Abstract
BACKGROUND: Total bilirubin (TBIL) is closely related to obesity, metabolic syndrome (MetS) and stroke. This study aimed to determine whether elevated TBIL could modify the association of obesity, MetS and stroke. METHODS: We included participants from the National Health and Nutrition Examination Survey from 2005 to 2018. TBIL was stratified according to the median (11.97µmol/L). Weighted logistic regression models were used to quantify the association between obesity, MetS, and stroke. Interactions were calculated with the use of likelihood ratio tests. Mediation analysis was used to determine whether elevated TBIL could inhibit the mediating factors between obesity and stroke. RESULTS: A total of 13,958 participants were included in the study. After adjusting for all confounding factors, obesity and MetS were independent risk factors for stroke (OR = 1.52, 95%CI 1.17–1.98; OR = 1.71, 95%CI 1.35–2.16). TBIL was associated with reduced risk of obesity and MetS (OR = 0.94, 95%CI 0.93–0.95; OR = 0.95, 95%CI 0.94–0.96) but not stroke. When TBIL < 11.97 µmol/L, obesity and MetS were associated with stroke (OR = 2.24, 95%CI 1.49–3.34; OR = 2.24, 95%CI 1.61–3.11), but when TBIL ≥ 11.97µmol/L, obesity and MetS were not associated with stroke (OR = 1.09, 95%CI 0.77–1.54; OR = 1.37, 95%CI 0.98–1.93). The interaction showed that elevated TBIL modified the association between obesity and stroke (P for interaction = 0.007), but not MetS (P for interaction = 0.089). Mediating effect analysis suggested that TBIL might change the relationship between obesity and stroke by inhibiting MetS. CONCLUSION: Elevated TBIL may change the relationship between obesity and stroke by inhibiting the mediating effect of MetS. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13098-025-01951-x.