Interleukin-6 and C-reactive protein and risk for death and cardiovascular events in patients with atrial fibrillation

• Published in: The American heart journal Vol. 170; no. 6; pp. 1151 - 1160
• Main Authors: Aulin, Julia, MD, Siegbahn, Agneta, MD, PhD, Hijazi, Ziad, MD, PhD, Ezekowitz, Michael D., MB, ChB, Andersson, Ulrika, MSc, Connolly, Stuart J., MD, Huber, Kurt, MD, PhD, Reilly, Paul A., PhD, Wallentin, Lars, MD, PhD, Oldgren, Jonas, MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2015; Elsevier Limited
• Subjects: Aged; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Atrial Fibrillation - blood; Atrial Fibrillation - complications; Atrial Fibrillation - drug therapy; Biomarkers - blood; C-Reactive Protein - analysis; Cardiac arrhythmia; Cardiovascular; Dabigatran - administration & dosage; Dabigatran - adverse effects; Female; Health risk assessment; Heart attacks; Hemorrhage - chemically induced; Hemorrhage - prevention & control; Humans; Interleukin-6 - blood; Male; Myocardial Infarction - blood; Myocardial Infarction - diagnosis; Myocardial Infarction - etiology; Myocardial Infarction - prevention & control; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Assessment; Stroke; Stroke - blood; Stroke - diagnosis; Stroke - etiology; Stroke - prevention & control; Thromboembolism - blood; Thromboembolism - diagnosis; Thromboembolism - etiology; Thromboembolism - prevention & control; Warfarin - administration & dosage; Warfarin - adverse effects
• ISSN: 0002-8703; 1097-6744; 1097-6744
• DOI: 10.1016/j.ahj.2015.09.018

Background Inflammation has been associated with cardiovascular disease and the burden of atrial fibrillation (AF). In this study we evaluate inflammatory biomarkers and future cardiovascular events in AF patients in the RE-LY study. Methods Interleukin-6 (IL-6), C-reactive protein (CRP) (n = 6,187), and fibrinogen (n = 4,893) were analyzed at randomization; outcomes were evaluated by Cox models and C-statistics. Results Adjusted for clinical risk factors IL-6 was independently associated with stroke or systemic embolism ( P = .0041), major bleedings ( P = .0001), vascular death ( P < .0001), and a composite thromboembolic outcome (ischemic stroke, systemic embolism, myocardial infarction, pulmonary embolism and vascular death) ( P < .0001). CRP was independently related to myocardial infarction ( P = .0047), vascular death ( P = .0004), and the composite thromboembolic outcome ( P = .0001). When further adjusted for cardiac (troponin and N-terminal fragment B-type natriuretic peptide [NT-proBNP]) and renal (cystatin-C) biomarkers on top of clinical risk factors IL-6 remained significantly related to vascular death ( P < .0001), major bleeding ( P < .0170) and the composite thromboembolic outcome ( P < .0001), and CRP to myocardial infarction (.0104). Fibrinogen was not associated with any outcome. C-index for stroke or systemic embolism increased from 0.615 to 0.642 ( P = .0017) when adding IL-6 to the clinically used CHA2 DS2 -VASc risk score with net reclassification improvement of 28%. Conclusion In patients with AF, IL-6 is related to higher risk of stroke and major bleeding, and both markers are related to higher risk of vascular death and the composite of thromboembolic events independent of clinical risk factors. Adjustment for cardiovascular biomarkers attenuated the prognostic value, although IL-6 remained related to mortality, the composite of thromboembolic events, and major bleeding, and CRP to myocardial infarction.