title: High sensitive C-reactive protein and serum amyloid A are inversely related to serum bilirubin: effect-modification by metabolic syndrome.
abstract: 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: β = 0.366, P = 0.003 and β = 0.289, P = 0.025, respectively) in age- and sex-adjusted analyses. Effect modification was also found for HOMA-IR (β = 0.790, P = 0.020). Of the individual MetS components, the strongest interaction of bilirubin on SAA was observed with low HDL cholesterol (β = 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.
authors.forename: Petronella E
authors.initials: PE
authors.lastname: Deetman
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.affiliation: Department of Endocrinology, University of Groningen, University Medical Center Groningen, P,O, Box 30,001, Groningen 9700 RB, The Netherlands. r.p.f.dullaart@umcg.nl.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
mesh_terms: D000368:Aged; D001663:Bilirubin / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D016014:Linear Models; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D000685:Serum Amyloid A Protein / Q000378:metabolism*
chemical_list: D008076:Cholesterol, HDL; D000685:Serum Amyloid A Protein; D002097:C-Reactive Protein; D001663:Bilirubin