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  • 251. Feigin, Valery L.
    et al.
    Parmar, Priya G.
    Barker-Collo, Suzanne
    Bennett, Derrick A.
    Anderson, Craig S.
    Thrift, Amanda G.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Rothwell, Peter M.
    Giroud, Maurice
    Bejot, Yannick
    Carvil, Phillip
    Krishnamurthi, Rita
    Kasabov, Nikola
    Geomagnetic Storms Can Trigger Stroke Evidence From 6 Large Population-Based Studies in Europe and Australasia2014Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 45, nr 6, s. 1639-1645Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose-Although the research linking cardiovascular disorders to geomagnetic activity is accumulating, robust evidence for the impact of geomagnetic activity on stroke occurrence is limited and controversial. Methods-We used a time-stratified case-crossover study design to analyze individual participant and daily geomagnetic activity (as measured by Ap Index) data from several large population-based stroke incidence studies (with information on 11 453 patients with stroke collected during 16 031 764 person-years of observation) in New Zealand, Australia, United Kingdom, France, and Sweden conducted between 1981 and 2004. Hazard ratios and corresponding 95% confidence intervals (CIs) were calculated. Results-Overall, geomagnetic storms (Ap Index 60+) were associated with 19% increase in the risk of stroke occurrence (95% CI, 11%-27%). The triggering effect of geomagnetic storms was most evident across the combined group of all strokes in those aged <65 years, increasing stroke risk by >50%: moderate geomagnetic storms (60-99 Ap Index) were associated with a 27% (95% CI, 8%-48%) increased risk of stroke occurrence, strong geomagnetic storms (100-149 Ap Index) with a 52% (95% CI, 19%-92%) increased risk, and severe/extreme geomagnetic storms (Ap Index 150+) with a 52% (95% CI, 19%-94%) increased risk (test for trend, P<2x10(-16)). Conclusions-Geomagnetic storms are associated with increased risk of stroke and should be considered along with other established risk factors. Our findings provide a framework to advance stroke prevention through future investigation of the contribution of geomagnetic factors to the risk of stroke occurrence and pathogenesis.

  • 252. Feitosa, Mary F.
    et al.
    Kraja, Aldi T.
    Chasman, Daniel I.
    Sung, Yun J.
    Winkler, Thomas W.
    Ntalla, Ioanna
    Guo, Xiuqing
    Franceschini, Nora
    Cheng, Ching-Yu
    Sim, Xueling
    Vojinovic, Dina
    Marten, Jonathan
    Musani, Solomon K.
    Li, Changwei
    Bentley, Amy R.
    Brown, Michael R.
    Schwander, Karen
    Richard, Melissa A.
    Noordam, Raymond
    Aschard, Hugues
    Bartz, Traci M.
    Bielak, Lawrence F.
    Dorajoo, Rajkumar
    Fisher, Virginia
    Hartwig, Fernando P.
    Horimoto, Andrea R. V. R.
    Lohman, Kurt K.
    Manning, Alisa K.
    Rankinen, Tuomo
    Smith, Albert V.
    Tajuddin, Salman M.
    Wojczynski, Mary K.
    Alver, Maris
    Boissel, Mathilde
    Cai, Qiuyin
    Campbell, Archie
    Chai, Jin Fang
    Chen, Xu
    Divers, Jasmin
    Gao, Chuan
    Goel, Anuj
    Hagemeijer, Yanick
    Harris, Sarah E.
    He, Meian
    Hsu, Fang-Chi
    Jackson, Anne U.
    Kahonen, Mika
    Kasturiratne, Anuradhani
    Komulainen, Pirjo
    Kuhnel, Brigitte
    Laguzzi, Federica
    Luan, Jian'an
    Matoba, Nana
    Nolte, Ilja M.
    Padmanabhan, Sandosh
    Riaz, Muhammad
    Rueedi, Rico
    Robino, Antonietta
    Said, M. Abdullah
    Scott, Robert A.
    Sofer, Tamar
    Stancakova, Alena
    Takeuchi, Fumihiko
    Tayo, Bamidele O.
    van der Most, Peter J.
    Varga, Tibor V.
    Vitart, Veronique
    Wang, Yajuan
    Ware, Erin B.
    Warren, Helen R.
    Weiss, Stefan
    Wen, Wanqing
    Yanek, Lisa R.
    Zhang, Weihua
    Zhao, Jing Hua
    Afaq, Saima
    Amin, Najaf
    Amini, Marzyeh
    Arking, Dan E.
    Aung, Tin
    Boerwinkle, Eric
    Borecki, Ingrid
    Broeckel, Ulrich
    Brown, Morris
    Brumat, Marco
    Burke, Gregory L.
    Canouil, Mickael
    Chakravarti, Aravinda
    Charumathi, Sabanayagam
    Chen, Yii-Der Ida
    Connell, John M.
    Correa, Adolfo
    Fuentes, Lisa de las
    de Mutsert, Renee
    de Silva, H. Janaka
    Deng, Xuan
    Ding, Jingzhong
    Duan, Qing
    Eaton, Charles B.
    Ehret, Georg
    Eppinga, Ruben N.
    Evangelou, Evangelos
    Fau, Jessica D.
    Felix, Stephan B.
    Forouhi, Nita G.
    Forrester, Terrence
    Franco, Oscar H.
    Friedlander, Yechiel
    Gandin, Ilaria
    Gao, He
    Ghanbari, Mohsen
    Gigante, Bruna
    Gu, C. Charles
    Gu, Dongfeng
    Hagenaars, Saskia P.
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Harris, Tamara B.
    He, Jiang
    Heikkinen, Sami
    Heng, Chew-Kiat
    Hirata, Makoto
    Howard, Barbara V.
    Ikram, M. Arfan
    John, Ulrich
    Katsuya, Tomohiro
    Khor, Chiea Chuen
    Kilpelainen, Tuomas O.
    Koh, Woon-Puay
    Krieger, Jose E.
    Kritchevsky, Stephen B.
    Kubo, Michiaki
    Kuusisto, Johanna
    Lakka, Timo A.
    Langefeld, Carl D.
    Langenberg, Claudia
    Launer, Lenore J.
    Lehne, Benjamin
    Lewis, Cora E.
    Li, Yize
    Lin, Shiow
    Liu, Jianjun
    Liu, Jingmin
    Loh, Marie
    Louie, Tin
    Magi, Reedik
    McKenzie, Colin A.
    Meitinger, Thomas
    Metspalu, Andres
    Milaneschi, Yuri
    Milani, Lili
    Mohlke, Karen L.
    Momozawa, Yukihide
    Nalls, Mike A.
    Nelson, Christopher P.
    Sotoodehnia, NelsonNona
    Norris, Jill M.
    O'Connell, Jeff R.
    Palmer, Nicholette D.
    Perls, Thomas
    Pedersen, Nancy L.
    Peters, Annette
    Peyser, Patricia A.
    Poulter, Neil
    Raffel, Leslie J.
    Raitakari, Olli T.
    Roll, Kathryn
    Rose, Lynda M.
    Rosendaal, Frits R.
    Rotter, Jerome I.
    Schmidt, Carsten O.
    Schreiner, Pamela J.
    Schupf, Nicole
    Scott, William R.
    Sever, Peter S.
    Shi, Yuan
    Sidney, Stephen
    Sims, Mario
    Sitlani, Colleen M.
    Smith, Jennifer A.
    Snieder, Harold
    Starr, John M.
    Strauch, Konstantin
    Stringham, Heather M.
    Tan, Nicholas Y. Q.
    Tang, Hua
    Taylor, Kent D.
    Teo, Yik Ying
    Tham, Yih Chung
    Turner, Stephen T.
    Uitterlinden, Andre G.
    Vollenweider, Peter
    Waldenberger, Melanie
    Wang, Lihua
    Wang, Ya Xing
    Bin Wei, Wen
    Williams, Christine
    Yao, Jie
    Yu, Caizheng
    Yuan, Jian-Min
    Zhao, Wei
    Zonderman, Alan B.
    Becker, Diane M.
    Boehnke, Michael
    Bowden, Donald W.
    Chambers, John C.
    Deary, Ian J.
    Esko, Tonu
    Farrall, Martin
    Franks, Paul W.
    Freedman, Barry I.
    Froguel, Philippe
    Gasparini, Paolo
    Gieger, Christian
    Jonas, Jost Bruno
    Kamatani, Yoichiro
    Kato, Norihiro
    Kooner, Jaspal S.
    Kutalik, Zoltan
    Laakso, Markku
    Laurie, Cathy C.
    Leander, Karin
    Lehtimaki, Terho
    Study, Lifelines Cohort
    Magnusson, Patrik K. E.
    Oldehinkel, Albertine J.
    Penninx, Brenda W. J. H.
    Poiasek, Ozren
    Porteous, David J.
    Rauramaa, Rainer
    Samani, Nilesh J.
    Scott, James
    Shu, Xiao-Ou
    van der Harst, Pim
    Wagenknecht, Lynne E.
    Wareham, Nicholas J.
    Watkins, Hugh
    Weir, David R.
    Wickremasinghe, Ananda R.
    Wu, Tangchun
    Zheng, Wei
    Bouchard, Claude
    Christensen, Kaare
    Evans, Michele K.
    Gudnason, Vilmundur
    Horta, Bernardo L.
    Kardia, Sharon L. R.
    Liu, Yongmei
    Pereira, Alexandre C.
    Psaty, Bruce M.
    Ridker, Paul M.
    van Dam, Rob M.
    Gauderman, W. James
    Zhu, Xiaofeng
    Mook-Kanamori, Dennis O.
    Fornage, Myriam
    Rotimi, Charles N.
    Cupples, L. Adrienne
    Kelly, Tanika N.
    Fox, Ervin R.
    Hayward, Caroline
    van Duijn, Cornelia M.
    Tai, E. Shyong
    Wong, Tien Yin
    Kooperberg, Charles
    Palmas, Walter
    Rice, Kenneth
    Morrison, Alanna C.
    Elliott, Paul
    Caulfield, Mark J.
    Munroe, Patricia B.
    Rao, Dabeeru C.
    Province, Michael A.
    Levy, Daniel
    Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries2018Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, nr 6, artikel-id e0198166Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.

  • 253. Ferrario, Marco M
    et al.
    Veronesi, Giovanni
    Chambless, Lloyd E
    Tunstall-Pedoe, Hugh
    Kuulasmaa, Kari
    Salomaa, Veikko
    Borglykke, Anders
    Hart, Nigel
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Cesana, Giancarlo
    The contribution of educational class in improving accuracy of cardiovascular risk prediction across European regions: the MORGAM Project Cohort Component2014Ingår i: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 100, nr 15, s. 1179-1187Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective To assess whether educational class, an index of socioeconomic position, improves the accuracy of the SCORE cardiovascular disease (CVD) risk prediction equation.

    Methods In a pooled analysis of 68 455 40-64-year-old men and women, free from coronary heart disease at baseline, from 47 prospective population-based cohorts from Nordic countries (Finland, Denmark, Sweden), the UK (Northern Ireland, Scotland), Central Europe (France, Germany, Italy) and Eastern Europe (Lithuania, Poland) and Russia, we assessed improvements in discrimination and in risk classification (net reclassification improvement (NRI)) when education was added to models including the SCORE risk equation.

    Results The lowest educational class was associated with higher CVD mortality in men (pooled age-adjusted HR=1.64, 95% CI 1.42 to 1.90) and women (HR=1.31, 1.02 to 1.68). In men, the HRs ranged from 1.3 (Central Europe) to 2.1 (Eastern Europe and Russia). After adjustment for the SCORE risk, the association remained statistically significant overall, in the UK and Eastern Europe and Russia. Education significantly improved discrimination in all European regions and classification in Nordic countries (clinical NRI=5.3%) and in Eastern Europe and Russia (NRI=24.7%). In women, after SCORE risk adjustment, the association was not statistically significant, but the reduced number of deaths plays a major role, and the addition of education led to improvements in discrimination and classification in the Nordic countries only.

    Conclusions We recommend the inclusion of education in SCORE CVD risk equation in men, particularly in Nordic and East European countries, to improve social equity in primary prevention. Weaker evidence for women warrants the need for further investigations.

  • 254.
    Flank, Peter
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Ramnemark, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Levi, Richard
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Rehabiliteringsmedicin.
    Wahman, Kerstin
    Fahlström, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Professionell utveckling.
    Dyslipidemia is common after spinal cord injury - independent of clinical measures2015Ingår i: Jacobs Journal of Physical Rehabilitation Medicine, ISSN 2469-3103, Vol. 1, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: To survey the incidence of clinical risk markers and its correlation with established clinical measurements for cardiovascular disease (CVD) in a heterogeneous spinal cord injured (SCI) patient population.

    Design: Descriptive, cross-sectional study.

    Subjects: 78 patients with SCI, at different injury and functional level.

    Methods: Anthropometric data, blood pressure, a blood lipid panel, blood glucose and a questionnaire were analyzed.

    Results: Eighty-one percent of all patients had dyslipidemia (DL) and a majority of the patients with abdominal measures below the recommended cut-off levels had DL. Self-reported physical activity above the cut-off level was reported by 32.1%of the patients. There were no differences in clinical measures, serum lipid values and blood glucose between physically active and not active patients. No differences were seen between men/women, tetraplegia/paraplegia and wheelchair dependent/not wheelchair dependent patients.

    Conclusion: DL is common and seems to be not treated or undertreated in the studied SCI patient group with different neurological lesion and functional levels. General anthropometric clinical measures do not seem to be valid for evaluating risk for CVD in this patient group.

  • 255. Fokkema, Marieke L.
    et al.
    James, Stefan K.
    Albertsson, Per
    Åkerblom, Axel
    Calais, Fredrik
    Eriksson, Peter
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Jensen, Jens
    Nilsson, Tage
    de Smet, Bart J.
    Sjogren, Iwar
    Thorvinger, Bjorn
    Lagerqvist, Bo
    Population Trends in Percutaneous Coronary Intervention 20-Year Results From the SCAAR (Swedish Coronary Angiography and Angioplasty Registry)2013Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 61, nr 12, s. 1222-1230Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives The aim of this study was to describe the characteristics and outcome of all consecutive patients treated with percutaneous coronary intervention (PCI) in an unselected nationwide cohort over the past 2 decades. Background Over the last 20 years, treatment with PCI has evolved dramatically, but the change in patient characteristics has not been well described. Methods We included all patients undergoing a PCI procedure for the first time between January 1990 and December 2010 from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Patients were divided into different cohorts on the basis of the year of the first PCI procedure. Results A total of 144,039 patients was included. The mean age increased from 60.1 +/- 9.9 years in 1990 to 1995 to 67.1 +/- 11.2 years in 2009 to 2010. The proportion of patients presenting with unstable coronary artery disease and ST-segment elevation myocardial infarction increased from 27.4% and 6.2% to 47.7% and 32.5%, respectively. Diabetes mellitus and multivessel disease were more often present in the later-year cohorts. The 1-year mortality increased from 2.2% in 1990 to 1995 to 5.9% in 2009 to 2010, but after adjustment for age and indication, a modest decrease was shown, mainly in ST-segment elevation myocardial infarction patients. Conclusions Characteristics of PCI patients have changed substantially over time, reflecting the establishment of new evidence. The increasing age and proportion of patients undergoing PCI for acute coronary syndromes greatly influence outcome. Understanding the changing patient characteristics is important for the translation of evidence to real-world clinical practice. 

  • 256.
    Forslund, Ann-Sofie
    et al.
    Department of Research, Norrbotten County Council, Luleå ; Department of Health Science, Division of Nursing, Luleå University of Technology.
    Lundblad, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Medicine, Sunderby Hospital, Luleå.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Medicine, Skellefteå Hospital.
    Zingmark, Karin
    Department of Research, Norrbotten County Council, Luleå ; Department of Health Science, Division of Nursing, Luleå University of Technology.
    Söderberg, Siv
    Department of Health Science, Division of Nursing, Luleå University of Technology.
    Risk factors among people surviving out-of-hospital cardiac arrest and their thoughts about what lifestyle means to them: a mixed methods study2013Ingår i: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 13, s. 62-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The known risk factors for coronary heart disease among people prior suffering an out-of-hospital cardiac arrest with validated myocardial infarction aetiology and their thoughts about what lifestyle means to them after surviving have rarely been described. Therefore the aim of the study was to describe risk factors and lifestyle among survivors. Methods: An explanatory mixed methods design was used. All people registered in the Northern Sweden MONICA myocardial registry between the year 1989 to 2007 who survived out-of-hospital cardiac arrest with validated myocardial infarction aetiology and were alive at the 28th day after the onset of symptoms (n = 71) were included in the quantitative analysis. Thirteen of them participated in interviews conducted in 2011 and analysed via a qualitative manifest content analysis. Results: About 60% of the people had no history of ischemic heart disease before the out-of-hospital cardiac arrest, but 20% had three cardiovascular risk factors (i.e., hypertension, diabetes mellitus, total cholesterol of more or equal 5 mmol/l or taking lipid lowering medication, and current smoker). Three categories (i.e., significance of lifestyle, modifying the lifestyle to the new life situation and a changed view on life) and seven sub-categories emerged from the qualitative analysis. Conclusions: For many people out-of-hospital cardiac arrest was the first symptom of coronary heart disease. Interview participants were well informed about their cardiovascular risk factors and the benefits of risk factor treatment. In spite of that, some chose to ignore this knowledge to some extent and preferred to live a "good life", where risk factor treatment played a minor part. The importance of the support of family members in terms of feeling happy and having fun was highlighted by the interview participants and expressed as being the meaning of lifestyle. Perhaps the person with illness together with health care workers should focus more on the meaningful and joyful things in life and try to adopt healthy behaviours linked to these things.

  • 257.
    Forslund, Ann-Sofie
    et al.
    The Northern Sweden MONICA Myocardial Registry, Department of Research, Norrbotten County Council, Luleå, Sweden; Division of Nursing, Department of Health Science, Luleå University of Technology, Luleå, Sweden.
    Söderberg, Siv
    Division of Nursing, Department of Health Science, Luleå University of Technology, Luleå, Sweden.
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Medicine, Skellefteå Hospital, Skellefteå, Sweden.
    Lundblad, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Medicine, Sunderby Hospital, Luleå, Sweden.
    Trends in incidence and outcome of out-of-hospital cardiac arrest among people with validated myocardial infarction2013Ingår i: European Journal of Cardiovascular Prevention & Rehabilitation, ISSN 1741-8267, E-ISSN 1741-8275, Vol. 20, nr 2, s. 260-267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: To describe trends in incidence, outcome, and background characteristics among people who suffered an out-of-hospital cardiac arrest with validated myocardial infarction aetiology (OHCA-V).

    Methods and results: People from the northern Sweden MONICA myocardial registry (1989-2007) with OHCA-V (n = 2977) were divided in two age groups (25-64 and 65-74 years). Both those who were resuscitated outside hospital and those who died before resuscitation was started were included in the study. The younger age group was studied during 1989-2007 and the older group during 2000-2007. The incidence of OHCA-V decreased in both the younger group (men p < 0.0001, women p = 0.04) and the older group (men p < 0.0001, women p < 0.0007, respectively). The proportion with a history of ischaemic heart disease prior to the event decreased (p < 0.0001). The proportion of previous myocardial infarction decreased (p < 0.0001), diabetes mellitus increased (p = 0.001), coronary interventions increased (p < 0.0001), and survival after OHCA-V increased (p < 0.0001) in the younger group but not in the older group. Long-term survival after OHCA-V was better in the younger than in the older group (p = 0.026).

    Conclusion: The incidence of OHCA-V decreased in both sexes. The proportion surviving after OHCA-V was small but increased, and long-term survival (≥28 days) was better in the younger age group. Primary preventive measures may explain most of the improvements. However, the effects of secondary preventive measures cannot be excluded.

  • 258. Forslund, Ann-Sofie
    et al.
    Zingmark, Karin
    Jansson, Jan-Håkan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundblad, Dan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Söderberg, Siv
    Meanings of people's lived experiences of surviving an out-of-hospital cardiac arrest, 1 month after the event2014Ingår i: Journal of Cardiovascular Nursing, ISSN 0889-4655, E-ISSN 1550-5049, Vol. 29, nr 5, s. 464-471Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The out-of-hospital cardiac arrest (OHCA) survival rate has been poor and stable for a long time, but more recent studies describe its increase. However, there are few studies in which people narrate their experiences from surviving. Objective: The aim of this study was to elucidate meanings of people's lived experiences of surviving an OHCA with validated myocardial infarction (MI) etiology, 1 month after the event. Methods: A purposive sample of 2 women and 9 men was interviewed between February 2011 and May 2012. A phenomenological hermeneutical method was used for analysis, which involved 3 steps: naive reading and understanding, structural analysis, and comprehensive understanding. Results: There were 2 themes, (1) returning to life and (2) revaluing life, and five subthemes, (1a) waking up and missing the whole picture, (1b) realizing it was not time to die, (2a) wondering why and seeking explanations, (2b) feeling ambiguous in relations, and (2c) wondering whether life will be the same. All were constructed from the analysis. Conclusions: Surviving an OHCA with validated MI etiology meant waking up and realizing that one had experienced a cardiac arrest and had been resuscitated. These survivors had memory loss and a need to know what had happened during the time they were dead/unconscious. They searched for a reason why they experienced an MI and cardiac arrest and had gone from being "heart-healthy'' to having a lifelong illness. They all had the experience of passing from life to death and back to life again. For the participants, these differences led to a revaluation of what is important in life.

  • 259. Fransson, Eleonor I.
    et al.
    Nordin, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi.
    Magnusson Hanson, Linda L.
    Westerlund, Hugo
    Job strain and atrial fibrillation: results from the Swedish Longitudinal Occupational Survey of Health and meta-analysis of three studies2018Ingår i: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 25, nr 11, s. 1142-1149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Knowledge about the impact of occupational exposures, such as work stress, on the risk of atrial fibrillation is limited. The present study aims to investigate the association between job strain, a measure of work stress, and atrial fibrillation.

    Design: Prospective cohort study design and fixed-effect meta-analysis.

    Methods: Data from the Swedish Longitudinal Occupational Survey of Health (SLOSH) was utilised for the main analysis, combining self-reported data on work stress at baseline with follow-up data on atrial fibrillation from nationwide registers. Cox proportional hazard regression analyses were used to estimate hazard ratios and 95% confidence intervals (CIs). A fixed-effect meta-analysis was conducted to pool the results from the present study with results from two similar previously published studies.

    Results: Based on SLOSH data, job strain was associated with an almost 50% increased risk of atrial fibrillation (hazard ratio 1.48, 95% CI 1.00-2.18) after adjustment for age, sex and education. Further adjustment for smoking, physical activity, body mass index and hypertension did not alter the estimated risk. The meta-analysis of the present and two previously published studies showed a consistent pattern, with job strain being associated with increased risk of atrial fibrillation in all three studies. The estimated pooled hazard ratio was 1.37 (95% CI 1.13-1.67).

    Conclusion: The results highlight that occupational exposures, such as work stress, may be important risk factors for incident atrial fibrillation.

  • 260. Fransson, Eleonor I
    et al.
    Stadin, Magdalena
    Nordin, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Institutionen för psykologi. Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Malm, Dan
    Knutsson, Anders
    Alfredsson, Lars
    Westerholm, Peter J M
    The Association between Job Strain and Atrial Fibrillation: Results from the Swedish WOLF Study2015Ingår i: BioMed Research International, ISSN 2314-6133, E-ISSN 2314-6141, artikel-id 371905Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Atrial fibrillation (AF) is a common heart rhythmdisorder. Several life-style factors have been identified as risk factors for AF, but less is known about the impact of work-related stress. This study aims to evaluate the association between work-related stress, defined as job strain, and risk of AF. Methods: Data from the Swedish WOLF study was used, comprising 10,121 working men and women. Job strain was measured by the demand-control model. Information on incident AF was derived from national registers. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between job strain and AF risk. Results: In total, 253 incident AF cases were identified during a total follow-up time of 132,387 person-years. Job strain was associated with AF risk in a time-dependent manner, with stronger association after 10.7 years of follow-up (HR 1.93, 95% CI 1.10-3.36 after 10.7 years, versus HR 1.11, 95% CI 0.67-1.83 before 10.7 years). The results pointed towards a dose-response relationship when taking accumulated exposure to job strain over time into account. Conclusion: This study provides support to the hypothesis that work-related stress defined as job strain is linked to an increased risk of AF.

  • 261. Friberg, Leif
    et al.
    Rosenqvist, Marten
    Lindgren, Arne
    Terent, Andreas
    Norrving, Bo
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    High prevalence of atrial fibrillation among patients with ischemic stroke2014Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 45, nr 9, s. 2599-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose-Atrial fibrillation (AF) is a common cause of devastating but potentially preventable stroke. Estimates of the prevalence of AF among patients with stroke vary considerably because of difficulties in detection of intermittent, silent AF. Better recognition of AF in this patient group may help to identify and offer protection to individuals at risk. Our aim was to determine the nationwide prevalence of AF among patients with ischemic stroke, as well as their use of oral anticoagulation. Methods-Cross-sectional study of unselected patients in cross-linked nationwide Swedish health registers. All 94 083 patients with a diagnosis of ischemic stroke in the nationwide stroke register Riks-Stroke between 2005 and 2010 were studied. Information about previously diagnosed AF, and comorbidity, was obtained from the nationwide Patient Register and cross-referenced with the national Drug Register containing data on all dispensed pharmacological prescriptions in Sweden. Results-Combination of data from Riks-Stroke and from the Patient Register showed that 31 428 (33.4%) patients with ischemic stroke had previously known, or newly diagnosed, AF. Of those, only 16.2% had received warfarin in a pharmacy within 6 months before stroke onset. After hospital discharge, only 35.0% of the survivors received warfarin within the first 3 months after discharge. The likelihood for underlying AF was strongly correlated to the CHA(2)DS(2)-VASC score, which is a point based scheme for assessment of stroke risk in AF but which also predicts likelihood of AF. In this scheme points are given for age, previous stroke or transient ischemic attack, hypertension, heart failure, diabetes, vascular disease and female sex. Conclusions-Access to nationwide register data shows that AF is more common among patients with ischemic stroke than those previously reported. Few patients with stroke and AF had anticoagulant treatment before the event, and few got it after the event. CHA(2)DS(2)-VASc could be a useful monitoring tool to intensify efforts to diagnose AF among patients with cryptogenic stroke.

  • 262. Frobert, Ole
    et al.
    Lagerqvist, Bo
    Olivecrona, Goran K.
    Omerovic, Elmir
    Gudnason, Thorarinn
    Maeng, Michael
    Aasa, Mikael
    Angeras, Oskar
    Calais, Fredrik
    Danielewicz, Mikael
    Erlinge, David
    Hellsten, Lars
    Jensen, Ulf
    Johansson, Agneta C.
    Karegren, Amra
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Heart Centrum.
    Robertson, Lotta
    Sandhall, Lennart
    Sjogren, Iwar
    Ostlund, Ollie
    Harnek, Jan
    James, Stefan K.
    Thrombus Aspiration during ST-Segment Elevation Myocardial Infarction2013Ingår i: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 369, nr 17, s. 1587-1597Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BackgroundThe clinical effect of routine intracoronary thrombus aspiration before primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) is uncertain. We aimed to evaluate whether thrombus aspiration reduces mortality. MethodsWe conducted a multicenter, prospective, randomized, controlled, open-label clinical trial, with enrollment of patients from the national comprehensive Swedish Coronary Angiography and Angioplasty Registry (SCAAR) and end points evaluated through national registries. A total of 7244 patients with STEMI undergoing PCI were randomly assigned to manual thrombus aspiration followed by PCI or to PCI only. The primary end point was all-cause mortality at 30 days. ResultsNo patients were lost to follow-up. Death from any cause occurred in 2.8% of the patients in the thrombus-aspiration group (103 of 3621), as compared with 3.0% in the PCI-only group (110 of 3623) (hazard ratio, 0.94; 95% confidence interval [CI], 0.72 to 1.22; P=0.63). The rates of hospitalization for recurrent myocardial infarction at 30 days were 0.5% and 0.9% in the two groups, respectively (hazard ratio, 0.61; 95% CI, 0.34 to 1.07; P=0.09), and the rates of stent thrombosis were 0.2% and 0.5%, respectively (hazard ratio, 0.47; 95% CI, 0.20 to 1.02; P=0.06). There were no significant differences between the groups with respect to the rate of stroke or neurologic complications at the time of discharge (P=0.87). The results were consistent across all major prespecified subgroups, including subgroups defined according to thrombus burden and coronary flow before PCI. ConclusionsRoutine thrombus aspiration before PCI as compared with PCI alone did not reduce 30-day mortality among patients with STEMI. (Funded by the Swedish Research Council and others; ClinicalTrials.gov number, NCT01093404.)

  • 263. Fröbert, Ole
    et al.
    Götberg, Matthias
    Angerås, Oskar
    Jonasson, Lena
    Erlinge, David
    Engstrøm, Thomas
    Persson, Jonas
    Jensen, Svend E.
    Omerovic, Elmir
    James, Stefan K.
    Lagerqvist, Bo
    Nilsson, Johan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Kåregren, Amra
    Moer, Rasmus
    Yang, Cao
    Agus, David B.
    Erglis, Andrejs
    Jensen, Lisette O.
    Jakobsen, Lars
    Christiansen, Evald H.
    Pernow, John
    Design and rationale for the Influenza vaccination After Myocardial Infarction (IAMI) trial: a registry-based randomized clinical trial2017Ingår i: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 189, s. 94-102Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background Registry studies and case-control studies have demonstrated that the risk of acute myocardial infarction (AMI) is increased following influenza infection. Small randomized trials, underpowered for clinical end points, indicate that future cardiovascular events can be reduced following influenza vaccination in patients with established cardiovascular disease. Influenza vaccination is recommended by international guidelines for patients with cardiovascular disease, but uptake is varying and vaccination is rarely prioritized during hospitalization for AMI. Methods/design The Influenza vaccination After Myocardial Infarction (IAMI) trial is a double-blind, multicenter, prospective, registry-based, randomized, placebo-controlled, clinical trial. A total of 4,400 patients with ST-segment elevation myocardial infarction (STEMI) or non-STEMI undergoing coronary angiography will randomly be assigned either to in-hospital influenza vaccination or to placebo. Baseline information is collected from national heart disease registries, and follow-up will be performed using both registries and a structured telephone interview. The primary end point is a composite of time to all cause death, a new AMI, or stent thrombosis at 1 year. Implications The IAMI trial is the largest randomized trial to date to evaluate the effect of in-hospital influenza vaccination on death and cardiovascular outcomes in patients with STEMI or non-STEMI. The trial is expected to provide highly relevant clinical data on the efficacy of influenza vaccine as secondary prevention after AMI.

  • 264.
    Funegård, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Fractionated irradiation of salivary glands: loss and protection of function1995Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Radiotherapy of malignancies in the head and neck often involves the major and minor salivary glands in the radiation field. Adverse effects, such as dry mouth symptoms, are common after such therapy. The aim of this thesis was to study longitudinal effects of fractionated irradiation to the head and neck on salivary gland function in man and in the rat and to test radioprotection from antioxidant vitamins (retinol, a-tocopherol and ^-carotene).

    A sharp decrease in parotid saliva flow rate was seen after one week of irradiation in cancer patients, but in some patients recovery was seen two months after completed treatment. Loss and recovery of salivary gland function were dependent on the total dose given. Irradiation with doses of >65 Gy to the parotid glands led to permanent loss of function in the majority of parotid glands, while recovery could be seen after irradiation with doses of <52 Gy. Concentrations of some proteins and electrolytes in saliva were increased during irradiation but no changes remained 18 months after radiotherapy. However, large inter-individual differences were seen.

    The irradiation effects observed in rats did not greatly differ from those seen in humans, but no recovery of salivary gland function was seen. On the one hand the impairments of saliva flow and composition w ere dose and time dependent, but on the other hand the response pattem differed between salivary components. Morphological alterations were not seen in the rat salivary' glands after tw'O or five weeks but 26 weeks after irradiation. No single model seems to be optimal for studying all parameters. Therefore, to study effects on salivary glands after irradiation the rat model must be adjusted to meet the questions addressed. Supplementation with vitamin A provided no radioprotection, whereas it w'as found that supplementation with a-tocopherol (3.4 mg/day) and ß-carotene (6 mg/day) during irradiation reduced the degree of inflammation and partly preserved salivary gland function. It did not, however, lead to morphometrically detectable differences in proportions of acinar or ductal cells or stroma.Keywords: Irradiation, salivary glands, saliva composition, antioxidants

  • 265.
    Gennebäck, Nina
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Cardiac hypertrophy: transcription patterns, hypertrophicprogression and extracellular signalling2012Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Bakgrund: Syftet med den här avhandlingen var att studera transkriptions-mönster och extracellulär signalering vid hjärthypertrofi för att bättre förstå de mekanismer som startar, styr och underhåller tillväxten. Hjärthypertrofi, onormal tillväxt av hjärtmuskeln, är en riskfaktor för andra hjärt-kärlsjukdomar och dödlighet. Hypertrofi av hjärtmuskeln är ett tillstånd, oberoende av bakomliggande sjukdom, där hjärtmuskeln strävar efter att kompensera för ökad arbetsbelastning. Denna omställning av hjärtat innefattar fysiologiska förändringar orsakade av ett förändrat genuttryck, modifiering av miljön utanför cellen och ändrad cell-till-cell signalering.

    Mikrovesiklar och exosomer är små membranomslutna bubblor som frisätts från cellmembranet, ut i cellens omgivning. De kan förmedla budskap mellan celler och påverka olika processer i målceller.

    Metoder och material: Avhandlingen innefattar två olika microarraystudier på olika material. I den första studien användes hjärtbiopsier från 8 patienter med hypertrofisk obstruktiv kardiomyopati (HOCM) och 5 kontroller utan hjärtsjukdom. I det andra projektet användes hjärtvävnad från 6 aortaligerade och 6 skenopererade (kontroller) råttor vid tre olika tidpunkter (1, 6 och 42 dagar efter kirurgiskt ingrepp). För att påvisa skillnader i genuttryck analyserades proverna med Illumina helgenom microarray och multivariat dataanalys.

    Avhandlingens andra del innehåller två studier om mikrovesiklar och exosomer. Odlade hjärtmuskelceller (HL-1) stimulerades med tillväxt-faktorer (TGF-β2 eller PDGF BB) och ostimulerade celler användes som kontroll. Mikrovesiklar och exosomer renades fram med centrifugeringar och ultracentrifugering av cellodlingsmediet för att sedan karakteriseras med olika metoder för att studera storlek, ytmarkörer och innehåll. Illumina helgenom microarray användes för att studera microvesiklarnas och exosomernas mRNA innehåll.

    Resultat: I de två olika microarraystudierna hittades gentranskript och grupper av gentranskript som skiljde sig mellan kontroller och den hypertrofa hjärtvävnaden. När HOCM patientproverna jämfördes med kontroller hittades nedreglering av MYH6, EGR1 och FOS samt uppreglering av ACE2, JAK2 och HDAC5. Efter multivariat dataanalys av materialet från råtta, hittades 5 grupper av gentranskript med intressanta mönster som kunde kopplas till den hypertrofiska utvecklingen av hjärtmuskeln: "Ateroskleros", "ECM och adhesionsmolekyler", "Fettsyrametabolism", "Glukosmetabolis-men" och "Mitokondrien".

    Mikrovesiklarna hade en diameter på 40-300 nm och innehöll kromosomala DNA-sekvenser. När mikrovesiklarna överfördes till en annan celltyp (fibroblaster) resulterade det i ett förändrat genuttryck i fibroblasterna. Exosomer från hjärtmuskelcellerna som odlats med eller utan tillväxtfaktor hade en diameter på 50-80 nm. En stor pool av olika gentranskript var gemensam för alla exosomer oavsett stimulering eller ej. En mindre pool av gentranskript varierade i innehåll mellan de stimulerade och ostimulerade hjärtmuskelcellerna. I den gemensamma gentranskript poolen var ca 14 % ribosomala, ca 14 % var okända och ca 5 % var associerade till mitokondrien och dess funktion.

    Slutsats: Microarraystudierna visade att transkriptionsreglering i ett stabilt skede av hypertrofiutvecklingen är en balans mellan pro- och anti-hypertrofiska mekanismer och att olika gengrupper var olika reglerade vid olika tidpunkter i hjärtmuskeltillväxten.

    OPLS-DA är ett mycket användbart och kraftfullt verktyg när man analyserar genexpressionsdata, särskilt för att hitta grupper av gen-transkript som är svåra att upptäcka med traditionell statistik.

    Microvesikel- och exosomstudierna visade att mikrovesiklar och exosomer som frisätts från hjärtmuskelceller innehåller både DNA och RNA och kan vara inblandade i händelserna i målceller genom att underlätta en rad processer, inklusive ändringar av genuttryck. Olika stimulering av hjärtmuskelcellen kan påverka innehållet i exosomernas som produceras, vilket indikerar att exosomernas signalfunktion kan variera beroende på hjärtmuskelcellens tillstånd.

  • 266.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Malm, Linus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Larsson, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Ronquist, Gunnar
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Growth factor stimulation of cardiomyocytes induces changes in the transcriptional contents of secreted exosomes2013Ingår i: Journal of Extracellular Vesicles, ISSN 2001-3078, E-ISSN 2001-3078, Vol. 2Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Exosomes are nano-sized extracellular vesicles, released from various cells, which can stimulate or repress responses in targets cells. We recently reported that cultured cardiomyocytes are able to release exosomes and that they, in turn, are involved in facilitating events in target cells by alteration of gene expression. We investigated whether external stimuli of the cardiomyocyte might influence the transcriptional content of the released exosomes. Exosomes were isolated from media collected from cultured cardiomyocytes (HL-1) with or without growth factor treatment (TGF-β2 and PDGF-BB), with a series of differential centrifugations, including preparative ultracentrifugation and separation with a sucrose gradient. The exosomes were characterized with dynamic light scattering (DLS), electron microscopy (EM) and Western blot and analyzed with Illumina whole genome microarray gene expression. The exosomes were rounded in shape and had an average size of 50-90 nm in diameter with no difference between treatment groups. Analysis of the mRNA content in repeated experiments conclusively revealed 505 transcripts in the control group, 562 in the TGF-β2-treated group and 300 in the PDGF-BB-treated group. Common transcripts (217) were found in all 3 groups. We show that the mode of stimulation of parental cells affects the characteristics of exosomes released. Hence, there is a difference in mRNA content between exosomes derived from cultured cardiomyocytes stimulated, or not stimulated, with growth factors. We also conclude that all exosomes contain a basic package consisting of ribosomal transcripts and mRNAs coding for proteins with functions within the energy supply system.

  • 267.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Malm, Linus
    Institutionen för skoglig genetik och växtfysiologi, Sveriges lantbruks universitet.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    OPLS-DA of myocardial gene expression in the progression of cardiac hypertrophy in aorta ligated ratArtikel i tidskrift (Refereegranskat)
  • 268.
    Gennebäck, Nina
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wikström, Gerhard
    Institutionen för Medicinska Vetenskaper, Kardiologi, Uppsala univerisitet.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Samuel, Jane-Lise
    INSERM U 942, Hôpital Lariboisière, Paris, France.
    Waldenström, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mörner, Stellam
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Transcriptional regulation of cardiac genes balance pro and anti hypertrophic mechanisms in hypertrophic cardiomyopathy2012Ingår i: Cardiogenetics, ISSN 2035-8148, Vol. 2, nr 1Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Hypertrophic cardiomyopathy (HCM) is characterised by unexplained left ventricular hypertrophy. HCM is often hereditary, but the knowledge about the mechanisms leading from mutation to phenotype is incomplete. The transcriptional expression patterns in the myocardium of HCM patients may contribute to the understanding of the mechanisms that drive and stabilize the hypertrophy.

    Design and Methods: Cardiac myectomies/biopsies from 8 patients with hypertrophic obstructive cardiomyopathy (HOCM) and 5 controls were studied with whole genome Illumina microarray gene expression (detecting 18 189 mRNA).

    Results: When comparing HOCM myocardium to controls, there was significant transcriptional down-regulation of the MYH6, EGR1, APOB and FOS genes, and significant transcriptional up-regulation of the ACE2, JAK2, NPPA (ANP), APOA1 and HDAC5genes. 

    Conclusion: The transcriptional regulation revealed both pro and anti hypertrophic mechanisms. The pro hypertrophic response was explained by the transcriptional down-regulation of MYH6, indicating that the switch to the fetal gene program is maintained, and the transcriptional up-regulation of JAK2 in JAK-STAT pathway. The anti hypertrophic response was seen as a transcriptional down-regulation of the immediate early genes (IEGs), FOS and EGR1, and a transcriptional up-regulation of ACE2 and HDAC5. This can be interpreted as a transcriptional endogenous protection system in the heart of the HOCM patients, neither growing nor suppressing the already hypertrophic myocardium.

  • 269. Gerdts, Eva
    et al.
    Okin, Peter M
    de Simone, Giovanni
    Cramariuc, Dana
    Wachtell, Kristian
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Devereux, Richard B
    Gender differences in left ventricular structure and function during antihypertensive treatment: the Losartan intervention for endpoint reduction in hypertension study2008Ingår i: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 51, nr 4, s. 1109-1114Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In hypertensive patients with left ventricular hypertrophy, antihypertensive treatment induces changes in left ventricular structure and function. However, less is known about gender differences in this response. Baseline and annual echocardiograms until the end of study or a primary end point occurred were assessed in 863 hypertensive patients with electrocardiographic left ventricular hypertrophy aged 55 to 80 years (mean: 66 years) during 4.8 years of randomized losartan- or atenolol-based treatment in the Losartan Intervention for Endpoint Reduction in Hypertension Echocardiography substudy. Left ventricular hypertrophy was diagnosed as left ventricular mass divided by height(2.7) >or=46.7 g/m(2.7) and 49.2 g/m(2.7) in women and men, respectively, and systolic function as ejection fraction and stress-corrected midwall fractional shortening. Women included more patients with obesity, isolated systolic hypertension, and mitral regurgitation (all P<0.01). Ejection fraction, stress-corrected midwall shortening, and prevalence of left ventricular hypertrophy were higher in women at baseline and at the end of study (all P<0.01). In particular, more women had residual eccentric hypertrophy (47% versus 32%; P<0.01) in spite of similar in-treatment reduction in mean blood pressure. In logistic regression, left ventricular hypertrophy at study end was more common in women (odds ratio: 1.61; 95% CI: 1.16 to 2.26; P<0.01) independent of other significant covariates. In linear regression analyses, female gender also predicted 2% higher mean in-treatment ejection fraction and 2% higher mean stress-corrected midwall shortening (both beta=0.07; P<0.01). Hypertensive women in this study retained higher left ventricular ejection fraction and stress-corrected midwall shortening in spite of less hypertrophy regression during long-term antihypertensive treatment.

  • 270. Gerdts, Eva
    et al.
    Rossebø, Anne Bjørhovde
    Pedersen, Terje Rolf
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Brudi, Philippe
    Chambers, John Boyd
    Egstrup, Kenneth
    Gohlke-Bärwolf, Christa
    Holme, Ingar
    Kesäniemi, Y Antero
    Malbecq, William
    Nienaber, Christoph
    Ray, Simon
    Skjærpe, Terje
    Wachtell, Kristian
    Willenheimer, Ronnie
    Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study)2010Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 106, nr 11, s. 1634-1639Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Retrospective studies have suggested a beneficial effect of lipid-lowering treatment on the progression of aortic stenosis (AS) in milder stages of the disease. In the randomized, placebo-controlled Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, 4.3 years of combined treatment with simvastatin 40 mg and ezetimibe 10 mg did not reduce aortic valve events (AVEs), while ischemic cardiovascular events (ICEs) were significantly reduced in the overall study population. However, the impact of baseline AS severity on treatment effect has not been reported. Baseline and outcomes data in 1,763 SEAS patients (mean age 67 years, 39% women) were used. The study population was divided into tertiles of baseline peak aortic jet velocity (tertile 1: <= 2.8 m/s; tertile 2: >2.8 to 3.3 m/s; tertile 3: >3.3 m/s). Treatment effect and interaction were tested in Cox regression analyses. The rates of AVEs and ICEs increased with increasing baseline severity of AS. In Cox regression analyses, higher baseline peak aortic jet velocity predicted higher rates of AVEs and ICEs in all tertiles (all p values <0.05) and in the total study population (p <0.001). Simvastatin-ezetimibe treatment was not associated with a statistically significant reduction in AVEs in any individual tertile. A significant quantitative interaction between the severity of AS and simvastatin-ezetimibe treatment effect was demonstrated for ICEs (p <0.05) but not for AVEs (p = 0.10). In conclusion, the SEAS study results demonstrate a strong relation between baseline the severity of AS and the rate of cardiovascular events but no significant effect of lipid-lowering treatment on AVEs, even in the group with the mildest AS.

  • 271.
    Gharibyan, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Narayana, Vinod
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Habib, Ahsan
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Sulniute, Rima
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Olofsson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Morozova-Roche, Ludmilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Inflammatory S100A9 and Aβ amyloids in heart valve of patient with aortic stenosisManuskript (preprint) (Övrigt vetenskapligt)
  • 272.
    Gistera, A.
    et al.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Robertson, A. K.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Andersson, J.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Ketelhuth, D. F. J.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Oychinnikova, O.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Nilsson, Stefan K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Lundberg, A. M.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Li, M. O.
    Department of Immunobiology, Yale University School of Medicine, New Haven CT, USA.
    Flavell, R. A.
    Department of Immunobiology, Yale University School of Medicine, New Haven CT, USA.
    Hansson, G. K.
    Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
    Transforming growth factor-beta signaling in t cells promotes stabilization of atherosclerotic plaques through an interleukin-17 dependent pathway2014Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 235, nr 2, s. E88-E89Artikel i tidskrift (Övrigt vetenskapligt)
  • 273.
    Glader, Eva-Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Edlund, Hilda
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Sukhova, Maria
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Asplund, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Norrving, Bo
    Department of Clinical Sciences, Section of Neurology, Lund University, Sweden.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Reduced inequality in access to stroke unit care over time: a 15-year follow-up of socioeconomic disparities in Sweden2013Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 36, nr 5-6, s. 407-411Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Despite the compelling scientific evidence on the superiority of stroke unit care, far from all acute stroke patients have access to stroke unit care. In congruence with what has been observed when other new methods are introduced in health care, we hypothesized that there has been an inequality in the buildup phase of stroke units but that the gradients between patient groups have decreased as the total capacity of stroke unit care has increased. The purpose of this study was to explore if patients in a national sample who were socioeconomically disadvantaged (low education or low income) had reduced access to stroke unit care and if differences varied over time.

    Methods: All patients 18-74 years of age registered between 1995 and 2009 in Riks-Stroke, the Swedish stroke register, were included. The Stroke Unit Trialists' definition of a stroke unit has been adopted by Riks-Stroke and hospitals participating in the registry. Basic patient characteristics, stroke risk factors, process and outcome variables are recorded in Riks-Stroke. Socioeconomic data were accessed from Statistics Sweden. Multiple logistic regression analyses were used to calculate odds ratios (ORs) for stroke unit care between prespecified patient subgroups.

    Results: A total of 319,240 stroke patients were included in Riks-Stroke during the years 1995-2009, and 124,173 were aged between 18 and 74 years; they were included in the final analyses. After adjustment for confounders in a multiple regression model, women were treated in stroke units slightly less often [OR 0.97, 95% confidence interval (CI) 0.95-0.99]. There were no statistically significant associations between stroke unit care and age or between stroke unit care and cohabiting or living alone. The highest level of education predicted access to stroke unit care (secondary vs. primary school: OR 1.04, 95% CI 1.01-1.07; university vs. primary school: OR 1.06, 95% CI 1.02-1.10). Differences according to level of education diminished over time (p = 0.001). Income was not independently associated with stroke unit care, and over time the proportion of patients treated in stroke units increased at a similar rate in all income groups (p = 0.12).

    Conclusions: Even in a country with modest socioeconomic differences in the general population and public financing of all acute hospital care, socioeconomic inequalities in access to stroke unit care were evident during the early years, but they diminished as the total capacity for stroke unit care increased.

    © 2013 S. Karger AG, Basel.

  • 274.
    Glader, Eva-Lotta
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Jonsson, B.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Socioeconomic status predicts return to work after first stroke in younger adults2015Ingår i: International Journal of Stroke, ISSN 1747-4930, E-ISSN 1747-4949, Vol. 10, s. 174-174Artikel i tidskrift (Övrigt vetenskapligt)
  • 275. Glise, Lars
    et al.
    Larsson, Pia
    Jern, Sverker
    Borén, Jan
    Levin, Malin
    Ny, Tor
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Fogelstrand, Per
    Bergh, Niklas
    Disturbed Laminar Blood Flow Causes Impaired Fibrinolysis and Endothelial Fibrin Deposition In Vivo2019Ingår i: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 119, nr 2, s. 223-233Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Endothelial expression of tissue-type plasminogen activator (t-PA) is crucial for maintaining an adequate endogenous fibrinolysis. It is unknown how endothelial t-PA expression and fibrinolysis are affected by blood flow in vivo. In this study, we investigated the impact of different blood flow profiles on endothelial t-PA expression and fibrinolysis in the arterial vasculature. Induction of disturbed laminar blood flow (D-flow) in the mouse carotid artery potently reduced endothelial t-PA messenger ribonucleic acid and protein expression, and caused fibrin deposition. En face immunohistochemistry demonstrated that arterial areas naturally exposed to D-flow had markedly lower endothelial t-PA levels than areas with sustained laminar blood flow (S-flow), and displayed pronounced fibrin deposition despite an intact endothelium. In t-PA and plasminogen-deficient mice, fibrin deposition did not extend into S-flow areas, indicating that areas of D-flow and S-flow differ, not only in fibrinolytic capacity, but also in coagulation. Furthermore, plasminogen accumulation was found at D-flow areas, and infusion of recombinant t-PA activated fibrinolysis and significantly reduced the fibrin deposits. In conclusion, D-flow potently impairs the fibrinolytic capacity and causes endothelial fibrin deposition in vivo. Our data also indicate that t-PA is the limiting factor for efficient fibrinolysis at the thrombosis-prone D-flow areas in the arterial vasculature.

  • 276.
    Gonzalez Garcia, Manuel Cruz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    The role of leptin in endothelial dysfunction and cardiovascular disease2013Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Objective:  Obesity has become the leading cause of mortality worldwide; however, the fundamental pathophysiology underlying this association remains unclear. The discovery of adipokines, i.e., cytokines produced by adipose cells (adipocytes), revealed that adipose tissue is a highly endocrine organ, thus opening new lines of investigation. The prototypical adipokine leptin increases in obesity, and leptin receptors are found in vascular cells. However, results are contradictory regarding the role of leptin in vascular and endothelial functions. Leptin has been shown to elicit vasodilatation, but has also been linked with atherosclerotic and thrombotic disease. The main aim of the present thesis was to study the association of circulating levels of leptin with markers of endothelial function, and to analyze the effects of leptin infusion in vivo  on vasomotor function and endogenous fibrinolysis.

    Material:  Four associative studies and two interventional studies were conducted. The former included DISARM (studies 1 and 2), the PIVUS study (study 3), and the Scottish post-infarction study (study 4). The DISARM studies and study 4, respectively, recruited 20 men and 83 men and women with stable ischemic heart disease. Study 3 included a random sample of 1016 subjects (54% women, 70 years old) living in the community of Uppsala, Sweden. For the interventional studies (studies 5 and 6), 10 healthy men were recruited for each study.

    Methods:  In all studies, endothelial function was estimated based on forearm blood flow (FBF) as measured by strain-gauge venous occlusion plethysmography, at rest or during infusion of vasodilators. In study 3, additional measurement techniques were used, such as brachial ultrasound flow-mediated dilation (FMD) and the aortic augmentation index (AoAIx) by tonometry in the radial artery. Fibrinolytic status was estimated based on basal and stimulated levels of tissue plasminogen activator antigen (t-PA), and by assessment of the endothelial release of t-PA (net t-PA release). Plasma leptin levels were measured by radioimmunoassay. In the associative studies, endothelial function and fibrinolytic status were related to circulating plasma leptin levels. In the experimental studies, exogenous leptin was administered in the brachial artery and endothelial function was assessed by strain-gauge plethysmography

    Results:  In elderly men and women, leptin was independently associated with decreased endothelial-dependent and -independent vasodilatation, reflecting disturbed endothelial function in resistance vessels. This association was attenuated after adjustment for BMI, and when analyzed among subjects with high plasma leptin levels. FMD (a measure of endothelial function in conduit vessels) was not associated with leptin. Exogenous leptin infusion did not alter vasomotor tone, but the endothelium-dependent and -independent vasodilatation was impaired during concomitant infusion of leptin and vasodilators. Infused leptin in the forearm did not affect blood pressure or pulse rate. Chronic hyperleptinemia, but not acutely induced hyperleptinemia, was associated with release of endothelial tissue plasminogen activator (net t-PA).

    Conclusions:  In humans, leptin was associated with impaired vasodilatation. However, this relationship was blunted after adjustment for BMI, suggesting that leptin could be the mediator between obesity and impaired vascular function. Furthermore, the observed lack of association in hyperleptinemic subjects may reflect a state of leptin resistance. The experimental result showing attenuated vascular reactivity following leptin infusion is in accordance with the results of the associative studies. The augmented net t-PA release in patients with chronic hyperleptinemia may indicate a state of “vascular activation,” which was not observed in healthy endothelium during a short period of leptin infusion. This thesis addresses several controversial issues regarding the action of leptin on vascular tissue in humans. The final results indicate that the in vivo action of leptin on vascularity is complex and mediated by several mechanisms. Our findings suggest that leptin is an important mediator between obesity and endothelial dysfunction, and should stimulate further investigation of this matter.

  • 277.
    Gonzalez Garcia, Manuel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Australian eHealth Research Centre, CSIRO, Brisbane, QLD, Australia; Heart Centre, University Hospital of Umeå.
    Fatehi, Farhad
    Bashi, Nazli
    Varnfield, Marlien
    Iyngkaran, Pupalan
    Driscoll, Andrea
    Neil, Christopher
    Hare, David L.
    Oldenburg, Brian
    A Review of Randomized Controlled Trials Utilizing Telemedicine for Improving Heart Failure Readmission: Can a Realist Approach Bridge the Translational Divide?2019Ingår i: Clinical Medicine Insights: Cardiology, ISSN 1179-5468, E-ISSN 1179-5468, Vol. 13Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Telemedicine and digital health technologies hold great promise for improving clinical care of heart failure. However, inconsistent and contradictory findings from randomized controlled trials have so far discouraged widespread adoption of digital health in routine clinical practice. We undertook this review study to summarize the study outcomes of the use of exploring the evidence for telemedicine in the clinical care of patients with heart failure and readmissions.

    Methods: We inspected the references of guidelines and searched PubMed for randomized controlled trials published over the past 10 years on the use of telemedicine for reducing readmission in heart failure. We utilized a modified realist review approach to identify the underlying contextual mechanisms for the intervention(s) in each randomized controlled trial, evaluating outcomes of the intervention and understanding how and under what conditions they worked. To provide uniformity, all extracted data were synthesized using adapted domains from the taxonomy for disease management created by the Disease Management Taxonomy Writing Group.

    Results: A total of 12 papers were eligible, 6 of them supporting and 6 others undermining the use of telemedicine for improving heart failure readmission. In general terms, those studies not supporting the use of telemedicine were multicentre, publicly funded, with large amount of participants, and long duration. The patients had also better rates of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker and beta-blockers, and telemonitoring and automatic transmission of vital signs were less utilized, in comparison with the studies in which telemedicine use was supported. The analysis of the environment, intensity, content of interventions, method of communication, quality of the underlying model of care and the ability, capability, and interest from health workers can help us to envisage probabilities of success of telemedicine use.

    Conclusions: A realist lens may aid to understand whom and in which circumstances the use of telemedicine can add any substantial value to traditional models of care. Wider outcome criteria beyond major adverse cardiovascular events, for example, cost efficacy, should also be considered as appropriate for effecting guidelines on care delivery when robust prognostic therapeutics already exist.

  • 278.
    Gonzalez, Manuel Cruz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Robinson, Simon
    Mills, Nicholas L
    Eriksson, Marie
    Umeå universitet, Samhällsvetenskapliga fakulteten, Handelshögskolan vid Umeå universitet, Statistik.
    Sandström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Newby, David E
    Olsson, Tommy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blomberg, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Lungmedicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Hyperleptinemia is associated with altered endothelial functionManuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Introduction The adipocyte-derived hormone leptin has been associated with increased risk of cardiovascular disease but the underlying mechanisms are unclear. Leptin effects on vascular endothelium may be a key mediator although contradictory results have been presented. We aimed to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary heart disease.

    Methods and Results The vascular effects of leptin were assessed using venous occlusion plethysmography in healthy volunteers (n=17) and in patients with stable coronary heart disease (CHD) (n=83). In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n=10) did not affect forearm blood flow or plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 (PAI-1) concentrations (all P>0.05).  However, during concomitant co-infusion with leptin (800 ng/min; n=10), induced vasodilatation was reduced (P=0.001), and tPA activity increased (P=0.002). In line with this, patients with coronary heart disease included in the highest tertile of plasma leptin concentrations had reduced substance P-induced vasodilatation (P<0.001), and increased tPA antigen and activity release (p<0.001 and p=0.03 respectively) compared to those in the lowest tertile.

    Conclusions Although leptin does not directly affect basal vascular function, acute local and chronic systemic hyperleptinemia are associated with altered endothelial function in healthy volunteers and patients with coronary heart disease respectively. These results support hyperleptinemia as a link between obesity and cardiovascular disease.

  • 279.
    Gonzalez, Manuel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lind, Lars
    Uppsala Univ, Dept Med, Uppsala, Sweden.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Leptin and endothelial function in the elderly: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study2013Ingår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 228, nr 2, s. 485-490Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Leptin levels are elevated in obese humans. Several studies have shown an association between hyperleptinemia and development of atherosclerosis and cardiovascular disease (CVD), but the relationship between leptin and vascular function remains unclear.

    Aim: To evaluate associations between circulating plasma leptin and measures of vascular function in a large sample of elderly individuals from the community.

    Methods: This cross-sectional study included 1016 subjects aged 70 (50% women) from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS). The invasive technique forearm plethysmography with intra-arterial infusions of acetylcholine and sodium nitroprusside was used for estimation of endothelial dependent vasodilatation (EDV) and endothelial independent vasodilatation (EIDV), respectively, in resistance arteries, and the non-invasive technique ultrasound assessed flow mediated vasodilation (FMD) in conduit arteries. The aortic augmentation index (AoAI), a surrogate measure of arterial stiffness, was evaluated by pulse wave analysis. Associations of vascular function, arterial stiffness and blood pressure with leptin were explored.

    Results: In sex-adjusted models, high levels of leptin were inversely associated with EDV and EIDV. These associations remained after stratification for sex, traditional risk factors of CVD and insulin resistance, but were attenuated after taking a measure of obesity (body mass index) into account. In addition, leptin associated with arterial stiffness and systolic and diastolic blood pressure.

    Conclusion: Hyperleptinemia associated inversely with vasodilatation in resistance arteries. Furthermore, hyperleptinemia associated with arterial stiffness and hypertension. These associations were attenuated after adjusting for body mass index suggesting that leptin may be the mediator between obesity and impaired vascular function. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

  • 280.
    Graipe, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Section of Cardiology, Department of Internal Medicine, Östersund Hospital, Östersund, Sweden.
    Binsell-Gerdin, Emil
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Internal Medicine, Östersund Hospital, Östersund, Sweden .
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Incidence, Time Trends, and Predictors of Intracranial Hemorrhage During Long-Term Follow-up After Acute Myocardial Infarction2015Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 4, nr 12, artikel-id e002290Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

  • 281.
    Graipe, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Söderström, Lars
    Mooe, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Increased Use of Ticagrelor After Myocardial Infarction Is Not Associated With Intracranial Hemorrhage: Results From a Nationwide Swedish Registry2018Ingår i: Stroke, ISSN 0039-2499, E-ISSN 1524-4628, Vol. 49, nr 12, s. 2877-2882Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and Purpose: Guidelines recommend dual antiplatelet treatment with ticagrelor instead of clopidogrel after acute myocardial infarction. Ticagrelor increases major and minor noncoronary artery bypass graft bleeding compared with clopidogrel, but whether the risk of intracranial hemorrhage (ICH) increases is unknown. We aimed to examine any association between ticagrelor and ICH and to identify predictors of ICH among unselected patients after acute myocardial infarction.

    Methods: Patients with acute myocardial infarction were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions, and the data were combined with the Swedish National Patient Registry to identify ICH occurrence. To avoid obvious selection bias related to the choice of dual antiplatelet treatment, we divided the study cohorts into 2 time periods of similar length using the first prescription of ticagrelor as a cutoff point (December 20, 2011). The risk of ICH during the first period (100% clopidogrel treatment) versus the second period (52.1% ticagrelor and 47.8% clopidogrel treatment) was assessed using Kaplan-Meier analysis. Cox proportional-hazards regression analyses, with assessment of interactions between all significant variables, were used to identify predictors of ICH.

    Results: The analysis included 47 674 patients with acute myocardial infarction. The cumulative incidence of ICH during the first period was 0.59% (91 cases [95% CI, 0.49-0.69]) versus 0.52% (97 cases [95% CI, 0.43-0.61]) during the second period (P=0.83). In multivariable Cox analysis, study period (second versus first period) was not predictive of ICH. Interaction analyses showed that age and prior cardiovascular morbidities were of importance in predicting the risk of ICH.

    Conclusions: The increased use of ticagrelor was not associated with ICH, whereas age and prior cardiovascular morbidities were related to the risk of ICH and interacted significantly.

  • 282.
    Granåsen, Gabriel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Multivariate Classification of Cardiac Autonomic Function and Echocardiographic Abnormalities2013Ingår i: 2013 COMPUTING IN CARDIOLOGY CONFERENCE (CINC), 2013, s. 1151-1154Konferensbidrag (Refereegranskat)
    Abstract [en]

    Abnormalities in the function, physiology and the regulation of the heart can be diagnosed using echocardiography (ECHO) and analysis of heart rate variability (HRV). Patients with transthyretin amyloidosis often present increased wall thickness in the myocardium and/ or autonomic dysfunction. We used a novel approach to analyse the relationship between these findings, using a combination of dimension reduction techniques and model based clustering.

  • 283.
    Greiser, K. H.
    et al.
    German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg, Germany.
    Tiller, D.
    Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
    Kuss, O.
    Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
    Kluttig, A.
    Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany .
    Rudge, G.
    Public Health, Epidemiology and Biostatistics Unit, The College of Medical and Dental Sciences, The University of Birmingham, Birmingham, UK.
    Schumann, Barbara
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Werdan, K.
    University Clinic for Internal Medicine III, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
    Haerting, J.
    Institute of Medical Epidemiology, Biostatistics, and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
    Association of neighbourhood socioeconomic status and individual socioeconomic status with cardiovascular risk factors in an Eastern German population: the CARLA Study 2002–20062011Ingår i: IEA World Congress of Epidemiology, 7–11 August 2011, Edinburgh International Conference Centre, Edinburgh, Scotland Programme and abstracts, 2011, Vol. 65, nr A249, s. A249-Konferensbidrag (Refereegranskat)
    Abstract [en]

    Introduction/objectives: Individual socioeconomic status (SES) is a determinant of cardiovascular risk factors (RF). Recent studies suggest an independent association of neighbourhood SES with cardiovascular RF, but the mechanisms have not fully been understood. Our aim was to assess the association of neighbourhood and individual SES with cardiovascular RF in an Eastern German population.

    Methods: We used cross-sectional data of 1779 participants aged 45–83 years of the population-based CARLA study. We calculated linear mixed models to assess the age-adjusted influence of neighbourhood-specific unemployment rates and individual SES on smoking, systolic blood pressure (SBP), and body mass index (BMI). Spatial dependencies within and between neighbourhoods were adjusted for by using ICAR models.

    Results: Neighbourhood-specific unemployment rates varied between 6.3 and 35.3%. Per 1% increase in the neighbourhood's unemployment rate, the number of cigarettes smoked/day increased by 0.11 in men (95% CI 0.09 to 0.12) and 0.05, (CI 0.04 to 0.07) in women. In women, SBP increased by 0.04 mm Hg with unemployment rate (CI 0.03 to 0.06), while there was no statistically significant association of SBP with SES in men. BMI was only in women significantly associated with unemployment (increase in BMI per 1% increase in unemployment rate 0.04 (CI 0.02 to 0.05)). Associations of RF with individual SES were stronger than with neighbourhood SES in multiple models.

    Conclusions: Our findings confirm the previously described association of neighbourhood SES with smoking independent of individual SES, while we found inconsistent associations with SBP and BMI. The neighbourhood environment may be more relevant for behavioural than for biomedical risk factors.

  • 284. Greve, A.
    et al.
    Gohlke-Baerwolf, C.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Egstrup, K.
    Kesianemi, Y. A.
    Ray, S.
    Pedersen, T.
    Best, P.
    Rajamannan, N.
    Wachtell, K.
    The low-density lipoprotein-density-pressure theory identifies asymptomatic aortic stenosis patients benefiting from cholesterol lowering therapy: the seas study2014Ingår i: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 35, nr Supplement 1, Meeting abstract P2392, s. 419-420Artikel i tidskrift (Övrigt vetenskapligt)
  • 285. Greve, A. M.
    et al.
    Bang, C. N.
    Gohlke-Baerwolf, C.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Egstrup, K.
    Kesaniemi, Y. A.
    Ray, S.
    Pedersen, T. R.
    Rajamannan, N. M.
    Wachtell, K.
    LIPID LOWERING IN PATIENTS WITH MILD AORTIC STENOSIS AND ELEVATED LOW DENSITY LIPOPROTEIN: THE SEAS STUDY2015Ingår i: Cardiology, ISSN 0008-6312, E-ISSN 1421-9751, Vol. 131, nr suppl 2, s. 193-193Artikel i tidskrift (Övrigt vetenskapligt)
  • 286. Greve, Anders M.
    et al.
    Bang, Casper N.
    Berg, Ronan M. G.
    Egstrup, Kenneth
    Rossebo, Anne B.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nienaber, Christoph A.
    Ray, Simon
    Gohlke-Baerwolf, Christa
    Nielsen, Olav W.
    Okin, Peter M.
    Devereux, Richard B.
    Kober, Lars
    Wachtell, Kristian
    Resting heart rate and risk of adverse cardiovascular outcomes in asymptomatic aortic stenosis: The SEAS study2015Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 180, s. 122-128Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: An elevated resting heart rate (RHR) may be an early sign of cardiac failure, but its prognostic value during watchful waiting in asymptomatic aortic stenosis (AS) is largely unknown. Methods: RHR was determined by annual ECGs in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study of asymptomatic mild-to-moderate AS patients. Primary endpoint in this substudy was major cardiovascular events (MCEs) and secondary outcomes its individual components. Multivariable Cox-models using serially-measured RHR were used to examine the prognostic impact of RHR per se. Results: 1563 patients were followed for a mean of 4.3 years (6751 patient-years of follow-up), 553 (35%) MCEs occurred, 10% (n = 151) died, including 75 cardiovascular deaths. In multivariable analysis, baseline RHR was independently associated with MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.0-1.3) and cardiovascular mortality (HR 1.3 per 10 min(-1) faster, 95% CI: 1.0-1.7, both p <= 0.03). Updating RHR with annual in-study reexaminations, time-varying RHR was highly associated with excess MCEs (HR 1.1 per 10 min(-1) faster, 95% CI: 1.1-1.3) and cardiovascular mortality (HR 1.4 per 10 min(-1) faster, 95% CI: 1.2-1.7, both p <= 0.006). The association of RHR with MCEs and cardiovascular mortality was not dependent on atrial fibrillation status (both p >= 0.06 for interaction). Conclusions: RHR is independently associated with MCEs and cardiovascular death in asymptomatic AS (Clinicaltrials.gov; unique identifier NCT00092677).

  • 287. Greve, Anders M.
    et al.
    Bang, Casper N.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Egstrup, Kenneth
    Forman, Julie L.
    Kesäniemi, Y. Antero
    Ray, Simon
    Pedersen, Terje R.
    Best, Patricia
    Rajamannan, Nalini M.
    Wachtell, Kristian
    Effect Modifications of Lipid-Lowering Therapy on Progression of Aortic Stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis [SEAS] Study)2018Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 121, nr 6, s. 739-745Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Observational studies indicate that low-density lipoprotein (LDL) cholesterol acts as a primary contributor to an active process leading to aortic stenosis (AS) development. However, randomized clinical trials have failed to demonstrate an effect of lipid lowering on impeding AS progression. This study explored if pretreatment LDL levels and AS severity altered the efficacy of lipid-lowering therapy. The study goal was evaluated in the analysis of surviving patients with baseline data in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) trial of 1,873 asymptomatic patients with mild-to-moderate AS. Serially measured peak aortic jet velocity was the primary effect estimate. Linear mixed model analysis adjusted by baseline peak jet velocity and pretreatment LDL levels was used to assess effect modifications of treatment. Data were available in 1,579 (84%) patients. In adjusted analyses, lower baseline peak aortic jet velocity and higher pretreatment LDL levels increased the effect of randomized treatment (p >= 0.04 for interaction). As such, treatment impeded progression of AS in the highest quartile of LDL among patients with mild AS at baseline (0.06 m/s per year slower progression vs placebo in peak aortic jet velocity, 95% confidence interval 0.01 to 0.11, p = 0.03), but not in the 3 other quartiles of LDL. Conversely, among patients with moderate AS, there was no detectable effect of treatment in any of the pretreatment LDL quartiles (all p In conclusion, in a non prespecified post hoc analysis, the efficacy of lipid-lowering therapy on impeding AS progression increased with higher pretreatment LDL and lower peak aortic jet velocity (SEAS study: NCT00092677). 

  • 288. Greve, Anders M.
    et al.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gohlke-Baerwolf, Christa
    Kesaniemi, Y. Antero
    Nienaber, Christoph
    Ray, Simon
    Egstrup, Kenneth
    Rossebo, Anne B.
    Devereux, Richard B.
    Kober, Lars
    Willenheimer, Ronnie
    Wachtell, Kristian
    Clinical implications of electrocardiographic left ventricular strain and hypertrophy in asymptomatic patients with aortic stenosis the simvastatin and ezetimibe in aortic stenosis study2012Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 125, nr 2, s. 346-353Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background-The prognostic impact of ECG left ventricular strain and left ventricular hypertrophy (LVH) in asymptomatic aortic stenosis is not well described.

    Methods and Results-Data were obtained in asymptomatic patients randomized to simvastatin/ezetimibe combination versus placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Primary end point was the first of myocardial infarction, nonhemorrhagic stroke, heart failure, aortic valve replacement, or cardiovascular death. The predictive value of ECG left ventricular strain (defined as T-wave inversion in leads V(4) through V(6)) and LVH, assessed by Sokolow-Lyon voltage criteria (R(V5-6) +/- S(V1) >= 35 mV) and Cornell voltage-duration criteria {[RaVL + S(V3) + (6 mV in women)] x QRS duration >= 2440 mV.ms}, was evaluated by adjustment for other prognostic covariates. A total of 1533 patients were followed for 4.3 +/- 0.8 years (6592 patient-years of follow-up), and 627 cardiovascular events occurred. ECG strain was present in 340 patients (23.6%), with LVH by Sokolow-Lyon voltage in 260 (17.1%) and by Cornell voltage-duration product in 220 (14.6%). In multivariable analyses, ECG left ventricular strain was associated with 3.1-fold higher risk of in-study myocardial infarction (95% confidence interval, 1.4-6.8; P = 0.004). Similarly, ECG LVH by both criteria predicted, compared with no ECG LVH, 5.8-fold higher risk of heart failure (95% confidence interval, 2.0 -16.8), 2.0-fold higher risk of aortic valve replacement (95% confidence interval, 1.3-3.1; both P = 0.001), and 2.5-fold higher risk of a combined end point of myocardial infarction, heart failure, or cardiovascular death (95% confidence interval, 1.3-4.9; P = 0.008).

    Conclusions-ECG left ventricular strain and LVH were independently predictive of poor prognosis in patients with asymptomatic aortic stenosis.

  • 289. Greve, Anders M.
    et al.
    Dalsgaard, Morten
    Bang, Casper N.
    Egstrup, Kenneth
    Rossebø, Anne B.
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Cramariuc, Dana
    Nienaber, Christoph A.
    Ray, Simon
    Gohlke-Baerwolf, Christa
    Okin, Peter M.
    Devereux, Richard B.
    Køber, Lars
    Wachtell, Kristian
    Usefulness of the electrocardiogram in predicting cardiovascular mortality in asymptomatic adults with aortic stenosis (from the Simvastatin and Ezetimibe in Aortic Stenosis study)2014Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 114, nr 5, s. 751-756Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Hypertension and coronary heart disease are common in aortic stenosis (AS) and may impair prognosis for similar AS severity. Different changes in the electrocardiogram may be reflective of the separate impacts of AS, hypertension, and coronary heart disease, which could lead to enhanced risk stratification in AS. The aim of this study was therefore to examine if combining prognostically relevant electrocardiographic (ECG) findings improves prediction of cardiovascular mortality in asymptomatic AS. All patients with baseline electrocardiograms in the SEAS study were included. The primary end point was cardiovascular death. Backward elimination (p > 0.01) identified heart rate, Q waves, and Cornell voltage-duration product as independently associated with cardiovascular death. Multivariate logistic and Cox regression models were used to evaluate if these 3 ECG variables improved prediction of cardiovascular death. In 1,473 patients followed for a mean of 4.3 years (6,362 patient-years of follow-up), 70 cardiovascular deaths (5%) occurred. In multivariate analysis, heart rate (hazard ratio [FIR] 1.5 per 11.2 minute(-1) [1 SD], 95% confidence interval [CI] 1.2 to 1.8), sum of Q-wave amplitude (HR 1.3 per 2.0 nun [1 SD], 95% CI 1.1 to 1.6), and Cornell voltage-duration product (FIR 1.4 per 763 mm x ms [1 SD], 95% CI 1.2 to 1.7) remained independently associated with cardiovascular death. Combining the prognostic information contained in each of the 3 ECG variables improved integrated discrimination for prediction of cardiovascular death by 2.5%, net reclassification by 14.3%, and area under the curve by 0.06 (all p <= 0.04) beyond other important risk factors. ECG findings add incremental predictive information for cardiovascular mortality in asymptomatic patients with AS.

  • 290. Greve, Anders M.
    et al.
    Gerdts, Eva
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gohlke-Baerwolf, Christa
    Rossebo, Anne B.
    Devereux, Richard B.
    Kober, Lars
    Ray, Simon
    Willenheimer, Ronnie
    Wachtell, Kristian
    Impact of QRS Duration and Morphology on the Risk of Sudden Cardiac Death in Asymptomatic Patients With Aortic Stenosis The SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) Study2012Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 59, nr 13, s. 1142-1149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives: The aim of the study was to examine the predictive value of QRS duration and morphology during watchful waiting in asymptomatic patients with aortic stenosis (AS).

    Background: QRS duration and morphology are associated with poor prognosis in many different populations, but the predictive value, particularly of the risk of sudden cardiac death (SCD), in asymptomatic patients with AS has not been well studied.

    Methods: Data were obtained in asymptomatic AS patients randomized to simvastatin/ezetimibe combination versus placebo in the SEAS (Simvastatin and Ezetimibe in Aortic Stenosis) study. The impact of QRS duration, evaluated as a categorical variable of <85 ms versus 85 to 99 ms and >= 100 ms (excluding bundle branch block [BBB]) and QRS morphology in those with BBB, on cardiovascular morbidity and mortality was assessed by adjusting for clinical and echocardiographic covariates.

    Results: QRS data were available in 1,542 patients who were followed for a mean of 4.3 +/- 0.8 years (6,631 patient-years of follow-up). There were 68 cardiovascular deaths (4.6%), including 27 SCDs (1.8%). QRS duration was <85 ms in 900 patients (58.4%), 85 to 99 ms in 396 (25.7%), >= 100 ms in those without BBB in 144 (9.3%), and 102 (6.6%) in those with BBB. In multivariable analyses, those with QRS duration >= 100 ms had, compared with those with QRS duration <85 ms, a 5-fold higher risk of SCD (95% confidence interval: 1.8 to 13.7, p = 0.002) and a 2.5-fold higher risk of cardiovascular death (95% confidence interval: 1.2 to 5.1, p = 0.01).

    Conclusions: QRS duration and morphology in asymptomatic patients with AS are independently associated with a poor prognosis, particularly the risk of SCD.

    (Simvastatin Ezetimibe in Aortic Stenosis [SEAS]; NCT00092677) (J Am Coll Cardiol 2012; 59: 1142-9) (C) 2012 by the American College of Cardiology Foundation

  • 291. Greve, Anders M.
    et al.
    Gerdts, Eva
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Gohlke-Baerwolf, Christa
    Rossebo, Anne B.
    Hammer-Hansen, Sophia
    Kober, Lars
    Willenheimer, Ronnie
    Wachtell, Kristian
    Differences in Cardiovascular Risk Profile Between Electrocardiographic Hypertrophy Versus Strain in Asymptomatic Patients With Aortic Stenosis (from SEAS Data)2011Ingår i: American Journal of Cardiology, ISSN 0002-9149, E-ISSN 1879-1913, Vol. 108, nr 4, s. 541-547Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Electrocardiograms are routinely obtained in clinical follow-up of patients with asymptomatic aortic stenosis (AS). The association with aortic valve, left ventricular (LV) response to long-term pressure load, and clinical covariates is unclear and the clinical value is thus uncertain. Data from clinical examination, electrocardiogram, and echocardiogram in 1,563 patients in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study were used. Electrocardiograms were Minnesota coded for arrhythmias and atrioventricular and intraventricular blocks; LV hypertrophy was assessed by Sokolow-Lyon voltage and Cornell voltage duration criteria; and strain by T-wave inversion and ST-segment depression. Degree of AS severity was evaluated by echocardiography as peak aortic jet velocity and LV mass was indexed by body surface area. After adjustment for age, gender, LV mass index, heart rate, systolic and diastolic blood pressures, blood glucose, digoxin, antiarrhythmic drugs, drugs acting on the renin angiotensin system, diuretics, beta blockers and calcium receptor blockers; peak aortic jet velocity was significantly greater in patients with electrocardiographic strain (mean difference 0.13 m/s, p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria (mean difference 0.12 m/s, p = 0.004). After similar adjustment, LV mass index was significantly greater in patients with electrocardiographic strain (mean difference 14.8 g/cm(2), p <0.001) and LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria (mean differences 8.8 and 17.8 g/cm(2), respectively, p <0.001 for the 2 comparisons). In multiple comparisons patients with electrocardiographic strain had increased peak aortic jet velocity, blood glucose, and uric acid, whereas patients with LV hypertrophy by Sokolow-Lyon voltage criteria were younger and patients with LV hypertrophy by Cornell voltage duration criteria more often were women. In conclusion, electrocardiographic criteria for LV hypertrophy and strain are independently associated with peak aortic jet velocity and LV mass index. Moreover, clinical covariates differ significantly between patients with electrocardiographic strain and those with LV hypertrophy by Sokolow-Lyon voltage criteria and Cornell voltage duration criteria. 

  • 292. Greve, Anders M.
    et al.
    Gerdts, Eva
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Dept Med Skellefta, Skellefta, Sweden.
    Gohlke-Baerwolf, Christa
    Rossebo, Anne B.
    Nienaber, Christoph A.
    Ray, Simon
    Egstrup, Kenneth
    Pedersen, Terje R.
    Kober, Lars
    Willenheimer, Ronnie
    Wachtell, Kristian
    Prognostic importance of atrial fibrillation in asymptomatic aortic stenosis: The Simvastatin and Ezetimibe in Aortic Stenosis study2013Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 166, nr 1, s. 72-76Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The frequency and prognostic importance of atrial fibrillation (AF) in asymptomatic mild-to-moderate aortic stenosis (AS) has not been well described. Methods: Clinical examination, electrocardiography and echocardiography were obtained in asymptomatic patients with mild-to-moderate AS and preserved left ventricular (LV) systolic function, randomized to simvastatin/ezetimibe combination vs. placebo in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. At inclusion, AF was categorized as episodic or longstanding. Rhythm change was assessed on annual in-study electrocardiograms. Impact of AF on cardiovascular morbidity and mortality was determined by adjusting for biomarkers, clinical- and echocardiographic covariates. Results: Mean follow-up was 4.3 +/- 0.8 years (6,721 patient-years of follow-up). At baseline, episodic AF was present in 87 patients (5.6%), longstanding AF in 55 (3.5%) and no AF in 1,421 (90.9%). Incidence of new-onset AF was 1.2%/year; highest in those with impaired LV function. In multivariable analysis, longstanding AF was compared to no AF at baseline, associated with a 4.1-fold higher risk of heart failure (CI 1.2 to 13.8, p = 0.02) and a 4.8-fold higher risk of non-hemorrhagic stroke (CI 1.7 to 13.6, p = 0.003). Conclusion: Rate of AF is moderate in asymptomatic AS. Longstanding but not episodic AF was, independently predictive of increased risk of heart failure and non-hemorrhagic stroke. New-onset AF was associated with cardiac decompensation. (c) 2011 Elsevier Ireland Ltd. All rights reserved.

  • 293. Greve, Anders M.
    et al.
    Olsen, Michael H.
    Bella, Jonathan N.
    Lonnebakken, Mai T.
    Gerdts, Eva
    Okin, Peter M.
    Palmieri, Vittorio
    Boman, Kurt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nieminen, Markku S.
    Omvik, Per
    Dahlof, Bjorn
    Devereux, Richard B.
    Wachtell, Kristian
    Contrasting Hemodynamic Mechanisms of Losartan- vs. Atenolol-Based Antihypertensive Treatment: A LIFE Study2012Ingår i: American Journal of Hypertension, ISSN 0895-7061, E-ISSN 1941-7225, Vol. 25, nr 9, s. 1017-1023Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND Pharmaceutical differences in central hemodynamics might influence cardiac response to antihypertensive treatment despite similar lowering of brachial blood pressure (BP). METHODS Data from all patients with at least two echocardiographic examinations in the Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) echocardiographic substudy (n = 801); high-risk patients on losartan- vs. atenolol-based antihypertensive therapy. Echocardiography was performed annually for 4 years to measure stroke index (SI), heart rate, cardiac index (CI), conduit artery stiffness assessed as pulse pressure/stroke index (PP/SI) and total peripheral resistance index (TPRI). RESULTS Atenolol- and losartan-based therapy reduced BP similarly (cumulative difference in mean brachial blood pressure 0.3 mm Hg, P = 0.65). After 4 years the cumulative means of SI and heart rate were 1.8 ml/m(2) higher and 5.7 beats/min lower on atenolol-based treatment, respectively (both P < 0.001). This kept CI below baseline in atenolol-treated patients, whereas in the losartan group CI was unchanged from baseline throughout the study. TPRI was decreased more and remained lower in the losartan group (cumulative difference in mean TPRI 287 dynes/sec(-5)/cm/m(2), P < 0.001). These findings partly explained univariate differences in systolic- and diastolic function indices between the two treatments; fully adjusted losartan was only associated with a smaller left atrial diameter (cumulative mean difference 0.07 cm; 95% confidence intervals, -0.13 to -0.01, P = 0.03). CONCLUSIONS Contrasting hemodynamics impacted cardiac response to similar reductions in brachial BP on losartan- vs. atenolol-based therapy. The similar reduction of PP/SI suggests that the antihypertensive regimens used in the LIFE study had comparable effects on arterial stiffness (LIFE study; NCT00338260)

  • 294.
    Grzymala-Lubanski, Bartosz
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Anticoagulation treatment in patients with a mechanical heart valve2016Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background

    Every year about 2,500 patients in Sweden undergo surgery for heart valve disease, primarily in the aortic valve.  In contrast to the mitral valve, which can be repaired in 70% of the cases, the aortic valve is normally replaced by a mechanical or biological prosthesis. A mechanical heart valve (MHV) necessitates lifelong anticoagulation treatment with a vitamin K antagonist, most commonly warfarin, due to the high thrombogenicity of the prosthesis. The quality of the warfarin treatment is crucial in these patients. Compared to other countries, treatment quality in Sweden is very high; nonetheless, there is always room for improvement. One of the ways to achieve this improvement is to implement computerized dosing assistance. Treatment recommendations for anticoagulation intensity are based on few and old studies, making these recommendations uncertain. There is therefore a need for studies designed to establish the appropriate level of anticoagulation therapy.

    Aim

    The aim of these studies was to investigate the efficacy and safety of anticoagulation treatment among patients with mechanical heart valve prostheses in Sweden; to assess whether computerized dosing can increase the treatment quality; to investigate the influence of the treatment quality, measured by Time in Therapeutic Range (TTR) and INR variability, on the risk of complications and, finally, to establish the optimal intensity of anticoagulation treatment in this group of patients.

    Methods

    Data were obtained from AuriculA – a national quality registry established in 2006, which currently includes approximately 50% of all patients treated with oral anticoagulation in Sweden.

    Study II used only data from AuriculA. 769,933 warfarin-dosing suggestions proposed by the dosing algorithm in AuriculA were analysed. Accepted dose suggestions (590,939) were compared with 178,994 manually-changed doses in regard to the resultant INR value, measured as mean error (deviation from target INR) and hit rate (number of INR samples within the target range 2-3).

    In study III, AuriculA was used to identify patients in Sundsvall and Malmö in the period 2008 – 2011 who were receiving warfarin for a mechanical heart valve prosthesis, as well as to retrieve their INR data. Data on background characteristics and bleedings or thromboembolic complications were manually retrieved from medical records by two investigators.  A total of 534 patients with mechanical heart valve prostheses were divided into quartiles based on TTR and were compared regarding the risk of complications.

    For Studies I and IV, data from AuriculA were merged with the Swedish National Patient Register, SWEDEHEART/ Heart surgery, and the Swedish Cause of Death Register, comprising in total 77,423 patients on warfarin with 217,804 treatment years. Every treatment period registered in AuriculA was given an individual identification number. During the study period a patient could have any number of treatment periods. The number of complications in total and in different patient groups within the study population was investigated. Complications were defined by ICD-10 codes. Major bleeding was defined as an event necessitating hospital treatment and given a discharge diagnosis with one of the ICD-10 codes reflecting bleeding, as listed in the Appendix. Bleeding events were divided into intracranial, gastrointestinal and other bleedings. Thromboembolic complications consist of venous events (deep vein thrombosis, pulmonary embolism, venous stroke) or arterial events (stroke, TIA, acute myocardial infarction, peripheral arterial embolism).

    Data were analysed using both simple, descriptive statistical methods and various tests such as Mann-Whitney (or two sample Wilcoxon), T-test, Chi 2 test, ANOVA, multivariate analysis with logistic regression and survival analysis with Cox Regression with proportional hazard assumption.

    Results

    Treatment quality 

    Mean TTR among all patients in Study I was 76.5% whereas patients with mechanical heart valve prostheses had a TTR of 74.5%. The annual incidence of major bleeding or thromboembolic events among all patients was 2.24% and 2.65%, respectively. The incidence of intracranial bleeding was 0.37% per year in the general population and 0.51% among patients with mechanical heart valve prostheses, who also had a higher bleeding rate in total (3.37% per year).

    Both the mean and median errors were smaller (0.44 vs. 0.48 and 0.3 vs. 0.4, respectively) and the hit rate was higher (0.72 vs. 0.67) when the dose suggested by the algorithm was accepted, compared to when it was manually changed.

    TTR 

    In Study III there was no significant difference in the risk of thromboembolism regardless of TTR level. Risk of bleeding in quartiles I and II was more than two times higher than in the quartile with TTR >82.9.

    In Study IV, lower TTR (≤70%) was associated with a significantly higher rate of complications when compared with TTR >70%. Bleeding risk was higher in the group with lower TTR (HR=2.43, CI 2.02-2.89, p<0.001). After dividing patients into TTR quartiles, the rate of complications in total was significantly higher in quartiles I to III compared with quartile IV, which had the highest TTR. Risk of thromboembolism, major bleeding and death was higher in the first and second quartile compared to the quartile with the highest TTR.

    INR variability 

    Higher INR variability above mean (≥0.40) was related to a higher rate of complications compared with lower INR variability (<0.40) as shown in Study IV. Bleeding risk was higher in the group with INR variability ≥0.40 (HR = 2.15, CI 1.75-2.61, p<0.001).

    Comparison of quartile IV, which had the lowest INR variability, with the other three revealed that quartiles I and II, which had the highest INR variability, had significantly worse outcomes for all complications except for thromboembolic events, plus also death in quartile II.

    TTR and INR variability combined 

    High variability and low TTR combined was associated with a higher risk of bleedings (HR 2.50, CI 1.99-3.15), death (3.34, CI 2.62-4-27) and thrombosis (1.55, CI 1.21-1.99) compared to the best group.

    Level of anticoagulation

    Higher warfarin treatment intensity (mean INR 2.8-3.2 vs. 2.2-2.7) was associated with a higher rate of bleedings (HR 1.29, CI 1.06-1.58), death (1.73, CI 1.38-2.16) and complications in total (1.24, CI 1.06-1.41) after adjustment for MHV position, age and comorbidity.

    Conclusion

    Warfarin treatment quality is crucial for patients with mechanical heart valve prostheses. Computerized dosing assistance could help maintain high warfarin treatment quality.

    Well-managed treatment with TTR ≥70% and INR variability below mean <0.40 is associated with a lower risk of serious complications compared with a lower TTR and higher INR variability.

    No benefit of higher warfarin treatment intensity was found for any valve type or position.

  • 295.
    Grzymala-Lubanski, Bartosz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Internal medicine, Sundsvall Hospital.
    Labaf, Ashkan
    Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
    Englund, Erling
    Department of Research and Development, County Council of Västernorrland, Sundsvall Hospital, Sundsvall, Sweden.
    Svensson, Peter J.
    Department for Coagulation Disorders, University of Lund, Malmö, Sweden.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Mechanical heart valve prosthesis and warfarin: treatment quality and prognosis2014Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 133, nr 5, s. 795-798Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction: Every year about 2500 patients in Sweden undergo surgery due to heart valve disease. A mechanical heart valve prosthesis causes risk of thromboembolic stroke or thrombus formation in the valve while anticoagulant treatment increases the risk of bleeding. Treatment quality with warfarin is crucial for patients with mechanical valve prostheses. It has previously been shown that poorly controlled warfarin treatment increases mortality in this patient group. TTR (Time in Therapeutic Range) on warfarin has been shown to affect the risk of complications in atrial fibrillation, but has not been studied in patients with mechanical heart valves. Our aim is to evaluate the impact of TTR on the risk of complications in this patient group. Materials and Methods: A non-randomized, prospective study of 534 adults with mechanical heart valve prostheses from Malmo and Sundsvall registered in the Swedish National Quality Registry Auricula between 01.01.2008 and 31.12.2011. Quartiles regarding individual TTR levels were compared regarding risk of complications. Results: The risk of complications was significantly higher at lower TTR levels for all complications (p = 0.005), bleeding (p = 0.01) and death (p = 0.018) but not for thromboembolism. In multivariate analysis the risk was significantly increased at lower TTR levels for bleeding and all complications but not for death or thromboembolism. Conclusion: Patients with a lower warfarin treatment quality measured by TTR have a higher risk of complications such as severe bleeding or death. A TTR of 83% or higher at the individual level should be obtained for best outcome.

  • 296.
    Grzymala-Lubanski, Bartosz
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Själander, Sara
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Renlund, Henrik
    Svensson, Peter J.
    Själander, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Computer aided warfarin dosing in the Swedish national quality registry AuriculA: algorithmic suggestions are performing better than manually changed doses2013Ingår i: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 131, nr 2, s. 130-134Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Warfarin treatment with a high time in therapeutic range (TTR) is correlated to fewer complications. The TTR in Sweden is generally high but varies partly depending on local expertise and traditions. A dosing algorithm could minimize variations and increase treatment quality. Here we evaluate the performance of a computerized dosing algorithm.

    MATERIALS AND METHODS: 53.779 warfarin treated patients from 125 centers using the Swedish national quality registry AuriculA. If certain criteria are met, the algorithm gives one of seven possible dose suggestions, which can be unchanged, decreased or increased weekly dose by 5, 10 or 15%. The outcome evaluated by the resulting INR value was compared between dose suggestions arising from the algorithm that were accepted and those that were manually changed. There were no randomization, and outcomes were retrospectively analyzed.

    RESULTS: Both the algorithm-based and the manually changed doses had worse outcome if only two instead of three previous INR values were available. The algorithm suggestions were superior to manual dosing regarding percent samples within the target range 2-3 (hit-rate) or deviation from INR 2.5 (mean error). Of the seven possible outcomes from the algorithm, six were significantly superior and one equal to the manually changed doses when three previous INR:s were present.

    CONCLUSIONS: The algorithm-based dosing suggestions show better outcome in most cases. This can make dosing of warfarin easier and more efficient. There are however cases where manual dosing fares better. Here the algorithm will be improved to further enhance its dosing performance in the future.

  • 297.
    Grönlund, Christer
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Albano, Amanda
    Gustavsson, Sandra
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Wiklund, Urban
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lindqvist, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Significant beat-to-beat variability of E/e’ irrespective of respiration2013Ingår i: International cardiovascular forum, ISSN 2409-3424, Vol. 1, nr 2, s. 88-89Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The E/e’ ratio is commonly used in Doppler echocardiographic examinations to estimate the pulmonary capillary wedge pressure. The rationale of using this ratio is to combine left ventricular (LV) filling (E) and relaxation (e’) velocities to indirectly assess left atrial pressure. However, the accuracy of this index has recently been questioned, particularly in patients with controlled heart failure. Likewise, the potential beat-to-beat variability of such measurements remains undetermined. The cardiovascular system is subject to several oscillations with the potential of influencing LV function and its intra-cavitary pressures, hence measurements of its filling and relaxation velocities. The aim of this pilot study was to assess the beat-to-beat variability of the E/e’ ratio in one minute long examination in healthy subjects, and patients with various severity of amyloid heart disease. The results show that despite critical application of the standard echocardiographic recording recommendations, E/e’ beat-to-beat variability was 36 % (22 to 50%) in healthy subjects and 17 % (11-26%) in patients, and where the most severe amyloid heart disease had the least variability. Thus, clinical use of a single or few cardiac beats might not necessarily reflect an accurate ratio between the two velocities, and hence casts doubt over their diagnostic value.

  • 298. Grøntved, Anders
    et al.
    Koivula, Robert W
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Wennberg, Patrik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Østergaard, Lars
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Renström, Frida
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Franks, Paul W
    Umeå universitet, Medicinska fakulteten, Enheten för biobanksforskning. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin. Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Skåne University Hospital Malmö, Malmö, Sweden.
    Bicycling to Work and Primordial Prevention of Cardiovascular Risk: A Cohort Study Among Swedish Men and Women2016Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 5, nr 11, artikel-id e004413Artikel i tidskrift (Refereegranskat)
    Abstract [en]

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

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

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

  • 299.
    Gu, Weigang
    Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
    Thrombectomy versus intravenous thrombolysis for treating acute anterior and posterior circulation stroke2016Ingår i: Cerebrovascular Diseases, ISSN 1015-9770, E-ISSN 1421-9786, Vol. 41, s. 145-145Artikel i tidskrift (Övrigt vetenskapligt)
  • 300. Gueyffier, Francois
    et al.
    Marchant, Ivanny
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Modeling the impact of cardiovascular prevention strategies: toward better information for public health decisions2012Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 30, nr 1, s. 51-52Artikel i tidskrift (Refereegranskat)
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