Prognostic value of the CONUT nutritional score in HFpEF: a large-scale cohort study evaluating inflammation-driven effect modification
J Yang, J Zhang, Y H ZhangAbstract
Background
Despite the recognised co-occurrence of malnutrition and systemic inflammation in heart failure with preserved ejection fraction (HFpEF), the incremental prognostic value of a simple nutritional score beyond NT-proBNP—and the clinical relevance of inflammation-driven effect modification—has not been established.
Aims
We evaluated the prognostic utility of the Controlling Nutritional Status (CONUT) score in HFpEF, tested effect modification by inflammation (hsCRP), compared CONUT with PNI and GNRI, and quantified incremental utility using NRI and decision-curve analysis (DCA).
Methods
From a retrospective single-centre HFpEF registry (n=2,190), 1,061 patients with complete NT-proBNP and hsCRP were analysed. CONUT (albumin, cholesterol, lymphocyte count) was evaluated alongside PNI and GNRI. The primary composite comprised all-cause mortality, cardiovascular death, HF hospitalisation, or sudden cardiac death. Cox models adjusted for age, sex, BMI, eGFR, LVEF, log(NT-proBNP), comorbidities and therapy, including a pre-specified CONUT×hsCRP interaction (≥3 vs <3 mg/L). Incremental utility was assessed by ΔC-index, category-free NRI, and 1-year DCA.
Results
Over a median follow-up of 2.8 years, 400 composite events and 284 all-cause deaths occurred. CONUT was independently associated with the composite outcome (adjusted HR 1.129 per point; 95% CI 1.084–1.175; P<0.001). Discrimination gains were modest (ΔC-index 0.0080), but reclassification improved (category-free NRI 2.3%, bootstrap 95% CI 0.9–4.0%; P=0.002), outperforming PNI and GNRI. Clinical+CONUT increased net benefit on 1-year DCA across 10–30% thresholds (30%: 0.85 fewer missed events/100). Interaction was significant (P=0.014): HR per point 1.153 with hsCRP ≥3 mg/L vs 1.082 with hsCRP <3 mg/L.
Conclusions
CONUT provides incremental prognostic and clinical utility beyond NT-proBNP, particularly with elevated hsCRP, defining a malnutrition–inflammation phenotype that may inform triage and nutritional evaluation. As a retrospective single-centre study without external validation, prospective confirmation is required.Inflammation amplifies CONUT risk in HFpEF