Abstract | OBJECTIVE: 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:
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Authors | Ziad Hijazi, Jonas Oldgren, Ulrika Andersson, Stuart J Connolly, John W Eikelboom, Michael D Ezekowitz, Paul A Reilly, Salim Yusuf, Agneta Siegbahn, Lars Wallentin |
Journal | American heart journal
(Am Heart J)
Vol. 190
Pg. 94-103
(Aug 2017)
ISSN: 1097-6744 [Electronic] United States |
PMID | 28760218
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
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Copyright | Copyright © 2017 Elsevier Inc. All rights reserved. |
Chemical References |
- Anticoagulants
- Biomarkers
- GDF15 protein, human
- Growth Differentiation Factor 15
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Topics |
- Aged
- Anticoagulants
(administration & dosage, adverse effects)
- Atrial Fibrillation
(complications, drug therapy)
- Biomarkers
(blood)
- Canada
(epidemiology)
- Dose-Response Relationship, Drug
- Female
- Follow-Up Studies
- Growth Differentiation Factor 15
(blood)
- Hemorrhage
(blood, chemically induced, epidemiology)
- Humans
- Incidence
- Male
- Middle Aged
- Prognosis
- Retrospective Studies
- Risk Assessment
- Risk Factors
- Stroke
(epidemiology, etiology, prevention & control)
- Survival Rate
(trends)
- Sweden
(epidemiology)
- Time Factors
- United States
(epidemiology)
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