Abstract

Introduction: Natriuretic peptides and cardiac troponin are associated with clinical outcomes in patients with atrial fibrillation (AF) but the search for disease-specific biomarkers is ongoing. We evaluated a novel candidate biomarker of endothelial remodeling and vascular growth, Angiopoietin-2 (Ang2), and its associations with clinical characteristics and outcomes in patients with AF not receiving oral anticoagulation. Methods: We used a prototype electroimmunoassay (Roche Diagnostics) to measure levels of Ang2 in plasma samples obtained at baseline from patients with AF randomized to aspirin monotherapy in two clinical trials. Associations of Ang2 with clinical characteristics and outcomes were explored using linear and Cox regression models. Results: A total of 2,987 patients were included (median age 71 years, 58% male and 13% with prior stroke). Median (25th-75th percentile) Ang2 plasma level was 3.12 (2.15-4.88) ng/mL. In adjusted analyses, Ang2 showed significant associations with AF-rhythm on the baseline ECG, age, heart failure, non-paroxysmal AF, female sex, active smoking, higher body mass index, creatinine and diabetes. Adjusting for age and other clinical characteristics, Ang2 was associated with subsequent ischemic stroke (third vs. first quartile, hazard ratio [HR] 1.76, 95% confidence interval [CI] 1.19-2.61), heart failure hospitalization (HR 1.75, 95% CI 1.27-2.41), cardiovascular (HR 2.01, 95% CI 1.36-2.97) and all-cause death (HR 1.24, 95% CI 1.01-1.53), but not major bleeding. The association with heart failure remained after additional adjustment for N-terminal pro-B-type natriuretic peptide (p=0.002). There was no interaction with cardiac rhythm at baseline for any of the outcomes. Conclusions: Plasma levels of circulating Ang2 were associated with clinical characteristics and outcomes in patients with AF not receiving oral anticoagulation. Ang2 was a particularly strong predictor of heart failure hospitalization.

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