Association of bilirubin with coronary artery calcification and cardiovascular events in the general population without known liver disease: the Heinz Nixdorf Recall study

Bilirubin is a product of heme oxygenase and an antioxidant per se. In selected cohorts and patient studies, bilirubin was associated with decreased risk for cardiovascular events. We aimed to determine the association of serum bilirubin with coronary artery calcification (CAC) and incident cardiovascular disease in the unselected general population. Participants without prior coronary heart or liver disease were drawn from the population-based Heinz Nixdorf Recall study. CAC was measured from electron beam computed tomography and quantified using the Agatston method. Incident major cardiovascular events (coronary events, stroke, cardiovascular death) were assessed during follow-up. The association of bilirubin with CAC score and incident events was calculated using regression analysis. A total of 3,553 subjects (mean age 59.4 years, 44 % male) were included. Bilirubin was inversely correlated with CAC in men [estimated % change in (CAC + 1) per each gender-specific standard deviation of bilirubin [95 % confidence interval (CI): -6.1 (-11.6; -1.7) %, p = 0.032] but less so in women [-3.6 (-7.7; 0.2) %, p = 0.065], when adjusting for age only. With adjustment for traditional cardiovascular risk factors, the association was less pronounced [men: -2.5 (-7.5; 2.6) %, p = 0.35, women: -0.2 (-4.1; 3.5) %, p = 0.9]. Likewise, higher bilirubin by one standard deviation was associated with 19 % lower frequency of incident cardiovascular events in age- and gender-adjusted Cox regression analysis [hazard ratio (95 % CI): 0.81 (0.68; 0.96), p = 0.014]; this effect was slightly attenuated after adjustment for traditional cardiovascular risk factors [0.87 (0.73; 1.04), p = 0.13]. Our data from a general population suggest that a potential protective role of bilirubin in the atherosclerosis process is largely secondary to a more beneficial risk factor profile.