Role of bilirubin in the prognosis of coronary artery disease and its relationship with cardiovascular risk factors: a meta-analysis

Background Bilirubin is a heme catabolism product with antioxidant, anti-inflammatory, and anti-apoptotic properties and is implicated in the prognosis of several diseases. This study evaluates the prognostic role of bilirubin in coronary artery disease (CAD) patients. Methods After identifying studies from the literature, meta-analyses were performed to achieve a) overall estimates of serum total bilirubin levels in patients with myocardial infarction (MI), non-MI CAD and healthy individuals; b) odds ratios (OR) of adverse outcomes between higher and lower total bilirubin levels; c) standardized mean difference (SMD) in total bilirubin levels in patients with high vs low CAD severity; and d) correlation between disease severity and total bilirubin. Metaregression analyses were performed to examine the relationship between cardiovascular risk factors and increasing quantiles of total bilirubin levels. Results Forty-three studies were identified. Pooled serum total bilirubin levels were 0.72 mg/dl [95% confidence interval (CI): 0.60, 0.83] in MI patients; 0.65 mg/dl [95% CI: 0.60, 0.69] in non-MI CAD patients; and 0.66 mg/dl [95% CI: 0.56, 0.75] in healthy individuals. Higher total bilirubin levels were associated with greater odds of adverse outcomes in MI patients (OR: 1.08 [95% CI: 0.99, 1.18]) but lower odds in non-MI CAD patients (OR: 0.80 [95%CI: 0.73, 0.88]). Compared to non-severe cases, total bilirubin levels were higher in patients with severe MI (SMD 0.96 [95% CI: - 0.10, 2.01]; p = 0.074) but were lower in severe non-MI CAD patients (SMD - 0.30 [95%CI: - 0.56, - 0.03]; p = 0.02). Total bilirubin levels correlated positively with MI severity (r = 0.41 [95% CI: 0.24, 0.59]; p < 0.01) but correlated negatively with non-MI CAD severity (r = - 0.17 [95% CI: - 0.48, 0.14]; p = 0.28). Female sex was inversely associated with increasing quantiles of bilirubin (meta-regression coefficient: - 8.164 [- 14.531, - 1.769]; p = 0.016) in MI patients. Conclusion Prognostic role of bilirubin for CAD appears complicated, as different odds are observed for MI and non-MI CAD patients which weakens the case of causal involvement of bilirubin in CAD etiology or prognosis. Keywords: Coronary heart disease, Bilirubin, Prognosis