Plasma angiopoietin-2 and its association with heart failure in patients with atrial fibrillation.

BACKGROUND: Several biomarkers are associated with clinical outcomes in patients with atrial fibrillation (AF), but a causal relationship has not been established. This study aimed to evaluate angiopoietin-2, a novel candidate biomarker of endothelial inflammation and vascular remodeling, in patients with AF.

METHODS: Angiopoietin-2 was measured in plasma obtained from patients with AF treated with aspirin monotherapy (exploration cohort, n=2,987) or with oral anticoagulation (validation cohort, n=13,079). Regression models were built to assess the associations between angiopoietin-2, clinical characteristics and outcomes.

RESULTS: In both cohorts, plasma angiopoietin-2 was independently associated with AF on the baseline ECG and persistent/permanent AF, age, history of heart failure, female sex, tobacco use/smoking, body mass index, renal dysfunction, diabetes, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Angiopoietin-2 was independently associated with subsequent hospitalization for heart failure after adjusting for age, creatinine and clinical characteristics in the exploration cohort (c-index 0.79, 95% confidence interval [CI] 0.75-0.82; third vs. first quartile, hazard ratio [HR] 1.74, 95% CI 1.26-2.41) and in the validation cohort (c-index 0.76, 95% CI 0.74-0.78; HR 1.58, 95% CI 1.37-1.82). In both cohorts, the association persisted when also adjusting for NT-proBNP (p≤0.001). In full multivariable models also adjusted for NT-proBNP, angiopoietin-2 did not show statistically significant associations with ischemic stroke, cardiovascular and all-cause death, or major bleeding that were consistent across the two cohorts.

CONCLUSIONS: In patients with AF, plasma levels of angiopoietin-2 were independently associated with subsequent hospitalization for heart failure, and provided incremental prognostic value to clinical risk factors and NT-proBNP.