Concurrent elevation of NLR and CAR identifies a high-risk subgroup in hospitalized patients with heart failure

Systemic inflammation is associated with adverse outcomes in heart failure (HF). We evaluated whether admission neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein-to-albumin ratio (CAR), individually and jointly, identify high-risk hospitalized patients with HF. This post hoc biomarker analysis included 498 consecutive adults from a prospective cohort of patients hospitalized with HF between August 2021 and January 2022. Admission NLR and CAR were calculated from laboratory tests obtained within 24 h. The primary outcome was 12-month all-cause mortality and the secondary outcome was 90-day unplanned readmission. NLR and CAR were analyzed primarily as log₂-transformed continuous variables in multivariable Cox models. Their joint association, multiplicative interaction, restricted cubic spline relationships, incremental discrimination beyond a base clinical model, competing-risk analyses for readmission, and exploratory cut-off-based categories were evaluated. Internal validation used patient-level bootstrap resampling. During follow-up, 71 patients (14.3%) died and 64 (12.9%) experienced unplanned readmission. In continuous models, CAR was associated with 12-month mortality (adjusted hazard ratio (HR) per doubling, 1.27; 95% confidence interval (CI), 1.13–1.43; P < 0.001), whereas NLR was not (HR, 1.12; 95% CI, 0.91–1.39; P = 0.287). Both NLR and CAR were associated with 90-day readmission (HR, 1.68; 95% CI, 1.37–2.07; and HR, 1.38; 95% CI, 1.23–1.56; both P < 0.001). In the joint model, both markers remained associated with readmission, whereas only CAR remained associated with mortality. Adding NLR and CAR to the base model improved bootstrap-corrected discrimination more clearly for readmission (ΔC-index, 0.075; 95% CI, 0.029–0.110) than for mortality (ΔC-index, 0.007; 95% CI, − 0.017–0.022). In exploratory adjusted categorical analyses, the both-high subgroup had the greatest risks of mortality (HR, 4.55; 95% CI, 2.30–9.00) and readmission (HR, 11.85; 95% CI, 5.55–25.29). These estimates remained stable in bootstrap resampling. Competing-risk and extended covariate-adjustment analyses yielded consistent results. Admission NLR and CAR showed outcome-specific prognostic associations in hospitalized patients with HF, with greater prognostic relevance for 90-day readmission. Concurrent elevation of both markers identified a small subgroup at markedly increased risk, supporting an exploratory risk-enrichment interpretation. External validation is required.