Inflammatory burden index predicts long-term mortality: evidence from population-based cohorts with clinical validation

Systemic inflammation is increasingly recognized as a key determinant of long-term health outcomes. The Inflammatory Burden Index (IBI), derived from C-reactive protein, neutrophil count, and lymphocyte count, integrates multiple components of systemic inflammatory and immune status. However, evidence regarding its association with long-term mortality among individuals with and without a history of cancer remains limited.

We investigated the associations of IBI with mortality outcomes using two population-based cohorts, the UK Biobank (UKB) and the National Health and Nutrition Examination Survey (NHANES, 1999-2010), and an independent clinical cohort of patients with gastric cancer. Multivariable Cox proportional hazards models were used to evaluate the associations between IBI and mortality outcomes. Stratified analyses were performed by history of cancer and among participants with digestive tract cancers, and sensitivity analyses were conducted to assess robustness.

The UKB included 455,423 participants, of whom 54,813 had a history of cancer, and NHANES included 24,708 participants, of whom 2,159 had a history of cancer. Participants with a history of cancer were more frequently represented in the highest IBI quartile in both cohorts. Higher IBI was consistently associated with increased all-cause, cancer-specific, and CVD-specific mortality. In the UKB, among participants with a history of cancer, the highest versus lowest IBI quartile was associated with higher risks of all-cause (HR = 1.62, 95% CI: 1.53-1.71), cancer-specific (HR = 1.55, 95% CI: 1.45-1.64), and CVD-specific mortality (HR = 1.81, 95% CI: 1.41-2.33). Consistent associations were observed in NHANES and remained robust in continuous and sensitivity analyses. Among participants with digestive tract cancers, higher IBI was associated with increased all-cause and cancer-specific mortality. In the independent gastric cancer cohort (n = 793), the highest IBI quartile was associated with poorer overall survival after multivariable adjustment (HR = 2.53, 95% CI: 1.59-4.02).

Higher IBI was consistently associated with increased all-cause, cancer-specific, and CVD-specific mortality across population-based cohorts, with additional evidence from participants with digestive tract cancers and an independent gastric cancer cohort. These findings support the potential prognostic relevance of IBI as a readily accessible marker of systemic inflammatory burden.