Abstract
OBJECTIVE: To investigate the association between the prognostic nutritional index (PNI) and major adverse cardiovascular events (MACE) and all-cause mortality in patients with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). METHODS: A total of 734 consecutive patients with AF and HFpEF were included in this retrospective cohort study, which was conducted at Yancheng First Hospital from July 2022 to July 2025. Cox proportional hazards regression models were applied to evaluate the relationship between PNI with MACE and all-cause mortality, with additional subgroup analyses performed across major clinical strata. The discriminative ability of PNI was examined using receiver operating characteristic (ROC) curve analysis, and restricted cubic spline (RCS) modeling was used to examine dose-response patterns. RESULTS: During a median follow-up of 35 months, 131 MACE were recorded (17.8%). In multivariable Cox regression, PNI analyzed as a continuous variable was inversely associated with MACE risk, with an adjusted hazard ratio (HR) of 0.904 (95% CI: 0.869-0.940); standardized PNI showed a similar and consistent association (HR = 0.578). Similarly, higher PNI was significantly associated with a reduced risk of all-cause mortality (P < 0.001). When assessed categorically by tertiles, patients in the highest PNI group (T3) had significantly lower risks of both MACE (HR = 0.366) and all-cause mortality (HR = 0.174) compared with the lowest tertile (P < 0.05). Similar inverse trends were observed across median, optimal cutoff, and quartile-based groupings (P < 0.05). Most subgroup analyses supported the inverse relationship between PNI and MACE (P < 0.05). ROC curve analysis showed that PNI demonstrated limited discriminatory ability for MACE with an area under the curve (AUC) of 0.654 (95% CI: 0.603-0.705). RCS analysis indicated a significant linear inverse association between PNI and MACE (P-overall < 0.001), with no evidence of non-linearity (P-nonlinear = 0.330). CONCLUSION: In patients with AF and HFpEF, higher PNI levels were independently associated with a reduced risk of MACE and all-cause mortality, indicating that PNI may serve as a potential adjunctive marker for risk stratification.