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Fasting serum total bile acid level is associated with coronary artery disease, myocardial infarction and severity of coronary lesions

  • Wenyuan Li
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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  • Shan Shu
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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  • Lele Cheng
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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  • Xiang Hao
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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  • Lijun Wang
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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  • Yue Wu
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
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  • Zuyi Yuan
    Correspondence
    Corresponding author. Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

    Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, Shaanxi, China

    Key Laboratory of Environment and Genes Related to Diseases, Xi'an Jiaotong University, Ministry of Education, Xi'an, Shaanxi, China
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  • Juan Zhou
    Correspondence
    Corresponding author. Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, Shaanxi, 710061, China.
    Affiliations
    Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China

    Key Laboratory of Molecular Cardiology of Shaanxi Province, Xi'an, Shaanxi, China
    Search for articles by this author

      Highlights

      • A total of 7438 patients with suspected coronary artery disease were included.
      • Lower fasting serum total bile acids levels were highly and independently associated with the presence and severity of coronary artery disease (CAD).
      • No additional protective association was found above the normal upper limit of serum total bile acids.
      • Fasting serum total bile acids might be a useful biomarker to predict the presence and severity of CAD.

      Abstract

      Background and aims

      Bile acids play important roles in lipid metabolism. Several studies have found that patients with coronary artery disease (CAD) have lower bile acid fecal excretion compared to individuals without CAD. However, few studies have focused on the roles of more accessible serum total bile acids (TBA) in the progression of CAD. The aim of this study was to explore the potential relationship between fasting serum TBA and the presence of CAD, myocardial infarction (MI) and severity of coronary lesions.

      Methods

      A total of 7438 consecutive patients with suspected CAD, who had undergone coronary angiography, were enrolled. The severity of coronary lesions was evaluated using the Gensini score (GS). The relationships between fasting serum TBA and the presence and severity of CAD were evaluated.

      Results

      CAD patients had lower serum TBA than individuals without CAD, and patients with MI had lower TBA than those without CAD. Spline analyses showed an L-shaped relationship of the fasting serum TBA with the presence and severity of CAD, and the breakpoint approximated the normal upper limit (10 μmol/L). A lower TBA concentration (less than the median 3.6 μmol/L) was independently and significantly associated with the presence and severity of CAD, especially for the presence of MI (odds ratios 2.04, 95% confidence interval (1.71–2.44), C-index 0.9269).

      Conclusions

      Fasting serum TBA level is highly associated with the presence and severity of CAD in patients undergoing coronary angiography for suspected CAD.

      Graphical abstract

      Keywords

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      References

        • Batta A.K.
        • Salen G.
        • Rapole K.R.
        • Batta M.
        • Batta P.
        • et al.
        Highly simplified method for gas-liquid chromatographic quantitation of bile acids and sterols in human stool.
        J. Lipid Res. 1999; 40: 1148-1154
        • de Aguiar Vallim T.Q.
        • Tarling E.J.
        • Edwards P.A.
        Pleiotropic roles of bile acids in metabolism.
        Cell Metabol. 2013; 17: 657-669https://doi.org/10.1016/j.cmet.2013.03.013
        • Charach G.
        • Rabinovich A.
        • Argov O.
        • Weintraub M.
        • Rabinovich P.
        The role of bile Acid excretion in atherosclerotic coronary artery disease.
        Int J Vasc Med. 2012; 2012: 949672https://doi.org/10.1155/2012/949672
        • Charach G.
        • Grosskopf I.
        • Rabinovich A.
        • Shochat M.
        • Weintraub M.
        • et al.
        The association of bile acid excretion and atherosclerotic coronary artery disease.
        Therap Adv Gastroenterol. 2011; 4: 95-101https://doi.org/10.1177/1756283X10388682
        • Wahlstrom A.
        • Sayin S.I.
        • Marschall H.U.
        • Backhed F.
        Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism.
        Cell Metabol. 2016; 24: 41-50https://doi.org/10.1016/j.cmet.2016.05.005
        • Bhat B.G.
        • Rapp S.R.
        • Beaudry J.A.
        • Napawan N.
        • Butteiger D.N.
        • et al.
        Inhibition of ileal bile acid transport and reduced atherosclerosis in apoE-/- mice by SC-435.
        J. Lipid Res. 2003; 44: 1614-1621https://doi.org/10.1194/jlr.M200469-JLR200
        • Post S.M.
        • de Crom R.
        • van Haperen R.
        • van Tol A.
        • Princen H.M.
        Increased fecal bile acid excretion in transgenic mice with elevated expression of human phospholipid transfer protein.
        Arterioscler. Thromb. Vasc. Biol. 2003; 23: 892-897https://doi.org/10.1161/01.ATV.0000067702.22390.20
        • Lutton C.
        Cholesterol and bile acid dynamics: comparative aspects.
        Reprod. Nutr. Dev. 1990; 30: 145-160
        • Li H.
        • Xu G.
        • Shang Q.
        • Pan L.
        • Shefer S.
        • et al.
        Inhibition of ileal bile acid transport lowers plasma cholesterol levels by inactivating hepatic farnesoid X receptor and stimulating cholesterol 7 alpha-hydroxylase.
        Metabolism. 2004; 53: 927-932
        • Izzat N.N.
        • Deshazer M.E.
        • Loose-Mitchell D.S.
        New molecular targets for cholesterol-lowering therapy.
        J. Pharmacol. Exp. Ther. 2000; 293: 315-320
        • Charach G.
        • Argov O.
        • Geiger K.
        • Charach L.
        • Rogowski O.
        • et al.
        Diminished bile acids excretion is a risk factor for coronary artery disease: 20-year follow up and long-term outcome.
        Therap Adv Gastroenterol. 2018; 11 (1756283X17743420)https://doi.org/10.1177/1756283X17743420
        • Charach G.
        • Rabinovich P.D.
        • Konikoff F.M.
        • Grosskopf I.
        • Weintraub M.S.
        • et al.
        Decreased fecal bile acid output in patients with coronary atherosclerosis.
        J. Med. 1998; 29: 125-136
        • Finn A.V.
        • Nakano M.
        • Narula J.
        • Kolodgie F.D.
        • Virmani R.
        Concept of vulnerable/unstable plaque.
        Arterioscler. Thromb. Vasc. Biol. 2010; 30: 1282-1292https://doi.org/10.1161/ATVBAHA.108.179739
        • Gensini G.G.
        A more meaningful scoring system for determining the severity of coronary heart disease.
        Am. J. Cardiol. 1983; 51: 606
        • Weiwei C.
        • Runlin G.
        • Lisheng L.
        • Manlu Z.
        • Wen W.
        • et al.
        Outline of the report on cardiovascular diseases in China, 2014.
        Eur. Heart J. Suppl. 2016; 18: F2-F11https://doi.org/10.1093/eurheartj/suw030
        • Simonen H.
        • Miettinen T.A.
        Coronary artery disease and bile acid synthesis in familial hypercholesterolemia.
        Atherosclerosis. 1987; 63: 159-166
        • Rajaratnam R.A.
        • Gylling H.
        • Miettinen T.A.
        Cholesterol absorption, synthesis, and fecal output in postmenopausal women with and without coronary artery disease.
        Arterioscler. Thromb. Vasc. Biol. 2001; 21: 1650-1655
        • Steiner C.
        • Othman A.
        • Saely C.H.
        • Rein P.
        • Drexel H.
        • et al.
        Bile acid metabolites in serum: intraindividual variation and associations with coronary heart disease, metabolic syndrome and diabetes mellitus.
        PLoS One. 2011; 6e25006https://doi.org/10.1371/journal.pone.0025006
        • Hansen M.
        • Sonne D.P.
        • Mikkelsen K.H.
        • Gluud L.L.
        • Vilsboll T.
        • et al.
        Bile acid sequestrants for glycemic control in patients with type 2 diabetes: a systematic review with meta-analysis of randomized controlled trials.
        J. Diabet. Complicat. 2017; 31: 918-927https://doi.org/10.1016/j.jdiacomp.2017.01.011
        • Angelin B.
        • Bjorkhem I.
        • Einarsson K.
        • Ewerth S.
        Hepatic uptake of bile acids in man. Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum.
        J. Clin. Investig. 1982; 70: 724-731
        • Fiamoncini J.
        • Curi R.
        • Daniel H.
        Metabolism of bile acids in the post-prandial state.
        Essays Biochem. 2016; 60: 409-418https://doi.org/10.1042/EBC20160052
        • Ali A.H.
        • Carey E.J.
        • Lindor K.D.
        Recent advances in the development of farnesoid X receptor agonists.
        Ann. Transl. Med. 2015; 3: 5https://doi.org/10.3978/j.issn.2305-5839.2014.12.06
        • Bode N.
        • Grebe A.
        • Kerksiek A.
        • Lutjohann D.
        • Werner N.
        • et al.
        Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice.
        Biochem. Biophys. Res. Commun. 2016; 478: 356-362https://doi.org/10.1016/j.bbrc.2016.07.047
        • Qin P.
        • Tang X.
        • Elloso M.M.
        • Harnish D.C.
        Bile acids induce adhesion molecule expression in endothelial cells through activation of reactive oxygen species, NF-kappaB, and p38.
        Am. J. Physiol. Heart Circ. Physiol. 2006; 291: H741-H747https://doi.org/10.1152/ajpheart.01182.2005
        • Yang Y.Y.
        • Shang J.
        • Liu H.G.
        Role of endoplasmic reticular stress in aortic endothelial apoptosis induced by intermittent/persistent hypoxia.
        Chin Med J (Engl). 2013; 126: 4517-4523
        • Guo G.L.
        • Santamarina-Fojo S.
        • Akiyama T.E.
        • Amar M.J.
        • Paigen B.J.
        • et al.
        Effects of FXR in foam-cell formation and atherosclerosis development.
        Biochim. Biophys. Acta. 2006; 1761: 1401-1409https://doi.org/10.1016/j.bbalip.2006.09.018
        • Zhang Y.
        • Wang X.
        • Vales C.
        • Lee F.Y.
        • Lee H.
        • et al.
        FXR deficiency causes reduced atherosclerosis in Ldlr-/- mice.
        Arterioscler. Thromb. Vasc. Biol. 2006; 26: 2316-2321https://doi.org/10.1161/01.ATV.0000235697.35431.05
        • Hanniman E.A.
        • Lambert G.
        • McCarthy T.C.
        • Sinal C.J.
        Loss of functional farnesoid X receptor increases atherosclerotic lesions in apolipoprotein E-deficient mice.
        J. Lipid Res. 2005; 46: 2595-2604https://doi.org/10.1194/jlr.M500390-JLR200
        • Tang W.H.
        • Kitai T.
        • Hazen S.L.
        Gut microbiota in cardiovascular health and disease.
        Circ. Res. 2017; 120: 1183-1196https://doi.org/10.1161/CIRCRESAHA.117.309715
        • Ding L.
        • Chang M.
        • Guo Y.
        • Zhang L.
        • Xue C.
        • et al.
        Trimethylamine-N-oxide (TMAO)-induced atherosclerosis is associated with bile acid metabolism.
        Lipids Health Dis. 2018; 17: 286https://doi.org/10.1186/s12944-018-0939-6
        • Bennion L.J.
        • Drobny E.
        • Knowler W.C.
        • Ginsberg R.L.
        • Garnick M.B.
        • et al.
        Sex differences in the size of bile acid pools.
        Metabolism. 1978; 27: 961-969https://doi.org/10.1016/0026-0495(78)90140-3
        • Xie G.
        • Wang Y.
        • Wang X.
        • Zhao A.
        • Chen T.
        • et al.
        Profiling of serum bile acids in a healthy Chinese population using UPLC-MS/MS.
        J. Proteome Res. 2015; 14: 850-859https://doi.org/10.1021/pr500920q
        • Xiang X.
        • Backman J.T.
        • Neuvonen P.J.
        • Niemi M.
        Gender, but not CYP7A1 or SLCO1B1 polymorphism, affects the fasting plasma concentrations of bile acids in human beings.
        Basic Clin. Pharmacol. Toxicol. 2012; 110: 245-252https://doi.org/10.1111/j.1742-7843.2011.00792.x
        • Kawasaki H.
        • Yamanishi Y.
        • Miyake M.
        • Mura T.
        • Ikawa S.
        Age- and sex-related profiles of serum primary and total bile acids in infants, children and adults.
        Tohoku J. Exp. Med. 1986; 150: 353-357https://doi.org/10.1620/tjem.150.353
        • Luo L.
        • Aubrecht J.
        • Li D.
        • Warner R.L.
        • Johnson K.J.
        • et al.
        Assessment of serum bile acid profiles as biomarkers of liver injury and liver disease in humans.
        PLoS One. 2018; 13e0193824https://doi.org/10.1371/journal.pone.0193824
        • Costarelli V.
        • Sanders T.
        • Reddy S.
        Fasting plasma bile acid concentrations in Asian vegetarians, Caucasian vegetarians and Caucasian omnivores.
        Nutr. Food Sci. 2006; 36: 153-158https://doi.org/10.1108/00346650610664887
        • Tran T.T.
        • Ahn J.
        • Reau N.S.
        ACG clinical guideline: liver disease and pregnancy.
        Am. J. Gastroenterol. 2016; 111 (quiz 96): 176-194https://doi.org/10.1038/ajg.2015.430
        • Obstetrics Subgroup CSoO.
        • Gynecology C.M.A.
        [Guidelines for diagnosis and treatment of intrahepatic cholestasis of pregnancy (2015)].
        Zhonghua Fu Chan Ke Za Zhi. 2015; 50: 481-485