Neutrophil-to-prognostic nutritional index ratio and short-term mortality in heart failure: an exploratory association without demonstrated superiority over PNI, NLR, or SII

Abstract

Systemic inflammation and greater illness severity are associated with adverse short-term outcomes in heart failure (HF). The neutrophil-to-prognostic nutritional index ratio (NPNR) combines neutrophil count with the prognostic nutritional index (PNI), a composite derived from serum albumin and lymphocyte count that is influenced by inflammation and acute illness. This study examined the association of NPNR with 28-day and 90-day all-cause mortality in hospitalized patients with HF and assessed its replication in MIMIC-IV. The analysis included 1,885 patients with calculable NPNR from the Zigong Heart Failure Database and 1,150 adult ICU patients with HF from MIMIC-IV. Log2-transformed NPNR was examined using Cox regression, Kaplan–Meier analysis, restricted cubic splines (RCS), and sensitivity analyses, including parsimonious and Firth-penalized Cox models. MIMIC-IV provided an independent clinical setting for assessing the direction of the association. In Zigong, each doubling of NPNR was associated with higher 28-day mortality (HR 1.728, 95% CI 1.130–2.642, p  = 0.012) and 90-day mortality (HR 1.684, 95% CI 1.124–2.524, p  = 0.012). However, the expanded models included only 32 and 36 deaths, respectively, and the tertile-based estimates had wide confidence intervals. RCS analyses suggested nonlinearity at both time horizons. NPNR AUCs were 0.727 and 0.717, with no significant superiority over PNI, NLR, or SII in DeLong comparisons. In MIMIC-IV, the continuous association was borderline significant at 28 days (HR 1.112, p  = 0.049) and not statistically significant at 90 days (HR 1.081, p  = 0.096). Higher NPNR tertiles were associated with greater mortality, while RCS analyses showed no clear nonlinearity. Higher NPNR was associated with short-term all-cause mortality in the Zigong HF cohort, with weaker evidence in the MIMIC-IV ICU cohort. NPNR may be considered an exploratory laboratory-derived marker associated with systemic inflammation and illness severity. It did not demonstrate superior discrimination over PNI, NLR, or SII, and its incremental prognostic value remains uncertain. These findings do not support its routine use as a clinical decision tool.