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

Abstract

AIMS:

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 remodelling, in patients with AF.

METHODS AND RESULTS:

Angiopoietin-2 was measured in plasma obtained from patients with AF treated with aspirin monotherapy (exploration cohort, n = 2987) or with oral anticoagulation (validation cohort, n = 13 079). Regression models were built to assess the associations between angiopoietin-2, clinical characteristics, and outcomes. In both cohorts, plasma angiopoietin-2 was independently associated with AF on the baseline electrocardiogram 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 ischaemic 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.

• Authors: Alexander P Benz, Ziad Hijazi, Johan Lindbäck, Stuart J Connolly, John W Eikelboom, Peter Kastner, André Ziegler, John H Alexander, Christopher B Granger, Renato D Lopes, Jonas Oldgren, Agneta Siegbahn, Lars Wallentin
• Journal: Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology (Europace) Vol. 25 Issue 7 (07 04 2023) ISSN: 1532-2092 [Electronic] England
• PMID: 37461214 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Chemical References

• Angiopoietin-2
• Biomarkers
• Peptide Fragments
• Natriuretic Peptide, Brain

Topics

• Humans
• Female
• Atrial Fibrillation (complications, diagnosis, drug therapy)
• Angiopoietin-2
• Brain Ischemia
• Stroke
• Heart Failure (complications)
• Prognosis
• Biomarkers
• Peptide Fragments
• Natriuretic Peptide, Brain