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).

Conclusion: 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.