Association Between Obesity Status and Hypertension Phenotypes: Are Inflammatory Indicators the Missing Link? Evidence From a Large Population Study

ABSTRACT Hypertension exhibits variability in diagnosis and treatment across phenotypes. Obesity and metabolic disorders are key risk factors, interacting with inflammatory states. This study explores their associations with hypertension phenotypes and the mediating role of inflammation. This study analyzed 17 158 participants from NHANES (2007–2018). Hypertension phenotypes were diagnosed per guidelines. Associations were evaluated using weighted generalized linear models, with the receiver operating characteristic(ROC) curves identifying optimal obesity indices. Stratified analyses were conducted by gender, lifestyle, and diet. Mediation analysis assessed inflammation's role. Among six obesity indicators, Weight‐Waist Index (WWI) was better for Isolated Systolic Hypertension (ISH) (area under curveAUC:0.64, 95%confidence intervalCI:0.62–0.67), Waist Circumference (WC) was better for Isolated Diastolic Hypertension (IDH) (AUC:0.68, 95%CI:0.67–0.69). High obesity indicators (WC for IDH, WWI for ISH and WC for SDH) without metabolic disorders linked to IDH (odds ratioOR 3.02, 95% CI 1.57–5.82), not ISH or Systolic‐Diastolic Hypertension (SDH) ( p > 0.05). High obesity indicators (WC for IDH, WWI for ISH and WC for SDH) with metabolic disorders associated with all phenotypes (IDH: OR 3.62, 95% CI 2.19–5.97; ISH: OR 1.76, 95% CI 1.09–2.84; SDH: OR 2.04, 95% CI 1.25–3.34). Inflammation mediated partially: 6.44% via RBC in IDH (non‐obesity metabolic disorders, P < 0.001), 18.4% via Monocyte in ISH (obesity without metabolic disorders, P < 0.05). Stratified analyses showed phenotype‐specific differences: IDH nonsignificant, ISH by smoking, SDH by age. High WC without metabolic disorders is linked to IDH, while metabolically disordered obesity correlates with all phenotypes. These effects are mediated by distinct variables, aiding phenotype‐specific diagnosis and treatment.