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  • 201.
    Buccheri, Sergio
    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.
    Sarno, Giovanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Olivecrona, Göran
    Hambraeus, Kristina
    Witt, Nils
    Lindholm, Daniel
    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.
    Erlinge, David
    Angerås, Oskar
    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.
    Bioabsorbable polymer everolimus-eluting stents in patients with acute myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry.2018In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 14, no 5, p. e562-e569Article in journal (Refereed)
    Abstract [en]

    AIMS: The clinical performance of the SYNERGY drug-eluting stent (DES) in patients with acute myocardial infarction (MI) has not been investigated in detail. We sought to report on the outcomes after SYNERGY DES (Boston Scientific, Marlborough, MA, USA) implantation in patients with MI undergoing percutaneous revascularisation (PCI).

    METHODS AND RESULTS: We included all consecutive patients with MI undergoing PCI with the SYNERGY DES and newer-generation DES (n-DES group) in Sweden. From March 2013 to September 2016, a total of 36,292 patients, of whom 39.7% presented with ST-elevation MI, were included. As compared to patients in the n-DES group (n=31,403), patients in the SYNERGY group (n=4,889) were older and presented more often with left main or three-vessel disease involvement, as well as with restenotic lesions (p<0.001 for all parameters). The Kaplan-Meier estimates of ST at two years in the SYNERGY and n-DES groups were 0.69% and 0.81%, respectively (adjusted HR 1.00, 95% CI: 0.69-1.46; p=0.99). Clinically relevant restenosis was encountered in 1.48% and 1.25% of patients in the SYNERGY and n-DES groups, respectively (adjusted HR 1.05, 95% CI: 0.81-1.37; p=0.72). No differences in the risk of all-cause death and recurrent MI were found between the two groups after adjustment (adjusted HR 1.12, 95% CI: 0.98-1.28; p=0.10, and adjusted HR 0.95, 95% CI: 0.82-1.10; p=0.49, respectively).

    CONCLUSIONS: In a large and unselected cohort of patients with MI undergoing percutaneous revascularisation with the SYNERGY DES, stent performance and clinical outcomes did not differ compared with other n-DES up to two years.

  • 202. Bugiardini, Raffaele
    et al.
    Badimon, Lina
    Collins, Peter
    Erbel, Raimund
    Fox, Kim
    Hamm, Christian
    Pinto, Fausto
    Rosengren, Annika
    Stefanadis, Christodoulos
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research Center.
    Van de Werf, Frans
    Angina, "normal" coronary angiography, and vascular dysfunction: risk assessment strategies2007In: PLoS Medicine, ISSN 1549-1277, E-ISSN 1549-1676, Vol. 4, no 2, p. e12-Article in journal (Refereed)
    Abstract [en]

    Chest pain may be associated with coronary arteries that appear "normal". Normal is defined here as no visible disease or luminal irregularities (less than 50%) as judged visually at coronary angiography. Normal angiography in patients with chest pain is five times more common in women than in men [1]. Among patients with chest pain and normal angiography, an unknown number are suffering from cardiac pain of ischemic origin. Uncertainty is often difficult to allay, for medical attendants as well as for patients, resulting in perpetuation of symptoms, difficulties in management, and establishment of risk of subsequent coronary events [2]. In this article, we discuss how to stratify risk in patients with chest pain and a normal coronary angiogram.

  • 203.
    Bui, An H.
    et al.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Cannon, Christopher P.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Steg, Philippe Gabriel
    INSERM Unite 1148, Paris, France.;Hop Bichat Claude Bernard, AP HP, Dept Hosp Univ FIRE, F-75877 Paris, France.;Univ Paris Diderot, Sorbonne Paris Cite, Dept Cardiol, Paris, France.;NHLI Imperial Coll, ICMS, Dept Cardiol, Royal Brompton Hosp, London, England..
    Storey, Robert F.
    Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England..
    Husted, Steen
    Hosp Unit West, Dept Med, Herning Holstebro, Denmark..
    Guo, Jianping
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Im, KyungAh
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michelson, Eric L.
    Thomas Jefferson Univ, Dept Med, Philadelphia, PA 19107 USA..
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    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.
    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.
    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.
    Scirica, Benjamin M.
    Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med,Cardiovasc Div, Thrombolysis Myocardial Infarct TIMI Study Grp, Boston, MA 02115 USA..
    Relationship Between Early and Late Nonsustained Ventricular Tachycardia and Cardiovascular Death in Patients With Acute Coronary Syndrome in the Platelet Inhibition and Patient Outcomes (PLATO) Trial2016In: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 9, no 2, article id e002951Article in journal (Refereed)
    Abstract [en]

    Background- Nonsustained ventricular tachycardia (NSVT) is common after acute coronary syndrome (ACS) and a marker of increased risk of arrhythmogenic death. However, the prognostic significance of NSVT when evaluated with other contemporary risk markers and at later time points after ACS remains uncertain. Methods and Results- In the Platelet Inhibition and Patient Outcomes (PLATO) trial, continuous ECGs were performed during the first 7 days after ACS (n=2866) and repeated for another 7 days at day 30 (n=1991). Median follow-up was 1 year. There was a time-varying interaction between NSVT and cardiovascular death such that NSVT was significantly associated with increased risk within the first 30 days after randomization (22/999 [2.2%] versus 16/1825 [0.9%]; adjusted hazard ratio, 2.84; 95% confidence interval, 1.39-5.79; P=0.004) but not after 30 days (28/929 [3.0%] versus 42/1734 [2.4%]; P=0.71). Detection of NSVT during the convalescent phase (n=428/1991; 21.5%) was also associated with an increased risk of cardiovascular death, and was most marked within the first 2 months after detection (1.9% versus 0.3%; adjusted hazard ratio, 5.48; 95% confidence interval, 1.07-28.20; P=0.01), and then decreasing over time such that the relationship was no longer significant by approximate to 5 months after ACS. Conclusions- NSVT occurred frequently during the acute and convalescent phases of ACS. The risk of cardiovascular death associated with NSVT was the greatest during the first 30 days after presentation; however, patients with NSVT detected during the convalescent phase were also at a significantly increased risk of cardiovascular death that persisted for an additional several months after the index event.

  • 204.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
    Cars, Thomas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Kilander, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Prediction of fracture risk in men: A cohort study2012In: Journal of Bone and Mineral Research, ISSN 0884-0431, E-ISSN 1523-4681, Vol. 27, no 4, p. 797-807Article in journal (Refereed)
    Abstract [en]

    FRAX is a tool that identifies individuals with high fracture risk who will benefit from pharmacological treatment of osteoporosis. However, a majority of fractures among elderly occur in people without osteoporosis and most occur after a fall. Our aim was to accurately identify men with a high future risk of fracture, independent of cause. In the population-based Uppsala Longitudinal Study of Adult Men (ULSAM) and using survival analysis we studied different models' prognostic values (R(2) ) for any fracture and hip fracture within 10 years from age 50 (n = 2322), 60 (n = 1852), 71 (n = 1221), and 82 (n = 526). During the total follow-up period from age 50, 897 fractures occurred in 585 individuals. Of these, 281 were hip fractures occurring in 189 individuals. The rates of any fracture were 5.7/1000 person-years at risk from age 50 and 25.9/1000 person-years at risk from age 82. Corresponding hip fractures rates were 2.9 and 11.7/1000 person-years at risk. The FRAX model included all variables in FRAX except bone mineral density. The full model combining FRAX variables, comorbidity, medications, and behavioral factors explained 25-45% of all fractures and 80-92% of hip fractures, depending on age. The corresponding prognostic values of the FRAX model were 7-17% for all fractures and 41-60% for hip fractures. Net reclassification improvement (NRI) comparing the full model with the FRAX model ranged between 40 and 53% for any fracture and between 40 and 87% for hip fracture. Within the highest quintile of predicted fracture risk with the full model, 1/3 of the men will have a fracture within 10 years after age 71 years and 2/3 after age 82 years. We conclude that the addition of comorbidity, medication and behavioral factors to the clinical components of FRAX can substantially improve the ability to identify men at high risk of fracture, especially hip fracture. 

  • 205.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Internal Medicine.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort2009In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 338, p. b688-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation. DESIGN: Population based cohort study with follow-up over 35 years. SETTING: Municipality of Uppsala, Sweden. PARTICIPANTS: 2205 men aged 50 in 1970-3 who were re-examined at ages 60, 70, 77, and 82 years. MAIN OUTCOME MEASURE: Total (all cause) mortality. RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking). CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation.

  • 206.
    Byberg, Liisa
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Melhus, Håkan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Pharmacology.
    Gedeborg, Rolf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ahlbom, Anders
    Zethelius, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Geriatrics.
    Berglund, Lars G.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wolk, Alicja
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Total mortality after changes in leisure time physical activity in 50 year old men: 35 year follow-up of population based cohort (Reprinted from BMJ, vol 338, b688, 2009)2009In: British Journal of Sports Medicine, ISSN 0306-3674, E-ISSN 1473-0480, Vol. 43, no 7, p. 482-Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To examine how change in level of physical activity after middle age influences mortality and to compare it with the effect of smoking cessation.

    DESIGN: Population based cohort study with follow-up over 35 years.

    SETTING: Municipality of Uppsala, Sweden.

    PARTICIPANTS: 2205 men aged 50 in 1970-3 who were reexamined at ages 60, 70, 77, and 82 years.

    MAIN OUTCOME MEASURE: Total (all cause) mortality.

    RESULTS: The absolute mortality rate was 27.1, 23.6, and 18.4 per 1000 person years in the groups with low, medium, and high physical activity, respectively. The relative rate reduction attributable to high physical activity was 32% for low and 22% for medium physical activity. Men who increased their physical activity level between the ages of 50 and 60 continued to have a higher mortality rate during the first five years of follow-up (adjusted hazard ratio 2.64, 95% confidence interval 1.32 to 5.27, compared with unchanged high physical activity). After 10 years of follow-up their increased physical activity was associated with reduced mortality to the level of men with unchanged high physical activity (1.10, 0.87 to 1.38). The reduction in mortality associated with increased physical activity (0.51, 0.26 to 0.97, compared with unchanged low physical activity) was similar to that associated with smoking cessation (0.64, 0.53 to 0.78, compared with continued smoking).

    CONCLUSIONS: Increased physical activity in middle age is eventually followed by a reduction in mortality to the same level as seen among men with constantly high physical activity. This reduction is comparable with that associated with smoking cessation

  • 207.
    Bylund, Nina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Jensson, David
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Enghag, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Berg, T
    Marsk, E
    Hultcrantz, M
    Hadziosmanovic, Nermin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Rodriguez-Lorenzo, Andres
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Plastic Surgery.
    Jonsson, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
    Synkinesis in Bell's palsy in a randomised controlled trial2017In: Clinical Otolaryngology, ISSN 1749-4478, E-ISSN 1365-2273, Vol. 42, no 3, p. 673-680Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: To study the development of synkinesis in Bell's palsy. Frequency, severity, gender aspects and predictors were analysed.

    DESIGN: Data from the randomised controlled Scandinavian Bell's palsy trial including 829 patients.

    MAIN OUTCOME MEASURES: Frequency and severity of synkinesis at 12 months were the main outcome measures. Mean Sunnybrook synkinesis scores, voluntary movement scores and composite scores between 6 and 12 months were compared.

    RESULTS: In 743 patients with a 12-month follow-up, synkinesis frequency was 21.3%. There was no gender difference. Synkinesis was moderate to severe in 6.6% of patients. Those with synkinesis at 6 months had a synkinesis score of 4.1 (±2.8 sd), which increased to 4.7 (±3.2) (P = 0.047) at 12 months (n = 93). Sunnybrook composite score at 1 month was the best predictor for synkinesis development with receiver operating characteristics and area under the curve (AUC) 0.87. Risk for synkinesis increased with a lower Sunnybrook composite score. Furthermore, at 1 month, symmetry of voluntary movement had higher predictive value for synkinesis than resting symmetry with AUC 0.87 and 0.77, respectively. Gentle eye closure and open-mouth smile were the only independent significant predictive items (AUC 0.86).

    CONCLUSIONS: Moderate-to-severe synkinesis was present in 6.6% of patients. The mean synkinesis score increased between 6 and 12 months, and outcome should therefore be evaluated after at least 12 months. Sunnybrook composite score and symmetry of voluntary movement at 1 month were good predictors for synkinesis.

  • 208.
    Byrne, Robert A.
    et al.
    Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany..
    Serruys, Patrick W.
    Erasmus MC, Rotterdam, Netherlands..
    Baumbach, Andreas
    Bristol Heart Inst, Bristol, Avon, England..
    Escaned, Javier
    Hosp San Carlos, Intervent Cardiol, Madrid, Spain..
    Fajadet, Jean
    Clin Pasteur, Intervent Cardiol, Toulouse, France..
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Joner, Michael
    CVPath Inst Inc, Gaithersburg, MD USA..
    Oktay, Semih
    Cardio Med Device Consultants, Baltimore, MD USA..
    Jueni, Peter
    Univ Bern, Inst Primary Hlth Care BIHAM, Bern, Switzerland..
    Kastrati, Adnan
    Tech Univ Munich, Deutsch Herzzentrum Munchen, D-80290 Munich, Germany..
    Sianos, George
    AHEPA Univ Hosp, Thessaloniki, Greece..
    Stefanini, Giulio G.
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Wijns, William
    Cardiovasc Ctr OLVZ, Aalst, Belgium..
    Windecker, Stephan
    Univ Hosp Bern, Swiss Cardiovasc Ctr Bern, CH-3010 Bern, Switzerland..
    Report of a European Society of Cardiology-European Association of Percutaneous Cardiovascular Interventions task force on the evaluation of coronary stents in Europe: executive summary2015In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 36, no 38, p. 2608-2620Article in journal (Refereed)
    Abstract [en]

    The evaluation for European Union market approval of coronary stents falls under the Medical Device Directive that was adopted in 1993. Specific requirements for the assessment of coronary stents are laid out in supplementary advisory documents. In response to a call by the European Commission to make recommendations for a revision of the advisory document on the evaluation of coronary stents (Appendix 1 of MEDDEV 2.7.1), the European Society of Cardiology (ESC) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI) established a Task Force to develop an expert advisory report. As basis for its report, the ESC-EAPCI Task Force reviewed existing processes, established a comprehensive list of all coronary drug-eluting stents that have received a CE mark to date, and undertook a systematic review of the literature of all published randomized clinical trials evaluating clinical and angiographic outcomes of coronary artery stents between 2002 and 2013. Based on these data, the TF provided recommendations to inform a new regulatory process for coronary stents. The main recommendations of the task force include implementation of a standardized non-clinical assessment of stents and a novel clinical evaluation pathway for market approval. The two-stage clinical evaluation plan includes recommendation for an initial pre-market trial with objective performance criteria (OPC) benchmarking using invasive imaging follow-up leading to conditional CE-mark approval and a subsequent mandatory, large-scale randomized trial with clinical endpoint evaluation leading to unconditional CE-mark. The data analysis from the systematic review of the Task Force may provide a basis for determination of OPC for use in future studies. This paper represents an executive summary of the Task Force's report.

  • 209. Byrne, Robert A
    et al.
    Stefanini, Giulio G
    Capodanno, Davide
    Onuma, Yoshinobu
    Baumbach, Andreas
    Escaned, Javier
    Haude, Michael
    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.
    Joner, Michael
    Jüni, Peter
    Kastrati, Adnan
    Oktay, Semih
    Wijns, William
    Serruys, Patrick W
    Windecker, Stephan
    Report of an ESC-EAPCI Task Force on the evaluation and use of bioresorbable scaffolds for percutaneous coronary intervention: executive summary2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 18, p. 1591-1601Article in journal (Refereed)
    Abstract [en]

    A previous Task Force of the European Society of Cardiology (ESC) and European Association of Percutaneous Cardiovascular Interventions (EAPCI) provided a report on recommendations for the non-clinical and clinical evaluation of coronary stents. Following dialogue with the European Commission, the Task Force was asked to prepare an additional report on the class of devices known as bioresorbable scaffolds (BRS). Five BRS have CE-mark approval for use in Europe. Only one device-the Absorb bioresorbable vascular scaffold-has published randomized clinical trial data and this data show inferior outcomes to conventional drug-eluting stents (DES) at 2-3 years. For this reason, at present BRS should not be preferred to conventional DES in clinical practice. The Task Force recommends that new BRS devices should undergo systematic non-clinical testing according to standardized criteria prior to evaluation in clinical studies. A clinical evaluation plan should include data from a medium sized, randomized trial against DES powered for a surrogate end point of clinical efficacy. Manufacturers of successful devices receive CE-mark approval for use and must have an approved plan for a large-scale randomized clinical trial with planned long-term follow-up.

  • 210.
    Byrne, Robert A.
    et al.
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Stefanini, Giulio G.
    Humanitas Res Hosp, Cardio Ctr, Div Cardiol, Milan, Italy..
    Capodanno, Davide
    Univ Catania, Ferrarotto Hosp, Cardiothorac Vasc Dept, Catania, Italy..
    Onuma, Yoshinobu
    Erasmus MC, Dept Intervent Cardiol, Rotterdam, Netherlands..
    Baumbach, Andreas
    St Bartholomews Hosp, William Harvey Res Inst, Dept Cardiol, London, England.;Queen Mary Univ London, London, England..
    Escaned, Javier
    Hosp San Carlos, Intervent Cardiol, Madrid, Spain..
    Haude, Michael
    Lukaskrankenhaus GmbH, Stadtisches Kliniken Neuss, Med Clin 1, Neuss, Germany..
    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.
    Joner, Michael
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Jüni, Peter
    Univ Toronto, St Michaels Hosp, Li Ka Shing Knowledge Inst, Appl Hlth Res Ctr, Toronto, ON, Canada..
    Kastrati, Adnan
    Tech Univ Munich, Deutsch Herzzentrum Munchen, Munich, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Munich Heart Alliance, Munich, Germany..
    Oktay, Semih
    Cardio Med Device Consultants, Baltimore, MD USA..
    Wijns, William
    Saolta Univ, Healthcare Grp, Galway, Ireland.;Natl Univ Ireland, Lambe Inst Translat Med & Curam, Galway, Ireland..
    Serruys, Patrick W.
    Erasmus Univ, Rotterdam, Netherlands.;Imperial Coll London, Natl Heart & Lung Inst, Int Ctr Circulatory Hlth, London, England..
    Windecker, Stephan
    Bern Univ Hosp, Cardiovasc Ctr Bern, Bern, Switzerland..
    Report of an ESC-EAPCI Task Force on the evaluation and use of bioresorbable scaffolds for percutaneous coronary intervention: executive summary2018In: EuroIntervention, ISSN 1774-024X, E-ISSN 1969-6213, Vol. 13, no 13, p. 1574-1586Article in journal (Refereed)
    Abstract [en]

    A previous Task Force of the European Society of Cardiology (ESC) and European Association of Percutaneous Cardiovascular Interventions (EAPCI) provided a report on recommendations for the non-clinical and clinical evaluation of coronary stents. Following dialogue with the European Commission, the Task Force was asked to prepare an additional report on the class of devices known as bioresorbable scaffolds (BRS). Five BRS have CE-mark approval for use in Europe. Only one device - the Absorb bioresorbable vascular scaffold - has published randomized clinical trial data and this data show inferior outcomes to conventional drug-eluting stents (DES) at 2-3 years. For this reason, at present BRS should not be preferred to conventional DES in clinical practice. The Task Force recommends that new BRS devices should undergo systematic non-clinical testing according to standardized criteria prior to evaluation in clinical studies. A clinical evaluation plan should include data from a medium sized, randomized trial against DES powered for a surrogate end point of clinical efficacy. Manufacturers of successful devices receive CE-mark approval for use and must have an approved plan for a large-scale randomized clinical trial with planned long-term follow-up.

  • 211.
    Byström, P.
    et al.
    Department of Oncology and Pathology, Karolinska Institutet, Stockholm, .
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Wernroth, Mona-Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Einarsson, R.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
    An explorative study on the clinical utility of baseline and serial serum tumour marker measurements in advanced upper gastrointestinal cancer2010In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 24, no 6, p. 1645-1652Article in journal (Refereed)
    Abstract [en]

    The value of early tumour marker changes during palliative chemotherapy in patients with upper gastrointestinal adenocarcinoma (UGIA) is unclear. Seventy-three patients with advanced UGIA were randomised to receive 45 mg/m2 docetaxel or 180 mg/m2 irinotecan with 5-FU/leucovorin. After every 2nd course the patients were crossed over to the other regimen. Serum was sampled before start of chemotherapy and every 2nd week during 8 weeks for CEA, TPA, TPS, CA72-4, CA19-9 and CA242 measurements. Eighteen patients (25%) had partial response (PR) and 21 patients had stable disease for at least 4 months (SD4). All baseline marker levels, except CA72-4, correlated with time to progression and survival. Patients with normal levels, except CA72-4, also had more clinical responses (PR+SD4) than patients with elevated values. Tumour marker changes early during treatment provided modest predictive information for tumour response and survival. A model combining baseline level, the change and the interaction between them gave the best prediction of outcome, however, insignificantly better than baseline level for all markers except CA242. Baseline tumour marker levels provide prognostic information for patients with UGIA on palliative chemotherapy. Early changes generally failed to provide accurate information for tumour response and survival.

  • 212.
    Byström, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Berglund, Åke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Nygren, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Wernroth, Lisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Johansson, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Glimelius, Bengt
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Oncology.
    Evaluation of predictive markers for patients with advanced colorectal cancer2012In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 51, no 7, p. 849-859Article in journal (Refereed)
    Abstract [en]

    Background.

    To evaluate the predictive and prognostic value of serum and plasma tumor markers, in comparison with clinical and biomedical parameters for response rate (RR), progression-free survival (PFS) and overall survival (OS) among patients with metastatic colorectal cancer (mCRC) treated with combination chemotherapy.

    Material and methods.

    One-hundred and six patients with mCRC from three centers, part of a multicenter study, received irinotecan with the Nordic bolus 5-fluorouracil (5-FU) and folinic acid schedule (FLIRI) or the de Gramont schedule (Lv5FU2-IRI). Blood samples for CEA, CA19-9, TPA, TIMP-1, SAA, transthyretin and CRP were taken at baseline and after two, four and eight weeks of treatment. Tumor marker levels at baseline and longitudinally were compared with responses evaluated (CT/MRI) after two and four months of treatment. The correlations to RR, PFS and OS were evaluated with regression analyses.

    Results.

    A significant correlation to OS was seen for baseline levels of all markers. In multivariate analyses with clinical parameters, TPA, CRP, SAA and TIMP-1 provided independent information. The baseline values of CEA, TPA and TIMP-1 were also significantly correlated to PFS and TPA to RR. Changes during treatment, i.e. the slope gave with the exception of CA19-9 for OS less information about outcomes. The best correlation to response was seen for CEA, CA19-9 and TPA with AUC values of 0.78, 0.83 and 0.79, respectively, using a combined model based upon an interaction between the slope and the baseline value.

    Conclusions.

    Baseline tumor markers together with clinical parameters provide prognostic information about survival in patients with mCRC. The ability of the individual tumor markers to predict treatment response and PFS is limited. Changes in marker levels during the first two months of treatment are less informative of outcome.

  • 213. Böhm, Michael
    et al.
    Ezekowitz, Michael D
    Connolly, Stuart J
    Eikelboom, John W
    Hohnloser, Stefan H
    Reilly, Paul A
    Schumacher, Helmut
    Brueckmann, Martina
    Schirmer, Stephan H
    Kratz, Mario T
    Yusuf, Salim
    Diener, Hans-Christoph
    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.
    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.
    Reply: Anticoagulant-Related Nephropathy2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 66, no 23, p. 2682-Article in journal (Refereed)
  • 214. Calais, Fredrik
    et al.
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    Fröbert, Ole
    Proximal Coronary Artery Stenting: DES Versus BMS and LAD Versus the Rest2012In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, no 17, p. B174-B175Article in journal (Other academic)
  • 215.
    Calais, Fredrik
    et al.
    Univ Orebro, Fac Hlth, SE-70182 Orebro, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frobert, Ole
    Orebro Univ Hosp, Orebro, Sweden..
    Thrombus aspiration in patients with large anterior myocardial infarction: a TASTE trial substudy2015In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 66, no 15, p. B2-B2Article in journal (Other academic)
  • 216.
    Calais, Fredrik
    et al.
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Leppert, Jerzy
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Frobert, Ole
    Univ Orebro, Fac Hlth, Dept Cardiol, S-70362 Orebro, Sweden..
    Thrombus aspiration in patients with large anterior myocardial infarction: A Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia trial substudy2016In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 172, p. 129-134Article in journal (Refereed)
    Abstract [en]

    Background The TASTE trial did not demonstrate clinical benefit of thrombus aspiration (TA). High-risk patients might benefit from TA. Methods The TASTE trial was a multicenter, randomized, controlled, open-label trial obtaining end points from national registries. Patients (n = 7,244) with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI) were randomly assigned 1: 1 to TA and PCI or to PCI alone. We assessed the 1-year clinical effect of TA in a subgroup with potentially large anterior STEMI: mid or proximal left anterior descending coronary artery infarct lesion, thrombolysis in myocardial infarction 0 to 2 flow, and symptom onset to PCI time = 5 hours. In this substudy, patient eligibility criteria corresponded to that of the INFUSE-AMI study. Results In total, 1,826 patients fulfilled inclusion criteria. All-cause mortality at 1 year of patients randomized to TA did not differ from those randomized to PCI only (hazard ratio [HR] 1.05, 95% CI 0.74-1.49, P = .77). Rates of rehospitalization for myocardial infarction, heart failure, and stent thrombosis did not differ between groups (HR 0.87, 95% CI 0.51-1.46, P = .59; HR 1.10 95% CI 0.77-1.58, P = .58; and HR 0.75, 95% CI 0.30-1.86, P = .53, respectively). This was also the case for the combined end point of all-cause mortality and rehospitalization for myocardial infarction, heart failure, or stent thrombosis (HR 1.00, 95% CI 0.79-1.26, P = .99). Conclusion In patients with STEMI and large area of myocardium at risk, TA did not affect outcome within 1 year.

  • 217. Califf, Robert M
    et al.
    Armstrong, Paul W
    Granger, Christopher B
    Harrington, Robert A
    Lee, Kerry
    Simes, R John
    Van de Werf, Frans
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    White, Harvey D
    Towards a new order in cardiovascular medicine: re-engineering through global collaboration2010In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 31, no 8, p. 911-917Article in journal (Refereed)
  • 218.
    Cannon, Christopher P.
    et al.
    Baim Inst Clin Res, 930 Commonwealth Ave, Boston, MA 02215 USA.;Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Heart & Vasc Ctr, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    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.
    Lip, Gregory Y. H.
    Univ Birmingham, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Ellis, Stephen G.
    Cleveland Clin, Cleveland, OH 44106 USA..
    Kimura, Takeshi
    Kyoto Univ, Dept Cardiovasc Med, Kyoto, Japan..
    Maeng, Michael
    Aarhus Univ Hosp, Skejby, Denmark..
    Merkely, Bela
    Univ Heart & Vasc Ctr, Budapest, Hungary..
    Zeymer, Uwe
    Klinikum Stadt Ludwigshafen Rhein, Med Klin B, Ludwigshafen, Germany..
    Gropper, Savion
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Nordaby, Matias
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Kleine, Eva
    Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany..
    Harper, Ruth
    Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England..
    Manassie, Jenny
    Boehringer Ingelheim GmbH & Co KG, Bracknell, Berks, England..
    Januzzi, James L.
    Baim Inst Clin Res, 930 Commonwealth Ave, Boston, MA 02215 USA.;Harvard Med Sch, Boston, MA USA.;Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA..
    ten Berg, Jurrien M.
    St Antonius Hosp, Nieuwegein, Netherlands..
    Steg, Gabriel
    Imperial Coll, London, England.;Univ Paris Diderot, French Alliance Cardiovasc Trials, F CRIN Network, DHU FIRE,INSERM,Unite 1148, Paris, France.;Hop Bichat Assistance Publ, Paris, France..
    Hohnloser, Stefan H.
    Goethe Univ Frankfurt, Dept Med, Div Cardiol, Frankfurt, Germany..
    Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation2017In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 377, no 16, p. 1513-1524Article in journal (Refereed)
    Abstract [en]

    BACKGROUND Triple antithrombotic therapy with warfarin plus two antiplatelet agents is the standard of care after percutaneous coronary intervention (PCI) for patients with atrial fibrillation, but this therapy is associated with a high risk of bleeding.

    METHODS In this multicenter trial, we randomly assigned 2725 patients with atrial fibrillation who had undergone PCI to triple therapy with warfarin plus a P2Y(12) inhibitor (clopidogrel or ticagrelor) and aspirin (for 1 to 3 months) (triple-therapy group) or dual therapy with dabigatran (110 mg or 150 mg twice daily) plus a P2Y(12) inhibitor (clopidogrel or ticagrelor) and no aspirin (110-mg and 150-mg dual-therapy groups). Outside the United States, elderly patients (>= 80 years of age; >= 70 years of age in Japan) were randomly assigned to the 110-mg dual-therapy group or the triple-therapy group. The primary end point was a major or clinically relevant nonmajor bleeding event during follow-up (mean follow-up, 14 months). The trial also tested for the noninferiority of dual therapy with dabigatran (both doses combined) to triple therapy with warfarin with respect to the incidence of a composite efficacy end point of thromboembolic events (myocardial infarction, stroke, or systemic embolism), death, or unplanned revascularization.

    RESULTS The incidence of the primary end point was 15.4% in the 110-mg dual-therapy group as compared with 26.9% in the triple-therapy group (hazard ratio, 0.52; 95% confidence interval [CI], 0.42 to 0.63; P<0.001 for noninferiority; P<0.001 for superiority) and 20.2% in the 150-mg dual-therapy group as compared with 25.7% in the corresponding triple-therapy group, which did not include elderly patients outside the United States (hazard ratio, 0.72; 95% CI, 0.58 to 0.88; P<0.001 for noninferiority). The incidence of the composite efficacy end point was 13.7% in the two dual-therapy groups combined as compared with 13.4% in the triple-therapy group (hazard ratio, 1.04; 95% CI, 0.84 to 1.29; P=0.005 for noninferiority). The rate of serious adverse events did not differ significantly among the groups.

    CONCLUSIONS Among patients with atrial fibrillation who had undergone PCI, the risk of bleeding was lower among those who received dual therapy with dabigatran and a P2Y(12) inhibitor than among those who received triple therapy with warfarin, a P2Y(12) inhibitor, and aspirin. Dual therapy was noninferior to triple therapy with respect to the risk of thromboembolic events.

  • 219.
    Cannon, Christopher P.
    et al.
    Harvard Clin Res Inst, 930 Commonwealth Ave, Boston, MA 02215 USA.;Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Gropper, Savion
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany..
    Bhatt, Deepak L.
    Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA.;Harvard Med Sch, Boston, MA USA..
    Ellis, Stephen G.
    Cleveland Clin, Cleveland, OH 44106 USA..
    Kimura, Takeshi
    Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan..
    Lip, Gregory Y. H.
    Univ Birmingham, City Hosp, Inst Cardiovasc Sci, Birmingham, W Midlands, England..
    Steg, Ph. Gabriel
    Univ Paris Diderot, Sorbonne Paris Cite, Hop Bichat, AP HP,Dept Hosp Univ FIRE,FACT,INSERM,U 1148, Paris, France.;ICMS Royal Brompton Hosp, NHLI Imperial Coll, London, England..
    ten Berg, Jurrien M.
    St Antonius Hosp, Nieuwegein, Netherlands..
    Manassie, Jenny
    Boehringer Ingelheim Ltd, Div Med, Bracknell, Berks, England..
    Kreuzer, Jorg
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med, Heidelberg, Germany..
    Blatchford, Jon
    Boehringer Ingelheim Ltd, Div Med, Bracknell, Berks, England..
    Massaro, Joseph M.
    Boston Univ, Sch Publ Hlth, Boston, MA USA..
    Brueckmann, Martina
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.;Heidelberg Univ, Fac Med Mannheim, Mannheim, Germany..
    Ripoll, Ernesto Ferreiros
    Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany..
    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.
    Hohnloser, Stefan H.
    Goethe Univ Frankfurt, Dept Cardiol, Frankfurt, Germany..
    Design and Rationale of the RE-DUAL PCI Trial: A Prospective, Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting2016In: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 39, no 10, p. 555-564Article in journal (Refereed)
    Abstract [en]

    Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest-sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE-DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open-label, blinded-endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibtor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibtor (either clopidogrel or ticagrelor, and low-dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize similar to 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.

  • 220. Cannon, Christopher P.
    et al.
    Harrington, Robert A.
    James, Stefan
    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.
    Ardissino, Diego
    Becker, Richard C.
    Emanuelsson, Håkan
    Husted, Steen
    Katus, Hugo
    Keltai, Matyas
    Khurmi, Nardev S.
    Kontny, Frederic
    Lewis, Basil S.
    Steg, Philippe Gabriel
    Storey, Robert F.
    Wojdyla, Daniel
    Wallentin, Lars
    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.
    Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO): a randomised double-blind study2010In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 375, no 9711, p. 283-293Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients. METHODS: At randomisation, an invasive strategy was planned for 13 408 (72.0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872. FINDINGS: 6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9.0%] vs 668 [10.7%], hazard ratio 0.84, 95% CI 0.75-0.94; p=0.0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11.6%] vs 689 [11.5%], 0.99 [0.89-1.10]; p=0.8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3.2%] vs 185 [2.9%], 0.91 [0.74-1.12]; p=0.3785). INTERPRETATION: Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.

  • 221.
    Cannon, Christopher P.
    et al.
    Baim Inst Clin Res, Boston, MA, USA.
    Lip, Gregory Y. H.
    Univ Birmingham, Birmingham, England.
    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.
    Dual Antithrombotic Therapy with Dabigatran after PCI in Atrial Fibrillation: The authors reply2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 378, no 5, p. 485-486Article in journal (Other academic)
  • 222.
    Carlhed, Rickard
    et al.
    Onkologi, Landstinget i Värmland.
    Bellman, Christina
    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.
    Bojestig, Mats
    Landstinget i Jönköping.
    Bojö, Leif
    Klinisk Fysiologi, Landstinget i Värmland.
    Peterson, Anette
    Landstinget i Jönköping.
    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.
    Quality improvement in coronary care: Analysis of sustainability and impact on adjacent clinical measures after a Swedish controlled, multicenter quality improvement collaborative2012In: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 1, no 4, article id e000737Article in journal (Refereed)
    Abstract [en]

    Background Quality Improvement in Coronary Care, a Swedish multicenter, controlled quality-improvement (QI) collaborative, has shown significant improvements in adherence to national guidelines for acute myocardial infarction, as well as improved clinical outcome. The objectives of this report were to describe the sustainability of the improvements after withdrawal of study support and a consolidation period of 3 months and to report whether improvements were disseminated to treatments and diagnostic procedures other than those primarily targeted.

    Methods and Results Multidisciplinary teams from 19 Swedish hospitals were educated in basic QI methodologies. Another 19 matched hospitals were included as blinded controls. All evaluations were made on the hospital level, and data were obtained from a national quality registry, Swedish Register of Information and Knowledge About Swedish Heart Intensive Care Admissions (RIKS-HIA). Sustainability indicators consisted of use of angiotensin-converting enzyme inhibitors, lipid-lowering therapy, clopidogrel, low-molecular weight heparin, and coronary angiography. Dissemination indicators were use of echocardiography, stress tests, and reperfusion therapy; time delays; and length of stay. At the reevaluation period of 6 months, the improvements at the QI intervention hospitals were sustained in all indicators but 1 (angiotensin-converting enzyme inhibitor). Between the 2 measurements, the control group improved significantly in all but 1 indicator (angiotensin-converting enzyme inhibitor). However, at the second measurement, the absolute adherence rates of the intervention hospitals were still numerically higher in all 5 indicators, and significantly so in 1 (clopidogrel). No significant changes were observed for the dissemination indicators.

    Conclusions The combination of a systematic QI collaborative with a national, interactive quality registry might lead to substantial and sustained improvements in the quality of acute myocardial infarction care. However, to achieve disseminated improvements in adjacent clinical measures, those adjacent measures probably should be made explicit before any QI intervention.

  • 223. Carlhed, Rickard
    et al.
    Bojestig, Mats
    Peterson, Anette
    Åberg, Christina
    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.
    Garmo, Hans
    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.
    Lindahl, Bertil
    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.
    Improved clinical outcome after acute myocardial infarction in hospitals participating in a Swedish quality improvement initiative2009In: Circulation. Cardiovascular quality and outcomes, ISSN 1941-7713, Vol. 2, no 5, p. 458-464Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The Swedish quality improvement initiative Quality Improvement in Coronary Care previously demonstrated significant improvements in caregiver adherence to national guidelines for acute myocardial infarction. The associated impact on 1-year clinical outcome is presented here. METHODS AND RESULTS: During the baseline period July 2001 to June 2002, 6878 consecutive acute myocardial infarction patients <80 years were included at the 19 intervention and 19 control hospitals and followed for a mean of 12 months. During the postintervention period of May 2003 to April 2004, 6484 patients were included and followed in the same way. From baseline to postintervention, improvements in mortality and cardiovascular readmission rates (events per 100 patient-years) were significant in the intervention group (-2.82, 95% CI -5.26 to -0.39; -9.31, 95% CI -15.48 to -3.14, respectively). However, in the control hospitals, there were no significant improvements (0.04, 95% CI -2.40 to 2.47; -4.93, 95% CI -11.10 to 1.24, respectively). Bleedings in the control group increased in incidence (0.92, 95% CI 0.41 to 1.43), whereas the incidence remained unchanged in the intervention group (0.07, 95% CI -0.44 to 0.58). When the difference of changes between the study groups were evaluated, the results still were in favor of the intervention group, albeit significant only for bleeding complications (mortality: -2.70, 95% CI -6.37 to 0.97; cardiovascular readmissions: -6.85, 95% CI -16.62 to 2.93; bleeding complications: -0.82, 95% CI -1.66 to 0.01). CONCLUSIONS: With a systematic quality improvement initiative aiming to increase the adherence to acute myocardial infarction guidelines, it is possible to achieve long-term positive effects on clinical outcome.

  • 224.
    Carlhed, Rickard
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bojestig, Mats
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindström, Gunilla
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Peterson, Anette
    Åberg, Christina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lindahl, Bertil
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Improved adherence to Swedish national guidelines for acute myocardial infarction: the Quality Improvement in Coronary Care (QUICC) study2006In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 152, no 6, p. 1175-1181Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The adherence to evidence-based treatment guidelines for acute myocardial infarction (AMI) is still suboptimal. Therefore, we designed a study to evaluate the effects of a collaborative quality improvement (QI) intervention on the adherence to AMI guidelines. The intervention used a national web-based quality registry to generate local and regular real-time performance feedback. METHODS: A 12-month baseline measurement of the adherence rates was retrospectively collected, comprising the period July 1, 2001, through June 30, 2002. During the intervention period of November 1, 2002, through April 30, 2003, multidisciplinary teams from 19 nonrandomized intervention hospitals were subjected to a multifaceted QI-oriented intervention. Another 19 hospitals, unaware of their status as controls, were matched to the intervention hospitals. During the postintervention measurement period of May 1, 2003, through April 30, 2004, a total of 6726 consecutive patients were included at the intervention (n = 3786) and control (n = 2940) hospitals. The outcome measures comprised 5 Swedish national guideline-derived quality indicators, compared between baseline and postintervention levels in the control and QUICC intervention hospitals. RESULTS: In the control and QI intervention hospitals, the mean absolute increase of patients receiving angiotensin-converting enzyme inhibitors was 1.4% vs 12.6% (P = .002), lipid-lowering therapy 2.3% vs 7.2% (P = .065), clopidogrel 26.3% vs 41.2% (P = .010), heparin/low-molecular weight heparin 5.3% vs 16.3% (P = .010), and coronary angiography 6.2% vs 16.8% (P = .027), respectively. The number of QI intervention hospitals reaching a treatment level of at least 70% in 4 or 5 of the 5 indicators was 15 and 5, respectively. In the control group, no hospital reached 70% or more in just 4 of the 5 indicators. CONCLUSIONS: By combining a systematic and multidisciplinary QI collaborative with a web-based national quality registry with functionality allowing real-time performance feedback, major improvements in the adherence to national AMI guidelines can be achieved.

  • 225.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ingelsson, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology. Uppsala University, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Med, Div Cardiovasc Med, Sch Med, Stanford, CA 94305 USA.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Carrero, Juan Jesus
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Feldreich, Tobias
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Use of Proteomics To Investigate Kidney Function Decline over 5 Years2017In: American Society of Nephrology. Clinical Journal, ISSN 1555-9041, E-ISSN 1555-905X, Vol. 12, no 8, p. 1226-1235Article in journal (Refereed)
    Abstract [en]

    BACKGROUND AND OBJECTIVES: Using a discovery/replication approach, we investigated associations between a multiplex panel of 80 circulating proteins associated with cardiovascular pathology or inflammation, and eGFR decline per year and CKD incidence.

    DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two cohorts, the Prospective Investigation of the Vasculature in Uppsala Seniors Study (PIVUS; n=687, mean age of 70 years, 51% women) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=360 men, mean age of 78 years), with 5-year follow-up data on eGFR. There were 231 and 206 incident cases of CKD during follow-up in the PIVUS and ULSAM studies, respectively. Proteomic profiling of 80 proteins was assessed by a multiplex assay (proximity extension assay). The assay uses two antibodies for each protein and a PCR step to achieve a high-specific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations.

    RESULTS: In the discovery cohort from the PIVUS Study, 28 plasma proteins were significantly associated with eGFR decline per year, taking into account the multiple testing. Twenty of these proteins were significantly associated with eGFR decline per year in the replication cohort from the ULSAM Study after adjustment for age, sex, cardiovascular risk factors, medications, and urinary albumin-to-creatinine ratio (in order of significance: TNF-related apoptosis-inducing ligand receptor 2*, CD40L receptor, TNF receptor 1*, placenta growth factor*, thrombomodulin*, urokinase plasminogen activator surface receptor*, growth/differentiation factor 15*, macrophage colony-stimulating factor 1, fatty acid-binding protein*, cathepsin D, resistin, kallikrein 11*, C-C motif chemokine 3, proteinase-activated receptor 1*, cathepsin L, chitinase 3-like protein 1, TNF receptor 2*, fibroblast growth factor 23*, monocyte chemotactic protein 1, and kallikrein 6). Moreover, 11 of the proteins predicted CKD incidence (marked with * above). No protein consistently predicted eGFR decline per year independently of baseline eGFR in both cohorts.

    CONCLUSIONS: Several circulating proteins involved in phosphate homeostasis, inflammation, apoptosis, extracellular matrix remodeling, angiogenesis, and endothelial dysfunction were associated with worsening kidney function. Multiplex proteomics appears to be a promising way of discovering novel aspects of kidney disease pathology.

  • 226.
    Carlsson, Axel C.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Karolinska Inst, Div Family Med, Dept Neurobiol, Care Sci & Soc, Karlskrona, Sweden..
    Sundström, Johan
    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.
    Carrero, Juan Jesus
    Karolinska Inst, Div Renal Med, Dept Clin Sci, Intervent & Technol, Karlskrona, Sweden..
    Gustafsson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Stenemo, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular epidemiology.
    Larsson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Biochemial structure and function.
    Lind, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences. Dalarna Univ, Sch Hlth & Social Sci, Dalarna, Sweden..
    Use of a proximity extension assay proteomics chip to discover new biomarkers associated with albuminuria2017In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, no 4, p. 340-348Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The underlying mechanisms for the development of albuminuria and the increased cardiovascular risk in patients with elevated albuminuria levels are incompletely understood. We therefore investigated the associations between 80 cardiovascular proteins and the urinary albumin to creatinine ratio (ACR).

    METHODS: We used a discovery/replication approach in two independent community-based cohorts of elderly patients: the Uppsala Longitudinal Study of Adult Men (n = 662; mean age 78 years) and the Prospective Investigation of the Vasculature in Uppsala Seniors (n = 757; mean age 75 years; 51% women). A proteomic chip with a panel of 80 plasma proteins associated with different aspects of cardiovascular disease was analysed. In the discovery cohort, we used a false discovery rate of 5% to take into account the multiple statistical testing. Nominal p values were used in the replication.

    RESULTS: Higher levels of T-cell immunoglobulin mucin-1, placenta growth factor, growth/differentiation factor-15, urokinase plasminogen activator surface receptor and kallikrein-11 were robustly associated with a higher ACR in both cohorts in multivariable linear regression models adjusted for sex, established cardiovascular risk factors, antihypertensive treatment, prevalent cardiovascular disease and glomerular filtration rate (p < 0.02 for all). All associations were also significant in separate analyses of patients without diabetes.

    CONCLUSIONS: We discovered and replicated associations between ACR and five cardiovascular proteins involved in tubular injury, atherosclerosis, endothelial function, heart failure, inflammation, glomerulosclerosis and podocyte injury. Our findings put forward multiplex proteomics as a promising approach to explore novel aspects of the complex detrimental interplay between kidney function and the cardiovascular system.

  • 227.
    Carlsson, Axel C
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Ärnlöv, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Byberg, Liisa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. 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, Cardiovascular epidemiology.
    Physical activity, obesity and risk of cardiovascular disease in middle-aged men during a median of 30 years of follow-up2016In: European Journal of Preventive Cardiology, ISSN 2047-4873, E-ISSN 2047-4881, Vol. 23, no 4, p. 359-365Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    We aimed to investigate associations between combinations of body mass index (BMI)-categories, levels of physical activity and long-term risk of cardiovascular disease.

    METHOD AND RESULTS:

    At age 50 years, cardiovascular risk factors were assessed in 2196 participating men of the ULSAM-study. This investigation was repeated at age 60, 70, 77 and 82 years. Being physically active (PA) was defined as three hours of recreational or hard physical training per week. The men were categorized according to BMI/PA-status, as PA/normal weight (n = 593 at baseline), non-PA/normal weight (BMI < 25 kg/m(2), n = 580), PA/overweight (n = 418), non-PA/overweight (BMI 25-30 kg/m(2), n = 462), PA/obese (n = 62), non-PA/obese (BMI >30 kg/m(2), n = 81). We used updated data on BMI and physical activity obtained at all examinations. During follow-up (median 30 years) 850 individuals suffered a cardiovascular disease (myocardial infarction, stroke or heart failure). Using updated data on BMI/PA categories, an increased risk for cardiovascular disease was seen with increasing BMI, but a high physical activity was associated with a lower risk of cardiovascular disease within each BMI category: non-PA/normal weight (hazard ratio (HR) 1.31, 95% confidence interval (CI) 1.04-1.66), PA/overweight (HR 1.52, 95% CI 1.20-1.94), non-PA/overweight (HR 1.65, 95% CI 1.31-2.07) PA/obese (HR 2.05, 95% CI 1.44-2.92) and non-PA/obese (HR 2.39, 95% CI 1.74-3.29), using PA/normal weight men as referent.

    CONCLUSIONS:

    Although physical activity was beneficial at all levels of BMI regarding the risk of future cardiovascular disease, there was still a substantial increased risk associated with being overweight or obese during 30 years of follow-up.

  • 228. Carlsson, Sofia
    et al.
    Andersson, Tomas
    de Faire, Ulf
    Lichtenstein, Paul
    Michaelsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Ahlbom, Anders
    Using Twin Controls to Study the Effects of BMI on Mortality2011In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 22, no 1, p. 107-108Article in journal (Refereed)
  • 229. Carlsson, Sofia
    et al.
    Andersson, Tomas
    de Faire, Ulf
    Lichtenstein, Paul
    Michaëlsson, Karl
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm , UCR-Uppsala Clinical Research center.
    Ahlbom, Anders
    Body mass index and mortality: is the association explained by genetic factors?2011In: Epidemiology, ISSN 1044-3983, E-ISSN 1531-5487, Vol. 22, no 1, p. 98-103Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Numerous studies have shown that higher body mass index (BMI) is associated with higher mortality. We investigated the extent to which this association might be explained by genetic factors. METHODS: We used data from the Swedish Twin Registry on twins born 1886-1958 who answered a questionnaire in 1969/1970 or 1972 (n = 44,258). Information on mortality from all-causes (n = 14,217), cardiovascular disease (CVD; n = 9009), and coronary heart disease (CHD; n = 3564) was obtained by linkage to the national Causes of Death Registry for the years 1972-2004. The association between BMI and mortality was studied without control for genetic factors in cohort analyses and with control for genetic factors in co-twin control analyses. RESULTS: In cohort analyses, there was a clear dose-response relationship between BMI and mortality. Hazard ratios per 1 unit increase in BMI in subjects with BMI ≥18.5 were 1.05 (95% confidence interval = 1.05-1.06) for all-cause mortality, 1.07 (1.07-1.09) for CVD mortality, and 1.09 (1.08-1.10) for CHD mortality. Similar results were seen in co-twin control analyses of dizygotic twins. However, within monozygotic twins, BMI was associated with death from CHD (OR = 1.06; 1.00-1.12), whereas the association with all-cause mortality (1.01, 0.98-1.04) and CVD mortality (1.02, 0.98-1.06) was weak. CONCLUSIONS: Our findings indicate that there is an association between high BMI and mortality from CHD that is not explained by genetic confounding. However, a large part of the association between BMI and other causes of death may be explained by genes rather than by a causal link between these factors.

  • 230. Carrero, J. J.
    et al.
    Evans, M.
    Szummer, K.
    Spaak, J.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Edfors, R.
    Stenvinkel, P.
    Jacobsson, S.
    Jernberg, T.
    Warfarin treatment, kidney dysfunction and outcome in acute myocardial infarction patients with a history of atrial fibrillation2013In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 34, no S1, p. 188-188Article in journal (Other academic)
  • 231.
    Carrero, Juan J.
    et al.
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jensevik, Karin
    Szummer, Karolina
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden..
    Evans, Marie
    Karolinska Inst, Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Karolinska Inst, Clin Sci, Stockholm, Sweden..
    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.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Cardiol, Stockholm, Sweden..
    Clinical Outcomes Associated With The Duration Of Dual Antiplatelet Therapy With Clopidogrel And Aspirin In Chronic Kidney Disease Patients With Acute Coronary Syndrome2016In: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 31, p. 1441-1441Article in journal (Other academic)
  • 232. Carrero, Juan Jesus
    et al.
    Evans, Marie
    Szummer, Karolina
    Spaak, Jonas
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Edfors, Robert
    Stenvinkel, Peter
    Jacobson, Stefan H.
    Jernberg, Tomas
    Warfarin, Kidney Dysfunction, and Outcomes Following Acute Myocardial Infarction in Patients With Atrial Fibrillation2014In: Journal of the American Medical Association (JAMA), ISSN 0098-7484, E-ISSN 1538-3598, Vol. 311, no 9, p. 919-928Article in journal (Refereed)
    Abstract [en]

    IMPORTANCE Conflicting evidence exists regarding the association between warfarin treatment, death, and ischemic stroke incidence in patients with advanced chronic kidney disease (CKD) and atrial fibrillation. OBJECTIVE To study outcomes associated with warfarin treatment in relation to kidney function among patients with established cardiovascular disease and atrial fibrillation. DESIGN, SETTING, AND PARTICIPANTS Observational, 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 (SWEDEHEART) registry (2003-2010), which includes all Swedish hospitals that provide care for acute cardiac diseases. Participants included consecutive survivors of an acute myocardial infarction (MI) with atrial fibrillation and known serum creatinine (N = 24 317), including 21.8% who were prescribed warfarin at discharge. Chronic kidney disease stages were classified according to estimated glomerular filtration rate (eGFR). MAIN OUTCOMES AND MEASURES (1) Composite end point analysis of death, readmission due to MI, or ischemic stroke; (2) bleeding (composite of readmission due to hemorrhagic stroke, gastrointestinal bleeding, bleeding causing anemia, and others); or (3) the aggregate of these 2 outcomes within 1 year from discharge date. RESULTS A total of 5292 patients (21.8%) were treated with warfarin at discharge, and 51.7% had manifest CKD (eGFR <60 mL/min/1.73 m(2) [eGFR(<60)]). Compared with no warfarin use, warfarin was associated with a lower risk of the first composite outcome (n = 9002 events) in each CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 28.0 for warfarin vs 36.1 for no warfarin; adjusted hazard ratio (HR), 0.73 (95% CI, 0.65 to 0.81); eGFR(>30-60): event rate, 48.5 for warfarin vs 63.8 for no warfarin; HR, 0.73 (95% CI, 0.66 to 0.80); eGFR(>15-30): event rate, 84.3 for warfarin vs 110.1 for no warfarin; HR, 0.84 (95% CI, 0.70-1.02); eGFR(<= 15): event rate, 83.2 for warfarin vs 128.3 for no warfarin; HR, 0.57 (95% CI, 0.37-0.86). The risk of bleeding (n = 1202 events) was not significantly higher in patients treated with warfarin in any CKD stratum for event rates per 100 person-years: eGFR(>60) event rate, 5.0 for warfarin vs 4.8 for no warfarin; HR, 1.10 (95% CI, 0.86-1.41); eGFR(>30-60) event rate, 6.8 forwarfarin vs 6.3 for no warfarin; HR, 1.04 (95% CI, 0.81-1.33); eGFR(>15-30) event rate, 9.3 forwarfarin vs 10.4 for nowarfarin; HR, 0.82 (95% CI, 0.48-1.39); eGFR(<= 15) event rate, 9.1 forwarfarin vs 13.5 for nowarfarin; HR, 0.52 (95% CI, 0.16-1.65). Warfarin use in each CKD stratum was associated with lower hazards of the aggregate outcome (n = 9592 events) for event rates per 100 person-years: eGFR(>60) event rate, 32.1 for warfarin vs 40.0 for no warfarin; HR, 0.76 (95% CI, 0.69-0.84); eGFR(>30-60) event rate, 53.6 forwarfarin vs 69.0 for nowarfarin; HR, 0.75 (95% CI, 0.68-0.82); eGFR(>15-30) event rate, 90.2 forwarfarin vs 117.7 for nowarfarin; HR, 0.82 (95% CI, 0.68-0.99); eGFR(<= 15) event rate, 86.2 forwarfarin vs 138.2 for nowarfarin; HR, 0.55 (95% CI, 0.37-0.83). CONCLUSIONS AND RELEVANCE Warfarin treatment was associated with a lower 1-year risk for the composite outcome of death, MI, and ischemic stroke without a higher risk of bleeding in consecutive acute MI patients with atrial fibrillation. This association was not related to the severity of concurrent CKD.

  • 233.
    Carrero, Juan-Jesus
    et al.
    Karolinska Inst, Div Renal Med, Stockholm, Sweden.;Karolinska Inst, Ctr Mol Med, Stockholm, Sweden..
    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.
    Jensevik, Karin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Szummer, Karolina
    Karolinska Inst, Div Cardiol, Stockholm, Sweden..
    Lagerqvist, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Evans, Marie
    Karolinska Inst, Div Renal Med, Stockholm, Sweden..
    Spaak, Jonas
    Danderyd Hosp, Karolinska Inst, Dept Clin Sci, Stockholm, Sweden..
    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.
    James, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Jernberg, Tomas
    Karolinska Inst, Div Cardiol, Stockholm, Sweden..
    Long-term versus short-term dual antiplatelet therapy was similarly associated with a lower risk of death, stroke, or infarction in patients with acute coronary syndrome regardless of underlying kidney disease2017In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 91, no 1, p. 216-226Article in journal (Refereed)
    Abstract [en]

    Scarce and conflicting evidence exists on whether clopidogrel is effective and whether dual antiplatelet treatment (DAPT) is safe in patients with acute coronary syndrome and chronic kidney disease (CKD). To study this, we performed an observational, prospective, multicenter cohort study of 36,001 patients of the SWEDEHEART registry. The exposure was DAPT prolonged after 3 months versus DAPT stopped at 3 months in consecutive patients with acute coronary syndrome and known serum creatinine. DAPT duration with clopidogrel and aspirin was assessed by dispensed tablets. CKD stages were classified according to estimated glomerular filtration rate (eGFR). Study outcomes were 1) the composite of death, myocardial infarction, or ischemic stroke; 2) bleeding; or 3) the aggregate of these two outcomes within day 111 and 365 from discharge. A longer DAPT duration, as compared with 3-month DAPT, was associated with lower hazard ratios for outcome one in each CKD stratum (eGFR over 60, adjusted hazard ratio [95% confidence interval] 0.76 [0.67-0.85]; eGFR 60 and less, 0.84 [0.73-0.96], of which eGFR between 45 and 60, 0.85 [0.70-1.05], eGFR between 30 and 45, 0.78 [0.62-0.97]; eGFR 30 and less ml/min/1.73 m(2), 0.93 [0.70-1.24]. Bleeding (outcome 2) was in general more common in the longer DAPT group of each aforementioned CKD stratum. Aggregated outcome analysis (outcome 3) similarly favored longer DAPT in each stratum. There was no interaction between DAPT duration and CKD strata for any of the study outcomes. Thus, a prolonged as compared with three-month DAPT was similarly associated with a lower risk of death, stroke, or reinfarction regardless of underlying CKD.

  • 234.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmstrom, Rickard E.
    Karolinska Inst, Karolinska Univ Hosp, Dept Med, Div Clin Pharmacol, Stockholm, Sweden.
    Neovius, Martin
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
    Schwieler, Jonas
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden.
    Wettermark, Bjorn
    Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Dronedarone and Hepatic Toxicity?: A Model for Evaluation of Post-Marketing Safety of Drugs in Routine Care2017In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 26, p. 381-382Article in journal (Other academic)
  • 235.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology. Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden..
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmström, R. E.
    Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Clin Pharmacol, Stockholm, Sweden..
    Neovius, M.
    Karolinska Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden..
    Schwieler, J.
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Wettermark, B.
    Stockholm Cty Council, Publ Healthcare Serv Comm Adm, Stockholm, Sweden.;Karolinska Inst, Dept Med, Ctr Pharmacoepidemiol, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Effectiveness of Drugs in Routine Care: A Model for Sequential Monitoring of New Medicines Using Dronedarone as Example2018In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 103, no 3, p. 493-501Article in journal (Refereed)
    Abstract [en]

    Although there is no doubt about the scientific value of randomized controlled clinical trials, they are usually conducted in selected populations different fromthose treated in clinical practice. Therefore, it is important to optimize real-time post-marketing evaluation of the effectiveness, safety, and cost of new drugs. Using electronic health records and administrative health databases froma well-defined region with universal access to healthcare, we have built a framework for real-time sequential monitoring of the effectiveness of newly marketed drugs in routine care. We chose the antiarrhythmic agent dronedarone as the study drug and flecainide as the comparator drug for illustration of the model. We demonstrate that this model produces consistent results with increasing precision over time as data accumulates in the clinical systems. We believe that use of this model at the introduction of new drugs can provide complementary evidence, especially in settings of adaptive licensing of new drugs.

  • 236.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Epidemiology.
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, 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 Epidemiology.
    A framework for monitoring of new drugs in Sweden2019In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 124, no 1, p. 46-50Article in journal (Refereed)
    Abstract [en]

    In order to monitor the net public health benefit of new drugs, especially in the light of recent stepwise approval approaches, there is a need to optimize real-time post-marketing evaluation of new drugs using data collected in routine care. Sweden, with its unique possibilities for observational research, can provide these data. We herein propose a framework for continuous monitoring of the effectiveness, safety, and cost-effectiveness of new drugs, using prospectively determined protocols designed in collaboration between all relevant stakeholders. We believe that this framework can be a useful tool for healthcare authorities and reimbursement agencies in the introduction of new drugs.

  • 237.
    Cars, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiovascular epidemiology.
    Neovius, Martin
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Lindhagen, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmström, Rickard E.
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Schwieler, Jonas
    Karolinska Inst, Dept Cardiol, Stockholm, Sweden..
    Wettermark, Bjon
    Karolinska Inst, Dept Med, Stockholm, Sweden..
    Sundström, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    An Automatized Model for Sequential Monitoring of Effectiveness of New Drugs Using Dronedarone as Example2016In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 25, p. 504-504Article in journal (Refereed)
  • 238.
    Cato, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Sylvén, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Rubertsson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Risk factors of exclusive breastfeeding less than two months: identifying women in need of targeted breastfeeding supportArticle in journal (Other academic)
  • 239.
    Cato, Karin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Sylvén, Sara M
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Lindbäck, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Skalkidou, Alkistis
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, Obstetrics and Gynaecology.
    Rubertsson, Christine
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH).
    Risk factors for exclusive breastfeeding lasting less than two months-Identifying women in need of targeted breastfeeding support2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, article id e0179402Article in journal (Refereed)
    Abstract [en]

    Background: Breastfeeding rates in Sweden are declining, and it is important to identify women at risk for early cessation of exclusive breastfeeding.

    Objective: The aim of this study was to investigate factors associated with exclusive breastfeeding lasting less than two months postpartum.

    Methods: A population-based longitudinal study was conducted at Uppsala University Hospital, Sweden. Six hundred and seventy-nine women were included in this sub-study. Questionnaires were sent at five days, six weeks and six months postpartum, including questions on breastfeeding initiation and duration as well as several other background variables. The main outcome measure was exclusive breastfeeding lasting less than two months postpartum. Multivariable logistic regression analysis was used in order to calculate adjusted Odds Ratios (AOR) and 95% Confidence Intervals (95% CI).

    Results: Seventy-seven percent of the women reported exclusive breastfeeding at two months postpartum. The following variables in the multivariate regression analysis were independently associated with exclusive breastfeeding lasting less than two months postpartum: being a first time mother (AOR 2.15, 95% CI 1.32 +/- 3.49), reporting emotional distress during pregnancy (AOR 2.21, 95% CI 1.35 +/- 3.62) and giving birth by cesarean section (AOR 2.63, 95% CI 1.34 +/- 5.17).

    Conclusions: Factors associated with shorter exclusive breastfeeding duration were determined. Identification of women experiencing emotional distress during pregnancy, as well as scrutiny of caregiving routines on cesarean section need to be addressed, in order to give individual targeted breastfeeding support and promote longer breastfeeding duration.

  • 240.
    Cavalli, Marco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Pan, Gang
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Nord, Helena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Eriksson, Niclas
    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.
    Wadelius, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Wadelius, Mia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical pharmacogenomics and osteoporosis. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Novel regulatory variant detected on the VKORC1 haplotype that is associated with warfarin dose2016In: Pharmacogenomics (London), ISSN 1462-2416, E-ISSN 1744-8042, Vol. 17, no 12, p. 1305-1314Article in journal (Refereed)
    Abstract [en]

    Aim: Warfarin dose requirement is associated with VKORC1 rs9923231, and we studied whether it is a functional variant.

    Materials & methods: We selected variants in linkage disequilibrium with rs9923231 that bind transcription factors in an allele-specific way. Representative haplotypes were cloned or constructed, nuclear protein binding and transcriptional activity were evaluated.

    Results: rs56314408C>T and rs2032915C>T were detected in a liver enhancer in linkage disequilibrium with rs9923231. The rs56314408-rs2032915 C-C haplotype preferentially bound nuclear proteins and had higher transcriptional activity than T-T and the African-specific T-C. A motif for TFAP2A/C was disrupted by rs56314408T. No difference in transcriptional activity was detected for rs9923231G>A.

    Conclusion: Our results supported an activating role for rs56314408C, while rs9923231G>A had no evidence of being functional.

  • 241. Cecilia Bahit, Maria
    et al.
    Lopes, Renato D.
    Wojdyla, Daniel M.
    Hohnloser, Stefan H.
    Alexander, John H.
    Lewis, Basil S.
    Aylward, Philip E.
    Verheugt, Freek W. A.
    Keltai, Matyas
    Diaz, Rafael
    Hanna, Michael
    Granger, Christopher B.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Apixaban in patients with atrial fibrillation and prior coronary artery disease: Insights from the ARISTOTLE trial2013In: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 170, no 2, p. 215-220Article in journal (Refereed)
    Abstract [en]

    Background: A substantial portion of patients with atrial fibrillation (AF) also have coronary artery disease (CAD) and are at risk for coronary events. Warfarin is known to reduce these events, but increase the risk of bleeding. We assessed the effects of apixaban compared with warfarin in AF patients with and without prior CAD. Methods and results: In ARISTOTLE, 18,201 patients with AF were randomized to apixaban or warfarin. History of CAD was defined as documented CAD, prior myocardial infarction, and/or history of coronary revascularization. We analyzed baseline characteristics and clinical outcomes of patients with and without prior CAD and compared outcomes by randomized treatment using Cox models. A total of 6639 (36.5%) patients had prior CAD. These patients were more often male, more likely to have prior stroke, diabetes, and hypertension, and more often received aspirin at baseline (42.2% vs. 24.5%). The effects of apixaban were similar among patients with and without prior CAD on reducing stroke or systemic embolism and death from any cause (hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.71-1.27, P for interaction = 0.12; HR 0.96, 95% CI 0.81-1.13, P for interaction = 0.28). Rates of myocardial infarction were numerically lower with apixaban than warfarin among patients with and without prior CAD. The effect of apixaban on reducing major bleeding and intracranial hemorrhage was consistent in patients with and without CAD. Conclusions: In patients with AF, apixaban more often prevented stroke or systemic embolism and death and caused less bleeding than warfarin, regardless of the presence of prior CAD. Given the common occurrence of AF and CAD and the higher rates of cardiovascular events and death, our results indicate that apixaban may be a better treatment option than warfarin for these high-risk patients.

  • 242.
    Chami, Nathalie
    et al.
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Chen, Ming-Huei
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Slater, Andrew J.
    GlaxoSmithKline, Genet Target Sci, Res Triangle Pk, Res Triangle Pk, NC 27709 USA.;OmicSoft Corp, Cary, NC 27513 USA..
    Eicher, John D.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Evangelou, Evangelos
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina 45110, Greece..
    Tajuddin, Salman M.
    NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA..
    Love-Gregory, Latisha
    Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA..
    Kacprowski, Tim
    Ernst Moritz Arndt Univ Greifswald, Dept Funct Gen, Interfaculty Inst Genet & Funct Gen, Univ Med, D-17475 Greifswald, Germany.;DZHK German Ctr Cardiovasc Res, Partner Site Greifswald, Greifswald, Germany..
    Schick, Ursula M.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA..
    Nomura, Akihiro
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA.;Kanazawa Univ, Grad Sch Med Sci, Div Cardiovasc Med, Kanazawa, Ishikawa 9200942, Japan..
    Giri, Ayush
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Div Epidemiol, Nashville, TN 37235 USA..
    Lessard, Samuel
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Brody, Jennifer A.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Schurmann, Claudia
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Pankratz, Nathan
    Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55454 USA..
    Yanek, Lisa R.
    Johns Hopkins Univ, Sch Med, Dept Med Div Gen Internal Med icine, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Manichaikul, Ani
    Univ Virginia, Ctr Publ Hlth Gen, Charlottesville, VA 22908 USA..
    Pazoki, Raha
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands..
    Mihailov, Evelin
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Hill, W. David
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland..
    Raffield, Laura M.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Burt, Amber
    Univ Washington, Div Med Genet, Dept Med, Seattle, WA 98195 USA..
    Bartz, Traci M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Becker, Diane M.
    Johns Hopkins Univ, Sch Med, Dept Med Div Gen Internal Med icine, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Becker, Lewis C.
    Johns Hopkins Univ Sch Med, Dept Med, Div Cardiol & Gen Internal Med, Baltimore, MD 21205 USA..
    Boerwinkle, Eric
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Bork-Jensen, Jette
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Bottinger, Erwin P.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA..
    O'Donoghue, Michelle L.
    Brigham & Womens Hosp, Cardiovasc Div, TIMI Study Grp, Boston, MA 02115 USA..
    Crosslin, David R.
    Univ Washington, Dept Biomed Informat & Med Educ, Seattle, WA 98195 USA..
    de Denus, Simon
    Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada.;Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada..
    Dube, Marie-Pierre
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Elliott, Paul
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England..
    Engstrom, Gunnar
    Lund Univ, Dept Clin Sci, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Evans, Michele K.
    NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA..
    Floyd, James S.
    Univ Washington, Dept Med, Seattle, WA 98101 USA..
    Fornage, Myriam
    Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA..
    Gao, He
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England..
    Greinacher, Andreas
    Univ Med Greifswald, Inst Immunol & Transfus Med, D-17475 Greifswald, Germany..
    Gudnason, Vilmundur
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Hansen, Torben
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Harris, Tamara B.
    NIA, Intramural Res Program, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Hayward, Caroline
    Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland..
    Hernesniemi, Jussi
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland.;Univ Tampere, Sch Med, Tampere 33014, Finland..
    Highland, Heather M.
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.;Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27514 USA..
    Hirschhorn, Joel N.
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Boston Childrens Hosp, Dept Endocrinol, Boston, MA 02115 USA..
    Hofman, Albert
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands.;Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA..
    Irvin, Marguerite R.
    Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35233 USA..
    Kahonen, Mika
    Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.;Univ Tampere, Dept Clin Physiol, Sch Med, Tampere 33014, Finland..
    Lange, Ethan
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.;Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA..
    Launer, Lenore J.
    NIA, Intramural Res Program, NIH, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA..
    Lehtimaki, Terho
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Li, Jin
    Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Palo Alto, CA 94305 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..
    Linneberg, Allan
    Capital Region Denmark, Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark.;Rigshosp, Dept Clin Expt Res, DK-2100 Glostrup, Denmark.;Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, DK-2200 Copenhagen, Denmark..
    Liu, Yongmei
    Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA..
    Lu, Yingchang
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA..
    Lyytikainen, Leo-Pekka
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Magi, Reedik
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mathias, Rasika A.
    Johns Hopkins Univ Sch Med, Dept Med, Div Allergy & Clin Immunol, Baltimore, MD 21205 USA.;Johns Hopkins Univ Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA..
    Melander, Olle
    Lund Univ, Dept Clin Sci, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Metspalu, Andres
    Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Mononen, Nina
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Nalls, Mike A.
    NIA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA..
    Nickerson, Deborah A.
    Univ Washington, Dept Genome Sci, Seattle, WA 98105 USA..
    Nikus, Kjell
    Univ Tampere, Sch Med, Tampere 33014, Finland.;Tampere Univ Hosp, Dept Cardiol, Ctr Heart, Tampere 33521, Finland..
    O'Donnell, Chris J.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA.;Boston Vet Adm VA Healthcare, Cardiol Sect, Boston, MA 02118 USA.;Boston Vet Adm VA Healthcare, Ctr Populat Gen, Boston, MA 02118 USA..
    Orho-Melander, Marju
    Lund Univ, Dept Clin Sci, S-22100 Malmo, Sweden.;Skane Univ Hosp, S-22241 Malmo, Sweden..
    Pedersen, Oluf
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Petersmann, Astrid
    Univ Med Greifswald, Inst Clin Chem & Lab Med, D-17475 Greifswald, Germany..
    Polfus, Linda
    Univ Texas Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA..
    Psaty, Bruce M.
    Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA.;Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA 98101 USA..
    Raitakari, Olli T.
    Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20521, Finland.;Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland..
    Raitoharju, Emma
    Fimlab Labs, Dept Clin Chem, Tampere 33520, Finland.;Univ Tampere, Dept Clin Chem, Sch Med, Tampere 33014, Finland..
    Richard, Melissa
    Univ Texas Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA..
    Rice, Kenneth M.
    Univ Washington, Dept Biostat, Seattle, WA 98195 USA..
    Rivadeneira, Fernando
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands.;Erasmus MC, Dept Internal Med, NL-3000 Rotterdam, Netherlands.;NCHA, NL-3015 Rotterdam, Netherlands..
    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..
    Schmidt, Frank
    Ernst Moritz Arndt Univ Greifswald, Dept Funct Gen, Interfaculty Inst Genet & Funct Gen, Univ Med, D-17475 Greifswald, Germany..
    Smith, Albert Vernon
    Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland..
    Starr, John M.
    Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.;Alzheimer Scotland Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland..
    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..
    Teumer, Alexander
    Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany..
    Thuesen, Betina H.
    Capital Region Denmark, Res Ctr Prevent & Hlth, DK-2600 Copenhagen, Denmark..
    Torstenson, Eric S.
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Div Epidemiol, Nashville, TN 37235 USA..
    Tracy, Russell P.
    Univ Vermont Coll Med, Dept Pathol, Colchester, VT 05446 USA.;Univ Vermont Coll Med, Dept Lab Med, Colchester, VT 05446 USA.;Univ Vermont Coll Med, Dept Biochem, Colchester, VT 05446 USA..
    Tzoulaki, Ioanna
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, England.;Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Ioannina 45110, Greece..
    Zakai, Neil A.
    Univ Vermont Coll Med, Dept Med, Burlington, VT 05405 USA.;Univ Vermont Coll Med, Dept Pathol, Burlington, VT 05405 USA..
    Vacchi-Suzzi, Caterina
    SUNY Stony Brook, Dept Family Populat & Prevent Med, Stony Brook, NY 11794 USA..
    van Duijn, Cornelia M.
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands..
    van Rooij, Frank J. A.
    Erasmus, Dept Epidemiol, NL-3000 Mcrotterdam, Netherlands..
    Cushman, Mary
    Univ Vermont Coll Med, Dept Med, Burlington, VT 05405 USA.;Univ Vermont Coll Med, Dept Pathol, Burlington, VT 05405 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..
    Edwards, Digna R. Velez
    Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Dept Obstet & Gynecol, Inst Med & Publ Hlth,Vanderbilt Genet Inst, Nashville, TN 37203 USA..
    Vergnaud, Anne-Claire
    Imperial Coll London, Dept Epidemiol & Biostat, MRC PHE Ctr Environm & Hlth, Sch Publ Hlth, London W2 1PG, 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.
    Waterworth, Dawn M.
    Genet Target Sci, GlaxoSmithKline, King Of Prussia, PA 19406 USA..
    White, Harvey D.
    Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand.;Univ Auckland, Auckland 1142, New Zealand..
    Wilson, James G.
    Univ Mississippi Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA..
    Zonderman, Alan B.
    NIA, Lab Epidemiol & Populat Sci, Baltimore, MD 21224 USA..
    Kathiresan, Sekar
    Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.;Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.;Harvard Med Sch, Dept Med, Boston, MA 02115 USA..
    Grarup, Niels
    Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn, Ctr Basic Metabol Res, DK-2100 Copenhagen, Denmark..
    Esko, Tonu
    Broad Inst, Program Med & Populat Genet, Cambridge, MA 02142 USA.;Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia..
    Loos, Ruth J. F.
    Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10069 USA.;Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10069 USA..
    Lange, Leslie A.
    Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA..
    Faraday, Nauder
    Johns Hopkins Univ, Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USA..
    Abumrad, Nada A.
    Washington Univ, Sch Med, Dept Med, Ctr Human Nutr, St Louis, MO 63110 USA..
    Edwards, Todd L.
    Vanderbilt Univ, Inst Med & Publ Hlth, Vanderbilt Genet Inst, Div Epidemiol, Nashville, TN 37235 USA..
    Ganesh, Santhi K.
    Univ Michigan, Dept Internal Med, Ann Arbor, MI 48108 USA.;Univ Michigan, Dept Human Genet, Ann Arbor, MI 48108 USA..
    Auer, Paul L.
    Univ Wisconsin, Zilber Sch Publ Hlth, Milwaukee, WI 53205 USA..
    Johnson, Andrew D.
    NHLBI, Populat Sci Branch, Framingham Heart Study, Framingham, MA 01702 USA..
    Reiner, Alexander P.
    Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.;Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA..
    Lettre, Guillaume
    Univ Montreal, Dept Med, Montreal, PQ H3T 1J4, Canada.;Montreal Heart Inst, Montreal, PQ H1T 1CB, Canada..
    Exome Genotyping Identifies Pleiotropic Variants Associated with Red Blood Cell Traits2016In: American Journal of Human Genetics, ISSN 0002-9297, E-ISSN 1537-6605, Vol. 99, no 1, p. 8-21Article in journal (Refereed)
    Abstract [en]

    Red blood cell (RBC) traits are important heritable clinical biomarkers and modifiers of disease severity. To identify coding genetic variants associated with these traits, we conducted meta-analyses of seven RBC phenotypes in 130,273 multi-ethnic individuals from studies genotyped on an exome array. After conditional analyses and replication in 27,480 independent individuals, we identified 16 new RBC variants. We found low-frequency missense variants in MAP1A (rs55707100, minor allele frequency [MAF] = 3.3%, p = 2 x 10(-10) for hemoglobin [HGB]) and HNF4A (rs1800961, MAF = 2.4%, p < 3 x 10(-8) for hematocrit [HCT] and HGB). In African Americans, we identified a nonsense variant in CD36 associated with higher RBC distribution width (rs3211938, MAF = 8.7%, p = 7 x 10(-11)) and showed that it is associated with lower CD36 expression and strong allelic imbalance in ex vivo differentiated human erythroblasts. We also identified a rare missense variant in ALAS2 (rs201062903, MAF = 0.2%) associated with lower mean corpuscular volume and mean corpuscular hemoglobin (p < 8 x 10(-9)). Mendelian mutations in ALAS2 are a cause of sideroblastic anemia and erythropoietic protoporphyria. Gene-based testing highlighted three rare missense variants in PKLR, a gene mutated in Mendelian non-spherocytic hemolytic anemia, associated with HGB and HCT (SKAT p < 8 x 10(-7)). These rare, low-frequency, and common RBC variants showed pleiotropy, being also associated with platelet, white blood cell, and lipid traits. Our association results and functional annotation suggest the involvement of new genes in human erythropoiesis. We also confirm that rare and low-frequency variants play a role in the architecture of complex human traits, although their phenotypic effect is generally smaller than originally anticipated.

  • 243. Chasman, Daniel I.
    et al.
    Fuchsberger, Christian
    Pattaro, Cristian
    Teumer, Alexander
    Boeger, Carsten A.
    Endlich, Karlhans
    Olden, Matthias
    Chen, Ming-Huei
    Tin, Adrienne
    Taliun, Daniel
    Li, Man
    Gao, Xiaoyi
    Gorski, Mathias
    Yang, Qiong
    Hundertmark, Claudia
    Foster, Meredith C.
    O'Seaghdha, Conall M.
    Glazer, Nicole
    Isaacs, Aaron
    Liu, Ching-Ti
    Smith, Albert V.
    O'Connell, Jeffrey R.
    Struchalin, Maksim
    Tanaka, Toshiko
    Li, Guo
    Johnson, Andrew D.
    Gierman, Hinco J.
    Feitosa, Mary F.
    Hwang, Shih-Jen
    Atkinson, Elizabeth J.
    Lohman, Kurt
    Cornelis, Marilyn C.
    Johansson, Åsa
    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 Immunology, Genetics and Pathology, Genomics.
    Toenjes, Anke
    Dehghan, Abbas
    Lambert, Jean-Charles
    Holliday, Elizabeth G.
    Sorice, Rossella
    Kutalik, Zoltan
    Lehtimaeki, Terho
    Esko, Tonu
    Deshmukh, Harshal
    Ulivi, Sheila
    Chu, Audrey Y.
    Murgia, Federico
    Trompet, Stella
    Imboden, Medea
    Coassin, Stefan
    Pistis, Giorgio
    Harris, Tamara B.
    Launer, Lenore J.
    Aspelund, Thor
    Eiriksdottir, Gudny
    Mitchell, Braxton D.
    Boerwinkle, Eric
    Schmidt, Helena
    Cavalieri, Margherita
    Rao, Madhumathi
    Hu, Frank
    Demirkan, Ayse
    Oostra, Ben A.
    de Andrade, Mariza
    Turner, Stephen T.
    Ding, Jingzhong
    Andrews, Jeanette S.
    Freedman, Barry I.
    Giulianini, Franco
    Koenig, Wolfgang
    Illig, Thomas
    Meisinger, Christa
    Gieger, Christian
    Zgaga, Lina
    Zemunik, Tatijana
    Boban, Mladen
    Minelli, Cosetta
    Wheeler, Heather E.
    Igl, Wilmar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Zaboli, Ghazal
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wild, Sarah H.
    Wright, Alan F.
    Campbell, Harry
    Ellinghaus, David
    Noethlings, Ute
    Jacobs, Gunnar
    Biffar, Reiner
    Ernst, Florian
    Homuth, Georg
    Kroemer, Heyo K.
    Nauck, Matthias
    Stracke, Sylvia
    Voelker, Uwe
    Voelzke, Henry
    Kovacs, Peter
    Stumvoll, Michael
    Maegi, Reedik
    Hofman, Albert
    Uitterlinden, Andre G.
    Rivadeneira, Fernando
    Aulchenko, Yurii S.
    Polasek, Ozren
    Hastie, Nick
    Vitart, Veronique
    Helmer, Catherine
    Wang, Jie Jin
    Stengel, Benedicte
    Ruggiero, Daniela
    Bergmann, Sven
    Kahonen, Mika
    Viikari, Jorma
    Nikopensius, Tiit
    Province, Michael
    Ketkar, Shamika
    Colhoun, Helen
    Doney, Alex
    Robino, Antonietta
    Kraemer, Bernhard K.
    Portas, Laura
    Ford, Ian
    Buckley, Brendan M.
    Adam, Martin
    Thun, Gian-Andri
    Paulweber, Bernhard
    Haun, Margot
    Sala, Cinzia
    Mitchell, Paul
    Ciullo, Marina
    Kim, Stuart K.
    Vollenweider, Peter
    Raitakari, Olli
    Metspalu, Andres
    Palmer, Colin
    Gasparini, Paolo
    Pirastu, Mario
    Jukema, J. Wouter
    Probst-Hensch, Nicole M.
    Kronenberg, Florian
    Toniolo, Daniela
    Gudnason, Vilmundur
    Shuldiner, Alan R.
    Coresh, Josef
    Schmidt, Reinhold
    Ferrucci, Luigi
    Siscovick, David S.
    van Duijn, Cornelia M.
    Borecki, Ingrid B.
    Kardia, Sharon L. R.
    Liu, Yongmei
    Curhan, Gary C.
    Rudan, Igor
    Gyllensten, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Genomics.
    Wilson, James F.
    Franke, Andre
    Pramstaller, Peter P.
    Rettig, Rainer
    Prokopenko, Inga
    Witteman, Jacqueline
    Hayward, Caroline
    Ridker, Paul M.
    Parsa, Afshin
    Bochud, Murielle
    Heid, Iris M.
    Kao, W. H. Linda
    Fox, Caroline S.
    Koettgen, Anna
    Integration of genome-wide association studies with biological knowledge identifies six novel genes related to kidney function2012In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 21, no 24, p. 5329-5343Article in journal (Refereed)
    Abstract [en]

    In conducting genome-wide association studies (GWAS), analytical approaches leveraging biological information may further understanding of the pathophysiology of clinical traits. To discover novel associations with estimated glomerular filtration rate (eGFR), a measure of kidney function, we developed a strategy for integrating prior biological knowledge into the existing GWAS data for eGFR from the CKDGen Consortium. Our strategy focuses on single nucleotide polymorphism (SNPs) in genes that are connected by functional evidence, determined by literature mining and gene ontology (GO) hierarchies, to genes near previously validated eGFR associations. It then requires association thresholds consistent with multiple testing, and finally evaluates novel candidates by independent replication. Among the samples of European ancestry, we identified a genome-wide significant SNP in FBXL20 (P 5.6 10(9)) in meta-analysis of all available data, and additional SNPs at the INHBC, LRP2, PLEKHA1, SLC3A2 and SLC7A6 genes meeting multiple-testing corrected significance for replication and overall P-values of 4.5 10(4)2.2 10(7). Neither the novel PLEKHA1 nor FBXL20 associations, both further supported by association with eGFR among African Americans and with transcript abundance, would have been implicated by eGFR candidate gene approaches. LRP2, encoding the megalin receptor, was identified through connection with the previously known eGFR gene DAB2 and extends understanding of the megalin system in kidney function. These findings highlight integration of existing genome-wide association data with independent biological knowledge to uncover novel candidate eGFR associations, including candidates lacking known connections to kidney-specific pathways. The strategy may also be applicable to other clinical phenotypes, although more testing will be needed to assess its potential for discovery in general.

  • 244.
    Chen, Yundai
    et al.
    Chinese PLA Gen Hosp 301 Hosp, Dept Cardiol, Beijing, Peoples R China..
    Li, Dandan
    Chinese PLA Gen Hosp 301 Hosp, Dept Hematol, Beijing, Peoples R China..
    Jing, Jing
    Chinese PLA Gen Hosp 301 Hosp, Dept Hematol, Beijing, Peoples R China..
    Yan, Hongbing
    Natl Ctr Cardiovasc Dis, Cardiovasc Inst, Beijing, Peoples R China.;FuWai Hosp, Beijing, Peoples R China..
    Liu, Jinghua
    Capital Med Univ, Beijing Anzhen Hosp, Dept Cardiol, Beijing, Peoples R China..
    Shen, Zhujun
    Beijing Union Med Coll Hosp, Dept Cardiol, Beijing, Peoples R China..
    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.
    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.
    Treatment Trends, Effectiveness, and Safety of Statins on Lipid Goal Attainment in Chinese Percutaneous Coronary Intervention Patients: a Multicenter, Retrospective Cohort Study2017In: Clinical Therapeutics, ISSN 0149-2918, E-ISSN 1879-114X, Vol. 39, no 9, p. 1827-1839Article in journal (Refereed)
    Abstract [en]

    Purpose: Limited data exist on the use of statins in Chinese patients with coronary artery disease (CAD) treated with percutaneous coronary intervention (PCI). We therefore conducted this study to observe the usage trend and the effectiveness of statins on LDL-C goal attainment and other lipid parameters among PCI-treated patients.

    Methods: This multicenter, retrospective, observational, longitudinal cohort study was conducted in PCI-treated patients with CAD between July 1, 2011, and February 28, 2015. Primary study outcomes included statin treatment pattern after PCI and proportion of patients achieving target (LDL-C) levels 1 month after PCI and initiating statin therapy.

    Findings: Data were analyzed for 2708 patients (mean age, 59 [10] years; median body mass index, 25.6 [4.0] kg/m(2)). From baseline to the end of 1 month, atorvastatin and rosuvastatin were the most prescribed statins; 20 mg and 10 mg were the most prescribed doses and therefore chosen for efficacy comparisons. In patients without dose changes, LDL-C reduction with rosuvastatin 10 mg was significantly greater compared with atorvastatin 20 mg (-0.67 mmol/L [from 2.44 mmol/L to 1.77 mmol/L] vs 0.54 mmol/L [from 2.40 mmol/L to 1.86 mmol/L]; P = 0.008). However, there was no difference in HDL-C, triglyceride, or total cholesterol values between groups. Age and LDL-C levels at baseline were significantly associated with target LDL-C achievement.

  • 245.
    Chew, Michelle S.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Mangelus, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Enlund, Gunnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Spetz, Peter
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Lyckner, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Surgery was successful - but how did it go for the patient?: Experiences from and hopes for the Swedish Perioperative Register2015In: European Journal of Anaesthesiology, ISSN 0265-0215, E-ISSN 1365-2346, Vol. 32, no 7, p. 453-454Article in journal (Other academic)
  • 246.
    Christersson, Albert
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nysjö, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Berglund, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Malmberg, Filip
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Nyström, Ingela
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Comparison of 2D radiography and a semi-automatic CT-based 3D method for measuring change in dorsal angulation over time in distal radius fractures2016In: Skeletal Radiology, ISSN 0364-2348, E-ISSN 1432-2161, Vol. 45, no 6, p. 763-769Article in journal (Refereed)
    Abstract [en]

    Objective The aim of the present study was to compare the reliability and agreement between a computer tomography-based method (CT) and digitalised 2D radiographs (XR) when measuring change in dorsal angulation over time in distal radius fractures. Materials and methods Radiographs from 33 distal radius fractures treated with external fixation were retrospectively analysed. All fractures had been examined using both XR and CT at six times over 6 months postoperatively. The changes in dorsal angulation between the first reference images and the following examinations in every patient were calculated from 133 follow-up measurements by two assessors and repeated at two different time points. The measurements were analysed using Bland-Altman plots, comparing intra- and inter-observer agreement within and between XR and CT. Results The mean differences in intra- and inter-observer measurements for XR, CT, and between XR and CT were close to zero, implying equal validity. The average intra- and inter-observer limits of agreement for XR, CT, and between XR and CT were +/- 4.4 degrees, +/- 1.9 degrees and +/- 6.8 degrees respectively. Conclusions For scientific purpose, the reliability of XR seems unacceptably low when measuring changes in dorsal angulation in distal radius fractures, whereas the reliability for the semi-automatic CT-based method was higher and is therefore preferable when a more precise method is requested.

  • 247.
    Christersson, Christina
    et al.
    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, 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.
    Jönelid, Birgitta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Thulin, Åsa
    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.
    The change of the amount of circulating microparticles and their association to the general atherosclerotic burden after acute coronary syndrome2015In: Journal of Thrombosis and Haemostasis, ISSN 1538-7933, E-ISSN 1538-7836, Vol. 13, no S2, p. 214-214, article id OR312Article in journal (Other academic)
  • 248.
    Christersson, Christina
    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.
    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.
    Berglund, Lars
    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, Clinical Chemistry.
    Oldgren, Jonas
    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.
    The utility of coagulation activity for prediction of risk of mortality and cardiovascular events in guideline-treated myocardial infarction patients2017In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 4, p. 224-233Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Despite improved treatment of myocardial infarction (MI), real-world patients still suffer substantial risk for subsequent cardiovascular events. Little is known about coagulation activity shortly after MI and whether coagulation activity markers may identify patients at increased risk despite contemporary treatment.

    OBJECTIVE: To evaluate D-dimer concentration and thrombin generation potential shortly after discharge after MI and evaluate if these markers could predict the risk of future cardiovascular and bleeding events.

    METHODS: Unselected MI patients (n = 421) were included in the observational REBUS study (NCT01102933) and followed for two years. D-dimer concentrations, thrombin peak, and endogenous thrombin potential (ETP) were analyzed at inclusion (3-5 days after MI) and at early follow-up (after 2-3 weeks).

    RESULTS: Seventy-five patients (17.8%) experienced the composite endpoint (all-cause death, MI, congestive heart failure, or all-cause stroke), and 31 patients (7.4%) experienced a clinically relevant bleeding event. D-dimer concentrations at early follow-up were associated with the composite endpoint (HR [per SD increase] 1.51 [95% CI 1.22-1.87]) and with clinically relevant bleeding (HR [per SD increase] 1.80 [95% CI 1.32-2.44]). Thrombin generation potential was not significantly associated with either the composite endpoint or with clinically relevant bleeding. Higher thrombin peak and ETP at early follow-up were both inversely associated with stroke (HR [per SD increase] 0.50 [95% CI 0.30-0.81] and 0.43 [95% CI 0.22-0.83], respectively).

    CONCLUSION: In unselected MI patients treated according to contemporary guidelines, D-dimer measurements may identify patients at increased risk of new cardiovascular and bleeding events. The inverse association of thrombin generation potential and risk of stroke has to be further investigated.

  • 249.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    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.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    The composition and daily variation of microparticles in whole blood in stable coronary artery disease2016In: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 76, no 1Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The knowledge of circadian variation of microparticles (MPs) in stable coronary artery disease (SCAD) is limited. The aim of this study was to evaluate the daily variation of platelet-, endothelial- and monocyte-derived MPs in whole blood and their tissue factor expression (TF) in SCAD and whether these MPs were related to other endothelial and coagulation markers.

    MATERIALS AND METHODS: Serial blood samples from patients with SCAD were collected during one day. Flow cytometry was used to evaluate the amount of large MPs 0.5-1.0 μm, positive for annexin, and their expression of CD41, CD62P, CD144, CD14 and TF. The lag time and endogenous thrombin potential (ETP) was calculated by Calibrated Automated Thrombogram and soluble (s)P-selectin, sTF and vWF by ELISA.

    RESULTS: The majority of MPs in whole blood consisted of CD41 + MPs with no significant daily variation. In contrast, the concentration of CD62P + MPs described a daily variation with the lowest concentrations found in the evening (p = 0.031). CD62P + and CD144 + MPs had the highest expression of TF, 52.6% and 42.9%, respectively, and correlated to the endothelial activity evaluated by vWF. There was a circadian rhythm of lag time (p < 0.001) and ETP (p = 0.001). The CD62P+, CD14 + and CD144 + MPs correlated to the lag time.

    CONCLUSION: The different subsets of platelet-, endothelial- and monocyte-derived MPs do not present the same circadian variation and they differ in TF expression in SCAD. The MPs from activated platelets, endothelial cells and monocytes exist in low concentrations in whole blood but are related to the endothelial and coagulation activity found in SCAD.

  • 250.
    Christersson, Christina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Oldgren, Jonas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bylock, Anders
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Early decrease in coagulation activity after myocardial infarction is associated with lower risk of new ischaemic events: observations from the ESTEEM: Reply2007In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 28, no 14, p. 1783-1783Article in journal (Refereed)
2345678 201 - 250 of 1574
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