Association of Hyperbilirubinemia with Lipid Profile and Lipid-Related Diseases: A Large Community-Based Cohort Study

<b>Objectives:</b> Emerging evidence suggests that bilirubin, beyond being a metabolic byproduct, may exert protective effects against metabolic and cardiovascular diseases due to its antioxidant properties. However, its relationship with hyperlipidemia remains unclear. This study investigated the relationship between hyperbilirubinemia and hyperlipidemia in a large, community-based cohort. <b>Methods:</b> Data from 8464 participants in the Jidong Community Cohort were analyzed using a cross-sectional design. Hyperbilirubinemia was defined as serum total bilirubin (STB) ≥ 17.1 μmol/L, whereas hyperlipidemia was determined based on a prior diagnosis or elevated lipid profile. <b>Results:</b> Of all participants, 31.6% had hyperbilirubinemia and 51.8% had hyperlipidemia. Multivariable logistic regression revealed a significant inverse association between hyperbilirubinemia and hyperlipidemia [odds ratio (OR) = 0.764, 95% confidence interval (CI) = 0.686-0.851]. This association was significant in participants aged <65 years (OR = 0.762, <i>p</i> < 0.0001) but not in those aged ≥65 years. Stratified analysis by smoking status further revealed a 29% reduced risk of hyperlipidemia among never-smokers (OR = 0.708, <i>p</i> < 0.001), but not among current (OR = 0.831, <i>p</i> = 0.087) or former smokers (OR = 0.685, <i>p</i> = 0.175). Hyperbilirubinemia was also negatively associated with TC (<i>p</i> < 0.0001), TGs (<i>p</i> < 0.0001), LDL-C (<i>p</i> = 0.0061), very LDL-C (VLDL-C; <i>p</i> = 0.0043), and apolipoprotein B (ApoB; <i>p</i> < 0.0001) levels, as well as the ApoB/apolipoprotein A1 (ApoA1) ratio (<i>p</i> = 0.0003). Restricted cubic spline analysis revealed an inverse relationship of high STB levels with the TC, TG, LDL-C, VLDL-C, and ApoB levels, as well as the ApoB/ApoA1 ratio. Moreover, elevated STB levels were inversely linked to obesity (OR = 0.747, <i>p</i> < 0.0001), arterial stenosis (OR = 0.806, <i>p</i> = 0.0462), and metabolic syndrome (OR = 0.784, <i>p</i> = 0.0008). <b>Conclusions:</b> hyperbilirubinemia may be an independent factor protective against hyperlipidemia and related lipid abnormalities; these results provide insights for the prevention and management of lipid-related diseases.