Genetic predictors of complications after coronary artery bypass grafting

Authors: Abramovskikh O.S., Belov D.V., Zotova M.A., Fokin A.A., Lukin O.P.

Company: 1 South Ural State Medical University; Chelyabinsk, Russian Federation
2 Federal Center for Cardiovascular Surgery, Chelyabinsk; Chelyabinsk, Russian Federation

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Type:  Reviews


For citation: Abramovskikh O.S., Belov D.V., Zotova M.A., Fokin A.A., Lukin O.P. Genetic predictors of complications after coronary artery bypass grafting. Creative Cardiology. 2023; 17 (1): 11–24 (in Russ.). DOI: 10.24022/1997-3187-2023-17-1-11-24

Received / Accepted:  22.04.2022 / 06.03.2023

Keywords: cardiac surgery complications genetic predictors cardiopulmonary bypass

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Despite the improvement of surgical techniques, anesthetic management and perioperative management of patients, the problem of the development of complications after cardiac surgery remains relevant. The purpose of our study: to present literature data on the role of genetic predictors of postoperative complications (myocardial infarction and postoperative bleeding). Genetic predictors can be used as tools for predicting the risks of postoperative complications in operated patients under cardiopulmonary bypass. In the future, the development of predictive models based on preoperative genetic analysis will help reduce in-hospital cardiovascular mortality.


  1. Guo S., Wu J., Zhou W., Liu X., Liu Y., Zhang J. et al. Identification and analysis of key genes associated with acute myocardial infarction by integrated bioinformatics methods. Medicine (Baltimore). 2021; 100 (15): 25553 DOI: 10.1097/ MD.0000000000025553.
  2. Koksheneva I.V., Zakaraya I.T. Perioperative genomics: methodological approaches, genetic variability andresponse to surgical injury. Part 1. Clinical Physiology of Circulation. 2021; 18 (1): 5–15 (in Russ.). DOI: 10.24022/1814-6910-2021- 18-1-5-15
  3. Podgoreanu M.V., White W.D., Morris R.W., Mathew J.P., Stafford-Smith M., Welsby I.J. et al. Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery. Circulation. 2006; 114 (1 Suppl.): 275–81. DOI: 10.1161/CIRCULATIONAHA.105.001032.
  4. Kertai M.D., LiY.J., Li Y.W., Ji Y., Alexander J., Newman M.F. et al. Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery. BMJ Open. 2015; 5 (5): 006920. DOI: 10.1136/bmjopen-2014- 006920.
  5. Burzotta F., Iacoviello L., Di Castelnuovo A., Glieca F., Luciani N., Zamparelli R. et al. Relation of the -174 G/C polymorphism of interleukin-6 to interleukin-6 plasma level and to length of hospitalization after surgical coronary revascularization. Am. J. Cardiol. 2001; 88: 1125–8. DOI: 10.1016/s0002-9149(01)02046-x.
  6. Borozdenkova S., Smith J., Marshall S., Yacoub M., Rose M. Identification of ICAM-1 polymorphism that is associated with protection from transplant associated vasculopathy after cardiac transplantation. Hum. Immunol. 2001; 62: 247–55. DOI: 10.1016/s0198-8859(01)00208-7.
  7. Frey U.H., Muehlschlegel J.D., Ochterbeck C., Fox A.A., Shernan S.K., Collard C.D., Lichtner P., Peters J., Body S. GNAS gene variants affect β-blocker-related survival after coronary artery bypass grafting. Anesthesiology. 2014; 120 (5): 1109–17. DOI: 10.1097/ALN.0000000000000189.
  8. Muehlschlegel J.D., Liu K.Y., Perry T.E., Fox A.A., Collard C.D., Shernan S.K., Body S.C. Chromosome 9p21 variant predicts mortality after coronary artery bypass graft surgery. Circulation. 2010; 122: 60–5. DOI: 10.1161/CIRCULATIONAHA.109.924233.
  9. Welsby I.J., Podgoreanu M.V., Phillips-Bute B., Morris R., Mathew J.P., Smith P.K. et al. Association of the 98T ELAM-1 polymorphism with increased bleeding after cardiac surgery. J. Cardiothorac. Vasc. Anesth. 2010; 24 (3): 427–33. DOI: 10.1053/j.jvca.2009.10.030.
  10. Greiff G., Pleym H., Stenseth R., Wahba A., Videm V. Genetic variation influences the risk of bleeding after cardiac surgery: novel associations and validation of previous findings. Acta Anaesthesiol. Scand. 2015; 59 (6): 796–806. DOI: 10.1111/aas.12504.
  11. Ozolina A., Strike E., Nikitina-Zake L., Jaunalksne I., Krumina A., Lacis R. et al. Polymorphisms on PAI-1 and ACE genes in association with fibrinolytic bleeding after on-pump cardiac surgery. BMC Anesthesiol. 2015; 15: 122. DOI: 10.1186/s12871-015-0101-1.
  12. Кокшенева И.В., Закарая И.Т., Малороева А.И. Генетические факторы риска развития периоперационного инфаркта миокарда. Часть 2. Клиническая физиология кровообращения. 2021; 18 (2): 109–17. DOI: 10.24022/1814-6910-2021-18-2-109-117.
  13. Unlu G., Levic D.S., Melville D.B., Knapik E.W. Trafficking mechanisms of extracellular matrix macromolecules: insights from vertebrate development and human diseases. Int. J. Biochem. Cell. Biol. 2014; 47: 57–67. DOI: 10.1016/j.biocel.2013.11.005
  14. Kluge A., Zimmermann R., Münkel B., Mohri M., Sack S., Schaper J., Schaper W. Insulin-like growth factor I is involved in inflammation linked angiogenic processes after microembolisation in porcine heart. Cardiovasc. Res. 1995; 29: 407–15.
  15. Vogt A.M., Htun P., Kluge A., Zimmermann R., Schaper W. Insulin-like growth factor-II delays myocardial infarction in experimental coronary artery occlusion. Cardiovasc. Res. 1997; 33: 469–77. DOI: 10.1016/s0008-6363(96)00212-x
  16. Heeschen C., Dimmeler S., Hamm C.W., Fichtlscherer S., Simoons M.L., Zeiher A.M. Pregnancy-associated plasma protein-A levels in patients with acute coronary syndromes: comparison with markers of systemic inflammation, platelet activation, and myocardial necrosis. J. Am. Coll. Cardiol. 2005; 45: 229–37. DOI: 10.1016/j.jacc.2004.09.060
  17. Brull D.J., Montgomery H.E., Sanders J., Dhamrait S., Luong L., Rumley A. et al. Interleukin-6 gene -174g > c and -572g > c promoter polymorphisms are strong predictors of plasma interleukin-6 levels after coronary artery bypass surgery. Arterioscler. Thromb. Vasc. Biol. 2001; 21: 1458–63. DOI: 10.1161/hq0901.094280
  18. Greiner T.O., Volkmann A.S., Hildenbrand S., Wodarz R., Perle N., Ziemer G. et al. DEHP and its active metabolites: leaching from different tubing types, impact on proinflammatory cytokines and adhesion molecule expression. Is there a subsumable context? Perfusion. 2012; 27 (1): 21–9. DOI: 10.1177/0267659111419990.
  19. Wenzel K., Stahn R., Speer A., Denner K., Glaser C., Affeldt M. et al. Functional characterization of atherosclerosis-associated Ser128Arg and Leu554Phe E-selectin mutations. Biol. Chem. 1999; 380: 661–7. DOI: 10.1515/BC.1999.082
  20. Yoshida M., Takano Y., Sasaoka T., Izumi T., Kimura A. E-selectin polymorphism associated with myocardial infarction causes enhanced leukocyte-endothelial interactions under flow conditions. Arterioscler. Thromb. Vasc. Biol. 2003; 23: 783–8. DOI: 10.1161/01.ATV.0000067427.40133.59
  21. Kovacs V., Gasz B., Balatonyi B., Jaromi L., Kisfali P., Borsiczky B. et al. Polymorphisms in glutathione S-transferase are risk factors for perioperative acute myocardial infarction after cardiac surgery: a preliminary study. Mol. Cell. Biochem. 2014; 389 (1–2): 79–84. DOI: 10.1007/s11010-013-1929-7
  22. Eifert S., Rasch A., Beiras-Fernandez A., Nollert G., Reichart B., Lohse P. Gene polymorphisms in APOE, NOS3, and LIPC genes may be risk factors for cardiac adverse events after primary CABG. J. Cardiothorac. Surg. 2009; 4: 46. DOI: 10.1186/1749-8090-4-46
  23. Packer M. Neurohormonal interactions and adaptations in congestive heart failure. Circulation. 1988; 77: 721–30. DOI: 10.1161/01.CIR.77.4.721
  24. Virani S.S., Brautbar A., Lee V.V., MacArthur E., Morrison A.C., Grove M.L. et al. Chromosome 9p21 single nucleotide polymorphisms are not associated with recurrent myocardial infarction in patients with established coronary artery disease. Circ. J. 2012; 76: 950–6. DOI: 10.1253/circj.cj-11-1166
  25. Liu Y., Sanoff H.K., Cho H., Burd C.E., Torrice C., Mohlke K.L. et al. INK4/ARF transcript expression is associated with chromosome 9p21 variants linked to atherosclerosis. PLoS ONE. 2009; 4: 5027. DOI: 10.1371/journal.pone.0005027
  26. Kim W.Y., Sharpless N.E. The regulation of INK4/ARF in cancer and aging. Cell. 2006; 127: 265–75. DOI: 10.1016/j.cell.2006.10.003
  27. Collard C.D., Shernan S.K., Fox A.A., Bernig T., Chanock S.J., Vaughn W.K. et al. The MBL2 'LYQA secretor' haplotype is an independent predictor of postoperative myocardial infarction in whites undergoing coronary artery bypass graft surgery. Circulation. 2007; 116 (11 Suppl.): 106–12. DOI: 10.1161/CIRCULATIONAHA.106.679530
  28. Grinshtein Yu.I., Kosinova A.A., Grinshtein I.Yu., Subbotina T.N., Savchenko A.A. Possible genetic predictors of cardiovascular complications after coronary artery bypass surgery. Kardiologiya – Cardiology. 2018; 58 (7): 77–84 (in Russ.). DOI: 10.18087/cardio.2018.7.10148
  29. Dropinski J., Musial J., Sanak M., Wegrzyn W., Nizankowski R., Szczeklik A. Antithrombotic effects of aspirin based on PLA1/A2 glycoprotein Illa polymorphism in patients with coronary artery disease. Thromb. Res. 2007; 119 (3): 301–3. DOI: 10.1016/j.thromres.2006.03.005
  30. Perry T.E., Muehlschlegel J.D., Body SC. Genomics: risk and outcomes in cardiac surgery. Anesthesiol. Clin. 2008; 26: 399–417. DOI: 10.1016/j.anclin.2008.04.002
  31. Welsby I.J., Podgoreanu M.V., Phillips-Bute B., Mathew J.P., Smith P.K., Newman M.F. et al. Genetic factors contribute to bleeding after cardiac surgery. J. Thromb. Haemost. 2005; 3 (6): 1206–12. DOI: 10.1111/j.1538-7836.2005.01337.x
  32. Donahue B.S., Gailani D., Higgins M.S., Drinkwater D.C., George A.L., Jr. Factor V Leiden protects against blood loss and transfusion after cardiac surgery. Circulation. 2003; 107: 1003–8. DOI: 10.1161/01.cir.0000051864.28048.01
  33. Jimenez Rivera J.J., Iribarren J.L., Raya J.M., Nassar I., Lorente L., Perez R. et al. Factors associated with excessive bleeding in cardiopulmonary bypass patients: A nested case-control study. J. Cardiothorac. Surg. 2007; 2: 17. DOI: 10.1186/1749-8090-2-17
  34. Iribarren J.L., Jimenez J.J., Hernandez D., Brouard M., Riverol D., Lorente L. et al. Postoperative bleeding in cardiac surgery: The role of tranexamic acid in patients homozygous for the 5G polymorphism of the plasminogen activator inhibitor-1 gene. Anesthesiology. 2008; 108: 596–602. DOI: 10.1097/ALN.0b013e318167aecc
  35. Khan M.S., Yamashita K., Sharma V., Ranjan R., Dosdall D.J. RNAs and gene expression predicting postoperative atrial fibrillation in cardiac surgery patients undergoing coronary artery bypass grafting. J. Clin. Med. 2020; 9 (4): 1139. DOI: 10.3390/jcm9041139
  36. Błażejowska E., Urbanowicz T., Gąsecka A., Olasińska-Wiśniewska A., Jaguszewski M.J., Targoński R. et al. Diagnostic and prognostic value of mirnas after coronary artery bypass grafting: a review. Biology (Basel). 2021; 10 (12): 1350. DOI: 10.3390/biology10121350
  37. Liu H., Yan X., Yu J. Long noncoding RNA NEAT1/microRNA-125a axis predicts increased major adverse cardiac and cerebrovascular event risk independently in patients with unprotected left main coronary artery disease underwent coronary artery bypass grafting. J. Clin. Lab. Anal. 2020; 34 (7): e23299. DOI: 10.1002/jcla.23299
  38. Bayoumi A.S., Aonuma T., Teoh J.P., Tang Y.L., Kim I.M. Circular noncoding RNAs as potential therapies and circulating biomarkers for cardiovascular diseases. Acta Pharmacol. Sin. 2018; 39 (7): 1100–9. DOI: 10.1038/aps.2017.196
  39. Rahimi K., Færch Nielsen A., Veno/ M.T., Kjems J. Nanopore long-read sequencing of circRNAs. Methods. 2021; 196: 23–9. DOI: 10.1016/j.ymeth.2021.09.010
  40. Grigoriev E., Ponasenko A.V., Sinitskaya A.V., Ivkin A.A., Kornelyuk R.A. Mitochondrial DNA as a candidate marker of multiple organ failure after cardiac surgery. Int. J. Mol. Sci. 2022; 23 (23): 14748. DOI: 10.3390/ijms232314748
  41. Sandler N., Kaczmarek E., Itagaki K., Zheng Y., Otterbein L., Khabbaz K. et al. Mitochondrial DAMPs are released during cardiopulmonary bypass surgery and are associated with postoperative atrial fibrillation. Heart Lung Circ. 2018; 27 (1): 122–9. DOI: 10.1016/j.hlc.2017.02.014
  42. Nikitin M.P. Non-complementary strand commutation as a fundamental alternative for information processing by DNA and gene regulation. Nature Chemistry. 2023; 15 (1): 70–82. DOI: 10.1038/s41557-022-01111-y

About Authors

  • Olga S. Abramovskikh, Dr. Med. Sci., Associate Professor, Chief of Chair; ORCID
  • Dmitriy V. Belov, Cand. Med. Sci., Associate Professor of the Department of Hospital Surgery of SUSMU, Cardiovascular Surgeon of FCCS; ORCID
  • Mariya A. Zotova, Cand. Biol. Sci., Senior Researcher; ORCID
  • Aleksey A. Fokin, Dr. Med. Sci., Professor, Chief of Chair;
  • Oleg P. Lukin, Dr. Med. Sci., Chief Physician of FCCS, Professor of the Department of Hospital Surgery of SUSMU; ORCID

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery