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Background—Serum bilirubin is an endogenous antioxidant that is routinely measured before a statin is prescribed primarily to assess liver function, but the association with cardiovascular disease (CVD) in this population has not been explored. Method and Results—We identified patients from a United Kingdom primary care database (The Health Improvement Network) with measurements of serum total bilirubin levels recorded 3 months before the first statin treatment between January 1, 2000, and December 31, 2010, and no history of liver disease or CVD. In total, 130 052 patients met the inclusion criteria, and after a median follow-up of 43 months, there were 7850 CVD events. In men, the incidence of CVD in the lowest decile category of bilirubin (1–6 mol/L [0.06–0.35 mg/dL]) was 215 per 10 000 person-years compared with 163 per 10 000 person-years in the highest decile (19–40 mol/L [1.1–2.3 mg/dL]). Similar differences were seen for women. After conventional CVD risk factors were accounted for, the associations with bilirubin were nonlinear (L shaped), and the models predicted that, compared with patients with a bilirubin level of 10 mol/L (0.6 mg/dL), those with a similar CVD risk profile but a bilirubin level of 5 mol/L (0.3 mg/dL) had an 18% (95% confidence interval, 9–27) higher risk of any CVD event, a 34% (95% confidence interval, 13–56) higher risk of myocardial infarction, and a 33% (95% confidence interval, 21–46) higher risk of death resulting from any cause. Conclusions—Serum bilirubin level measured before a statin prescription to assess liver function is an independent risk factor for CVD and death in both men and women. (Circulation. 2012;126:2556-2564.)

Response to Letter Regarding Article, “Cardiovascular Events as a Function of Serum Bilirubin Levels in a Large, Statin-Treated Cohort”