Background--Elevated serum bilirubin concentrations protect against atherosclerotic diseases; however, it is not clear whether higher serum bilirubin concentrations in physiological ranges work in favor of the cardiovascular system in younger persons with no cardiovascular risk factors. Accordingly, we investigated the effects of high, intermediate, and low serum bilirubin concentrations on coronary flow reserve (CFR).

Methods and Results--Fifty-two healthy subjects with hyperbilirubinemia (total bilirubin 1.43±0.33 mg/dL; mean age 35.9±7.3), 55 subjects with intermediate bilirubin level (total bilirubin: 0.69±0.11 mg/dL; mean age: 36.4±6.8), and 53 healthy subjects with hypobilirubinemia (total bilirubin 0.37±0.08 mg/dL; mean age, 37.6±6.6) were studied. Transthoracic second harmonic Doppler echocardiography examination was performed using an Acuson Sequoia C256 Echocardiography System. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion (0.84 mg/kg over 6 minutes). CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. Demographic features, coronary risk factors, echocardiographic measurements, and biochemical measurements were similar among the 3 groups, except high-sensitivity C-reactive protein (hsCRP). CFR values were significantly higher in subjects with high bilirubin concentrations than those were in the intermediate and the low bilirubin groups (3.19±0.73; 2.75±0.42; 2.56±0.52, respectively; P<0.0001), and hsCRP levels were significantly lower in subjects with high bilirubin concentrations than those in both intermediate and low bilirubin groups (1.4±1.0, 2.0±1.7, 3.0±1.9 mg/L, respectively; P<0.001). hsCRP levels correlated with total bilirubin concentration and with CFR.

Conclusion--Elevated serum bilirubin concentrations protect from CFR impairment, coronary microvascular dysfunction, and possibly coronary atherosclerosis.