title: Association of lower total bilirubin level with statin usage: the United States National Health and Nutrition Examination Survey 1999-2008.
abstract: OBJECTIVE
  A low circulating level of bilirubin is associated with increased cardiovascular risk. As statins can stimulate heme oxygenase-1 (HO-1), which increases bilirubin production, we investigated whether statins in routine use increase total bilirubin levels in subjects at high cardiovascular risk.
  
  
  METHODS
  Data from 3290 subjects with self-reported history of hypercholesterolemia, diabetes, or cardiovascular diseases in the United States National Health and Nutrition Examination Survey (NHANES) 1999-2008 were analyzed.
  
  
  RESULTS
  Subjects taking statins (n = 1156) had lower total bilirubin levels than those not taking any lipid-lowering medication (n = 2134) after adjusting for age, sex, race/ethnicity, and survey period (adjusted mean = 0.699 vs 0.729 mg/dl respectively, P=0.001). The association remained significant after adjusting for more covariates (P = 0.002), but was attenuated after further adjusting for glycosylated hemoglobin, insulin resistance index, and low-density lipoprotein (LDL) cholesterol (P = 0.043). The use of lovastatin, rosuvastatin, and cerivastatin was associated with lower total bilirubin levels in the full adjustment model (P < 0.05).
  
  
  CONCLUSIONS
  The use of statins was associated unexpectedly with lower total bilirubin levels. This could be explained at least partly by the effect of statins on glycemia and LDL cholesterol. Our results do not suggest that the anti-oxidant and anti-inflammatory effects of statins are due to HO-1 induction and increased serum bilirubin levels.
authors.affiliation: Lipid Research Group, Heart Research Institute, 7 Eliza Street, Newtown, Sydney, NSW 2042, Australia. ongk@hri.org.au
authors.forename: Kwok Leung
authors.initials: KL
authors.lastname: Ong
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Wu
authors.forename: Bernard M Y
authors.initials: BM
authors.lastname: Cheung
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D015536:Down-Regulation; D004363:Drug Utilization; D017723:Drug Utilization Review; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy* / Q000208:ethnology; D005260:Female; D019538:Health Care Surveys; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D014481:United States / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001663:Bilirubin