Systemic markers of inflammation and immune activation in patients with obstructive sleep apnea and paroxysmal atrial fibrillation

T E Hunt; G M Traaen; L Aakerøy; B Øverland; C Bendz; A E Michelsen; S Steinshamn; K H Haugaa; O G Anfinsen; P Aukrust; K Broch; H Akre; J P Loennechen; L Gullestad; T Ueland

doi:10.1016/j.ejim.2025.05.028

Systemic markers of inflammation and immune activation in patients with obstructive sleep apnea and paroxysmal atrial fibrillation

Eur J Intern Med. 2025 Jun 12:S0953-6205(25)00220-1. doi: 10.1016/j.ejim.2025.05.028. Online ahead of print.

Authors

T E Hunt¹, G M Traaen², L Aakerøy³, B Øverland⁴, C Bendz², A E Michelsen⁵, S Steinshamn⁶, K H Haugaa⁷, O G Anfinsen², P Aukrust⁸, K Broch⁹, H Akre¹⁰, J P Loennechen¹¹, L Gullestad⁹, T Ueland¹²

Affiliations

¹ Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ProCardio Center for Innovation, Oslo University Hospital, Oslo, Norway. Electronic address: tovebetta@msn.com.
² Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
³ Department of Thoracic Medicine, St. Olavs University Hospital, Trondheim, Norway; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway.
⁴ Department of Otorhinolaryngology, Head & Neck Surgery, Sleep Unit, Lovisenberg Diakonale Hospital, Oslo, Norway.
⁵ Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
⁶ Department of Circulation and Medical Imaging, Faculty of Medicine and Health Science, Norwegian University of Science and Technology, Trondheim, Norway; Department of Otorhinolaryngology, Head & Neck Surgery, Sleep Unit, Lovisenberg Diakonale Hospital, Oslo, Norway.
⁷ Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; ProCardio Center for Innovation, Oslo University Hospital, Oslo, Norway.
⁸ Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Department of Rheumatology, Dermatology and Infectious Disease, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁹ Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
¹⁰ Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Otorhinolaryngology, Head & Neck Surgery, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
¹¹ Department of Cardiology, St. Olavs University Hospital, Trondheim, Norway.
¹² Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Thrombosis Research Center (TREC), Division of Internal Medicine, University Hospital of North Norway, Tromsø Norway.

PMID: 40514250
DOI: 10.1016/j.ejim.2025.05.028

Abstract

Background: Atrial fibrillation (AF) and obstructive sleep apnea (OSA) frequently coexist, contributing to cardiovascular risk, possibly through shared inflammatory pathways. The specific role of inflammatory markers in patients with AF and OSA is not well established.

Aim: This study aimed to determine whether markers of inflammation and immune activation are elevated in patients with paroxysmal AF and OSA, assess the effects of continuous positive airway pressure (CPAP) and pulmonary vein isolation (PVI) on these markers, and evaluate their association with clinical outcomes, such as AF recurrence and thromboembolic risk.

Methods: We studied 143 patients with paroxysmal AF and moderate to severe OSA (apnea-hypopnea index ≥15). Of these, 99 were randomised to receive CPAP plus standard care (n = 51) or standard care alone (n = 48). A comparison group of 19 patients with paroxysmal AF and mild/no OSA (AHI <15) and 22 healthy controls were also included. Inflammatory markers related to leukocyte activation, vascular inflammation, and extracellular matrix remodelling were assessed at baseline, 6 months and 12 months follow-up.

Results: Patients with OSA and paroxysmal AF had higher levels of NGAL, PTX-3, GDF-15, MMP-9, VCAM1 and ANGP2 than healthy controls. These markers correlated poorly with AF and OSA severity. There was no modifying effect of CPAP on any marker. PTX3 was associated with AF recurrence and a high-risk score for thromboembolic stroke.

Conclusion: Moderate to severe OSA and AF are associated with elevated inflammatory markers. However, CPAP therapy did not significantly affect these levels. PTX-3 may hold prognostic value for AF recurrence and thromboembolic risk.

Keywords: Atrial fibrillation; Catheter ablation; Continuous positive airway pressure breathing; Implantable loop recorder; Inflammatory markers; Leukocyte activation; Obstructive sleep apnea; Polygraphy.