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  • 151.
    Alavian, S.M.
    et al.
    Baqiyatallah Research Center for Gastroenterology and Liver Diseases, Tehran.
    Ande, S.R.
    University of Manitoba.
    Coombs, K.M.
    University of Manitoba.
    Yeganeh, B.
    University of Manitoba.
    Davoodpour, Padideh
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences.
    Hashemi, M.
    Zahedan University of Medical Sceince, Iran.
    Los, Marek Jan
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Cell Biology.
    Ghavami, S.
    University of Manitoba.
    Virus-triggered autophagy in viral hepatitis - possible novel strategies for drug development2011In: Journal of Viral Hepatitis, ISSN 1352-0504, E-ISSN 1365-2893, Vol. 18, no 12, p. 821-830Article, review/survey (Refereed)
    Abstract [en]

    . Autophagy is a very tightly regulated process that is important in many cellular processes including development, differentiation, survival and homoeostasis. The importance of this process has already been proven in numerous common diseases such as cancer and neurodegenerative disorders. Emerging data indicate that autophagy plays an important role in some liver diseases including liver injury induced by ischaemia reperfusion and alpha-1 antitrypsin Z allele-dependent liver disease. Autophagy may also occur in viral infection, and it may play a crucial role in antimicrobial host defence against pathogens, while supporting cellular homoeostasis processes. Here, the latest findings on the role of autophagy in viral hepatitis B and C infection, which are both serious health threats, will be reviewed.

  • 152.
    Albrecht, Knut
    et al.
    Hannover Medical School, Deparment of Legal Medicine, Hannover, Germany.
    Ückert, Stefan
    Hanover Medical School, Department of Urology, Hannover, Germany.
    Oelke, Matthias
    University of Amsterdam, Academic Medical Center (AMC), Department of Urology, Amsterdam, The Netherlands.
    Andersson, Karl-Erik
    Lund University Hospital, Department of Clinical and Experimental Pharmacology, Lund, Sweden.
    Jonas, Udo
    University of Amsterdam, Academic Medical Center (AMC), Department of Urology, Amsterdam, The Netherlands.
    Tröger, Hans-Dieter
    Hannover Medical School, Deparment of Legal Medicine, Hannover, Germany.
    Hedlund, Petter
    Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology.
    Immunohistochemical distribution of cyclic nucleotide phosphodiesterase (PDE) isoenzymes in the human vagina:: A potential forensic value?2007In: Journal of forensic and legal medicine, ISSN 1752-928X, Vol. 14, no 5, p. 270-274Article in journal (Refereed)
    Abstract [en]

    Objectives

    Phosphodiesterase (PDE) isoenzymes are key proteins involved in the maintenance of the normal function of various tissues of the human body including those of the male and female urogenital tract. More recently, PDEs and their main substrates, cyclic GMP and cyclic AMP, have also been assumed to play a crucial role in the control of the human vagina. In order to elucidate the potential significance of phosphodiesterases as marker proteins in female genital organs, it was the aim of the present study to evaluate by means of immunohistochemistry the distribution of cGMP- and cAMP-PDE isoenzymes in specimens of the human vagina.

    Methods

    Conventional immunohistochemical techniques (double antibody technique, laser fluorescence microscopy) were applied to sections of the human vaginal wall in order to evaluate the presence of the PDE isoenzymes 1, 2, 3, 4, 5 and 10.

    Results

    Immunoreactivities (IR) specific for PDE1 (cAMP/cGMP-PDE, Ca2+/Calmodulin-dependent), PDE2 (cAMP-PDE, cGMP-dependent) and PDE5 (cGMP-PDE) were exclusively registered in the smooth musculature of vaginal arterial vessels, whereas no signals were detected in non-vascular tissue. IR indicating the expression of the cAMP-degrading PDE4 was mainly observed in the vaginal epithelium. Vaginal epithelial cells also presented immunosignals specific for PDE3 (cAMP-PDE, inhibited by cGMP) and PDE10 (dual substrate PDE), nevertheless, these stainings were less abundant than those related to the PDE4. IR for PDE10 was also registered in inflammatory cells located in the subepithelial region of the vaginal wall.

    Conclusion

    Our study revealed the presence of IR specific for PDE1, PDE2, PDE4, PDE5 and PDE10 in sections of the human vagina and demonstrated that these enzymes are not evenly distributed in the tissue. Especially, the prominent expression of the cyclic AMP-PDE4A in the vaginal epithelium may give hint to a potential significance of this isoenzyme as a forensic marker protein. The findings give a rationale to investigate further as to whether the immunohistochemical detection of PDE4 may represent a new forensic tool in order to identify human vaginal epithelial cells.

  • 153.
    Albrecht, Matthew A.
    et al.
    Curtin University, Australia .
    Stuart, Geoffrey W.
    La Trobe University, Australia .
    Falkmer, Marita
    Curtin University, Australia, Jonköping University, Sweden .
    Ordqvist, Anna
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Leung, Denise
    Curtin University, Australia .
    Foster, Jonathan K.
    Curtin University, Australia Health Department WA, Australia .
    Falkmer, Torbjörn
    Linköping University, Department of Medical and Health Sciences, Division of Community Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Pain and Rehabilitation Center.
    Brief Report: Visual Acuity in Children with Autism Spectrum Disorders2014In: Journal of autism and developmental disorders, ISSN 0162-3257, E-ISSN 1573-3432, Vol. 44, no 9, p. 2369-2374Article in journal (Refereed)
    Abstract [en]

    Recently, there has been heightened interest in suggestions of enhanced visual acuity in autism spectrum disorders (ASD) which was sparked by evidence that was later accepted to be methodologically flawed. However, a recent study that claimed children with ASD have enhanced visual acuity (Brosnan et al. in J Autism Dev Disord 42:2491-2497, 2012) repeated a critical methodological flaw by using an inappropriate viewing distance for a computerised acuity test, placing the findings in doubt. We examined visual acuity in 31 children with ASD and 33 controls using the 2 m 2000 Series Revised Early Treatment Diabetic Retinopathy Study chart placed at twice the conventional distance to better evaluate possible enhanced acuity. Children with ASD did not demonstrate superior acuity. The current findings strengthen the argument that reports of enhanced acuity in ASD are due to methodological flaws and challenges the reported association between visual acuity and systemising type behaviours.

  • 154.
    Al-Dury, Nooraldeen
    et al.
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Rawshani, Araz
    University of Gothenburg, Sweden.
    Israelsson, Johan
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Kalmar County Hospital, Sweden; Linnaeus University, Sweden.
    Stromsoe, Anneli
    School Health Care and Social Welf, Sweden.
    Aune, Solveig
    Sahlgrens University Hospital, Sweden.
    Agerstrom, Jens
    Linnaeus University, Sweden.
    Karlsson, Thomas
    University of Gothenburg, Sweden.
    Ravn-Fischer, Annica
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden.
    Herlitz, Johan
    University of Gothenburg, Sweden; Sahlgrens University Hospital, Sweden; University of Boras, Sweden.
    Characteristics and outcome among 14,933 adult cases of in-hospital cardiac arrest: A nationwide study with the emphasis on gender and age2017In: American Journal of Emergency Medicine, ISSN 0735-6757, E-ISSN 1532-8171, Vol. 35, no 12, p. 1839-1844Article in journal (Refereed)
    Abstract [en]

    Aim: To investigate characteristics and outcome among patients suffering in-hospital cardiac arrest (IHCA) with the emphasis on gender and age. Methods: Using the Swedish Register of Cardiopulmonary Resuscitation, we analyzed associations between gender, age and co-morbidities, etiology, management, 30-day survival and cerebral function among survivors in 14,933 cases of IHCA. Age was divided into three ordered categories: young (18-49 years), middle-aged (5064 years) and older (65 years and above). Comparisons between men and women were age adjusted. Results: The mean age was 72.7 years and women were significantly older than men. Renal dysfunction was the most prevalent co-morbidity. Myocardial infarction/ischemia was the most common condition preceding IHCA, with men having 27% higher odds of having MI as the underlying etiology. A shockable rhythm was found in 31.8% of patients, with men having 52% higher odds of being found in VT/VF. After adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30 days. Older individuals were managed less aggressively than younger patients. Increasing age was associated with lower 30-day survival but not with poorer cerebral function among survivors. Conclusion: When adjusting for various confounders, it was found that men had a 10% lower chance than women of surviving to 30 days after in-hospital cardiac arrest. Older individuals were managed less aggressively than younger patients, despite a lower chance of survival. Higher age was, however, not associated with poorer cerebral function among survivors. (C) 2017 Elsevier Inc. All rights reserved.

  • 155.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Chamberlain Wilmoth, Margaret
    School of Nursing, College of Health and Human Services, UNC Charlotte, Charlotte, North Carolina, USA.
    Berterö, Carina
    Linköping University, Department of Medical and Health Sciences, Division of Nursing Science. Linköping University, Faculty of Health Sciences.
    Defining and Clarifying Sexual Health: A Simultaneous Concept analysis2012In: Advances in Medicine and Biology vol 28 / [ed] Leon V. Berhardt, Nova Science Publishers, Inc., 2012, p. 177-198Chapter in book (Refereed)
    Abstract [en]

    Purpose: The concepts of health and sexuality are complex and the discussion of how to clarify them seems to be ongoing. This continuing work is essential also according to the joined concept sexual health as it is central in national and international public health programs. Hence, the aim of this paper was to clarify the concept of sexual health by making a simultaneous concept analysis of sexuality and health.

    Methods: A qualitative content analysis defined the meanings, the major concepts and the components of the superior concepts Sexuality and Health, respectively. The data for this analysis were dictionaries, definitions, reports, guidelines, books and articles. Next, a simultaneous concept analysis (SCA) was chosen in order to answer the research questions and develop a process model of sexual health.

    Findings: The definitions of the processed concepts and the developing outcome from sexual health were: Prime mover, Interconnectedness, Interdependence, Norms, Completeness, Functional physiology, Insight, Relatedness, Adaptiveness and Contentedness. These outcomes are presented in a process model.

    Conclusions: This study adds a theoretical perspective clarifying the concept sexual health. The clarifications of this study contribute with knowledge, which can be used in practise, enabling health care professionals promoting sexual health and develop sexual health issues in further research.

  • 156.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Finnström, Orvar
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Hermansson, Göran
    Linköping University, Department of Clinical and Experimental Medicine, Pediatrics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Paediatrics in Linköping.
    Somasunduram, Konduri
    Centre for Social Medicine, Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Bangal, Vidyadhar
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Patil, Ashok
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Chandekar, Pratibha
    Pravara Institute of Medical Sciences-Deemed University, Loni, Maharashtra, India.
    Johansson, AnnaKarin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Nurse-based antenatal and child health care in rural India, implementation and effects - an Indian-Swedish collaboration2012In: Rural and remote health, ISSN 1445-6354, Vol. 12, no 3Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION:

    Improving maternal and child health care are two of the Millennium Development Goals of the World Health Organization. India is one of the countries worldwide most burdened by maternal and child deaths. The aim of the study was to describe how families participate in nurse-based antenatal and child health care, and the effect of this in relation to referrals to specialist care, institutional deliveries and mortality.

    METHODS:

    The intervention took place in a remote rural area in India and was influenced by Swedish nurse-based health care. A baseline survey was performed before the intervention commenced. The intervention included education program for staff members with a model called Training of Trainers and the establishment of clinics as both primary health centers and mobile clinics. Health records and manuals, and informational and educational materials were produced and the clinics were equipped with easily handled instruments. The study period was between 2006 and 2009. Data were collected from antenatal care and child healthcare records. The Chi-square test was used to analyze mortality differences between years. A focus group discussion and a content analysis were performed.

    RESULTS:

    Families' participation increased which led to more check-ups of pregnant women and small children. Antenatal visits before 16 weeks among pregnant women increased from 32 to 62% during the period. Women having at least three check-ups during pregnancy increased from 30 to 60%. Maternal mortality decreased from 478 to 121 per 100 000 live births. The total numbers of children examined in the project increased from approximately 6000 to 18 500 children. Infant mortality decreased from 80 to 43 per 1000 live births. Women and children referred to specialist care increased considerably and institutional deliveries increased from 47 to 74%.

    CONCLUSION:

    These results suggest that it is possible in a rural and remote area to influence peoples' awareness of the value of preventive health care. The results also indicate that this might decrease maternal and child mortality. The education led to a more patient-friendly encounter between health professionals and patients.

  • 157.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Hägg, Monica
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Kalén-Enterlöv, Maria
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Johansson, AnnaKarin
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Experiences of community health nurses regarding father participation in child health care2011In: Journal of Child Health Care, ISSN 1367-4935, E-ISSN 1741-2889, Vol. 15, no 3, p. 153-162Article in journal (Refereed)
    Abstract [en]

    Traditionally child health care (CHC) has been an arena where mothers and nurses meet, but in recent years fathers are entering CHC with increasing frequency. The aim of this study was to describe nurses’ experiences of fathers’ participation in CHC. Nine Swedish nurses working in CHC were interviewed and asked to give a description of their experiences from meetings with fathers in CHC. Phenomenology according to Giorgi was used for the analysis and the essence of the findings was that father participation was seen from the perspective of mother participation and was constantly compared to mother participation in CHC. The essence is explicated in the following themes: participation through activities; equal participation although diverse; influence of structures in society; and strengthening participation. Clinical implications include the need for creating a separate identity in CHC for fathers and more communication directed at fathers.

  • 158.
    Alehagen, Siw
    et al.
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Wambui, Theresah
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences.
    Ek, Anna Christina
    Linköping University, Department of Medical and Health Sciences, Nursing Science. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in Central Östergötland, Department of Acute Internal Medicine.
    Perceptions of family planning among low-income men in Western Kenya: Original Article2009In: International Nursing Review, ISSN 0020-8132, E-ISSN 1466-7657, Vol. 56, no 3, p. 340-345Article in journal (Refereed)
    Abstract [en]

    Background: Men have rarely been involved in either receiving or providing information on sexuality, reproductive health or birth spacing. They have also been ignored or excluded in one way or the other from participating in many family planning programmes as family planning is viewed as a womans affair.

    Aim: To describe the perceptions of family planning among low-income men in Western Kenya. Methods: A qualitative study using focus group interviews and content analysis was conducted, with 64 men aged 15-54 years participating actively.

    Findings: Perceptions of family planning were manifold. For example, some perceived it as meaning having the number of children one is able to provide for. Most men knew about traditional and modern methods of birth control, although their knowledge was poor and misconceived. Modern methods were thought to give side effects, discouraging family planning. Low instances of family planning were also because of the fact that culturally, children are considered wealth. A law advocating family size limitation was regarded as necessary for the future.

    Conclusion: Mens perceptions of family planning are manifold. Their knowledge about contraception is poor and sometimes misconceived. Preferences regarding a childs gender are strong, thus attitudes and cultural beliefs that might hinder family planning have to be considered. A policy on male contraception and contraceptive services is seen as necessary.

  • 159.
    Alehagen, Urban
    et al.
    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.
    Aaseth, Jan
    Innlandet Hospital Trust, N-2226 Kongsvinger, Norway.
    Selenium and coenzyme Q10 interrelationship in cardiovascular diseases - A clinician's point of view2015In: Journal of Trace Elements in Medicine and Biology, ISSN 0946-672X, E-ISSN 1878-3252, Vol. 31, p. 157-162Article in journal (Refereed)
    Abstract [en]

    A short review is given of the potential role of selenium deficiency and selenium intervention trials in atherosclerotic heart disease. Selenium is an essential constituent of several proteins, including the glutathione peroxidases and selenoprotein P. The selenium intake in Europe is generally in the lower margin of recommendations from authorities. Segments of populations in Europe may thus have a deficient intake that may be presented by a deficient anti-oxidative capacity in various illnesses, in particular atherosclerotic disease, and this may influence the prognosis of the disease. Ischemic heart disease and heart failure are two conditions where increased oxidative stress has been convincingly demonstrated. Some of the intervention studies of anti-oxidative substances that have focused on selenium are discussed in this review. The interrelationship between selenium and coenzyme Q10, another anti-oxidant, is presented, pointing to a theoretical advantage in using both substances in an intervention if there are deficiencies within the population. Clinical results from an intervention study using both selenium and coenzyme Q10 in an elderly population are discussed, where reduction in cardiovascular mortality, a better cardiac function according to echocardiography, and finally a lower concentration of the biomarker NT-proBNP as a sign of lower myocardial wall tension could be seen in those on active treatment, compared to placebo.

  • 160.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Johansson, Peter
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Still reduced cardiovascular mortality 12 years after supplementation with selenium and coenzyme Q10 for four years: A validation of previous 10-year follow-up results of a prospective randomized double-blind placebo-controlled trial in elderly2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 4, article id e0193120Article in journal (Refereed)
    Abstract [en]

    Background Selenium and coenzyme Q10 are both necessary for optimal cell function in the body. The intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases. Therefore, an intervention trial using selenium and coenzyme Q10 for four years as a dietary supplement was performed. The main publication reported reduced cardiovascular mortality as a result of the intervention. In the present sub-study the objective was to determine whether reduced cardiovascular (CV) mortality persisted after 12 years, in the supplemented population or in subgroups with diabetes, hypertension, ischemic heart disease or reduced functional capacity due to impaired cardiac function. Methods From a rural municipality in Sweden, four hundred forty-three healthy elderly individuals were included. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results, mortality was registered. Findings After 12 years a significantly reduced CV mortality could be seen in those supplemented with selenium and coenzyme Q10, with a CV mortality of 28.1% in the active treatment group, and 38.7% in the placebo group. A multivariate Cox regression analysis demonstrated a reduced CV mortality risk in the active treatment group (HR: 0.59; 95% CI 0.42-0.81; P = 0.001). In those with ischemic heart disease, diabetes, hypertension and impaired functional capacity we demonstrated a significantly reduced CV mortality risk. Conclusions This is a 12-year follow-up of a group of healthy elderly participants that were supplemented with selenium and coenzyme Q10 for four years. Even after twelve years we observed a significantly reduced risk for CV mortality in this group, as well as in subgroups of patients with diabetes, hypertension, ischemic heart disease or impaired functional capacity. The results thus validate the results obtained in the 10-year evaluation. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanisms behind this effect remain to be fully elucidated, although various effects on cardiac function, oxidative stress, fibrosis and inflammation have previously been identified. Since this was a small study, the observations should be regarded as hypothesis-generating.

  • 161.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hosp, Norway; Hedmark Univ Coll, Norway.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Svensson, Erland
    Swedish Def Res Agcy, Linkoping, Sweden.
    Johansson, Peter
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in East Östergötland, Department of Internal Medicine in Norrköping.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Less fibrosis in elderly subjects supplemented with selenium and coenzyme Q10A mechanism behind reduced cardiovascular mortality?2018In: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 44, no 2, p. 137-147Article in journal (Refereed)
    Abstract [en]

    Background: In an intervention study where 221 healthy elderly persons received selenium and coenzyme Q10 as a dietary supplement, and 222 received placebo for 4 years we observed improved cardiac function and reduced cardiovascular mortality. As fibrosis is central in the aging process, we investigated the effect of the intervention on biomarkers of fibrogenic activity in a subanalysis of this intervention study. Material and Methods: In the present subanalysis 122 actively treated individuals and 101 controls, the effect of the treatment on eight biomarkers of fibrogenic activity were assessed. These biomarkers were: Cathepsin S, Endostatin, Galectin 3, Growth Differentiation Factor-15 (GDF-15), Matrix Metalloproteinases 1 and 9, Tissue Inhibitor of Metalloproteinases 1 (TIMP 1) and Suppression of Tumorigenicity 2 (ST-2). Blood concentrations of these biomarkers after 6 and 42 months were analyzed by the use of T-tests, repeated measures of variance, and factor analyses. Results: Compared with placebo, in those receiving supplementation with selenium and coenzyme Q10, all biomarkers except ST2 showed significant decreased concentrations in blood. The changes in concentrations, that is, effects sizes as given by partial eta(2) caused by the intervention were considered small to medium. Conclusion: The significantly decreased biomarker concentrations in those on active treatment with selenium and coenzyme Q10 compared with those on placebo after 36 months of intervention presumably reflect less fibrogenic activity as a result of the intervention. These observations might indicate that reduced fibrosis precedes the reported improvement in cardiac function, thereby explaining some of the positive clinical effects caused by the intervention. (c) 2017 BioFactors, 44(2):137-147, 2018

  • 162.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Less increase of copeptin and MR-proADM due to intervention with selenium and coenzyme Q10 combined: Results from a 4-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens.2015In: Biofactors, ISSN 0951-6433, E-ISSN 1872-8081, Vol. 41, no 6, p. 443-452Article in journal (Refereed)
    Abstract [en]

    Intervention with selenium and coenzyme Q10 have recently been found to reduce mortality and increase cardiac function. The mechanisms behind these effects are unclear. As selenium and coenzyme Q10 is involved in the anti-oxidative defence, the present study aimed to evaluate effects of selenium and coenzyme Q10 on copeptin and adrenomedullin as oxidative stress biomarkers. Therefore 437 elderly individuals were included and given intervention for 4 years. Clinical examination and blood samples were undertaken at start and after 18 and 48 months. Evaluations of copeptin and MR-proADM changes were performed using repeated measures of variance. Cardiovascular mortality was evaluated using a 10-year-period of follow-up, and presented in Kaplan-Meier plots. A significant increase in copeptin level could be seen in the placebo group during the intervention period (from 9.4 pmol/L to 15.3 pmol/L), compared to the active treatment group. The difference between the groups was confirmed in the repeated measurement of variance analyses (P = 0.031) with less copeptin increase in the active treatment group. Furthermore, active treatment appeared to protect against cardiovascular death both in those with high and with low copeptin levels at inclusion. Less increase of MR-proADM could also be seen during the intervention in the active treatment group compared to controls (P=0.026). Both in those having an MR-proADM level above or below median level, significantly less cardiovascular mortality could be seen in the active treatment group (P=0.0001, and P=0.04 respectively). In conclusion supplementation with selenium and coenzyme Q10 during four years resulted in less concentration of both copeptin and MR-proADM. A cardioprotective effect of the supplementation was registered, irrespective of the initial levels of these biomarkers, and this protection was recognized also after 10 years of observation. © 2015 BioFactors, 41(6):443-452, 2015.

  • 163.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Reduced Cardiovascular Mortality 10 Years after Supplementation with Selenium and Coenzyme Q10 for Four Years: Follow-Up Results of a Prospective Randomized Double-Blind Placebo-Controlled Trial in Elderly Citizens2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 12, p. e0141641-Article in journal (Refereed)
    Abstract [en]

    Background Selenium and coenzyme Q10 are important antioxidants in the body. As the intake of selenium is low in Europe, and the endogenous production of coenzyme Q10 decreases as age increases, an intervention trial using selenium and coenzyme Q10 for four years was performed. As previously reported, the intervention was accompanied by reduced cardiovascular mortality. The objective of the present study was to analyze cardiovascular mortality for up to 10 years after intervention, to evaluate if mortality differed in subgroups differentiated by gender, diabetes, ischemic heart disease (IHD), and functional class. Methods Four-hundred forty-three healthy elderly individuals were included from a rural municipality in Sweden. All cardiovascular mortality was registered, and no participant was lost to the follow-up. Based on death certificates and autopsy results mortality was registered. Findings Significantly reduced cardiovascular mortality could be seen in those on selenium and coenzyme Q10 intervention. A multivariate Cox regression analysis demonstrated a reduced cardiovascular mortality risk in the active treatment group (HR: 0.51; 95% CI 0.36-0.74; P = 0.0003). The reduced mortality could be seen to persist during the 10-year period. Subgroup analysis showed positive effects in both genders. An equally positive risk reduction could be seen in those with ischemic heart disease (HR: 0.51; 95% CI 0.27-0.97; P = 0.04), but also in the different functional classes. Conclusions In a 10-year follow-up of a group of healthy elderly participants given four years of intervention with selenium and coenzyme Q10, significantly reduced cardiovascular mortality was observed. The protective action was not confined to the intervention period, but persisted during the follow-up period. The mechanism explaining the persistency remains to be elucidated. Since this was a small study, the observations should be regarded as hypothesis-generating.

  • 164.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Supplementation with Selenium and Coenzyme Q10 Reduces Cardiovascular Mortality in Elderly with Low Selenium Status. A Secondary Analysis of a Randomised Clinical Trial2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 7, article id e0157541Article in journal (Refereed)
    Abstract [en]

    Background Selenium is needed by all living cells in order to ensure the optimal function of several enzyme systems. However, the selenium content in the soil in Europe is generally low. Previous reports indicate that a dietary supplement of selenium could reduce cardiovascular disease but mainly in populations in low selenium areas. The objective of this secondary analysis of a previous randomised double-blind placebo-controlled trial from our group was to determine whether the effects on cardiovascular mortality of supplementation with a fixed dose of selenium and coenzyme Q10 combined during a four-year intervention were dependent on the basal level of selenium. Methods In 668 healthy elderly individuals from a municipality in Sweden, serum selenium concentration was measured. Of these, 219 individuals received daily supplementation with selenium (200 mu g Se as selenized yeast) and coenzyme Q10 (200 mg) combined for four years. The remaining participants (n = 449) received either placebo (n = 222) or no treatment (n = 227). All cardiovascular mortality was registered. No participant was lost during a median follow-up of 5.2 years. Based on death certificates and autopsy results, all mortality was registered. Findings The mean serum selenium concentration among participants at baseline was low, 67.1 mu g/L. Based on the distribution of selenium concentration at baseline, the supplemented group was divided into three groups; amp;lt;65 mu g/L, 65-85 mu g/L, and amp;gt;85 mu g/L (45 and 90 percentiles) and the remaining participants were distributed accordingly. Among the non-treated participants, lower cardiovascular mortality was found in the high selenium group as compared with the low selenium group (13.0% vs. 24.1%; P = 0.04). In the group with the lowest selenium basal concentration, those receiving placebo or no supplementation had a mortality of 24.1%, while mortality was 12.1% in the group receiving the active substance, which was an absolute risk reduction of 12%. In the middle selenium concentration group a mortality of 14.0% in the non-treated group, and 6.0% in the actively treated group could be demonstrated; thus, there was an absolute risk reduction of 8.0%. In the group with a serum concentration of amp;gt;85 mu g/L, a cardiovascular mortality of 17.5% in the non-treated group, and 13.0% in the actively treated group was observed. No significant risk reduction by supplementation could thus be found in this group. Conclusions In this evaluation of healthy elderly Swedish municipality members, two important results could be reported. Firstly, a low mean serum selenium concentration, 67 mu g/L, was found among the participants, and the cardiovascular mortality was higher in the subgroup with the lower selenium concentrations amp;lt; 65 mu g/L in comparison with those having a selenium concentration amp;gt; 85 mu g/L. Secondly, supplementation was cardio-protective in those with a low selenium concentration, amp;lt;= 85 at inclusion. In those with serum seleniumamp;gt; 85 mu g/L and no apparent deficiency, there was no effect of supplementation. This is a small study, but it presents interesting data, and more research on the impact of lower selenium intake than recommended is therefore warranted.

  • 165.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Alexander, Jan
    Norwegian Inst Publ Hlth, Norway.
    Aaseth, Jan
    Innlandet Hosp Trust, Norway; Inland Norway Univ Appl Sci, Norway.
    Larsson, Anders
    Uppsala Univ, Sweden.
    Decrease in inflammatory biomarker concentration by intervention with selenium and coenzyme Q10: a subanalysis of osteopontin, osteoprotergerin, TNFr1, TNFr2 and TWEAK2019In: Journal of Inflammation, ISSN 1476-9255, E-ISSN 1476-9255, Vol. 16, article id 5Article in journal (Refereed)
    Abstract [en]

    Background: Inflammation is central to the pathogenesis of many diseases. Supplementation with selenium and coenzyme Q10 has been shown to reduce cardiovascular mortality, and increase cardiac function in elderly persons with a low intake of selenium. There are indications that one of the mechanisms of this positive effect is a decrease in inflammation. Methods: Osteopontin, osteoprotegerin, sTNF receptor 1, sTNF receptor 2 and the tumor necrosis factor-like weak inducer of apoptosis called TWEAK, were determined in plasma after 6 months and 42months in 219 community-living elderly persons, of whom 119 received supplements of selenium (200g/day) and coenzyme Q10 (200mg/day), and 101 received a placebo. Repeated measures of variance were used to evaluate the levels, and the results were validated through ANCOVA analyses with adjustments for important covariates. Results: Significantly lower concentrations of four of the five biomarkers for inflammation were observed as a result of the intervention with the supplements. Only TWEAK did not show significant differences. Conclusion: In this sub-analysis of the intervention with selenium and coenzyme Q10 or placebo in an elderly community-living population, biomarkers for inflammation were evaluated. A significantly lower concentration in four of the five biomarkers tested could be demonstrated as a result of the supplementation, indicating a robust effect on the inflammatory system. The decrease in inflammation could be one of the mechanisms behind the positive clinical results on reduced cardiovascular morbidity and mortality reported earlier as a result of the intervention. The study is small and should be regarded as hypothesis-generating, but nonetheless adds important data about mechanisms presently known to increase the risk of clinical effects such as reduced cardiovascular mortality, increased cardiac function and better health-related quality of life scoring, as previously demonstrated in the active treatment group.

  • 166.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska University Hospital, Sweden; Karolinska Institute, Sweden.
    Association Between Use of Statins and Mortality in Patients With Heart Failure and Ejection Fraction of greater than= 50%2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 5, p. 862-870Article in journal (Refereed)
    Abstract [en]

    Background The pathophysiology of heart failure with preserved ejection fraction is poorly understood, but may involve a systemic proinflammatory state. Therefore, statins might improve outcomes in patients with heart failure with preserved ejection fraction defined as 50%. Methods and Results Of 46 959 unique patients in the prospective Swedish Heart Failure Registry, 9140 patients had heart failure and ejection fraction 50% (age 7711 years, 54.0% women), and of these, 3427 (37.5%) were treated with statins. Propensity scores for statin treatment were derived from 40 baseline variables. The association between statin use and primary (all-cause mortality) and secondary (separately, cardiovascular mortality, and combined all-cause mortality or cardiovascular hospitalization) end points was assessed with Cox regressions in a population matched 1:1 based on age and propensity score. In the matched population, 1-year survival was 85.1% for statin-treated versus 80.9% for untreated patients (hazard ratio, 0.80; 95% confidence interval, 0.72-0.89; Pless than0.001). Statins were also associated with reduced cardiovascular death (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98; P=0.026) and composite all-cause mortality or cardiovascular hospitalization (hazard ratio, 0.89; 95% confidence interval, 0.82-0.96; P=0.003). Conclusions In heart failure with ejection fraction 50%, the use of statins was associated with improved outcomes. The mechanisms should be evaluated and the effects tested in a randomized trial.

  • 167.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Benson, Lina
    Karolinska Institute, Sweden.
    Edner, Magnus
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lund, Lars H.
    Karolinska Institute, Sweden; Karolinska University Hospital, Sweden.
    Association Between Use of Statins and Outcomes in Heart Failure With Reduced Ejection Fraction Prospective Propensity Score Matched Cohort Study of 21 864 Patients in the Swedish Heart Failure Registry2015In: Circulation Heart Failure, ISSN 1941-3289, E-ISSN 1941-3297, Vol. 8, no 2, p. 252-260Article in journal (Refereed)
    Abstract [en]

    Background-In heart failure (HF) with reduced ejection fraction, randomized trials of statins did not demonstrate improved outcomes. However, randomized trials may not always be generalizable. The aim was to determine whether statins are associated with improved outcomes in an unselected nationwide population of patients with HF with reduced ejection fraction overall and in relation to ischemic heart disease (IHD). Methods and Results-In the Swedish Heart Failure Registry, 21 864 patients with HF with reduced ejection fraction (age +/- SD, 72+/-12 years; 29% women), of whom 10 345 (47%) were treated with statins, were studied. Propensity scores for statin use were derived from 42 baseline variables. The associations between statin use and outcomes were assessed with Cox regressions in a population matched 1: 1 based on propensity score and age and in the overall population with adjustment for propensity score and age. The primary outcome was all-cause mortality; secondary outcomes were cardiovascular mortality; HF hospitalization; and combined all-cause mortality or cardiovascular hospitalization. Survival at 1 year in the matched population was 83% for statin-treated versus 79% for untreated patients (hazard ratio, 0.81; 95% confidence interval, 0.76-0.86; Pless than0.001). In the unmatched population, 1-year survival was 85% for statin-treated versus 79% for untreated patients, hazard ratio after adjustment for propensity score and age was 0.84 (95% confidence interval, 0.80-0.89; Pless than0.001). No examined baseline variables interacted with statin use except for IHD (P=0.001), with a hazard ratio of 0.76 (95% confidence interval, 0.70-0.82, Pless than0.001) with IHD and 0.95 (95% confidence interval, 0.85-1.07; P=0.430 without IHD. Statin use was also associated with reduced risk for all 3 secondary outcomes. Conclusions-In an unselected nationwide population of patients with HF with reduced ejection fraction, statins were associated with improved outcomes, specifically in the presence of IHD. This contrasts with previous randomized controlled trials. Additional randomized controlled trials with more generalized inclusion or focused on IHD may be warranted.

  • 168.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Can NT-proBNP predict risk of cardiovascular mortality within 10 years? Results from an epidemiological study of elderly patients with symptoms of heart failure2009In: International journal of cardiology, ISSN 0167-5273, Vol. 133, no 2, p. 233-240Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure has a serious prognosis. However, among elderly patients the panorama of concomitant diseases makes it difficult to implement the results from epidemiological studies. The aim of this study was to evaluate the influence of different clinical variables on cardiovascular mortality during a long-term follow-up.

    Methods and results: In all, 474 elderly patients (age 65-82 years) in primary health care were evaluated and followed during a 10 year period. All patients had symptoms associated with heart failure and were examined by a cardiologist. Blood samples including NT-proBNP were analyzed, and ECG and Doppler echocardiography were assessed. Both the systolic and diastolic function was evaluated. Functional capacity was evaluated according to the NYHA classification.

    During the 10 years of follow-up those with the highest quartile of plasma concentration of NT-proBNP had almost four times increased risk of cardiovascular mortality. Impaired systolic function, diabetes and reduced functional capacity were all markers of increased risk of cardiovascular mortality. All variables were also evaluated after 5 years, with higher risk ratios for a majority of variables.

    Conclusion: In this study 474 patients with symptoms of heart failure were followed during 10 years. High plasma concentration of NT-proBNP could predict almost four times increased risk of cardiovascular mortality up to 10 years. Also, impaired cardiac function according to echocardiography, and reduced functional capacity as well as diabetes all had influence on risk of cardiovascular mortality up to 10 years.

     

  • 169.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Carstensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Rehfeld, J. F.
    University of Copenhagen, Denmark .
    Gotze, J. P.
    University of Copenhagen, Denmark .
    Combined measurement of copeptin, high sensitivity Troponin T, and NT-proBNP improves the identification of elderly patients at risk of cardiovascular death in REGULATORY PEPTIDES, vol 177, issue , pp S14-S142012In: REGULATORY PEPTIDES, Elsevier , 2012, Vol. 177, p. S14-S14Conference paper (Refereed)
    Abstract [en]

    n/a

  • 170.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Cartensen, John
    Linköping University, Department of Medical and Health Sciences, Health and Society. Linköping University, Faculty of Arts and Sciences.
    Refeld, Jens
    Rigshospitalet, University of Copenhagen, Denmark.
    Goetze, Jens
    Rigshospitalet, University of Copenhagen, Denmark.
    Combined measurement of copeptin, high-sensitivity troponin T, and N-terminal proBNP improves the identification of patients at risk of cardiovascular death2012In: Cardiovascular Endocrinology, ISSN 2162-688X, Vol. 1, no 4, p. 68-73Article in journal (Refereed)
    Abstract [en]

    Objectives: A multimarker strategy for the handling of patients with heart failure has been suggested in the literature. Therefore, the potential prognostic relevance of combined copeptin, high-sensitivity troponin T (HS-TnT), and N-terminal proBNP (NT-proBNP) measurement in plasma from elderly patients with symptoms of heart failure was evaluated

    Methods: This study included 470 elderly patients (mean age 73 years) from a rural municipality with symptoms of heart failure. Clinical examination, echocardiography, and biomarker measurements were performed. All patients were followed for 13 years and all mortality was registered. Cardiovascular mortality was evaluated using Kaplan-Meier plots and multivariate Cox proportional hazard regression analyses.

    Results: Copeptin, HS-TnT, and NT-proBNP measurements provided independent prognostic information in a multivariate setting over 5 years (hazard ratio, HR: 3.66; 95% confidence interval, CI 1.27-10.53, HR: 2.52; 95% CI 1.20-5.28, HR: 2.73; 95% CI 1.19-6.26, respectively). Also, the group with all three biomarkers below cut-off values had a low risk for cardiovascular death (1.8% of the patients in this group died in the 5-year follow-up period). In the 13-year follow-up, combined copeptin and HS-TnT measurement did not provide independent prognostic information.

    Conclusion: Combined copeptin, HS-TnT, and NT-proBNP plasma measurements provide prognostic information on cardiovascular mortality that is superior to single biomarker use.

  • 171.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Cystatin C and NT-proBNP, a powerful combination of biomarkers for predicting cardiovascular mortality in elderly patients with heart failure: results from a 10-year study in primary care2009In: EUROPEAN JOURNAL OF HEART FAILURE, ISSN 1388-9842, Vol. 11, no 4, p. 354-360Article in journal (Refereed)
    Abstract [en]

    Heart failure (HF) is common among the elderly patients. It is essential to identify those at high risk in order to optimize the use of resources. We aimed to evaluate whether a combination of two biomarkers might give better prognostic information about the risk of cardiovascular (CV) mortality in patients with symptoms associated with HF, compared with only one biomarker. Four hundred and sixty-four primary health-care patients (mean age 73 years, range 65-87) with symptoms of HF were examined. All patients were evaluated using Doppler echocardiography and blood samples, including measurement of cystatin C and NT-proBNP. The patients were followed over a 10-year period. Patients with serum cystatin C levels within the highest quartile had almost three times the risk (HR: 2.92; 95% CI: 1.23-4.90) of CV mortality compared with those patients who had levels within the first, second, or third quartiles. If, at the same time, the patient had a plasma concentration of NT-proBNP within the highest quartile, the risk increased to andgt; 13 times (HR: 13.61; 95% CI: 2.56-72.24) during 10 years of follow-up or andgt; 17 times (HR: 17.04; 95% CI: 1.80-163.39) after 5 years of follow-up. Combined analysis of cystatin C and NT-proBNP could provide important prognostic information among elderly patients in the community with symptoms of HF.

  • 172.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Clinical Chemistry. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Laboratory Medicine, Department of Clinical Chemistry.
    Low plasma concentrations of coagulation factors II, VII and XI indicate increased risk among elderly with symptoms of heart failure.2010In: Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, ISSN 1473-5733, Vol. 21, no 1, p. 62-9Article in journal (Refereed)
    Abstract [en]

    Heart failure is a serious condition, and it is, therefore, important to identify patients at high risk as early as possible in order to initiate appropriate treatment. The condition results in complicated disease mechanisms including disturbances in blood coagulation. The aim of the present study was to evaluate whether low plasma concentrations of coagulation factors (F) II, VII and XI influence cardiovascular mortality in an elderly population with possible heart failure. A cardiologist evaluated 450 elderly patients who attended primary healthcare because of symptoms associated with heart failure. He recorded new patient history, conducted a clinical examination, took blood samples, determined concentrations of B-type natriuretic peptide and FII, FVII, FXI and performed Doppler echocardiography. The patients were followed over almost a 10-year period during which all mortality was registered. In patients with suspected heart failure, those with low plasma concentrations of FII, FVII, FXI or all had a significantly higher mortality rate during the follow-up period of 10 years as compared with those with higher plasma concentrations, in contrast with findings in previous reports on patients with acute coronary syndromes. In the group with a plasma concentration of the first versus the ninth decile of FII, FVII, FXI or all, the risk of cardiovascular mortality increased two to three times.

  • 173.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Rehfeld, Jens F
    University of Copenhagen, Denmark.
    Goetze, Jens P
    University of Copenhagen, Denmark.
    Association of Copeptin and N-Terminal proBNP Concentrations With Risk of Cardiovascular Death in Older Patients With Symptoms of Heart Failure2011In: JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, ISSN 0098-7484, Vol. 305, no 20, p. 2088-2095Article in journal (Refereed)
    Abstract [en]

    Context Measurement of plasma concentrations of the biomarker copeptin may help identify patients with heart failure at high and low risk of mortality, although the value of copeptin measurement in elderly patients is not fully known. Objective To evaluate the association between plasma concentrations of copeptin, a surrogate marker of vasopressin, combined with concentrations of the N-terminal fragment of the precursor to B-type natriuretic peptide (NT-proBNP), and mortality in a cohort of elderly patients with symptoms of heart failure. Design, Setting, and Participants Primary health care population in Sweden enrolling 470 elderly patients with heart failure symptoms between January and December 1996. Clinical examination, echocardiography, and measurement of peptide concentrations were performed, with follow-up through December 2009. Main Outcome Measures All-cause mortality and cardiovascular mortality. Results After a median follow-up of 13 years, there were 226 deaths from all causes, including 146 deaths from cardiovascular causes. Increased concentration of copeptin was associated with increased risk of all-cause mortality (fourth quartile vs first quartile: 69.5% vs 38.5%, respectively; hazard ratio [HR], 2.04 [95% confidence interval {CI}, 1.38-3.02]) and cardiovascular mortality (fourth quartile vs first quartile: 46.6% vs 26.5%; HR, 1.94 [95% CI, 1.20-3.13]). The combination of elevated NT-proBNP concentrations and elevated copeptin concentrations also was associated with increased risk of all-cause mortality (copeptin fourth quartile: HR, 1.63 [95% CI, 1.08-2.47]; P=.01; NT-proBNP fourth quartile: HR, 3.17 [95% CI, 2.02-4.98]; Pandlt;.001). Using the 2 biomarkers simultaneously in the evaluation of cardiovascular mortality, there was a significant association for copeptin in the presence of NT-proBNP (log likelihood trend test, P=.048) and a significant association for NT-proBNP (fourth quartile: HR, 4.68 [95% CI 2.63-8.34]; Pandlt;.001). Conclusion Among elderly patients with symptoms of heart failure, elevated concentrations of copeptin and the combination of elevated concentrations of copeptin and NT-proBNP were associated with increased risk of all-cause mortality.

  • 174.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Rehfeld, Jens F.
    University of Copenhagen, Denmark .
    Goetze, Jens P.
    University of Copenhagen, Denmark .
    Pro-A-Type Natriuretic Peptide, Proadrenomedullin, and N-Terminal Pro-B-Type Natriuretic Peptide Used in a Multimarker Strategy in Primary Health Care in Risk Assessment of Patients With Symptoms of Heart Failure2013In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 19, no 1, p. 31-39Article in journal (Refereed)
    Abstract [en]

    Objective: Use of new biomarkers in the handling of heart failure patients has been advocated in the literature, but most often in hospital-based populations. Therefore, we wanted to evaluate whether plasma measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP), midregional pro A-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM), individually or combined, gives prognostic information regarding cardiovascular and all-cause mortality that could motivate use in elderly patients presenting with symptoms suggestive of heart failure in primary health care. less thanbrgreater than less thanbrgreater thanMethods and Results: The study included 470 elderly patients (mean age 73 years) with symptoms of heart failure in primary health care. All participants underwent clinical examination, 2-dimenstional echocardiography, and plasma measurement of the 3 propeptides and were followed for 13 years. All mortality was registered during the follow-up period. The 4th quartiles of the biomarkers were applied as cutoff values. NT-proBNP exhibited the strongest prognostic information with andgt;4-fold increased risk for cardiovascular mortality within 5 years. For all-cause mortality MR-proADM exhibited almost 2-fold and NT-proBNP 3-fold increased risk within 5 years. In the 5-13-year perspective, NT-proBNP and MR-proANP showed significant and independent cardiovascular prognostic information. NT-proBNP and MR-proADM showed significant prognostic information regarding all-cause mortality during the same time. In those with ejection fraction (EF) andlt;40%, MR-proADM exhibited almost 5-fold increased risk of cardiovascular mortality with 5 years, whereas in those with EF andgt;50% NT-proBNP exhibited andgt;3-fold increased risk if analyzed as the only biomarker in the model. If instead the biomarkers were all below the cutoff value, the patients had a highly reduced mortality risk, which also could influence the handling of patients. less thanbrgreater than less thanbrgreater thanConclusions: The 3 biomarkers could be integrated in a multimarker strategy for use in primary health care. (J Cardiac Fail 2013;19:31-39)

  • 175.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Rehfeld, Jens F
    University of Copenhagen.
    Goetze, Jens P
    University of Copenhagen.
    Prognostic Assessment of Elderly Patients with Symptoms of Heart Failure by Combining High-Sensitivity Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide Measurements2010In: CLINICAL CHEMISTRY, ISSN 0009-9147, Vol. 56, no 11, p. 1718-1724Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a useful biomarker in heart failure assessment, whereas measurement of cardiac troponin is central in the diagnosis of patients with acute coronary syndromes. This report examined the prognostic use of combining high-sensitivity cardiac troponin T (hs-cTnT) and NT-proBNP measurements in elderly patients presenting to a primary care center with symptoms associated with heart failure. METHODS: A total of 470 elderly patients (age range 65-86 years) presenting with symptoms of heart failure were recruited from primary healthcare. In addition to clinical examination and echocardiography, hs-cTnT and NT-proBNP plasma concentrations were measured. All patients were followed for 10 years, and cardiovascular mortality was registered. RESULTS: By use of the hs-cTnT assay, 80.4% of the population had plasma concentrations above the lower detection limit of the assay. Of those displaying a plasma concentration of hs-cTnT andgt;99th percentile of a healthy population, 43% also had an NT-proBNP concentration in the fourth quartile (andgt;507 ng/L). In the multivariate analysis, we observed a 2.5-fold increased risk for cardiovascular mortality in individuals with a plasma NT-proBNP concentration andgt;507 ng/L (P andlt; 0.0001). Conversely, patients with hs-cTnT andgt;99th percentile displayed an approximately 2-fold increased risk for cardiovascular mortality (P = 0.0002). Combining the 2 biomarkers, NT-proBNP concentrations andgt;507 ng/L with hs-cTnT andgt;99th percentile increased the risk 3-fold, even after adjustment for clinical variables such as age, sex, impaired estimated glomerular filtration rate, and anemia (P andlt; 0.0001). CONCLUSIONS: hs-cTnT and NT-proBNP measurements combined provide better prognostic information than using either biomarker separately in elderly patients with symptoms associated with heart failure.

  • 176.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Ericsson, Anne
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Dahlström, Ulf
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Are There Any Significant Differences Between Females and Males in the Management of Heart Failure? Gender Aspects of an Elderly Population With Symptoms Associated With Heart Failure2009In: JOURNAL OF CARDIAC FAILURE, ISSN 1071-9164, Vol. 15, no 6, p. 501-507Article in journal (Refereed)
    Abstract [en]

    Background: An increasing interest has been shown in potential l., 11 With heart failure (HF), a serious condition for the individual. To evaluate whether there are any differences ill the prevalence of HF, cardiac function, biomarkers. and the treatment of HF with respect to gender. Methods and Results: All persons ages 70 to 80 in a rural municipality were invited to participate ill the project 876 persons accepted. Three cardiologists evaluated the patients including a new history, clinical examination. electrocardiogram, chest x-ray. blood samples. and Doppler echocardiography to assess both Systolic and diastolic function. The patients were followed during a mean period of 8 years. Conclusion: Females hypertension more frequently and included fewer smokers than their male Counterparts. A Female preponderance was seen in those with preserved systolic function. whereas males predominated among those with systolic dysfunction. During the follow-up period, 20% of the males and 14% of the females died of cardiovascular diseases. The results did not show any inferior treatment of females with HF. but it clearly was more difficult to correctly classify female patients presenting with symptoms of HE

  • 177.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, H
    Hall, C
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    B-type natriuretic peptides as markers of left ventricular function in the elderly2001In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 22, p. 304-304Conference paper (Other academic)
  • 178.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Eriksson, H
    Nylander, E
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Overtreatment as well as undertreatment of heart failure is common in elderly patients in primary health care. Objective diagnostics tools are needed2001In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 22, p. 143-143Conference paper (Other academic)
  • 179.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Eriksson, H.
    Department of Medicine, Sahlgrenska Univ. Hosp.-Östra, Gothenburg, Sweden.
    Nylander, Eva
    Linköping University, Department of Medical and Health Sciences, Clinical Physiology. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences.
    Heart failure in the elderly: characteristics of a Swedish primary health care population2002In: Heart Drug, ISSN 1422-9528, E-ISSN 1424-0556, Vol. 2, no 5, p. 211-220Article in journal (Refereed)
    Abstract [en]

    Background: Heart failure (HF) is a challenge to diagnose and treat according to guidelines. Few studies have been performed in elderly subjects with symptoms that might be associated with HF in primary health care.

    Objective: To study elderly patients presenting with symptoms possibly associated with HF, with respect to systolic and diastolic function, B-type natriuretic peptide (BNP) levels and treatment.

    Methods: A cardiologist examined 415 elderly (65–82 years) patients with symptoms of dyspnoea, fatigue and/or peripheral oedema. All patients underwent echocardiography and plasma BNP determination. Systolic function was determined semiquantitatively, and ejection fraction (EF) <40% was considered to be reduced. Abnormal diastolic function was defined as a reduced ratio of peak early diastolic filling velocity to peak filling velocity at atrial contraction (E/A ratio; age adjusted) or an abnormal pattern of pulmonary venous flow.

    Results: Forty-eight percent of the patients showed abnormal systolic (26%) or diastolic function (22%). A majority of the patients with diastolic HF had relaxation abnormalities and neither pseudonormal nor restrictive filling patterns. Increased levels of BNP were found in the group with impaired systolic function. More than half of those with EF <40% were not receiving angiotensin-converting enzyme inhibitions at all, or were on a suboptimal dose, whereas others were on treatment for an HF diagnosis despite normal cardiac function.

    Conclusion: Diagnostic tools that are more objective than clinical examination are needed for the diagnosis of HF.

  • 180.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Janzon, Magnus
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    A clinician’s experience of using the Cardiac Reader NT-proBNP point-of-care assay in a clinical setting2008In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 10, no 3, p. 260-266Article in journal (Refereed)
    Abstract [en]

    The evaluation of natriuretic peptides has become increasingly valuable in a clinical setting, where information is often needed promptly.

    Objectives: To compare the usefulness of the recently released Roche Cardiac Reader ® NT-proBNP assay against the Roche Elecsys® NT-proBNP laboratory system in a clinical setting.

    Design and Results: Blood samples from 440 patients admitted for acute coronary syndromes, worsening of heart failure, or as policlinic heart failure patients were evaluated. The relation between the assays was analysed and the diagnostic concordance calculated. A good correlation was found between the assays (r=0.96, 95% CI: 0.94-0.97) with a diagnostic concordance of 0.93. A separate analysis was performed in the range where most clinical decisions are made (60-3000 ng/L), with a diagnostic concordance of 88%. The usefulness in a clinical setting where time is important was high.

    Conclusion: The Roche Cardiac Reader® NT-proBNP assay has been evaluated in a clinical setting. The point-of-care method shows good results, although with a restricted analytical range compared with the reference.

  • 181.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Johansson, Peter
    Linköping University, Department of Social and Welfare Studies, Division of Nursing Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Appl Science, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Brismar, Kerstin
    Karolinska University Hospital, Sweden.
    Increase in insulin-like growth factor 1 (IGF-1) and insulin-like growth factor binding protein 1 after supplementation with selenium and coenzyme Q10. A prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0178614Article in journal (Refereed)
    Abstract [en]

    Background Insulin-like growth factor-1(IGF-1) has a multitude of effects besides cell growth and metabolism. Reports also indicate anti-inflammatory and antioxidative effects. The concentrations of IGF-1 decrease with age and during inflammation. As selenium and coenzyme Q10 are involved in both the antioxidative defense and the inflammatory response, the present study aimed to examine the effects of supplementation with selenium and coenzyme Q10 on concentrations of IGF-1 and its binding protein IGFBP-1 in a population showing reduced cardiovascular mortality following such supplementation. Methods 215 elderly individuals were included and given the intervention for four years. A clinical examination was performed and blood samples were taken at the start and after 48 months. Evaluations of IGF-1, the age adjusted IGF-1 SD score and IGFBP-1 were performed using group mean values, and repeated measures of variance. Findings After supplementation with selenium and coenzyme Q10, applying group mean evaluations, significantly higher IGF-1 and IGF-1 SD scores could be seen in the active treatment group, whereas a decrease in concentration could be seen of the same biomarkers in the placebo group. Applying the repeated measures of variance evaluations, the same significant increase in concentrations of IGF-1 (F = 68; P amp;gt; 0.0001), IGF-1 SD score (F = 29; P amp;lt; 0.0001) and of IGFBP-1 (F = 6.88; P = 0.009) could be seen, indicating the effect of selenium and coenzyme Q10 also on the expression of IGF-1 as one of the mechanistic effects of the intervention. Conclusion Supplementation with selenium and coenzyme Q10 over four years resulted in increased levels of IGF-1 and the postprandial IGFBP-1, and an increase in the age-corrected IGF-1 SD score, compared with placebo. The effects could be part of the mechanistic explanation behind the surprisingly positive clinical effects on cardiovascular morbidity and mortality reported earlier. However, as the effects of IGF-1 are complex, more research on the result of intervention with selenium and coenzyme Q10 is needed.

  • 182.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Alexander, Jan
    Norwegian Institute Public Heatlh, Norway; Norwegian University of Life Science NMBU, Norway.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Significant changes in circulating microRNA by dietary supplementation of selenium and coenzyme Q10 in healthy elderly males. A subgroup analysis of a prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 4, article id e0174880Article in journal (Refereed)
    Abstract [en]

    Background Selenium and coenzyme Q10 is essential for important cellular functions. A low selenium intake is reported from many European countries, and the endogenous coenzyme Q10 production is decreasing in the body with increasing age. Supplementation with selenium and coenzyme Q10 in elderly have shown reduced cardiovascular mortality and reduced levels of markers of inflammation. However, microRNA analyses could give important information on the mechanisms behind the clinical effects of supplementation. Methods Out of the 443 healthy elderly participants that were given supplementation with 200 mu g Se/ day as organic selenium yeast tablets, and 200 mg/day of coenzyme Q10 capsules, or placebo for 4 years, 25 participants from each group were randomized and evaluated regarding levels of microRNA. Isolation of RNA from plasma samples and quantitative PCR analysis were performed. Volcano- and principal component analyses (PCA)-plots were used to illustrate the differences in microRNA expression between the intervention, and the placebo groups. Serum selenium concentrations were measured before intervention. Findings On average 145 different microRNAs out of 172 were detected per sample. In the PCA plots two clusters could be identified indicating significant difference in microRNA expression between the two groups. The pre-treatment expression of the microRNAs did not differ between active treatment and the placebo groups. When comparing the post- treatment microRNAs in the active and the placebo groups, 70 microRNAs exhibited significant differences in expression, also after adjustment for multiple measurements. For the 20 microRNAs with the greatest difference in expression the difference was up to more than 4 fold and with a P-value that were less than 4.4e(-8). Conclusions Significant differences were found in expression of more than 100 different microRNAs with up to 4 fold differences as a result of the intervention of selenium and coenzyme Q10 combined. The changes in microRNA could be a part of mechanisms underlying the clinical effects earlier reported that reduced cardiovascular mortality, gave better cardiac function, and showed less signs of inflammation and oxdative stress following the intervention. However, more research is needed to understand biological mechanisms of the protective effects of selenium and Q10 supplementation.

  • 183.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Johansson, Peter
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Björnstedt, Mikael
    Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Cell Biology. Linköping University, Faculty of Health Sciences.
    Dahlström, Ulf
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Center, Department of Cardiology in Linköping.
    Cardiovascular mortality and N-terminal-proBNP reduced after combined selenium and coenzyme Q10 supplementation: a 5-year prospective randomized double-blind placebo-controlled trial among elderly Swedish citizens2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 167, no 5, p. 1860-1866Article in journal (Refereed)
    Abstract [en]

    Background

    Selenium and coenzyme Q10 are essential for the cell. Low cardiac contents of selenium and coenzyme Q10 have been shown in patients with cardiomyopathy, but inconsistent results are published on the effect of supplementation of the two components separately. A vital relationship exists between the two substances to obtain optimal function of the cell. However, reports on combined supplements are lacking.

    Methods

    A 5-year prospective randomized double-blind placebo-controlled trial among Swedish citizens aged 70 to 88 was performed in 443 participants given combined supplementation of selenium and coenzyme Q10 or a placebo. Clinical examinations, echocardiography and biomarker measurements were performed. Participants were monitored every 6th month throughout the intervention.

    The cardiac biomarker N-terminal proBNP (NT-proBNP) and echocardiographic changes were monitored and mortalities were registered. End-points of mortality were evaluated by Kaplan–Meier plots and Cox proportional hazard ratios were adjusted for potential confounding factors. Intention-to-treat and per-protocol analyses were applied.

    Results

    During a follow up time of 5.2 years a significant reduction of cardiovascular mortality was found in the active treatment group vs. the placebo group (5.9% vs. 12.6%; P = 0.015). NT-proBNP levels were significantly lower in the active group compared with the placebo group (mean values: 214 ng/L vs. 302 ng/L at 48 months; P = 0.014). In echocardiography a significant better cardiac function score was found in the active supplementation compared to the placebo group (P = 0.03).

    Conclusion

    Long-term supplementation of selenium/coenzyme Q10 reduces cardiovascular mortality. The positive effects could also be seen in NT-proBNP levels and on echocardiography.

  • 184.
    Alehagen, Urban
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Björnstedt, Mikael
    Division of Pathology F42, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
    Rosén, Anders
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Post, Claes
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Aaseth, Jan
    Research Department, Innlandet Hospital Trust and Hedmark University College, Norway.
    Relatively high mortality risk in elderly Swedish subjects with low selenium status2016In: European Journal of Clinical Nutrition, ISSN 0954-3007, E-ISSN 1476-5640, Vol. 70, no 1, p. 91-96Article in journal (Refereed)
    Abstract [en]

    Background/Objectives: 

    The daily dietary intake of selenium (Se), an essential trace element, is still low in Sweden in spite of decades of nutritional information campaigns and the effect of this on the public health is presently not well known. The objective of this study was to determine the serum Se levels in an elderly Swedish population and to analyze whether a low Se status had any influence on mortality.

    Subjects/Methods: 

    Six-hundred sixty-eight (n=668) elderly participants were invited from a municipality and evaluated in an observational study. Individuals were followed for 6.8 years and Se levels were re-evaluated in 98 individuals after 48 months. Clinical examination of all individuals included functional classification, echocardiography, electrocardiogram and serum Se measurement. All mortality was registered and endpoints of mortality were assessed by Kaplan–Meier plots, and Cox proportional hazard ratios adjusted for potential confounding factors were calculated.

    Results: 

    The mean serum Se level of the study population (n=668) was 67.1 μg/l, corresponding to relatively low Se intake. After adjustment for male gender, smoking, ischemic heart disease, diabetes, chronic obstructive pulmonary disease and impaired heart function, persons with serum Se in the lowest quartile had 43% (95% confidence interval (CI): 1.02–2.00) and 56% (95% CI: 1.03–2.36) increased risk for all-cause and cardiovascular mortality, respectively. The result was not driven by inflammatory effects on Se concentration in serum.

    Conclusion: 

    The mean serum Se concentration in an elderly Swedish population was 67.1 μg/l, which is below the physiological saturation level for several selenoprotein enzymes. This result may suggest the value of modest Se supplementation in order to improve the health of the Swedish population.

  • 185.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Chemistry.
    Aaseth, Jan
    Innlandet Hospital Trust, Norway; Hedmark University of Coll, Norway.
    Svensson, Erland
    Swedish Def Research Agency, Sweden.
    Johansson, Peter
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Levels of sP-selectin and hs-CRP Decrease with Dietary Intervention with Selenium and Coenzyme Q10 Combined: A Secondary Analysis of a Randomized Clinical Trial2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, p. e0137680-Article in journal (Refereed)
    Abstract [en]

    Background/Objectives Inflammation and oxidative stress are central in many disease states. The major anti-oxidative enzymes contain selenium. The selenium intake in Europe is low, and supplementation with selenium and coenzyme Q(10) , important anti-oxidants, was evaluated in a previous study. The aim of this study was to evaluate response on the inflammatory biomarkers C-reactive protein, and sP-selectin, and their possible impact on cardiovascular mortality. Subjects/Methods 437 elderly individuals were included in the study. Clinical examination, echocardiography, electrocardiography and blood samples were drawn. The intervention time was 48 months, and median follow-up was 5.2 years. The effects on inflammation/atherosclerosis were evaluated through analyses of CRP and sP-selectin. Evaluations of the effect of the intervention was performed using repeated measures of variance. All mortality was registered, and endpoints of mortality were assessed by Kaplan-Meier plots. Results The placebo group showed a CRP level of 4.8 ng/mL at the start, and 5.1 ng/mL at the study end. The active supplementation group showed a CRP level of 4.1 ng/mL at the start, and 2.1 ng/mL at the study end. SP-selectin exhibited a level of 56.6mg/mL at the start in the placebo group and 72.3 mg/mL at the study end, and in the active group the corresponding figures were 55.9 mg/mL and 58.0 mg/mL. A significantly smaller increase was demonstrated through repeated measurements of the two biomarkers in those on active supplementation. Active supplementation showed an effect on the CRP and sP-selectin levels, irrespective of the biomarker levels. Reduced cardiovascular mortality was demonstrated in both those with high and low levels of CRP and sP-selectin in the active supplementation group. Conclusion CRP and sP-selectin showed significant changes reflecting effects on inflammation and atherosclerosis in those given selenium and coenzyme Q(10) combined. A reduced cardiovascular mortality could be demonstrated in the active group, irrespective of biomarker level. This result should be regarded as hypothesis-generating, and it is hoped it will stimulate more research in the area.

  • 186.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Rahmqvist, Mikael
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics.
    Paulsson, Thomas
    AstraZeneca Sverige AB.
    Levin, Lars-Åke
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Health Technology Assessment and Health Economics.
    Quality-adjusted life year weights among elderly patients with heart failure2008In: European journal of heart failure, ISSN 1388-9842, Vol. 10, no 10, p. 1033-1039Article in journal (Refereed)
    Abstract [en]

    Background

    When assessing health-related quality of life (HRQoL) in elderly patients with heart failure (HF), the process of obtaining quality-adjusted life year (QALY) weights is generally complicated and time-consuming.

    Aim

    To evaluate whether information regarding HRQoL and QALY weights can be derived directly from the established and widely used New York Heart Association (NYHA) functional classification system.

    Methods

    NYHA functional status was assessed independently both by the individual patients and by the examining cardiologist in 323 elderly patients with symptoms of HF recruited from primary care. HRQoL was evaluated using the SF-36 questionnaire and a time trade-off (TTO) scenario. The TTO technique generates direct QALY weights.

    Results

    Both the TTO technique and SF-36 values demonstrated a statistically significant correlation with NYHA functional status. The TTO values also correlated with all SF-36 dimensions. Increasing impairment was associated with statistically significant drops in both SF-36 values and TTO-based QALY weights. For patients in NYHA classes I–IV the QALY weights were 0.77, 0.68, 0.61, and 0.50, respectively. Thus in elderly patients, symptoms of HF have a major impact on perceived quality of life.

    Conclusion

    The results of the present study show that QALY weights, an important instrument in the health economic evaluation of treatment strategies, can be derived directly from NYHA classification in elderly HF patients.

  • 187.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Slind Olsen, Renate
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. County Hospital Ryhov, Sweden.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Matussek, Andreas
    County Hospital Ryhov, Sweden.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    PDGF-D gene polymorphism is associated with increased cardiovascular mortality in elderly men2016In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 17, no 62Article in journal (Refereed)
    Abstract [en]

    Background: Platelet-derived growth factor (PDGF) D has been reported to be active in fibroblasts, and in areas of myocardial infarction. In this longitudinal study we evaluated the association between PDGF-D polymorphism and cardiovascular mortality, and attempted to discover whether specific genotype differences regarding risk could be observed, and if gender differences could be seen. Methods: Four hundred seventy-six elderly community participants were included in this study. All participants underwent a clinical examination, echocardiography, and blood sampling including PDGF-D single nucleotide polymorphism (SNP) analyses of the rs974819 A/A, G/A and G/G SNP. The follow-up time was 6.7 years. Results: No specific genotype of rs974819 demonstrated increased cardiovascular mortality in the total population, however, the male group with genotypes A/A and G/A demonstrated an increased risk that persisted in a multivariate evaluation where adjustments were made for well-known cardiovascular risk factors (2.7 fold compared with the G/G genotype). No corresponding finding was observed in the female group. Conclusion: We report here for the first time that the genotypes G/A or A/A of the SNP rs974819 near PDGF-D exhibited a 2.7 fold increased cardiovascular mortality risk in males. Corresponding increased risk could not be observed in either the total population and thus not in the female group. However, the sample size is was small and the results should be regarded as hypothesis-generating, and thus more research in the field is recommended.

  • 188.
    Alehagen, Urban
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Svensson, E.
    Swedish Defence Research Agency, Division of Command and Control Systems, Department of Man-System Interaction, Linköping, Sweden.
    Dahlström, Ulf
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Natriuretic Peptide Biomarkers as Information Indicators in Elderly Patients With Possible Heart Failure Followed Over Six Years: A Head-to-Head Comparison of Four Cardiac Natriuretic Peptides2007In: Journal of Cardiac Failure, ISSN 1071-9164, E-ISSN 1532-8414, Vol. 13, no 6, p. 452-461Article in journal (Refereed)
    Abstract [en]

    Background: Little is known about the differences between natriuretic peptides used to evaluate elderly patients with heart failure. The aim of the study was to evaluate the information and the power to predict cardiovascular mortality derived from an analysis of cardiac natriuretic peptides from the same study population and at the same time. Methods and Results: In all, 415 elderly patients (age 65-82 years) in primary health care were evaluated and followed for 6 years. All patients had symptoms of heart failure and were examined by a cardiologist. An electrocardiogram and chest x-rays were taken, and the systolic and diastolic functions were assessed using Doppler echocardiography. Brain natriuretic peptide (BNP), N-terminal proBNP, atrial natriuretic peptide (ANP), and N-terminal proANP were analyzed. All 4 peptides were associated with age, and only 1 of them showed any gender difference. Three of the 4 peptides (not ANP) provided important information for identifying patients with impaired systolic function and diastolic dysfunction (pseudonormal or restrictive filling pattern), and for assessing the risk of cardiovascular death. Conclusions: Cardiac natriuretic peptides are useful tools for evaluating elderly patients with heart failure. Three of the 4 peptides were very similar. ANP exhibits inferior properties and cannot be recommended in clinical practice. © 2007 Elsevier Inc. All rights reserved.

  • 189.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Vorkapic, Emina
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Ljungberg, Liza
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Länne, Toste
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Thoracic and Vascular Surgery.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
    Gender difference in adiponectin associated with cardiovascular mortality2015In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 16, no 9Article in journal (Refereed)
    Abstract [en]

    Background: It is important to identify cardiovascular diseases in patients at high risk. To include genetics into routine cardiological patients has therefore been discussed recently. We wanted to evaluate the association between high-molecular weight adiponectin and cardiovascular risk, and secondly in the same population evaluate if specific genotype differences regarding risk could be observed, and thirdly if gender differences could be seen. Method: Four hundred seventy-six elderly participants recruited from a rural community were included. All participants underwent a clinical examination, echocardiography, and blood sampling and the single nucleotide polymorphism (SNP) (rs266729) of adiponectin was analysed. Follow-up time was 6.7 years. Results: Those with high serum concentration of adiponectin had a more 2 fold increased cardiovascular risk, and it might be that females exhibits even higher risk where a more than 5 fold increased risk could be seen. The result could be demonstrated even in a multivariate model adjusting for well-known clinical risk factors. However, as the sample size was small the gender differences should be interpreted with caution. In the genotype evaluation the C/C carriers of the female group had a more than 9-fold increased risk of cardiovascular mortality, however the confidence interval was wide. Such genotype difference could not be found in the male group. Conclusion: High level of adiponectin was associated with increased cardiovascular risk. Also a gender difference in the genotype evaluation could be seen where the C/C carriers obtained higher risk in the female group but not in the male group. Thus, in order to identify patients at risk early, genetic analyses may add to the armamentarium used in the clinical routine. However, information should be regarded as hypothesis generating as the sample size was small and should stimulate further research in individualized cardiovascular prevention and treatment.

  • 190.
    Alehagen, Urban
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Wågsäter, Dick
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Uppsala Univ, Sweden.
    Gender difference and genetic variance in lipoprotein receptor-related protein 1 is associated with mortality2019In: BIOMEDICAL REPORTS, ISSN 2049-9434, Vol. 11, no 1Article in journal (Refereed)
    Abstract [en]

    Cardiovascular diseases are an important health resource problem and studies have shown a genetic association between single nucleotide polymorphisms (SNPs) and cardiovascular diseases. According to the literature, lipoprotein receptor-related protein 1 (LRP1) is associated with coronary artery disease. The aim of the present study was to evaluate a possible association between different genotypes of LRP1 and all-cause and cardiovascular mortality from a gender perspective. In the present study, 489 elderly community-living people were invited to participate. Clinical examination, echocardiography and blood sampling including SNP analyses of LRP1 (rs1466535) were performed, including the T/T, C/T and C/C genotypes, and the participants were followed for 6.7 years. During the follow-up period, 116 (24%) all-cause and 75 (15%) cardiovascular deaths were registered. In the female population, the LRP1 of the T/T or C/T genotype exhibited a 5.6-fold increased risk of cardiovascular mortality and a 2.8-fold increased risk of all-cause mortality compared with the C/C genotype. No such genotype differences could be seen in the male population. Gender differences could be seen regarding the risk of mortality in the different genotypes. Females with the LRP1 T/T or C/T genotypes exhibited a significantly increased risk of both all-cause and cardiovascular mortality compared with the C/C genotypes. Therefore, more individualized cardiovascular prevention and treatment should be prioritized. However, since this was a small study, the observations should only be regarded as hypothesis-generating.

  • 191.
    Alexanderson, Kristina
    et al.
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Borg, Karin E.
    Linköping University, Department of Medicine and Health Sciences, Division of Preventive and Social Medicine and Public Health Science. Linköping University, Faculty of Health Sciences.
    Hensing, Gunnel K.E.
    Department of Social Medicine, The Sahlgrenska Academy at Göteborg University.
    Sickness absence with low-back, shoulder, or neck diagnoses: An 11-year follow-up regarding gender differences in sickness absence and disability pension2005In: Work: A journal of Prevention, Assesment and rehabilitation, ISSN 1051-9815, E-ISSN 1875-9270, Vol. 25, no 2, p. 115-124Article in journal (Refereed)
    Abstract [en]

    Background: There is very little knowledge on the long-term outcomes of sickness absence. The aim was to investigate sickness absence and disability pensions over 11 years in a cohort of young persons initially long-term sick listed with back, neck, or shoulder diagnoses.

    Method: A prospective population-based cohort study of all 213 individuals in the Municipality of Linköping, Sweden, who in 1985 were aged 25-34 and had at least one new sick-leave spell > 28 days with such diagnoses.

    Main results: More women (61%) than men fulfilled the inclusion criteria. In 1996, 22% of the cohort (14% of the men, 26% of the women) had been granted disability pension; 76% of these individuals with musculoskeletal and the rest with psychiatric diagnoses. Partial disability pension was granted to 59% of the women, 17% of the men. Women were more often granted temporary disability pension than men.

    Conclusions: This proved to be a high-risk group for disability pension. There were large and somewhat unexpected gender differences regarding incidence and type of disability pension. It has been debated how soon physicians should be concerned about the risk of long-term disability regarding these diagnoses; at four or eight weeks of sickness absence - our results support the former, at least for women.

  • 192.
    Alexandersson, Sofie
    et al.
    Linköping University, Department of Medical and Health Sciences.
    Brickarp, Louise
    Linköping University, Department of Medical and Health Sciences.
    Sjuksköterskors erfarenheter av att vårda satellitpatienter: Jakten på vårdplatser i den svenska hälso- och sjukvården.2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Background: A shortage of hospital beds prevails in Swedish hospitals at the moment. This has led to care unit overcrowdings, which so far has been solved by outlocation of patients. This study’s background presents a variety of aspects related to these patients’ care, who sometimes also are called satellite patients.

    Aim: To describe nurses’ experiences of caring for satellite patients.

    Method: An interview study with a deductive approach has been conducted. Data was collected by semi-structured interviews with eight registered nurses. The interviews were recorded, transcribed and lastly analyzed from Hsieh and Shannon’s description of qualitative content analysis.

    Result: Six categories were identified; Effects of Outlocating Patients, Communication Between Caregivers, Competence Among Nursing Staff, Work Environment, Teamwork and Suggestions for Improvement. Together, these describe the nurses’ experiences of caring for satellite patients.

    Conclusion: Nurses’ experiences of caring for these patients were mainly characterized by a concern for patient safety. The participants also mentioned that nurses’ work environment and work terms needs to improve in order to open hospital beds, reduce the number of satellite patients and thereby maintain a safe and equivalent care. 

  • 193.
    Alfredsson, Joakim
    Linköping University, Department of Medicine and Health Sciences, Cardiology . Linköping University, Faculty of Health Sciences.
    Management and Outcome in Non ST-Elevation Acute Coronary Syndromes: Similarities and Differences Between Women nad Men2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Non ST-elevation Acute Coronary Syndromes are the most frequent manifestations of acute ischemic heart disease. Gender differences in treatment intensity, including differences in level of care, have been reported. Also differences in benefit from certain treatments, especially invasive treatment, have been discussed. Finally, difference in outcome between men and women, have been proposed. Results have been inconsistent, partly depending on if and how adjustment for differences in background characteristics has been made. The aims of the studies in this thesis were to assess differences between the genders in baseline characteristics, level of care, medical treatment and non-invasive and invasive cardiac procedures. The aims were also to determine gender differences in short and long-term mortality, including impact of level of care, and to determine differences between the genders in benefit from an invasive strategy, with special reference to benefit in women.

    Method: We used prospectively collected data from the RIKS-HIA registry in two studies (Paper I and IV). In one study we merged data from patients admitted to general wards in the south-east region of Sweden (The AKUT registry), with data from patients admitted to CCU´s (RIKS-HIA) at participating hospitals during the same time (Paper II). We also randomly assigned women to a routine invasive or a selective invasive treatment strategy, and performed a meta-analysis, to determine gender differences in benefit from a routine invasive strategy (Paper III).

    Results: Women were older than men and more likely to have a history of diabetes and hypertension, while men were more likely to have a history of myocardial infarction and revascularisation. Women were also more likely to have normal coronary arteries on the angiogram. After adjustment for baseline differences there were only minor, and directionally inconsistent, differences between women and men in pharmacological treatment. Men were more often referred for coronary angiography, even after adjustment. While CABG-rate was lower in women, after adjustment PCI-rate was similar or even higher compared to men. After adjustment for differences in age, longterm outcome was better in women. In our small but randomised trial there was no benefit from a routine invasive strategy in women. A meta-analysis indicated interaction between gender and treatment strategy, with lack of benefit in women, in contrast to in men. However, our large observational study indicated no gender difference with an invasive strategy. Moreover, benefit was similar in women and men with invasive treatment.

    Conclusion: There are substantial differences between women and men in baseline characteristics that affect management and outcome more than gender per se. After adjustment women have better long-term outcome than men. There appear to be a difference in benefit from a routine invasive strategy between the genders, with less benefit in women, but in routine clinical management there was no difference between women and men managed with an invasive strategy.

    List of papers
    1. Gender differences in management and outcome in non-ST-elevation acute coronary syndrome
    Open this publication in new window or tab >>Gender differences in management and outcome in non-ST-elevation acute coronary syndrome
    2007 (English)In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 93, no 11, p. 1357-1362Article in journal (Refereed) Published
    Abstract [en]

    Objective: To study gender differences in management and outcome in patients with non-ST-elevation acute coronary syndrome. Design, setting and patients: Cohort study of 53 781 consecutive patients (37% women) from the Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), with a diagnosis of either unstable angina pectoris or non-ST-elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 1998 and 2002, and followed for 1 year. Main outcome measures: Treatment intensity and in-hospital, 30-day and 1 -year mortality. Results: Women were older (73 vs 69 years, p<0.001) and more likely to have a history of hypertension and diabetes, but less likely to have a history of myocardial infarction or revascularisation. After adjustment, there were no major differences in acute pharmacological treatment or prophylactic medication at discharge. Revascularisation was, however, even after adjustment, performed more often in men (OR 1.15, 95% CI, 1.09 to 1.21). After adjustment, there was no significant difference in in-hospital (OR 1.03, 95% CI, 0.94 to 1.13) or 30-days (OR 1.07, 95% CI, 0.99 to 1.15) mortality, but at 1 year being male was associated with higher mortality (OR 1.12, 95% CI, 1.06 to 1.19). Conclusion: Although women are somewhat less intensively treated, especially regarding invasive procedures, after adjustment for differences in background characteristics, they have better long-term outcomes than men.

    Place, publisher, year, edition, pages
    BMJ Publishing group Ltd, 2007
    Keywords
    acute coronary syndrome, gender
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-47844 (URN)10.1136/hrt.2006.102012 (DOI)17085528 (PubMedID)
    Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2017-12-13
    2. Although women are less likely to be admitted to coronary care units, they are treated equally to men and have better outcome: A prospective cohort study in patients with non ST-elevation acute coronary syndromes
    Open this publication in new window or tab >>Although women are less likely to be admitted to coronary care units, they are treated equally to men and have better outcome: A prospective cohort study in patients with non ST-elevation acute coronary syndromes
    2009 (English)In: Acute cardiac care, ISSN 1748-295X, Vol. 11, no 3, p. 173-180Article in journal (Refereed) Published
    Abstract [en]

    Background: The aim of this study was to assess gender differences in admission level of care, management and outcome in patients with non ST-elevation acute coronary syndromes (NSTE-ACS), initially admitted to either coronary care units (CCU) or general wards. Method: Patients admitted to CCUs were routinely registered in the RIKS-HIA registry. In addition, patients admitted to general wards with suspected ACS were also identified and registered. Multivariable regression analysis was used to adjust for baseline differences between the genders. Results: We included 570 consecutive patients with a discharge diagnosis of NSTE-ACS. Women were less likely to be admitted to coronary care units (56% versus 69%, P=0.002), even after adjustment (odds ratio (OR), 0.65; 95% confidence interval (CI): 0.43-0.98). After adjustment for differences in baseline characteristics, women were treated similarly to men. We found no significant differences in crude short-, or long-term mortality between the genders. However, adjustment for background characteristics revealed lower one-year mortality in women (OR: 0.58; 95% CI: 0.34-0.99). Conclusion: In this study on patients with NSTE-ACS, women were less likely to be admitted to coronary care units. However, the overall treatment was as intensive for women as for men. Moreover, after adjustment, one-year mortality was lower in women.

    Place, publisher, year, edition, pages
    Informa Healthcare, 2009
    Keywords
    Myocardial infarction; NSTE-ACS; gender differences; level of care
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53576 (URN)10.1080/17482940903215190 (DOI)19742351 (PubMedID)
    Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2013-09-11
    3.
    The record could not be found. The reason may be that the record is no longer available or you may have typed in a wrong id in the address field.
    4. Similar outcome with an invasive strategy in men and women with Non ST-Elevation Acute Coronary Syndromes
    Open this publication in new window or tab >>Similar outcome with an invasive strategy in men and women with Non ST-Elevation Acute Coronary Syndromes
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Background: Gender differences in benefit from an early invasive strategy in patients with Non ST-elevation Acute Coronary Syndromes (NSTE ACS) have been debated and results are conflicting. Some studies have even indicated harm for women associated with a routine invasive strategy.

    Method: We included 46 455 patients ( 14 819 women (32%) and 31 636 men (68%)) from The Register of Information and Knowledge about Swedish Heart Intensive care Admissions (RIKS-HIA), with a diagnosis of either unstable angina pectoris or non-ST-elevation myocardial infarction. All patients were admitted to intensive coronary care units in Sweden, between 2000 and 2006, and followed for 1 year. Adjustment for baseline differences between the genders was made.

    Results: In the non-invasive strategy arm relative risk (RR) of death was (women vs. men) 1.02 (95% CI, 0.94-1.11) and in the invasive strategy arm 1.12 (95% CI, 0.96-1.29). After adjustment for baseline differences between the genders with propensity score and discharge medication there was a trend towards lower mortality among women, RR 0.90 (95% CI, 0.82-0.99) in the early non-invasive group but still no difference in the early invasive cohort RR 0.90 (95% CI, 0.76-1.06). Results were similar with the combined end-point death/MI. The risk reduction with an invasive strategy was similar in women (RR 0.46 (95% CI 0.38-0.55)) and men (RR 0.45 (95% CI 0.40-0.52).

    Conclusion: In this large cohort of patients with NSTE ACS, reflecting real life management, women and men had similar outcome and similar benefit with an early invasive strategy.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-53578 (URN)
    Available from: 2010-01-25 Created: 2010-01-25 Last updated: 2013-09-11
  • 194.
    Alfredsson, Joakim
    et al.
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Duke University, NC 27710 USA.
    Alexander, Karen P.
    Duke University, NC 27710 USA.
    Multiple Chronic Conditions in Older Adults with Acute Coronary Syndromes2016In: Clinics in Geriatric Medicine, ISSN 0749-0690, E-ISSN 1879-8853, Vol. 32, no 2, p. 291-+Article in journal (Refereed)
    Abstract [en]

    Older adults presenting with acute coronary syndromes (ACSs) often have multiple chronic conditions (MCCs). In addition to traditional cardiovascular (CV) risk factors (ie, hypertension, hyperlipidemia, and diabetes), common CV comorbidities include heart failure, stroke, and atrial fibrillation, whereas prevalent non-CV comorbidities include chronic kidney disease, anemia, depression, and chronic obstructive pulmonary disease. The presence of MCCs affects the presentation (eg, increased frequency of type 2 myocardial infarctions [MIs]), clinical course, and prognosis of ACS in older adults. In general, higher comorbidity burden increases mortality following MI, reduces utilization of ACS treatments, and increases the importance of developing individualized treatment plans.

  • 195.
    Alfredsson, Joakim
    et al.
    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.
    Clayton, Tim
    London School Hyg and Trop Med, England.
    Damman, Peter
    University of Amsterdam, Netherlands.
    Fox, Keith A. A.
    Royal Infirm, Scotland.
    Fredrikson, Mats
    Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
    Lagerqvist, Bo
    Department of Cardiology, Cardiothoracic Centre, University Hospital, Uppsala, Sweden.
    Wallentin, Lars
    Department of Cardiology, Cardiothoracic Centre, University Hospital, Uppsala, Sweden.
    de Winter, Robbert J.
    University of Amsterdam, Netherlands.
    Swahn, Eva
    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.
    Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes2014In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 168, no 4, p. 522-529Article in journal (Refereed)
    Abstract [en]

    Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.

  • 196.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Duke Univ, NC USA.
    Green, Jennifer B.
    Duke Univ, NC USA.
    Stevens, Susanna R.
    Duke Univ, NC USA.
    Reed, Shelby D.
    Duke Univ, NC USA.
    Armstrong, Paul W.
    Univ Alberta, Canada.
    Bethel, M. Angelyn
    Univ Oxford, England.
    Engel, Samuel S.
    Merck and Co Inc, NJ USA.
    McGuire, Darren K.
    Univ Texas Southwestern Med Ctr Dallas, TX 75390 USA.
    Van de Werf, Frans
    Univ Leuven, Belgium.
    Hramiak, Irene
    Univ Western Ontario, Canada.
    White, Harvey D.
    Auckland City Hosp, New Zealand.
    Peterson, Eric D.
    Duke Univ, NC USA.
    Holman, Rury R.
    Univ Oxford, England.
    Sex differences in management and outcomes of patients with type 2 diabetes and cardiovascular disease: A report from TECOS2018In: Diabetes, obesity and metabolism, ISSN 1462-8902, E-ISSN 1463-1326, Vol. 20, no 10, p. 2379-2388Article in journal (Refereed)
    Abstract [en]

    Aim: To examine sex differences in baseline characteristics and outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. Materials and methods: Cox models were used to analyse the association between sex and outcomes in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS), a randomized, placebo-controlled trial assessing the impact of sitagliptin on cardiovascular (CV) outcomes in patients with type 2 diabetes and atherosclerotic vascular disease. Results: A total of 4297 women and 10 374 men were followed for a median of 3.0 years. Women were slightly older and more often had cerebrovascular disease and peripheral arterial disease but less often coronary heart disease than men. At baseline, women were less likely to use aspirin or statins. The primary composite outcome of CV death, myocardial infarction, stroke, or hospitalization for unstable angina occurred in 418 women (9.7%) and 1272 men (12.3%; 3.48 vs 4.38 events/100 participant-years, crude hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.71-0.89, adjusted HR 0.64, 95% CI 0.55-0.74; P amp;lt; .0001). Women also had a significantly lower risk of secondary CV outcomes and all-cause death. Conclusions: In this large prospective study of people with type 2 diabetes and CV disease, women had different CV disease burden, worse CV risk factor profiles, and less use of indicated medications than men. Despite this, women had significantly lower risk of CV events, suggesting that the cardioprotective effects of female sex extend to populations with type 2 diabetes.

  • 197.
    Alfredsson, Joakim
    et al.
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Käll, Anna
    Tilander, Hanna
    Janzon, Magnus
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Swahn, Eva
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Jonasson, Lena
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology . Östergötlands Läns Landsting, Heart Centre, Department of Cardiology.
    Sex matters-lipid goal achievement in a population admitted to a coronary care unit2008In: X Svenska Kardiovaskulära Vårmötet,2008, 2008Conference paper (Refereed)
    Abstract [en]

     Number A13731

  • 198.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Lindahl, Tomas L
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Chemistry.
    Gustafsson, Kerstin M
    Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Janzon, Magnus
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Jonasson, Lena
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Logander, Elisabeth
    Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Nilsson, Lennart
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel: Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).2015In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 136, no 2, p. 335-340Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.

    METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.

    CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.

  • 199.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Lindbäck, Johan
    Uppsala University.
    Wallentin, Lars
    Uppsala University.
    Swahn, Eva
    Linköping University, Department of Medical and Health Sciences, Cardiology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Cardiology UHL.
    Similar outcome with an invasive strategy in men and women with non-ST-elevation acute coronary syndromes From the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART)2011In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 32, no 24, p. 3128-3136Article in journal (Refereed)
    Abstract [en]

    Aims To assess gender differences in outcome with an early invasive or non-invasive strategy in patients with non-ST-elevation acute coronary syndromes (NSTE ACS). less thanbrgreater than less thanbrgreater thanMethods and results We included 46 455 patients [14 819 women (32%) and 31 636 men (68%)] from the SWEDEHEART register, with NSTE ACS, between 2000 and 2006, and followed them for 1 year. In the non-invasive strategy arm, the relative risk (RR) of death was (women vs. men) 1.02 [95% confidence interval (CI), 0.94-1.11] and in the invasive strategy arm 1.12 (95% CI, 0.96-1.29). After adjustment for baseline differences between the genders, with propensity score and discharge medication, there was a similar trend towards better outcome among women in both the early non-invasive cohort [RR 0.90 (95% CI, 0.82-0.99)] and the early invasive cohort [RR 0.90 (95% CI, 0.76-1.06)], although it did not reach statistical significance in the early invasive cohort. Results were similar with the combined endpoint death/myocardial infarction. An early invasive treatment was associated with a marked, and similar, mortality reduction in women [RR 0.46 (95% CI, 0.38-0.55)] and men [RR 0.45 (95% CI, 0.40-0.52)], without interaction with gender. less thanbrgreater than less thanbrgreater thanConclusion In this large cohort of patients with NSTE ACS, reflecting real-life management, women and men had similar and better outcome associated with an invasive strategy.

  • 200.
    Alfredsson, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping. Duke Clin Research Institute, NC USA.
    Neely, Benjamin
    Duke Clin Research Institute, NC USA.
    Neely, Megan L.
    Duke Clin Research Institute, NC USA.
    Bhatt, Deepak L.
    Brigham and Womens Hospital, MA 02115 USA; Harvard Medical Sch, MA USA.
    Goodman, Shaun G.
    St Michaels Hospital, Canada; University of Alberta, Canada; University of Alberta, Canada.
    Tricoci, Pierluigi
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Mahaffey, Kenneth W.
    Stanford University, CA 94305 USA.
    Cornel, Jan H.
    Medical Centre Alkmaar, Netherlands.
    White, Harvey D.
    Auckland City Hospital, New Zealand.
    Fox, Keith A. A.
    University of Edinburgh, Scotland.
    Prabhakaran, Dorairaj
    Centre Chron Disease Control and Public Health Fdn India, India.
    Winters, Kenneth J.
    Eli Lilly and Co, IN 46285 USA.
    Armstrong, Paul W.
    University of Alberta, Canada; University of Alberta, Canada.
    Magnus Ohman, E.
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Roe, Matthew T.
    Duke Clin Research Institute, NC USA; Duke University, NC 27706 USA.
    Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 15, p. 1168-1176Article in journal (Refereed)
    Abstract [en]

    Objectives Dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome (ACS), with shorter durations considered for patients with increased bleeding risk. However, there are no decision support tools available to predict an individual patients bleeding risk during DAPT treatment in the post-ACS setting. Methods To develop a longitudinal bleeding risk prediction model, we analysed 9240 patients with unstable angina/non-ST segment elevation myocardial infarction (NSTEMI) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, who were managed without revascularisation and treated with DAPT for a median of 14.8 months. Results We identified 10 significant baseline predictors of non-coronary artery bypass grafting (CABG)-related Global Use of Strategies to Open Occluded Arteries (GUSTO) severe/life-threatening/moderate bleeding: age, sex, weight, NSTEMI (vs unstable angina), angiography performed before randomisation, prior peptic ulcer disease, creatinine, systolic blood pressure, haemoglobin and treatment with beta-blocker. The five significant baseline predictors of Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding included age, sex, angiography performed before randomisation, creatinine and haemoglobin. The models showed good predictive accuracy with Therneaus C-indices: 0.78 (SE=0.024) for the GUSTO model and 0.67 (SE=0.023) for the TIMI model. Internal validation with bootstrapping gave similar C-indices of 0.77 and 0.65, respectively. External validation demonstrated an attenuated C-index for the GUSTO model (0.69) but not the TIMI model (0.68). Conclusions Longitudinal bleeding risks during treatment with DAPT in patients with ACS can be reliably predicted using selected baseline characteristics. The TRILOGY ACS bleeding models can inform riskbenefit considerations regarding the duration of DAPT following ACS.

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