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 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). 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. Higher WWI was strongly associated with HTN risk (OR = 1.79; 95% CI: 1.66–1.93; <i>P</i> &lt; 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. 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. Obesity is a known risk factor for high blood pressure (hypertension), but not all measures of body fat provide the same insights. A new measure called the weight-adjusted waist index (WWI) reflects fat levels around the waist while accounting for a person’s body weight. This study looked at whether WWI is linked to the risk of developing hypertension and whether inflammation inside the body helps explain this relationship. We analysed health data from over 10,000 U.S. adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2010. We found that higher WWI values were strongly associated with higher blood pressure and a greater likelihood of having hypertension. Additionally, we discovered that people with higher WWI levels had more signs of inflammation in their blood. Three specific inflammation markers—CALLY, LCR, and CAR—partially explained the connection between WWI and hypertension. Our findings suggest that excess abdominal fat, even after adjusting for body weight, may contribute to high blood pressure in part through inflammatory processes. This research highlights the importance of using newer and more precise obesity indicators, like WWI, to assess heart and blood pressure risks. It also suggests that reducing inflammation could be a target for preventing high blood pressure in people with central obesity. These results can help doctors and policymakers better identify at-risk populations and design more effective public health interventions.