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 7.95 micromol/l; interquartile range 5.32-12.33 micromol/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 (chi2=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.