Prognostic and diagnostic significance of the cardiac biomarker NT-proBNP in the perioperative period of vascular surgery procedures

The objective was to study the dynamics of NT-proBNP blood level during the perioperative period of vascular surgery and to study the association of this biomarker level at the stages of treatment with developed cardiovascular complications (CVC).

Materials and Methods. The study involved 129 patients aged 66 [61–70] years who underwent elective vascular surgery. NT-proBNP blood level was determined at stages: I – before surgery, II – 24 hours after surgery, III – before discharge from the hospital. Correlation analysis, logistic regression and ROC-analysis were used for data processing.

Results. Median NT-proBNP (pg/ml) at stage I was 54[42–215], stage II – 149[63–298] (p1–2 = 0.0001) and stage III – 78[48–288] (p1–3 = 0.037). NT-proBNP blood level at stage I correlated with the biomarker level at stages II (rho = 0.558, p < 0.0001) and III (rho = 0.689, p < 0.0001). The biomarker was associated with CVC at all stages: I – OR 1.0048, 95% CI 1.0021–1.0074, p < 0.0001, AUC 0.825; II – OR 1.0040, 95% CI 1.0020–1.0060, p < 0.0001, AUC 0.820; III – OR 1.0026, 95% CI 1.006–1.0046, p = 0.015, AUC 0.687. At stage I, NT-proBNP > 218 pg/ml was a CVC predictor (sensitivity 82%, specificity 85%), this biomarker level was registered in 30 (23.2%) patients; at stage II, NT-proBNP > 281 pg/ml was associated with CVR (sensitivity 81%, specificity 80%), at stage III NT-proBNP > 158 pg/ml was associated with CCC (sensitivity 79%, specificity 65%).

Conclusions. After vascular surgery, the median NT-proBNP value increases significantly, remaining within the reference limits, and does not de[1]crease until the patients discharge from the hospital. The perioperative NT-proBNP dynamics may differ in patients with different initial biomarker levels. In 23.2% of vascular surgical patients, the preoperative NT-proBNP blood level increased to a level of more than 218 pg/ml, indicating CVC risk (very good quality predictor model). After surgery, the level of NT-proBNP associated with CVC (very good quality model) exceeds 281 pg/ml. Prior to discharge of patients from the hospital, the association of NT-proBNP with CVC is characterized by a moderate quality model (AUC 0.687). The prognostic significance of the biomarker at this stage of surgical treatment needs further research.

1. Budarova K.V., Shmakov A.N. Significance of markers of transient myocardial ischemia and hemodynamic overload in critically ill neonates. Messenger of Anesthesiology and Resuscitation, 2022, vol. 19, no. 5, pp. 79–86. (In Russ.) Doi: 10.21292/2078-5658-2022-19-5-79-86.

2. Zabolotskikh I.B., Bautin A.E., Zamyatin M.N., Lebedinskii K.M., Potievskaya V.I., Trembach N.V. Perioperative management of patients with chronic heart failure. Russian Journal of Anaesthesiology and Reanimatology, 2019, no. 3, pp. 5–24. (In Russ.) Doi: 10.17116/anaesthesiology20190315.

3. Zabolotskikh I.B., Potievskaya V.I., Bautin A.E., Grigor’ev E.V., Grigoryev S.V. et al. Perioperative management of patients with coronary artery disease. Russian Journal of Anaesthesiology and Reanimatology, 2020, no. 3, pp. 5–16. (In Russ.) Doi: 10.17116/anaesthesiology20200315.

4. Kovalev A.A., Kuznetsov B.K., Yadchenko A.A., Ignatenko V.A. Assessment of the quality of a binary classifier in research. Health and Ecology Issues, 2020, no. 4, pp. 105–113. (In Russ.) Doi: 10.51523/2708-6011.2020-17-4-15.

5. Kozlov I.A., Sokolov D.A. Assessment of the Myocardial Stress Biomarker NT-proBNP in Real Clinical Practice. General Reanimatology, 2023, vol. 19, no. 1, pp. 4–12. (In Russ.) Doi: 10.15360/1813-9779-2023-1-2272.

6. Komarov S.A., Kirov M.Yu. Evaluation of correlation between NT-proBNP biomarker with rates of hemodynamics and pulmonary extravascular water in patients with acute respiratory distress syndrome. Messenger of Anesthesiology and Resuscitation, 2015, vol. 12, no. 5, pp. 31–35. (In Russ.) Doi: 10.21292/2078-5658-2015-12-5-31-35.

7. Likhvantsev V.V., Marchenko D.N., Grebenshchikov O.A., Ubasev Yu.V., Zabelina T.S. et al. Preventiоn of heart failure patients with decreased ejection fraction in non-cardiac surgery: levosimendan or anesthetic cardioprotection? Russian Journal of Anaesthesiology and Reanimatology, 2016, vol. 61, no. 6, pp. 411–417. Doi: 10.18821/0201-7563-2016-6-411-417.

8. Moroz V.V., Marchenko D.N., Skripkin Yu.V., Zabelina T.S., Ovezov A.M., Likhvantsev V.V. Perioperative predictors of unfavorable outcome of vascular surgery. General Reanimatology, 2017, vol. 13, no. 3, pp. 6–12. Doi: 10.15360/1813-9779-2017-3-6-12.

9. Sitkin S.I., Drugova I.K., Mazur E.S. Perioperative changes aminoterminal fragment of brain natriuretic peptide (NT-proBNP) in elderly patients operated on under general and spinal anesthesia. Regional anesthesia and acute pain management, 2012, vol. 6, no. 3, pp. 28–33. (In Rus) Doi: 10.17816/RA36134.

10. Sokolov D.A., Kozlov I.A. Informativeness of various predictors of perioperative cardiovascular complications in non-cardiac surgery. Messenger of Anesthesiology and Resuscitation, 2023, vol. 20, no. 2, pp. 6–16. (In Russ.) Doi: 10.24884/2078-5658-2022-20-2-6-16.

11. Ubasev Yu.V., Skripkin Yu.V., Zabelina T.S., Sungurov V.A., Lomivorotov V.V. et al. Positive impact of infusion with levosimendan on the elder patients (60–75 years old) with lower ejection fraction of the left ventricle (< 50%) in the peri-operative period in non-cardiac surgery. Messenger of Anes thesiology and Resuscitation, 2016, vol.13, no. 2, pp. 29–36. (In Russ.) Doi: 10.21292/2078-5658-2016-13-2-29-36.

12. Shakhin D.G., Shmyrev V.A., Efremov S.M., Ponomarev D.N., Moroz G.B. et al. Predictors of continuous hospital stay in adult patients with acquired valvular disease, operated with hypothermic and normothermic cardiopulmonary bypass. Messenger of Anesthesiology and Resuscitation, 2017, vol. 14, no. 1, pp. 14–23. (In Russ.) Doi: 10.21292/2078-5658-2017-14-1-14-23.

13. Alphonsus C.S., Naidoo N., Motshabi Chakane P. et al. South African cardiovascular risk stratification guideline for non-cardiac surgery. S. Afr. Med. J, 2021, vol. 111, no. 10b, pp. 13424. PMID: 34949237.

14. Álvarez Zurro C., Planas Roca A., Alday Muñoz E. et al. High levels of preoperative and postoperative N terminal B-type natriuretic propeptide influence mortality and cardiovascular complications after noncardiac surgery: A prospective cohort study. Eur J Anaesthesiol, 2016, vol. 33, no. 6, pp. 444–449. Doi: 10.1097/EJA.0000000000000419.

15. Banfi G., Lippi G., Susta D. et al. NT-proBNP concentrations in mountain marathoners. J Strength Cond Res, 2010, vol. 24, no. 5, pp. 1369–1372. Doi: 10.1519/JSC.0b013e3181d1562d.

16. Baxter G.F. Natriuretic peptides and myocardial ischaemia. Basic Res Cardiol, 2004, vol. 99, no. 2, pp. 90–93. Doi: 10.1007/s00395-004-0458-7.

17. Borges F.K., Furtado M.V., Rossini A.P. et al. Prognostic value of perioperative N-terminal pro-B-type natriuretic peptide in noncardiac surgery. Arq Bras Cardiol, 2013, vol. 100, no. 6, pp. 561–570. Doi: 10.5935/abc.20130090.

18. Chen S., Redfors B., O’Neill B.P. et al. Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry. Eur Heart J, 2020, vol. 41, no. 8, pp. 958–969. Doi: 10.1093/eurheartj/ehz892.

19. Chong C.P., Lim W.K., Velkoska E. et al. N-terminal pro-brain natriuretic peptide and angiotensin-converting enzyme-2 levels and their association with postoperative cardiac complications after emergency orthopedic surgery. Am J Cardiol, 2012, vol. 109, no. 9, pp. 1365–1373. Doi: 10.1016/j.amjcard.2011.12.032.

20. Chong C.P., Ryan J.E., van Gaal W.J. et al. Usefulness of N-terminal pro-brain natriuretic peptide to predict postoperative cardiac complications and long-term mortality after emergency lower limb orthopedic surgery. Am J Cardiol, 2010, vol. 106, no. 6, pp. 865–872. Doi: 10.1016/j.amjcard.2010.05.012.

21. Chong C.P., van Gaal W.J., Ryan J.E. et al. Troponin I and NT-proBNP (N-terminal pro-brain natriuretic peptide) do not predict 6-month mortality in frail older patients undergoing orthopedic surgery. J Am Med Dir Assoc, 2010, vol. 11, no. 6, pp. 415–420. Doi: 10.1016/j.jamda.2010.01.003.

22. Costache A.D., Leon-Constantin M.M., Roca M. et al. Cardiac biomarkers in sports cardiology. J Cardiovasc Dev Dis, 2022, vol. 9, no. 12, pp. 453. Doi: 10.3390/jcdd9120453.

23. De Hert S., Staender S., Fritsch G. et al. Pre-оperative evaluation of adults undergoing elective noncardiac surgery: Updated guideline from the European Society of Anaesthesiology. Eur J Anaesthesiol, 2018, vol. 35, no. 6, pp. 407–465. Doi: 10.1097/EJA.0000000000000817.

24. Di Somma S., Pittoni V., Raffa S. et al. IL-18 stimulates B-type natriuretic peptide synthesis by cardiomyocytes in vitro and its plasma levels correlate with B-type natriuretic peptide in non-overloaded acute heart failure patients. Eur Heart J Acute Cardiovasc Care, 2017, vol. 6, no. 5, pp. 450–461. Doi: 10.1177/2048872613499282.

25. Duceppe E., Parlow J., MacDonald P. et al. Canadian cardiovascular society guidelines on perioperative cardiac risk assessment and management for patients who undergo noncardiac surgery. Can. J. Cardiol, 2017, vol. 33, no. 1, pp. 17–32. Doi: 10.1016/j.cjca.2016.09.008.

26. Duceppe E., Patel A., Chan M.T.V. et al. Preoperative N-Terminal Pro-BType natriuretic peptide and cardiovascular events after noncardiac surgery: a cohort study. Ann Intern Med, 2020, vol. 172, no. 2, pp. 96–104. Doi: 10.7326/M19-2501.

27. Duma A., Maleczek M., Wagner C. et al. NT-proBNP in young healthy adults undergoing non-cardiac surgery. Clin Biochem, 2021, vol. 96, pp. 38–42. Doi: 10.1016/j.clinbiochem.2021.07.009.

28. Fox A.A. Perioperative B-type Natriuretic Peptide/N-terminal pro-B-type Natriuretic Peptide: next steps to clinical practice. Anesthesiology, 2015, vol. 123, no. 2, pp. 246–248. Doi: 10.1097/ALN.0000000000000729.

29. Fung E., Fiscus R.R. Adrenomedullin induces direct (endothelium-independent) vasorelaxations and cyclic adenosine monophosphate elevations that are synergistically enhanced by brain natriuretic peptide in isolated rings of rat thoracic aorta. J Cardiovasc Pharmacol, 2003, vol. 41, no. 6, pp. 849–855. Doi: 10.1097/00005344-200306000-00004

30. Gallo G., Rubattu S., Autore C. et al. Natriuretic peptides: it is time for guided therapeutic strategies based on their molecular mechanisms. Int J Mol Sci, 2023, vol. 24, no. 6, pp. 5131. Doi: 10.3390/ijms24065131.

31. Goei D., van Kuijk J.P., Flu W.J. et al. Usefulness of repeated N-terminal pro-B-type natriuretic peptide measurements as incremental predictor for long-term cardiovascular outcome after vascular surgery. Am J Cardiol, 2011, vol. 107, no. 4, pp. 609–614. Doi: 10.1016/j.amjcard.2010.10.021.

32. Green S.B. How many subjects does it take to do a regression analysis. Multivariate Behav Res, 1991, vol. 26, no. 3, pp. 499–510. Doi: 10.1207/s15327906mbr2603_7.

33. Halvorsen S., Mehilli J., Cassese S. et al. ESC Scientific Document Group. 2022 ESC Guidelines on cardiovascular assessment and management of patients undergoing non-cardiac surgery. Eur Heart J, 2022, vol. 43, no. 39, pp. 3826–3924. Doi: 10.1093/eurheartj/ehac270.

34. Khan A., Johnson D.K., Carlson S. et al. NT-Pro bnp predicts myocardial injury post-vascular surgery and is reduced with CoQ10: a randomized double-blind trial. Ann Vasc Surg, 2020, vol. 64, pp. 292–302. Doi: 10.1016/j. avsg.2019.09.017.

35. Kim H.N., Januzzi J.L. Jr. Natriuretic peptide testing in heart failure. Circulation, 2011, vol. 123, no. 18, pp. 2015–2019. Doi: 10.1161/ CIRCULATIONAHA.110.979500.

36. Lurati Buse G., Bollen Pinto B., Abelha F. et al. ESAIC focused guideline for the use of cardiac biomarkers in perioperative risk evaluation. Eur J Anaesthesiol, 2023, vol. 40, pp. 1–26. Doi: 10.1097/EJA.0000000000001865.

37. Mahla E., Baumann A., Rehak P. et al. N-terminal pro-brain natriuretic peptide identifies patients at high risk for adverse cardiac outcome after vascular surgery. Anesthesiology, 2007, vol. 106, no. 6, pp. 1088–1095. Doi: 10.1097/01.anes.0000267591.34626.b0.

38. Mauermann E., Bolliger D., Fassl J. et al. Absolute postoperative B-Type Natriuretic Peptide concentrations, but not their general trend, are associated with 12-month, all-cause mortality after on-pump cardiac surgery. Anesth Analg, 2017, vol. 125, no. 3, pp. 753–761. Doi: 10.1213/ANE.0000000000002291.

39. Paladugu S., Donato A.A. Adding NT-proBNP to the Revised Cardiac Risk Index improved prediction of CV events after noncardiac surgery. Ann Intern Med, 2020, vol. 172, no. 10, pp. JC59. Doi: 10.7326/ACPJ202005190-059.

40. Potter L.R., Abbey-Hosch S., Dickey D.M. Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr Rev, 2006, vol. 27, no. 1, pp. 47–72. Doi: 10.1210/er.2005-0014.

41. Qamar A., Bangalore S. Biomarkers to personalize preoperative cardiovascular risk stratification: ready for prime time? Ann Intern Med, 2020, vol. 172, no. 2, pp. 149–150. Doi: 10.7326/M19-3718.

42. Rodseth R.N., Biccard B.M., Le Manach Y. et al. The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: a systematic review and individual patient data meta-analysis. J Am Coll Cardiol, 2014, vol. 63, no. 2, pp. 170–180. Doi: 10.1016/j.jacc.2013.08.1630.

43. Samad M., Malempati S., Restini C.B.A. Natriuretic peptides as biomarkers: narrative review and considerations in cardiovascular and respiratory dysfunctions. Yale J Biol Med, 2023, vol. 96, no. 1, pp. 137–149. Doi: 10.59249/NCST6937.

44. Santhekadur P.K., Kumar D.P., Seneshaw M. et al. The multifaceted role of natriuretic peptides in metabolic syndrome. Biomed Pharmacother, 2017, vol. 92, pp. 826–835. Doi: 10.1016/j.biopha.2017.05.136.

45. Schouten O., Hoeks S.E., Goei D. et al. Plasma N-terminal pro-B-type natriuretic peptide as a predictor of perioperative and long-term outcome after vascular surgery. J Vasc Surg, 2009, vol. 49, no. 2, pp. 435–441. Doi: 10.1016/j. jvs.2008.08.063.

46. Smilowitz N.R., Berger J.S. Perioperative management to reduce cardiovascular events. Circulation, 2016, vol. 133, no. 11, pp. 1125–1130. Doi: 10.1161/CIRCULATIONAHA.115.017787.

47. Sugawa S., Masuda I., Kato K. et al. Increased levels of cardiac troponin I in subjects with extremely low B-type Natriuretic peptide levels. Sci Rep, 2018, vol. 8, no. 1, pp. 5120. Doi: 10.1038/s41598-018-23441-z.

48. Tsutsumi J., Minai K., Kawai M. et al. Manifold implications of obesity in ischemic heart disease among Japanese patients according to covariance structure analysis: Low reactivity of B-type natriuretic peptide as an intervening risk factor. PLoS One, 2017, vol. 12, no. 5, pp. e0177327. Doi: 10.1371/journal. pone.0177327.

49. Yurttas T., Hidvegi R., Filipovic M. Biomarker-based preoperative risk stratification for patients undergoing non-cardiac surgery. J. Clin. Med, 2020, vol. 9, no. 2, pp. 351. Doi: 10.3390/jcm9020351