ORIGINAL RESEARCH article
Front. Nutr.
Sec. Clinical Nutrition
Tumor Necrosis Factor-α Intensifies Cancer Risk Through Nutrient-Inflammation Crosstalk in Heart-Failure Patients: A retrospective cohort study with external validation
Provisionally accepted
- The First Affiliated Hospital of Nanchang University, Nanchang, China
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Background: Heart-failure (HF) survivors experience a disproportionate burden of incident malignancy, yet the biological bridge linking the two syndromes remains elusive. Tumour necrosis factor-α (TNF-α) promotes inflammation-driven oncogenesis, while protein–energy malnutrition amplifies catabolic signalling. We postulated that a nutrient–inflammation interaction score (NIIS), combining circulating TNF-α with the geriatric nutritional risk index (GNRI), would capture this synergistic axis and forecast de-novo cancer in HF. Methods: In a retrospective hospital cohort, 415 clinically-stable adults ≥ 60 years with chronic HF were followed for a median of 5.2 years. Baseline TNF-α (high-sensitivity ELISA) and GNRI were measured after an overnight fast; NIIS was computed as log-TNF-α × inverse-normalised GNRI. The primary endpoint was re-admission to our hospital for treatment or a scheduled follow-up appointment during which a tumour was detected; events were identified from our hospital admission and outpatient records and adjudicated in blinded fashion. Multivariable Cox models adjusted for demographic, clinical and biochemical covariates quantified associations per 1-SD increment and across tertiles. External validity was tested in 1,912 community-dwelling HF participants. Results: Sixty-two endpoint events (re-admission or follow-up visit at our hospital during which a tumour was detected) occurred (14.9 %; 2,122 person-years). Cancer incidence rose step-wise across NIIS tertiles (7.2 %, 13.7 %, 23.9 %; log-rank P < 0.001). Each 1-SD higher NIIS conferred a 68 % greater hazard (HR 1.68, 95 % CI 1.32–2.14), exceeding the prognostic strength of TNF-α or GNRI alone. Participants in the highest NIIS tertile had a tripled risk versus the lowest (HR 3.02, 1.71–5.32). Adding NIIS to a clinical model improved Harrell's C-index from 0.71 to 0.77 (Δ 0.06, P = 0.010) with good calibration; discrimination persisted in the validation cohort (C-index 0.75). Conclusion: An elevated NIIS independently predicts our hospital-defined endpoint of tumour detection at re-admission/follow-up in older adults with HF and enhances risk stratification beyond conventional factors. Routine assessment of nutrient–inflammation crosstalk may enable targeted cardio-oncology surveillance and intervention.
Keywords: Geriatric Nutritional Risk Index, Heart Failure, tumour necrosis factor-α, Nutrient–Inflammation Interaction Score, systemic inflammation, Protein-Energy Malnutrition
Received: 15 Jul 2025; Accepted: 10 Nov 2025.
Copyright: © 2025 Liao, Huang, Weng, Lu, Chen, Zuo, Jiang and Peng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoping Peng
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