Growth Differentiation Factor 15, a Marker of Oxidative Stress and Inflammation, for Risk Assessment in Patients With Atrial Fibrillation: Insights From the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) Trial

• Published in: Circulation (New York, N.Y.) N.Y.), 2014-11, Vol.130 (21), p.1847-1858
• Main Authors: Wallentin, Lars, Hijazi, Ziad, Andersson, Ulrika, Alexander, John H, De Caterina, Raffaele, Hanna, Michael, Horowitz, John D, Hylek, Elaine M, Lopes, Renato D, Åsberg, Signild, Granger, Christopher B, Siegbahn, Agneta
• Format: Article
• Language: English
• Subjects: Aged; atrial fibrillation; Atrial Fibrillation - blood; Atrial Fibrillation - diagnosis; Atrial Fibrillation - drug therapy; Biological and medical sciences; biological markers; Biomarkers - blood; Blood and lymphatic vessels; Blood. Blood coagulation. Reticuloendothelial system; brain; Cardiac dysrhythmias; Cardiology. Vascular system; cardiovascular physiological processes; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Double-Blind Method; Factor Xa Inhibitors - pharmacology; Factor Xa Inhibitors - therapeutic use; Female; Follow-Up Studies; growth differentiation factor 15; Growth Differentiation Factor 15 - blood; Heart; Humans; Inflammation - blood; Inflammation - diagnosis; Inflammation - drug therapy; Male; Medical sciences; Middle Aged; natriuretic peptide; Neurology; Oxidative Stress - drug effects; Oxidative Stress - physiology; Pharmacology. Drug treatments; Pyrazoles - pharmacology; Pyrazoles - therapeutic use; Pyridones - pharmacology; Pyridones - therapeutic use; Risk Assessment; Stroke - blood; Stroke - diagnosis; Stroke - drug therapy; Thromboembolism - blood; Thromboembolism - diagnosis; Thromboembolism - drug therapy; troponin; Vascular diseases and vascular malformations of the nervous system
• ISSN: 0009-7322; 1524-4539; 1524-4539
• DOI: 10.1161/CIRCULATIONAHA.114.011204

BACKGROUND—Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide 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 Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (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 of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977–2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P