Decoding the Nonlinear Association Between Visceral Adiposity Index and All-Cause Mortality: The Mediating Role of White Blood Cells and Neutrophils.

Background: The visceral adiposity index (VAI) is recognized as a crucial metabolic risk indicator associated with mortality and is widely used in clinical and epidemiological studies. Evidence suggests that systemic inflammation may mediate this link; however, the underlying mechanisms remain poorly understood. To advance our understanding of these critical health risks, additional studies are required to clarify the underlying pathways connecting VAI, inflammation, and mortality. Methods: Using data from the National Health and Nutrition Examination Survey (NHANES), to investigate the link between log2-VAI and all-cause mortality. To evaluate correlations, this study applied Kaplan-Meier survival curves alongside Cox proportional hazards models, and potential nonlinear associations were analyzed through the application of restricted cubic spline (RCS) models. The consistency of associations in populations with different demographic and clinical characteristics was assessed by subgroup analyses, and the role of inflammatory markers was investigated by mediation analyses. Results: This study highlighted a nonlinear connection between log2-VAI and all-cause mortality, pinpointing a risk threshold at log2-VAI = 1.81. Beyond this threshold, the likelihood of all-cause mortality increased significantly. Subgroup analyses identified a notably stronger association among middle-aged groups (40-60 years) and those without coronary heart disease (CHD). Mediation analysis demonstrated that systemic inflammatory markers, specifically white blood cell count (WBC) and neutrophil count, mediated 45.07% and 37.91% of the association, respectively. E-value analysis suggested robustness to unmeasured confounding. Conclusion: This study underscores the importance of WBC and neutrophil counts as key mediators linking VAI to all-cause mortality, offering fresh perspectives on the metabolic and inflammatory pathways underlying this association. These results highlight the critical role of public health interventions targeting inflammation to mitigate obesity-related mortality risks.