Inflammatory Hematological Indices in Heart Failure with Preserved Ejection Fraction: Associations with Disease Severity and 12-Month Outcomes

Abstract

Background/Objectives: Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a systemic inflammatory syndrome with limited diagnostic and prognostic tools applicable in routine practice. Hematological indices derived from complete blood count, including neutrophil-to-lymphocyte ratio (NLR), red cell distribution width (RDW), and platelet-to-lymphocyte ratio (PLR), have emerged as potential markers of systemic inflammation and cardiovascular risk. This study aimed to compare these indices between patients with HFpEF and individuals without heart failure and to examine their associations with disease severity and 12-month clinical outcomes. Methods: In this retrospective observational study, 221 patients with confirmed HFpEF were compared with 143 control subjects without heart failure. NLR, RDW, and PLR were calculated from routine laboratory tests. Associations with echocardiographic parameters, NT-proBNP levels, and clinical outcomes were analyzed. Patients were followed for 12 months to assess major adverse cardiovascular events (MACEs), all-cause mortality, and heart failure-related rehospitalization. Multivariable Cox regression models were used to evaluate independent prognostic value. Results: Patients with HFpEF exhibited significantly higher NLR (3.98 ± 0.98 vs. 2.72 ± 0.81), RDW (14.62 ± 1.09% vs. 13.48 ± 0.92%), and PLR (152.4 ± 38.7 vs. 131.9 ± 29.6) compared with controls (all p < 0.001). NLR and RDW correlated with NT-proBNP, E/e′ ratio, left atrial volume index, and NYHA class. Higher tertiles of NLR and RDW were associated with progressively increased rates of MACEs and all-cause mortality, with statistically significant trends across tertiles (all p-trend ≤ 0.008). In multivariable analysis, NLR (HR 1.28, p = 0.001) and RDW (HR 1.32, p < 0.001) remained independently associated with 12-month MACEs, while PLR showed borderline significance. However, ROC analysis demonstrated limited discrimination, with AUC values ranging from approximately 0.55 to 0.61, indicating that none of the three indices reliably discriminated between patients with and without MACEs when considered individually. Conclusions: NLR and RDW were elevated in patients with HFpEF and were independently associated with disease severity and 12-month MACEs. However, all three indices showed limited individual discrimination and should not be considered standalone prognostic tools. Their potential clinical value, if any, requires evaluation as part of validated multivariable prediction models.