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

The weight-adjusted waist index (WWI) is a novel measure of obesity that standardizes waist circumference by body weight, offering a new perspective on metabolic health. Although WWI has been associated with cardiovascular and metabolic disorders, its relationship with hypertension (HTN) remains insufficiently studied. Systemic inflammation is a known contributor to HTN, but its mediating role in the WWI-HTN association is unclear. This study evaluated the relationship between WWI and HTN and examined the mediating effects of systemic inflammation using the C-reactive protein-albumin-lymphocyte ratio (CALLY), C-reactive protein-albumin ratio (CAR), and lymphocyte-C-reactive protein ratio (LCR). We analyzed data from 10,869 adults aged ≥20 years from the NHANES (1999-2010). Key variables included WWI, HTN status, and inflammatory markers. Associations were assessed using multivariable regression, restricted cubic splines (RCS), and generalized additive models (GAM). Mediation and bootstrap analyses were performed to evaluate indirect effects. Higher WWI was significantly associated with increased HTN risk (OR = 1.79; 95% CI: 1.66-1.93; P < 0.001). Participants in the highest WWI quartile (Q4) had markedly higher risk compared with Q1 (OR = 3.79; 95% CI: 3.04-4.72). The association remained robust after adjustment for inflammatory markers (OR = 1.62; 95% CI: 1.49-1.75). Elevated log-CALLY and log-LCR were associated with lower HTN risk, whereas higher log-CAR predicted greater risk. Mediation analysis indicated that inflammatory markers explained 12.81% (log-CALLY), 12.54% (log-LCR), and 15.89% (log-CAR) of the WWI-HTN relationship, for a combined effect of 13.91%. Subgroup analyses confirmed WWI as a risk factor across diverse populations. RCS and GAM analyses further demonstrated a nonlinear positive association, with a threshold at WWI = 11.70. WWI is independently and nonlinearly associated with hypertension risk, particularly when WWI ≤11.70. Systemic inflammation partially mediates this relationship, highlighting its role in obesity-related hypertension.