Growth Differentiation Factor 15, a Marker of Oxidative Stress and Inflammation, for Risk Assessment in Patients with Atrial Fibrillation: Insights from the ARISTOTLE Trial
Background—Growth Differentiation Factor 15 (GDF-15), high sensitivity troponin and NT-proBNP levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome and heart failure. Hs-TnI and NT-proBNP are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation.
Methods and Results—The ARISTOTLE trial randomized 18,201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14,798 patients. Efficacy and safety outcomes during 1.9 years follow-up were compared across quartiles of GDF-15 using Cox analyses adjusting for clinical characteristics, randomized treatment and other biomarkers. The GDF-15 level showed a median (interquartile range) of 1383 (977, 2052) ng/L. Annual rates of stroke or systemic embolism ranged from 0.9 % to 2.03 % (p<0.001), of major bleeding from 1.22 % to 4.53 % (p<0.001) and mortality from 1.34 % to 7.19 % (p<0.001) in the lowest compared to the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, while the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality and bleeding, regardless of GDF-15 levels.
Conclusions—GDF-15 is a risk factor for major bleeding, mortality and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of NT-proBNP and hs-TnI.
Clinical Trial Registration Information—www.clinicaltrials.gov. Identifier: NCT00412984.
- cardiac biomarkers
- cardiovascular events
- atrial fibrillation
- growth-differentiation factor-15 coronary disease
- brain natriuretic peptide
- risk assessment
- Received May 17, 2014.
- Revision received August 5, 2014.
- Accepted August 18, 2014.