Sex-specific associations of perioperative Resolvin D1 and D2 dynamics with postoperative atrial fibrillation in cardiac surgery: a secondary analysis of a prospective observational study

Abstract Aims Postoperative atrial fibrillation (POAF) is a prevalent and clinically significant complication that occurs after cardiac surgery. While inflammation has been linked to its onset, the role of active inflammatory resolution—mediated by a group of mediators named specialized pro-resolving mediators (SPMs)—remains unclear. Since SPMs, such as resolvins, actively terminate inflammation and restore tissue homeostasis, impaired resolution could contribute to persistent postoperative inflammation and the development of POAF. Methods This study is a secondary analysis of a single-centre prospective cohort of 319 adult patients who underwent cardiac surgery. The occurrence of POAF was identified. Resolvin D1 (RvD1) and D2 (RvD2) levels were measured during the perioperative period. The association between resolvin levels and POAF was assessed using a mixed-effects Tobit regression model. The interaction between gender, POAF, and resolvin levels was furthermore investigated. Results Patients who developed POAF exhibited significantly higher predicted perioperative levels of RvD1 [mean ratio (MR—interpreted analogously to an odds ratio): 1.19, P < 0.001] and significantly lower predicted levels of RvD2 (MR: 0.80, P < 0.001) compared to those without POAF. The association between POAF and RvD1 was amplified in women compared to men (P = 0.012). A similar pattern was noted for RvD2, with women tending to show a more pronounced decrease in RvD2 levels associated with POAF. However, this finding did not reach statistical significance (P = 0.054). Conclusion POAF is associated with elevated RvD1 and reduced RvD2 levels, suggesting a differential response and potentially distinct roles of the two pro-resolving mediators in patients with POAF. Additionally, these associations differ by sex, indicating that inflammatory resolution mechanisms may vary between males and females. Registration German Clinical Trials Registry (DRKS No. 00017057), Date of registration 5 April 2019, www.drks.de.