Fu, Michael
    et al.
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Rosengren, Annika
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Thunström, Erik
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Mandalenakis, Zacharias
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Welin, Lennart
    Lidkoping Hosp, Dept Med, Lidkoping, Sweden.
    Caidahl, Kenneth
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden;Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
    Pivodic, Aldina
    Stat Consulting, Gothenburg, Sweden.
    Zhong, You
    Beijing Hosp, Dept Cardiol, Beijing, Peoples R China.
    Ergatoudes, Constantinos
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Morales, David
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Welin, Catharina
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Svärdsudd, Kurt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Dellborg, Mikael
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Hansson, Per-Olof
    Univ Gothenburg, Dept Mol & Clin Med, Inst Med, Sahlgrenska Acad, Gothenburg, Sweden.
    Although Coronary Mortality Has Decreased, Rates of Cardiovascular Disease Remain High: 21 Years of Follow-Up Comparing Cohorts of Men Born in 1913 With Men Born in 19432018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 9, article id e008769Article in journal (Refereed)
    Abstract [en]

    Background - Despite a decline in mortality rates from cardiovascular disease (CVD) in the past few decades, the burden of CVD in a contemporary population remains inadequately addressed. Therefore, this study was aimed to investigate secular trends in mortality from coronary artery disease and all-cause mortality over 2 decades, by comparing 2 cohorts of men born 30 years apart and evaluate the prediction of the risk of CVD and all-cause death in a contemporary random sample of Swedish men.

    Methods and Results - Two cohorts of randomly selected men born in 1913 (855 men) and 1943 (798 men) were first examined at age 50 in 1963 and 1993, respectively, and followed longitudinally over 21 years. All-cause mortality and coronary artery disease death were lower in 50-to 71-year-old men born in 1943 compared with those born in 1913, with unadjusted hazard ratios of 0.57 (0.45-0.71) and 0.34 (0.22-0.53), respectively. After adjustment for risk factors (smoking, serum cholesterol, hypertension, systolic blood pressure, diabetes mellitus, body mass index, and physical activity), the differences between the cohorts remained significant for coronary artery disease, hazard ratios 0.57 (0.34-0.94), P=0.029, but not for all-cause mortality hazard ratios 0.82 (0.62-1.07), P=0.14. However, the rate of CVD events during follow-up was still high (30.7%) for the men born in 1943. No statistically significant interaction by birth cohort in contribution of risk factors to death was found between 2 cohorts except physical inactivity.

    Conclusions - Despite a marked reduction in the rate of coronary artery disease death over the past 30 years, the burden of CVD events and all-cause mortality remains high. Therefore, intensified efforts to modify contributing risk factors are still required.

  • 27.
    Graipe, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Section of Cardiology, Department of Internal Medicine, Östersund Hospital, Östersund, Sweden.
    Binsell-Gerdin, Emil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Internal Medicine, Östersund Hospital, Östersund, Sweden .
    Söderström, Lars
    Mooe, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Incidence, Time Trends, and Predictors of Intracranial Hemorrhage During Long-Term Follow-up After Acute Myocardial Infarction2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 12, article id e002290Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: To address the lack of knowledge regarding the long-term risk of intracranial hemorrhage (ICH) after acute myocardial infarction (AMI), the aims of this study were to: (1) investigate the incidence, time trends, and predictors of ICH in a large population within 1 year of discharge after AMI; (2) investigate the comparative 1-year risk of ICH in AMI patients and a reference group; and (3) study the impact of previous ischemic stroke on ICH risk in patients treated with various antithrombotic therapies.

    METHODS AND RESULTS: Data about patients whose first AMI occurred between 1998 and 2010 were collected from the Swedish Register of Information and Knowledge about Swedish Heart-Intensive-Care Admissions (RIKS-HIA). Patients with an ICH after discharge were identified in the National Patient Register. Risk was compared against a matched reference population. Of 187 386 patients, 590 had an ICH within 1 year. The 1-year cumulative incidence (0.35%) was approximately twice that of the reference group, and it did not change significantly over time. Advanced age, previous ischemic or hemorrhagic stroke, and reduced glomerular filtration rate were associated with increased ICH risk, whereas female sex was associated with a decreased risk. Previous ischemic stroke did not increase risk of ICH associated with single or dual antiplatelet therapy, but increased risk with anticoagulant therapy.

    CONCLUSION: The 1-year incidence of ICH after AMI remained stable, at ≈0.35%, over the study period. Advanced age, decreased renal function, and previous ischemic or hemorrhagic stroke are predictive of increased ICH risk.

  • 28. Grøntved, Anders
    et al.
    Koivula, Robert W
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Østergaard, Lars
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Renström, Frida
    Umeå University, Faculty of Medicine, Department of Biobank Research. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 11, article id e004413Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Bicycling to work may be a viable approach for achieving physical activity that provides cardiovascular health benefits. In this study we investigated the relationship of bicycling to work with incidence of obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance across a decade of follow-up in middle-aged men and women.

    METHODS AND RESULTS: We followed 23 732 Swedish men and women with a mean age of 43.5 years at baseline who attended a health examination twice during a 10-year period (1990-2011). In multivariable adjusted models we calculated the odds of incident obesity, hypertension, hypertriglyceridemia, and impaired glucose tolerance, comparing individuals who commuted to work by bicycle with those who used passive modes of transportation. We also examined the relationship of change in commuting mode with incidence of these clinical risk factors. Cycling to work at baseline was associated with lower odds of incident obesity (odds ratio [OR]=0.85, 95% CI 0.73-0.99), hypertension (OR=0.87, 95% CI 0.79-0.95), hypertriglyceridemia (OR=0.85, 95% CI 0.76-0.94), and impaired glucose tolerance (OR=0.88, 95% CI 0.80-0.96) compared with passive travel after adjusting for putative confounding factors. Participants who maintained or began bicycling to work during follow-up had lower odds of obesity (OR=0.61, 95% CI 0.50-0.73), hypertension (OR=0.89, 95% CI 0.80-0.98), hypertriglyceridemia (OR=0.80, 95% CI 0.70-0.90), and impaired glucose tolerance (OR=0.82, 95% CI 0.74-0.91) compared with participants not cycling to work at both times points or who switched from cycling to other modes of transport during follow-up.

    CONCLUSIONS: These data suggest that commuting by bicycle to work is an important strategy for primordial prevention of clinical cardiovascular risk factors among middle-aged men and women.

  • 29.
    Guimaraes, Patricia Oliveira
    et al.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Granger, Christopher B.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stebbins, Amanda
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hochman, Judith S.
    NYU, Dept Med, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA..
    Krug-Gourley, Susan
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, Collegeville, PA USA..
    Lonn, Eva
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Lopes, Renato D.
    Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA.;Duke Univ, Med Ctr, Durham, NC USA..
    Stewart, Ralph A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Vinereanu, Dragos
    Univ Med & Pharm Carol Davila, Bucharest, Romania..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand.;Univ Auckland, Auckland, New Zealand..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Danchin, Nicolas
    Hop Europeen Georges Pompidou, AP HP, INSERM U970, Paris, France.;Univ Paris 05, Paris, France..
    Sex Differences in Clinical Characteristics, Psychosocial Factors, and Outcomes Among Patients With Stable Coronary Heart Disease: Insights from the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 9, article id e006695Article in journal (Refereed)
    Abstract [en]

    Background-Greater understanding of differences between men and women with coronary heart disease is needed. Methods and Results-In this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P<0.0001). The median duration of follow-up was 3.7 years (25th-75th percentiles: 3.5-3.8 years). Use of evidence-based medications for coronary heart disease at baseline and 24 months was similar between sexes, as were event rates for all outcomes analyzed. In the multivariable model including psychosocial measures, female sex was associated with lower cardiovascular risk. There was a statistically significant interaction (P=0.03) such that the lower risk in women varied by depressive symptom frequency, whereby women who were more depressed had a risk similar to men. Conclusions-Female sex was independently associated with better long-term clinical outcomes, although this was modified by frequency of depressive symptoms. This suggests that emotional state may be an important target for improving outcomes in patients with coronary heart disease, specifically in women.

  • 30.
    Guimares, Patricia O.
    et al.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.;Univ Sao Paulo, Fac Med, Hosp Clin, Inst Coracao InCor, Sao Paulo, Brazil..
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Stevens, Susanna R.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Zimerman, Andre
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Wruck, Lisa
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Haque, Ghazala
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Giraldez, Roberto Rocha C. V.
    Univ Sao Paulo, Fac Med, Hosp Clin, Inst Coracao InCor, Sao Paulo, Brazil..
    Alexander, John H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Alexander, Karen P.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA..
    Reporting Clinical End Points and Safety Events in an Acute Coronary Syndrome Trial: Results With Integrated Collection2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 4, article id e005490Article in journal (Refereed)
    Abstract [en]

    Background-End points and adverse events (AEs) are collected separately in clinical trials, yet regulatory requirements for serious AE reporting vary across regions, so classifying end points according to seriousness criteria can be useful in global trials. Methods and Results-In the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) trial, patients with a recent acute coronary syndrome were randomized to apixaban or placebo for the prevention of recurrent ischemic events. Suspected end points (myocardial infarction, stroke, or bleeding) were adjudicated by an independent clinical events classification committee. Safety criteria were collected for suspected end points and AEs. Patient-level event rates per 100 patient-days of follow-up, modeled using Poisson regression, explored the influence of region and patient characteristics on event reporting. Overall, 13 909 events were reported by 858 sites in 39 countries; 8.4% (n=1166) were suspected end points, and 91.6% (n=12 743) were AEs. Overall, 66.0% of suspected end points were confirmed by the clinical events classification committee. Most clinical events classification committee-confirmed end points met criteria to be classified as serious (94.0%); many clinical events classification committee-negated end points also did (63.2%), but fewer AEs met seriousness criteria (17.9%). The most common seriousness criterion was hospitalization (79.9%, n=2594). Region explained 28.7% of end point-and 26.4% of serious AE-reporting variation, and patient characteristics explained an additional 25.4% of end point and 13.4% of serious AE variation. Nonserious AE-reporting variation was not explained by adjustment. Conclusions-An integrated collection of end points and serious AEs is feasible in a multinational trial and illustrates the shared characteristics of events. Tailoring event collection to fit the phase and purpose of the trial is achievable and informative.

  • 31.
    Hallmarker, Ulf
    et al.
    Uppsala universitet; Mora Hospital.
    Asberg, Signild
    Uppsala universitet.
    Michaelsson, Karl
    Uppsala universitet.
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Hellberg, Dan
    Uppsala Univ, Dept Womens & Childrens Hlth, Uppsala, Sweden..
    Lindback, Johan
    Uppsala universitet.
    Wester, Per
    Umea universitet.
    James, Stefan
    Uppsala universitet.
    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.

  • 32.
    Hasselqvist-Ax, Ingela
    et al.
    Karolinska Institutet.
    Nordberg, Per
    Karolinska Institutet.
    Herlitz, Johan
    University of Borås, Faculty of Caring Science, Work Life and Social Welfare.
    Svensson, Leif
    Karolinska Institutet.
    Jonsson, Martin
    Karolinska Institutet.
    Lindqvist, Jonny
    Sahlgrenska University Hospital.
    Ringh, Mattias
    Karolinska Institutet.
    Claesson, Andreas
    Karolinska Institutet.
    Björklund, Johan
    Fire and Rescue Service Dala Middle, Falun.
    Andersson, Jan-Otto
    Emergency Medical Services, Skövde Emergency Department, Skövde.
    Ericson, Caroline
    Sahlgrenska University Hospital.
    Lindblad, Pär
    Värnamo County Hospital, Jönköping County.
    Engerström, Lars
    SOS Alarm Centers, Stockholm.
    Rosenqvist, Mårten
    Karolinska Institutet.
    Hollenberg, Jacob
    Karolinska Institutet.
    Dispatch of Firefighters and Police Officers in Out-of-Hospital Cardiac Arrest: A Nationwide Prospective Cohort Trial Using Propensity Score Analysis.2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 10, article id e005873Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Dispatch of basic life support-trained first responders equipped with automated external defibrillators in addition to advanced life support-trained emergency medical services personnel in out-of-hospital cardiac arrest (OHCA) has, in some minor cohort studies, been associated with improved survival. The aim of this study was to evaluate the association between basic life support plus advanced life support response and survival in OHCA at a national level.

    METHODS AND RESULTS: This prospective cohort study was conducted from January 1, 2012, to December 31, 2014. People who experienced OHCA in 9 Swedish counties covered by basic life support plus advanced life support response were compared with a propensity-matched contemporary control group of people who experienced OHCA in 12 counties where only emergency medical services was dispatched, providing advanced life support. Primary outcome was survival to 30 days. The analytic sample consisted of 2786 pairs (n=5572) derived from the total cohort of 7308 complete cases. The median time from emergency call to arrival of emergency medical services or first responder was 9 minutes in the intervention group versus 10 minutes in the controls (P<0.001). The proportion of patients admitted alive to the hospital after resuscitation was 31.4% (875/2786) in the intervention group versus 24.9% (694/2786) in the controls (conditional odds ratio, 1.40; 95% confidence interval, 1.24-1.57). Thirty-day survival was 9.5% (266/2786) in the intervention group versus 7.7% (214/2786) in the controls (conditional odds ratio, 1.27; 95% confidence interval, 1.05-1.54).

    CONCLUSIONS: In this nationwide interventional trial, using propensity score matching, dispatch of first responders in addition to emergency medical services in OHCA was associated with a moderate, but significant, increase in 30-day survival.

    CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02184468.

  • 33.
    Heinola, Ivika
    et al.
    Univ Helsinki, Dept Vasc Surg, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Sörelius, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Wyss, Thomas R.
    Univ Bern, Bern Univ Hosp, Inselspital, Dept Cardiovasc Surg, Bern, Switzerland.
    Eldrup, Nikolaj
    Aarhus Univ Hosp, Dept Cardiothorac & Vasc Surg, Aarhus, Denmark.
    Settembre, Nicla
    Nancy Univ Hosp, Dept Vasc Surg, Nancy, France.
    Setacci, Carlo
    Univ Siena, Dept Med Surg & Neurosci, Siena, Italy.
    Mani, Kevin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Vascular Surgery.
    Kantonen, Ilkka
    Univ Helsinki, Dept Vasc Surg, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Venermo, Maarit
    Univ Helsinki, Dept Vasc Surg, Helsinki, Finland;Helsinki Univ Hosp, Helsinki, Finland.
    Open Repair of Mycotic Abdominal Aortic Aneurysms With Biological Grafts: An International Multicenter Study2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 12, article id e008104Article in journal (Refereed)
    Abstract [en]

    Background-The treatment of mycotic abdominal aortic aneurysm requires surgery and antimicrobial therapy. Since prosthetic reconstructions carry a considerable risk of reinfection, biological grafts are noteworthy alternatives. The current study evaluated the durability, infection resistance, and midterm outcome of biological grafts in treatment of mycotic abdominal aortic aneurysm. Methods and Results-All patients treated with biological graft in 6 countries between 2006 and 2016 were included. Primary outcome measures were 30- and 90-day survival, treatment-related mortality, and reinfection rate. Secondary outcome measures were overall mortality and graft patency. Fifty-six patients (46 males) with median age of 69 years (range 35-85) were included. Sixteen patients were immunocompromised (29%), 24 (43%) had concomitant infection, and 12 (21%) presented with rupture. Bacterial culture was isolated from 43 (77%). In-situ aortic reconstruction was performed using autologous femoral veins in 30 patients (54%), xenopericardial tube-grafts in 12 (21%), cryopreserved arterial/venous allografts in 9 (16%), and fresh arterial allografts in 5 (9%) patients. During a median follow-up of 26 months (range 3 weeks-172 months) there were no reinfections and only 3 patients (5%) required assistance with graft patency. Thirty-day survival was 95% (n=53) and 90-day survival was 91% (n=51). Treatment-related mortality was 9% (n=5). Kaplan-Meier estimation of survival at 1 year was 83% (95% confidence interval, 73%-94%) and at 5 years was 71% (52%-89%). Conclusions-Mycotic abdominal aortic aneurysm repair with biological grafts is a durable option for patients fit for surgery presenting an excellent infection resistance and good overall survival.

  • 34.
    Held, Claes
    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.
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Stewart, Ralph A. H.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Budaj, Andrzej
    Grochowski Hosp, Postgrad Med Sch, Warsaw, Poland..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA..
    Hochman, Judith S.
    NYU, Dept Med, Langone Med Ctr, 550 1St Ave, New York, NY 10016 USA..
    Koenig, Wolfgang
    Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, Ulm, Germany.;Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    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.
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Paris, France.;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France.;NHLI Imperial Coll, Royal Brompton Hosp, ICMS, London, England.;INSERM, FACT, U1148, Paris, France..
    Soffer, Joseph
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, Collegeville, PA USA..
    Weaver, Douglas
    Henry Ford Heart & Vasc Inst, Detroit, MI USA..
    Östlund, Ollie
    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.
    Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 10, article id e005077Article in journal (Refereed)
    Abstract [en]

    Background

    Evaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population.

    Methods and Results

    Overall, 15 828 patients with coronary heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial werer and randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein were measured in plasma samples: median levels were2.1 (interquartile range, 1.4-3.2) ng/Land1.3 (interquartile range, 0.6-3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers. IL-6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.30-1.97; P< 0.0001); cardiovascular death (HR, 2.15; 95% CI, 1.53-3.04; P< 0.0001); myocardial infarction (HR, 1.53; 95% CI, 1.14-2.04; P< 0.05); all-cause mortality (HR, 2.11; 95% CI, 1.62-2.76; P< 0.0001); and risk of hospitalization for heart failure (HR, 2.28; 95% CI, 1.34-3.89; P< 0.001). Cancer death was doubled in the highest IL-6 quartile group (HR, 2.34; 95% CI, 1.20-4.53; P< 0.05). High-sensitivity C-reactive protein was associated with both cardiovascular and non-cardiovascular events in the unadjusted model, but these did not remain after multivariable adjustments.

    Conclusions

    IL-6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all-cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL-6 might reflect a pathophysiological process involved in the development of these events.

  • 35.
    Hess, Connie N.
    et al.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Roe, Matthew T.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Clare, Robert M.
    Duke Clin Res Inst, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Clin Res Inst, Durham, NC 27705 USA..
    Kelly, Joseph
    Duke Clin Res Inst, Durham, NC 27705 USA.;Duke Clin Res Inst, Ctr Learning Healthcare, Durham, NC 27705 USA..
    Tcheng, James E.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Dept Med Sci Cardiol, Uppsala, Sweden.;Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Khouri, Michel G.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA..
    Hirsch, Bradford R.
    Duke Clin Res Inst, Durham, NC 27705 USA.;Duke Canc Inst, Durham, NC USA..
    Kong, David F.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Abernethy, Amy P.
    Duke Univ, Div Med Oncol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Ctr Learning Healthcare, Durham, NC 27705 USA.;Duke Canc Inst, Durham, NC USA..
    Krucoff, Mitchell W.
    Duke Univ, Div Cardiol, Dept Med, Med Ctr, Durham, NC USA.;Duke Clin Res Inst, Durham, NC 27705 USA..
    Relationship Between Cancer and Cardiovascular Outcomes Following Percutaneous Coronary Intervention2015In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, no 7, article id e001779Article in journal (Refereed)
    Abstract [en]

    Background-Cardiovascular disease and cancer increasingly coexist, yet relationships between cancer and long-term cardiovascular outcomes post-percutaneous coronary intervention (PCI) are not well studied. Methods and Results-We examined stented PCI patients at Duke (1996-2010) using linked data from the Duke Information Systems for Cardiovascular Care and the Duke Tumor Registry (a cancer treatment registry). Our primary outcome was cardiovascular mortality. Secondary outcomes included composite cardiovascular mortality, myocardial infarction, or repeat revascularization and all-cause mortality. We used adjusted cause-specific hazard models to examine outcomes among cancer patients (cancer treatment pre-PCI) versus controls (no cancer treatment pre-PCI). Cardiovascular mortality was explored in a cancer subgroup with recent (within 1 year pre-PCI) cancer and in post-PCI cancer patients using post-PCI cancer as a time-dependent variable. Among 15 008 patients, 3.3% (n=496) were cancer patients. Observed rates of 14-year cardiovascular mortality (31.4% versus 27.7%, P=0.31) and composite cardiovascular death, myocardial infarction, or revascularization (51.1% versus 55.8%, P=0.37) were similar for cancer versus control groups; all-cause mortality rates were higher (79.7% versus 49.3%, P<0.01). Adjusted risk of cardiovascular mortality was similar for cancer patients versus controls (hazard ratio 0.95; 95% CI 0.76 to 1.20) and for patients with versus without recent cancer (hazard ratio 1.46; 95% CI 0.92 to 2.33). Post-PCI cancer, present in 4.3% (n=647) of patients, was associated with cardiovascular mortality (adjusted hazard ratio 1.51; 95% CI 1.11 to 2.03). Conclusions-Cancer history was present in a minority of PCI patients but was not associated with worse long-term cardiovascular outcomes. Further investigation into PCI outcomes in this population is warranted.

  • 36.
    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.
    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.
    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.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B.
    Duke Univ, Med Ctr, Durham, NC USA..
    Alexander, John H.
    Duke Univ, Med Ctr, Durham, NC USA..
    Gersh, Bernard J.
    Mayo Clin, Coll Med, Rochester, MN USA..
    Hanna, Michael
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Harjola, Veli-Pekka
    Helsinki Univ Cent Hosp, Div Emergency Care, Dept Med, Helsinki, Finland..
    Hylek, Elaine M.
    Boston Univ, Med Ctr, Boston, MA USA..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Durham, NC 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.
    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.
    Repeated Measurements of Cardiac Biomarkers in Atrial Fibrillation and Validation of the ABC Stroke Score Over Time2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 6, article id e004851Article in journal (Refereed)
    Abstract [en]

    Background: Cardiac biomarkers are independent risk markers in atrial fibrillation, and the novel biomarker-based ABC stroke score (age, biomarkers, and clinical history of prior stroke) was recently shown to improve the prediction of stroke risk in patients with atrial fibrillation. Our aim was to investigate the short-term variability of the cardiac biomarkers and evaluate whether the ABC stroke risk score provides a stable short- term risk estimate.

    Methods and Results: According to the study protocol, samples were obtained at entry and also at 2 months in 4796 patients with atrial fibrillation followed for a median of 1.8 years in the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial. Cardiac troponin I, cardiac troponin T, and N-terminal pro-B-type natriuretic peptide were measured with high-sensitivity immunoassays. Associations with outcomes were evaluated by Cox regression. C indices and calibration plots were used to evaluate the ABC stroke score at 2 months. The average changes in biomarker levels during 2 months were small ( median change cardiac troponin T +2.8%, troponin I +2.0%, and N-terminal pro-B-type natriuretic peptide +13.5%) and within-subject correlation was high ( all >= 0.82). Repeated measurement of cardiac biomarkers provided some incremental prognostic value for mortality but not for stroke when combined with clinical risk factors and baseline levels of the biomarkers. Based on 8702 person-years of follow-up and 96 stroke/systemic embolic events, the ABC stroke score at 2 months achieved a similar C index of 0.70 (95% CI, 0.65-0.76) as compared with 0.70 (95% CI, 0.65-0.75) at baseline. The ABC stroke score remained well calibrated using predefined risk classes.

    Conclusions: In patients with stable atrial fibrillation, the variability of the cardiac biomarkers and the biomarker- based ABC stroke score during 2 months are small. The prognostic information by the ABC stroke score remains consistent and well calibrated with similar good predictive performance if patients are retested after 2 months.

    Clinical Trial Registration --URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

  • 37.
    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.

  • 38.
    Hu, Peter T.
    et al.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA..
    Lopes, Renato D.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Stevens, Susanna R.
    Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Thomas, Laine
    Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Alexander, John H.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Hanna, Michael
    Bristol Myers Squibb Co, Princeton, NJ USA..
    Lewis, Basil S.
    Technion, Ruth & Bruce Rappaport Sch Med, Lady Davis Carmel Med Ctr, Haifa, Israel..
    Verheugt, Freek W. A.
    Radboud Univ Nijmegen, Med Ctr, Nijmegen, Netherlands..
    Granger, Christopher B.
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Jones, W. Schuyler
    Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.;Duke Univ, Duke Clin Res Inst, Durham, NC USA..
    Efficacy and Safety of Apixaban Compared With Warfarin in Patients With Atrial Fibrillation and Peripheral Artery Disease: Insights From the ARISTOTLE Trial2017In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 6, no 1, article id e004699Article in journal (Refereed)
    Abstract [en]

    Background- We studied (1) the rates of stroke or systemic embolism and bleeding in patients with atrial fibrillation and peripheral artery disease (PAD) and (2) the efficacy and safety of apixaban versus warfarin in patients with atrial fibrillation with and without PAD. Methods and Results- The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin for stroke/systemic embolism prevention; 884 (4.9%) patients had PAD at baseline. Patients with PAD had higher unadjusted rates of stroke and systemic embolism (hazard ratio [HR] 1.73, 95% CI 1.22-2.45; P=0.002) and major bleeding (HR 1.34, 95% CI 1.00-1.81; P=0.05), but after adjustment, no differences existed in rates of stroke and systemic embolism (HR 1.32, 95% CI 0.93-1.88; P=0.12) and major bleeding (HR 1.03, 95% CI 0.76-1.40; P=0.83) compared with patients without PAD. The risk of stroke or systemic embolism was similar in patients assigned to apixaban and warfarin with PAD (HR 0.63, 95% CI 0.32-1.25) and without PAD (HR 0.80, 95% CI 0.66-0.96; interaction P= 0.52). Patients with PAD did not have a statistically significant reduction in major or clinically relevant nonmajor bleeding with apixaban compared with warfarin (HR 1.05, 95% CI 0.69-1.58), whereas those without PAD had a statistically significant reduction (HR 0.65, 95% CI 0.58-0.73; interaction P=0.03). Conclusions- Patients with PAD in ARISTOTLE had a higher crude risk of stroke or systemic embolism compared with patients without PAD that was not present after adjustment. The benefits of apixaban versus warfarin for stroke and systemic embolism were similar in patients with and without PAD. These findings highlight the need to optimize the treatment of patients with atrial fibrillation and PAD.

  • 39. Hållmarker, Ulf
    et al.
    Åsberg, Signild
    Michaëlsson, Karl
    Ärnlöv, Johan
    Hellberg, Dan
    Lindbäck, Johan
    Wester, Per
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    James, Stefan
    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.

  • 40.
    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.

  • 41. Iggman, David
    et al.
    Rosqvist, Fredrik
    Larsson, Anders
    Ärnlöv, Johan
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Uppsala universitet.
    Beckman, Lena
    Rudling, Mats
    Risérus, Ulf
    Role of dietary fats in modulating cardiometabolic risk during moderate weight gain: a randomized double-blind overfeeding trial (LIPOGAIN study)2014In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 3, no 5, article id e001095Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.

    METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).

    CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.

    CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

  • 42.
    Iggman, David
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Rosqvist, Fredrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Ärnlöv, Johan
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Beckman, Lena
    Rudling, Mats
    Risérus, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Role of Dietary Fats in Modulating Cardiometabolic Risk During Moderate Weight Gain: A Randomized Double-Blind Overfeeding Trial (LIPOGAIN Study)2014In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 3, no 5, article id e001095Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Whether the type of dietary fat could alter cardiometabolic responses to a hypercaloric diet is unknown. In addition, subclinical cardiometabolic consequences of moderate weight gain require further study.

    METHODS AND RESULTS: In a 7-week, double-blind, parallel-group, randomized controlled trial, 39 healthy, lean individuals (mean age of 27±4) consumed muffins (51% of energy [%E] from fat and 44%E refined carbohydrates) providing 750 kcal/day added to their habitual diets. All muffins had identical contents, except for type of fat; sunflower oil rich in polyunsaturated fatty acids (PUFA diet) or palm oil rich in saturated fatty acids (SFA diet). Despite comparable weight gain in the 2 groups, total: high-density lipoprotein (HDL) cholesterol, low-density lipoprotein:HDL cholesterol, and apolipoprotein B:AI ratios decreased during the PUFA versus the SFA diet (-0.37±0.59 versus +0.07±0.29, -0.31±0.49 versus +0.05±0.28, and -0.07±0.11 versus +0.01±0.07, P=0.003, P=0.007, and P=0.01 for between-group differences), whereas no significant differences were observed for other cardiometabolic risk markers. In the whole group (ie, independently of fat type), body weight increased (+2.2%, P<0.001) together with increased plasma proinsulin (+21%, P=0.007), insulin (+17%, P=0.003), proprotein convertase subtilisin/kexin type 9, (+9%, P=0.008) fibroblast growth factor-21 (+31%, P=0.04), endothelial markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin (+9, +5, and +10%, respectively, P<0.01 for all), whereas nonesterified fatty acids decreased (-28%, P=0.001).

    CONCLUSIONS: Excess energy from PUFA versus SFA reduces atherogenic lipoproteins. Modest weight gain in young individuals induces hyperproinsulinemia and increases biomarkers of endothelial dysfunction, effects that may be partly outweighed by the lipid-lowering effects of PUFA.

    CLINICAL TRIAL REGISTRATION URL: http://ClinicalTrials.gov. Unique identifier: NCT01427140.

  • 43.
    Kjellqvist, Sanela
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Klose, Christian
    Surma, Michal A.
    Hindy, George
    Mollet, Ines G.
    Johansson, Anna
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Chavaux, Patrick
    Gottfries, Johan
    Simons, Kai
    Melander, Olle
    Fernandez, Celine
    Identification of Shared and Unique Serum Lipid Profiles in Diabetes Mellitus and Myocardial Infarction2016In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, no 12, article id e004503Article in journal (Refereed)
    Abstract [en]

    Background-Diabetes mellitus (DM) and cardiovascular disease are associated with dyslipidemia, but the detailed lipid molecular pattern in both diseases remains unknown. Methods and Results-We used shotgun mass spectrometry to determine serum levels of 255 molecular lipids in 316 controls, 171 DM, and 99 myocardial infarction (MI) events from a cohort derived from the Malmo Diet and Cancer study. Orthogonal projections to latent structures analyses were conducted between the lipids and clinical parameters describing DM or MI. Fatty acid desaturases (FADS) and elongation of very long chain fatty acid protein 5 (ELOVL5) activities were estimated by calculating product to precursor ratios of polyunsaturated fatty acids in complex lipids. FADS genotypes encoding these desaturases were then tested for association with lipid levels and ratios. Differences in the levels of lipids belonging to the phosphatidylcholine and triacylglyceride (TAG) classes contributed the most to separating DM from controls. TAGs also played a dominating role in discriminating MI from controls. Levels of C18:2 fatty acids in complex lipids were lower both in DM and MI versus controls (DM, P=0.004; MI, P=6.0E-06) at least due to an acceleration in the metabolic flux from C18: 2 to C20:4 (eg, increased estimated ELOVL5: DM, P=0.02; MI, P=0.04, and combined elongase-desaturase activities: DM, P=3.0E-06; MI, P=2.0E-06). Minor allele carriers of FADS genotypes were associated with increased levels of C18: 2 (P <= 0.007) and lower desaturase activity (P <= 0.002). Conclusions-We demonstrate a possible relationship between decreased levels of C18: 2 in complex lipids and DM or MI. We thereby highlight the importance of molecular lipids in the pathogenesis of both diseases.

  • 44. Koul, Sasha
    et al.
    Andell, Pontus
    Martinsson, Andreas
    Smith, J. Gustav
    van der Pals, Jesper
    Schersten, Fredrik
    Jernberg, Tomas
    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.
    Erlinge, David
    Delay From First Medical Contact to Primary PCI and All-Cause Mortality: A Nationwide Study of Patients With ST-Elevation Myocardial Infarction2014In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 3, no 2, p. e000486-Article in journal (Refereed)
    Abstract [en]

    Background-Early reperfusion in the setting of an ST-elevation myocardial infarction (STEMI) is of utmost importance. However, the effects of early versus late reperfusion in this patient group undergoing primary percutaneous coronary intervention (PCI) have so far been inconsistent in previous studies. The purpose of this study was to evaluate in a nationwide cohort the effects of delay from first medical contact to PCI (first medical contact [FMC]-to-PCI) and secondarily delay from symptom-to-PCI on clinical outcomes. Methods and Results-Using the national Swedish Coronary Angiography and Angioplasty Register (SCAAR) registry, STEMI patients undergoing primary PCI between the years 2003 and 2008 were screened for. A total of 13 790 patients were included in the FMC-to-PCI analysis and 11 489 patients were included in the symptom-to-PCI analyses. Unadjusted as well as multivariable analyses showed an overall significant association between increasing FMC-to-PCI delay and 1-year mortality. A statistically significant increase in mortality was noted at FMC-to-PCI delays exceeding 1 hour in an incremental fashion. FMC-to-PCI delays in excess of 1 hour were also significantly associated with an increase in severe left ventricular dysfunction at discharge. An overall significant association between increasing symptom-to-PCI delays and 1-year mortality was noted. However, when stratified into time delay cohorts, no symptom-to-PCI delay except for the highest time delay showed a statistically significant association with increased mortality. Conclusions-Delays in FMC-to-PCI were strongly associated with increased mortality already at delays of more than 1 hour, possibly through an increase in severe heart failure. A goal of FMC-to-PCI of less than 1 hour might save patient lives.

  • 45. Lallukka, Tea
    et al.
    Ervasti, Jenni
    Lundström, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Neurology.
    Mittendorfer-Rutz, Ellenor
    Friberg, Emilie
    Virtanen, Marianna
    Alexanderson, Kristina
    Trends in Diagnosis-Specific Work Disability Before and After Stroke: A Longitudinal Population-Based Study in Sweden.2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e006991Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although a stroke event often leads to work disability, diagnoses behind work disability before and after stroke are largely unknown. We examined the pre-event and postevent trends in diagnosis-specific work disability among patients of working age.

    METHODS AND RESULTS: We included all new nonfatal stroke events in 2006-2008 from population-based hospital registers in Sweden among women and men aged 25 to 60 years (n=12 972). Annual days of diagnosis-specific work disability were followed for 4 years before and after stroke. Repeated measures negative binomial regression models using the generalized estimating equations method were fitted to examine trends in diagnosis-specific work disability before and after the event. Already during the 4 pre-event years, work disability attributed to circulatory diseases increased among women (rate ratio, 1.99; 95% confidence interval, 1.68-2.36) and men (rate ratio, 2.20; 95% confidence interval, 1.88-2.57). Increasing trends before stroke were also found for work disability attributed to mental disorders, musculoskeletal diseases, neoplasms, diseases of the nervous, respiratory, and digestive systems, injuries, and diabetes mellitus. As expected, a sharp increase in work disability days attributed to circulatory diseases was found during the first year after the event among both sexes. Overall, during 4 years after the stroke, there was a decreasing trend for circulatory diseases and injuries, whereas the trend was increasing for nervous diseases and diabetes mellitus.

    CONCLUSIONS: Work disability attributed to several mental and somatic diagnoses is higher already before a stroke event.

  • 46. Langrish, Jeremy P
    et al.
    Unosson, Jon
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Bosson, Jenny
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Barath, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Muala, Ala
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Blackwell, Scott
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Pourazar, Jamshid
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Megson, Ian L
    Treweeke, Andrew
    Sandström, Thomas
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Newby, David E
    Blomberg, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Mills, Nicholas L
    Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man2013In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 2, no 1, p. e004309-Article in journal (Refereed)
    Abstract [en]

    Background Diesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects.

    Methods and Results In 2 randomized double-blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air. Study 1: Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 mu g/min) and sodium nitroprusside (SNP; 2 to 8 mu g/min) in the presence of the NO clamp (NO synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) 8 mu g/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow). Study 2: Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenous L-NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68 +/- 48 versus 41 +/- 32 nmol/L; P=0.006) despite similar L-NMMA-induced reductions in basal blood flow (-20.6 +/- 14.7% versus -21.1 +/- 14.6%; P=0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose-dependent vasodilatation that was not affected by diesel exhaust inhalation (P>0.05 for both). Following exposure to diesel exhaust, L-NMMA caused a greater increase in blood pressure (P=0.048) and central arterial stiffness (P=0.007), but reductions in cardiac output and increases in systemic vascular resistance (P>0.05 for both) were similar to those seen with filtered air.

    Conclusions Diesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability.

  • 47.
    Lennie, Terry A
    et al.
    College of Nursing, University of Kentucky, Lexington, KY, USA.
    Andreae, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Rayens, Mary K
    College of Nursing, University of Kentucky, Lexington, KY, USA.
    Song, Eun Kyeung
    Department of Nursing, College of Medicine, University of Ulsan, Korea.
    Dunbar, Sandra B
    Emory University, Atlanta, GA, USA.
    Pressler, Susan J
    Indiana University, Indianapolis, IN, USA.
    Heo, Seongkum
    College of Nursing, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
    Kim, JinShil
    Gachon University College of Nursing, Incheon, Korea.
    Moser, Debra K
    College of Nursing, University of Kentucky, Lexington, KY, USA.
    Micronutrient Deficiency Independently Predicts Time to Event in Patients with Heart Failure2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 17, p. 1-10, article id e007251Article in journal (Refereed)
    Abstract [en]

    Dietary micronutrient deficiencies have been shown to predict event‐free survival in other countries but have not been examined in patients with heart failure living in the United States. The purpose of this study was to determine whether number of dietary micronutrient deficiencies in patients with heart failure was associated with shorter event‐free survival, defined as a combined end point of all‐cause hospitalization and death.

  • 48. Lennie, Terry A
    et al.
    Andreae, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD).
    Rayens, Mary Kay
    Song, Eun Kyeung
    Dunbar, Sandra B
    Pressler, Susan J
    Heo, Seongkum
    Kim, JinShil
    Moser, Debra K
    Micronutrient Deficiency Independently Predicts Time to Event in Patients With Heart Failure.2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 17, article id e007251Article in journal (Refereed)
    Abstract [en]

    Background Dietary micronutrient deficiencies have been shown to predict event-free survival in other countries but have not been examined in patients with heart failure living in the United States. The purpose of this study was to determine whether number of dietary micronutrient deficiencies in patients with heart failure was associated with shorter event-free survival, defined as a combined end point of all-cause hospitalization and death. Methods and Results Four-day food diaries were collected from 246 patients with heart failure (age: 61.5±12 years; 67% male; 73% white; 45% New York Heart Association [NYHA] class III / IV ) and analyzed using Nutrition Data Systems for Research. Micronutrient deficiencies were determined according to methods recommended by the Institute of Medicine. Patients were followed for 1 year to collect data on all-cause hospitalization or death. Patients were divided according to number of dietary micronutrient deficiencies at a cut point of ≥7 for the high deficiency category versus <7 for the no to moderate deficiency category. In the full sample, 29.8% of patients experienced hospitalization or death during the year, including 44.3% in the high-deficiency group and 25.1% in the no/moderate group. The difference in survival distribution was significant (log rank, P=0.0065). In a Cox regression, micronutrient deficiency category predicted time to event with depression, NYHA classification, comorbidity burden, body mass index, calorie and sodium intake, and prescribed angiotensin-converting enzyme inhibitors, diuretics, or β-blockers included as covariates. Conclusions This study provides additional convincing evidence that diet quality of patients with heart failure plays an important role in heart failure outcomes.

  • 49.
    Lind, Lars
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lampa, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Impact of Aging on the Strength of Cardiovascular Risk Factors: A Longitudinal Study Over 40 Years2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007061Article in journal (Refereed)
    Abstract [en]

    Background-The knowledge of the impact of cardiovascular risk factors at different ages has mainly been based on different studies performed at different ages. This study aimed to investigate the change in impact of traditional cardiovascular risk factors over the aging process in subjects followed for 4 decades. Methods and Results-In the ULSAM (Uppsala Longitudinal Study of Adult Men) study, 2322 men originally investigated in 1970 to 1974 have been followed regarding cardiovascular diseases until the end of 2013. This cohort has been investigated physically at ages 50, 60, 70, 77, and 82 years regarding body mass index, low-density lipoprotein-and high-density lipoprotein-cholesterol, triglycerides, systolic blood pressure and diastolic blood pressure, fasting glucose, and smoking. These data were used to model the interactions between risk factors and age regarding incident myocardial infarction (n=540), ischemic stroke (n=343), or heart failure (n=397). Significant interactions were observed between age and the set of traditional risk factors regarding all 3 outcomes (P<0.05 for all). Generally, a decline in the rate ratios was seen with aging for most risk factors, being most pronounced for body mass index regarding myocardial infarction and for systolic blood pressure regarding ischemic stroke and heart failure. However, low-density lipoprotein-cholesterol was significantly related to incident myocardial infarction, whereas both body mass index and fasting glucose were significantly related to incident heart failure also at a high age. Conclusions-Using a longitudinal design in middle-aged men spanning 4 decades showed that the impact of traditional cardiovascular risk factors generally declined with aging. However, some of the risk factors remained significantly associated with incident cardiovascular disease also at old age.

  • 50.
    Lindholm, Daniel
    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.
    Fukaya, Eri
    Leeper, Nicholas J
    Ingelsson, Erik
    Bioimpedance and New-Onset Heart Failure: A Longitudinal Study of >500 000 Individuals From the General Population.2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 13, article id e008970Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Heart failure constitutes a high burden on patients and society, but although lifetime risk is high, it is difficult to predict without costly or invasive testing. We aimed to establish new risk factors of heart failure, which potentially could enable early diagnosis and preemptive treatment.

    METHODS AND RESULTS: We applied machine learning in the UK Biobank in an agnostic search of risk factors for heart failure in 500 451 individuals, excluding individuals with prior heart failure. Novel factors were then subjected to several in-depth analyses, including multivariable Cox models of incident heart failure, and assessment of discrimination and calibration. Machine learning confirmed many known and putative risk factors for heart failure and identified several novel candidates. Mean reticulocyte volume appeared as one novel factor and leg bioimpedance another, the latter appearing as the most important new marker. Leg bioimpedance was lower in those who developed heart failure during an up to 9.8-year follow-up. When adjusting for known heart failure risk factors, leg bioimpedance was inversely related to heart failure (hazard ratio [95% confidence interval], 0.60 [0.48-0.73] and 0.75 [0.59-0.94], in age- and sex-adjusted and fully adjusted models, respectively, comparing the upper versus lower quartile). A model including leg bioimpedance, age, sex, and self-reported history of myocardial infarction showed good discrimination for future heart failure hospitalization (Concordance index [C-index]=0.82) and good calibration.

    CONCLUSIONS: Leg bioimpedance is inversely associated with heart failure incidence in the general population. A simple model of exclusively noninvasive measures, combining leg bioimpedance with history of myocardial infarction, age, and sex provides accurate predictive capacity.

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