Abstract
AIMS: To explore sex-specific heterogeneity in the prognostic discrimination of inflammatory markers for mortality across different glycaemic states.
METHODS: This prospective cohort study included 450 438 participants from the UK Biobank (median follow-up: 15.3 years), stratified by sex and glycaemic status. Cox models were applied to evaluate associations between eight inflammatory markers-CRP, WBC, neutrophil-to-lymphocyte ratio (NLR), CRP-to-lymphocyte ratio (CLR), inflammatory burden index (IBI), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), and systemic inflammation response index (SIRI)-and all-cause and cardiovascular mortality, with markers analysed in parallel using independent models. Dose-response associations and discriminative performance were assessed using restricted cubic splines (RCS) and time-dependent receiver operating characteristic (ROC) analyses, respectively. Spearman correlation analyses were conducted to contextualize relationships between inflammatory markers and cardiometabolic phenotypes.
RESULTS: Deteriorating glycaemic status was associated with progressively higher all-cause and cardiovascular mortality in both sexes, together with sex-specific differences in inflammatory marker trajectories. As glycaemia worsened, the discriminative performance of inflammatory markers for mortality tended to attenuate in women but remained generally more stable in men. Time-dependent ROC analyses suggested stage- and sex-specific heterogeneity. In diabetes, NLR showed stronger early discrimination in women, whereas SIRI showed more stable discrimination in men and at later follow-up in women.
CONCLUSION: Inflammatory biomarkers show sex- and glycaemia-specific patterns in mortality discrimination, with NLR and SIRI showing comparatively stable discrimination, particularly in diabetes.