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  • 3401.
    Venetsanos, D.
    et al.
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    Lawesson, S. Sederholm
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Erlinge, D.
    Skane Univ Hosp, Lund, Sweden..
    Koul, S.
    Skane Univ Hosp, Lund, Sweden..
    Swahn, E.
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    Alfredsson, J.
    Linkoping Univ Hosp, Cardiol, Linkoping, Sweden..
    Bivalirudin versus UFH with or without GP IIb/IIIa inhibitors in patients with ST-elevation myocardial infarction undergoing primary PCI2016Conference paper (Refereed)
  • 3402.
    Venetsanos, D.
    et al.
    Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Sederholm Lawesson, S.
    Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Omerovic, E.
    Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Henareh, L.
    Department of Medicine, Karolinska Institute, Stockholm, Sweden.
    Robertsson, L.
    Department of Cardiology, Södra Älvsborgs Sjukhus, Borås, Sweden.
    Linder, R.
    Department of Cardiology, Danderyd Hospital, Stockholm, Sweden.
    Götberg, M.
    Department of Cardiology, Skåne University Hospital, Sweden.
    James, S.
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Alfredsson, J.
    Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Erlinge, D.
    Department of Cardiology, Skåne University Hospital, Sweden.
    Swahn, E.
    Department of Cardiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
    Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A subgroup analysis of the VALIDATE-SWEDEHEART trial2018In: European heart journal: Acute cardiovascular care, ISSN 2048-8734Article in journal (Refereed)
    Abstract [en]

    AIMS: Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.

    METHODS: This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.

    RESULTS: There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54-1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94-1.43) in men, p for interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54-1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93-1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women.

    CONCLUSION: In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

  • 3403.
    Venetsanos, Dimitrios
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Improving management of STEMI patients treated with primary PCI: Pharmacotherapy, renal function estimation and gender perspective2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI.

    In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p<0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03).

    In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01).

    In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment.

    In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI.

    MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03).

    Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients

  • 3404.
    Venetsanos, Dimitrios
    et al.
    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.
    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.
    Segelmark, Mårten
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Nephrology.
    Swahn, Eva
    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.
    Lawesson, Sofia
    Linköping University, Department of Medical and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Glomerular filtration rate (GFR) during and after STEMI: a single-centre, methodological study comparing estimated and measured GFR2015In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 5, no 9, p. 1-8, article id e007835Article in journal (Refereed)
    Abstract [en]

    Objectives: To validate the performance of the most commonly used formulas for estimation of glomerular filtration rate (GFR) against measured GFR during the index hospitalisation for ST-elevation myocardial infarction (STEMI). Setting: Single centre, methodological study. Participants: 40 patients with percutaneous coronary intervention-treated STEMI were included between November 2011 and February 2013. Patients on dialysis, cardiogenic shock or known allergy to iodine were excluded. Outcome measures: Creatinine and cystatin C were determined at admission and before discharge in 40 patients with STEMI. Clearance of iohexol was measured (mGFR) before discharge. We evaluated and compared the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rG-CystC) with GFR regarding correlation, bias, precision and accuracy (P30). Agreement between eGFR and mGFR to discriminate CKD was assessed by Cohens. statistics. Results: MDRD-IDMS and CKD-EPI demonstrated good performance to estimate GFR (correlation 0.78 vs 0.81%, bias -1.3% vs 1.5%, precision 17.9 vs 17.1 mL/min 1.73 m(2) and P30 82.5% vs 82.5% for MDRD-IDMS vs CKD-EPI). CKD was best classified by CKD-EPI (. 0.83). CG showed the worst performance (correlation 0.73%, bias -1% to 3%, precision 22.5 mL/min 1.73 m(2) and P30 75%). The rG-CystC formula had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). At arrival, CKD-EPI and rG-CystC had almost perfect agreement in CKD classification (kappa=0.87), whereas at discharge agreement was substantially lower (kappa=0.59) and showed a significant discrepancy in CKD classification (p=0.02). Median cystatin C concentration increased by 19%. Conclusions: In acute STEMI, CKD-EPI showed the best CKD-classification ability followed by MDRD-IDMS, whereas CG performed the worst. STEMI altered the performance of the cystatin C equation during the acute phase, suggesting that other factors might be involved in the rise of cystatin C.

  • 3405.
    Venetsanos, Dimitrios
    et al.
    Linkoping Univ, Dept Cardiol, SE-58183 Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
    Lawesson, Ofia Sederholm
    Linkoping Univ, Dept Cardiol, SE-58183 Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Koul, Sasha
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Clin Sci, Lund, Sweden.
    Swahn, Eva
    Linkoping Univ, Dept Cardiol, SE-58183 Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, SE-58183 Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, SE-58183 Linkoping, Sweden.
    Bivalirudin versus heparin with primary percutaneous coronary intervention2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 201, p. 9-16Article in journal (Refereed)
    Abstract [en]

    Background: Optimal adjunctive therapy in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI (PPCI) remains a matter of debate. Our aim was to compare the efficacy and safety of bivalirudin to unfractionated heparin (UFH), with or without glycoprotein IIb/IIIa inhibitors (GPI) in a large real-world population, using data from the Swedish national registry, SWEDEHEART. Method: From 2008 to 2014 we identified 23,800 STEMI patients presenting within 12 hours from symptom onset treated with PPCI and UFH +/- GPI or bivalirudin +/- GPI. Primary outcomes included 30-day all-cause mortality and major in-hospital bleeding. Multivariable regression models and propensity score modelling were utilized to study adjusted association between treatment and outcome. Results: Treatment with UFH +/- GPI was associated with similar risk of 30-day mortality compared to bivalirudin +/- GPI (5.3% vs 5.5%, adjusted HR 0.94; 95% CI 0.82-1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between UFH +/- GPI and bivalirudin +/- GPI. In contrast, treatment with UFH +/- GPI was associated with a significant higher risk of major in-hospital bleeding (adjusted OR 1.62; 95% CI 1.30-2.03). When including GPI use in the multivariable analysis, the difference was attenuated and no longer significant (adjusted OR 1.25; 95% CI 0.92-1.70). Conclusion: Bivalirudin +/- GPI was associated with significantly lower risk for major in hospital bleeding but no significant difference in 30-day or one year mortality, stent thrombosis or re-infarction compared with UFH +/- GPI. The bleeding reduction associated with bivalirudin could be explained by the greater GPI use with UFH.

  • 3406.
    Venetsanos, Dimitrios
    et al.
    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, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Sederholm Lawesson, Sofia
    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.
    Gustafsson, Kerstin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Wallen, Hakan
    Karolinska Institute, Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Stockholm, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Swahn, Eva
    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.
    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.
    Pretreatment with ticagrelor may offset additional inhibition of platelet and coagulation activation with bivalirudin compared to heparin during primary percutaneous coronary intervention2018In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 171, p. 38-44Article in journal (Refereed)
    Abstract [en]

    Background

    It remains unknown if bivalirudin compared to heparin confers any additional inhibition of platelet and coagulation activation during primary percutaneous coronary intervention(PPCI) after pretreatment with ticagrelor.

    Methods

    In this substudy of VALIDATE-SWEDEHEART trial, 103 patients pretreated with ticagrelor were randomized before PPCI to heparin or bivalirudin. Blood samples were collected before and 1 and 12 h after PPCI. We measured platelet reactivity (PR) using Multiplate, soluble P-selectin, thrombin-antithrombin complexes (TAT) and prothrombin fragments 1 + 2 (F1 + 2) as markers of platelet and coagulation activation.

    Results

    The median (IQR) time from ticagrelor administration to randomization was 63 (29) vs 60 (24) minutes, p = 0.28. ADP-induced PR did not significantly differ between groups over time (heparin vs bivalirudin, AUC 73 (62) vs 74 (68), p = 0.74, 32 (42) vs 43 (51), p = 0.38, 15 (15) vs 19 (15), p = 0.29, before, 1 and 12 h after PPCI). Soluble P-selectin did not significantly differ between groups. At 1 h TAT significantly increased with bivalirudin (3.0 (1.3) to 4.3 (4.2) ug/L; p < 0.01), but not with UFH (3.1 (2.1) to 3.5 (1.6) ug/L, p = 0.24). F1 + 2 increased in both groups but the rise was numerically higher with bivalirudin (170 (85) to 213 (126) pmol/L vs 168 (118) to 191 (103) pmol/L). At 12 h, a comparable significant increase in thrombin generation was observed in both groups.

    Conclusion

    In patients treated with ticagrelor, we found no major differences between bivalirudin and heparin in platelet aggregation or coagulation markers, which is in agreement with the neutral clinical results of the VALIDATE-SWEDEHEART study.

  • 3407.
    Venetsanos, Dimitrios
    et al.
    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.
    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.
    Janzon, Magnus
    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.
    Cequier, Angel
    University of Barcelona, Spain.
    Chettibi, Mohamed
    CHU Frantz Fanon, Algeria.
    Goodman, Shaun G.
    University of Toronto, Canada.
    vant Hof, Arnoud W.
    Isala Clin, Netherlands.
    Montalescot, Gilles
    Sorbonne University, France.
    Swahn, Eva
    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.
    Association between gender and short-term outcome in patients with ST elevation myocardial infraction participating in the international, prospective, randomised Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial: a prespecified analysis2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 9, article id e015241Article in journal (Refereed)
    Abstract [en]

    Objectives To evaluate gender differences in outcomes in patents with ST-segment elevation myocardial infarction (STEMI) planned for primary percutaneous coronary intervention (PPCI). Settings A prespecified gender analysis of the multicentre, randomised, double-blind Administration of Ticagrelor in the catheterisation Laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery. Participants Between September 2011 and October 2013, 1862 patients with STEMI and symptom duration amp;lt;6 hours were included. Interventions Patients were assigned to prehospital versus in-hospital administration of 180 mg ticagrelor. Outcomes The main objective was to study the association between gender and primary and secondary outcomes of the main study with a focus on the clinical efficacy and safety outcomes. Primary outcome: the proportion of patients who did not have 70% resolution of ST-segment elevation and did not meet the criteria for Thrombolysis In Myocardial Infarction (TIMI) flow 3 at initial angiography. Secondary outcome: the composite of death, MI, stent thrombosis, stroke or urgent revascularisation and major or minor bleeding at 30 days. Results Women were older, had higher TIMI risk score, longer prehospital delays and better TIMI flow in the infarct-related artery. Women had a threefold higher risk for all-cause mortality compared with men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 to 5.51). After adjustment, the difference was attenuated but remained statistically significant (HR 2.08, 95% CI 1.03 to 4.20). The incidence of major bleeding events was twofold to threefold higher in women compared with men. In the multivariable model, female gender was not an independent predictor of bleeding (Platelet Inhibition and Patient Outcomes major HR 1.45, 95% CI 0.73 to 2.86, TIMI major HR 1.28, 95% CI 0.47 to 3.48, Bleeding Academic Research Consortium type 3-5 HR 1.45, 95% CI 0.72 to 2.91). There was no interaction between gender and efficacy or safety of randomised treatment. Conclusion In patients with STEMI planned for PPCI and treated with modern antiplatelet therapy, female gender was an independent predictor of short-term mortality. In contrast, the higher incidence of bleeding complications in women could mainly be explained by older age and clustering of comorbidities.

  • 3408.
    Venetsanos, Dimitrios
    et al.
    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.
    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.
    Fröbert, O.
    Department of Cardiology, Örebro University, Sweden.
    Omerovic, E.
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Henareh, L.
    Department of Medicine, Karolinska Institute, Sweden.
    Robertsson, L.
    Department of Cardiology, Södra Älvsborgs Sjukhus, Sweden.
    Linder, R.
    Department of Cardiology, Danderyd Hospital, Sweden.
    Götberg, M.
    Department of Cardiology, Skåne University Hospital, Sweden.
    James, S.
    Department of Medical Sciences, Uppsala University, Sweden.
    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.
    Erlinge, D.
    Department of Cardiology, Skåne University Hospital, Sweden.
    Swahn, Eva
    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.
    Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention: A subgroup analysis of the VALIDATE-SWEDEHEART trial2018In: European Heart Journal. Acute Cardiovascular Care, ISSN 2048-8734Article in journal (Refereed)
    Abstract [en]

    Aims:

    Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.

    Methods:

    This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.

    Results:

    There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60–1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89–1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54–1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94–1.43) in men, pfor interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54–1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93–1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women.

    Conclusion:

    In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.

  • 3409.
    Venetsanos, Dimitrios
    et al.
    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.
    Sederholm Lawesson, Sofia
    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.
    James, Stefan
    Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
    Koul, Sasha
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Erlinge, David
    Department of Cardiology, Clinical Sciences, Lund University, Skåne University Hospital, Lund, Sweden.
    Swahn, Eva
    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.
    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.
    Bivalirudin versus heparin with primary percutaneous coronary intervention2018In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 201, p. 9-16Article in journal (Refereed)
    Abstract [en]

    Background: Optimal adjunctive therapy in ST-segment elevation myocardial infarction (STEMI) patients treated with primary PCI (PPCI) remains a matter of debate. Our aim was to compare the efficacy and safety of bivalirudin to unfractionated heparin (UFH), with or without glycoprotein IIb/IIIa inhibitors (GPI) in a large real-world population, using data from the Swedish national registry, SWEDEHEART. Method: From 2008 to 2014 we identified 23,800 STEMI patients presenting within 12 hours from symptom onset treated with PPCI and UFH +/- GPI or bivalirudin +/- GPI. Primary outcomes included 30-day all-cause mortality and major in-hospital bleeding. Multivariable regression models and propensity score modelling were utilized to study adjusted association between treatment and outcome. Results: Treatment with UFH +/- GPI was associated with similar risk of 30-day mortality compared to bivalirudin +/- GPI (5.3% vs 5.5%, adjusted HR 0.94; 95% CI 0.82-1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between UFH +/- GPI and bivalirudin +/- GPI. In contrast, treatment with UFH +/- GPI was associated with a significant higher risk of major in-hospital bleeding (adjusted OR 1.62; 95% CI 1.30-2.03). When including GPI use in the multivariable analysis, the difference was attenuated and no longer significant (adjusted OR 1.25; 95% CI 0.92-1.70). Conclusion: Bivalirudin +/- GPI was associated with significantly lower risk for major in hospital bleeding but no significant difference in 30-day or one year mortality, stent thrombosis or re-infarction compared with UFH +/- GPI. The bleeding reduction associated with bivalirudin could be explained by the greater GPI use with UFH. (C) 2018 Elsevier Inc. All rights reserved.

  • 3410.
    Venetsanos, Dimitrios
    et al.
    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.
    Sederholm Lawesson, Sofia
    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.
    Panayi, Georgios
    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.
    Todt, Tim
    Lund Univ, Sweden.
    Berglund, 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.
    Swahn, Eva
    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.
    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.
    Long-term efficacy of drug coated balloons compared with new generation drug-eluting stents for the treatment of de novo coronary artery lesions2018In: Catheterization and cardiovascular interventions, ISSN 1522-1946, E-ISSN 1522-726X, Vol. 92, no 5, p. E317-E326Article in journal (Refereed)
    Abstract [en]

    Background Studies comparing drug coated balloons (DCB) with new generation drug-eluting stents (nDES) for the treatment of de novo coronary artery lesions are lacking. Methods From 2009 to 2016, DCB or nDES used for treatment of de novo coronary lesions at our institution were included, in total 1,197 DEB and 6,458 nDES. We evaluated target lesions restenosis (TLR) and definite target lesion thrombosis (TLT). Propensity score modeling were utilized to study adjusted associations between treatment and outcomes. Results Median follow-up was 901days. DCB patients were older, with higher cardiovascular risk profile. Bailout stenting after DCB was performed in 8% of lesions. The cumulative rate of TLR and TLT was 7.0 vs. 4.9% and 0.2 vs. 0.8% for DCB vs. nDES, respectively. Before adjustment, DCB was associated with a higher risk of TLR [hazard ratio (HR) 1.44; 95% confidence interval (CI) 1.07-1.94] and a non-significantly lower risk of TLT (HR 0.30; 95% CI 0.07-1.24), compared to nDES. In the propensity matched population consisted of 1,197 DCB and 1,197 nDES, treatment with DCB was associated with similar risk for TLR (adjusted HR 1.05; 95% CI 0.72-1.53) but significantly lower risk for TLT (adjusted HR 0.18; 95% CI 0.04-0.82) compared to nDES. Conclusions Treatment with DCB was associated with a similar risk of TLR and a lower risk of definite TLT compared with nDES. In selected cases, DCB appears as a good alternative to nDES for the treatment of de novo coronary lesions.

  • 3411.
    Venkata Ramanarao, Parasa
    et al.
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Karolinska Inst, Sweden.
    Forsslund, Helena
    Karolinska Inst, Sweden.
    Enger, Tobias
    Karolinska Inst, Sweden.
    Lorenz, Daniel
    Karolinska Inst, Sweden.
    Kullberg, Susanna
    Karolinska Inst, Sweden.
    Eklund, Anders
    Karolinska Inst, Sweden.
    Skold, Magnus
    Karolinska Inst, Sweden.
    Wahlstrom, Jan
    Karolinska Inst, Sweden.
    Grunewald, Johan
    Karolinska Inst, Sweden.
    Brighenti, Susanna
    Karolinska Inst, Sweden.
    Enhanced CD8(+) cytolytic T cell responses in the peripheral circulation of patients with sarcoidosis and non-Lofgrens disease2018In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 138, p. S38-S44Article in journal (Refereed)
    Abstract [en]

    Background: The role of CD4(+) T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8(+) cytolytic T cells (CTLs). Methods: CD8(+) CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8(+) T cells, using flow cytometry. Cytolytic function in blood lymphocytes was assessed using a standard 51Cr-release assay. Patients with Lofgrens syndrome (LS) and an acute disease onset, were compared to non-LS patients with an insidious onset. Results: Higher proportions of peripheral CD8(+) CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to healthy controls. Blood CTLs from non-LS patients had significantly higher expression of perforin, granzyme B and granulysin compared to matched BAL, while LS patients maintained lower levels of effector molecules in both compartments. Mitogen-stimulated peripheral lymphocytes from sarcoidosis patients, particularly from the non-LS group, showed a higher target cell lysis compared to controls. Conclusion: These results demonstrated enhanced peripheral CD8(+) CTL responses in sarcoidosis, especially in non-LS patients who have an increased risk of chronic disease. Further comprehensive clinical studies are warranted to increase our understanding of CD8(+) CTL responses in sarcoidosis.

  • 3412.
    Verdecchia, Paolo
    et al.
    Hosp Assisi, Dept Med, Assisi, Italy..
    Reboldi, Gianpaolo
    Univ Perugia, Dept Med, Perugia, Italy..
    Angeli, Fabio
    Hosp SM Misericordia, Dept Cardiol & Cardiovasc Pathophysiol, Perugia, Italy..
    Mazzotta, Giovanni
    Hosp Assisi, Dept Med, Assisi, Italy..
    Lip, Gregory Y. H.
    Univ Birmingham, Inst Cardiovasc Sci, City Hosp, Birmingham, W Midlands, England..
    Brueckmann, Martina
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany..
    Kleine, Eva
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ezekowitz, Michael D.
    Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA USA.;Coll Med, Wynnewood, PA USA.;Lankenau Med Ctr, Wynnewood, PA USA..
    Yusuf, Salim
    McMaster Univ, Hamilton, ON, Canada..
    Connolly, Stuart J.
    McMaster Univ, Hamilton, ON, Canada..
    Di Pasquale, Giuseppe
    Maggiore Hosp, Dept Cardiol, Bologna, Italy..
    Dabigatran vs. warfarin in relation to the presence of left ventricular hypertrophy in patients with atrial fibrillation-the Randomized Evaluation of Long-term anticoagulation therapY (RE-LY) study2018In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 20, no 2, p. 253-262Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 3413.
    Verheijden Klompstra, Leonie
    et al.
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Jaarsma, Tiny
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Strömberg, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Univ Calif Irvine, CA 92717 USA.
    Self-efficacy Mediates the Relationship Between Motivation and Physical Activity Patients With Heart Failure2018In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 3, p. 211-216Article in journal (Refereed)
    Abstract [en]

    Motivation is necessary in patients with heart failure (HF) who are attempting to become more physically active but may not be sufficient to initiate physical activity. Self-efficacy might explain the relationship between motivation and physical activity. Objective: The aim of this study was to examine the role of exercise self-efficacy in the relationship between exercise motivation and physical activity in patients with HF. Methods: A total of 100 stable patients with HF (88% in New York Heart Association class IVIII; mean age, 67 +/- 13 years; 62% men) were studied. Self-efficacy was measured with the Exercise Self-Efficacy Scale; motivation, with the Exercise Motivation Index; and physical activity, with a self-report questionnaire. Logistic regression analyses were made to examine the mediation effect of exercise self-efficacy on the relationship between exercise motivation and physical activity. Result: Forty-two percent of the 100 patients reported engaging in less than 60 minutes per week of physical activity. Motivation predicted physical activity (b = 0.58, P amp;lt; .05), but after controlling for self-efficacy, the relationship between motivation and physical activity was no longer significant (b = 0.76, P = .06), indicating full mediation. Conclusion: Motivation to be physically active is important but not sufficient. In addition to a high level of motivation to be physically active, it is important that patients with HF have a high degree of self-efficacy.

  • 3414.
    Verhoeven, E. L. G.
    et al.
    Dept Vasc & Endovasc Surg, Paracelsus Med Univ, Nürnberg, Germany.
    Katsargyris, A.
    Dept Vasc & Endovasc Surg, Paracelsus Med Univ, Nürnberg, Germany.
    Bachoo, P.
    Dept Vasc Surg, Aberdeen Royal Infirm, Aberdeen, UK.
    Larzon, Thomas
    Örebro University Hospital. Dept Cardiothorac & Vasc Surg, Örebro University Hospital, Örebro, Sweden.
    Fisher, R.
    Liverpool Vasc & Endovasc Serv, Royal Liverpool Univ Hosp, Liverpool, England.
    Ettles, D.
    Dept Radiol, Hull Royal Infirm, Kingston Upon Hull, England.
    Boyle, J. R.
    Dept Vasc Surg, Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England.
    Brunkwall, J.
    Univ Clin, Dept Vasc & Endovasc Surg, Univ Cologne, Cologne, Germany.
    Boeckler, D.
    Dept Vasc & Endovasc Surg, Univ Heidelberg Hosp, Heidelberg, Germany.
    Florek, H-J
    Dept Vasc & Endovasc Surg, Weisseritztal Kliniken, Freital, Germany.
    Stella, A.
    Dept Vasc Surg, Policlin S Orsola Malpighi, Univ Bologna, Bologna, Italy.
    Kasprzak, P.
    Dept Surg Vasc Surg & Endovasc Surg, Univ Hosp, Univ Regensburg, Regensburg, Germany.
    Verhagen, H.
    Med Ctr, Dept Vasc Surg, Erasmus Univ, Rotterdam, Netherlands.
    Riambau, V.
    Hosp Clin, Thorax Inst, Vasc Surg Div,Dept Cardiovasc Surg, Univ Barcelona, Barcelona, Spain.
    Real-world Performance of the New C3 Gore Excluder Stent-Graft: 1-year Results from the European C3 Module of the Global Registry for Endovascular Aortic Treatment (GREAT)2014In: European Journal of Vascular and Endovascular Surgery, ISSN 1078-5884, E-ISSN 1532-2165, Vol. 48, no 2, p. 131-137Article in journal (Refereed)
    Abstract [en]

    Objectives: The European C3 module of the Global Registry for Endovascular Aortic Treatment (GREAT) provides "real-world" outcomes for the new C3 Gore Excluder stent-graft, and evaluates the new deployment mechanism. This report presents the 1-year results from 400 patients enrolled in this registry. Methods: Between August 2010 and December 2012, 400 patients (86.8% male, mean age 73.9 +/- 7.8 years) from 13 European sites were enrolled in this registry. Patient demographics, treatment indication, case planning, operative details including repositioning and technical results, and clinical outcome were analyzed. Results: Technical success was achieved in 396/400 (99%) patients. Two patients needed intraoperative open conversion, one for iliac rupture, the second because the stent-graft was pulled down during a cross-over catheterization in an angulated anatomy. Two patients required an unplanned chimney renal stent to treat partial coverage of the left renal artery because of upward displacement of the stent-graft. Graft repositioning occurred in 192/399 (48.1%) patients, most frequently for level readjustment with regard to the renal arteries, and less commonly for contralateral gate reorientation. Final intended position of the stent-graft below the renal arteries was achieved in 96.2% of patients. Thirty-day mortality was two (0.5%) patients. Early reintervention (<= 30 days) was required in two (0.5%) patients. Mean follow-up duration was 15.9 +/- 8.8 months (range 0-37 months). Late reintervention (>30 days) was required in 26 (6.5%) patients. Estimated freedom from reintervention at 1 year was 95.2% (95% CI 92.3-97%), and at 2 years 91.5% (95% CI 86.8-94.5%). Estimated patient survival at 1 year was 96% (95% CI 93.3-97.6%) and at 2 years 90.6% (95% CI 85.6-93.9%). Conclusions: Early real-world experience shows that the new C3 delivery system offers advantages in terms of device repositioning resulting in high deployment accuracy. Longer follow-up is required to confirm that this high deployment accuracy results in improved long-term durability.

  • 3415.
    Verma, Subodh
    et al.
    Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, St Michaels Hosp, Toronto ON, Canada; Dept Surg, Univ Toronto, Toronto ON, Canada.
    Lovren, Fina
    Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, St Michaels Hosp, Toronto ON, Canada.
    Pan, Yi
    Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, St Michaels Hosp, Toronto ON, Canada.
    Yanagawa, Bobby
    Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, St Michaels Hosp, Toronto ON, Canada; Dept Surg, Univ Toronto, Toronto ON, Canada.
    Deb, Saswata
    Dept Surg, Univ Toronto, Toronto ON, Canada; Schulich Heart Ctr, Div Cardiac Surg, Sunnybrook Hlth Sci Ctr, Toronto ON, Canada.
    Karkhanis, Reena
    Schulich Heart Ctr, Div Cardiac Surg, Sunnybrook Hlth Sci Ctr, Toronto ON, Canada.
    Quan, Adrian
    Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, St Michaels Hosp, Toronto ON, Canada.
    Teoh, Hwee
    Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, St Michaels Hosp, Toronto ON, Canada; Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Endocrinol & Metab, St Michaels Hosp, Toronto ON, Canada.
    Feder-Elituv, Randi
    Li Ka Shing Knowledge Inst, Keenan Res Ctr, Div Cardiac Surg, St Michaels Hosp, Toronto ON, Canada.
    Moussa, Fuad
    Dept Surg, Univ Toronto, Toronto ON, Canada; Schulich Heart Ctr, Div Cardiac Surg, Sunnybrook Hlth Sci Ctr, Toronto ON, Canada.
    Souza, Domingos S. R.
    Örebro University Hospital. Dept Cardiovasc & Thorac Surg, Örebro University Hospital, Örebro, Sweden.
    Fremes, Stephen E.
    Dept Surg, Univ Toronto, Toronto ON, Canada; Schulich Heart Ctr, Div Cardiac Surg, SunnybrookHlth Sci Ctr, Toronto ON, Canada.
    Pedicled no-touch saphenous vein graft harvest limits vascular smooth muscle cell activation: the PATENT saphenous vein graft study2014In: European Journal of Cardio-Thoracic Surgery, ISSN 1010-7940, E-ISSN 1873-734X, Vol. 45, no 4, p. 717-725Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Neointimal hyperplasia secondary to vascular smooth muscle cell (VSMC) activation limits the long-term patency of saphenous vein grafts (SVGs). We compared markers of vascular injury and VSMC activation in SVGs harvested using the pedicled 'no-touch' (NT) vs the conventional (CON) technique. METHODS: Patients undergoing coronary artery bypass surgery were enrolled in the PATENT SVG trial (clinicaltrials.gov NCT01488084). Patients were randomly allocated to have SVGs harvested with the NT technique from one leg and the CON method from the other. SVG segments underwent morphometry, histological and electron microscopy assessments and transcript measurements of VSMC activation and differentiation markers. Leg wound functional recovery and harvest site complications were assessed using a quality-of-life questionnaire. RESULTS: A total of 17 patients (65.3 +/- 7.3 years) were enrolled. SVGs harvested using the NT vs CON technique exhibited preserved intimal, medial and adventitial architecture. CON harvest was associated with greater medial Kruppel-like factor 4 transcript levels (0.26 +/- 0.05 vs 0.11 +/- 0.02, P < 0.05). CON samples had significantly lower medial serum response factor (0.53 +/- 0.11 vs 1.44 +/- 0.50, P < 0.05) and myocardin (0.59 +/- 0.08 vs 1.33 +/- 0.33, P < 0.05) transcript levels. MicroRNA-145, an inhibitor of VSMC activation and differentiation, was higher in the NT vs CON samples (1.84 +/- 1.03 vs 0.50 +/- 0.19, P < 0.05). Leg assessment scores were worse in the NT legs at 3 months, but similar to CON scores at 12 months. CONCLUSIONS: SVGs harvested using the 'NT' technique exhibit an early molecular and morphological pattern consistent with decreased VSMC activation compared with CON harvesting. Functional leg recovery was similar in both groups at 12 months. Larger studies are required to corroborate these findings.

  • 3416. Veronesi, Giovanni
    et al.
    Ferrario, Marco M.
    Kuulasmaa, Kari
    Bobak, Martin
    Chambless, Lloyd E.
    Salomaa, Veikko
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Pajak, Andrzej
    Jorgensen, Torben
    Amouyel, Philippe
    Arveiler, Dominique
    Drygas, Wojciech
    Ferrieres, Jean
    Giampaoli, Simona
    Kee, Frank
    Iacoviello, Licia
    Malyutina, Sofia
    Peters, Annette
    Tamosiunas, Abdonas
    Tunstall-Pedoe, Hugh
    Cesana, Giancarlo
    Educational class inequalities in the incidence of coronary heart disease in Europe2016In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 102, no 12, p. 958-965Article in journal (Refereed)
    Abstract [en]

    Objective: To estimate the burden of social inequalities in coronary heart disease (CHD) and to identify their major determinants in 15 European populations.

    Methods: The MORGAM (MOnica Risk, Genetics, Archiving and Monograph) study comprised 49 cohorts of middle-aged European adults free of CHD (110 928 individuals) recruited mostly in the mid-1980s and 1990s, with comparable assessment of baseline risk and follow-up procedures. We derived three educational classes accounting for birth cohorts and used regression-based inequality measures of absolute differences in CHD rates and HRs (ie, Relative Index of Inequality, RII) for the least versus the most educated individuals.

    Results: N=6522 first CHD events occurred during a median follow-up of 12 years. Educational class inequalities accounted for 343 and 170 additional CHD events per 100 000 person-years in the least educated men and women compared with the most educated, respectively. These figures corresponded to 48% and 71% of the average event rates in each gender group. Inequalities in CHD mortality were mainly driven by incidence in the Nordic countries, Scotland and Lithuania, and by 28-day case-fatality in the remaining central/South European populations. The pooled RIIs were 1.6 (95% CI 1.4 to 1.8) in men and 2.0 (1.7 to 2.4) in women, consistently across population. Risk factors accounted for a third of inequalities in CHD incidence; smoking was the major mediator in men, and High-Density-Lipoprotein (HDL) cholesterol in women.

    Conclusions: Social inequalities in CHD are still widespread in Europe. Since the major determinants of inequalities followed geographical and gender-specific patterns, European-level interventions should be tailored across different European regions.

  • 3417. Veronesi, Giovanni
    et al.
    Tunstall-Pedoe, Hugh
    Ferrario, Marco M.
    Kee, Frank
    Kuulasmaa, Kari
    Chambless, Lloyd E.
    Amouyel, Philippe
    Arveiler, Dominique
    Bobak, Martin
    Ferrieres, Jean
    Giampaoli, Simona
    Jorgensen, Torben
    Peters, Annette
    Salomaa, Veikko
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Tamosiunas, Abdonas
    Cesana, Giancarlo
    Combined effect of educational status and cardiovascular risk factors on the incidence of coronary heart disease and stroke in European cohorts: implications for prevention2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 24, no 4, p. 437-445Article in journal (Refereed)
    Abstract [en]

    Background: The combined effect of social status and risk factors on the absolute risk of cardiovascular disease has been insufficiently investigated, but results provide guidance on who could benefit most through prevention.

    Methods: We followed 77,918 cardiovascular disease-free individuals aged 35-74 years at baseline, from 38 cohorts covering Nordic and Baltic countries, the UK and Central Europe, for a median of 12 years. Using Fine-Gray models in a competing-risks framework we estimated the effect of the interaction of education with smoking, blood pressure and body weight on the cumulative risk of incident acute coronary heart disease and stroke.

    Results: Compared with more educated smokers, the less educated had an added increase in absolute risk of cardiovascular disease of 3.1% ( 95% confidence interval+0.1%, +6.2%) in men and of 1.5% ( = 1.9%, +5.0%) in women, consistent across smoking categories. Conversely, the interaction was negative for overweight: -2.6% ( 95% CI: -5.6%, +0.3%) and obese: -3.6% ( -7.6%, +0.4%) men, suggesting that the more educated would benefit more from the same reduction in body weight. A weaker interaction was observed for body weight in women, and for blood pressure in both genders. Less educated men and women with a cluster of two or more risk factors had an added cardiovascular disease risk of 3.6% ( +0.1%, +7.0%) and of 2.6% ( - 0.5%, +5.6%), respectively, compared with their more educated counterparts.

    Conclusions: Socially disadvantaged subjects have more to gain from lifestyle and blood pressure modification, hopefully reducing both their risk and also social inequality in disease.

  • 3418. Vestesson, E.
    et al.
    Bray, B.
    James, M.
    Paley, L.
    Kavanagh, M.
    Tyrrell, P.
    Cloud, G.
    Eriksson, Marie
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Norrving, B.
    Rudd, A.
    An international comparison of thrombolysis in England and Wales, and Sweden using national registers2016In: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 11, p. 38-38Article in journal (Other academic)
  • 3419.
    Vetrano, Davide L.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Catholic University of Rome, Italy.
    Pisciotta, Maria S.
    Brandi, Vincenzo
    Lo Monaco, Maria R.
    Laudisio, Alice
    Onder, Graziano
    Fusco, Domenico
    L'Angiocola, Paolo D.
    Bentivoglio, Anna R.
    Bernabei, Roberto
    Zuccalà, Giuseppe
    Impact of disease duration and cardiovascular dysautonomia on hypertension in Parkinson's disease2017In: The Journal of Clinical Hypertension, ISSN 1524-6175, E-ISSN 1751-7176, Vol. 19, no 4, p. 418-423Article in journal (Refereed)
    Abstract [en]

    The authors evaluated the association of Parkinson's disease (PD) duration with hypertension, assessed by office measurements and 24-hour (ambulatory) monitoring, in 167 patients. Hypertension was evaluated through both office and ambulatory blood pressure (BP) measurements. Among participants (mean age 73.4 +/- 7.6years; 35% women), the prevalence of hypertension was 60% and 69% according to office and ambulatory BP measurements, respectively (Cohen's k=0.61; P<.001). PD duration was inversely associated with hypertension as diagnosed by office measurements (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.86-0.98) but not by ambulatory monitoring (OR, 0.94; 95% CI, 0.81-1.01). Ambulatory BP patterns showed higher nocturnal BP among patients with long-lasting disease. In conclusion, ambulatory BP monitoring improves the detection of hypertension by 15% in PD, compared with office evaluation. The likelihood of having hypertension does not decrease during the PD course; rather, BP pattern shifts towards nocturnal hypertension.

  • 3420.
    Vidal-Petiot, Emmanuelle
    et al.
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Cardiol Dept, 46 Rue Henri Huchard, F-75018 Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Dept Physiol, 46 Rue Henri Huchard, F-75018 Paris, France.;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France.;INSERM, U1149, Paris, France..
    Stebbins, Amanda
    Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Chiswell, Karen
    Duke Univ, Med Ctr, Duke Clin Res Inst, 2400 Pratt St, Durham, NC 27705 USA..
    Ardissino, Diego
    Univ Parma, Azienda Osped, Via Gramsci 14, I-43126 Parma, Italy..
    Aylward, Philip E.
    Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Cardiovasc Div, 70 Francis St, Boston, MA 02115 USA.;Harvard Clin Res Inst, Boston, MA USA..
    Corrales, Marco A. Ramos
    San Jose Satelite Hosp, Circunvalac Poniente 53, Naucalpan De Juarez 53100, Mexico..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lopez-Sendon, Jose Luis
    Hosp Univ La Paz, IdiPaz, Paseo Castellana 261,Planta 1, Madrid 28046, Spain..
    Stewart, Ralph A. H.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Steg, Philippe Gabriel
    Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Cardiol Dept, 46 Rue Henri Huchard, F-75018 Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, Dept Physiol, 46 Rue Henri Huchard, F-75018 Paris, France.;Paris Diderot Univ, Sorbonne Paris Cite, Paris, France.;NHLI Imperial Coll, ICMS, Royal Brompton Hosp, London, England.;FACT, F CRIN Network, INSERM, U1148, Paris, France..
    Visit-to-visit variability of blood pressure and cardiovascular outcomes in patients with stable coronary heart disease. Insights from the STABILITY trial2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 37, p. 2813-2822Article in journal (Refereed)
    Abstract [en]

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

  • 3421.
    Viitanen, Matti
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Rehabilitation Medicine. Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Geriatric Medicine. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Long-term effects of stroke1987Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Stroke, which has an increasing incidence with age, causes an irreversible brain damage which may lead to impairment, disability and decreased life satisfaction or death.

    Risk factors for death, recurrent stroke and myocardial infarction, were analyzed in 409 stroke patients treated at the Stroke Unit, Department of Medicine, Umeå University Hospital, between Jan. 1, 1978 and Dec. 31, 1982. The causes of death were related with the time of survival. In fully co-operable (n=62) 4-6 year stroke survivors, the occurrence of motor and perceptual impairments, of self-care (ADL) disability and of self-reported decreased life satisfaction due to stroke was determined.

    The probability of survival was 77% three months after stroke, 69% after one year, and 37% after five years. Multivariate statistical analysis indicated that impairment of consciousness was the most important risk factor for death followed by age, previous cardiac failure, diabetes mellitus, intracerebral hemorrhage and male sex. During the first week, cerebrovascular disease (90%) was the most dominant primary cause of death, from the second to the fourth week pulmonary embolism (30%), bronchopneumonia during the second and third months and cardiac disease (37%) later than three months after stroke. The risk of recurrence was 14% during the first year after stroke and the accumulated risk of stroke recurrence after 5 years was 37% after stroke. The estimated probability of myocardial infarction was 7% at one year and 19% at 5 years. High age and a history of cardiac failure increased the risk of recurrent stroke. The risk of myocardial infarction was associated with high age, angina pectoris and diabetes mellitus. The highest risk of epilepsy was found between 6 and 12 months after stroke. Motor impairment prevailed in 36% of the long-term survivors, perceptual impairments in up to 57% and decreased ADL-capacity in 32%. As regards ecological perception, perceptual function variables were distinctly grouped into low and high level perception which together with motor function explained 71% of the variance of self-care ADL. While levels of global and of domain specific variables of life satisfaction appeared stable in clinically healthy reference populations aged 60 and 80 years, the stroke had produced a decrease in one or more aspects of life satisfaction for 61% of the long-term survivors. Although significantly associated with motor impairments and ADL disability, these changes could not only be attributed to physical problems.

  • 3422.
    Vikholm, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Ivert, Torbjorn
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    Nilsson, Johan
    Skane Univ Hosp, Dept Clin Sci Cardiothorac Surg, Lund, Sweden.
    Holmgren, Anders
    Umea Univ Hosp, Dept Surg & Perioperat Sci, Umea, Sweden.
    Freter, Wolfgang
    Linkoping Univ Hosp, Dept Med & Hlth Sci, Linkoping, Sweden.
    Temstrom, Lisa
    Sahlgrens Univ Hosp, Dept Cardiothorac Surg, Gothenburg, Sweden.
    Ghaidan, Haider
    Blekinge Hosp, Dept Cardiothorac Surg, Karlskrona, Sweden.
    Sartipy, Ulrik
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    Olsson, Christian
    Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden;Karolinska Univ Hosp, Heart & Vasc Theme, Stockholm, Sweden.
    Granfeldt, Hans
    Linkoping Univ Hosp, Dept Med & Hlth Sci, Linkoping, Sweden.
    Ragnarsson, Sigurdur
    Skane Univ Hosp, Dept Clin Sci Cardiothorac Surg, Lund, Sweden.
    Friberg, Orjan
    Orebro Univ Hosp, Fac Med & Hlth, Dept Cardiothorac Surg & Vasc Surg, Orebro, Sweden.
    Validity of the Swedish Cardiac Surgery Registry2018In: Interactive Cardiovascular and Thoracic Surgery, ISSN 1569-9293, E-ISSN 1569-9285, Vol. 27, no 1, p. 67-74Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Our goal was to validate the Swedish Cardiac Surgery Registry by reviewing the reported cardiac operations to assess the completeness and quality of the registered data and the EuroSCORE II variables. METHODS: A total of 5837 cardiac operations were reported to the Swedish Cardiac Surgery Registry in Sweden during 2015. A randomly selected sample of 753 patient records (13%) was scrutinized by 3 surgeons at all 8 units in Sweden performing open cardiac surgery in adults. RESULTS: Coverage was excellent with 99% [95% confidence interval (CI) 98-99%] of the performed procedures found in the registry. Reported waiting times for surgery were correct in 78% (95% CI 76-79%) of the cases. The main procedural code was correctly reported in 96% (95% CI 95-97%) of the cases. The correlation between reported and monitored logistic EuroSCORE II had a coefficient of 0.79 (95% CI 0.76-0.82), and the median difference in EuroSCORE II was 0% (interquartile range -0.4% to 0.4%). The majority of EuroSCORE II variables had good agreement and coherence; however, New York Heart Association functional class, preoperative renal dysfunction, left ventricular ejection fraction, Canadian Cardiovascular Society Class IV angina and poor mobility were less robust Postoperative complications were rare and in general had a high degree of completeness and agreement. CONCLUSIONS: The reliability of the variables in the national Swedish Cardiac Surgery Registry was excellent. Thus, the registry is a valuable source of data for quality studies and research. Some EuroSCORE II variables require improved and stricter definitions to obtain uniform reporting and high validity.

  • 3423.
    Viktorisson, Adam
    et al.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Rehabil Med, Gothenburg, Sweden.
    Sunnerhagen, Katharina S.
    Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Rehabil Med, Gothenburg, Sweden.
    Pöder, Ulrika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Caring Sciences.
    Herlitz, Johan
    Sahlgrens Univ Hosp, Inst Internal Med, Dept Metab & Cardiovasc Res, Gothenburg, Sweden;Prehospen Univ Coll Boras, Prehosp Res Ctr Western Sweden, Boras, Sweden.
    Axelsson, Åsa B.
    Univ Gothenburg, Sahlgrenska Acad, Inst Hlth & Care Sci, Gothenburg, Sweden.
    Well-being among survivors of out-of-hospital cardiac arrest: a cross-sectional retrospective study in Sweden2018In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 8, no 6, article id e021729Article in journal (Refereed)
    Abstract [en]

    Objectives The psychological outcome of out-of-hospital cardiac arrest (OHCA) has been studied more extensively in recent years. Still, not much is known about the well-being among OHCA survivors. In this retrospective cross-sectional study, we aim to investigate post-OHCA well-being among patients with a good neurological outcome, 3 months after the cardiac event. To assess well-being, we analyse the frequency of anxiety, depression, post-traumatic stress disorder (PTSD) and health within this group. Further, we aim to evaluate the importance of five prognostic factors for post-OHCA well-being. Methods Data collection took place between 2008 and 2012, and every OHCA survivor within one region of Sweden, with a cerebral performance category (CPC) score of <= 2 at discharge, was asked to participate. Survivors were identified through the Swedish Cardiopulmonary Resuscitation Registry, and postal questionnaires were sent out 3 months after the OHCA. The survey included Hospital Anxiety and Depression scale (HADS), PTSD Checklist Civilian version (PCL-C) and European Quality of Life 5 Dimensions 3 level (EQ-5D-3L). Results Of 298 survivors, 150 were eligible for this study and 94 responded. The mean time from OHCA to follow-up was 88 days. There was no significant difference between respondents and non-respondents in terms of sex, age, cardiac arrest circumstances or in-hospital interventions. 48 participants reported reduced well-being, and young age was the only factor significantly correlated to this outcome (p=0.02). Women reported significantly higher scores in HADS (p=0.001) and PCL-C (p<0.001). Women also reported significantly lower EQ-5D index values (p=0.002) and EQ-visual analogue scale scores (p=0.002) compared with men. Conclusion Reduced well-being is experienced by half of OHCA survivors with a CPC score <= 2, and young age is negatively correlated to this outcome. The frequency of anxiety and PTSD is higher among women, who also report worse health.

  • 3424. Vilahur, Gemma
    et al.
    Hernández-Vera, Rodrigo
    Molins, Blanca
    Casaní, Laura
    Duran, Xevi
    Padró, Teresa
    Badimon, Lina
    Short-term myocardial ischemia induces cardiac modified C-reactive protein expression and proinflammatory gene (cyclo-oxygenase-2, monocyte chemoattractant protein-1, and tissue factor) upregulation in peripheral blood mononuclear cells2009In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 7, no 3, p. 485-493Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Prompt coronary thrombus resolution, reducing time of ischemia, improves cardiac recovery. The factors triggered by ischemia that contribute to the clinical outcome are not fully known. We hypothesize that unabated inflammation due to cardiac ischemia may be a contributing factor.

    AIMS: As a proof-of-concept, we evaluated the effect of short-term myocardial ischemia on the local and systemic inflammatory response.

    METHODS: Pigs underwent either 90-min mid-left anterior descending (LAD) coronary artery balloon occlusion (infarct size 25% +/- 1% left ventricle; 29% heart function deterioration) or a sham-operation procedure. Peri-infarcted and non-ischemic cardiac tissue was obtained for histopathologic, molecular and immunohistochemical analysis of inflammatory markers [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), modified C-reactive protein (mCRP), and human alveolar macrophage-56 (HAM-56)]. Blood (femoral vein) was withdrawn prior to myocardial infarction (MI) induction (t = 0) and at 30 and 90 min to evaluate: (i) systemic cytokine levels (IL-6, TNF-alpha, CRP); (ii) proinflammatory gene and protein expression in peripheral blood mononuclear cells (PBMCs) of tissue factor (TF), cyclo-oxygenase-2 (Cox-2), monocyte chemoattractant protein-1 (MCP-1), and CRP; and (iii) platelet activation (assessed by perfusion studies and RhoA activation).

    RESULTS: Short-term ischemia triggered cardiac IL-6 and TNF-alpha expression, recruitment of inflammatory cells, and mCRP expression in infiltrated macrophages (P < 0.05 vs. t = 0 and sham). PBMC mRNA and protein expression of MCP-1, Cox-2 and TF was significantly increased by ischemia, whereas no differences were detected in CRP. Ischemia increased cardiac troponin-I, IL-6 and TNF-alpha systemic levels, and was associated with higher platelet deposition and RhoA activation (P < 0.001 vs. t = 0 and sham).

    CONCLUSION: Short-term myocardial ischemia, even without atherosclerosis, induces an inflammatory phenotype by inducing local recruitment of macrophages and systemic activation of mononuclear cells, and renders platelets more susceptible to activation.

  • 3425. Villani, Emanuele R.
    et al.
    Tummolo, Anita M.
    Palmer, Katie
    Manes Gravina, Ester
    Vetrano, Davide L.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Catholic University of the Sacred Heart, Italy.
    Bernabei, Roberto
    Onder, Graziano
    Acampora, Nicola
    Frailty and atrial fibrillation: A systematic review2018In: European journal of internal medicine, ISSN 0953-6205, E-ISSN 1879-0828, Vol. 56, p. 33-38Article, review/survey (Refereed)
    Abstract [en]

    Atrial fibrillation (AF) is a common cardiac arrhythmia and its prevalence increases with age. There is a significant correlation between frailty, morbidity and mortality in elderly patients with cardiovascular disease, but the relation between AF and frailty is still under debate. The aim of this study is to systematically review evidence on the association between AF and frailty. A systematic review of articles published between 02/01/2002 and 09/28/2017 according to PRISMA recommendations was carried out. PubMed, Web of Science, and Embase were searched for relevant articles. 11 studies were included; one longitudinal, 10 cross-sectional. Only 4 studies assessed the association of frailty with AF, while 7 studies were performed in a sample of participants with AF and did not provide any measure of association between these two conditions. The prevalence of frailty in AF patients ranged from 4.4%-75.4% while AF prevalence in the frail population ranged from 48.2%-75.4%. Selected studies enrolled an overall sample of 9420 participants. Among them, 2803 participants were diagnosed with AF and of these 1517 (54%) were frail and 1286 (46%) were pre-frail or robust. The four studies assessing the association of AF and frailty provided conflicting results. Evidence suggests that frailty is common in persons with AF. More research is needed to better assess the association of these conditions and to identify the optimal therapeutic approach to AF in persons with frailty.

  • 3426. Villard, Eric
    et al.
    Perret, Claire
    Gary, Françoise
    Proust, Carole
    Dilanian, Gilles
    Hengstenberg, Christian
    Ruppert, Volker
    Arbustini, Eloisa
    Wichter, Thomas
    Germain, Marine
    Dubourg, Olivier
    Tavazzi, Luigi
    Aumont, Marie-Claude
    DeGroote, Pascal
    Fauchier, Laurent
    Trochu, Jean-Noël
    Gibelin, Pierre
    Aupetit, Jean-François
    Stark, Klaus
    Erdmann, Jeanette
    Hetzer, Roland
    Roberts, Angharad M
    Barton, Paul J R
    Regitz-Zagrosek, Vera
    Aslam, Uzma
    Duboscq-Bidot, Laëtitia
    Meyborg, Matthias
    Maisch, Bernhard
    Madeira, Hugo
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Galve, Enrique
    Cleland, John G
    Dorent, Richard
    Roizes, Gerard
    Zeller, Tanja
    Blankenberg, Stefan
    Goodall, Alison H
    Cook, Stuart
    Tregouet, David A
    Tiret, Laurence
    Isnard, Richard
    Komajda, Michel
    Charron, Philippe
    Cambien, François
    A genome-wide association study identifies two loci associated with heart failure due to dilated cardiomyopathy2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 9, p. 1065-1076Article in journal (Refereed)
    Abstract [en]

    Aims: Dilated cardiomyopathy (DCM) is a major cause of heart failure with a high familial recurrence risk. So far, the genetics of DCM remains largely unresolved. We conducted the first genome-wide association study (GWAS) to identify loci contributing to sporadic DCM.

    Methods and results: One thousand one hundred and seventy-nine DCM patients and 1108 controls contributed to the discovery phase. Pools of DNA stratified on disease status, population, age, and gender were constituted and used for testing association of DCM with 517 382 single nucleotide polymorphisms (SNPs). Three DCM-associated SNPs were confirmed by individual genotyping (P < 5.0 10−7), and two of them, rs10927875 and rs2234962, were replicated in independent samples (1165 DCM patients and 1302 controls), with P-values of 0.002 and 0.009, respectively. rs10927875 maps to a region on chromosome 1p36.13 which encompasses several genes among which HSPB7 has been formerly suggested to be implicated in DCM. The second identified locus involves rs2234962, a non-synonymous SNP (c.T757C, p. C151R) located within the sequence of BAG3 on chromosome 10q26. To assess whether coding mutations of BAG3 might cause monogenic forms of the disease, we sequenced BAG3 exons in 168 independent index cases diagnosed with familial DCM and identified four truncating and two missense mutations. Each mutation was heterozygous, present in all genotyped relatives affected by the disease and absent in a control group of 347 healthy individuals, strongly suggesting that these mutations are causing the disease.

    Conclusion: This GWAS identified two loci involved in sporadic DCM, one of them probably implicates BAG3. Our results show that rare mutations in BAG3 contribute to monogenic forms of the disease, while common variant(s) in the same gene are implicated in sporadic DCM.

  • 3427. Vimaleswaran, Karani S.
    et al.
    Franks, Paul W.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, UK.
    Barroso, Inês
    Brage, Soren
    Ekelund, Ulf
    Wareham, Nicholas J.
    Loos, Ruth J. F.
    Habitual Energy Expenditure Modifies the Association Between NOS3 Gene Polymorphisms and Blood Pressure2008In: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 21, no 3, p. 297-302Article in journal (Refereed)
    Abstract [en]

    Background: The endothelial nitric-oxide synthase (NOS3) gene encodes the enzyme (eNOS) that synthesizes the molecule nitric oxide, which facilitates endothelium-dependent vasodilation in response to physical activity. Thus, energy expenditure may modify the association between the genetic variation at NOS3and blood pressure.

    Methods: To test this hypothesis, we genotyped 11 NOS3 polymorphisms, capturing all common variations, in 726 men and women from the Medical Research Council (MRC) Ely Study (age (mean ± s.d.): 55 ± 10 years, body mass index: 26.4 ± 4.1 kg/m2). Habitual/non-resting energy expenditure (NREE) was assessed via individually calibrated heart rate monitoring over 4 days.

    Results: The intronic variant, IVS25+15 [G→A], was significantly associated with blood pressure; GG homozygotes had significantly lower levels of diastolic blood pressure (DBP) (−2.8 mm Hg; P = 0.016) and systolic blood pressure (SBP) (−1.9 mm Hg; P = 0.018) than A-allele carriers. The interaction between NREE and IVS25+15 was also significant for both DBP (P = 0.006) and SBP (P = 0.026), in such a way that the effect of the GG-genotype on blood pressure was stronger in individuals with higher NREE (DBP: −4.9 mm Hg, P = 0.02. SBP: −3.8 mm Hg, P= 0.03 for the third tertile). Similar results were observed when the outcome was dichotomously defined as hypertension.

    Conclusions: In summary, the NOS3 IVS25+15 is directly associated with blood pressure and hypertension in white Europeans. However, the associations are most evident in the individuals with the highest NREE. These results need further replication and have to be ideally tested in a trial before being informative for targeted disease prevention. Eventually, the selection of individuals for lifestyle intervention programs could be guided by knowledge of genotype.

  • 3428. Vinereanu, Dragos
    et al.
    Lopes, Renato D
    Mulder, Hillary
    Gersh, Bernard J
    Hanna, Michael
    de Barros E Silva, Pedro G M
    Atar, Dan
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Granger, Christopher B
    Alexander, John H
    Echocardiographic Risk Factors for Stroke and Outcomes in Patients With Atrial Fibrillation Anticoagulated With Apixaban or Warfarin2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 12, p. 3266-3273Article in journal (Refereed)
    Abstract [en]

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

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

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

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

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

  • 3429. Vinereanu, Dragos
    et al.
    Stevens, Susanna R
    Alexander, John H
    Al-Khatib, Sana M
    Avezum, Alvaro
    Bahit, Marıa Cecilia
    Granger, Christopher B
    Lopes, Renato D
    Halvorsen, Sigrun
    Hanna, Michael
    Husted, Steen
    Hylek, Elaine M
    Mărgulescu, Andrei D
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Atar, Dan
    Clinical outcomes in patients with atrial fibrillation according to sex during anticoagulation with apixaban or warfarin: a secondary analysis of a randomized controlled trial2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 46, p. 3268-+Article in journal (Refereed)
    Abstract [en]

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

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

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

    TRIAL REGISTRATION: ARISTOTLE ClinicalTrials.gov number, NCT00412984.

  • 3430.
    Vinereanu, Dragos
    et al.
    Univ Med & Pharm Carol Davila, Cardiol, Bucharest, Romania;Univ & Emergency Hosp, Cardiol, Bucharest, Romania.
    Wang, Alice
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Mulder, Hillary
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Lopes, Renato D.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Jansky, Petr
    Univ Hosp Motol, Prague, Czech Republic.
    Lewis, Basil S.
    Lady Davis Carmel Med Ctr, Haifa, Israel.
    Gersh, Bernard J.
    Mayo Clin, Rochester, MN USA.
    Avezum, Alvaro
    Univ Sao Paulo, Dante Pazzanese Inst, Sao Paulo, Brazil.
    Hanna, Michael
    Bristol Myers Squibb, Princeton, NJ USA.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Granger, Clristopler B.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Alexander, Jam H.
    Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
    Outcomes in anticoagulated patients with atrial fibrillation and with mitral or aortic valve disease2018In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 104, no 15, p. 1292-1299Article in journal (Refereed)
    Abstract [en]

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

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

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

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

  • 3431. Vinnars, Marie-Therese
    et al.
    Nasiell, Josefine
    Holmström, Gerd
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Ophthalmology.
    Norman, Mikael
    Westgren, Magnus
    Papadogiannakis, Nikos
    Association between placental pathology and neonatal outcome in preeclampsia: a large cohort study2014In: Hypertension in Pregnancy, ISSN 1064-1955, E-ISSN 1525-6065, Vol. 33, no 2, p. 145-158Article in journal (Refereed)
    Abstract [en]

    Objective: To study associations between placental histopathology and neonatal outcome in preeclampsia (PE). Study design: The cohort consisted of 544 singleton pregnancies complicated by PE and managed at Karolinska University Hospital, Stockholm, Sweden during 2000-2009. Evaluation of placental histopathology was made by one senior perinatal pathologist, blinded to outcome. Clinical outcome was obtained from prospectively collected medical registry data and medical records. Main outcome measures were intrauterine fetal death, smallness for gestational age, admission to neonatal unit, major neonatal morbidity (defined as presence of intraventricular hemorrhage >= grade 3, retinopathy of prematurity >= grade 3, necrotizing enterocolitis, cystic periventricular leucomalacia and/or severe bronchopulmonary dysplasia) and neonatal mortality. Logistic regression analyses including gestational age were performed. Results: Abnormal placental weight, both low (adjusted odds ratio (OR) [95% confidence interval] 5.2 [1.1-24], p = 0.03) and high (adjusted OR 1048 [21-51 663], p < 0.001) for gestational age, was associated with major neonatal morbidity in preterm infants. Accelerated villous maturation was less prevalent in intrauterine fetal death pregnancies (adjusted OR 0.18 [0.04-0.77], p = 0.02). Decidual arteriopathy increased the odds for admission to neonatal care (adjusted OR 2.7 [1.1-6.5], p = 0.03). Infarction involving >= 5% of the placenta was associated with intrauterine fetal death and small for gestational age infants (adjusted OR's 75 [5.5-1011], p = 0.001 and 3.2 [1.7-5.9], p < 0.001; respectively). No relations between histological variables and neonatal mortality could be found. Conclusion: Placental pathology in PE reflects adverse perinatal events and deviant placental weight predicts adverse neonatal outcome in preeclamptic women delivering preterm. Placental investigation without delay can contribute to neonatal risk assessment.

  • 3432.
    Virtanen, Marianna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Kivimäki, Mika
    Long Working Hours and Risk of Cardiovascular Disease2018In: Current Cardiology Reports, ISSN 1523-3782, E-ISSN 1534-3170, Vol. 20, no 11, article id 123Article, review/survey (Refereed)
    Abstract [en]

    To summarize the evidence on the relationship between long working hours and cardiovascular disease, such as coronary heart disease and stroke. Large-scale meta-analyses with published and individual participant observational data on more than 740,000 men and women free of cardiovascular disease report a link between long working hours (>= 55 h a week) and the onset of cardiovascular events. Our meta-analytic update of summary evidence suggests a 1.12-fold (95% CI 1.03-1.21) increased risk associated with coronary heart disease and a 1.21-fold (95% CI 1.01-1.45) increased risk of stroke, although the evidence is somewhat inconsistent and the possibility of residual confounding and bias cannot be ruled out. Few studies have examined the mechanisms which may be stress-related, behavioral, or biological. The recent pooled analyses suggest that increased cardiac electric instability and hypercoagulability might play a role. The evidence that long working hours are a risk factor for cardiovascular disease is accumulating and suggests a small risk. Studies on the effects of long working hours in high-risk populations and those with pre-existing cardiovascular disease, mechanistic research, and intervention studies are needed to advance this research field.

  • 3433.
    Virtanen, Marianna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Public Health. Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Kivimäki, Mika
    Long Working Hours and Risk of Cardiovascular Disease2018In: Current Cardiology Reports, ISSN 1523-3782, E-ISSN 1534-3170, Vol. 20, no 11, article id 123Article in journal (Refereed)
    Abstract [en]

    To summarize the evidence on the relationship between long working hours and cardiovascular disease, such as coronary heart disease and stroke. Large-scale meta-analyses with published and individual participant observational data on more than 740,000 men and women free of cardiovascular disease report a link between long working hours (>= 55 h a week) and the onset of cardiovascular events. Our meta-analytic update of summary evidence suggests a 1.12-fold (95% CI 1.03-1.21) increased risk associated with coronary heart disease and a 1.21-fold (95% CI 1.01-1.45) increased risk of stroke, although the evidence is somewhat inconsistent and the possibility of residual confounding and bias cannot be ruled out. Few studies have examined the mechanisms which may be stress-related, behavioral, or biological. The recent pooled analyses suggest that increased cardiac electric instability and hypercoagulability might play a role. The evidence that long working hours are a risk factor for cardiovascular disease is accumulating and suggests a small risk. Studies on the effects of long working hours in high-risk populations and those with pre-existing cardiovascular disease, mechanistic research, and intervention studies are needed to advance this research field.

  • 3434. Virtanen, Marianna
    et al.
    Nyberg, Solja T
    Batty, G David
    Jokela, Markus
    Heikkilä, Katriina
    Fransson, Eleonor I
    Alfredsson, Lars
    Bjorner, Jakob B
    Borritz, Marianne
    Burr, Hermann
    Casini, Annalisa
    Clays, Els
    De Bacquer, Dirk
    Dragano, Nico
    Elovainio, Marko
    Erbel, Raimund
    Ferrie, Jane E
    Hamer, Mark
    Jöckel, Karl-Heinz
    Kittel, France
    Knutsson, Anders
    Koskenvuo, Markku
    Koskinen, Aki
    Lunau, Thorsten
    Madsen, Ida EH
    Nielsen, Martin L
    Nordin, Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Oksanen, Tuula
    Pahkin, Krista
    Pejtersen, Jan H
    Pentti, Jaana
    Rugulies, Reiner
    Salo, Paula
    Shipley, Martin J
    Siegrist, Johannes
    Steptoe, Andrew
    Suominen, Sakari B
    Theorell, Töres
    Toppinen-Tanner, Salla
    Väänänen, Ari
    Vahtera, Jussi
    Westerholm, Peter JM
    Westerlund, Hugo
    Slopen, Natalie
    Kawachi, Ichiro
    Singh-Manoux, Archana
    Kivimäki, Mika
    Perceived job insecurity as a risk factor for incident coronary heart disease: systematic review and meta-analysis2013In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 347, p. f4746-Article in journal (Refereed)
  • 3435. Vishram, Julie K. K.
    et al.
    Borglykke, Anders
    Andreasen, Anne H.
    Jeppesen, Jorgen
    Ibsen, Hans
    Jorgensen, Torben
    Palmieri, Luigi
    Giampaoli, Simona
    Donfrancesco, Chiara
    Kee, Frank
    Mancia, Giuseppe
    Cesana, Giancarlo
    Kuulasmaa, Kari
    Salomaa, Veikko
    Sans, Susana
    Ferrieres, Jean
    Dallongeville, Jean
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Arveiler, Dominique
    Wagner, Aline
    Tunstall-Pedoe, Hugh
    Drygas, Wojciech
    Olsen, Michael H.
    Impact of Age and Gender on the Prevalence and Prognostic Importance of the Metabolic Syndrome and Its Components in Europeans. The MORGAM Prospective Cohort Project2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e107294-Article in journal (Refereed)
    Abstract [en]

    Objective: To investigate the influence of age and gender on the prevalence and cardiovascular disease (CVD) risk in Europeans presenting with the Metabolic Syndrome (MetS). Methods: Using 36 cohorts from the MORGAM-Project with baseline between 1982-1997, 69094 men and women aged 19-78 years, without known CVD, were included. During 12.2 years of follow-up, 3.7%/2.1% of men/women died due to CVD. The corresponding percentages for fatal and nonfatal coronary heart disease (CHD) and stroke were 8.3/3.8 and 3.1/2.5. Results: The prevalence of MetS, according to modified definitions of the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII), increased across age groups for both genders (P<0.0001); with a 5-fold increase in women from ages 19-39 years to 60-78 years (7.4%/7.6% to 35.4%/37.6% for IDF/NCEP-ATPIII) and a 2-fold increase in men (5.3%/10.5% to 11.5%/21.8%). Using multivariate-adjusted Cox regressions, the associations between MetS and all three CVD events were significant (P<0.0001). For IDF/NCEP-ATPIII in men and women, hazard ratio (HR) for CHD was 1.60/1.62 and 1.93/2.03, for CVD mortality 1.73/1.65 and 1.77/2.06, and for stroke 1.51/1.53 and 1.58/1.77. Whereas in men the HRs for CVD events were independent of age (MetS*age, P>0.05), in women the HRs for CHD declined with age (HRs 3.23/3.98 to 1.55/1.56; MetS*age, P = 0.01/P = 0.001 for IDF/NCEP-ATPIII) while the HRs for stroke tended to increase (HRs 1.31/1.25 to 1.55/1.83; MetS*age, P>0.05). Conclusion: In Europeans, both age and gender influenced the prevalence of MetS and its prognostic significance. The present results emphasise the importance of being critical of MetS in its current form as a marker of CVD especially in women, and advocate for a redefinition of MetS taking into account age especially in women.

  • 3436. Von Wangenheim, Burkard
    et al.
    Israelsson, Johan
    Lindstaedt, Michael
    Carlsson, Jörg
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences. Kalmar County Hospital, Sweden.
    Halvautomatiska hjärtstartare tolkar inte alltid rätt: fem patienter defibrillerades trots icke-defibrillerbar rytm2015In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 112, no 32-33, p. 1-4Article in journal (Refereed)
    Abstract [sv]

    Halvautomatiska defibrillatorer är en viktig del i kampen mot plötslig hjärtdöd. 

    Höga krav på sensitivitet och specificitet vid rytmtolkning ska säkerställa effektivt och säkert bruk. 

    Vi rapporterar fem fall där brister i specificitet hos defibrillatorn ledde till defibrillering av icke-defibrillerbara rytmer.

    Systematisk undersökning av halvautomatiska defibrillatorers prestationsförmåga vid rytmtolkning är nödvändig och skulle kunna bidra till utveckling av förbättrade analysalgoritmer och utbildningsprogram.

  • 3437.
    Voora, Deepak
    et al.
    Duke Clinical Research Institute, Durham, NC, USA.
    Ginsburg, GS
    Åkerblom, Axel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Platelet RNA as a novel biomarker for the response to antiplatelet therapy2014In: Future Cardiology, ISSN 1479-6678, Vol. 10, no 1, p. 9-12Article in journal (Refereed)
  • 3438.
    Vorkapic, Emina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Folkesson, Maggie
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Magnell, Kerstin
    Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden.
    Bohlooly-Y, Mohammad
    Innovative Medicines, AstraZeneca R&D, Mölndal, Sweden.
    Länne, Toste
    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 Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    ADAMTS-1 in abdominal aortic aneurysm2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0178729Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Extracellular matrix degradation is a hallmark of abdominal aortic aneurysm (AAA). Among proteases that are capable of degrading extracellular matrix are a disintegrin and metalloproteases with thrombospondin motifs (ADAMTS). Pathogenesis of these proteases in AAA has not been investigated until date.

    METHODS AND RESULTS: Human aneurysmal and control aortas were collected and analyzed with RT-PCR measuring the ADAMTS-1, 4,5,6,8,9,10,13,17 and ADAMTSL-1. Expression of a majority of the investigated ADAMTS members on mRNA level was decreased in aneurysm compared to control aorta. ADAMTS-1 was one of the members that was reduced most. Protein analysis using immunohistochemistry and western blot for localization and expression of ADAMTS-1 revealed that ADAMTS-1 was present predominantly in areas of SMCs and macrophages in aneurysmal aorta and higher expressed in AAA compared to control aortas. The role of ADAMTS-1 in AAA disease was further examined using ADAMTS-1 transgenic/apoE-/- mice with the experimental angiotensin II induced aneurysmal model. Transgenic mice overexpressing ADAMTS-1 showed to be similar to ADAMTS-1 wild type mice pertaining collagen, elastin content and aortic diameter.

    CONCLUSION: Several of the ADAMTS members, and especially ADAMTS-1, are down regulated at mRNA level in AAA, due to unknown mechanisms, at the same time ADAMTS-1 protein is induced. The cleavage of its substrates, don't seem to be crucial for the pathogenesis of AAA but rather more important in the development of thoracic aortic aneurysm and atherosclerosis as shown in previous studies.

  • 3439. Vorkas, P. A.
    et al.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Want, E. J.
    Issac, G.
    Millar, A.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. ulf.naslund@medicin.umu.se.
    Holmes, E.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Apoptosis is a potential mechanism for severe calcific coronary artery disease2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, no Supplement 1, Meeting abstract P2550, p. 456-456Article in journal (Other academic)
  • 3440. Vorkas, P. A.
    et al.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Want, E. J.
    Isaac, G.
    Millar, A.
    Holmes, E.
    Henein, Michael Y.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Serum metabolic phenotypes correlate with the extent of coronary artery calcification in symptomatic patients with no flow limiting lesions2012In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 33, no Suppl. 1, p. 283-283Article in journal (Other academic)
  • 3441.
    Vorkas, P.
    et al.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Want, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmes, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. ulf.naslund@medicin.umu.se.
    Issac, G.
    Corporation, Waters Corporation, Milford, USA.
    Millar, A.
    Corporation, Waters Corporation, Milford, USA.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Apoptosis is a potential mechanism for severe calcific coronary artery disease2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E157-E158Article in journal (Other academic)
  • 3442.
    Vorkas, P.
    et al.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Want, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmes, E.
    Section of Biomolecular Medicine, Imperial College, London, United Kingdom.
    Holmgren, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Näslund, Ulf
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology. ulf.naslund@medicin.umu.se.
    Issac, G
    Corporation, Waters Corporation, Milford, USA.
    Millar, A
    Corporation, Waters Corporation, Milford, USA.
    Henein, Michael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Significant inflammation pathophysiology features calcific coronary artery disease2014In: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, no 2, p. E140-E140Article in journal (Other academic)
  • 3443.
    Vranckx, Pascal
    et al.
    Hartctr Hasselt, Hasselt, Belgium..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Huang, Zhen
    Duke Clin Res Inst, Durham, NC USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Stanford, CA 94305 USA..
    Armstrong, Paul W.
    Univ Alberta, Div Cardiol, Edmonton, AB, Canada..
    Van de Werf, Frans
    Univ Leuven, Dept Cardiol, Leuven, Belgium..
    Moliterno, David J.
    Univ Kentucky, Gill Heart Inst, Lexington, KY USA.;Univ Kentucky, Div Cardiovasc Med, Lexington, KY USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Aylward, Philip E.
    Flinders Univ S Australia, SAHMRI, Adelaide, SA 5001, Australia.;Med Ctr, Adelaide, SA, Australia..
    Cornel, Jan H.
    Med Ctr Alkmaar, Dept Cardiol, Alkmaar, Netherlands..
    Bode, Christoph
    Univ Klinikum, Internal Med & Cardiol, Freiburg, Germany..
    Huber, Kurt
    Wilhelminen Hosp, Dept Med Cardiol & Intens Care Med 3, Vienna, Austria..
    Nicolau, Jose C.
    Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil..
    Ruzyllo, Witold
    Inst Cardiol, Dept Coronary Artery Dis, Warsaw, Poland.;Inst Cardiol, Cardiac Catheterizat Lab, Warsaw, Poland..
    Harrington, Robert A.
    Stanford Univ, Stanford, CA 94305 USA..
    Tricoci, Pierluigi
    Duke Clin Res Inst, Durham, NC USA..
    Validation of BARC Bleeding Criteria in Patients With Acute Coronary Syndromes: The TRACER Trial2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 18, p. 2135-2144Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The Bleeding Academic Research Consortium (BARC) scale has been proposed to standardize bleeding endpoint definitions and reporting in cardiovascular trials. Validation in large cohorts of patients is needed.

    OBJECTIVES This study sought to investigate the relationship between BARC-classified bleeding and mortality and compared its prognostic value against 2 validated bleeding scales: TIMI (Thrombolysis In Myocardial Infarction) and GUSTO (Global Use of Strategies to Open Occluded Arteries).

    METHODS We analyzed bleeding in 12,944 patients with acute coronary syndromes without ST-segment elevation, with or without early invasive strategy. The main outcome measure was all-cause death.

    RESULTS During follow-up (median: 502 days), noncoronary artery bypass graft (CABG) bleeding occurred in 1,998 (15.4%) patients according to BARC (grades 2, 3, or 5), 484 (3.7%) patients according to TIMI minor/major, and 514 (4.0%) patients according to GUSTO moderate/severe criteria. CABG-related bleeding (BARC 4) occurred in 155 (1.2%) patients. Patients with BARC (2, 3, or 4) bleeding had a significant increase in risk of death versus patients without bleeding (BARC 0 or 1); the hazard was highest in the 30 days after bleeding (hazard ratio: 7.35; 95% confidence interval: 5.59 to 9.68; p < 0.0001) and remained significant up to 1 year. The hazard of mortality increased progressively with non-CABG BARC grades. BARC 4 bleeds were significantly associated with mortality within 30 days (hazard ratio: 10.05; 95% confidence interval: 5.41 to 18.69; p < 0.0001), but not thereafter. Inclusion of BARC (2, 3, or 4) bleeding in the 1-year mortality model with baseline characteristics improved it to an extent comparable to TIMI minor/major and GUSTO moderate/severe bleeding.

    CONCLUSIONS In patients with acute coronary syndromes without ST-segment elevation, bleeding assessed with the BARC scale was significantly associated with risk of subsequent death up to 1 year after the event and risk of mortality increased gradually with higher BARC grades. Our results support adoption of the BARC bleeding scale in ACS clinical trials. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER] [Study P04736]; NCT00527943)

  • 3444.
    Vánky, Farkas
    et al.
    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 Thoracic and Vascular Surgery.
    Hultkvist, Henrik
    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 Thoracic and Vascular Surgery.
    Svedjeholm, Rolf
    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 Thoracic and Vascular Surgery.
    Nilsson, Lennart
    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.
    Is the present definition of mycardial infarction in transcatheter aortic valve implantation relevant for the postprocedulal outcome?2015Conference paper (Other academic)
    Abstract [en]

    Background: The association between biomarkers and adverse procedural outcome has been established. However, the additive prognostic importance of signs and symptoms according to the Valve Academic Research Consortium (VARC)-2 criteria for periprocedural myocardial infarction (MI) are more uncertain.

    Aim: To evaluate the relevance of the individual components of the VARC-2 criteria for periprocedural myocardial infarction (MI) in transcatheter aortic valve implantation (TAVI).Methods: A total of 125 consecutive TAVI patients were prospectively included in this study. Biomarkers for MI were analyzed and signs and symptoms according to VARC-2 criteria were collected from clinical records.

    Results: The criteria of elevated biomarkers and of signs or symptoms were found in 27 ( 22%) and 32 ( 26%) of the patients, respectively. According to VARC-2 definition, 12 (10%) had MI. VARC-2 definition of MI, Troponin T (TnT) >600 ng/L, and presence of signs or symptoms correlated with 6 month mortality, prolonged ICU stay, elevation of N-terminal prohormone brain natriuretic peptide, and renal impairment. No signs or symptoms were found in 7 (4 4%) of the patients who fulfilled the criterion of elevated TnT>600 ng/L. In the group with positive TnT criterion, there were no significant differences between those with and without signs or symptoms in respect to levels of TnT (1014 [585-1720] ng/L versus 704 [515-905] ng/L, p=0.17) or creatine kinase-MB ( 36 [25-52] μg/L versus 29 [25-39] μg/L, p=0.32). In the multiple logistic regression model, TnT>600 ng/L turned out as the only independent variable associated with 6-month mortality, OR 7.89 (95% CI 2.21-28.1, p = 0.001).

    Conclusion: Myocardial injury in TAVI, measured with TnT, correlates well with adverse procedural outcome. The additional requirement of signs or symptoms for the diagnosis of MI results in omission of a considerable number of clinically significant MI.

  • 3445.
    Völz, Sebastian
    et al.
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Angerås, Oskar
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Koul, Sasha
    Department of Cardiology, Lund University, Sweden.
    Haraldsson, Inger
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Sarno, Giovanna
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Sweden.
    Venetsanos, Dimitrios
    Department of Cardiology, Karolinska University Hospital, Sweden.
    Grimfärd, Per
    Department of Internal Medicine, Västmanlands Sjukhus, Sweden.
    Ulvenstam, Anders
    Department of Cardiology, Östersund Hospital, Sweden.
    Hofmann, Robin
    Department of Clinical Science and Education, Karolinska Institutet, Sweden.
    Hamid, Mehmet
    Department of Cardiology, Mälarsjukhuset, Sweden.
    Henareh, Loghman
    Department of Cardiology, Karolinska University Hospital, Sweden.
    Wagner, Henrik
    Department of Cardiology, Helsingborg Lasarett, Sweden.
    Jensen, Jens
    Unit of Cardiology, Capio S:t Görans Sjukhus, Sweden.
    Danielewicz, Mikael
    Department of Cardiology, Karlstad Hospital, Sweden.
    Östlund, Ollie
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Sweden.
    Eriksson, Peter
    Department of Cardiology, Umeå University, Sweden.
    Scherstén, Fredrik
    Department of Cardiology, Lund University, Sweden.
    Linder, Rickard
    Department of Cardiology, Danderyd Hospital, Sweden.
    Råmunddal, Truls
    Department of Cardiology, Århus University Hospital, Sweden.
    Pétursson, Pétur
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    James, Stefan
    Department of Medical Sciences and Uppsala Clinical Research Center, Uppsala University, Sweden.
    Erlinge, David
    Department of Cardiology, Lund University, Sweden.
    Omerovic, Elmir
    Department of Cardiology, Sahlgrenska University Hospital, Sweden.
    Radial versus femoral access in patients with acute coronary syndrome undergoing invasive management: A prespecified subgroup analysis from VALIDATE-SWEDEHEART2019In: European heart journal. Acute cardiovascular care., ISSN 2048-8726, article id 2048872618817217Article in journal (Refereed)
    Abstract [en]

    AIMS: In the Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART), bivalirudin was not superior to unfractionated heparin in patients with acute coronary syndrome undergoing invasive management. We assessed whether the access site had an impact on the primary endpoint of death, myocardial infarction or major bleeding at 180 days and whether it interacted with bivalirudin/unfractionated heparin.

    METHODS AND RESULTS: =0.801).

    CONCLUSIONS: Transradial access was associated with lower risk of death, myocardial infarction or major bleeding at 180 days. Bivalirudin was not associated with less bleeding, irrespective of access site.

  • 3446.
    Völz, Sebastian
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Dept Cardiol, Gothenburg, Sweden..
    Spaak, Jonas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Elf, Johan
    Skane Univ Hosp, Dept Vasc Dis, Malmo, Sweden..
    Jägrén, Christina
    South Gen Hosp, Dept Cardiol, Stockholm, Sweden..
    Lundin, Christer
    Orebro Univ Hosp, Dept Cardiol, Orebro, Sweden..
    Stenborg, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Andersson, Jonas
    Umea Univ Hosp, Dept Cardiol, Umea, Sweden..
    Rundqvist, Bengt
    Gothenburg Univ, Sahlgrenska Acad, Dept Cardiol, Gothenburg, Sweden..
    Kahan, Thomas
    Karolinska Inst, Danderyd Hosp, Dept Clin Sci, Div Cardiovasc Med, Stockholm, Sweden..
    Andersson, Bert
    Gothenburg Univ, Sahlgrenska Acad, Dept Cardiol, Gothenburg, Sweden..
    Renal sympathetic denervation in Sweden: a report from the Swedish registry for renal denervation2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 1, p. 151-158Article in journal (Refereed)
    Abstract [en]

    Background: Renal denervation (RDN) is a catheter-based intervention to treat patients with resistant hypertension. The biological effects of RDN are not fully understood, and randomized controlled trials have generated conflicting evidence. This report presents data from the Swedish Registry for Renal Denervation, an investigator-driven nationwide registry.

    Purpose: To assess the safety and efficacy of RDN on patients with resistant hypertension in a real-world clinical setting.

    Methods: This nationwide database contains patient characteristics, procedural details, and follow-up data on all RDN procedures performed in Sweden. Consecutive procedures between 2011 and 2015 were included.

    Results: The data analysis consists of 252 patients (mean age 61 +/- 10 years, 38% women; mean 4.5 +/- 1.5 antihypertensive drugs). Office SBP and DBP and 24-h ambulatory blood pressure (BP) decreased 6 months after RDN (176 +/- 23/97 +/- 17 to 161 +/- 26/91 +/- 16 mmHg, both P<0.001; and 155 +/- 17/89 +/- 14 to 147 +/- 18/82 +/- 12 mmHg, both P<0.001). Significant office and ambulatory BP reductions persisted throughout the observation period of 36 months. Major procedure-related vascular complications occurred in four patients. Renal function and number of antihypertensive drugs were unchanged during follow-up.

    Conclusion: In this complete national cohort, RDN was associated with a sustained reduction in office and ambulatory BP in patients with resistant hypertension. The procedure proved to be feasible and associated with a low-complication rate, including long-term adverse events.

  • 3447. Völz, Sebastian
    et al.
    Spaak, Jonas
    Elf, Johan
    Jägrén, Christina
    Lundin, Christer
    Stenborg, Anna
    Andersson, Jonas
    Department of Cardiology, Umeå University Hospital, Umeå.
    Rundqvist, Bengt
    Kahan, Thomas
    Andersson, Bert
    Renal sympathetic denervation in Sweden: a report from the Swedish registry for renal denervation2018In: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, no 1, p. 151-158Article in journal (Refereed)
    Abstract [en]

    Background: Renal denervation (RDN) is a catheter-based intervention to treat patients with resistant hypertension. The biological effects of RDN are not fully understood, and randomized controlled trials have generated conflicting evidence. This report presents data from the Swedish Registry for Renal Denervation, an investigator-driven nationwide registry. Purpose: To assess the safety and efficacy of RDN on patients with resistant hypertension in a real-world clinical setting. Methods: This nationwide database contains patient characteristics, procedural details, and follow-up data on all RDN procedures performed in Sweden. Consecutive procedures between 2011 and 2015 were included. Results: The data analysis consists of 252 patients (mean age 61 +/- 10 years, 38% women; mean 4.5 +/- 1.5 antihypertensive drugs). Office SBP and DBP and 24-h ambulatory blood pressure (BP) decreased 6 months after RDN (176 +/- 23/97 +/- 17 to 161 +/- 26/91 +/- 16 mmHg, both P<0.001; and 155 +/- 17/89 +/- 14 to 147 +/- 18/82 +/- 12 mmHg, both P<0.001). Significant office and ambulatory BP reductions persisted throughout the observation period of 36 months. Major procedure-related vascular complications occurred in four patients. Renal function and number of antihypertensive drugs were unchanged during follow-up. Conclusion: In this complete national cohort, RDN was associated with a sustained reduction in office and ambulatory BP in patients with resistant hypertension. The procedure proved to be feasible and associated with a low-complication rate, including long-term adverse events.

  • 3448.
    Wachtell, Kristian
    et al.
    Univ Orebro, Fac Hlth, Dept Cardiol, SE-70182 Orebro, Sweden.;Oslo Univ Hosp, Div Cardiovasc & Pulm Dis, Sect Cardiol Intervent, Dept Cardiol, Oslo, Norway..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Olivecrona, Göran K.
    Lund Univ, Clin Sci Sect, Skane Univ Hosp, Dept Coronary Heart Dis, 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.
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, SE-70182 Orebro, Sweden..
    Novel Trial Designs: Lessons Learned from Thrombus Aspiration During ST-Segment Elevation Myocardial Infarction in Scandinavia (TASTE) Trial2016In: Current Cardiology Reports, ISSN 1523-3782, E-ISSN 1534-3170, Vol. 18, no 1, article id 11Article, review/survey (Refereed)
    Abstract [en]

    In ST-elevation myocardial infarction (STEMI), thrombus material is often present in partial or total coronary occlusion of the coronary vessel. However, prior to the thrombus aspiration during ST-Segment Elevation Myocardial Infarction in Scandinavia (TASTE) trial, it remained unclear whether routine thrombus aspiration during percutaneous coronary intervention (PCI) treatment of STEMI would result in patients overall survival benefit. The TASTE trial was a multicenter, prospective, open-label, randomized, controlled clinical trial. In order to randomize patients to treatment and collect data, the infrastructure of a clinical population-based registry was used. Online data collection used the national comprehensive Swedish Coronary Angiography and Angioplasty Registry, a part of the SWEDEHEART registry. Monitoring and adjudication was done as part of the regular registry validation. There was no separate, dedicated monitoring or adjudication of endpoints. Included were 7244 patients with STEMI with chest pain and time of symptoms to hospital admission <24 h, in addition to new electrocardiographic ST-segment elevation or left bundle-branch block. Exclusion criteria were the need for emergency coronary artery bypass grafting. All-cause mortality at 30 days occurred in 2.8 % of the patients in the thrombus-aspiration group, as compared with 3.0 % in the PCI-only group (hazard ratio [HR] 0.94, 95 % confidence interval [CI] 0.72-1.22; p = 0.63). Allcause mortality at 1 year occurred in 5.3 % of the patients in the thrombus-aspiration group, as compared with 5.6 % in the PCI-only group (HR 0.94, 95 % CI 0.78-1.15; p = 0.57). No patients were lost to follow-up at 1 year. The incremental cost for trial execution was approximately US$ 300,000 or $50 per patient. Routine thrombus aspiration during PCI in patients with STEMI did not reduce the rate of all-cause mortality at 1 year. It is possible to design and conductmega-trial at only small cost compared to a similar-sized conventional randomized clinical trial.

  • 3449.
    Wadell, Daniel
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Jensen, Jens
    Englund, Erling
    Själander, Anders
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Section of Medicine.
    Triple therapy after PCI - Warfarin treatment quality and bleeding risk2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 12, article id e0209187Article in journal (Refereed)
    Abstract [en]

    Background: A combination of warfarin, aspirin and clopidogrel is indicated after percutaneous coronary intervention (PCI) in some patients, despite the higher risk of bleeding inferred by this triple therapy.

    Objectives: Whether the treatment quality of warfarin measured by iTTR (individual time within therapeutic INR range) is associated with bleeding complications during triple therapy after PCI.

    Methods: A retrospective register study consisting of 601 triple treated PCI patients from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR). The cohort was cross-matched with the Swedish Patient Registry for background characteristics and bleeding complications up to 6 months after PCI using ICD10 codes, the Prescribed Drug Registry for ongoing medications, and the national oral anticoagulation registry Auricula for warfarin treatment quality. The patients were grouped into four iTTR groups: <50%, 50–69.9%, 70–84.9% and >85% as well as iTTR above or below 70%.

    Results: Of 601 patients, 39 (6.5%) had a bleeding complication (type 2 according to BARC). Bleeding was more common for iTTR<70% compared to iTTR>70%, 28 (9.3%) vs. 11 (3.7%) (p = 0.005). The bleeding frequency increased gradually from the best group, iTTR>85% with four bleeders (3.3%) up to 17 bleeders (13.3%) in the worst group with iTTR<50% (p = 0.003), with a corresponding bleeding rate per 100 treatment years of 8.0 and 44.9, respectively. In multivariate analysis low BMI, HR 1.11 (95% CI 1.01–1.22), a medical history of anemia HR 3.17 (1.16–8.69) and iTTR < 70% HR 2.86 (1.25–6.53) increased the risk of bleeding.

    Conclusion: Triple therapy after PCI confers a high risk of bleeding events. Warfarin treatment quality measured by iTTR as well as a medical history of anemia are strong independent predictors of bleeding in these patients. Physicians should pay more attention to iTTR after PCI.

  • 3450.
    Wadell, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Physiotherapy.
    Janaudis-Ferreira, Tania
    Arne, M.
    Lisspers, K.
    Ställberg, B.
    Emtner, M.
    Hospital-based pulmonary rehabilitation in patients with COPD in Sweden-A national survey2013In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 107, no 8, p. 1195-1200Article in journal (Refereed)
    Abstract [en]

    Pulmonary rehabilitation (PR) is an evidence-based, multidisciplinary and cost-effective intervention that leads to improved health in patients with chronic obstructive pulmonary disease, COPD. However, the availability of PR programs varies between and within different countries. The aim of this study was to investigate the availability and content of hospital-based PR programs in patients with COPD in Sweden. A cross-sectional descriptive design was applied using a web-based questionnaire which was sent out to all hospitals in Sweden. The questionnaire consisted of 32 questions that concerned availability and content of PR in patients with COPD during 2011. Seventy out of 71 hospitals responded the electronic survey. Forty-six (66%) hospitals offered PR for patients with COPD. Around 75% of the hospitals in southern and middle parts of Sweden and 33% of the hospitals in the northern part offered PR. Thirty-four percent of the patients declined participation. A total number of 1355 patients participated in PR which represents 0.2% of the COPD population in Sweden. All hospitals had exercise training as major component and 76% offered an educational program. Not even half a percent of the patients with COPD in Sweden took part in a hospital-based PR program during 2011. There was a considerable geographic discrepancy in availability over the country. To enable a greater part of the increasing number of patients with COPD to take part in this evidence-based treatment, there is a need of evaluating other settings of PR programs; in primary care, at home and/or over the internet.

66676869707172 3401 - 3450 of 3690
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