Neutrophil-derived immune-inflammatory biomarkers associated with long-term mortality in patients with acute heart failure

Abstract

Acute heart failure (AHF) is associated with high mortality rates, highlighting the need for simple risk indicators. Inflammatory activation plays a key role in HF, and leukocyte-derived indices such as the neutrophil-to-lymphocyte ratio (NLR) have emerged as potential prognostic markers. However, data on other neutrophil-based indices including derived NLR (dNLR), neutrophil-to-monocyte ratio (NMR), and neutrophil-to-platelet ratio (NPR) are limited. This study aimed to evaluate the prognostic value of neutrophil-derived immune-inflammatory biomarkers for long-term prognosis in AHF. We conducted a retrospective study of patients hospitalized for HF exacerbation between 2009 and 2019, enrolled in the Lesser Poland Cracovian Heart Failure Registry (LECRA-HF registry). On admission we collected the whole patients characteristics, echocardiographic parameters and laboratory tests. Patients with concomitant infection, malignancy, or chronic inflammatory disorders such as autoimmune diseases or asthma were excluded. Neutrophil-derived immune-inflammatory biomarkers included NLR, dNLR, NMR, and NPR. NLR, NMR, and NPR were calculated by dividing the absolute neutrophil count by the respectively absolute lymphocyte, monocyte, and platelet counts obtained from the same blood sample, collected on admission. dNLR was calculated by dividing the absolute neutrophil count by the total white blood cell excluding the neutrophil count. The primary endpoint was 5-year all-cause mortality. In the long-term observation among 1140 patients, 600 (53%) died. Non-survivors had higher neutrophil (5.36 vs 4.98×10⁹/L, P<0.001), C-reactive protein (13.3 vs 5 mg/L, P<0.001), NLR (3.94 vs 2.94, P<0.001), dNLR (4.58 vs 3.51, P<0.001), and NPR (0.026 vs 0.024, P=0.001) values, and lower lymphocyte counts (1.32 vs 1.65×10⁹/L, P<0.001) in comparison to survivors. Over a 5-year follow-up in the overall HF cohort, mortality increased across quartiles of all biomarkers, peaking in the highest quartile. After adjustment for prognostic factors (age, sex, hemoglobin, glomerular filtration rate, and left ventricular ejection fraction) NLR (HR 1.03; [95% CI 1.01–1.05]; p<0.001), dNLR (HR 1.03; [95% CI 1.01–1.04]; p<0.001), and NPR (1.1 [95% CI 1.04-1.15]; p<0.001) were independent predictors of all-cause mortality. As has been shown for the first time not only NLR but also dNLR and NPR independently predict long-term mortality in AHF patients. These findings suggest that simple, neutrophil-derived hematologic indices may serve as practical prognostic tools in AHF.