Background and AimsPostoperative atrial fibrillation (POAF) is considered the most prevalent irregular heart rhythm after heart surgery. The cardiac autonomic nervous system significantly affects POAF, and neuropeptide Y (NPY), an abundant neuropeptide in the cardiovascular system, is involved in this autonomic regulation. The current work aimed to examine the potential association of NPY with POAF in individuals administered isolated off-pump coronary artery bypass grafting. MethodsFrom January 1 to May 31, 2020, we examined consecutive cases administered successful isolated off-pump coronary artery bypass grafting with no previously diagnosed atrial fibrillation (AF). Clinical characteristics and plasma samples were collected before surgery. NPY was quantified by enzyme-linked immunosorbent assay (ELISA) in peripheral blood, and POAF cases were identified through a 7-day Holter monitoring. ResultsAmong 120 cases with no previously diagnosed AF, 33 (27.5%) developed POAF during hospitalization. Median NPY levels were markedly elevated in the POAF group in comparison with the sinus rhythm group (31.72 vs. 27.95, P=0.014). Multivariable logistic regression analysis revealed age (OR=1.135, 95%CI 1.054-1.223; p=0.001), left atrial size (OR=1.136, 95%CI 1.004-1.285; p=0.043), and NPY levels in peripheral blood (OR=1.055, 95%CI 1.002-1.111; p=0.041) independently predicted POAF. Additionally, NPY levels were positively correlated with high-frequency (HF) (r=0.2774, p=0.0022) and low-frequency (LF) (r=0.2095, p=0.0217) components of heart rate variability. ConclusionIn summary, this study demonstrates an association between elevated NPY levels in peripheral blood before surgery and POAF occurrence.