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Postoperative atrial fibrillation (POAF) is a common complication in coronary artery bypass grafting (CABG). We investigated pre-existing biological derangements before CABG to provide molecular insights into the pathogenesis. Preoperative plasma samples of discovery set from matched cohorts in sinus rhythm and POAF respectively were analyzed using proteomic approaches to identify the differential proteins that were validated in a new cohort by ELISA. Bioinformatics analysis were performed to reveal the underlying mechanism of the onset of POAF. The results revealed that preoperative alteration of PPAR-alpha increased the susceptibility of POAF after CABG.