High sensitive C-reactive protein and serum amyloid A are inversely related to serum bilirubin: effect-modification by metabolic syndrome

Background: Bilirubin has been implicated in cardiovascular protection by virtue of its anti-inflammatory and anti-oxidative properties. The metabolic syndrome is featured by enhanced low-grade systemic inflammation and oxidative stress. Serum amyloid A (SAA) impairs anti-oxidative properties of high-density lipoprotein (HDL). We determined relationships of high sensitive C-reactive protein (hs-CRP) and SAA with bilirubin in subjects with and without metabolic syndrome (MetS). Methods: Serum total bilirubin, hs-CRP, SAA and homeostasis model assessment-insulin resistance (HOMA-IR) were documented in 94 subjects with and in 73 subjects without MetS (26 and 54 subjects with type 2 diabetes mellitus (T2DM), respectively). Results: Bilirubin was lower in MetS (P = 0.013), coinciding with higher hs-CRP (P < 0.001) and SAA levels (P = 0.002). In all subjects combined, hs-CRP was inversely related to bilirubin (r = -0.203, P = 0.008), irrespective of the presence of MetS or T2DM (interaction terms: P >= 0.75). The inverse relationship of bilirubin with SAA was confined to subjects without MetS (r = -0.267, P = 0.009). Furthermore, the presence of either MetS or T2DM modified the relationship of bilirubin with SAA (interaction terms: beta = 0.366, P = 0.003 and beta = 0.289, P = 0.025, respectively) in age-and sex-adjusted analyses. Effect modification was also found for HOMA-IR (beta = 0.790, P = 0.020). Of the individual MetS components, the strongest interaction of bilirubin on SAA was observed with low HDL cholesterol (beta = 0.435, P < 0.001). Conclusions: hs-CRP is inversely related to bilirubin, suggesting that low bilirubin is implicated in enhanced low-grade systemic inflammation. The inverse relationship of SAA with bilirubin was found to be absent in MetS, which could be attributable to MetS-associated abnormalities in HDL characteristics.