Direct, indirect and total bilirubin and risk of incident coronary heart disease in the Dongfeng-Tongji cohort

<p><b>Background:</b> Total bilirubin (TBIL) is known to be inversely associated with coronary heart disease (CHD) risk, however, whether this association is dose-response remains inconsistent and it is unclear which subtype of bilirubin is responsible for the potential protective effect.</p> <p><b>Methods:</b> We included 12,097 participants who were free of CHD, stroke, cancer and potential liver, biliary and renal diseases at baseline from September 2008 to June 2010 and were followed-up until October 2013. Cox proportional hazards models were used to assess the hazard ratios (HR) and 95% confidence interval (95% CI) of bilirubin with incident CHD risk.</p> <p><b>Results:</b> The adjusted HRs for incident CHD increased with increasing direct bilirubin (DBIL) (<i>p</i> for trend = .013). Participants within the highest quintile of DBIL had 30% higher risk of incident CHD compared to those in the lowest quintile (95% CI: 1.07, 1.58). In contrast, compared with subjects in the lowest quintile of TBIL, those in the third quintile had the lowest of 24% risk for CHD incidence (95% CI: 0.63, 0.92), which showed a U-shaped association (<i>p</i> for quadratic trend = .040).</p> <p><b>Conclusions:</b> DBIL was associated with a dose-response increased risk for CHD incidence. However, a U-shaped association existed between TBIL, indirect bilirubin and incident CHD risk.Key messages</p><p>Direct bilirubin is independently associated with incident coronary heart disease (CHD) in a dose-response manner.</p><p>A similarly consistent U-shaped association was found between total bilirubin, indirect bilirubin and incident CHD.</p><p>The potential protective effect of total bilirubin within the normal range on incident CHD should be mainly attributed to mild-to moderate elevated levels of indirect bilirubin.</p><p></p> <p>Direct bilirubin is independently associated with incident coronary heart disease (CHD) in a dose-response manner.</p> <p>A similarly consistent U-shaped association was found between total bilirubin, indirect bilirubin and incident CHD.</p> <p>The potential protective effect of total bilirubin within the normal range on incident CHD should be mainly attributed to mild-to moderate elevated levels of indirect bilirubin.</p