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1.
  • Deloukas, Panos, et al. (författare)
  • Large-scale association analysis identifies new risk loci for coronary artery disease
  • 2013
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 45:1, s. 25-33
  • Tidskriftsartikel (refereegranskat)abstract
    • Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR). Together, these variants explain approximately 10.6% of CAD heritability. Of the 46 genome-wide significant lead SNPs, 12 show a significant association with a lipid trait, and 5 show a significant association with blood pressure, but none is significantly associated with diabetes. Network analysis with 233 candidate genes (loci at 10% FDR) generated 5 interaction networks comprising 85% of these putative genes involved in CAD. The four most significant pathways mapping to these networks are linked to lipid metabolism and inflammation, underscoring the causal role of these activities in the genetic etiology of CAD. Our study provides insights into the genetic basis of CAD and identifies key biological pathways.
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4.
  • Grip, Lars, et al. (författare)
  • From European to National guidelines on heart disease
  • 2011
  • Ingår i: Scandinavian Cardiovascular Journal. - 1401-7431 .- 1651-2006. ; 45:1, s. 3-13
  • Forskningsöversikt (refereegranskat)abstract
    • <p>Background/aims. Guidelines from the European Society of Cardiology are important tools for defining and establishing current standards of care for various heart diseases. The aim of the present paper is to describe the process of how these international guidelines may be transformed and implemented at a national level in Sweden. Methods/results. The structure and process behind the national guidelines for heart diseases in Sweden and their relationship to the underlying European guidelines are described and differences between the national and European levels highlighted. We also give examples of how the scientific values of health care measures are weighted against health economic perspectives and integrated in a prioritization process. Compared to the European guidelines, the Swedish national guidelines have a broader economic perspective and aim to ensure that health care is cost effective and provided to all Swedish citizens on equal terms. Discussion. When certain health care measures are implemented, the national process can result in other priorities than could be expected from the European guidelines alone. On the other hand, a forceful implementation may be facilitated by the societal context in which these national guidelines are produced.</p>
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5.
  • Grip, Lars, et al. (författare)
  • From European to National guidelines on heart disease
  • 2011
  • Ingår i: SCANDINAVIAN CARDIOVASCULAR JOURNAL. - Informa Healthcare. - 1401-7431. ; 45:1, s. 3-13
  • Forskningsöversikt (refereegranskat)abstract
    • <p>Background/aims. Guidelines from the European Society of Cardiology are important tools for defining and establishing current standards of care for various heart diseases. The aim of the present paper is to describe the process of how these international guidelines may be transformed and implemented at a national level in Sweden. Methods/results. The structure and process behind the national guidelines for heart diseases in Sweden and their relationship to the underlying European guidelines are described and differences between the national and European levels highlighted. We also give examples of how the scientific values of health care measures are weighted against health economic perspectives and integrated in a prioritization process. Compared to the European guidelines, the Swedish national guidelines have a broader economic perspective and aim to ensure that health care is cost effective and provided to all Swedish citizens on equal terms. Discussion. When certain health care measures are implemented, the national process can result in other priorities than could be expected from the European guidelines alone. On the other hand, a forceful implementation may be facilitated by the societal context in which these national guidelines are produced.</p>
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6.
  • Grip, Lars, 1952-, et al. (författare)
  • From European to National guidelines on heart disease.
  • 2011
  • Ingår i: Scandinavian cardiovascular journal : SCJ. - 1651-2006. ; 45:1, s. 3-13
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract Background/aims. Guidelines from the European Society of Cardiology are important tools for defining and establishing current standards of care for various heart diseases. The aim of the present paper is to describe the process of how these international guidelines may be transformed and implemented at a national level in Sweden. Methods/results. The structure and process behind the national guidelines for heart diseases in Sweden and their relationship to the underlying European guidelines are described and differences between the national and European levels highlighted. We also give examples of how the scientific values of health care measures are weighted against health economic perspectives and integrated in a prioritization process. Compared to the European guidelines, the Swedish national guidelines have a broader economic perspective and aim to ensure that health care is cost effective and provided to all Swedish citizens on equal terms. Discussion. When certain health care measures are implemented, the national process can result in other priorities than could be expected from the European guidelines alone. On the other hand, a forceful implementation may be facilitated by the societal context in which these national guidelines are produced.
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7.
  • Levin, Lars-Ake, et al. (författare)
  • Health-Related Quality of Life of Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes-Results from the PLATO Trial
  • 2013
  • Ingår i: Value in Health. - 1098-3015 .- 1524-4733. ; 16:4, s. 574-580
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objectives: The purpose of this study was to compare the effects of ticagrelor versus clopidogrel on health-related quality of life in the PLATelet inhibition and patient Outcomes (PLATO) trial. Background: The PLATO trial showed that ticagrelor was superior to clopidogrel for the prevention of cardiovascular death, myocardial infarction, or stroke in a broad population of patients with acute coronary syndromes. Methods: HRQOL in the PLATO study was measured at hospital discharge, 6-month visit, and end of treatment (anticipated at 12 months) by using the EuroQol five-dimensional (EQ-5D) questionnaire. All patients who had an EQ-5D questionnaire assessment at discharge from the index hospitalization (n = 15,212) were included in the study. Patients who died prior to the end-of-treatment visit were assigned an EQ-5D questionnaire value of 0. Results: The EQ-5D questionnaire value at discharge among 7631 patients assigned to ticagrelor was 0.847 and among 7581 patients assigned to clopidogrel was 0.846 (P = 0.71). At 12 months, the mean EQ-5D questionnaire value was 0.840 for ticagrelor and 0.832 for clopidogrel (P = 0.046). Excluding patients who died resulted in mean EQ-5D questionnaire values of 0.864 among ticagrelor patients and 0.863 among clopidogrel patients (P = 0.69). Conclusions: In patients hospitalized with acute coronary syndromes with or without ST-segment elevation, treatment with ticagrelor was associated with a lower mortality but otherwise no difference in quality of life relative to treatment with clopidogrel. The improved survival and reduction in cardiovascular events with ticagrelor are therefore obtained with no loss in quality of life.</p>
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8.
  • Levin, Lars-Åke, et al. (författare)
  • Health-Related Quality of Life of Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes-Results from the PLATO Trial
  • 2013
  • Ingår i: Value in Health. - Wiley-Blackwell: No OnlineOpen / Elsevier. - 1098-3015 .- 1524-4733. ; 16:4, s. 574-580
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Objectives: The purpose of this study was to compare the effects of ticagrelor versus clopidogrel on health-related quality of life in the PLATelet inhibition and patient Outcomes (PLATO) trial. Background: The PLATO trial showed that ticagrelor was superior to clopidogrel for the prevention of cardiovascular death, myocardial infarction, or stroke in a broad population of patients with acute coronary syndromes. Methods: HRQOL in the PLATO study was measured at hospital discharge, 6-month visit, and end of treatment (anticipated at 12 months) by using the EuroQol five-dimensional (EQ-5D) questionnaire. All patients who had an EQ-5D questionnaire assessment at discharge from the index hospitalization (n = 15,212) were included in the study. Patients who died prior to the end-of-treatment visit were assigned an EQ-5D questionnaire value of 0. Results: The EQ-5D questionnaire value at discharge among 7631 patients assigned to ticagrelor was 0.847 and among 7581 patients assigned to clopidogrel was 0.846 (P = 0.71). At 12 months, the mean EQ-5D questionnaire value was 0.840 for ticagrelor and 0.832 for clopidogrel (P = 0.046). Excluding patients who died resulted in mean EQ-5D questionnaire values of 0.864 among ticagrelor patients and 0.863 among clopidogrel patients (P = 0.69). Conclusions: In patients hospitalized with acute coronary syndromes with or without ST-segment elevation, treatment with ticagrelor was associated with a lower mortality but otherwise no difference in quality of life relative to treatment with clopidogrel. The improved survival and reduction in cardiovascular events with ticagrelor are therefore obtained with no loss in quality of life.</p>
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9.
  • Oldgren, Jonas, et al. (författare)
  • Myocardial damage, coagulation activity and the response to thrombin inhibition in unstable coronary artery disease.
  • 2004
  • Ingår i: Thrombosis and haemostasis. - 0340-6245. ; 91:2, s. 381-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Unstable coronary artery disease is in most cases associated with plaque rupture, activation of the coagulation system and subsequent intracoronary thrombus formation which may cause myocardial cell damage. The aim of the present analysis was to assess the relation between troponin T, markers of coagulation activity, i.e. prothrombin fragment 1+2, thrombin-antithrombin complex, soluble fibrin and D-dimer, and ischemic events, i.e. death, myocardial (re-)infarction or refractory angina. 320 patients with unstable coronary artery disease were randomized to 72 hours infusion with inogatran, a low molecular weight direct thrombin inhibitor, or unfractionated heparin. Patients with elevated troponin levels had higher levels of prothrombin fragment 1+2, soluble fibrin and D-dimer before, during, and at 24 hours after cessation of anticoagulant treatment. These troponin-positive patients tended to have worse short-term clinical outcome, without relation to markers of coagulation activity. Troponin-negative patients with unchanged or early increased thrombin generation during treatment had a cluster of ischemic events within 24 hours after cessation of the study drug. The 30-day ischemic event rate was 19 % in troponin-negative patients with unchanged or early increased prothrombin fragment 1+2, and 5.7 % in patients with decreased prothrombin fragment 1+2, p=0.006, and similarly 15 % in troponin-negative patients with unchanged or early increased thrombin-antithrombin complex and 4.5 % in patients with decreased thrombin-antithrombin complex, p=0.02. In conclusion, in unstable coronary artery disease a troponin elevation indicates higher risk and higher coagulation activity. However, among the troponin negative patients, with a lower risk and lower coagulation activity, a part of the patients seem to be non-responders to treatment with a thrombin inhibitor expressed as unchanged or raised coagulation activity and a raised risk of ischemic events early after cessation of treatment.
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