Background Increased oxidative stress and vascular inflammation have been demonstrated in patients with cardiac syndrome X (CSX). Bilirubin, once considered simply the metabolic end product of haem degradation, has emerged as a potential endogenous inhibitor of atherosclerosis. This study was conducted to evaluate the prognostic role of serum bilirubin in disease progression and clinical outcome in patients with CSX.

Methods A total of 108 consecutive CSX patients were enrolled. Serum bilirubin levels were examined from blood samples collected before coronary angiography. All patients were prospectively followed up for 5 years for the composite end point of total adverse events including death and non-fatal cardiovascular events (non-fatal myocardial infarction, ischaemic stroke, rehospitalisation for unstable angina, and coronary revascularisation).

Results There were 20 adverse events, including five deaths, five ischaemic strokes and 10 rehospitalisations for unstable angina during follow-up. Patients with adverse events had lower baseline serum bilirubin levels (p<0.001). All patients were stratified into high-bilirubin, normal-bilirubin and low-bilirubin groups. The patients in the high-bilirubin group had the lowest incidence of total adverse events (p=0.008) and non-fatal cardiovascular events (p=0.008). In a multivariate Cox regression analysis, serum bilirubin, in addition to age and basal superoxide generation of circulating mononuclear cells, was also an independent predictor of total adverse events (HR 0.002; 95% CI 0.000 to 0.520; p=0.028).

Conclusions In patients with CSX, baseline serum bilirubin level was associated with long-term outcomes. Serum bilirubin could be a predictive and protective biomarker for disease progression and the development of cardiovascular events in CSX patients.