Background: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a systemic inflammatory and metabolic disorder. Diuretic resistance remains a major therapeutic challenge in this population. The neutrophil percentage-to-albumin ratio (NPAR), a novel marker of systemic inflammation, may serve as a predictor of diuretic resistance and adverse outcomes in HFpEF.

Methods: This retrospective cohort study included 1 487 HFpEF patients treated between January 2017 and August 2022. Patients were divided into 2 groups: those with and without diuretic resistance. Clinical, laboratory, and echocardiographic parameters were compared between groups. Receiver-operating characteristic (ROC) analysis, logistic regression, and Kaplan–Meier survival analyses were used to determine predictive and prognostic factors.

Results: Patients with diuretic resistance exhibited significantly higher NPAR values, H2FPEF scores, NT-proBNP levels, and echocardiographic indices of diastolic dysfunction. ROC analysis identified an NPAR cut-off of 13.98 for predicting diuretic resistance (AUC = 0.892, 95% CI: 0.741-0.993, P < .01). Multiple Cox’s proportional hazard regression analysis revealed that NPAR, hs-C-reactive protein, sodium, NT-proBNP, left atrial volume index, and E/e′ were independent predictors of diuretic resistance. Kaplan–Meier analysis demonstrated increased mid-term mortality in patients with NPAR > 13.98 (log-rank P < .001). Elevated NPAR independently predicted mortality in the diuretic-resistant HFpEF subgroup (OR = 1.95, 95% CI: 1.80-2.22, P < .001).

Conclusion: NPAR is a simple and accessible inflammatory biomarker that independently predicts diuretic resistance and mortality in HFpEF. The findings underscore the role of systemic inflammation in HFpEF pathophysiology and highlight NPAR as a potential tool for early risk stratification and therapeutic decision-making.