Is systemic inflammation the missing link between the weight-adjusted waist index and hypertension? Results from the NHANES study

Abstract

Background: The weight-adjusted waist index (WWI) is a novel obesity measure standardizing waist circumference by body weight. While linked to cardiometabolic disorders, its association with hypertension (HTN) and the mediating role of systemic inflammation remain unclear. This study investigated the WWI–HTN relationship and the mediating effects of C-reactive protein–albumin–lymphocyte ratio (CALLY), C-reactive protein–albumin ratio (CAR), and lymphocyte–C-reactive protein ratio (LCR). Methods: We analyzed data from 10,869 adults (≥20 years) in NHANES 1999–2010. Associations of WWI with HTN and inflammatory markers were examined using multivariable regression, restricted cubic splines (RCS), and generalized additive models (GAM). Mediation was evaluated through bootstrap analysis. Results: Higher WWI was strongly associated with HTN risk (OR = 1.79; 95% CI: 1.66–1.93; P < 0.001). Participants in the highest quartile had nearly fourfold greater risk than those in the lowest (OR = 3.79; 95% CI: 3.04–4.72). The relationship remained robust after adjusting for inflammatory markers (OR = 1.62; 95% CI: 1.49–1.75). Elevated log-CALLY and log-LCR were protective, whereas higher log-CAR increased HTN risk. Mediation analyses showed CALLY, LCR, and CAR explained 12.81%, 12.54%, and 15.89% of the association, respectively, with a combined effect of 13.91%. Subgroup analyses confirmed WWI as a consistent risk factor, and RCS/GAM demonstrated a nonlinear positive association with a threshold at WWI = 11.70. Conclusion: WWI is independently and nonlinearly associated with hypertension risk, particularly when WWI ≤11.70. Systemic inflammation partially mediates this association, underscoring its role in obesity-related hypertension.