Research on a diagnostic model for differentiating acute myocardial infarction from unstable angina based on bile acid profile_West China Medical Journal

Authors：

YU Qian ^1,2 , ZHAO Furong ^3,4 , JIA Xingwang ¹ , WANG Shuang ³ , LI Ying ^3,4 ,  LIU Xin ^1,2

1. Post Graduate School of Jinzhou Medical University, Jinzhou, Liaoning 121001, P. R. China;
2. Huludao Central Hospital Teaching Base of Jinzhou Medical University, Huludao, Liaoning 125001, P. R. China;
3. Dalian Boyuan Medical Technology Co., Ltd., Dalian, Liaoning 116000, P. R. China;
4. Liaoning Provincial Key Laboratory of Clinical Metabolomics for Oncology, Jinzhou Medical University, Jinzhou, Liaoning 121001, P. R. China;

Corresponding?author：

LIU Xin, Email: lyy66112@163.com

Keywords：

Bile acid profile; unstable angina; acute myocardial infarction; diagnostic model

DOI：

10.7507/1002-0179.202407283

Video：

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Objective To detect the bile acid profile in serum based on liquid chromatography-tandem mass spectrometry, and construct a combined biomarker diagnostic model for differentiating acute myocardial infarction (AMI) from unstable angina (UA). Methods A total of 180 patients with acute coronary syndrome who visited Huludao Central Hospital between August 2023 and February 2024 were randomly selected, and there were 117 patients with UA and 63 patients with AMI. Using liquid chromatography-tandem mass spectrometry, 15 bile acid subtypes in serum were detected. Orthogonal partial least squares discriminant analysis was used to compare the serum bile acid metabolic profiles of the subjects. Differences in metabolites were screened based on a significance level of P<0.05 and variable importance in projection (VIP)>1. Multiple logistic regression analysis was performed to construct a diagnostic model for differentiating AMI from UA, and the diagnostic performance of the model was evaluated using receiver operating characteristic (ROC) curve and other statistical methods. Results The differential bile acid biomarkers in the serum of UA and AMI patients included glycodeoxycholic acid, glycochenodeoxycholic acid (GCDCA), deoxycholic acid (DCA), glycocholic acid, and aurodeoxycholic acid (TDCA) (P<0.05, VIP>1). A binary logistic stepwise regression analysis showed that three bile acid biomarkers (GCDCA, DCA, and TDCA) and three common biochemical indicators (aspartate aminotransferase, creatine kinase, and total bile acid) were factors differentiating AMI from UA (P<0.05). The area under the ROC curve of the model was 0.986 [95% confidence interval (0.973, 0.999), P<0.001], demonstrating a good diagnostic performance. Conclusions GCDCA, DCA, and TDCA can serve as potential biomarkers for distinguishing AMI from UA. The model combining these three bile acids with aspartate aminotransferase, creatine kinase, and total bile acid can effectively identify AMI.

Citation： YU Qian, ZHAO Furong, JIA Xingwang, WANG Shuang, LI Ying, LIU Xin. Research on a diagnostic model for differentiating acute myocardial infarction from unstable angina based on bile acid profile. West China Medical Journal, 2024, 39(9): 1406-1412. doi: 10.7507/1002-0179.202407283 Copy

1.	GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2015, 385(9963): 117-171.
2.	Gulati R, Behfar A, Narula J, et al. Acute myocardial infarction in young individuals. Mayo Clin Proc, 2020, 95(1): 136-156.
3.	Jortveit J, Pripp AH, Lang?rgen J, et al. Incidence, risk factors and outcome of young patients with myocardial infarction. Heart, 2020, 106(18): 1420-1426.
4.	Karmen A, Wroblewski F, Ladue JS. Transaminase activity in human blood. J Clin Invest, 1955, 34(1): 126-131.
5.	Kristjansson RP, Oddsson A, Helgason H, et al. Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase. Nat Commun, 2016, 7: 10572.
6.	Jaffe AS, Ravkilde J, Roberts R, et al. It’s time for a change to a troponin standard. Circulation, 2000, 102(11): 1216-1220.
7.	Liu TT, Wang J, Liang Y, et al. The level of serum total bile acid is related to atherosclerotic lesions, prognosis and gut Lactobacillus in acute coronary syndrome patients. Ann Med, 2023, 55(1): 2232369.
8.	Li W, Shu S, Cheng L, et al. Fasting serum total bile acid level is associated with coronary artery disease, myocardial infarction and severity of coronary lesions. Atherosclerosis, 2020, 292: 193-200.
9.	Huang K, Liu C, Peng M, et al. Glycoursodeoxycholic acid ameliorates atherosclerosis and alters gut microbiota in apolipoprotein E-deficient mice. J Am Heart Assoc, 2021, 10(7): e019820.
10.	張新超, 于學忠, 陳鳳英, 等. 急性冠脈綜合征急診快速診治指南(2019). 中國急救醫學, 2019, 39(4): 301-308.
11.	Collet JP, Thiele H, Barbato E, et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Rev Esp Cardiol (Engl Ed), 2021, 74(6): 544.
12.	Yntema T, Koonen DPY, Kuipers F. Emerging roles of gut microbial modulation of bile acid composition in the etiology of cardiovascular diseases. Nutrients, 2023, 15(8): 1850.
13.	Zhang B, Kuipers F, de Boer JF, et al. Modulation of bile acid metabolism to improve plasma lipid and lipoprotein profiles. J Clin Med, 2021, 11(1): 4.
14.	Nowiński A, Chabowski D, Giebu?towicz J, et al. Deoxycholic acid, a secondary bile acid, increases cardiac output and blood pressure in rats. Nutrients, 2023, 16(1): 32.
15.	Wang J, Zhang J, Lin X, et al. DCA-TGR5 signaling activation alleviates inflammatory response and improves cardiac function in myocardial infarction. J Mol Cell Cardiol, 2021, 151: 3-14.
16.	Miyazaki-Anzai S, Masuda M, Levi M, et al. Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis. PLoS One, 2014, 9(9): e108270.
17.	Wang J, Xu T, Xu M. Roles and mechanisms of TGR5 in the modulation of CD4(+) T cell functions in myocardial infarction. J Cardiovasc Transl Res, 2022, 15(2): 350-359.
18.	Charach G, Rabinovich PD, Konikoff FM, et al. Decreased fecal bile acid output in patients with coronary atherosclerosis. J Med, 1998, 29(3/4): 125-136.
19.	Charach G, Argov O, Geiger K, 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, 2017, 11: 1756283X17743420.
20.	Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J, 2007, 28(13): 1598-1660.
21.	Ussher JR, Elmariah S, Gerszten RE, et al. The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease. J Am Coll Cardiol, 2016, 68(25): 2850-2870.
22.	Xia JG, Li B, Zhang H, et al. Precise metabolomics defines systemic metabolic dysregulation distinct to acute myocardial infarction associated with diabetes. Arterioscler Thromb Vasc Biol, 2023, 43(4): 581-596.
23.	Steyerberg EW, Vickers AJ, Cook NR, et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology, 2010, 21(1): 128-138.

1. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet, 2015, 385(9963): 117-171.
2. Gulati R, Behfar A, Narula J, et al. Acute myocardial infarction in young individuals. Mayo Clin Proc, 2020, 95(1): 136-156.
3. Jortveit J, Pripp AH, Lang?rgen J, et al. Incidence, risk factors and outcome of young patients with myocardial infarction. Heart, 2020, 106(18): 1420-1426.
4. Karmen A, Wroblewski F, Ladue JS. Transaminase activity in human blood. J Clin Invest, 1955, 34(1): 126-131.
5. Kristjansson RP, Oddsson A, Helgason H, et al. Common and rare variants associating with serum levels of creatine kinase and lactate dehydrogenase. Nat Commun, 2016, 7: 10572.
6. Jaffe AS, Ravkilde J, Roberts R, et al. It’s time for a change to a troponin standard. Circulation, 2000, 102(11): 1216-1220.
7. Liu TT, Wang J, Liang Y, et al. The level of serum total bile acid is related to atherosclerotic lesions, prognosis and gut Lactobacillus in acute coronary syndrome patients. Ann Med, 2023, 55(1): 2232369.
8. Li W, Shu S, Cheng L, et al. Fasting serum total bile acid level is associated with coronary artery disease, myocardial infarction and severity of coronary lesions. Atherosclerosis, 2020, 292: 193-200.
9. Huang K, Liu C, Peng M, et al. Glycoursodeoxycholic acid ameliorates atherosclerosis and alters gut microbiota in apolipoprotein E-deficient mice. J Am Heart Assoc, 2021, 10(7): e019820.
10. 張新超, 于學忠, 陳鳳英, 等. 急性冠脈綜合征急診快速診治指南(2019). 中國急救醫學, 2019, 39(4): 301-308.
11. Collet JP, Thiele H, Barbato E, et al. 2020 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Rev Esp Cardiol (Engl Ed), 2021, 74(6): 544.
12. Yntema T, Koonen DPY, Kuipers F. Emerging roles of gut microbial modulation of bile acid composition in the etiology of cardiovascular diseases. Nutrients, 2023, 15(8): 1850.
13. Zhang B, Kuipers F, de Boer JF, et al. Modulation of bile acid metabolism to improve plasma lipid and lipoprotein profiles. J Clin Med, 2021, 11(1): 4.
14. Nowiński A, Chabowski D, Giebu?towicz J, et al. Deoxycholic acid, a secondary bile acid, increases cardiac output and blood pressure in rats. Nutrients, 2023, 16(1): 32.
15. Wang J, Zhang J, Lin X, et al. DCA-TGR5 signaling activation alleviates inflammatory response and improves cardiac function in myocardial infarction. J Mol Cell Cardiol, 2021, 151: 3-14.
16. Miyazaki-Anzai S, Masuda M, Levi M, et al. Dual activation of the bile acid nuclear receptor FXR and G-protein-coupled receptor TGR5 protects mice against atherosclerosis. PLoS One, 2014, 9(9): e108270.
17. Wang J, Xu T, Xu M. Roles and mechanisms of TGR5 in the modulation of CD4(+) T cell functions in myocardial infarction. J Cardiovasc Transl Res, 2022, 15(2): 350-359.
18. Charach G, Rabinovich PD, Konikoff FM, et al. Decreased fecal bile acid output in patients with coronary atherosclerosis. J Med, 1998, 29(3/4): 125-136.
19. Charach G, Argov O, Geiger K, 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, 2017, 11: 1756283X17743420.
20. Bassand JP, Hamm CW, Ardissino D, et al. Guidelines for the diagnosis and treatment of non-ST-segment elevation acute coronary syndromes. Eur Heart J, 2007, 28(13): 1598-1660.
21. Ussher JR, Elmariah S, Gerszten RE, et al. The emerging role of metabolomics in the diagnosis and prognosis of cardiovascular disease. J Am Coll Cardiol, 2016, 68(25): 2850-2870.
22. Xia JG, Li B, Zhang H, et al. Precise metabolomics defines systemic metabolic dysregulation distinct to acute myocardial infarction associated with diabetes. Arterioscler Thromb Vasc Biol, 2023, 43(4): 581-596.
23. Steyerberg EW, Vickers AJ, Cook NR, et al. Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology, 2010, 21(1): 128-138.

West China Medical Journal

Research on a diagnostic model for differentiating acute myocardial infarction from unstable angina based on bile acid profile

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