Inverse Relation of Total Serum Bilirubin to Coronary Artery Calcification Score Detected by Multidetector Computed Tomography in Males

Abstract

Background:Serum total bilirubin has been suggested to have potential anti‐inflammatory and antioxidant effects on the vasculature, acting against plaque formation and subsequent atherosclerosis. This study was designed to assess the association of serum total bilirubin with coronary artery calcification (CAC).Hypothesis:Individuals with higher bilirubin level would be less likely to develop CAC.Methods:Male subjects (N = 3408) underwent evaluation of CAC by cardiac computed tomography. Correlation and logistic regression analysis were performed to assess the relationships between CAC score and other variables.Results:Subjects with a higher CAC score had significantly lower total bilirubin level (P = 0.001). Total bilirubin level was negatively correlated with CAC score (r = −0.052, P = 0.002). A 0.1‐mg/dL increase in bilirubin was associated with a reduced odds ratio (OR) of the risk by 29.2% for a CAC score above 100 (OR: 0.708, 95% confidence interval: 0.542‐0.927, P = 0.012) after adjustment for several variables. Bilirubin was inversely correlated with high‐sensitivity C‐reactive protein (hsCRP) (r = −0.117, P < 0.001).Conclusions:This study demonstrated an independent inverse association between serum total bilirubin and CAC score in males. Low serum bilirubin concentration would be useful as a potential risk factor for CAC in males. Additionally, reduced hsCRP may be 1 of the mechanisms for how bilirubin reduces CAC. © 2012 Wiley Periodicals, Inc.Additional Supporting Information may be found in the online version of this article.Zheng‐Yun Zhang, MD, and Lu‐Qin Bian, MD, contributed equally to this work.The authors have no funding, financial relationships, or conflicts of interest to disclose.

Circulating bilirubin and defense against kidney disease and cardiovascular mortality: mechanisms contributing to protection in clinical investigations

“…A supporting study showed an inverse relationship between total serum bilirubin and CAC score in healthy men. For example, an increase of 0.1 mg/dl bilirubin concentration was associated with reduced odds of patients having a CAC score of Ն100 by 29.2% (198). Furthermore, the CAC score was lowered in subjects with elevated bilirubin concentrations and was inversely associated with bilirubin concentrations (158).…”

The pharmacological features of bilirubin: the question of the century

“…Treatment with biliverdin decreased intragraft leukocyte infiltration and inhibited T cell proliferation [128]. Bilirubin protects grafts against nonspecific inflammation-induced injury in syngeneic intraportal islet transplantation in rat model [129]. Injection of bilirubin in mice islet allografts led to generation of T-regulatory cells (Treg cells), suggesting that bilirubin administration leads to graft tolerance by Treg cell generation [130].…”

Circulating Markers of Liver Function and Cardiovascular Disease Risk

“…30 TB has also been shown to be negatively correlated with arterial stiffness in men with established CHD, 31 and it has been suggested that lower TB is associated with increased risk of coronary artery calcium (CAC). 32,33 In 2012, further evidence for a beneficial role of TB in protecting against CVD events was provided by a large UK primary care-based study. After conventional risk factors were accounted for, the regression models predicted that, compared with patients with a TB level of 0.70 mg/dL, those with a similar CVD risk profile, but a TB level of only 0.35 mg/dL had an 18% higher risk of any CVD event, a 34% higher risk of myocardial infarction, and a 33% higher risk of death resulting from any cause.…”