Bilirubin and coronary heart disease risk in the Prospective Epidemiological Study of Myocardial Infarction (PRIME)

Background Classic coronary heart disease risk factors fail to explain the large coronary heart disease incidence gradient between Northern Ireland and France. The Prospective Epidemiological Study of Myocardial Infarction (PRIME), a multicentre prospective study of 10593 men, aims to investigate novel risk factors in these populations. We tested the hypothesis that higher bilirubin, a bile pigment possessing antioxidant properties, is associated with decreased coronary heart disease risk. Methods Bilirubin was measured in 216 participants who had developed coronary heart disease at 5-year follow-up and in 434 matched controls. Results Bilirubin was significantly lower in cases (geometric mean 795 mu mol/l; interquartile range 5.32-12.33 mu mol/l) compared with controls (9.07; 6.16-12.76; P=0.005). Conditional logistic regression, adjusted for classical and putative risk factors, showed a U-shaped pattern, with coronary heart disease risk significantly lower for bilirubin in the third and fourth fifths, compared with the first. Additionally, there was a significant quadratic relationship between coronary heart disease risk and fifths of bilirubin concentration (chi(2) = 6.80, df = 2; P = 0.035). Conclusions These findings suggest that bilirubin is a novel coronary heart disease risk marker in middle-aged men, with a U-shaped relationship observed between bilirubin concentration and coronary heart disease risk.