Correlation between cuproptosis-related proteins and postoperative delirium in cardiac valve replacement: a prospective, observational study

Background Postoperative delirium (POD) is a common neurological complication following cardiac valve replacement. Although cuproptosis, a novel form of copper-dependent cell death, has been implicated in neurological disorders, its relationship with POD remains unclear. This study aimed to investigate the association between perioperative changes in cuproptosis-related biomarkers and POD incidence. Methods This prospective observational study enrolled patients undergoing cardiac valve replacement. Serum levels of copper ion (Cu²⁺), ferredoxin 1 (FDX1), and lipoic acid (LA) were measured at four time points: before anesthesia induction (T1), at cardiopulmonary bypass (CPB) initiation (T2), at CPB cessation (T3), and immediately after surgery (T4). POD was assessed twice daily from postoperative days 1 to 7 using the Richmond Agitation-Sedation Scale (RASS) and the Confusion Assessment Method for the ICU (CAM-ICU). Propensity score matching (PSM) was applied to compare POD and non-POD groups in a 1:1 ratio. Results Among 126 analyzed patients, 58 (46.0%) developed POD. After PSM (34 pairs), FDX1 levels at T4 were significantly higher in the POD group (18.6 vs. 14.9 ng/mL, P < 0.05), while LA levels were lower at T1, T2, and T4 (all P < 0.05). Multivariate analysis showed that each unit increase in FDX1 change (ΔT4–T1) and LA change during CPB (ΔT3–T2) was associated with a 70% (OR = 1.7, P = 0.018) and 60% (OR = 1.6, P = 0.044) increase in POD risk, respectively. Conclusions Perioperative increases in FDX1 and decreases in LA are independently associated with higher POD risk, suggesting that cuproptosis-related pathways may represent potential mechanisms and therapeutic targets for POD. Trial registration Chinese Clinical Trial Registry, ChiCTR2400088024. Registered on August 9, 2024.