Risk factors and diagnostic markers for acute coronary syndrome in chronic kidney disease

Introduction. Acute coronary artery disease is the leading cause of death in patients with chronic kidney disease (CKD). In addition, CKD itself is the initiator of acute coronary syndrome (ACS), the prevalence of which is greater, the more pronounced the impairment of kidney function and the more concomitant risk factors in the patient.

Aim. To study the predictive value of various laboratory and instrumental markers in identifying the risk of developing ACS in patients with CKD.

Materials and methods. A search was made for articles for the last 10 years in the databases: PubMed, Medline, Google Scholar and eLIBRARY by keywords in Russian and English, the articles were selected in accordance with the purpose of the study.

Results. ACS manifests itself in CKD patients with an atypical picture, and in 3 % of cases it is generally asymptomatic. The risk of death from cardiovascular complications increases in proportion to the deterioration of the glomerular  filtration rate (GFR). This progression also increases the risk of coronary artery calcification. At the same time, it was found that cystatin C is a more universal marker of a decrease in GFR than creatinine. Other laboratory markers that indicate the risk of ACS are inflammatory markers, albuminuria, troponins, natriuretic peptide.

Conclusion. So far as ACS is atypical or asymptomatic, in addition to troponins and traditional instrumental diagnostic methods, markers such as GFR, albuminuria, an increase in serum cystatin C, phosphate, fibroblast growth factor-23, interleukin-6, tumor necrosis factor-alpha, total parathyroid hormone, fibrinogen, natriuretic peptide can help in its prediction.

1. Ogryzko E.V., Ivanova M.A., Odinets A.V. et al. Dynamics of morbidity and mortality in the adult population with acute forms of coronary heart disease in the Russian Federation in 2012–2017. Profilakticheskaya Meditsina = Preventive medicine 2019;22(5):23–6. (In Russ.). DOI: 10/17116//profmed20192205123

2. Sanchis J., Soler M., Núñez J. et al. Comorbidity assessment for mortality risk stratification in elderly patients with acute coronary syndrome. Eur J Intern Med 2019;62:48–53. DOI: 10.1016/j.ejim.2019.01.018

3. Mayer O.J., Seidlerová J., Bruthans J. et al. The prognostic impact of renal function decline during hospitalization for myocardial infarction. J Comp Eff Res 2021;10(3):219–28. DOI: 10.2217/cer-2020-0085

4. Tawfik A.M., Tawfik H.M. Nontraditional risk factors in chronic kidney disease: correlation between creatinine clearance, Framingham risk score, endothelial dysfunction, and inflammation. Egypt J Intern Med 2022;34:29. DOI: 10.1186/s43162-022-00110-2

5. Moisi M.I., Rus M., Bungau S. et al. Acute Coronary syndromes in chronic kidney disease: clinical and therapeutic characteristics. Medicina (Kaunas) 2020;56(3):118. DOI: 10.3390/medicina56030118

6. Hao Y., Liu J., Liu J. et al. Sex differences in in-hospital management and outcomes of patients with acute coronary syndrome. Circulation 2019;139(15):1776–85. DOI: 10.1161/CIRCULATIONAHA.118.037655

7. Brar A., Markell M. Impact of gender and gender disparities in patients with kidney disease. Curr Opin Nephrol Hypertens 2019;28(2):178–82. DOI: 10.1097/MNH.0000000000000482

8. Navarro M.A., Gosch K.L., Spertus J.A. et al. Chronic Kidney Review Disease and health status outcomes following acute myocardial infarction. J Am Heart Assoc 2016;5(5):e002772. DOI: 10.1161/JAHA.115.002772

9. Chang Y.T., Liu C.C., Tsai L.M. et al. Separate and joint effects of diabetes mellitus and chronic kidney disease on the risk of acute coronary syndrome: a population-based cohort study. Medicine (Baltimore) 2014;93(28):e261. DOI: 10.1097/MD.0000000000000261

10. Lawler P.R., Filion K.B., Dourian T. et al. Anemia and mortality in acute coronary syndromes: a systematic review and metaanalysis. Am Heart J 2013;165(2):143–53.e5. DOI: 10.1016/j.ahj.2012.10.024

11. Kamyshnikova L.A., Efremova O.A., Pivovar R.S. Features of cardiorenal relationship at patients with the chronic disease of kidneys. Тhe current state of the problem. Nauchny’e vedomosti Belgorodskogo gosudarstvennogo universiteta. Seriya: Medicina. Farmaciya = Belgorod State University Scientific bulletin. Medicine. Pharmacy 2017;5:13–21. (In Russ.).

12. Beska B., Mills G.B., Ratcovich H. et al. Impact of multimorbidity on long-term outcomes in older adults with non-ST elevation acute coronary syndrome in the North East of England: a multi-centre cohort study of patients undergoing invasive care. BMJ open 2022;12(7):e061830. DOI: 10.1136/bmjopen-2022-061830

13. Roy N., Rosas S.E. IL-6 is associated with progression of coronary artery calcification and mortality in incident dialysis patients. Am J Nephrol 2021;52(9):745–52. DOI: 10.1159/000518652

14. Salvador-González B., Gil-Terrón N., Cerain-Herrero M.J. et al. Estimated glomerular filtration rate, cardiovascular events and mortality across age groups among individuals older than 60 years in Southern Europe. Rev Esp Cardiol (Engl Ed) 2018;71(6):450–7. DOI: 10.1016/j.rec.2017.09.010

15. Efremova O.A., Kamyshnikova L.A., Obolonkova N.I. et al. Mechanisms of development of heart failure in chronic kidney disease. Challenges in Modern Medicine 2022;45(3):237–52. DOI: 10.52575/2687-0940-2022-45-3-237-252

16. Sarnak M.J., Amann K., Bangalore S. et al.; Conference Participants. Chronic kidney disease and coronary artery disease: JACC state-of-the-art review. J Am Coll Cardiol 2019;74(14):1823–38. DOI: 10.1016/j.jacc.2019.08.1017

17. Ballo P., Chechi T., Spaziani G. et al. Prognostic comparison between creatinine-based glomerular filtration rate formulas for the prediction of 10-year outcome in patients with non-ST elevation acute coronary syndrome treated by percutaneous coronary intervention. Eur Heart J Acute Cardiovasc Care 2018;7(8):689–702. DOI: 10.1177/2048872617697452

18. Jaques D.A., Müller H., Martinez C. et al. Nondipping pattern on 24-h ambulatory blood pressure monitoring is associated with left ventricular hypertrophy in chronic kidney disease. Blood Press Monit 2018;23(5):244–52. DOI: 10.1097/MBP.0000000000000337

19. Kamyshnikova L.А., Efremova O.A. Impact of comorbidities on myocardial remodeling and dysfunction in heart failure with preserved ejection fraction. Klinicheskaya Meditsina = Clinical medicine 2017;95(12):1070–6. (In Russ.). DOI: 10.18821/0023-2149-2017-95-12-1070-1076

20. Nitta K., Iimuro S., Imai E. et al. Risk factors for increased left ventricular hypertrophy in patients with chronic kidney disease: findings from the CKD-JAC study. Clin Exp Nephrol 2019;23(1):85–98. DOI: 10.1007/s10157-018-1605-z

21. Clinical practice guidelines for Acute ST-segment elevation myocardial infarction / Russian Society of Cardiology 2020. Rossijskij kardiologicheskij zhurnal = Russian Journal of Cardiology 2020;25(11):4103. (In Russ.). DOI: 10.15829/1560-4071-2020-4103

22. Bansal N., Hyre Anderson A., Yang W. et al. High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and risk of incident heart failure in patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC) Study. J Am Soc Nephrol 2015;26(4):946–56. DOI: 10.1681/ASN.2014010108

23. Guclu T., Bolat S., Şenes M. et al. Relationship between high sensitivity troponins and estimated glomerular filtration rate. Clin Biochem 2016;49(6):467–71. DOI: 10.1016/j.clinbiochem.2015.12.012

24. Bansal N., Zelnick L.R., Ballantyne C.M. et al. Upper reference limits for high-sensitivity cardiac troponin T and N-terminal fragment of the prohormone brain natriuretic peptide in patients with CKD. Am J Kidney Dis 2022;79(3):383–92. DOI: 10.1053/j.ajkd.2021.06.017

25. Cardinaels E.P., Daamen M.A., Bekers O. et al. Clinical interpretation of elevated concentrations of cardiac troponin T, but not troponin I, in nursing home residents. J Am Med Dir Assoc 2015;16(10):884–91. DOI: 10.1016/j.jamda.2015.06.026

26. Sun L., Ji Y., Wang Y. et al. High-sensitive cardiac troponin T: a biomarker of left-ventricular diastolic dysfunction in hemodialysis patients. J Nephrol 2018;31(6):967–73. DOI: 10.1007/s40620-018-0540-0

27. Arnadottir A., Vestergaard K.R., Pallisgaard J. et al. High-sensitivity cardiac troponin T is superior to troponin I in the prediction of mortality in patients without acute coronary syndrome. Int J Cardiol 2018;259:186–91. DOI: 10.1016/j.ijcard.2018.01.131

28. Buiten M.S., de Bie M.K., Rotmans J.I. et al. Serum cardiac troponin-I is superior to troponin-T as a marker for left ventricular dysfunction in clinically stable patients with end-stage renal disease. PloS One 2015;10(8):e0134245. DOI: 10.1371/journal.pone.0134245

29. Bansal N., Zelnick L.R., Soliman E.Z. et al. Change in cardiac biomarkers and risk of incident heart failure and atrial fibrillation in ckd: the Chronic Renal Insufficiency Cohort (CRIC) study. Am J Kidney Dis 2021;77(6):907–19. DOI: 10.1053/j.ajkd.2020.09.021

30. Colbert G., Jain N., de Lemos J.A. et al. Utility of traditional circulating and imaging-based cardiac biomarkers in patients with predialysis CKD. Clin J Am Soc Nephrol 2015;10(3):515–29. DOI: 10.2215/CJN.03600414

31. Kampmann J., Heaf J., Backer Mogensen C. et al. Troponin cutoffs for acute myocardial infarction in patients with impaired renal function – a systematic review and meta-analysis. Diagnostics 2022;12(2):276. DOI: 10.3390/diagnostics12020276

32. Sundqvist S., Larson T., Cauliez B. et al. Clinical value of natriuretic peptides in predicting time to dialysis in stage 4 and 5 chronic kidney disease patients. PLoS One 2016;11(8):e0159914. DOI: 10.1371/journal.pone.0159914

33. Park M., Hsu C.Y., Go A.S. et al. Urine kidney injury biomarkers and risks of cardiovascular disease events and all-cause death: the CRIC study. Clin J Am Soc Nephrol 2017;12(5):761–71. DOI: 10.2215/CJN.08560816

34. Wang K., Ni G., Wu Q. et al. Prognostic value of n-terminal Pro-B-type natriuretic peptide and glomerular filtration rate in patients with acute heart failure. Front Cardiovasc Med 2020;7:123. DOI: 10.3389/fcvm.2020.00123

35. Vinnakota S., Scott C.G., Rodeheffer R.J. et al. Estimated glomerular filtration rate, activation of cardiac biomarkers and long-term cardiovascular outcomes: a population-based cohort. Mayo Clin Proc 2019;94(11):2189–98. DOI: 10.1016/j.mayocp.2019.03.033

36. Aimo A., Januzzi J.L. Jr, Vergaro G. et al. High-sensitivity troponin T, NT-proBNP and glomerular filtration rate: A multimarker strategy for risk stratification in chronic heart failure. Int J Cardiol 2019;277:166–72. DOI: 10.1016/j.ijcard.2018.10.079

37. Schlieper G. Vascular calcification in chronic kidney disease: not all arteries are created equal. Kidney Int 2014;85(3):501–3. DOI: 10.1038/ki.2013.423

38. Nichols G.A., Déruaz-Luyet A., Hauske S.J. et al. The association between estimated glomerular filtration rate, albuminuria, and risk of cardiovascular hospitalizations and all-cause mortality among patients with type 2 diabetes. J Diabetes Complications 2018:32(3):291–7. DOI: 10.1016/j.jdiacomp.2017.12.003

39. Kühn A., van der Giet M., Kuhlmann M.K. et al. Kidney function as risk factor and predictor of cardiovascular outcomes and mortality among older adults. Am J Kidney Dis 2021;77(3):386–96. e1. DOI: 10.1053/j.ajkd.2020.09.015

40. Ishigami J., Grams M.E., Naik R.P. et al. hemoglobin, albuminuria, and kidney function in cardiovascular risk: The ARIC (Atherosclerosis Risk in Communities) study. J Am Heart Assoc 2018;7(2):e007209. DOI: 10.1161/JAHA.117.007209

41. Scialla J.J., Xie H., Rahman M. et al. Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol 2014;25(2):349–60. DOI: 10.1681/ASN.2013050465

42. Hyun Y.Y., Kim H., Oh Y.K. et al. High fibroblast growth factor 23 is associated with coronary calcification in patients with high adiponectin: analysis from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD) study. Nephrol Dial Transplant 2019;34(1):123–9. DOI: 10.1093/ndt/gfy110

43. Krishnasamy R., Tan S.J., Hawley C.M. et al. Progression of arterial stiffness is associated with changes in bone mineral markers in advanced CKD. BMC Nephrol 2017;18(1):281. DOI: 10.1186/s12882-017-0705-4

44. Balmukhanova A., Kabulbayev K., Alpay H. et al. FGF-23 and Phosphate in children with chronic kidney disease: a cross-sectional study in Kazakhstan. Medicina (Kaunas) 2020;57(1):15. DOI: 10.3390/medicina57010015/

45. Isakova T., Cai X., Lee J. et al. Longitudinal evolution of markers of mineral metabolism in patients with ckd: the Chronic Renal Insufficiency Cohort (CRIC) study. Am J Kidney Dis 2020;75(2):235–44. DOI: 10.1053/j.ajkd.2019.07.022

46. Hari P., Ramakrishnan L., Gupta R. et al. Cystatin C-based glomerular filtration rate estimating equations in early chronic kidney disease. Indian Pediatr 2014;51(4):273–7. DOI: 10.1007/s13312-014-0400-5

47. Khalid U.B., Haroon Z.H., Aamir M. et al. Comparison of estimated glomerular filtration rate with both serum creatinine and cystatin C (eGFRcr-cys) versus single analyte (eGFRcr or eGFRcys) using CKD-EPI and MDRD equations in tertiary care hospital settings. J Coll Physicians Surg Pak 2020;30(7):701–6. DOI: 10.29271/jcpsp.2020.07.701

48. Rothenbacher D., Rehm M., Iacoviello L. et al. Contribution of cystatin C- and creatinine-based definitions of chronic kidney disease to cardiovascular risk assessment in 20 population-based and 3 disease cohorts: the BiomarCaRE project. BMC Med 2020;18(1):300. DOI: 10.1186/s12916-020-01776-7

49. Matsushita K., Coresh J., Sang Y. et al. Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol 2015;3(7):514–25. DOI: 10.1016/S2213-8587(15)00040-6

50. Huang M.J., Wei R.B., Zhao J. et al. Albuminuria and endothelial dysfunction in patients with non-diabetic chronic kidney disease. Med Sci Monit 2017;23:4447–53. DOI: 10.12659/msm.903660

51. Ekart R., Šegula A., Hartman T. et al. Subendocardial viability ratio is impaired in highly proteinuric chronic kidney disease patients with low estimated glomerular filtration rate. Ther Apher Dial 2016;20(3):281–5. DOI: 10.1111/1744-9987.12438

52. Fung C.S., Wan E.Y., Chan A.K., Lam C.L. Association of estimated glomerular filtration rate and urine albumin-tocreatinine ratio with incidence of cardiovascular diseases and mortality in chinese patients with type 2 diabetes mellitus – a population-based retrospective cohort study. BMC Nephrol 2017;18(1):47. DOI: 10.1186/s12882-017-0468-y

53. Oshima M., Neuen B.L., Li J. et al. Early change in albuminuria with canagliflozin predicts kidney and cardiovascular outcomes: A PostHoc analysis from the CREDENCE trial. J Am Soc Nephrol 2020;31(12):2925–36. DOI: 10.1681/ASN.2020050723

54. Ishigami J., Grams M.E., Naik R.P. et al. Hemoglobin, albuminuria, and kidney function in cardiovascular risk: The ARIC (Atherosclerosis Risk in Communities) study. J Am Heart Assoc 2018;7(2):e007209. DOI: 10.1161/JAHA.117.007209

55. Batra G., Ghukasyan Lakic T., Lindbäck J. et al. STABILITY Investigators. Interleukin 6 and cardiovascular outcomes in patients with chronic kidney disease and chronic coronary syndrome. JAMA Cardiol 2021;6(12):1440–5. DOI: 10.1001/jamacardio.2021.3079

56. Roy N., Rosas S.E. IL-6 is associated with progression of coronary artery calcification and mortality in incident dialysis patients. Am J Nephrol 2021;52(9):745–52. DOI: 10.1159/000518652

57. Mukai H., Dai L., Chen Z. et al. Inverse J-shaped relation between coronary arterial calcium density and mortality in advanced chronic kidney disease. Nephrol Dial Transplant 2020;35(7):1202–11. DOI: 10.1093/ndt/gfy352

58. Kurozumi A., Nakano K., Yamagata K. et al. IL-6 and sIL-6R induces STAT3-dependent differentiation of human VSMCs into osteoblast-like cells through JMJD2B-mediated histone demethylation of RUNX2. Bone 2019;124:53–61. DOI: 10.1016/j.bone.2019.04.006

59. Fukuyo S., Yamaoka K., Sonomoto K. et al. IL-6-accelerated calcification by induction of ROR2 in human adipose tissue-derived mesenchymal stem cells is STAT3 dependent. Rheumatology (Oxford) 2014;53(7):1282–90. DOI: 10.1093/rheumatology/ket496

60. Wang X.R., Yuan L., Shi R. et al. Predictors of coronary artery calcification and its association with cardiovascular events in patients with chronic kidney disease. Ren Fail 2021;43(1):1172–9. DOI: 10.1080/0886022X.2021.1953529

61. Sun J., Axelsson J., Machowska A. et al. Biomarkers of Cardiovascular Disease and Mortality Risk in Patients with Advanced CKD. Clin J Am Soc Nephrol 2016;11(7):1163–72. DOI: 10.2215/CJN.10441015