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Growth-differentiation factor 15 and risk of major bleeding in atrial fibrillation: Insights from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial
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.
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.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
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2017 (English)In: American Heart Journal, ISSN 0002-8703, E-ISSN 1097-6744, Vol. 190, p. 94-103, article id S0002-8703(17)30172-2Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To evaluate and validate the prognostic value of growth-differentiation factor 15 (GDF-15) beyond clinical characteristics and other biomarkers concerning bleeding and stroke outcomes in patients with atrial fibrillation in the RE-LY trial.

METHODS: GDF-15 was measured in samples collected at randomization in 8,474 patients with a median follow-up time of 1.9 years. Patients were stratified based on predefined GDF-15 cutoffs: group 1, <1,200 ng/L (the 90th percentile in healthy individuals); group 2, 1,200-1,800; and group 3, >1,800 ng/L (high-risk individuals). Efficacy and safety outcomes were compared across groups of GDF-15 in Cox models adjusted for baseline characteristics, cardiac (N-terminal pro-b-type natriuretic peptide, high-sensitive troponin T), inflammatory (interleukin 6, C-reactive protein) and coagulation (D-dimer) biomarkers, and randomized treatment.

RESULTS: GDF-15 concentrations were <1,200 ng/L in 2,647 (31.2%), between 1,200 and 1,800 ng/L in 2,704 (31.9%), and >1,800 ng/L in 3,123 (36.9%) participants, respectively. Annual rates of stroke, major bleeding, and mortality increased with higher GDF-15 levels. The prognostic value of GDF-15 was independent of clinical characteristics for these outcomes. In models also adjusted for biomarkers, GDF-15 remained significantly associated with major bleeding (hazard ratio [95% CI] group 3 vs group 1 1.76 [1.28-2.42], P < .0005) and all-cause mortality (hazard ratio 1.72 [1.30-2.29], P < .0005). GDF-15 improved the c index of both the HAS-BLED (0.62-0.69) and ORBIT (0.68-0.71) bleeding risk scores.

CONCLUSIONS: In patients with atrial fibrillation, GDF-15 is an independent risk indicator for major bleeding and all-cause mortality, but not for stroke. Therefore, GDF-15 seems useful as a specific marker of bleeding in patients with AF on oral anticoagulant treatment.

Place, publisher, year, edition, pages
2017. Vol. 190, p. 94-103, article id S0002-8703(17)30172-2
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Cardiac and Cardiovascular Systems
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URN: urn:nbn:se:uu:diva-342941DOI: 10.1016/j.ahj.2017.06.001ISI: 000407410800012PubMedID: 28760218OAI: oai:DiVA.org:uu-342941DiVA, id: diva2:1185341
Available from: 2018-02-23 Created: 2018-02-23 Last updated: 2018-03-22Bibliographically approved

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Hijazi, ZiadOldgren, JonasAndersson, UlrikaSiegbahn, AgnetaWallentin, Lars

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