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  • 851.
    Stewart, Ralph A. H.
    et al.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Benatar, Jocelyne
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Danchin, Nicolas
    Univ Paris 05, Hop Europeen Georges Pompidou, AP HP, INSERM,U970, Paris, France..
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Lönn, Eva
    McMaster Univ, Dept Med, Hamilton, ON, Canada.;McMaster Univ, Populat Hlth Res Inst, Hamilton, ON, Canada..
    Stebbins, Amanda
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Chiswell, Karen
    Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA..
    Vedin, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Watson, David
    GlaxoSmithKline, Metab Pathways & Cardiovasc Therapeut Area, Res Triangle Pk, NC USA..
    White, Harvey D.
    Univ Auckland, Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024, Auckland 1030, New Zealand..
    Dietary patterns and the risk of major adverse cardiovascular events in a global study of high-risk patients with stable coronary heart disease2016In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 37, no 25, p. 1993-2001Article in journal (Refereed)
    Abstract [en]

    Objectives To determine whether dietary pattern assessed by a simple self-administered food frequency questionnaire is associated with major adverse cardiovascular events (MACE) in high-risk patients with stable coronary artery disease. Background A Mediterranean dietary pattern has been associated with lower cardiovascular (CV) mortality. It is less certain whether foods common in western diets are associated with CV risk. Methods At baseline, 15 482 (97.8%) patients (mean age 67 +/- 9 years) with stable coronary heart disease from 39 countries who participated in the Stabilisation of atherosclerotic plaque by initiation of darapladib therapy (STABILITY) trial completed a life style questionnaire which included questions on common foods. A Mediterranean diet score (MDS) was calculated for increasing consumption of whole grains, fruits, vegetables, legumes, fish, and alcohol, and for less meat, and a 'Western diet score' (WDS) for increasing consumption of refined grains, sweets and deserts, sugared drinks, and deep fried foods. A multi-variable Cox proportional hazards models assessed associations between MDS or WDS and MACE, defined as CV death, non-fatal myocardial infarction, or non-fatal stroke. Results After a median follow-up of 3.7 years MACE occurred in 7.3% of 2885 subjects with an MDS >= 15, 10.5% of 4018 subjects with an MDS of 13-14, and 10.8% of 8579 subjects with an MDS <= 12. A one unit increase in MDS > 12 was associated with lower MACE after adjusting for all covariates (+1 category HR 0.95, 95% CI 0.91, 0.98, P = 0.002). There was no association between WDS (adjusted model +1 category HR 0.99, 95% CI 0.97, 1.01) and MACE. Conclusion Greater consumption of healthy foods may be more important for secondary prevention of coronary artery disease than avoidance of less healthy foods typical of Western diets.

  • 852. Stewart, Ralph Alan Huston
    et al.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Psychology in Healthcare.
    Armstrong, Paul
    Aylward, Philip
    Cannon, Christopher
    Koenig, Wolfgang
    Lopez-Sendon, Jose
    Mohler, Emile
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Krug-Gourley, Susan
    Siddique, Saulat
    Steg, Philippe
    White, Harvey
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Self-Reported General Health And Outcomes In Patients With Stable Coronary Artery Disease: Experiences From The Global Stability Trial2016In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 67, no 13, p. 2113-2113Article in journal (Other academic)
  • 853.
    Stojkovic, Stefan
    et al.
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Thulin, Åsa
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Hell, Lena
    Med Univ Vienna, Dept Internal Med 1, Clin Div Hematol & Hemostaseol, Vienna, Austria..
    Thaler, Barbara
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Rauscher, Sabine
    Med Univ Vienna, Core Facil, Vienna, Austria..
    Baumgartner, Johanna
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria..
    Groeger, Marion
    Med Univ Vienna, Core Facil, Vienna, Austria..
    Ay, Cihan
    Med Univ Vienna, Dept Internal Med 1, Clin Div Hematol & Hemostaseol, Vienna, Austria..
    Demyanets, Svitlana
    Med Univ Vienna, Dept Lab Med, Vienna, Austria..
    Neumayer, Christoph
    Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Huk, Ihor
    Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Spittler, Andreas
    Med Univ Vienna, Core Facil, Vienna, Austria.;Med Univ Vienna, Dept Surg, Div Vasc Surg, Vienna, Austria..
    Huber, Kurt
    Wilhelminen Hosp, Med Dept Cardiol & Emergency Med 3, Vienna, Austria.;Sigmund FReud Private Univ, Med Sch, Vienna, Austria..
    Wojta, Johann
    Med Univ Vienna, Dept Internal Med 2, Vienna, Austria.;Med Univ Vienna, Core Facil, Vienna, Austria.;Sigmund FReud Private Univ, Med Sch, Vienna, Austria.;Ludwig Boltzmann Cluster Cardiovascular Res, Vienna, Austria..
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Åberg, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab.
    IL-33 stimulates the release of procoagulant microvesicles from human monocytes and differentially increases tissue factor in human monocyte subsets2017In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 117, no 7, p. 1379-1390Article in journal (Refereed)
    Abstract [en]

    Monocytes and monocyte-derived microvesicles (MVs) are the main source of circulating tissue factor (TF). Increased monocyte TF expression and increased circulating levels of procoagulant MVs contribute to the formation of a prothrombotic state in patients with cardiovascular disease. Interleukin (IL)-33 is a pro-inflammatory cytokine involved in atherosclerosis and other inflammatory diseases, but its role in regulating thrombosis is still unclear. The aim of the present study was to investigate the effects of IL-33 on the procoagulant properties of human monocytes and monocyte-derived MVs. IL-33 induced a time- and concentration-dependent increase of monocyte TF mRNA and protein levels via binding to the ST2-receptor and activation of the NF-kappa B-pathway. The IL-33 treated monocytes also released CD14+TF+ MVs and IL-33 was found to increase the TF activity of both the isolated monocytes and monocyte-derived MVs. The monocytes were classified into subsets according to their CD14 and CD16 expression. Intermediate monocytes (IM) showed the highest ST2 receptor expression, followed by non-classical monocytes (NCM), and classical monocytes (CM). IL-33 induced a significant increase of TF only in the IM (p<0.01), with a tendency in NCM (p=0.06), but no increase was observed in CM. Finally, plasma levels of IL-33 were positively correlated with CD14+TF+ MVs in patients undergoing carotid endarterectomy (r=0.480; p=0.032; n=20). We hereby provide novel evidence that the proinflammatory cytokine IL-33 induces differential TF expression and activity in monocyte subsets, as well as the release of procoagulant MVs. In this manner, IL-33 may contribute to the formation of a prothrombotic state characteristic for cardiovascular disease.

  • 854.
    Stolfo, Davide
    et al.
    Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden;Azienda Sanit Univ Integrata Trieste, Cardiovasc Dept, Div Cardiol, Trieste, Italy.
    Uijl, Alicia
    Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden;Univ Utrecht, Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
    Vedin, Ola
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Boehringer Ingelheim GmbH & Co KG, Clin Dev, Stockholm, Sweden.
    Stromberg, Anna
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Faxen, Ulrika Ljung
    Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden;Karolinska Univ Hosp, Perioperat Med & Intens Care, Stockholm, Sweden.
    Rosano, Giuseppe M. G.
    IRCCS San Raffaele Pisana Rome, Dept Med Sci, Ctr Clin & Basic Res, Rome, Italy.
    Sinagra, Gianfranco
    Azienda Sanit Univ Integrata Trieste, Cardiovasc Dept, Div Cardiol, Trieste, Italy.
    Dahlstrom, Ulf
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Savarese, Gianluigi
    Karolinska Inst, Dept Med, Div Cardiol, Stockholm, Sweden.
    Sex-Based Differences in Heart Failure Across the Ejection Fraction Spectrum Phenotyping, and Prognostic and Therapeutic Implications2019In: JACC. Heart failure, ISSN 2213-1779, E-ISSN 2213-1787, Vol. 7, no 6, p. 505-515Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum. BACKGROUND Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials. METHODS In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across mates and females. RESULTS Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly tower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF. CONCLUSIONS Mates and females with HF showed different characteristics across the EF spectrum. Mates reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generatizabitity.

  • 855. Storey, R. F.
    et al.
    Ardissino, D.
    Vignali, L.
    Cairns, R.
    Becker, R. C.
    Cannon, C. P.
    Himmelmann, A.
    Husted, S.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ischaemic events following planned discontinuation of study treatment with ticagrelor or clopidogrel in the PLATO study2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 826-826Article in journal (Other academic)
  • 856.
    Storey, Robert F.
    et al.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Ardissino, Diego
    Univ Parma, Div Cardiol, Azienda Osped, Parma, Italy..
    Vignali, Luigi
    Univ Parma, Div Cardiol, Azienda Osped, Parma, Italy..
    Cairns, Richard
    Worldwide Clin Trials, Nottingham, England..
    Becker, Richard C.
    Div Cardiovasc Hlth & Dis, Cincinnati, OH USA.;Heart Lung & Vasc Inst, Cincinnati, OH USA.;Univ Cincinnati, Coll Med, Cincinnati, OH USA..
    Cannon, Christopher P.
    Brigham & Womens Hosp, Div Cardiovasc, Baim Inst Clin Res, 75 Francis St, Boston, MA 02115 USA..
    Mahaffey, Kenneth W.
    Stanford Univ, Dept Med, Sch Med, Stanford Ctr Clin Res SCCR, Stanford, CA 94305 USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Katus, Hugo A.
    Univ Klinikum Heidelberg, Med Klin, Heidelberg, Germany..
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ischaemic Events and Stent Thrombosis following Planned Discontinuation of Study Treatment with Ticagrelor or Clopidogrel in the PLATO Study2018In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 118, no 2, p. 427-429Article in journal (Refereed)
  • 857. Storey, Robert F
    et al.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ycas, Joseph
    Husted, Steen E
    Cannon, Christopher P
    Becker, Richard C
    Steg, Ph Gabriel
    Åsenblad, Nils
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study2014In: Platelets, ISSN 0953-7104, E-ISSN 1369-1635, Vol. 25, no 7, p. 517-525Article in journal (Refereed)
    Abstract [en]

    In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.

  • 858.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Boman, K.
    Umea Univ, Res Unit, Skelleftea Cty Hosp, Med & Geriatr,Dept Publ Hlth, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Skelleftea Cty Hosp, Med & Geriatr,Dept Publ Hlth, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Ctr Heart, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    A description of unselected patients with heart failure: a swedish population-based study2016In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, p. 195-195Article in journal (Other academic)
  • 859.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Boman, K.
    Umea Univ, Res Unit, Med & Geriatr, Skelleftea Cty Hosp,Dept Publ Hlth, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Res Unit, Med & Geriatr, Skelleftea Cty Hosp,Dept Publ Hlth, Umea, Sweden..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Lahoz, R.
    Novartis Pharma AG, Basel, Switzerland..
    Corda, S.
    Novartis Pharma AG, Basel, Switzerland..
    Wintzell, V.
    IMS Hlth Sweden, Stockholm, Sweden..
    Linder, R.
    IMS Hlth Sweden, Stockholm, Sweden..
    Gondos, A.
    IMS Hlth Germany, Berlin, Germany..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Recent trends in diagnostic work-up among unselected patients newly diagnosed with heart failure: a Swedish population-based study2016In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 18, p. 54-55Article in journal (Other academic)
  • 860.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Boman, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Olofsson, M.
    Umea Univ, Dept Publ Hlth & Clin Med, Res Unit, Med, Umea, Sweden..
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Bergman, G. J.
    QuintilesIMS, Solna, Sweden..
    Tornblom, M.
    QuintilesIMS, Solna, Sweden..
    Wintzell, V.
    QuintilesIMS, Solna, Sweden..
    Wirta, S. Bruce
    Novartis Sweden AB, Stockholm, Sweden..
    Proenca, C. C.
    Wellmera AG, Basel, Switzerland..
    Schlienger, R.
    Novartis Pharma AG, Basel, Switzerland..
    Lindmark, K.
    Umea Univ, Dept Publ Hlth & Clin Med, Ctr Heart, Umea, Sweden..
    Management of patients with heart failure with preserved versus reduced ejection fraction: a retrospective population-based cohort study in Sweden2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, p. 54-55Article in journal (Other academic)
  • 861.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stern, Lee
    Linder, Ragnar
    Sherman, Steve
    Parikh, Rohan
    Ariely, Rinat
    Deschaseaux, Celine
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    The burden of preserved ejection fraction heart failure in a real-world Swedish patient population2014In: Journal of Medical Economics, ISSN 1369-6998, E-ISSN 1941-837X, Vol. 17, no 1, p. 43-51Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To evaluate resource use and associated costs in patients with a diagnosis of heart failure with preserved ejection fraction (HF-PEF) in Sweden.

    METHODS: This retrospective study identified real-world patients with an ICD-10 diagnosis code for heart failure (I50) for the period between July 1, 2005 and December 31, 2006 from electronic medical records of primary care centers in Uppsala County Council, and in the Swedish patient registry data. Patients were categorized as having HF-PEF (left ventricle ejection fraction [LVEF] > 50%) during the index period. The study assessed medication utilization, outpatient visits, hospitalizations, and associated healthcare costs, as well as the incidence rates and time to all-cause and heart failure mortality following the index period.

    RESULTS: The study included 137 HF-PEF patients with a mean age of 77.1 (SD = 9.1) years. Over 50% of HF-PEF patients were female and hypertensive. Nearly all patients received ≥ 1 medication post-index. Patients had an average of 1.5 heart failure related hospitalizations per follow-up year. The average annual per patient cost for the management of a HF-PEF patient was found in Sweden to be Swedish Krona (SEK) 108,246 (EURO [EUR] 11,344). Hospitalizations contributed to more than 80% of the total cost. All-cause mortality over the 18-month study period was 25.5%, and more than 50% of these deaths occurred within 1 year of index.

    LIMITATIONS: Due to the limitations of registry data, it is not possible to confirm the HF diagnosis, and therefore the accuracy of registry records must be assumed. Other factors such as short follow-up time, the study-mandated LVEF assessment, and a lack of drug duration data may also have an impact on the study results.

    CONCLUSIONS: All-cause mortality was high in the HF-PEF population, with more than half of patients dying within 1 year of study follow-up. Study results also indicate that 60% of HF-PEF patients have ≥ 1 hospitalization during follow-up. Hospitalizations, especially heart failure related admissions, represent a substantial proportion of the total healthcare burden of patients with HF-PEF in Sweden.

  • 862.
    Stålhammar, Jan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Stern, Lee
    Linder, Ragnar
    Sherman, Steven
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Parikh, Rohan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
    Ariely, Rinat
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Resource utilization and cost of heart failure associated with reduced ejection fraction in Swedish patients2012In: Journal of medical economics, ISSN 1941-837X, Vol. 15, no 5, p. 938-946Article in journal (Refereed)
    Abstract [en]

    AIM:

    The purpose of this study was to assess healthcare utilization and costs for heart failure patients with reduced ejection fraction (HF-REF) in Sweden.

    METHODS AND RESULTS:

    This was a retrospective, population-based cohort study of patients diagnosed with HF-REF during a period of 18 months at 31 primary care centers in Uppsala County, Sweden. Data was obtained from computerized records from these centers, the Swedish Patient Registry, the Swedish Prescription Registry, the Cause of Death Registry, and a local echocardiography registry maintained by the Department of Physiology, Uppsala University Hospital. Main outcome measures were cardiovascular and heart-failure-related hospitalizations, outpatient visits, medication utilization, mortality (all-cause, cardiovascular, and heart-failure), and healthcare costs for HF-REF patients. During the index period, 252 heart failure patients had a left ventricular ejection fraction measurement ≤ 40% and were categorized as having HF-REF. More than half of the patients had ≥ 1 cardiovascular or heart failure-related hospitalization. On average, patients had >2 such hospitalizations annually. They also averaged ∼1 cardiovascular or heart-failure-related outpatient visit per year. All-cause mortality was high: 15.9% patients died within 1 year after the index date. The mean annual cost per patient for heart-failure-related hospitalizations was SEK 72,613 (EUR 7610). In contrast, annual prescription costs were low, on average 3% of total cost (SEK 3503, EUR 367 per patient)

    LIMITATIONS:

    The main limitations of this study include a short follow-up time and small sample size. Also, certain data were missing, such as echocardiograms (available for only 28% of patients), and information on patients' New York Heart Association (NYHA) functional class, validity period for prescriptions or the units of medication prescribed, and medication dosing. Furthermore, the overall mortality could have been under-estimated, as only the primary cause of death was included in the analysis.

    CONCLUSIONS:

    The main burden associated with HF-REF is related to hospitalizations for heart-failure events. Effective treatment options that decrease hospitalization rates could reduce patients' suffering and potentially offer considerable cost savings.

  • 863.
    Sumaya, Wael
    et al.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Ajjan, Ramzi A.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England..
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 13, p. 1078-1085Article in journal (Other academic)
    Abstract [en]

    Aims To determine whether fibrin clot properties are associated with clinical outcomes following acute coronary syndrome (ACS).

    Methods and results Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma clot lysis time and maximum turbidity (a measure of clot density). One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After adjusting for CV risk factors, each 50% increase in lysis time was associated with CV death/spontaneous MI [HR 1.17, 95% confidence interval (CI) 1.05-1.31; P < 0.01] and CV death alone (HR 1.36, 95% CI 1.17-1.59; P < 0.001). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death (HR 1.24, 95% CI 1.03-1.50; P = 0.024). After adjustment for other prognostic biomarkers (leukocyte count, high-sensitivity C-reactive protein, high-sensitivity troponin T, cystatin C, N-terminal pro B-type natriuretic peptide, and growth differentiation factor15), the association with CV death remained significant for lysis time (HR 1.2, 95% CI 1.01-1.42; P = 0.042) but not for maximum turbidity. These associations were consistent regardless of randomized antiplatelet treatment (all interaction P > 0.05). Neither lysis time nor maximum turbidity was associated with major bleeding events.

    Conclusion Fibrin clots that are resistant to lysis independently predict adverse outcome in ACS patients. Novel therapies targeting fibrin clot properties might be a new avenue for improving prognosis in patients with ACS.

  • 864.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Arima, Hisatomi
    Jackson, Rod
    Turnbull, Fiona
    Rahimi, Kazem
    Chalmers, John
    Woodward, Mark
    Neal, Bruce
    Effects of Blood Pressure Reduction in Mild Hypertension: A Systematic Review and Meta-analysis2015In: Annals of Internal Medicine, ISSN 0003-4819, E-ISSN 1539-3704, Vol. 162, no 3, p. 184-191Article in journal (Refereed)
    Abstract [en]

    Background: Effects of blood pressure reduction in persons with grade 1 hypertension are unclear. Purpose: To investigate whether pharmacologic blood pressure reduction prevents cardiovascular events and deaths in persons with grade 1 hypertension. Data Sources: Trials included in the BPLTTC (Blood Pressure Lowering Treatment Trialists' Collaboration) and trials identified from a previous review and electronic database searches. Study Selection: Patients without cardiovascular disease with blood pressures in the grade 1 hypertension range (140 to 159/90 to 99 mm Hg) who were randomly assigned to an active (antihypertensive drug or more intensive regimen) or control (placebo or less intensive regimen) blood pressure-lowering regimen. Data Extraction: Individual-patient data from BPLTTC trials and aggregate data from other trials were extracted. Risk of bias was assessed for all trials. Data Synthesis: Individual-patient data involved 10 comparisons from trials where most patients had diabetes, and aggregate data involved 3 comparisons from trials of patients without diabetes. The average blood pressure reduction was about 3.6/2.4 mm Hg. Over 5 years, odds ratios were 0.86 (95% CI, 0.74 to 1.01) for total cardiovascular events, 0.72 (CI, 0.55 to 0.94) for strokes, 0.91 (CI, 0.74 to 1.12) for coronary events, 0.80 (CI, 0.57 to 1.12) for heart failure, 0.75 (CI, 0.57 to 0.98) for cardiovascular deaths, and 0.78 (CI, 0.67 to 0.92) for total deaths. Results were similar in secondary analyses. Withdrawal from treatment due to adverse effects was more common in the active groups. Limitation: Blood pressure reductions and numbers of events were small. Conclusion: Blood pressure-lowering therapy is likely to prevent stroke and death in patients with uncomplicated grade 1 hypertension.

  • 865.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Arima, Hisatomi
    Woodward, Mark
    Jackson, Rod
    Karmali, Kunal
    Lloyd-Jones, Donald
    Baigent, Colin
    Emberson, Jonathan
    Rahimi, Kazem
    MacMahon, Stephen
    Patel, Anushka
    Perkovic, Vlado
    Turnbull, Fiona
    Neal, Bruce
    Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data2014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, no 9943, p. 591-598Article in journal (Refereed)
    Abstract [en]

    Background

    We aimed to investigate whether the benefits of blood pressure-lowering drugs are proportional to baseline cardiovascular risk, to establish whether absolute risk could be used to inform treatment decisions for blood pressure-lowering therapy, as is recommended for lipid-lowering therapy.

    Methods

    This meta-analysis included individual participant data from trials that randomly assigned patients to either blood pressure-lowering drugs or placebo, or to more intensive or less intensive blood pressure-lowering regimens. The primary outcome was total major cardiovascular events, consisting of stroke, heart attack, heart failure, or cardiovascular death. Participants were separated into four categories of baseline 5-year major cardiovascular risk using a risk prediction equation developed from the placebo groups of the included trials (<11%, 11-15%, 15-21%, >21%).

    Findings

    11 trials and 26 randomised groups met the inclusion criteria, and included 67 475 individuals, of whom 51 917 had available data for the calculation of the risk equations. 4167 (8%) had a cardiovascular event during a median of 4.0 years (IQR 3.4-4.4) of follow-up. The mean estimated baseline levels of 5-year cardiovascular risk for each of the four risk groups were 6 0% (SD 2.0), 12.1% (1.5), 17.7% (1.7), and 26.8% (5.4). In each consecutive higher risk group, blood pressure-lowering treatment reduced the risk of cardiovascular events relatively by 18% (95% CI 7-27), 15% (4-25), 13% (2-22), and 15% (5-24), respectively (p=0.30 for trend). However, in absolute terms, treating 1000 patients in each group with blood pressure-lowering treatment for 5 years would prevent 14 (95% CI 8-21), 20 (8-31), 24 (8-40), and 38 (16-61) cardiovascular events, respectively (p=0.04 for trend). Interpretation Lowering blood pressure provides similar relative protection at all levels of baseline cardiovascular risk, but progressively greater absolute risk reductions as baseline risk increases. These results support the use of predicted baseline cardiovascular disease risk equations to inform blood pressure-lowering treatment decisions.

  • 866.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bruze, Gustaf
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Ottosson, Johan
    Orebro Univ, Fac Med & Hlth, Dept Surg, Orebro, Sweden..
    Marcus, Claude
    Karolinska Inst, Dept Clin Sci Intervent & Technol, Stockholm, Sweden..
    Naslund, Ingmar
    Orebro Univ, Fac Med & Hlth, Dept Surg, Orebro, Sweden..
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Weight Loss and Heart Failure A Nationwide Study of Gastric Bypass Surgery Versus Intensive Lifestyle Treatment2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 135, no 17, p. 1577-+Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Associations of obesity with incidence of heart failure have been observed, but the causality is uncertain. We hypothesized that gastric bypass surgery leads to a lower incidence of heart failure compared with intensive lifestyle modification in obese people. METHODS: We included obese people without previous heart failure from a Swedish nationwide registry of people treated with a structured intensive lifestyle program and the Scandinavian Obesity Surgery Registry. All analyses used inverse probability weights based on baseline body mass index and a propensity score estimated from baseline variables. Treatment groups were well balanced in terms of weight, body mass index, and most potential confounders. Associations of treatment with heart failure incidence, as defined in the National Patient Register, were analyzed with Cox regression. RESULTS: The 25 804 gastric bypass surgery patients had on average lost 18.8 kg more weight after 1 year and 22.6 kg more after 2 years than the 13 701 lifestyle modification patients. During a median of 4.1 years, surgery patients had lower heart failure incidence than lifestyle modification patients (hazard ratio, 0.54; 95% confidence interval, 0.36-0.82). A 10-kg achieved weight loss after 1 year was related to a hazard ratio for heart failure of 0.77 (95% confidence interval, 0.60-0.97) in both treatment groups combined. Results were robust in sensitivity analyses. CONCLUSIONS: Gastric bypass surgery was associated with approximately one half the incidence of heart failure compared with intensive lifestyle modification in this study of 2 large nationwide registries. We also observed a graded association between increasing weight loss and decreasing risk of heart failure.

  • 867.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hedberg, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Upper Abdominal Surgery.
    Thuresson, Marcus
    Statisticon AB, Uppsala, Sweden..
    Aarskog, Pernilla
    AstraZeneca Nord Balt, Sodertalje, Sweden..
    Johannesen, Kasper Munk
    Linkoping Univ, Linkoping, Sweden..
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Low-Dose Aspirin Discontinuation and Risk of Cardiovascular Events: A Swedish Nationwide, Population-Based Cohort Study2017In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 136, no 13, p. 1183-1192Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: There are increasing concerns about risks associated with aspirin discontinuation in the absence of major surgery or bleeding. We investigated whether long-term low-dose aspirin discontinuation and treatment gaps increase the risk of cardiovascular events.

    METHODS: We performed a cohort study of 601 527 users of low-dose aspirin for primary or secondary prevention in the Swedish prescription register between 2005 and 2009 who were >40 years of age, were free from previous cancer, and had >= 80% adherence during the first observed year of treatment. Cardiovascular events were identified with the Swedish inpatient and cause-of-death registers. The first 3 months after a major bleeding or surgical procedure were excluded from the time at risk.

    RESULTS: During a median of 3.0 years of follow-up, 62 690 cardiovascular events occurred. Patients who discontinued aspirin had a higher rate of cardiovascular events than those who continued (multivariable-adjusted hazard ratio, 1.37; 95% confidence interval, 1.34-1.41), corresponding to an additional cardiovascular event observed per year in 1 of every 74 patients who discontinue aspirin. The risk increased shortly after discontinuation and did not appear to diminish over time.

    CONCLUSIONS: In long-term users, discontinuation of low-dose aspirin in the absence of major surgery or bleeding was associated with a >30% increased risk of cardiovascular events. Adherence to low-dose aspirin treatment in the absence of major surgery or bleeding is likely an important treatment goal.

  • 868.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Jackson, Rod
    Woodward, Mark
    Baigent, Colin
    Neal, Bruce
    Blood pressure lowering and cardiovascular risk reply2014In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 384, no 9956, p. 1746-1747Article in journal (Other academic)
  • 869.
    Sundström, Johan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Nowrouzi, Shamim
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lytsy, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Social Medicine.
    Marttala, Kerstin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ekman, Inger
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Öhagen, Patrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Östlund, Ollie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    The Precision HYpertenSIon Care (PHYSIC) study: a double-blind, randomized, repeated cross-over study2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 51-58Article in journal (Refereed)
    Abstract [en]

    High blood pressure is the leading risk factor for premature deaths and a major cost to societies worldwide. Effective blood pressure-lowering drugs are available, but patient adherence to them is low, likely partly due to side effects. To identify patient-specific differences in treatment effects, a repeated cross-over design, where the same treatment contrasts are repeated within each patient, is needed. Such designs have been surprisingly rarely used, given the current focus on precision medicine. The Precision HYpertenSIon Care (PHYSIC) study aims to investigate if there is a consistent between-person variation in blood pressure response to the common blood pressure-lowering drug classes of a clinically relevant magnitude, given the within-person variation in blood pressure. The study will also investigate the between-person variation in side effects of the drugs. In a double-blind, randomized, repeated cross-over trial, 300 patients with mild hypertension will be treated with four blood pressure-lowering drugs (candesartan, lisinopril, amlodipine, and hydrochlorothiazide) in monotherapy, with two of the drugs repeated for each patient. If the study indicates that there is a potential for precision hypertension care, the most promising predictors of blood pressure and side effect response to the drugs will be explored, as will the potential for development of a biomarker panel to rank the suitability of blood pressure-lowering drug classes for individual patients in terms of anticipated blood pressure effects and side effects, with the ultimate goal to maximize adherence. The study follows a protocol pre-registered at ClinicalTrials.gov with the identifier NCT02774460.

  • 870.
    Svedberg, Niclas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Falun Cent Hosp, Dept Cardiol, S-79182 Falun, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hållmarker, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Mora Hosp, Dept Med, Mora, Sweden.
    Hambraeus, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Falun Cent Hosp, Dept Cardiol, S-79182 Falun, Sweden.
    Andersen, Kasper
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Long-Term Incidence of Atrial Fibrillation and Stroke Among Cross-Country Skiers Cohort Study of Endurance-Trained Male and Female Athletes2019In: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 140, no 11, p. 910-920Article in journal (Refereed)
    Abstract [en]

    Background: Studies have revealed a higher incidence of atrial fibrillation among well-trained athletes. We aim to investigate associations of endurance training with incidence of atrial fibrillation and stroke and to establish potential sex differences of such associations in a cohort of endurance trained athletes. Methods: All Swedish skiers (208 654) completing 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989-2011) and a matched sample (n=527 448) of nonskiers were followed until first event of atrial fibrillation or stroke. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of atrial fibrillation and stroke. Results: Female skiers in Vasaloppet had a lower incidence of atrial fibrillation than did female nonskiers (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), independent of finishing time and number of races. Male skiers had a similar incidence to that of nonskiers (HR, 0.98; 95% CI, 0.93-1.03). Skiers with the highest number of races or fastest finishing times had the highest incidence. Skiers of either sex had a lower incidence of stroke than did nonskiers (HR, 0.64; 95% CI, 0.60-0.67), independent of the number of races and finishing time. Skiers with atrial fibrillation had higher incidence of stroke than did skiers and nonskiers without atrial fibrillation (men: HR, 2.28; 95% CI, 1.93-2.70; women: HR, 3.51; 95% CI, 2.17-5.68; skiers with atrial fibrillation vs. skiers without atrial fibrillation). After diagnosis of atrial fibrillation, skiers with atrial fibrillation had a lower incidence of stroke (HR, 0.73; 95% CI, 0.50-0.91) and lower mortality compared with nonskiers with atrial fibrillation (HR, 0.57; 95% CI, 0.49-0.65). Conclusions: Female skiers in Vasaloppet had lower incidence of atrial fibrillation and stroke. Male skiers had similar incidence of atrial fibrillation and lower risk of stroke. Men with higher number of races and faster finishing times had the highest incidence of atrial fibrillation. After diagnosis of atrial fibrillation, skiers had lower incidence of stroke and death than did nonskiers with atrial fibrillation. This indicates that although on an individual level atrial fibrillation in well-trained individuals is associated with higher incidence of stroke, on population level, risk of stroke is low and that exercise should not be avoided.

  • 871.
    Svennberg, Emma
    et al.
    Danderyds Univ Hosp, Dept Clin Sci, Cardiol Unit, Karolinska Inst, Hjartkliniken Plan 2,Hus 18, SE-18288 Stockholm, Sweden..
    Henriksson, Peter
    Danderyds Univ Hosp, Dept Clin Sci, Cardiol Unit, Karolinska Inst, Hjartkliniken Plan 2,Hus 18, SE-18288 Stockholm, Sweden..
    Engdahl, Johan
    Danderyds Univ Hosp, Dept Clin Sci, Cardiol Unit, Karolinska Inst, Hjartkliniken Plan 2,Hus 18, SE-18288 Stockholm, Sweden..
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Al-Khalili, Faris
    Danderyds Univ Hosp, Dept Clin Sci, Cardiol Unit, Karolinska Inst, Hjartkliniken Plan 2,Hus 18, SE-18288 Stockholm, Sweden..
    Friberg, Leif
    Danderyds Univ Hosp, Dept Clin Sci, Cardiol Unit, Karolinska Inst, Hjartkliniken Plan 2,Hus 18, SE-18288 Stockholm, Sweden..
    Frykman, Viveka
    Danderyds Univ Hosp, Dept Clin Sci, Cardiol Unit, Karolinska Inst, Hjartkliniken Plan 2,Hus 18, SE-18288 Stockholm, Sweden..
    N-terminal pro B-type natriuretic peptide in systematic screening for atrial fibrillation2017In: Heart, ISSN 1355-6037, E-ISSN 1468-201X, Vol. 103, no 16, p. 1271-1277Article in journal (Refereed)
    Abstract [en]

    Objective Screening for atrial fibrillation (AF) in individuals aged 65 and above is recommended by the European Society of Cardiology. Increased levels of the biomarker N-terminal pro B-type natriuretic peptide (NT-proBNP) has in cohort studies been associated with incident AF. The aim of this study was to assess whether NT-proBNP could be useful for AF detection in systematic screening.

    Methods The Strokestop study entailed 7173 Swedish residents aged 75/76 that were screened for AF using twice daily intermittent ECG recordings during 2 weeks. In a substudy of 886 participants, the last 815 consecutive participants and 71 individuals with newly detected AF, levels of NT-proBNP were determined.

    Results Participants with newly detected AF (n=96) had a median NT-proBNP of 330 ng/L (IQR 121; 634). In individuals without AF (n=742), median NT-proBNP was 171 ng/L (IQR 95; 283), p<0.001. The CHA2DS2-VASc parameters did not differ significantly between individuals with newly detected AF and without AF nor between newly detected AF in the NT-proBNP cohort compared with the cohort where NT-proBNP was not assessed. Using an NT-proBNP cut-off of >= 125 ng/L in a non-acute setting yielded a negative predictive value of 92%, meaning that 35% fewer participants would need to be screened when applied to systematic AF screening. Adding weight to NT-proBNP further reduced participants needed to be screened with a preserved sensitivity.

    Conclusions NT-proBNP was increased in individuals with newly detected AF. Prospective studies could clarify if NT-proBNP can be used to correctly select individuals that benefit most from AF screening.

  • 872.
    Svennberg, Emma
    et al.
    Danderyds Univ Hosp, Karolinska Inst, Dept Clin Sci, Cardiol Unit, Stockholm, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Eggers, Kai M.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Venge, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics. Med Prod Agcy, Sci Support, Uppsala, Sweden.
    Rosenqvist, Mårten
    Danderyds Univ Hosp, Karolinska Inst, Dept Clin Sci, Cardiol Unit, Stockholm, Sweden.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    NT-proBNP is a powerful predictor for incident atrial fibrillation: Validation of a multimarker approach2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 223, p. 74-81Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Biomarkers may be of value to identify individuals at risk of developing atrial fibrillation (AF). Using a multimarker approach, this study investigated if the biomarkers; NT-proBNP, high-sensitivity cardiac troponin (hs-cTn), growth differentiation factor-15 (GDF-15), cystatin C and high-sensitivity C-reactive protein (CRP) are independent predictors for incident AF.

    METHODS: Blood samples were collected from 883 individuals in the Uppsala Longitudinal Study of Adult Men (ULSAM) and 978 individuals in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Participants were followed for 10-13years with n=113 incident AF cases in ULSAM and n=148 in PIVUS. The associations between biomarkers and incident AF were analysed in Cox proportional hazards regression models.

    RESULTS: The hazard ratio (HR) for incident AF was significant for all five biomarkers in unadjusted analyses in both cohorts. Only NT-proBNP remained significant when adjusting for cardiovascular risk factors and the other biomarkers (HR (1SD) 2.05 (1.62-2.59) (ULSAM) and 1.56 (1.30-1.86) (PIVUS), both p<0.001). The C-index improved from 0.64 to 0.69 in ULSAM and from 0.62 to 0.68 in PIVUS, by adding NT-proBNP to cardiovascular risk factors (both p<0.001). The C-index of the CHARGE-AF risk score increased from 0.62 to 0.68 (ULSAM) and 0.60 to 0.66 (PIVUS) by addition of NT-proBNP (p<0.001).

    CONCLUSIONS: Using a multimarker approach NT-proBNP was the strongest predictor of incident AF in two cohorts, and improved risk prediction when added to traditional risk factors. NT-proBNP significantly improved the predictive ability of the novel CHARGE-AF risk score, although the predictive value remained modest.

  • 873. Szarek, Michael
    et al.
    Hagström, Emil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Zobouyan, Isabelle
    Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events The ODYSSEY OUTCOMES Trial2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 73, no 4, p. 387-396Article in journal (Refereed)
    Abstract [en]

    BACKGROUND The ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial compared alirocumab with placebo, added to high-intensity or maximum-tolerated statin treatment, after acute coronary syndrome (ACS) in 18,924 patients. Alirocumab reduced the first occurrence of the primary composite endpoint and was associated with fewer all-cause deaths. OBJECTIVES This pre-specified analysis determined the extent to which alirocumab reduced total (first and subsequent) nonfatal cardiovascular events and all-cause deaths in ODYSSEY OUTCOMES. METHODS Hazard functions for total nonfatal cardiovascular events (myocardial infarction, stroke, ischemia-driven coronary revascularization, and hospitalization for unstable angina or heart failure) and death were jointly estimated, linked by a shared frailty accounting for patient risk heterogeneity and correlated within-patient nonfatal events. An association parameter also quantified the strength of the linkage between risk of nonfatal events and death. The model provides accurate relative estimates of nonfatal event risk if nonfatal events are associated with increased risk for death. RESULTS With 3,064 first and 5,425 total events, 190 fewer first and 385 fewer total nonfatal cardiovascular events or deaths were observed with alirocumab compared with placebo. Alirocumab reduced total nonfatal cardiovascular events (hazard ratio: 0.87; 95% confidence interval: 0.82 to 0.93) and death (hazard ratio: 0.83; 95% confidence interval: 0.71 to 0.97) in the presence of a strong association between nonfatal and fatal event risk. CONCLUSIONS In patients with ACS, the total number of nonfatal cardiovascular events and deaths prevented with alirocumab was twice the number of first events prevented. Consequently, total event reduction is a more comprehensive metric to capture the totality of alirocumab clinical efficacy after ACS. (c) 2019 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

  • 874. Szummer, K
    et al.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala Clinical research Center.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Carrero, J J
    Evans, M
    Spaak, J
    Edfors, R
    Jacobson, S H
    Andell, P
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, T
    Association between the use of fondaparinux vs low-molecular-weight heparin and clinical outcomes in patients with non-ST-segment elevation myocardial infarction2015In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 313, no 7, p. 707-716Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE: Fondaparinux was associated with reduced major bleeding events and improved survival compared with low-molecular-weight heparin (LMWH) in a large randomized clinical trial involving patients with non-ST-segment elevation myocardial infarction (NSTEMI). Large-scale experience of the use of fondaparinux vs LMWH in a nontrial setting is lacking.

    OBJECTIVE: To study the association between the use of fondaparinux vs LMWH and outcomes in patients with NSTEMI in Sweden.

    DESIGN, SETTING, AND PATIENTS: Prospective multicenter cohort study from the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies registry involving 40,616 consecutive patients with NSTEMI who received fondaparinux or LMWH between September 1, 2006, through June 30, 2010, with the last follow-up on December 31, 2010.

    EXPOSURES: In-hospital treatment with fondaparinux or LMWH during the hospital stay.

    MAIN OUTCOMES AND MEASURES: In-hospital severe bleeding events and death and 30- and 180-day death, MI, stroke, and major bleeding events. Logistic regression models adjusted for calendar time, admitting hospital, baseline characteristics, and in-hospital revascularization.

    RESULTS: In total, 14,791 patients (36.4%) were treated with fondaparinux and 25,825 (63.6%) with LMWH. One hundred sixty-five patients (1.1%) in the fondaparinux group vs 461 patients (1.8%) in the LMWH group experienced in-hospital bleeding events (adjusted odds ratio [OR], 0.54; 95% CI, 0.42-0.70). A total of 394 patients (2.7%) in the fondaparinux group died while in the hospital vs 1022 (4.0%) in the LMWH group (adjusted OR, 0.75; 95% CI, 0.63-0.89). The differences in major bleeding events and mortality between the 2 treatments were similar at 30 and 180 days. There were no significant differences in the number of recurrent MI and stroke events at 30 or 180 days among the 2 treatment groups.

    CONCLUSIONS AND RELEVANCE: In routine clinical care of patients with NSTEMI, fondaparinux was associated with lower odds than LMWH of major bleeding events and death both in-hospital and up to 180 days afterward.

  • 875.
    Szummer, Karolina
    et al.
    Karolinska Inst, Dept Med, Sect Cardiol, Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyd Univ Hosp, Dept Clin Sci, Stockholm, Sweden.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    From Early Pharmacology to Recent Pharmacology Interventions in Acute Coronary Syndromes: JACC State-of-the-Art Review2019In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 74, no 12, p. 1618-1636Article, review/survey (Refereed)
    Abstract [en]

    This focus seminar will take the reader through the history and pivotal trials that have formed the current state-of-the-art management for acute coronary syndromes. The identification of a ruptured plaque with thrombus formation and subsequent occlusion or downstream embolization in the coronary artery was the key to developing new and effective treatment strategies. The traditional wait-and-see approach with prolonged bedrest was replaced in the 1980s by immediate pharmacological reperfusion of the occluded coronary artery and long-term aspirin to prevent reinfarction. Mechanical reperfusion with percutaneous coronary intervention with stenting and more intense platelet inhibition with P2Y(12) inhibitors further improved outcomes from early 2000s. Adjunctive treatment regimens, including anticoagulants, statins, and neurohormonal inhibition, were found to further reduce mortality and prevent new infarctions. Taken together, the use of new combined pharmacological and interventional treatment strategies has led to a remarkable decrease in 1-year mortality from around 22% in 1995 to around 11% by 2014.

  • 876.
    Szummer, Karolina
    et al.
    Karolinska Inst, Sect Cardiol, Dept Med, S-14186 Stockholm, Sweden;Karolinska Univ Hosp, Dept Cardiol, Halsovagen 4, S-14186 Stockholm, Sweden.
    Wallentin, Lars C.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, S-58185 Linkoping, Sweden;Linkoping Univ, Dept Med & Hlth Sci, Fac Hlth Sci, Linkoping, Sweden.
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Clin Sci, Dept Cardiol, Akutgatan 4, S-22185 Lund, Sweden.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kellerth, Thomas
    Orebro Univ Hosp, Dept Cardiol, S-70185 Orebro, Sweden.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Dept Mol & Clin Med, Inst Med, S-41345 Gothenburg, Sweden.
    Rydberg, Erik
    Lund Univ, Skane Univ Hosp, Clin Sci, Dept Cardiol, Akutgatan 4, S-22185 Lund, Sweden.
    Yndigegn, Troels
    Lund Univ, Skane Univ Hosp, Clin Sci, Dept Cardiol, Akutgatan 4, S-22185 Lund, Sweden.
    Jernberg, Tomas
    Karolinska Inst, Danderyds Hosp, Dept Clin Sci, Morbygardsvagen 88, S-18288 Danderyd, Sweden.
    Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years: experiences from SWEDEHEART registry 1995 to 20142018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 42, p. 3766-3776Article in journal (Refereed)
    Abstract [en]

    Aims We assessed the changes in short- and long-term outcomes and their relation to implementation of new evidence- based treatments in all patients with non-ST-elevation myocardial infarction (NSTEMI) in Sweden over 20 years. Methods and results Cases with NSTEMI (n = 205 693) between 1995 and 2014 were included from the nationwide Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. During 20 years in-hospital invasive procedures increased from 1.9% to 73.2%, percutaneous coronary intervention or coronary artery bypass grafting 6.5% to 58.1%, dual antiplatelet medication 0% to 72.7%, statins 13.3% to 85.6%, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker 36.8% to 75.5%. The standardized 1-year mortality ratio compared with a control population decreased from 5.53 [95% confidence interval (CI) 5.30-5.75] to 3.03 (95% CI 2.89-3.19). If patients admitted the first 2 years were modelled to receive the same invasive treatments as the last 2 years the expected mortality/ myocardial infarction (MI) rate would be reduced from 33.0% to 25.0%. After adjusting for differences in baseline characteristics, the change of 1-year cardiovascular death/MI corresponded to a linearly decreasing odds ratio trend of 0.930 (95% CI 0.926-0.935) per 2-year period. This trend was substantially attenuated [0.970 (95% CI 0.964-0.975)] after adjusting for changes in coronary interventions, and almost eliminated [0.988 (95% CI 0.982-0.994)] after also adjusting for changes in discharge medications. Conclusion In NSTEMI patients during the last 20 years, there has been a substantial improvement in long-term survival and re- duction in the risk of new cardiovascular events. These improvements seem mainly explained by the gradual uptake and widespread use of in-hospital coronary interventions and evidence-based long-term medications.

  • 877.
    Szummer, Karolina
    et al.
    Karolinska Inst, Dept Med, Stockholm, Sweden.;Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Alfredsson, Joakim
    Linkoping Univ, Dept Cardiol, Linkoping, Sweden.;Linkoping Univ, Dept Med & Hlth Sci, Fac Hlth Sci, Linkoping, Sweden..
    Erlinge, David
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden.;Lund Univ, Skane Univ Hosp, Dept Clin Sci, Lund, Sweden..
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kellerth, Thomas
    Orebro Univ Hosp, Dept Cardiol, Orebro, Sweden..
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ravn-Fischer, Annica
    Sahlgrens Univ Hosp, Dept Mol & Clin Med, Inst Med, Gothenburg, Sweden..
    Rydberg, Erik
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden.;Lund Univ, Skane Univ Hosp, Dept Clin Sci, Lund, Sweden..
    Yndigegn, Troels
    Lund Univ, Skane Univ Hosp, Dept Cardiol, Lund, Sweden.;Lund Univ, Skane Univ Hosp, Dept Clin Sci, Lund, Sweden..
    Jernberg, Tomas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    Improved outcomes in patients with ST-elevation myocardial infarction during the last 20 years are related to implementation of evidence-based treatments: experiences from the SWEDEHEART registry 1995-20142017In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 38, no 41, p. 3056-3065Article in journal (Refereed)
    Abstract [en]

    Aims Impact of changes of treatments on outcomes in ST-elevation myocardial infarction (STEMI) patients in real-life health care has not been documented. Methods and results All STEMI cases (n=105.674) registered in the nation-wide SWEDEHEART registry between 1995 and 2014 were included and followed for fatal and non-fatal outcomes for up to 20 years. Most changes in treatment and outcomes occurred from 1994 to 2008. Evidence-based treatments increased: reperfusion from 66.2 to 81.7%; primary percutaneous coronary intervention: 4.5 to 78.0%; dual antiplatelet therapy from 0 to 89.6%; statin: 14.1 to 93.6%; beta-blocker: 78.2 to 91.0%, and angiotensin-converting-enzyme/angiotensin-2-receptor inhibitors: 40.8 to 85.2% (P-value for-trend<0.001 for all). One-year mortality decreased from 22.1 to 14.1%. Standardized incidence ratio compared with the general population decreased from 5.54 to 3.74 (P<0.001). Cardiovascular (CV) death decreased from 20.1 to 11.1%, myocardial infarction (MI) from 11.5 to 5.8%; stroke from 2.9 to 2.1%; heart failure from 7.1 to 6.2%. After standardization for differences in demography and baseline characteristics, the change of 1-year CV-death or MI corresponded to a linear trend of 0.915 (95% confidence interval: 0.906-0.923) per 2-year period which no longer was significant, 0.997 (0.984-1.009), after adjustment for changes in treatment. The changes in treatment and outcomes were most pronounced from 1994 to 2008. Conclusion Gradual implementation of new and established evidence-based treatments in STEMI patients during the last 20 years has been associated with prolonged survival and lower risk of recurrent ischaemic events, although a plateauing is seen since around 2008.

  • 878.
    Sörensen, Jens
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Ståhle, Elisabeth
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Thoracic Surgery.
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Frostfeldt, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Wikström, Gerhard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Hedenstierna, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Physiology.
    Simple and accurate assessment of forward cardiac output by use of 1-[11C]acetate PET verified in a pig model2003In: Journal of Nuclear Medicine, ISSN 0161-5505, E-ISSN 1535-5667, Vol. 44, no 7, p. 1176-1183Article in journal (Refereed)
    Abstract [en]

    Dynamic 1-(11)C-acetate PET (AC-PET) allows quantification of myocardial blood flow and oxidative metabolism. We wanted to determine the accuracy of AC-PET in measuring cardiac output (CO) using first-pass analysis and the indicator dilution principle. Further, we wanted to investigate the pulmonary uptake of acetate in relation to left atrial filling pressures and ventricular function.

    METHODS: Twenty-four steady-state experiments were performed in 5 domestic pigs. Pulmonary capillary wedge pressure (PCWP) and CO by thermodilution (CO(thermo)) were recorded invasively simultaneous with AC-PET scans at baseline (n = 9), dobutamine infusion (n = 6), high-dose metoprolol and morphine (n = 6), and angiotensinamide infusion (n = 3). 1-(11)C-Acetate was injected as a rapid manual bolus. Regions of interest (ROIs) were placed in the right (RV) and left (LV) heart cavities. Time-activity curves were constructed and the area under the curve (AUC) was integrated from beginning the scan to the time of visually determined recirculation by simple arithmetic. CO by PET (CO(PET)) was calculated as injected dose/AUC. Image handling and curve analysis were repeated by a blinded observer. Total pulmonary extravascular retention of (11)C, expressed as percentage of injected dose (lung-uptake %ID), was measured using a combination of transmission, (15)O-carbon monoxide, and AC-PET scans.

    RESULTS: CO(thermo) ranged from 2.1 to 8.2 L/min. CO(PET) determined from both LV and RV was linearly related to CO(thermo) with slopes close to 1 (LV, r = 0.98; RV, r = 0.96; both P < 0.001). Interobserver reproducibility was r = 0.98, P < 0.001. The PCWP range was 6-14 mm Hg and the lung-uptake %ID was 2.7-8.5 %ID. When normalized to baseline, lung-uptake %ID was correlated with PCWP (r = 0.56, P = 0.01) and linearly correlated with LV input resistance (PCWP divided by CO(thermo); r = 0.91, P < 0.001). When both lung-uptake %ID and stroke volume were normalized to baseline, a piecewise linear relation was found (r = 0.95, P < 0.001).

    CONCLUSION: Our results suggest that measurements of CO by AC-PET are feasible and accurate. Using RV ROIs might favor CO measurements by any injectable PET tracer. The lung-uptake %ID might be useful in evaluation of pulmonary congestion, but further studies are needed.

  • 879. Søndergaard, Lars
    et al.
    Saraste, Antti
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Vahanian, Alec
    The year in cardiology 2017: valvular heart disease2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 8, p. 650-657Article in journal (Refereed)
  • 880.
    Tajuddin, Salman M.
    et al.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Schick, Ursula M.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Eicher, John D.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Chami, Nathalie
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Giri, Ayush
    Vanderbilt Univ, Div Epidemiol, Inst Med & Publ Hlth, Nashville, TN 37235 USA..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Hill, W. David
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Kacprowski, Tim
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, D-17475 Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, D-17475 Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Greifswald, Germany..
    Li, Jin
    Stanford Univ, Sch Med, Dept Med, Div Cardiovasc Med, Palo Alto, CA 94305 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA..
    Pankratz, Nathan
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA..
    Pazoki, Raha
    Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Polfus, Linda M.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Smith, Albert Vernon
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Vacchi-Suzzi, Caterina
    SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA..
    Waterworth, Dawn M.
    GlaxoSmithKline, Target Sci, Genet, King Of Prussia, PA 19406 USA..
    Evangelou, Evangelos
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece..
    Yanek, Lisa R.
    Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Burt, Amber
    Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA..
    Chen, Ming-Huei
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    van Rooij, Frank J. A.
    Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    Floyd, James S.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Greinacher, Andreas
    Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany..
    Harris, Tamara B.
    NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Nalls, Mike A.
    NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA..
    Mathias, Rasika A.
    Johns Hopkins Univ, Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Nickerson, Deborah A.
    Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98105 USA..
    Nikus, Kjell
    Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland.;Univ Tampere, Sch Med, Tampere 33014, Finland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Tardif, Jean-Claude
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Tzoulaki, Ioanna
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Vanderbilt Epidemiol Ctr,Dept Obstet & Gynecol, Nashville, TN 37203 USA..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bartz, Traci M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Becker, Lewis C.
    Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA.;Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA..
    Denny, Joshua C.
    Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37203 USA..
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Rioux, John D.
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Friedrich, Nele
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med Greifswald, Inst Clin Chem & Lab Med, D-13347 Greifswald, Germany..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Gao, He
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Hirschhorn, Joel N.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA..
    Liewald, David C. M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Rich, Stephen S.
    Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA..
    Uitterlinden, Andre
    Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.;Erasmus Univ, Med Ctr, Dept Internal Med, NL-3000 DR Rotterdam, Netherlands.;NCHA, NL-3015 GD Rotterdam, Netherlands..
    Bastarache, Lisa
    Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37203 USA..
    Becker, Diane M.
    Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA..
    Hayward, Caroline
    Univ Edinburgh, Inst Genet & Mol Med, MRC Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hofman, Albert
    Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Homuth, Georg
    Univ Med Greifswald, Interfac Inst Genet & Funct Genom, Dept Funct Genom, D-17475 Greifswald, Germany.;Ernst Moritz Arndt Univ Greifswald, D-17475 Greifswald, Germany..
    Lange, Ethan
    Univ N Carolina, Dept Genet & Biostat, Chapel Hill, NC 27599 USA..
    Launer, Lenore J.
    NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Sch Med, Dept Clin Chem, Tampere 33014, Finland..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    O'Donnell, Chris J.
    NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Vet Adm Healthcare, Cardiol Sect, Boston, MA 02118 USA.;Boston Vet Adm Healthcare, Ctr Populat Genom, Boston, MA 02118 USA..
    Quarells, Rakale C.
    Morehouse Sch Med, Social Epidemiol Res Ctr, Cardiovasc Res Inst, Atlanta, GA 30310 USA..
    Richard, Melissa
    Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA..
    Torstenson, Eric S.
    Vanderbilt Univ, Div Epidemiol, Inst Med & Publ Hlth, Nashville, TN 37235 USA..
    Taylor, Kent D.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Vergnaud, Anne-Claire
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Crosslin, David R.
    Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA..
    Deary, Ian J.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Dorr, Marcus
    DZHK German Ctr Cardiovasc Res, Greifswald, Germany.;Univ Med Greifswald, Dept Cardiol, D-17475 Greifswald, Germany..
    Elliott, Paul
    Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, Dept Epidemiol & Biostat, London W2 1PG, England..
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA..
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Sch Med, Dept Clin Physiol, Tampere 33014, Finland..
    Psaty, Bruce M.
    Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98101 USA.;Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98101 USA.;Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA..
    Rotter, Jerome I.
    Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90502 USA.;Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90502 USA..
    Slater, Andrew J.
    OmicSoft Corp, Cary, NC 27513 USA.;GlaxoSmithKline, Genet Target Sci, Res Triangle Pk, NC 27709 USA..
    Dehghan, Abbas
    Erasmus Univ, Med Ctr, Dept Epidemiol, NL-3000 DR Rotterdam, Netherlands..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.;Univ Auckland, Auckland 1142, New Zealand..
    Ganesh, Santhi K.
    Univ Michigan, Dept Internal Med, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48108 USA..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA..
    Esko, Tonu
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA..
    Faraday, Nauder
    Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA..
    Wilson, James G.
    Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Cushman, Mary
    Univ Vermont, Dept Med, Div Hematol Oncol, Colchester, VT 05446 USA..
    Johnson, Andrew D.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Edwards, Todd L.
    Vanderbilt Univ, Vanderbilt Genet Inst, Inst Med & Publ Hlth, Div Epidemiol,Dept Med, Nashville, TN 37203 USA..
    Zakai, Neil A.
    Univ Vermont, Dept Med, Div Hematol Oncol, Colchester, VT 05446 USA..
    Lettre, Guillaume
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada..
    Reiner, Alex P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Auer, Paul L.
    Univ Wisconsin Milwaukee, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA..
    Large-Scale Exome-wide Association Analysis Identifies Loci for White Blood Cell Traits and Pleiotropy with Immune-Mediated Diseases2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, no 1, p. 22-39Article in journal (Refereed)
    Abstract [en]

    White blood cells play diverse roles in innate and adaptive immunity. Genetic association analyses of phenotypic variation in circulating white blood cell (WBC) counts from large samples of otherwise healthy individuals can provide insights into genes and biologic pathways involved in production, differentiation, or clearance of particular WBC lineages (myeloid, lymphoid) and also potentially inform the genetic basis of autoimmune, allergic, and blood diseases. We performed an exome array-based meta-analysis of total WBC and subtype counts (neutrophils, monocytes, lymphocytes, basophils, and eosinophils) in a multi-ancestry discovery and replication sample of similar to 157,622 individuals from 25 studies. We identified 16 common variants (8 of which were coding variants) associated with one or more WBC traits, the majority of which are pleiotropically associated with autoimmune diseases. Based on functional annotation, these loci included genes encoding surface markers of myeloid, lymphoid, or hematopoietic stem cell differentiation (CD69, CD33, CD87), transcription factors regulating lineage specification during hematopoiesis (ASXL1, IRF8, IKZF1, JMJD1C, ETS2-PSMG1), and molecules involved in neutrophil clearance/apoptosis (C10orf54, LTA), adhesion (TNXB), or centrosome and microtubule structure/function (KIF9, TUBD1). Together with recent reports of somatic ASXL1 mutations among individuals with idiopathic cytopenias or clonal hematopoiesis of undetermined significance, the identification of a common regulatory 3 ' UTR variant of ASXL1 suggests that both germline and somatic ASXL1 mutations contribute to lower blood counts in otherwise asymptomatic individuals. These association results shed light on genetic mechanisms that regulate circulating WBC counts and suggest a prominent shared genetic architecture with inflammatory and autoimmune diseases.

  • 881.
    Temporelli, Pier Luigi
    et al.
    IRCCS, Ist Clin Sci Maugeri, Div Cardiol, Veruno, NO, Italy.
    Tilz, Roland R
    Arbelo, Elena
    Dagres, Nikolaos
    Laroche, Cécile
    Crijns, Harry J
    Blomström-Lundqvist, Carina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology-Arrhythmia. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kirchhof, Paulus
    Lip, Gregory Y H
    Boriani, Giuseppe
    Pokushalov, Evengy
    Nakou, Eleni
    Brugada, Josep
    Tavazzi, Luigi
    Maria Cecilia Hosp, GVM Care & Res, Cotignola, RA, Italy.
    Clinical characteristics of heart failure patients undergoing atrial fibrillation ablation today in Europe. Data from the atrial fibrillation registries of the European Society of Cardiology and the European Heart Rhythm Association.2019In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 21, no 5, p. 690-693Article in journal (Other academic)
  • 882.
    Terént, Andreas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Åsberg, Signild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Hijazi, Ziad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Antikoagulation vid akut stroke med förmaksflimmer Fem frågor bör besvaras innan behandlingen kan anses vara evidensbaserad: [Anticoagulation in acute stroke with atrial fibrillation. Five questions should be answered before the treatment can be considered evidence-based].2014In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 111, no 20, p. 872-874, article id CRZRArticle in journal (Refereed)
    Abstract [sv]

    Flera frågor finns kring användningen av orala antikoagulantia vid akut ischemisk stroke med förmaksflimmer. 

    Hur stor är risken för ny embolisering vid senarelagd behandling? Epidemiologiska data saknas.

    Hur stor är risken för blödning vid akut insatt behandling? Betydelsen av hemorragisk omvandling av hjärninfarkten är oklar.

    Vilken nytta har vi av prognos­tiska modeller? Dessa modeller är inte baserade på studier av patienter med akut stroke.

    Vilken roll spelar högre ålder? Risken för blödning ökar med ökande ålder, särskilt efter 75 år.

  • 883.
    Thilen, M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dellborg, M.
    Sahlgrens Acad, Dept Med, Gothenburg, Sweden..
    Mattsson, E.
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Trzebiatowska-Krzynska, A.
    Linkoping Univ Hosp, Dept Cardiol, S-58185 Linkoping, Sweden..
    Thilen, U.
    Univ Lund Hosp, Dept Med Sci, S-22185 Lund, Sweden..
    Atrial septal defect device closure in the elderly, symptomatic benefits except for arrhythmia2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no Suppl. 1, p. 624-625Article in journal (Other academic)
  • 884.
    Thilén, Maria
    et al.
    Halmstad Cty Hosp, Dept Med, Halmstad, Sweden..
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Dellborg, Mikael
    Sahlgrens Univ Hosp, Dept Med, Ostra, Sweden.;Gothenburg Univ, Sahlgrenska Acad, Inst Med, S-41124 Gothenburg, Sweden..
    Mattsson, Eva
    Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden..
    Trzebiatowska-Krzynska, Aleksandra
    Linkoping Univ Hosp, Dept Cardiol, Linkoping, Sweden..
    Thilén, Ulf
    Lund Univ, Skane Univ Hosp, Dept Cardiol, S-22100 Lund, Sweden..
    Catheter closure of atrial septal defect in the elderly (>= 65 years): A worthwhile procedure2016In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 218, p. 25-30Article in journal (Refereed)
    Abstract [en]

    Background: Secundum atrial septal defect (ASD2) is one of the most common cardiac malformations diagnosed in adult life. Catheter closure has made treatment possible even in patients of high age. However, published outcome data for elderly patients is limited. The aim of this study was to report, on a national basis, the long-term outcome of ASD2 catheter closure in the elderly. Material and results: We report the clinical and echocardiographic outcome of catheter closure of ASD2 in 148 patients aged 65-87 years. Data was obtained from a national registry, medical records and a questionnaire. The proportion of patients in NYHAI increased from 34% to 61% (p < 0.001) one year after closure and remained stable at the latest follow-up 4,4 (SD 2,6) years post-closure. The proportion of patients with moderate/severe enlargement of the right ventricle and atrium fell from 77% and 76% to 25% and 40%, respectively, (p < 0.001) and right ventricular systolic pressure dropped significantly. Improvement of NYHA class was associated with reduced right ventricular systolic pressure but not with remodelling of the right heart. NYHA deteriorated in 9 patients, despite reduced right ventricular size. Overall, the prevalence of atrial fibrillation was unchanged after closure. Major complication rate was 2% and there was no procedure-or device-related mortality. Conclusion: Catheter closure of ASD2 in the elderly is a worthwhile procedure since it improves symptoms and has a low complication rate. However, a subset of patients do not improve, in which we suggest that concealed left ventricular dysfunction may play a causative role.

  • 885.
    Thulin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Alfredsson, Jenny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science.
    Circulating cell-derived microparticles as biomarkers in cardiovascular disease2016In: Biomarkers in Medicine, ISSN 1752-0363, E-ISSN 1752-0371, Vol. 10, no 9, p. 1009-1022Article, review/survey (Refereed)
    Abstract [en]

    Cardiovascular diseases (CVDs) are a common cause of death, and a search for biomarkers for risk stratification is warranted. Elevated levels of cell-derived microparticles (MPs) are found in patients with CVD and in groups with risk factors for CVD. Subpopulations of MPs are promising biomarkers for improving risk prediction, as well as monitoring treatment. However, the field has been hampered by technical difficulties, and the ongoing development of sensitive standardized techniques is crucial for implementing MP analyses in the clinic. Large prospective studies are required to establish which MPs are of prognostic value in different patient groups. In this review, we discuss methodological challenges and progress in the field, as well as MP populations that are of interest for further clinical evaluation.

  • 886.
    Thulin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Yan, J.
    Eindhoven Univ Technol, Inst Complex Mol Syst, Eindhoven, Netherlands..
    Åberg, Mikael
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kamali-Moghaddam, Masood
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Coagulation and inflammation science. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Sensitive detection of platelet-derived and tissue factor positive extracellular vesicles in plasma using solid-phase proximity ligation assay2018In: Cardiovascular Research, ISSN 0008-6363, E-ISSN 1755-3245, Vol. 114, p. S132-S132Article in journal (Other academic)
  • 887.
    Thulin, Åsa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Yan, Junhong
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Åberg, Mikael
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Christersson, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Kamali-Moghaddam, Masood
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Siegbahn, Agneta
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Sensitive and Specific Detection of Platelet-Derived and Tissue Factor-Positive Extracellular Vesicles in Plasma using Solid-Phase Proximity Ligation Assay2018In: Thrombosis and Haemostasis open, ISSN 2512-9465Article in journal (Refereed)
    Abstract [en]

    Extracellular vesicles (EVs) derived from blood cells are promising biomarkers for various diseases. However, they are difficult to measure accurately in plasma due to their small size. Here, we demonstrate that platelet-derived EVs in plasma can be measured using solid-phase proximity ligation assay with high sensitivity and specificity using very small sample volume of biological materials. The results correlate well with high-sensitivity flow cytometry with the difference that the smallest EVs are detected. Briefly, the EVs are first captured on a solid phase, using lactadherin binding, and detection requires recognition with two antibodies followed by qPCR. The assay, using cholera toxin subunit-B or lactadherin as capture agents, also allowed detection of the more rare population of tissue factor (TF)-positive EVs at a concentration similar to sensitive TF activity assays. Thus, this assay can detect different types of EVs with high specificity and sensitivity, and has the potential to be an attractive alternative to flow cytometric analysis of preclinical and clinical samples. Improved techniques for measuring EVs in plasma will hopefully contribute to the understanding of their role in several diseases.

  • 888. Thygesen, Kristian
    et al.
    Alpert, Joseph S
    Jaffe, Allan S
    Chaitman, Bernard R
    Bax, Jeroen J
    Morrow, David A
    White, Harvey D
    Fourth universal definition of myocardial infarction (2018)2019In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 40, no 3, p. 237-269Article in journal (Refereed)
  • 889. Thygesen, Kristian
    et al.
    Alpert, Joseph S
    Jaffe, Allan S
    Simoons, Maarten L
    Chaitman, Bernard R
    White, Harvey D
    Katus, Hugo A
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Morrow, David A