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  • 101.
    Andersson, T.
    et al.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Bryngelsson, I. L.
    Department of Occupational and Environmental Medicine, Örebro University, Örebro, Sweden.
    Magnuson, A.
    Clinical Epidemiology and Biostatistics, Örebro University, Örebro, Sweden.
    Fröbert, Ole
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Henriksson, K.
    Department of Medical Science, Uppsala University, Uppsala, Sweden.
    Edvardsson, N.
    Sahlgrenska University Hospital, Gothenburg, Sweden.
    Poci, Dritan
    Örebro University, School of Medical Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    What do patients with incident atrial fibrillation and no comorbidities at the time of diagnosis die of?2017Conference paper (Refereed)
    Abstract [en]

    Introduction: Little is known about the long-term mortality risk and the causes of death in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF).

    Purposes: To identify the causes of death in patients with AF and without comorbidities at the time of AF diagnosis.

    Methods: We identified 9 519 patients with first diagnosed AF and no co-morbidities at the time of AF diagnosis in a nation-wide registry of patients hospitalized between 1995 and 2008. They represented 3.5% of the original cohort of 271186 patients hospitalized with incident AF. Patients with any diagnosis from ICD9 and ICD10 at the time of AF diagnosis wereexcluded. They were matched for age, sex and calendar year of AF diagnosis with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes.

    Results: During follow-up, 11.1% and 8.3% of patients with AF and controls died, HR 1.3, 95% CI 1.2–1.4. Most of the difference was explained by deaths of cardiovascular causes, 8.3% versus 3.9%, (HR 2.0, 95% CI 1.8–2.3). The cause of death pattern was the same in controls although at much lower rates. The age adjusted relative risk was higher in women than in men, HR 2.3, 95% CI 1.9–2.8 versus HR 1.7, 95% CI 1.4–2.0. Myocardial infarction was the most common cardiovascular cause of death but was less common among patients with AF than in controls, 20.5% versus 32.0%. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8–4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6–1.5). The time from AF diagnosis to death was 6.0±3.1 years, as compared to the time from inclusion to death, 5.8±3.1 years, in controls.

    Conclusions: Only cardiovascular diseases were more often causes of death than in controls. Women carried a significantly higher relative risk than men. The duration between AF diagnosis and death suggests that there is often time enough for early intervention with antithrombotic therapy, rhythm and/or rate control and treatment of risk factors as they appear. Interestingly, controls had the same cause of death pattern although at much lower rates.

  • 102.
    Andersson, T.
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Carlberg, Bo
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Larsen, F.
    Soderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Searching for CTEPH: a Swedish National Follow-Up after en Episode of Acute Pulmonary Embolism2016In: The Journal of Heart and Lung Transplantation, ISSN 1053-2498, E-ISSN 1557-3117, Vol. 35, no 4, p. S149-S149Article in journal (Other academic)
  • 103.
    Andersson, Therese
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Söderberg, Stefan
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Incidence of acute pulmonary embolism, related comorbidities and survival: analysis of a Swedish national cohort2017In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 17, article id 155Article in journal (Refereed)
    Abstract [en]

    Background: The aim of the study was to determine the incidence of acute pulmonary embolism (PE) in Sweden and any regional differences. To assess short-and long-term survival analysis after an episode of PE, before and after excluding patients with known malignancies, and to determine the most common comorbidities prior to the PE event. Methods: All in-hospital patients, including children, diagnosed with acute PE in 2005 were retrieved from the Swedish National Patient Registry (NPR) and incidence rates were calculated. All registered comorbidities from 1998 until the index events were collected and survival up to 4 years after the event were calculated and compared to matched controls. Results: There were 5793 patients of all ages diagnosed with acute PE in 2005 resulting in a national incidence of 0.6/1000/year. The mean age was 70 years and 52% were women. The most frequent comorbidities were cardiac-, vascular-, infectious-and gastrointestinal diseases, injuries and malignancies. The mortality rates were more than doubled in patients with recent PE compared to that in a matched control group (49.1% vs 21.9%), and the excess mortality remained after exclusion of deaths occurring within one year and after exclusion of patients with any malignancy prior to the event. Conclusions: PE is associated with high age as well as with multiple comorbidities, and with an increased shortand long-term mortality. This study highlights the importance of a proper follow-up after an acute PE.

  • 104.
    Andersson, Tommy
    Örebro University, School of Medical Sciences.
    Atrial fibrillation and cause of death, sex differences in mortality, and anticoagulation treatment in low-risk patients2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Atrial fibrillation (AF) is the most common arrhythmia but information on cause of death in patients with AF is sparse, and whether individuals at low risk of cerebral infarction (CVL) should receive antico-agulant medication is controversial. Studies of sex differences with respect to mortality risk have shown conflicting results.

    Methods: Data were obtained from Swedish National Registers. In Study I, there were 272 186 AF patients and matched controls and in Studies II and III, 9519 AF patients and no other diagnosis and matched controls. Study IV compared treatment with warfarin to no treatment in 48 433 patients with AF. Hazard ratio (HR) was calculated with 95% confidence intervals and outcome rates as number per 1000 person-years.

    Results: Ischemic heart disease (IHD) was the most common underlying cause of death and was present in 40.2% of AF patients at a HR of 1.7 (1.4-2.1). CVL/stroke was a cause of death in 13.1%, HR 2.7 (1.8-4.0). Among underlying and contributing causes of death, the most common diagnoses were IHD in 43.5%, HR 1.7 (1.4-2.0) and heart failure in 33.1%, HR 2.9 (2.2-3.7). The HRs for mortality in females with AF in age categories ≤65, 65-74, and 75-85 were 2.15, 1.72, and 1.44, and for males 1.76, 1.36, and 1.24. The rates of mortality in females with AF in age categories 55-64, 65-74, and 75-85 were 6.2, 20.7, and 57.3, and for males 8.5, 27.3, and 64.5. In patients 65-74 years, females with a CHA2DS2-VASc score of 2, and males with a score of 1 receiving warfarin treatment showed a significantly reduced risk of cerebral infarc-tion/stroke, HR 0.46 (0.25-0.83) for females and for males, HR 0.39 (0.21-0.73).

    Conclusions: Most common causes of death in AF patients were CVL/stroke, heart failure, and IHD. HR of mortality in patients with AF was higher in females than in males but absolute risk was higher in males with AF compared to females with AF. Anticoagulant therapy was benefi-cial in patients ≥65 years, regardless of the CHA2DS2-VASc score.

  • 105. Andersson, Tommy
    et al.
    Magnuson, Anders
    Bryngelsson, Ing-Liss
    Frobert, Ole
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Edvardsson, Nils
    Poci, Dritan
    Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 1, p. 91-99Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies of patients with "lone" and "idiopathic" atrial fibrillation (AF) have provided conflicting evidence concerning the development, management and prognosis of this condition. Methods: In this nation-wide, retrospective, cohort study, we studied patients diagnosed with incidental AF recorded in national Swedish registries between 1995 and 2008. Controls were matched for age, sex and calendar year of the diagnosis of AF in patients. All subjects were free of any in-hospital diagnosis from 1987 and until patients were diagnosed with AF and also free of any diagnosis within one year from the time of inclusion. Follow-up continued until 2009. We identified 9519 patients (31% women) and 12,468 matched controls. Results: Relative risks (RR) versus controls for stroke or transient ischemic attack (TIA) in women were 19.6, 4.4, 3.4 and 2.5 in the age categories <55, 55-64, 65-74 and 75-85, years respectively. Corresponding figures for men were 3.4, 2.5, 1.7 and 1.9. RR for heart failure were 6.6, 6.6, 6.3 and 3.8 in women and 7.8, 4.6, 4.9 and 2.9 in men. All RR were statistically significant with p < 0.01. RR for myocardial infarction and all-cause mortality were statistically significantly increased only in the two oldest age categories in women and 65-74 years in men. Conclusions: Patients with AF and no co-morbidities at inclusion had at least a doubled risk of stroke or TIA and a tripled risk of heart failure, through all age categories, as compared to controls. Women were at higher RR of stroke or TIA than men. 

  • 106.
    Andersson, Tommy
    et al.
    Orebro Univ, Sch Med Sci, Dept Cardiol, Orebro, Sweden..
    Magnuson, Anders
    Orebro Univ, Sch Med Sci, Clin Epidemiol & Biostat, Orebro, Sweden..
    Bryngelsson, Ing-Liss
    Orebro Univ, Sch Med Sci, Dept Occupat & Environm Med, Orebro, Sweden..
    Frobert, Ole
    Orebro Univ, Sch Med Sci, Dept Cardiol, Orebro, Sweden..
    Henriksson, Karin M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. AstraZeneca R&D, Molndal, Sweden..
    Edvardsson, Nils
    Sahlgrens Univ Hosp, Sahlgrenska Acad, Gothenburg, Sweden..
    Poci, Dritan
    Orebro Univ, Sch Med Sci, Dept Cardiol, Orebro, Sweden..
    Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls2017In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 40, no 11, p. 1076-1082Article in journal (Refereed)
    Abstract [en]

    BackgroundLittle is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF). MethodsFrom a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes. ResultsDuring follow-up, 11.1% of patients with AF and 8.3% of controls died. Cardiovascular diseases were the most common causes of death and the only diagnoses which showed significantly higher relative risk in patients with AF than controls (HR 2.0, 95% CI 1.8-2.3), and the relative risk was significantly higher in women than in men. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8-4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6-1.5). The time from AF diagnosis to death was 6.03.1years. ConclusionsIn patients with incident AF and no known comorbidities at the time of AF diagnosis, only cardiovascular diseases were more often causes of death as compared to controls. Women carried a significantly higher relative risk than men.

  • 107.
    Andersson, Tommy
    et al.
    Dept Cardiology, Örebro Univ Hospital, Örebro, Sweden.
    Magnuson, Anders
    Bryngelsson, Ing-Liss
    Dept. Occupational & Environmental Medicine, Örebro Univ Hospital, Örebro, Sweden.
    Fröbert, Ole
    Örebro University Hospital, Örebro, Sweden.
    Henriksson, Karin M.
    Dept. Laboratory Medicine, Lund Univ, Lund, Sweden; The Sahlgrenska Academy, Sahlgrenska Univ. Hospital, Gothenburg, Sweden.
    Edvardsson, Nils
    The Sahlgrenska Academy, Sahlgrenska Univ. Hospital, Gothenburg, Sweden.
    Poci, Dritan
    Örebro University Hospital.
    All-cause mortality in 272 186 patients hospitalized with incident atrial fibrillation 1995-2008: a Swedish nationwide long-term case-control study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no 14, p. 1061-1067Article in journal (Refereed)
    Abstract [en]

    Aims To evaluate long-term all-cause risk of mortality in women and men hospitalized for the first time with atrial fibrillation (AF) compared with matched controls. Methods and results A total of 272 186 patients (44% women) <= 85 years at the time of hospitalization with incidental AF 1995-2008 and 544 344 matched controls free of in-hospital diagnosis of AF were identified. Patients were followed via record linkage of the Swedish National Patient Registry and the Cause of Death Registry. Using Cox regression models, the long-term relative all-cause mortality risk, adjusted for concomitant diseases, in women vs. controls was 2.15, 1.72, and 1.44 (P < 0.001) in the age categories <= 65, 65-74, and 75-85 years, respectively. The corresponding figures for men were 1.76, 1.36, and 1.24 (P < 0.001). Among concomitant diseases, neoplasm, chronic renal failure, and chronic obstructive pulmonary disease contributed most to the increased all-cause mortality vs. controls. In patients with AF as the primary diagnosis, the relative risk of mortality was 1.63, 1.46, and 1.28 (P < 0.001) in women and 1.45, 1.17, and 1.10 (P < 0.001) in men. Conclusion Atrial fibrillation was an independent risk factor of all-cause mortality in patients with incident AF. The concomitant diseases that contributed most were found outside the thromboembolic risk scores. The highest relative risk of mortality was seen in women and in the youngest patients compared with controls, and the differences between genders in each age category were statistically significant.

  • 108.
    Andersson, Tommy
    et al.
    Dept Cardiol, Örebro Univ Hosp, Örebro, Sweden.
    Magnuson, Anders
    Clin Epidemiol & Biostat Unit, Örebro University Hospital, Örebro, Sweden.
    Bryngelsson, Ing-Liss
    Dept Occupat & Environm Med, Örebro University Hospital, Örebro, Sweden.
    Fröbert, Ole
    Örebro University Hospital. Dept Cardiol, Örebro University Hospital, Örebro, Sweden.
    Henriksson, Karin M.
    Dept Med Sci, Uppsala Univ, Uppsala, Sweden; AstraZeneca R&D, Mölndal, Sweden.
    Edvardsson, Nils
    Sahlgrenska Univ Hosp, Sahlgrenska Acad, Gothenburg, Sweden.
    Poci, Dritan
    Örebro University Hospital. Dept Cardiol, Örebro University Hospital, Örebro, Sweden.
    Gender-related differences in risk of cardiovascular morbidity and all-cause mortality in patients hospitalized with incident atrial fibrillation without concomitant diseases: A nationwide cohort study of 9519 patients2014In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 177, no 1, p. 91-99Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies of patients with "lone" and "idiopathic" atrial fibrillation (AF) have provided conflicting evidence concerning the development, management and prognosis of this condition.

    Methods: In this nation-wide, retrospective, cohort study, we studied patients diagnosed with incidental AF recorded in national Swedish registries between 1995 and 2008. Controls were matched for age, sex and calendar year of the diagnosis of AF in patients. All subjects were free of any in-hospital diagnosis from 1987 and until patients were diagnosed with AF and also free of any diagnosis within one year from the time of inclusion. Follow-up continued until 2009. We identified 9519 patients (31% women) and 12,468 matched controls.

    Results: Relative risks (RR) versus controls for stroke or transient ischemic attack (TIA) in women were 19.6, 4.4, 3.4 and 2.5 in the age categories <55, 55-64, 65-74 and 75-85, years respectively. Corresponding figures for men were 3.4, 2.5, 1.7 and 1.9. RR for heart failure were 6.6, 6.6, 6.3 and 3.8 in women and 7.8, 4.6, 4.9 and 2.9 in men. All RR were statistically significant with p < 0.01. RR for myocardial infarction and all-cause mortality were statistically significantly increased only in the two oldest age categories in women and 65-74 years in men.

    Conclusions: Patients with AF and no co-morbidities at inclusion had at least a doubled risk of stroke or TIA and a tripled risk of heart failure, through all age categories, as compared to controls. Women were at higher RR of stroke or TIA than men. (C) 2014 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-SA license (http://creativecommons.org/licenses/by-nc-sa/3.0/).

  • 109.
    Andersson, Tommy
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Magnuson, Anders
    Örebro University Hospital.
    Bryngelsson, Ing-Liss
    Örebro University Hospital. Department of Occupational and Environmental Medicine, Örebro University Hospital, Örebro, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Henriksson, Karin M.
    Department of Medical Science, Uppsala University, Uppsala, Sweden.
    Edvardsson, Nils
    Sahlgrenska Academy at Sahlgrenska University Hospital, Göteborg, Sweden.
    Poci, Dritan
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Patients with atrial fibrillation and outcomes of cerebral infarction in those with treatment of warfarin versus no warfarin with references to CHA(2)DS(2)-VASc score, age and sex: A Swedish nationwide observational study with 48 433 patients2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 5, article id e0176846Article in journal (Refereed)
    Abstract [en]

    Aims: There is controversy in the guidelines as to whether patients with atrial fibrillation and a low risk of stroke should be treated with anticoagulation, especially those with a CHA(2)DS(2)-VASc score of 1 point.

    Methods: In a retrospective, nationwide cohort study, we used the Swedish National Patient Registry, the National Prescribed Drugs Registry, the Swedish Registry of Education and the Population and Housing Census Registry. 48 433 patients were identified between 1 January 2006 and 31 December 2008 with incident atrial fibrillation who were divided in age categories, sex and a CHA(2)DS(2)-VASc score of 0, 1, 2 and >= 3 and they were included in a time-varying analysis of warfarin treatment versus no treatment. The primary end-point was cerebral infarction and stroke, and patients were followed until 31 December 2009.

    Results: Patients with 1 point from the CHA(2)DS(2)-VASc score showed the following adjusted hazard ratios (HR) with a 95% confidence interval: men 65-74 years 0.46 (0.25-0.83), men < 65 years 1.11 (0.56-2.23) and women < 65 years 2.13 (0.94-4.82), where HR < 1 indicates protection with warfarin. In patients < 65 years and 2 points, HR in men was 0.35 (0.18-0.69) and in women 1.84 (0.86-3.94) while, in women with at least 3 points, HR was 0.31 (0.16-0.59). In patients 65-74 years and 2 points, HR in men was 0.37 (0.23-0.59) and in women 0.39 ( 0.21-0.73). Categories including age >= 65 years or >= 3 points showed a statistically significant protection from warfarin.

    Conclusions: Our results support that treatment with anticoagulation may be considered in all patients with an incident atrial fibrillation diagnosis and an age of 65 years and older, i.e. also when the CHA(2)DS(2)-VASc score is 1.

  • 110.
    Andersson, Tommy
    et al.
    Örebro University, School of Medical Sciences.
    Magnuson, Anders
    School of Medical Sciences, Örebro University, Örebro, Sweden.
    Bryngelsson, Ing-Liss
    Department of Occupational and Environmental Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
    Frøbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Henriksson, Karin M.
    Department of Medical Science, Uppsala University, Uppsala and AstraZeneca R&D, Mölndal, Sweden.
    Edvardsson, Nils
    Sahlgrenska Academy at Sahlgrenska University Hospital, Göteborg, Sweden.
    Poçi, Dritan
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Patients without comorbidities at the time of diagnosis of atrial fibrillation: causes of death during long-term follow-up compared to matched controls2017In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 40, no 11, p. 1076-1082Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Little is known about the long-term, cause-specific mortality risk in patients without comorbidities at the time of diagnosis of atrial fibrillation (AF).

    METHODS: From a nation-wide registry of patients hospitalized with incident AF between 1995 and 2008 we identified 9 519 patients with a first diagnosed AF and no comorbidities at the time of AF diagnosis. They were matched with 12 468 controls. The follow-up continued until December 2008. Causes of death were classified according to the ICD-10 codes.

    RESULTS: During follow-up, 11.1% of patients with AF and 8.3% of controls died. Cardiovascular diseases were the most common causes of death and the only diagnoses which showed significantly higher relative risk in patients with AF than controls (HR 2.0, 95% CI 1.8-2.3), and the relative risk was significantly higher in women than in men. Stroke was a more common cause among patients with AF, 13.1% versus 9.7% (HR 2.7, 95% CI 1.8-4.0), while cerebral hemorrhage was more common among controls, 4.7% versus 10.2% (HR 0.9, 95% CI 0.6-1.5). The time from AF diagnosis to death was 6.0 ± 3.1 years.

    CONCLUSIONS: In patients with incident AF and no known comorbidities at the time of AF diagnosis, only cardiovascular diseases were more often causes of death as compared to controls. Women carried a significantly higher relative risk than men.

  • 111. Andersson, Tommy
    et al.
    Nagy, Peter
    Niazi, Mohammad
    Nylander, Sven
    Galbraith, Hal
    Ranjan, Santosh
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effect of Esomeprazole With/Without Acetylsalicylic Acid, Omeprazole and Lansoprazole on Pharmacokinetics and Pharmacodynamics of Clopidogrel in Healthy Volunteers2014In: American Journal of Cardiovascular Drugs, ISSN 1175-3277, E-ISSN 1179-187X, Vol. 14, no 3, p. 217-227Article in journal (Refereed)
    Abstract [en]

    The effect of proton pump inhibitors (PPIs) on the pharmacokinetics and pharmacodynamics of clopidogrel was assessed in two healthy volunteer crossover studies. Study 1: subjects received clopidogrel alone (300-mg loading dose, then 75 mg/day for 28 days) and two of three PPIs (omeprazole 80 mg, esomeprazole 40 mg or lansoprazole 60 mg) plus clopidogrel for 29 days in three treatment periods (randomized treatment sequence assignment). Study 2: subjects received clopidogrel alone (75 mg/day for 9 days) and clopidogrel alone for 4 days followed by clopidogrel plus fixed-combination esomeprazole 20 mg/low-dose acetylsalicylic acid (ASA) 81 mg for 5 days in two treatment periods (randomized treatment sequence assignment). Pharmacokinetic effects were estimated by measuring active metabolite of clopidogrel, and pharmacodynamic effects by inhibition of adenosine diphosphate (ADP)-induced platelet aggregation. There was a relative decrease of up to 50 % in exposure to the active metabolite of clopidogrel with the different PPIs (study 1), and close to 40 % with esomeprazole/low-dose ASA (study 2), compared with clopidogrel alone. There was an absolute decrease of up to 17 % in inhibition of ADP-induced platelet aggregation with co-administration of different PPIs, compared with clopidogrel alone; however, no differences in platelet inhibition were observed during co-administration with the esomeprazole/low-dose ASA fixed-dose combination. Omeprazole, esomeprazole and lansoprazole decreased systemic exposure to the active metabolite of clopidogrel in healthy volunteers, leading to modest decreases in its antiplatelet effect. However, no apparent differences in platelet inhibition were observed when esomeprazole was co-administered with low-dose ASA as a fixed-dose combination.

  • 112.
    Andreae, Christina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences.
    Appetite in patients with heart failure: Assessment, prevalence and related factors2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Appetite is an important component in nutrition for maintaining the food intake needed by the body. Decreased appetite is a common clinical problem in patients with heart failure. It has a negative impact on food intake and possibly on malnutrition and health outcomes. There is a lack of evidence on how to assess appetite in heart failure. Furthermore, there are knowledge gaps about factors associated with appetite and which role appetite plays for health status in heart failure.  

    Aim: The overall aim of the thesis was to investigate appetite in patients with heart failure. Four studies were conducted with the goal to evaluate the psychometric properties of the Council on Nutrition Appetite Questionnaire (CNAQ) (I) and to explore the prevalence of decreased appetite and related factors associated with appetite in patients with heart failure (II-IV).  

    Methods: A multicenter study was conducted in three outpatient heart failure clinics in the center of Sweden during 2009-2012. Data were collected through a baseline measurement (I-IV) and an 18-month follow-up (IV). The first study was a psychometric evaluation study (I), while the other studies had an observational cross-sectional design (II-III) and an observational prospective design (IV). One hundred and eighty-six patients diagnosed with heart failure and experiencing heart failure symptoms participated at baseline. At the 18-month follow-up study (IV), one hundred and sixteen participants from the baseline participated. Data were collected from medical records (pharmacological treatment, comorbidity, left ventricle ejection fraction, time of diagnosis), self-reported questionnaires (demographic background data, appetite, symptoms of depression, health status, sleep, self-reported physical activity), objective measurements (anthropometric assessment of body size, blood samples, six minutes’ walk test, and physical activity measured with an actigraph) and clinical assessment (New York Heart Association (NYHA) functional classification, and cognitive assessment). The main outcome variables included appetite (I, II and IV) and health status (III). Descriptive and inferential statistics were used in the studies (I-IV).  

    Results: The majority of the participants had moderate heart failure symptoms, i.e., NYHA class II (n=114, 61%). Most of the participants were men (n=130, 70%). Mean age was 70,7 years, (SD=11,0), and mean BMI was 28.7 (SD=5.3). The CNAQ showed acceptable psychometric properties for assessing appetite in patients with heart failure (I). This thesis shows that 38% of the participants experienced an appetite level that put them at risk of weight loss (I). It was shown that factors such as biological, medical, psychological (II) and physical activity/exercise capacity (IV) are associated with appetite. Also, appetite was associated with impaired health status. However, this association was found to be moderated by symptoms of depression (III). Neither appetite nor physical activity changed during the 18-month follow-up (IV).  

    Conclusion: Decreased appetite is a serious phenomenon that needs attention in the care of patients with heart failure. Health care professionals can now use a validated and simple appetite instrument to assess appetite in heart failure. In addition, attention should be paid to elderly patients and those who have symptoms of depression, sleep problems, impaired cognitive function and impaired physical activity, as well as to patients on suboptimal medical treatment. Higher appetite was shown to contribute to a better health status, but this was only evident in patients without symptoms of depression. Therefore, special attention should be paid to symptoms of depression, as this risk factor affected the association between appetite and health status. This thesis enhances the understanding of the magnitude of the problem with decreased appetite in heart failure both in numbers and factors. New priorities in nutrition care and new ideas can be established, both in practice and in research, in order to improve a nutrition care that is vital for patients with heart failure.  

  • 113.
    Andreae, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Linköping Univ, Linköping, Sweden.
    Strömberg, Anna
    Linkoping Univ, Div Nursing Sci, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden;Univ Calif Irvine, Program Nursing Sci, Irvine, CA 92717 USA.
    Chung, Misook L.
    Univ Kentucky, Coll Nursing, Lexington, KY 40506 USA.
    Hjelm, Carina
    Linkoping Univ, Div Nursing Sci, Dept Med & Hlth Sci, Linkoping, Sweden.
    Arestedt, Kristofer
    Linkoping Univ, Div Nursing Sci, Dept Med & Hlth Sci, Linkoping, Sweden;Kalmar Cty Hosp, Dept Res, Kalmar, Sweden;Linnaeus Univ, Fac Hlth & Life Sci, Kalmar, Sweden.
    Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure2018In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 2, p. E15-E20Article in journal (Refereed)
    Abstract [en]

    Background: Decreased appetite and depressive symptoms are clinical problems in patients with heart failure. Both may result in impaired health status. Objective: The aims of this study were to investigate the association between appetite and health status in patients with heart failure and to explore whether depressive symptoms moderate this association. Methods: In this cross-sectional study, patients with heart failure (n = 186; mean age, 71 years), New York Heart Association class II to IV, participated. Data on appetite (Council of Nutrition Appetite Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and health status (EQ-5D 3-level scale [EQ-5D-3L] descriptive system, EQ-5D-3L index, and EQ Visual Analog Scale) were collected by self-rating questionnaires. Pearson correlation was used to investigate the association between appetite and health status. Multiple regression was performed to examine whether depressive symptoms moderate the association between appetite and health status. Results: There was a significant association between appetite and health status for EQ-5D-3L descriptive system, mobility (P < .001), pain/discomfort (P < .001), and anxiety/depression (P < .001). This association was also shown in EQ-5D-3L index (P < .001) and EQ Visual Analog Scale (P < .001). Simple slope analysis showed that the association between appetite and health status was only significant for patients without depressive symptoms (B = 0.32, t = 4.66, P < .001). Conclusions: Higher level of appetite was associated with better health status. In moderation analysis, the association was presented for patients without depressive symptoms. Decreased appetite is an important sign of poor health status. To improve health status, health professionals should have greater attention on appetite, as well on signs of depressive symptoms.

  • 114.
    Andreae, Christina
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden.
    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.
    Chung, Misook L
    College of Nursing, University of Kentucky, Lexington, USA.
    Hjelm, Carina
    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 Thoracic and Vascular Surgery.
    Årestedt, Kristofer
    Linnaeus University, Kalmar, Kalmar County Hospital, Kalmar Sweden.
    Depressive Symptoms Moderate the Association Between Appetite and Health Status in Patients With Heart Failure2018In: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 33, no 2, p. E15-E20Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Decreased appetite and depressive symptoms are clinical problems in patients with heart failure. Both may result in impaired health status.

    OBJECTIVE: The aims of this study were to investigate the association between appetite and health status in patients with heart failure and to explore whether depressive symptoms moderate this association.

    METHODS: In this cross-sectional study, patients with heart failure (n = 186; mean age, 71 years), New York Heart Association class II to IV, participated. Data on appetite (Council of Nutrition Appetite Questionnaire), depressive symptoms (Patient Health Questionnaire-9), and health status (EQ-5D 3-level scale [EQ-5D-3L] descriptive system, EQ-5D-3L index, and EQ Visual Analog Scale) were collected by self-rating questionnaires. Pearson correlation was used to investigate the association between appetite and health status. Multiple regression was performed to examine whether depressive symptoms moderate the association between appetite and health status.

    RESULTS: There was a significant association between appetite and health status for EQ-5D-3L descriptive system, mobility (P < .001), pain/discomfort (P < .001), and anxiety/depression (P < .001). This association was also shown in EQ-5D-3L index (P < .001) and EQ Visual Analog Scale (P < .001). Simple slope analysis showed that the association between appetite and health status was only significant for patients without depressive symptoms (B = 0.32, t = 4.66, P < .001).

    CONCLUSIONS: Higher level of appetite was associated with better health status. In moderation analysis, the association was presented for patients without depressive symptoms. Decreased appetite is an important sign of poor health status. To improve health status, health professionals should have greater attention on appetite, as well on signs of depressive symptoms.

  • 115.
    Andreae, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centrum för klinisk forskning i Sörmland (CKFD). Linkoping Univ, Dept Med & Hlth Sci, Div Nursing Sci, Linkoping, Sweden..
    Strömberg, Anna
    Linkoping Univ, Dept Med & Hlth Sci, Div Nursing Sci, Linkoping, Sweden.;Fac Med & Hlth Sci, Dept Cardiol, Linkoping, Sweden..
    Sawatzky, Richard
    Trinity Western Univ, Sch Nursing, Langley, BC, Canada.;Providence Hlth Care Res Inst, Ctr Hlth Evaluat & Outcome Sci, Vancouver, BC, Canada..
    Arestedt, Kristofer
    Linkoping Univ, Dept Med & Hlth Sci, Div Nursing Sci, Linkoping, Sweden..
    Psychometric Evaluation of Two Appetite Questionnaires in Patients With Heart Failure2015In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 21, no 12, p. 954-958Article in journal (Refereed)
    Abstract [en]

    Background: Decreased appetite in heart failure (HF) may lead to undemutrition which could negatively influence prognosis. Appetite is a complex clinical issue that is often best measured with the use of self-report instruments. However, there is a lack of self-rated appetite instruments. The Council on Nutrition Appetite Questionnaire (CNAQ) and the Simplified Nutritional Appetite Questionnaire (SNAQ) are validated instruments developed primarily for elderly people. Yet, the psychometric properties have not been evaluated in HF populations. The aim of the present study was to evaluate the psychometric properties of CNAQ and SNAQ in patients with HE Methods and Results: A total of 186 outpatients with reduced ejection fraction and New York Heart Association (NYHA) functional classifications II-IV were included (median age 72 y; 70% men). Data were collected with the use of a questionnaire that included the CNAQ and SNAQ. The psychometric evaluation included data quality, factor structure, construct validity, known-group validity, and internal consistency. Unidimensionality was supported by means of parallel analysis and confirmatory factor analyses (CFAs). The CFA results indicated sufficient model fit. Both construct validity and known-group validity were supported. Internal consistency reliability was acceptable, with ordinal coefficient alpha estimates of 0.82 for CNAQ and 0.77 for SNAQ. Conclusions: CNAQ and SNAQ demonstrated sound psychometric properties and can be used to measure appetite in patients with HF.

  • 116.
    Andreassen, A.K.
    et al.
    University of Oslo, Norway .
    Andersson, B.
    Sahlgrens University Hospital, Sweden .
    Gustafsson, F.
    Rigshosp, Denmark .
    Eiskjaer, H.
    Aarhus University Hospital, Denmark .
    Rdegran, G.
    Skåne University Hospital, Sweden Lund University, Sweden .
    Gude, E.
    University of Oslo, Norway .
    Jansson, Kjell
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Solbu, D.
    Novartis Norge AS, Norway .
    Sigurdardottir, V.
    Sahlgrens University Hospital, Sweden .
    Arora, S.
    University of Oslo, Norway .
    Dellgren, G.
    Sahlgrens University Hospital, Sweden .
    Gullestad, L.
    University of Oslo, Norway University of Oslo, Norway University of Oslo, Norway .
    Everolimus Initiation and Early Calcineurin Inhibitor Withdrawal in Heart Transplant Recipients: A Randomized Trial2014In: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143, Vol. 14, no 8, p. 1828-1838Article in journal (Refereed)
    Abstract [en]

    In a randomized, open-label trial, everolimus was compared to cyclosporine in 115 de novo heart transplant recipients. Patients were assigned within 5 days posttransplant to low-exposure everolimus (3-6 ng/mL) with reduced-exposure cyclosporine (n 56), or standard-exposure cyclosporine (n = 59), with both mycophenolate mofetil and corticosteroids. In the everolimus group, cyclosporine was withdrawn after 7-11 weeks and everolimus exposure increased (6-10 ng/mL). The primary efficacy end point, measured GFR at 12 months posttransplant, was significantly higher with everolimus versus cyclosporine (mean +/- SD: 79.8 +/- 17.7 mL/min/1.73m 2 vs. 61.5 +/- 19.6 mL/min/1.73m 2; pless than0.001). Coronary intravascular ultrasound showed that the mean increase in maximal intimal thickness was smaller (0.03 mm [95% CI 0.01, 0.05 mm] vs. 0.08 mm [95% CI 0.05, 0.12 mm], p = 0.03), and the incidence of cardiac allograft vasculopathy (CAV) was lower (50.0% vs. 64.6%, p = 0.003), with everolimus versus cyclosporine at month 12. Biopsy-proven acute rejection after weeks 7-11 was more frequent with everolimus (p = 0.03). Left ventricular function was not inferior with everolimus versus cyclosporine. Cytomegalovirus infection was less common with everolimus (5.4% vs. 30.5%, pless than0.001); the incidence of bacterial infection was similar. In conclusion, everolimus-based immunosuppression with early elimination of cyclosporine markedly improved renal function after heart transplantation. Since postoperative safety was not jeopardized and development of CAV was attenuated, this strategy may benefit long-term outcome.

  • 117. Andreotti, Felicita
    et al.
    Rocca, Bianca
    Husted, Steen
    Ajjan, Ramzi A
    Ten Berg, Jurrien
    Cattaneo, Marco
    Collet, Jean-Philippe
    De Caterina, Raffaele
    Fox, Keith A A
    Halvorsen, Sigrun
    Huber, Kurt
    Hylek, Elaine M
    Lip, Gregory Y H
    Montalescot, Gilles
    Morais, Joao
    Patrono, Carlo
    Verheugt, Freek W A
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Weiss, Thomas W
    Storey, Robert F
    Antithrombotic therapy in the elderly: expert position paper of the European Society of Cardiology Working Group on Thrombosis2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 46, p. 3238-+Article in journal (Refereed)
  • 118. Angeras, O.
    et al.
    Albertsson, P.
    Ramunddal, T.
    Petursson, P.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Persson, J.
    Jensen, U.
    Sjogren, I.
    Olsson, H.
    Omerovic, E.
    Impact of left main stenosis on one-year mortality in patients undergoing coronary angiography2014In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, p. 150-150Article in journal (Refereed)
  • 119.
    Angeras, Oskar
    et al.
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Haraldsson, Inger
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Redfors, Bjorn
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Frobert, Ole
    Orebro Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Petursson, Petur
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Albertsson, Per
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Ioanes, Dan
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Odenstedt, Jacob
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Olsson, Hans
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden..
    Witt, Nils
    South Hosp Stockholm, Dept Cardiol, Stockholm, Sweden..
    Ruck, Andreas
    Karolinska Univ Hosp, Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Millgard, Jonas
    Sunderby Hosp, Dept Cardiol, Sunderbyn, Sweden..
    Nilsson, Johan
    Umea Univ Hosp, Dept Cardiol, Heart Ctr, Umea, Sweden..
    Persson, Jonas
    Danderyd Hosp, Dept Cardiol, Stockholm, Sweden..
    Soderbom, Mans
    Univ Gothenburg, Dept Econ, Gothenburg, Sweden..
    Wedel, Hans
    Univ Gothenburg, Hlth Metr, Sahlgrenska Acad, Gothenburg, Sweden..
    Erlinge, David
    Lund Univ, Dept Cardiol, Lund, Sweden..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ramunddal, Truls
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Omerovic, Elmir
    Gothenburg Univ, Sahlgrenska Acad, Inst Med, Dept Mol & Clin Med, Gothenburg, Sweden.;Sahlgrens Univ Hosp, Dept Cardiol, Gothenburg, Sweden..
    Impact of Thrombus Aspiration on Mortality, Stent Thrombosis, and Stroke in Patients With ST-Segment-Elevation Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007680Article in journal (Refereed)
    Abstract [en]

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

  • 120.
    Angerås, Oskar
    et al.
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Haraldsson, Inger
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Redfors, Björn
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Fröbert, Ole
    Örebro University, School of Medical Sciences. Department of Cardiology.
    Petursson, Petur
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Albertsson, Per
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ioanes, Dan
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Odenstedt, Jacob
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Olsson, Hans
    Department of Cardiology, Karlstad Hospital, Karlstad, Sweden.
    Witt, Nils
    Department of Cardiology, South Hospital Stockholm, Stockholm, Sweden.
    Rück, Andreas
    Department of Cardiology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Millgård, Jonas
    Department of Cardiology, Sunderby Hospital, Sunderbyn, Sweden.
    Nilsson, Johan
    Department of Cardiology, Heart Centre, Umeå University Hospital, Umeå, Sweden.
    Persson, Jonas
    Department of Cardiology, Danderyd University Hospital, Stockholm, Sweden.
    Söderbom, Måns
    Department of Economics, University of Gothenburg, Gothenburg, Sweden.
    Wedel, Hans
    Health Metrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Erlinge, David
    Department of Cardiology, Lund University, Lund, Sweden.
    James, Stefan
    Department of Medical Sciences, Uppsala Clinical Research Center, Uppsala University, Uppsala, Sweden.
    Ramunddal, Truls
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Omerovic, Elmir
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Impact of Thrombus Aspiration on Mortality, Stent Thrombosis, and Stroke in Patients With ST-Segment-Elevation Myocardial Infarction: A Report From the Swedish Coronary Angiography and Angioplasty Registry2018In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 7, no 1, article id e007680Article in journal (Refereed)
    Abstract [en]

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

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

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

  • 121.
    Angiolillo, Dominick J.
    et al.
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Rollini, Fabiana
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Sheffield, S Yorkshire, England..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Harvard Med Sch, Heart & Vasc Ctr, Boston, MA USA..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Schneider, David J.
    Univ Vermont, Cardiovasc Res Inst, Cardiol Unit, Dept Med, Burlington, VT 05405 USA..
    Sibbing, Dirk
    Ludwig Maximilians Univ Munchen, Dept Cardiol, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Berlin, Germany..
    So, Derek Y. F.
    Univ Ottawa, Heart Inst, Div Cardiol, Ottawa, ON, Canada..
    Trenk, Dietmar
    Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol 2, Freiberg, Germany..
    Alexopoulos, Dimitrios
    Natl & Capodistrian Univ Athens, Dept Cardiol 2, Attikon Univ Hosp, Athens, Greece..
    Gurbel, Paul A.
    Inova Heart & Vasc Inst, Inova Ctr Thrombosis Res & Drug Dev, Falls Church, VA USA..
    Hochholzer, Willibald
    Univ Heart Ctr Freiburg Bad Krozingen, Dept Cardiol & Angiol 2, Freiberg, Germany..
    De Luca, Leonardo
    San Giovanni Evangelista Hosp, Lab Intervent Cardiol, Div Cardiol, Tivoli Rome, Italy.;Mediterranean Acad Assoc Res & Studies Cardiol, Marseille, France.;Aix Marseille Univ, INSERM, UMRS 1076, Marseille, France..
    Bonello, Laurent
    Hop Nord Marseille, AP HP, Dept Cardiol, Marseille, France..
    Aradi, Daniel
    Heart Ctr Balatonfured, Budapest, Hungary.;Semmelweis Univ Budapest, Budapest, Hungary..
    Cuisset, Thomas
    CHU Timone, Dept Cardiol, Marseille, France.;Aix Marseille Univ, Fac Med, Marseille, France..
    Tantry, Udaya S.
    Inova Heart & Vasc Inst, Inova Ctr Thrombosis Res & Drug Dev, Falls Church, VA USA..
    Wang, Tracy Y.
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Valgimigli, Marco
    Bern Univ Hosp, Swiss Cardiovasc Ctr Bern, Bern, Switzerland..
    Waksman, Ron
    MedStar Washington Hosp Ctr, Sect Intervent Cardiol, Washington, DC USA..
    Mehran, Roxana
    Icahn Sch Med Mt Sinai, New York, NY USA..
    Montalescot, Gilles
    Sorbonne Univ Paris 6, Hop Pitie Salpetriere, ACTION Study Grp, Paris, France..
    Franchi, Francesco
    Univ Florida, Coll Med, Div Cardiol, Jacksonville, FL USA..
    Price, Matthew J.
    Scripps Clin, Div Cardiovasc Dis, La Jolla, CA USA..
    International Expert Consensus on Switching Platelet P2Y(12) Receptor-Inhibiting Therapies2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 136, no 20, p. 1955-+Article in journal (Refereed)
    Abstract [en]

    Dual antiplatelet therapy with aspirin and a P2Y(12) inhibitor is the treatment of choice for the prevention of atherothrombotic events in patients with acute coronary syndromes and for those undergoing percutaneous coronary interventions. The availability of different oral P2Y(12) inhibitors (clopidogrel, prasugrel, ticagrelor) has enabled physicians to contemplate switching among therapies because of specific clinical scenarios. The recent introduction of an intravenous P2Y(12) inhibitor (cangrelor) further adds to the multitude of modalities and settings in which switching therapies may occur. In clinical practice, it is not uncommon to switch P2Y(12) inhibitor, and switching may be attributed to a variety of factors. However, concerns about the safety of switching between these agents have emerged. Practice guidelines have not fully elaborated on how to switch therapies, leaving clinicians with limited guidance on when and how to switch therapies when needed. This prompted the development of this expert consensus document by key leaders from North America and Europe with expertise in basic, translational, and clinical sciences in the field of antiplatelet therapy. This expert consensus provides an overview of the pharmacology of P2Y(12) inhibitors, different modalities and definitions of switching, and available literature and recommendations for switching between P2Y(12) inhibitors.

  • 122. Antoni, Gunnar
    et al.
    Lubberink, Mark
    Estrada, Sergio
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Carlson, Kristina
    Lindsjö, Lars
    Kero, Tanja
    Långström, Bengt
    Granstam, Sven-Olof
    Rosengren, Sara
    Vedin, Ola
    Wassberg, Cecilia
    Wikstrom, Gerhard
    Westermark, Per
    Sörensen, Jens
    In Vivo Visualization of Amyloid Deposits in the Heart with C-11-PIB and PET2013In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 54, no 2, p. 213-220Article in journal (Refereed)
    Abstract [en]

    Cardiac amyloidosis is a differential diagnosis in heart failure and is associated with high mortality. There is currently no noninvasive imaging test available for specific diagnosis. N-[methyl-C-11]2-(4'-methylamino-phenyl)-6-hydroxybenzothiazole (C-11-PIB) PET is used in the evaluation of brain amyloidosis. We evaluated the potential use of C-11-PIB PET in systemic amyloidosis affecting the heart. Methods: Patients (n = 10) diagnosed with systemic amyloidosis-including heart involvement of either monoclonal immunoglobulin light-chain (AL) or transthyretin (ATTR) type- and healthy volunteers (n = 5) were investigated with PET/CT using C-11-PIB to study cardiac amyloid deposits and with C-11-acetate to measure myocardial blood flow to study the impact of global and regional perfusion on PIB retention. Results: Myocardial C-11-PIB uptake was visually evident in all patients 15-25 min after injection and was not seen in any volunteer. A significant difference in C-11-PIB retention in the heart between patients and healthy controls was found. The data indicate that myocardial amyloid deposits in patients diagnosed with systemic amyloidosis could be visualized with C-11-PIB. No correlation between C-11-PIB retention index and myocardial blood flow as measured with C-11-acetate was found on the global level, whereas a positive correlation on the segmental level was seen in a single patient. Conclusion: C-11-PIB and PET could be a method to study systemic amyloidosis of type AL and ATTR affecting the heart and should be investigated further both as a diagnostic tool and as a noninvasive method for treatment follow-up.

  • 123. Antoniewicz, L.
    et al.
    Kabele, Mikael
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lundback, M.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Increased Arterial Stiffness In Chronic Swedish Snus Users2017In: American Journal of Respiratory and Critical Care Medicine, ISSN 1073-449X, E-ISSN 1535-4970, Vol. 195Article in journal (Refereed)
  • 124.
    Antoniewicz, Lukasz
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Karolinska Institutet, Department of Clinical Sciences, Division of Internal Medicine, Danderyd Hospital, Stockholm, Sweden.
    Novo, Mirza
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Bosson, Jenny A.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine.
    Lundbäck, Magnus
    Brief exposure to Swedish snus causes divergent vascular responses in healthy male and female volunteers2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0195493Article in journal (Refereed)
    Abstract [en]

    Introduction: The use of Swedish oral moist snuff, known as snus, has for a long time been limited to the Scandinavian countries. With declining cigarette sales in the western world, tobacco companies have looked to the development of alternative tobacco products. In 2006 snus products were launched in the US. Even though several studies have demonstrated negative health effects, snus is often depicted as harmless.

    The aim of the present study was to investigate acute vascular effects of snus as measured by arterial stiffness as well as blood pressure and heart rate.

    Methods: Two separate randomized double-blind crossover studies with the same study design were pooled for analysis. Twenty-nine healthy snus-users (17 females, 12 males) were included. Snus (Göteborgs Rapé) and tobacco free snus (Onico) were administered in a randomized order at two separate visits. Arterial stiffness, blood pressure and heart rate were measured at baseline as well as every five minutes for 40 minutes during exposure. Following snus removal, measurements continued for 30 minutes post exposure. Arterial stiffness was measured using pulse wave velocity (Vicorder) and pulse wave analysis (Sphygmocor).

    Results: Compared to placebo, snus significantly increased systolic and diastolic blood pressure as well as heart rate, however, only in females (p = 0.004, p = 0.006 and p<0.001 respectively). No changes were seen in arterial stiffness measurements in either gender.

    Conclusion: We observed an increase in blood pressure and heart rate only in females, but not in males due to snus usage as compared to placebo. This novel finding was surprising and needs to be further investigated considering most of the earlier studies have mainly focused on male snus users and the increasing usage of snus among females.

  • 125. Apers, Silke
    et al.
    Kovacs, Adrienne H.
    Luyckx, Koen
    Alday, Luis
    Berghammer, Malin
    Budts, Werner
    Callus, Edward
    Caruana, Maryanne
    Chidambarathanu, Shanthi
    Cook, Stephen C.
    Dellborg, Mikael
    Enomoto, Junko
    Eriksen, Katrine
    Fernandes, Susan M.
    Jackson, Jamie L.
    Johansson, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Khairy, Paul
    Kutty, Shelby
    Menahem, Samuel
    Rempel, Gwen
    Sluman, Maayke A.
    Soufi, Alexandra
    Thomet, Corina
    Veldtman, Gruschen
    Wang, Jou-Kou
    White, Kamila
    Moons, Philip
    Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study (APPROACH-IS): Rationale, design, and methods2015In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 179, p. 334-342Article in journal (Refereed)
    Abstract [en]

    Background: Data on patient-reported outcomes (PROs) in adults with congenital heart disease (CHD) are inconsistent and vary across the world. Better understanding of PROs and their differences across cultural and geographic barriers can best be accomplished via international studies using uniform research methods. The APPROACH-IS consortium (Assessment of Patterns of Patient-Reported Outcomes in Adults with Congenital Heart disease - International Study) was created for this purpose and investigates PROs in adults with CHD worldwide. This paper outlines the project rationale, design, and methods. Methods/design: APPROACH-IS is a cross-sectional study. The goal is to recruit 3500-4000 adults with CHD from 15 countries in five major regions of the world (Asia, Australia, Europe, North and South America). Self-report questionnaires are administered to capture information on PRO domains: (i) perceived health status (12-item Short-form Health Survey & EuroQOL-5D); (ii) psychological functioning (Hospital Anxiety and Depression Scale); (iii) health behaviors (Health-Behavior Scale-Congenital Heart Disease); and (iv) quality of life (Linear Analog Scale & Satisfaction With Life Scale). Additionally, potential explanatory variables are assessed: (i) socio-demographic variables; (ii) medical history (chart review); (iii) sense of coherence (Orientation to Life Questionnaire); and (iv) illness perceptions (Brief Illness Perception Questionnaire). Descriptive analyses and multilevel models will examine differences in PROs and investigate potential explanatory variables. Discussion: APPROACH-IS represents a global effort to increase research understanding and capacity in the field of CHD, and will have major implications for patient care. Results will generate valuable information for developing interventions to optimize patients' health and well-being. 

  • 126.
    Appelros, Peter
    et al.
    Örebro Univ Hosp.
    Farahmand, Bahman
    Alzheimer Dis Res Ctr, Epiconsultant Formerly Karolinska Inst, Stockholm, Sweden..
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    To Treat or Not to Treat: Anticoagulants as Secondary Preventives to the Oldest Old With Atrial Fibrillation2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 6, p. 1617-1622Article in journal (Refereed)
    Abstract [en]

    Background and Purpose-Anticoagulant treatment is effective for preventing recurrent ischemic strokes in patients who have atrial fibrillation. This benefit is paid by a small increase of hemorrhages. Anticoagulant-related hemorrhages seem to increase with age, but there are few studies showing whether the benefits of treatment persist in old age.

    Methods-For this observational study, 4 different registers were used, among them Riksstroke, the Swedish Stroke Register. Patients who have had a recent ischemic stroke, were 80 to 100 years of age, and had atrial fibrillation, were included from 2006 through 2013. The patients were stratified into 3 age groups: 80 to 84, 85 to 89, and ?90 years of age. Information on stroke severity, risk factors, drugs, and comorbidities was gathered from the registers. The patients were followed with respect to ischemic or hemorrhagic stroke, other hemorrhages, or death.

    Results-Of all 23 356 patients with atrial fibrillation, 6361 (27%) used anticoagulants after an ischemic stroke. Anticoagulant treatment was associated with less recurrent ischemic stroke in all age groups. Hemorrhages increased most in the >= 90-year age group, but this did not offset the overall beneficial effect of the anticoagulant. Apart from age, no other cardiovascular risk factor or comorbidity was identified that influenced the risk of anticoagulant-associated hemorrhage. Drugs other than anticoagulants did not influence the incidence of major hemorrhage.

    Conclusions-Given the patient characteristics in this study, there is room for more patients to be treated with anticoagulants, without hemorrhages to prevail. In nonagenarians, hemorrhages increased somewhat more, but this did not affect the overall outcome in this age stratum.

  • 127.
    Appelros, Peter
    et al.
    Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Farahmand, Bahman
    Epi-consultants (Formerly Karolinska Institute), Alzheimer Disease Research Center, Stockholm, Sweden.
    Terént, Andreas
    Department of Medical Sciences,Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden.
    Åsberg, Signild
    Department of Medical Sciences, Akademiska Sjukhuset, Uppsala University, Uppsala, Sweden.
    To Treat or Not to Treat: Anticoagulants as Secondary Preventives to the Oldest Old With Atrial Fibrillation.2017In: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 48, no 6, p. 1617-1623Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND PURPOSE: Anticoagulant treatment is effective for preventing recurrent ischemic strokes in patients who have atrial fibrillation. This benefit is paid by a small increase of hemorrhages. Anticoagulant-related hemorrhages seem to increase with age, but there are few studies showing whether the benefits of treatment persist in old age.

    METHODS: For this observational study, 4 different registers were used, among them Riksstroke, the Swedish Stroke Register. Patients who have had a recent ischemic stroke, were 80 to 100 years of age, and had atrial fibrillation, were included from 2006 through 2013. The patients were stratified into 3 age groups: 80 to 84, 85 to 89, and ≥90 years of age. Information on stroke severity, risk factors, drugs, and comorbidities was gathered from the registers. The patients were followed with respect to ischemic or hemorrhagic stroke, other hemorrhages, or death.

    RESULTS: Of all 23 356 patients with atrial fibrillation, 6361 (27%) used anticoagulants after an ischemic stroke. Anticoagulant treatment was associated with less recurrent ischemic stroke in all age groups. Hemorrhages increased most in the ≥90-year age group, but this did not offset the overall beneficial effect of the anticoagulant. Apart from age, no other cardiovascular risk factor or comorbidity was identified that influenced the risk of anticoagulant-associated hemorrhage. Drugs other than anticoagulants did not influence the incidence of major hemorrhage.

    CONCLUSIONS: Given the patient characteristics in this study, there is room for more patients to be treated with anticoagulants, without hemorrhages to prevail. In nonagenarians, hemorrhages increased somewhat more, but this did not affect the overall outcome in this age stratum.

  • 128.
    Appelros, Peter
    et al.
    University of Örebro, Sweden.
    Hals Berglund, Maria
    University Hospital Norrland, Sweden.
    Ström, Jakob O.
    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. University of Örebro, Sweden.
    Long-Term Risk of Stroke after Transient Ischemic Attack2017In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 43, no 1-2, p. 25-30Article in journal (Refereed)
    Abstract [en]

    Background: In the absence of active management, the stroke risk after a transient ischemic attack (TIA) may be high. Almost 10 years ago, the results of the EXPRESS and SOS-TIA studies called for a more rapid management of TIA patients. The purpose of this study was to investigate the other stroke risks in the longer term, after the implementation of a more active approach to TIA. We also wanted to assess the predictive value of the ABCD2 score in this context. Methods: Riksstroke is the national stroke registry in Sweden. Data from Riksstrokes TIA module, and the national cause-of-death register, for the years 2011 and 2012 were used in this study. Stroke occurrence was monitored via Riksstroke. Coxs regression was used for risk evaluation. The predictive value of the ABCD2 score was assessed by calculating the area under the receiver operating characteristics curve. Results: A total of 15,068 TIA episodes occurred in 14,102 patients. The follow-up time varied between 0 and 819 days, with an average of 417 days. The mortality for all TIA patients during the follow-up time was 7.1%. Of the unique patients, 545 had one or more strokes (3.9%), corresponding to 34 events per 1,000 person years. Significant risk factors for stroke were: age, previous TIA, atrial fibrillation (AF), oral anticoagulant (OAC) treatment, hypertension treatment, and the ABCD2 items speech impairment, unilateral weakness, and diabetes mellitus. The ABCD2 score correlated with a subsequent stroke, but its predictive value was low. Conclusion: The risk of stroke is low after the acute phase of a TIA, probably lower than in previous studies. This may be due to better secondary prevention in recent years. Several risk factors predict stroke, notably hypertensive treatment, which may be inadequate; and AF, where OACs may be under-used. It is difficult to identify the role of the ABCD2 score in clinical practice. (C) 2016 S. Karger AG, Basel

  • 129.
    Appelros, Peter
    et al.
    Örebro University Hospital. Department of Neurology, Örebro University Hospital, Örebro, Sweden.
    Háls Berglund, Maria
    Riksstroke, Medicincentrum, University Hospital of Norrland, Umeå, Sweden.
    Ström, Jakob O.
    Örebro University, School of Medical Sciences. Department of Clinical Chemistry, Linköping University, Linköping, Sweden.
    Long-Term Risk of Stroke after Transient Ischemic Attack2017In: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 43, no 1-2, p. 25-30Article in journal (Refereed)
    Abstract [en]

    Background: In the absence of active management, the stroke risk after a transient ischemic attack (TIA) may be high. Almost 10 years ago, the results of the EXPRESS and SOS-TIA studies called for a more rapid management of TIA patients. The purpose of this study was to investigate the other stroke risks in the longer term, after the implementation of a more active approach to TIA. We also wanted to assess the predictive value of the ABCD2 score in this context.

    Methods: Riksstroke is the national stroke registry in Sweden. Data from Riksstroke's TIA module, and the national cause-of-death register, for the years 2011 and 2012 were used in this study. Stroke occurrence was monitored via Riksstroke. Cox's regression was used for risk evaluation. The predictive value of the ABCD2 score was assessed by calculating the area under the receiver operating characteristics curve.

    Results: A total of 15,068 TIA episodes occurred in 14,102 patients. The follow-up time varied between 0 and 819 days, with an average of 417 days. The mortality for all TIA patients during the follow-up time was 7.1%. Of the unique patients, 545 had one or more strokes (3.9%), corresponding to 34 events per 1,000 person years. Significant risk factors for stroke were: age, previous TIA, atrial fibrillation (AF), oral anticoagulant (OAC) treatment, hypertension treatment, and the ABCD2 items speech impairment, unilateral weakness, and diabetes mellitus. The ABCD2 score correlated with a subsequent stroke, but its predictive value was low.

    Conclusion: The risk of stroke is low after the acute phase of a TIA, probably lower than in previous studies. This may be due to better secondary prevention in recent years. Several risk factors predict stroke, notably hypertensive treatment, which may be inadequate; and AF, where OACs may be under-used. It is difficult to identify the role of the ABCD2 score in clinical practice.

  • 130. Appelros, Peter
    et al.
    Stegmayr, Birgitta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Terént, Andreas
    Riks-Stroke och hur fallgropar vid tolkning av resultaten undviks2008In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 105, no 8, p. 529-533Article in journal (Other academic)
  • 131. Appelros, Peter
    et al.
    Terént, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Thrombolysis in acute stroke2015In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, no 9976, p. 1394-1394Article in journal (Refereed)
  • 132. Apple, FS
    et al.
    Jaffe, AS
    Collinson, P
    Mockel, M
    Ordonez-Llanos, J
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hollander, J
    Plebani, M
    Than, M
    Chan, MH
    IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays2015In: Clinical Biochemistry, ISSN 0009-9120, E-ISSN 1873-2933, Vol. 48, no 4-5, p. 201-203Article in journal (Refereed)
    Abstract [en]

    In 2011, the IFCC Task Force on Clinical Applications of Cardiac Bio-Markers (TF-CB) was formed, with the purpose of providing evidence based educational materials to assist all biomarker users, i.e. laboratorians, clinicians, researchers, in-vitro diagnostics and regulatory agencies, in better understanding important analytical and clinical aspects of established and novel cardiac biomarkers for use in clinical practice and research. The goal of the task force was to promulgate the same information conjointly through the in vitro diagnostic industry to the laboratory, emergency department and cardiologists. The initial undertaking of the TF-CB, which is comprised of laboratory medicine scientists, emergency medicine physicians and cardiologists, was to address two key issues pertaining to implementing high-sensitivity cardiac troponin (hs-cTn) assays in clinical practice: the 99th percentile upper reference limit (URL) and calculating serial change values in accord with the Universal Definition of AMI. The highlights of both concepts from IFCC statements are described.

  • 133. Aradi, Daniel
    et al.
    Collet, Jean-Philippe
    Mair, Johannes
    Plebani, Mario
    Merkely, Bela
    Jaffe, Allan S.
    Moeckel, Martin
    Giannitsis, Evangelos
    Thygesen, Kristian
    ten Berg, Jurrien M.
    Mueller, Christian
    Storey, Robert F.
    Lindah, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Huber, Kurt
    Platelet function testing in acute cardiac care - is there a role for prediction or prevention of stent thrombosis and bleeding?2015In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 113, no 2, p. 221-230Article in journal (Refereed)
    Abstract [en]

    The role of platelet function testing in acute coronary syndrome patients undergoing percutaneous coronary intervention remains controversial despite the fact that high platelet reactivity is an independent predictor of stent thrombosis and emerging evidence suggests also a link between low platelet reactivity and bleeding. In this expert opinion paper, the Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association and the Working Group on Thrombosis of the European Society of Cardiology aim to provide an overview of current evidence in this area and recommendations for practicing clinicians.

  • 134.
    Arbelo, Elena
    et al.
    Univ Barcelona, Hosp Clin Barcelona, Cardiovasc Inst, Dept Cardiol, Barcelona, Spain..
    Brugada, Josep
    Univ Barcelona, Hosp Clin Barcelona, Cardiovasc Inst, Dept Cardiol, Barcelona, Spain..
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Laroche, Cecile
    European Soc Cardiol, EURObservat Res Programme, Sophia Antipolis, France..
    Kautzner, Josef
    Inst Clin & Expt Med, Dept Cardiol, Prague, Czech Republic..
    Pokushalov, Evgeny
    State Res Inst Circulat Pathol, Arrhythmia Dept, Novosibirsk, Russia.;State Res Inst Circulat Pathol, EP Lab, Novosibirsk, Russia..
    Raatikainen, Pekka
    Tampere Univ Hosp, Heart Ctr Co, Tampere, Finland..
    Efremidis, Michael
    Evangelismos Gen Hosp Athens, Lab Cardiac Electrophysiol, Dept Cardiol 2, Athens, Greece..
    Hindricks, Gerhard
    Univ Leipzig, Ctr Heart, Dept Electrophysiol, Leipzig, Germany..
    Barrera, Alberto
    Univ Hosp Virgen de la Victoria, Dept Cardiol, Arrhythmia Unit, Malaga, Spain..
    Maggioni, Aldo
    European Soc Cardiol, EURObservat Res Programme, Sophia Antipolis, France.;Assoc Nazl Med Cardiol Osped Res Ctr AMCO Res Ctr, Florence, Italy..
    Tavazzi, Luigi
    Maria Cecilia Hosp, ES Hlth Sci Fdn, GVM Care & Res, Cotignola, Italy..
    Dagres, Nikolaos
    Univ Leipzig, Ctr Heart, Dept Electrophysiol, Leipzig, Germany..
    Contemporary management of patients undergoing atrial fibrillation ablation: in-hospital and 1-year follow-up findings from the ESC-EHRA atrial fibrillation ablation long-term registry2017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 17, p. 1303-1316Article in journal (Refereed)
    Abstract [en]

    Aims The ESC-EHRA Atrial Fibrillation Ablation Long-Term registry is a prospective, multinational study that aims at providing an accurate picture of contemporary real-world ablation for atrial fibrillation (AFib) and its outcome. Methods and results A total of 104 centres in 27 European countries participated and were asked to enrol 20-50 consecutive patients scheduled for first and re-do AFib ablation. Pre-procedural, procedural and 1-year follow-up data were captured on a web-based electronic case record form. Overall, 3630 patients were included, of which 3593 underwent an AFib ablation (98.9%). Median age was 59 years and 32.4% patients had lone atrial fibrillation. Pulmonary vein isolation was attempted in 98.8% of patients and achieved in 95-97%. AFib-related symptoms were present in 97%. Inhospital complications occurred in 7.8% and one patient died due to an atrioesophageal fistula. One-year follow-up was performed in 3180 (88.6%) at a median of 12.4 months (11.9-13.4) after ablation: 52.8% by clinical visit, 44.2% by telephone contact and 3.0% by contact with the general practitioner. At 12-months, the success rate with or without antiarrhythmic drugs (AADs) was 73.6%. A significant portion (46%) was still on AADs. Late complications included 14 additional deaths (4 cardiac, 4 vascular, 6 other causes) and 333 (10.7%) other complications. Conclusion AFib ablation in clinical practice is mostly performed in symptomatic, relatively young and otherwise healthy patients. Overall success rate is satisfactory, but complication rate remains considerable and a significant portion of patients remain on AADs. Monitoring after ablation shows wide variations. Antithrombotic treatment after ablation shows insufficient guideline-adherence.

  • 135.
    Arefalk, Gabriel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Smokeless Tobacco (Snus) and Cardiovascular Disease: Associations with Heart Failure and Prognosis after Myocardial Infarction2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Previous investigations of snus use (oral moist snuff, a Swedish form of smokeless tobacco) and cardiovascular disease have generally focused on atherosclerotic events such as myocardial infarction and stroke, likely because smoking is such a well-established risk factor for atherosclerotic disease. Smokeless administration of tobacco circumvents most of the atherogenic effects of the combusted products from smoked tobacco, but it is possible that the potent autonomic and hemodynamic effects of snus and nicotine per se are detrimental for cardiovascular tissues.

    The aim of this thesis was to investigate if snus is associated with development of heart failure and the prognosis after myocardial infarction. We used data from Swedish cohort studies and the national quality register for myocardial infarctions (SWEDEHEART), with linkages to national registers.

    Snus use was associated with a higher risk of heart failure in a dose-response manner. This association was specific to non-ischemic heart failure, implying a direct myocardial effect, rather than an atherogenic effect (papers I and II).

    Acute, short-term or long-term outcomes following a myocardial infarction were not consistently worse among snus users relative to snus non-users, although snus use was associated with an increased risk of death after myocardial infarction among never-smokers (paper III).

    Discontinuation of snus use after a myocardial infarction was associated with an almost halved mortality risk, similar to the benefit associated with smoking cessation (paper IV).

    Although smoking was consistently stronger related to all adverse outcomes, and with reservations due to the observational design, the findings from this thesis indicate that snus should not be regarded as harmless. Snus use was associated with a higher risk of heart failure and post-myocardial infarction mortality, which may have public health implications for the risk assessment of snus, and potentially other modes of smokeless nicotine.

  • 136.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Galanti, Rosaria
    Lundberg, Michael
    Ye, Weimin
    Norberg, Margareta
    Lindmark, Krister
    Pedersen, Nancy
    Trolle Lagerros, Ylva
    Bellocco, Rino
    Lager, Anton
    Wennberg, Patrik
    Eriksson, Marie
    Östergren, Per-Olof
    Alfredsson, Lars
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Magnusson, Cecilia
    Smokeless Tobacco (Snus) and Risk of Heart Failure of Ischemic and Non-Ischemic Origin: a Pooled Analysis of Eight Prospective Cohort StudiesManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Snus, a Swedish type of smokeless tobacco, has potent acute hemodynamic effects, which could provoke stress on the cardiovascular system, including the myocardium. Snus has, however, not been linked to risk of ischemic heart disease. Therefore, we hypothesized that snus use increases the risk for heart failure of non-ischemic origin.

    Methods

    We conducted a pooled analysis of eight Swedish prospective cohort studies involving individual participant data from 350,711 men. Shared frailty models with random effects at the cohort level, were used to estimate hazard ratios (HRs) with 95 % confidence intervals (CIs) of heart failure in relation to snus use. We investigated dose-response associations, and association with ischemic and non-ischemic heart failure in separate. For positive control purposes, we also investigated associations between smoking and risk of heart failure.

    Results

    During a median follow-up time of 16 years, 5,404 men were hospitalized for heart failure. In models adjusting for age, smoking, previous myocardial infarction and educational level, current snus use was associated with a higher risk of heart failure (HR 1.27, 95 % CI 1.07-1.50), relative to non-current snus use. A dose-response pattern was observed, with higher risk with more snus cans used per week. We observed an association of snus use with non-ischemic heart failure, HR 1.34 (95 % CI 1.11-1.63), but not with ischemic heart failure, HR 1.01 (95 % CI 0.72-1.42). Smoking was more strongly associated with heart failure, particularly of ischemic origin, than snus use.

    Conclusions

    Snus use was associated with a modestly increased risk for heart failure of non-ischemic origin in a dose-response manner. This finding has public health implications for the risk assessment of snus use, and potentially other modes of smokeless use of nicotine.

  • 137.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction2014In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 130, no 4, p. 325-323Article in journal (Refereed)
    Abstract [en]

    Background-Given the indications of increased risk for fatal myocardial infarction (MI) in people who use snus, a moist smokeless tobacco product, we hypothesized that discontinuation of snus use after an MI would reduce mortality risk. Methods and Results-All patients who were admitted to coronary care units for an MI in Sweden between 2005 and 2009 and were <75 years of age underwent a structured examination 2 months after discharge (the baseline of the present study). We investigated the risk of mortality in post-MI snus quitters (n=675) relative to post-MI continuing snus users (n=1799) using Cox proportional hazards analyses. During follow-up (mean 2.1 years), 83 participants died. The mortality rate was 9.7 (95% confidence interval, 5.7-16.3) per 1000 person-years at risk in post-MI snus quitters and 18.7 (14.8-23.6) per 1000 person-years at risk in post-MI continuing snus users. After adjustment for age and sex, post-MI snus quitters had half the mortality risk of post-MI continuing snus users (hazard ratio, 0.51; 95% confidence interval, 0.29-0.91). In a multivariable-adjusted model, the hazard ratio was 0.57 (95% confidence interval, 0.32-1.02). The corresponding estimate for people who quit smoking after MI versus post-MI continuing smokers was 0.54 (95% confidence interval, 0.42-0.69). Conclusions-In this study, discontinuation of snus use after an MI was associated with a nearly halved mortality risk, similar to the benefit associated with smoking cessation. These observations suggest that the use of snus after MI should be discouraged.

  • 138.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hambraeus, Kristina
    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, Center for Clinical Research Dalarna.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Response to Letter Regarding Article, "Discontinuation of Smokeless Tobacco and Mortality Risk After Myocardial Infarction"2015In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 131, no 17, p. E423-E423Article in journal (Refereed)
  • 139.
    Arefalk, Gabriel
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Svennblad, Bodil
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Andersen, Kasper
    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, Cardiovascular epidemiology.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Smokeless Tobacco (Snus) and Outcome of Myocardial Infarction: a SWEDEHEART StudyManuscript (preprint) (Other academic)
    Abstract [en]

    Background

    Based on effects of nicotine and snus (a smokeless tobacco) on hemodynamics, pro-arrhythmia and remodelling, in combination with indications of increased risk for fatal myocardial infarction (MI) in snus users; we hypothesised that the outcome of an MI may be worse in snus users.

    Methods

    Data was extracted from the SWEDEHEART registry for all patients who underwent coronary angiography in Sweden due to MI between December 2009 and December 2014. In snus users (n=4,950) relative to snus non-users (n=55,412), we compared risks of a large MI (defined as hs-cTnT of  > 10,000 ng/L, cTnT > 10 μg/L or cTnI > 10 μg/L) and death in the acute (in-hospital) setting, and death+HF (a combined endpoint of all-cause death or hospitalization for heart failure) and all-cause death at short- (<28 days) and long-term follow-up. Relations of snus use to outcomes were also analysed in pre-specified subgroups of never, previous and current smokers.

    Results

    A large MI was diagnosed in 10,975 patients. During long-term follow-up (median 1.9 years), 7,758 either died (n=6,044) or were hospitalized due to heart failure (n=1,714). In models adjusting for age, gender, smoking, previous MI and occupational classification (employed, unemployed/sick leave and retired), snus use was not associated with risk of large MI (odds ratio 1.01; 95% confidence interval (CI) 0.93-1.09) or death+HF (long-term Cox proportional hazard ratio (HR) 0.99; 95% CI 0.90-1.10). Nonetheless, among never-smokers snus use was associated with an increased risk for death+HF (long-term HR 1.26, 95% CI 1.03-1.55), driven by a higher mortality risk (long-term HR for death of any cause 1.29, 95% CI 1.02-1.64).

    Conclusions

    In this study, snus use was unrelated to acute, short-term or long-term adverse outcomes after an MI. Among never-smokers, snus use was associated with an increased risk of post-MI death.

  • 140.
    Arenhall, Eva
    et al.
    Örebro Universitet, Department of Cardiology, Örebro, Sweden.
    Eriksson, Mats
    Uddevalla Hospital, Department of Pediatrics, Uddevalla, Sweden.
    Nilsson, Ulrica
    Örebro Universitet, School of Health Sciences, Örebro, Sweden.
    Steinke, Elaine E.
    Wichita State University, School of Nursing, Wichita, United States.
    Fridlund, Bengt
    Jönköping University, School of Health and Welfare, HHJ, Dep. of Nursing Science. Jönköping University, School of Health and Welfare, HHJ. ADULT.
    Decreased sexual function in partners after patients’ first-time myocardial infarction2018In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 17, no 6, p. 521-526Article in journal (Refereed)
    Abstract [en]

    Background: A myocardial infarction event affects not only patients but also partners, although how it affects the partners’ sexual function is not studied.

    Aim: The purpose of this study was to describe and compare how partners experienced their sexual function one year before with one year after first-time myocardial infarction of their partner.

    Methods: A longitudinal and comparative design was used. Self-reported data on Watts Sexual Function Questionnaire was collected retrospectively at two occasions from 123 partners (87 women and 36 men), measuring the year prior to the first-time myocardial infarction and the year after. Data were analysed using descriptive and inferential statistics.

    Results: The total score for Watts Sexual Function Questionnaire showed a significant decrease over time. In all four subscales a decrease was found, which were statistically significant in three out of the four subscales (sexual desire, 19.39 vs 18.61; p<0.001, orgasm, 14.11 vs 13.64; p=0.027 and satisfaction, 12.61 vs 12.31; p=0.042). Twenty-six partners reported that their intercourse frequencies decreased over time, while six partners reported an increased intercourse frequency.

    Conclusions: Partners’ sexual function decreased after patients’ first-time myocardial infarction. It is important for health personnel to offer information and discussion about sexual function and concerns with both patients and partners after a first-time myocardial infarction. 

  • 141.
    Arenhall, Eva
    et al.
    Örebro University, School of Medical Sciences. Department of Cardiology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Eriksson, Mats
    Örebro University, School of Health Sciences.
    Nilsson, Ulrica
    Örebro University, School of Health Sciences.
    Steinke, Elaine
    School of Nursing, Wichita State University, Wichita, USA.
    Fridlund, Bengt
    School of Health and Welfare, Jönköping University, Jönköping, Sweden.
    Decreased sexual function in partners after patients’ first-time myocardial infarction2018In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 17, no 6, p. 521-526Article in journal (Refereed)
    Abstract [en]

    Background: A myocardial infarction event affects not only patients but also partners, although how it affects the partners’ sexual function is not studied.

    Aim: The purpose of this study was to describe and compare how partners experienced their sexual function one year before with one year after first-time myocardial infarction of their partner.

    Methods: A longitudinal and comparative design was used. Self-reported data on Watts Sexual Function Questionnaire was collected retrospectively at two occasions from 123 partners (87 women and 36 men), measuring the year prior to the first-time myocardial infarction and the year after. Data were analysed using descriptive and inferential statistics.

    Results: The total score for Watts Sexual Function Questionnaire showed a significant decrease over time. In all four subscales a decrease was found, which were statistically significant in three out of the four subscales (sexual desire, 19.39 vs 18.61; p<0.001, orgasm, 14.11 vs 13.64; p=0.027 and satisfaction, 12.61 vs 12.31; p=0.042). Twenty-six partners reported that their intercourse frequencies decreased over time, while six partners reported an increased intercourse frequency.

    Conclusions: Partners’ sexual function decreased after patients’ first-time myocardial infarction. It is important for health personnel to offer information and discussion about sexual function and concerns with both patients and partners after a first-time myocardial infarction.

  • 142.
    Arenhall, Eva
    et al.
    Örebro University, School of Health and Medical Sciences. Department of Cardiology, Örebro University Hospital, Örebro, Sweden; Centre for Health Care Sciences, Örebro County Council, Örebro, Sweden.
    Kristofferzon, Marja-Leena
    Department of Health and Caring Sciences, University of Gävle, Gävle, Sweden; Department of Public Health and Caring Sciences, Section of Caring Sciences, Uppsala University, Uppsala, Sweden.
    Fridlund, Bengt
    School of Health and Caring Sciences, Linnéaus University, Växjö, Sweden; School of Health Sciences, Jönköping University, Jönköping, Sweden.
    Malm, Dan
    School of Health Sciences, Jönköping University, Jönköping, Sweden; Department of Internal Medicine, Division of Cardiology, County Hospital Ryhov, Jönkoping, Sweden.
    Nilsson, Ulrica
    Department of Anaesthesia and Intensive Care, Örebro University Hospital, Örebro, Sweden.
    The male partners' experiences of the intimate relationships after a first myocardial infarction2011In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 10, no 2, p. 108-114Article in journal (Refereed)
    Abstract [en]

    Background: Stress in the intimate relationship is found to worsen the prognosis in women suffering from myocardial infarction (MI). Little is known about how male spouses experience the intimate relationship.

    Aim: This study aimed to explore and describe the experience of men's intimate relationships in connection to and after their female partner's first MI.

    Methods: An explorative and qualitative design was used. Interviews were conducted with 16 men having a partner who the year before had suffered a first MI. The data were analysed with qualitative content analysis.

    Results: Three themes emerged: masculine image challenged; life takes another direction; and life remains unchanged. The men were forced to deal with an altered image of themselves as men, and as sexual beings. They were hesitant to approach their spouse in the same way as before the MI because they viewed her to be more fragile. The event also caused them to consider their own lifestyle, changing towards healthier dietary and exercise habits.

    Conclusions: After their spouse's MI, men experienced a challenge to their masculine image. They viewed their spouse as being more fragile, which led the men to be gentler in sexual intimacy and more hesitant to invite sexual activity. This knowledge about how male spouses experience the intimate relationship could be helpful for health personnel in hospitals and primary care when they interact with couples where the woman suffers from cardiac disease or other chronic disorders. (C) 2010 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.

  • 143.
    Arinell, Karin
    et al.
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden..
    Christensen, Kjeld
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden..
    Blanc, Stephane
    Institut Pluridisciplinaire Hubert Curien–De´partement d’Ecologie, Physiologie,.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Frobert, Ole
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden..
    Effect of prolonged standardized bed rest on cystatin C and other markers of cardiovascular risk2011In: BMC Physiology, ISSN 1472-6793, E-ISSN 1472-6793, Vol. 11, no 1, p. 17-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Sedentary lifestyle is associated with coronary artery disease but even shorter periods of physical inactivity may increase cardiovascular risk. Cystatin C is independently associated with cardiovascular disease and our objective was to investigate the relation between this novel biomarker and standardized bed rest. Research of immobilization physiology in humans is challenging because good biological models are in short supply. From the Women International Space simulation for Exploration study (WISE) we studied markers of atherosclerosis and kidney function, including cystatin C, in a standardized bed rest study on healthy volunteers. Fifteen healthy female volunteers participated in a 20-day ambulatory control period followed by 60 days of bed rest in head-down tilt position (-6degrees) 24 h a day, finalized by 20 days of recovery. The subjects were randomized into two groups during bed rest: a control group (n=8) that remained physically inactive and an exercise group (n=7) that participated in both supine resistance and aerobic exercise training.

    RESULTS:

    Compared to baseline values there was a statistically significant increase in cystatin C in both groups after bed rest (P<0.001). Glomerular filtration rate (GFR), calculated by both cystatin C and Cockcroft-Gault equation, decreased after bed rest while there were no differences in creatinine or creatine kinase levels. CRP did not change during bed rest in the exercise group, but there was an increase of CRP in the control group during recovery compared to both the baseline and the bed rest periods. The apo-B/apo-Ai ratio increased during bed rest and decreased again in the recovery period. Subjects experienced a small but statistically significant reduction in weight during bed rest and compared to baseline weights remained lower at day 8 of recovery.

    CONCLUSION:

    During and following prolonged standardized bed rest the concentrations of several clinically relevant cardiovascular risk markers change.

  • 144.
    Arinell, Karin
    et al.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Christensen, Kjeld
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Blanc, Stéphane
    Institut Pluridisciplinaire Hubert Curien-De'partement d'Ecologie, Physiologie, Ethologie Unite' Mixte de Recherche 7178. Centre National de la Recherche Scientifique, Universite' de Strasbourg, Strasbourg, France.
    Larsson, Anders
    Department of Medical Sciences, Clinical Chemistry, Uppsala University, Uppsala, Sweden.
    Fröbert, Ole
    Department of Cardiology, Örebro University Hospital, Örebro, Sweden.
    Effect of prolonged standardized bed rest on cystatin C and other markers of cardiovascular risk2011In: BMC Physiology, ISSN 1472-6793, E-ISSN 1472-6793, Vol. 11, article id 17Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sedentary lifestyle is associated with coronary artery disease but even shorter periods of physical inactivity may increase cardiovascular risk. Cystatin C is independently associated with cardiovascular disease and our objective was to investigate the relation between this novel biomarker and standardized bed rest. Research of immobilization physiology in humans is challenging because good biological models are in short supply. From the Women International Space simulation for Exploration study (WISE) we studied markers of atherosclerosis and kidney function, including cystatin C, in a standardized bed rest study on healthy volunteers. Fifteen healthy female volunteers participated in a 20-day ambulatory control period followed by 60 days of bed rest in head-down tilt position (-6°) 24 h a day, finalized by 20 days of recovery. The subjects were randomized into two groups during bed rest: a control group (n = 8) that remained physically inactive and an exercise group (n = 7) that participated in both supine resistance and aerobic exercise training.

    RESULTS: Compared to baseline values there was a statistically significant increase in cystatin C in both groups after bed rest (P < 0.001). Glomerular filtration rate (GFR), calculated by both cystatin C and Cockcroft-Gault equation, decreased after bed rest while there were no differences in creatinine or creatine kinase levels. CRP did not change during bed rest in the exercise group, but there was an increase of CRP in the control group during recovery compared to both the baseline and the bed rest periods. The apo-B/apo-Ai ratio increased during bed rest and decreased again in the recovery period. Subjects experienced a small but statistically significant reduction in weight during bed rest and compared to baseline weights remained lower at day 8 of recovery.

    CONCLUSION: During and following prolonged standardized bed rest the concentrations of several clinically relevant cardiovascular risk markers change.

  • 145.
    Arinell, Karin
    et al.
    Dept Cardiol, Örebro Univ Hosp, Örebro, Sweden.
    Fröbert, Ole
    Örebro University Hospital. Dept Cardiol.
    Blanc, Stephane
    Dept Ecol Physiol & Ethol, Dept Ecol, Inst Pluridisciplinaire Hubert Curien, Strasbourg, France.
    Larsson, Anders
    Dept Clin Chem, Uppsala Univ, Uppsala, Sweden.
    Christensen, Kjeld
    Örebro University Hospital. Dept Cardiol.
    Downregulation of platelet activation markers during long-term immobilization2013In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 24, no 5, p. 369-374Article in journal (Refereed)
    Abstract [en]

    Immobilization and sedentary lifestyle are risk factors for venous thromboembolism and cardiovascular disease, yet little is known about platelet function during long-term physical inactivity. Our aim was to investigate platelet activation markers and their coupling to standardized immobilization: platelet-derived growth factor (PDGF-BB) and P-selectin. We studied 15 healthy females participating in the Women International Space simulation for Exploration study. Following a 20-day ambulatory control period, the subjects underwent 60 days of bed rest in head-down tilt position (-6 degrees) 24 hours a day, finalized by 20 days of recovery. The subjects were randomized into two groups during bed rest: a control group (n = 8) that remained physically inactive and an exercise group (n = 7) that participated in both supine resistance and aerobic exercise training. Blood samples for the analysis of platelet activation markers were collected at baseline (5 days before bed rest), after 44 days of bed rest and 8 days into the recovery period. Compared to baseline, the levels of P-selectin and PDGF-BB decreased after bed rest (by 55%, p = 0.01 and 73%, p < 0.03, respectively) and remained decreased in the recovery period (by 76%, p < 0.001 and 78%, p < 0.02, respectively, compared to baseline). Platelet count (baseline value for the exercise group 260 000/mu l +/- 34 000 and baseline value for the control group 210 000/mu l +/- 30 000) did not change during the bed rest study (two-way repeated measurements ANOVA, p = ns). There were no statistical differences between the physically inactive and the exercise group. During long-term immobilization, a known risk factor for thrombosis, the levels of P-selectin and PDGF-BB decreased. Our findings indicate downregulation of platelet activation during immobilization.

  • 146. Arking, Dan E
    et al.
    Pulit, Sara L
    Crotti, Lia
    van der Harst, Pim
    Munroe, Patricia B
    Koopmann, Tamara T
    Sotoodehnia, Nona
    Rossin, Elizabeth J
    Morley, Michael
    Wang, Xinchen
    Johnson, Andrew D
    Lundby, Alicia
    Gudbjartsson, Daníel F
    Noseworthy, Peter A
    Eijgelsheim, Mark
    Bradford, Yuki
    Tarasov, Kirill V
    Dörr, Marcus
    Müller-Nurasyid, Martina
    Lahtinen, Annukka M
    Nolte, Ilja M
    Smith, Albert Vernon
    Bis, Joshua C
    Isaacs, Aaron
    Newhouse, Stephen J
    Evans, Daniel S
    Post, Wendy S
    Waggott, Daryl
    Lyytikäinen, Leo-Pekka
    Hicks, Andrew A
    Eisele, Lewin
    Ellinghaus, David
    Hayward, Caroline
    Navarro, Pau
    Ulivi, Sheila
    Tanaka, Toshiko
    Tester, David J
    Chatel, Stéphanie
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kumari, Meena
    Morris, Richard W
    Naluai, Asa T
    Padmanabhan, Sandosh
    Kluttig, Alexander
    Strohmer, Bernhard
    Panayiotou, Andrie G
    Torres, Maria
    Knoflach, Michael
    Hubacek, Jaroslav A
    Slowikowski, Kamil
    Raychaudhuri, Soumya
    Kumar, Runjun D
    Harris, Tamara B
    Launer, Lenore J
    Shuldiner, Alan R
    Alonso, Alvaro
    Bader, Joel S
    Ehret, Georg
    Huang, Hailiang
    Kao, W H Linda
    Strait, James B
    Macfarlane, Peter W
    Brown, Morris
    Caulfield, Mark J
    Samani, Nilesh J
    Kronenberg, Florian
    Willeit, Johann
    Smith, J Gustav
    Greiser, Karin H
    Meyer Zu Schwabedissen, Henriette
    Werdan, Karl
    Carella, Massimo
    Zelante, Leopoldo
    Heckbert, Susan R
    Psaty, Bruce M
    Rotter, Jerome I
    Kolcic, Ivana
    Polašek, Ozren
    Wright, Alan F
    Griffin, Maura
    Daly, Mark J
    Arnar, David O
    Hólm, Hilma
    Thorsteinsdottir, Unnur
    Denny, Joshua C
    Roden, Dan M
    Zuvich, Rebecca L
    Emilsson, Valur
    Plump, Andrew S
    Larson, Martin G
    O'Donnell, Christopher J
    Yin, Xiaoyan
    Bobbo, Marco
    D'Adamo, Adamo P
    Iorio, Annamaria
    Sinagra, Gianfranco
    Carracedo, Angel
    Cummings, Steven R
    Nalls, Michael A
    Jula, Antti
    Kontula, Kimmo K
    Marjamaa, Annukka
    Oikarinen, Lasse
    Perola, Markus
    Porthan, Kimmo
    Erbel, Raimund
    Hoffmann, Per
    Jöckel, Karl-Heinz
    Kälsch, Hagen
    Nöthen, Markus M
    den Hoed, Marcel
    Loos, Ruth J F
    Thelle, Dag S
    Gieger, Christian
    Meitinger, Thomas
    Perz, Siegfried
    Peters, Annette
    Prucha, Hanna
    Sinner, Moritz F
    Waldenberger, Melanie
    de Boer, Rudolf A
    Franke, Lude
    van der Vleuten, Pieter A
    Beckmann, Britt Maria
    Martens, Eimo
    Bardai, Abdennasser
    Hofman, Nynke
    Wilde, Arthur A M
    Behr, Elijah R
    Dalageorgou, Chrysoula
    Giudicessi, John R
    Medeiros-Domingo, Argelia
    Barc, Julien
    Kyndt, Florence
    Probst, Vincent
    Ghidoni, Alice
    Insolia, Roberto
    Hamilton, Robert M
    Scherer, Stephen W
    Brandimarto, Jeffrey
    Margulies, Kenneth
    Moravec, Christine E
    Greco M, Fabiola Del
    Fuchsberger, Christian
    O'Connell, Jeffrey R
    Lee, Wai K
    Watt, Graham C M
    Campbell, Harry
    Wild, Sarah H
    El Mokhtari, Nour E
    Frey, Norbert
    Asselbergs, Folkert W
    Mateo Leach, Irene
    Navis, Gerjan
    van den Berg, Maarten P
    van Veldhuisen, Dirk J
    Kellis, Manolis
    Krijthe, Bouwe P
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Franco, Oscar H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Hofman, Albert
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kors, Jan A
    Uitterlinden, André G
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Witteman, Jacqueline C M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Kedenko, Lyudmyla
    Lamina, Claudia
    Oostra, Ben A
    Abecasis, Gonçalo R
    Lakatta, Edward G
    Mulas, Antonella
    Orrú, Marco
    Schlessinger, David
    Uda, Manuela
    Markus, Marcello R P
    Völker, Uwe
    Snieder, Harold
    Spector, Timothy D
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Syvänen, Ann-Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Kivimaki, Mika
    Kähönen, Mika
    Mononen, Nina
    Raitakari, Olli T
    Viikari, Jorma S
    Adamkova, Vera
    Kiechl, Stefan
    Brion, Maria
    Nicolaides, Andrew N
    Paulweber, Bernhard
    Haerting, Johannes
    Dominiczak, Anna F
    Nyberg, Fredrik
    Whincup, Peter H
    Hingorani, Aroon D
    Schott, Jean-Jacques
    Bezzina, Connie R
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Ferrucci, Luigi
    Gasparini, Paolo
    Wilson, James F
    Rudan, Igor
    Franke, Andre
    Mühleisen, Thomas W
    Pramstaller, Peter P
    Lehtimäki, Terho J
    Paterson, Andrew D
    Parsa, Afshin
    Liu, Yongmei
    van Duijn, Cornelia M
    Siscovick, David S
    Gudnason, Vilmundur
    Jamshidi, Yalda
    Salomaa, Veikko
    Felix, Stephan B
    Sanna, Serena
    Ritchie, Marylyn D
    Stricker, Bruno H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stefansson, Kari
    Boyer, Laurie A
    Cappola, Thomas P
    Olsen, Jesper V
    Lage, Kasper
    Schwartz, Peter J
    Kääb, Stefan
    Chakravarti, Aravinda
    Ackerman, Michael J
    Pfeufer, Arne
    de Bakker, Paul I W
    Newton-Cheh, Christopher
    Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.2014In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 46, no 8, p. 826-836Article in journal (Refereed)
    Abstract [en]

    The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.

  • 147.
    Armaganijan, Luciana V.
    et al.
    Brazilian Clin Res Inst, Sao Paulo, Brazil..
    Alexander, Karen P.
    Duke Clin Res Inst, Durham, NC USA..
    Huang, Zhen
    Duke Clin Res Inst, Durham, NC USA..
    Tricoci, Pierluigi
    Duke Clin Res Inst, Durham, NC USA..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Van de Werf, Frans
    Univ Hosp Leuven, Dept Cardiol, Leuven, Belgium..
    Armstrong, Paul W.
    Univ Alberta, Edmonton, AB, Canada..
    Aylward, Philip E.
    Flinders Univ & Med Ctr, South Australian Hlth & Med Res Inst, Adelaide, SA, Australia..
    White, Harvey D.
    Green Lane Cardiovasc Serv, Auckland, New Zealand..
    Moliterno, David J.
    Gill Heart Inst, Lexington, KY USA.;Univ Kentucky, Lexington, KY USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Chen, Edmond
    Bayer HealthCare Pharmaceut Inc, Whippany, NJ USA..
    Harrington, Robert A.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Strony, John
    Johnson & Johnson, New Brunswick, NJ USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Stanford, CA 94305 USA..
    Lopes, Renato D.
    Duke Clin Res Inst, Durham, NC USA..
    Effect of age on efficacy and safety of vorapaxar in patients with non-ST-segment elevation acute coronary syndrome: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 178, p. 176-184Article in journal (Refereed)
    Abstract [en]

    Background Antithrombotic therapy plays an important role in the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS) but is associated with bleeding risk. Advanced age may modify the relationship between efficacy and safety. Methods Efficacy and safety of vorapaxar (a protease-activated receptor 1 antagonist) was analyzed across ages as a continuous and a categorical variable in the 12,944 patients with NSTE ACS enrolled in the TRACER trial. To evaluate the effect of age, Cox regression models were developed to estimate hazard ratios (HRs) with the adjustment of other baseline characteristics and randomized treatment for the primary efficacy composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, and the primary safety composite of moderate or severe Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding. Results The median age of the population was 64 years (25th, 75th percentiles = 58, 71). Also, 1,791 patients (13.8%) were <= 54 years of age, 4,968 (38.4%) were between 55 and 64 years, 3,979 (30.7%) were between 65 and 74 years, and 2,206 (17.1%) were 75 years or older. Older patients had higher rates of hypertension, renal insufficiency, and previous stroke and worse Killip class. The oldest age group (>= 75 years) had substantially higher 2-year rates of the composite ischemic end point and moderate or severe GUSTO bleeding compared with the youngest age group (<= 54 years). The relationships between treatment assignment (vorapaxar vs placebo) and efficacy outcomes did not vary by age. For the primary efficacy end point, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were as follows: 1.12 (0.88-1.43), 0.88 (0.76-1.02), 0.89 (0.76-1.04), and 0.88 (0.74-1.06), respectively (P value for interaction = .435). Similar to what was observed for efficacy outcomes, we did not observe any interaction between vorapaxar and age on bleeding outcomes. For the composite of moderate or severe bleeding according to the GUSTO classification, the HRs (95% CIs) comparing vorapaxar and placebo in the 4 age groups were 1.73 (0.89-3.34), 1.39 (1.04-1.86), 1.10 (0.85-1.42), and 1.73 (1.29-2.33), respectively (P value for interaction = .574). Conclusion Older patients had a greater risk for ischemic and bleeding events; however, the efficacy and safety of vorapaxar in NSTE ACS were not significantly influenced by age.

  • 148. Arnlov, Johan
    et al.
    Ruge, Toralph
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ingelsson, Erik
    Larsson, Anders
    Sundström, Johan
    Lind, Lars
    Serum Endostatin and Risk of Mortality in the Elderly Findings From 2 Community-Based Cohorts2013In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 33, no 11, p. 2689-2695Article in journal (Refereed)
    Abstract [en]

    Objective Experimental data imply that endostatin, a proteolytically cleaved fragment of collagen XVIII, could be involved in the development of cardiovascular disease and cancer. Prospective data concerning the relation between circulating endostatin and mortality are lacking. Accordingly, we aimed to study associations between circulating endostatin and mortality risk. Approach and Results Serum endostatin was analyzed in 2 community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 50%, n=931; mean age, 70 years; median follow-up, 7.9 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=748; mean age, 77 years; median follow-up, 9.7 years). During follow-up, 90 participants died in PIVUS (1.28/100 person-years at risk), and 417 participants died in ULSAM (6.7/100 person-years at risk). In multivariable Cox regression models adjusted for age and established cardiovascular risk factors, 1 SD higher ln(serum endostatin level) was associated with a hazard ratio of mortality of 1.39 and 95% confidence interval, 1.26 to 1.53, on average in both cohorts. In the ULSAM cohort, serum endostatin was also associated with cardiovascular mortality (177 deaths; hazard ratio per SD of ln[endostatin] 1.45, 95% confidence interval [1.25-1.71]) and cancer mortality (115 deaths; hazard ratio per SD of ln[endostatin] 1.35, 95% confidence interval [1.10-1.66]). Conclusions High serum endostatin was associated with increased mortality risk in 2 independent community-based cohorts of the elderly. Our observational data support the importance of extracellular matrix remodeling in the underlying pathophysiology of cardiovascular disease and cancer.

  • 149.
    Arvidsson, Sandra
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Cardiac function in hereditary transthyretin amyloidosis: an echocardiographic study2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Hereditary transthyretin amyloidosis (ATTR) is a lethal disease in which misfolded transthyretin (TTR) proteins accumulate as insoluble aggregates in tissues throughout the body. A common mutation is the exchange of valine to methionine at place 30 (TTR V30M), a form endemically found in the northern parts of Sweden. The main treatment option for ATTR amyloidosis is liver transplantation as the procedure halts production of mutated transthyretin. The disease is associated with marked phenotypic diversity ranging from predominant cardiac complications to pure neuropathy. Two different types of fibril composition – one in which both fragmented and full-length TTR are present (type A) and one consisting of only full-length TTR (type B) have been suggested to account for some phenotypic differences. Cardiac amyloidosis is associated with increased myocardial thickness and the disease could easily be mistaken for other entities characterised by myocardial thickening, such as sarcomeric hypertrophic cardiomyopathy (HCM). The aims in this thesis were to investigate echocardiographic characteristics in Swedish ATTR amyloidosis patients, and to identify markers aiding in differentiating ATTR heart disease from HCM. Another objective was to examine the impact of fibril composition and sex on the phenotypic variation in amyloid heart disease.

    Methods: A total of 122 ATTR amyloidosis patients that had undergone thorough echocardiographic examinations were included in the studies. Analyses of ventricular geometry as well as assessment of systolic and diastolic function were performed, using both conventional echocardiographic methods and speckle tracking technique. ECG analysis was conducted in study I, allowing measurement of QRS voltage. In study I and study II ATTR patients were compared to patients with HCM. In addition, 30 healthy controls were added to study II.

    Results: When parameters from ECG and echocardiography were investigated, the results revealed that the combination of QRS voltage <30 mm (<3 mV) and an interventricular/posterior wall thickness quotient <1.6 could differentiate cardiac ATTR amyloidosis from HCM. Differences in degree of right ventricular involvement were also demonstrated between HCM and ATTR amyloidosis, where ATTR patients displayed a right ventricular apical sparing pattern whereas the inverse pattern was found in HCM. Analysis of fibril composition revealed increased LV wall thickness in type A patients compared to type B, but in addition type A women displayed both lower myocardial thickness and more preserved systolic function as compared to type A males. When cardiac geometry and function were evaluated pre and post liver transplantation in type A and B patients, significant deterioration was detected in type A but not in type B patients after liver transplantation.

    Conclusions: Increasing awareness of typical cardiac amyloidotic signs by echocardiography is important to reduce the risk of delayed diagnosis. Our classification model based on ECG and echocardiography could aid in differentiating ATTR amyloidosis from HCM. Furthermore, the apical sparing pattern found in the right ventricle may pose another clue for amyloid heart disease, although it requires to be studied further. Furthermore, we disclosed that type A fibrils, male sex and increasing age were important determinants of increased myocardial thickness. As type A fibril patients displayed rapid cardiac deterioration after liver transplantation other treatment options should probably be sought for this group of patients.

  • 150.
    Arvidsson, Sandra
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Henein, Michael Y
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Cardiology.
    Wikström, Gerhard
    Suhr, Ole B
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Lindqvist, Per
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Right ventricular involvement in transthyretin amyloidosisManuscript (preprint) (Other academic)
    Abstract [en]

    Objectives

    Right heart involvement and dysfunction is frequently encountered in cardiomyopathies. In immunoglobulin light chain (AL) amyloidosis, right ventricular (RV) function has been described as a strong determinant of survival. However, RV involvement in transthyretin related amyloidosis (ATTR) has been somewhat overlooked. We therefore sought to establish the degree of RV involvement in ATTR amyloidosis and compare the findings with sarcomeric hypertrophic cardiomyopathy (HCM).

    Patients and methods

    Forty-two patients with diagnosed ATTR and echocardiographic evidence of cardiac amyloidosis (cardiac ATTR), 19 ATTR patients with normal left ventricular (LV) wall thickness (non-cardiac ATTR), 25 patients with diagnosed sarcomeric HCM and 30 healthy controls were included in the study. Echocardiographic examinations were analysed and standard measurements of LV and RV dimensions and function were carried out. In addition, LV global and RV global and segmental strain were analysed. The degree of cardiac involvement and function was compared between non-cardiac ATTR patients and healthy controls and between cardiac ATTR patients and with those having HCM.

    Results

    Non-cardiac ATTR amyloidosis patients did not differ from healthy controls, either in geometrical or functional measurements of the LV and RV. HCM patients had significantly thicker interventricular septal thickness (p=0.017) and thinner posterior wall thickness (p=0.004) as compared to cardiac ATTR. When comparing cardiac ATTR and HCM patients by means of RV structure and function only segmental strain differed between the two patient groups. In cardiac ATTR we found an RV apex-to-base strain gradient with highest deformation in the apex whereas the pattern was inverse in patients with HCM.

    Conclusions

    RV involvement is common only in ATTR patients with concomitant LV involvement. The present study also detected an apical sparing pattern for the RV in patients with ATTR cardiomyopathy, similar to what has previously been described for the LV. This pattern was not seen in HCM patients. Further studies are warranted to assess the clinical importance of these findings.

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