Leukocyte-to-HDL Ratios for Symptomatic Phenotyping in Heart Failure: Head-to-Head Comparison of Routine Inflammatory Indices and Benchmarking Against NT-proBNP

Background/Objectives: Inflammatory indices are increasingly studied in heart failure (HF), but direct comparisons remain limited. We compared eight indices across New York Heart Association (NYHA) classes and assessed the leading indices against N-terminal pro-B-type natriuretic peptide (NT-proBNP). Methods: This analysis included 85 patients with established HF. The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-HDL ratio (NHR), lymphocyte-to-HDL ratio (LHR), monocyte-to-HDL ratio (MHR), platelet-to-HDL ratio (PHR), and uric acid-to-HDL ratio (UHR) were evaluated using group comparisons, Spearman correlations, ordinal logistic regression, and multivariable models for NYHA III/IV versus I/II. Primary multivariable models used a parsimonious adjustment set comprising age, smoking status, and HF duration, while broader covariate adjustment was examined in sensitivity analyses. Internal validation used 1000 bootstrap resamples. Results: NHR and PHR differed across NYHA classes after FDR correction. In parsimoniously adjusted ordinal models, SII, SIRI, NLR, NHR, MHR, and PHR were associated with increasing NYHA class after FDR correction. In the NYHA III/IV versus I/II analysis, only NHR (OR per doubling 2.01, 95% CI 1.19–3.39) and MHR (OR 1.96, 95% CI 1.17–3.25) remained significant after FDR correction (q = 0.022 for both). AUCs were 0.688 for the reference model, 0.775 with NHR, 0.777 with MHR, and 0.978 with NT-proBNP. Bootstrap optimism-corrected AUCs were 0.739 for NHR, 0.739 for MHR, and 0.969 for NT-proBNP. Neither ratio improved model fit beyond NT-proBNP. Conclusions: NHR and MHR showed the most consistent adjusted associations with NYHA-defined symptomatic severity and remained robust across sensitivity analyses. They should be viewed as compact routine inflammatory-metabolic indices rather than independent biomarkers or replacements for NT-proBNP. External and prospective longitudinal validation is warranted.