Introduction: The aim of this study was to investigate the expression and predictive value of NOD-like receptor thermal protein domain-related protein 3 (NLRP3) in patients with non-valvular atrial fibrillation (NVAF) with heart failure with preserved ejection fraction (HFpEF). Methods: This was a retrospective analysis of 121 patients diagnosed with NVAF. According to the occurrence of HFpEF, 81 patients were assigned to the NVAF group and 40 patients to the NVAF/HFpEF group. The levels of NLRP3, B natriuretic peptide (BNP), and interleukin-1β (IL-1β) were determined using ELISA. Independent predictors for HFpEF in NVAF were determined using logistic regression. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of each factor. Results: Expression levels of NLRP3, BNP, and IL-1β in the NVAF/HFpEF group, as well as the H2FPEF score were significantly higher than those in the NVAF group. Pearson analysis showed that NLRP3, BNP, and IL-1β expression levels in NVAF patients and the H2FPEF score was positively correlated (r = 0.409, r = 0.244, r = 0.299, p < 0.001). Multivariate logistic regression analysis showed that the NLRP3, BNP, or H2FPEF score can be used as independent factor for predicting the occurrence of HFpEF in NVAF. ROC curves showed that the areas under the curve of NLRP3, BNP, and H2FPEF scores for predicting the occurrence of HFpEF in NVAF patients were 0.856, 0.831, and 0.811, respectively. Conclusion: The NLRP3 level is elevated in the peripheral blood of NVAF patients with HFpEF and is positively correlated with the H2FPEF score. NLRP3 may serve as a potential predictor of HFpEF in patients with NVAF.

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