Secondary Logo

Journal Logo

Assessment of Preoperative B-Type Natriuretic Peptide in Adult Surgeries

Is It Useful?

Fox, Amanda A., MD, MPH; Body, Simon C., MBChB, MPH

doi: 10.1213/ANE.0b013e318210c739
Editorials: Editorials

From the Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Massachusetts.

Funding: Dennis W. Jahnigen Career Development Scholars Award, American Geriatrics Society, New York, New York (Principle Investigator: A. A. Fox).

The authors declare no conflict of interest.

Reprints will not be available from the authors.

Address correspondence to Amanda A. Fox, MD, MPH, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, 75 Francis Street, CWN, L1, Boston, MA 02115. Address e-mail to

Accepted January 10, 2011

B-type natriuretic peptide (BNP) is secreted primarily by ventricular myocytes in response to increased wall stress induced by volume expansion, pressure overload, or ischemia of the cardiac chambers.1 Elevated plasma BNP is a proven diagnostic and prognostic biomarker in the setting of ambulatory heart failure and acute coronary syndromes.25 With BNP established as clinically relevant in nonsurgical cohorts, efforts have moved to determining whether preoperative BNP can be used to improve risk stratification of surgical patients. This interest is prompted by the fact that the majority of significant postoperative complications are cardiovascular.6 Worldwide, about 200 million noncardiac surgeries are performed annually, with conservative estimates indicating approximately 1 million accompanying adverse postoperative cardiac events.7,8 Surgical risk models that use patients' clinical risk factors alone miss a sizeable proportion of patients who go on to develop adverse postoperative cardiovascular events.9 Furthermore, the American College of Cardiology/American Heart Association's perioperative guidelines strongly emphasize patients' functional status when determining who warrants preoperative cardiac testing, yet surgical patients are frequently elderly and have limited preoperative physical activity levels.10

A preoperative biomarker test, therefore, could prove very useful for surgical risk stratification and perioperative patient care if it is easy and inexpensive to measure, is sensitive and specific for cardiac pathology and adverse postoperative cardiovascular outcomes, adds to what can be anticipated using clinical criteria or routine cardiac testing, and can be used to direct perioperative management changes to improve patient outcomes. Several meta-analyses of studies of noncardiac surgical patients have shown that elevated preoperative BNP or N-terminal proBNP (NT-proBNP) is strongly associated with adverse short1113 and longer term13 postoperative major adverse cardiovascular events and mortality. Furthermore, the meta-analysis by Lurati Buse et al. in this issue of Anesthesia & Analgesia illustrates that elevated preoperative BNP is associated with all-cause mortality in both noncardiac and cardiac surgical patients, with BNP thresholds providing high negative predictive value in both surgical groups.14 What remains to be delineated is precisely how physicians and patients should interpret and use preoperative BNP measurements for perioperative planning to prevent adverse postoperative patient outcomes.

Although there are strong associations between elevated circulating BNP and the development of adverse outcomes after surgery, a major challenge facing the use of BNP for surgical risk stratification and patient care lies in identifying useful preoperative BNP thresholds or cut-points above which a patient is deemed “at risk.” There is substantial heterogeneity in the BNP thresholds described in the studies reporting significant associations between elevated preoperative BNP and adverse postoperative outcomes.1114 Potential reasons for this heterogeneity include variability in commercially available BNP assays as well as between study differences in the types of surgical patients assessed (i.e., differences in overall cardiovascular health of studied surgical cohorts).

NT-proBNP has a longer half-life than does BNP, so its levels are elevated when compared with a BNP measurement performed on the same blood sample.15 Additionally, there are multiple commercially available assays for measuring both BNP (active fragment) and NT-proBNP (inactive fragment), with some between-assays variability.16 Cut-points identified in the literature for clinical use should therefore be considered specific to the assessed BNP assay. Also contributing to variability in reported BNP risk thresholds is the fact that BNP (or NT-proBNP) is elevated in the setting of even subtle myocardial stress or failure and becomes progressively more elevated as myocardial stress increases. Therefore, the normal range of BNP varies according to surgical population (i.e., preoperative BNP levels will differ according to the cardiac disease burden of specific surgical populations). For example, this is why aortic valve replacement patients generally have higher preoperative BNP values than do patients undergoing isolated coronary artery bypass grafting, or why vascular surgical patients (who often have coronary artery disease) generally have higher preoperative BNP values than do healthy day-surgery patients.1114,1719 To be useful for diagnosing and prognosticating, one may need to establish different preoperative BNP risk thresholds for different surgical populations, with studies focusing on surgical cohorts characterized by general homogeneity of the invasiveness of the surgeries included, as well as the degree of enrolled subjects' typical preoperative cardiac pathology. The ongoing multicenter VISION Study (Vascular Events in Noncardiac Surgery Patients Cohort Evaluation Study) is on target to enroll 40,000 noncardiac surgical patients, and will evaluate NT-proBNP for association with postoperative adverse cardiovascular events. This effort in noncardiac surgical patients will provide well-powered analyses of surgery-specific subcohorts.

In this issue, Lurati Buse et al.'s meta-analysis illustrates that overall, in studies of all-cause mortality in both noncardiac and cardiac surgical cohorts, preoperative BNP risk thresholds demonstrate high negative predictive value, but substantially lower positive predictive value.14 In other words, although preoperative BNP risk thresholds tend to exclude patients who are likely to die after surgery, having a BNP value above the risk threshold may or may not mean that a patient has a heightened risk of mortality. However, BNP is a biomarker of subclinical and clinical heart failure. Therefore, from a biological standpoint, elevated preoperative BNP is most likely to be associated with postoperative morbidity and mortality related to heart failure or, possibly, myocardial infarction. Studies assessing all-cause mortality will include patients as having the study outcome if they died from cardiac causes. However, an all-cause mortality outcome will not capture patients who suffer from postoperative heart failure but who do not die during the study period. Furthermore, many studies assessing postoperative major adverse cardiovascular events do not include heart failure in the composite outcome.12 Future studies focused on the hypothesis that elevated preoperative BNP predicts occurrence of postoperative heart failure–specific events may identify improvement in the positive predictive value of the BNP test. Additionally, the negative predictive value of a test will be higher when assessed in surgical cohorts at a generally low risk of developing the adverse outcome being tested for. Preoperative BNP is most likely to be useful for identifying potential cardiovascular problems not in the lowest-risk patients and not in the very highest risk patients (i.e., the patients with obvious clinical symptoms of cardiac disease), but in those surgical patients with moderate potential for cardiovascular complications. Therefore, it is most valuable to know the negative predictive value of preoperative BNP risk thresholds in moderate-risk surgical cohorts.

In cardiac surgical patients, postoperative C-reactive protein and cardiac troponin I measures have been shown to add to postoperative BNP's ability to predict major adverse cardiovascular events occurring up to 1 year after surgery, but the authors did not similarly evaluate these biomarkers preoperatively.20 Emerging heart failure biomarkers such as ST2, a member of the interleukin 1 receptor family, appear to augment what can be predicted in chronic heart failure patients using BNP alone.21 Future studies could evaluate whether assessment of multiple preoperative biomarkers could improve preoperative surgical risk assessment and the positive predictive value provided by BNP testing alone. Furthermore, increasingly sophisticated statistical methods are being used to evaluate optimal biomarker risk thresholds. Use of 2 pronged approaches of receiver operating characteristic curve and net reclassification index methods may improve the ability to identify preoperative BNP risk thresholds with the best balance between positive and negative predictive values.22

What is particularly appealing about evaluating preoperative BNP is its potential to be used to guide clinical care to improve patient outcomes. Although there have been no studies of BNP-guided perioperative management, it seems logical that patients with elevated preoperative BNP, particularly patients with no known contributing cardiac pathology, should undergo further cardiac evaluation, possibly including echocardiography, stress tests, and coronary angiography. This could allow otherwise undetected coronary artery disease or cardiac valve disease to be addressed prior to surgery. At a minimum, the anesthesiologist could be aware of significant cardiovascular abnormalities—such as coronary artery disease, cardiac valve disease, pulmonary hypertension, or low left ventricular ejection fraction—and could plan anesthetic management accordingly. Also, if patients and surgeons know of added risk of cardiac complications, they might be inclined to forgo an elective surgery or to choose a more conservative but less invasive surgical approach. Furthermore, patients with elevated preoperative BNP secondary to subclinical or clinical heart failure could potentially be medically optimized before and after surgery, with progress in this optimization evaluated using serial BNP measurements. Studies of ambulatory heart failure patients have found that medical management guided towards decreasing serial follow-up BNP or N-terminal proBNP measures (i.e., aggressive titration of medications including β-blockers and angiotensin converting enzyme inhibitors) is associated with improved heart failure readmission-free survival.2325 It is conceivable that surgical patients with elevated preoperative BNP may have fewer adverse postoperative cardiac events (particularly heart failure events) with similar models of pre- and postoperative surveillance.

Anesthesiologists and other perioperative clinicians work daily to try to identify patients who might benefit from even closer preoperative or postoperative surveillance and intervention. With regard to understanding how assessment of preoperative BNP might aid in this endeavor, the first step has clearly been established. Elevated preoperative BNP strongly associates with adverse postoperative outcomes, even after adjusting for important clinical risk factors such as low preoperative left ventricular ejection fraction,12,17,19 yet it is the next steps that will determine how BNP measurements can best be used to help surgical patients. Clinical investigators need to identify preoperative BNP risk thresholds that are specific for predicting outcomes such as postoperative heart failure or myocardial infarction in surgery-specific cohorts. Once these thresholds are established, further research can determine the most important step, which will be to establish the efficacy of BNP-guided interventions to reduce adverse postoperative cardiac events.

Back to Top | Article Outline


Name: Amanda A. Fox, MD, MPH.

Contribution: This author helped write the manuscript.

Attestation: Amanda A. Fox approved the final manuscript.

Name: Simon C. Body, MBChB, MPH.

Contribution: This author helped write the manuscript.

Attestation: Simon C. Body approved the final manuscript.

Back to Top | Article Outline


1. Daniels LB, Maisel AS. Natriuretic peptides. J Am Coll Cardiol 2007;50:2357–68
2. de Lemos JA, Morrow DA, Bentley JH, Omland T, Sabatine MS, McCabe CH, Hall C, Cannon CP, Braunwald E. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001;345:1014–21
3. Harrison A, Morrison LK, Krishnaswamy P, Kazanegra R, Clopton P, Dao Q, Hlavin P, Maisel AS. B-type natriuretic peptide predicts future cardiac events in patients presenting to the emergency department with dyspnea. Ann Emerg Med 2002;39:131–8
4. Doust JA, Pietrzak E, Dobson A, Glasziou P. How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure? Systematic review. BMJ 2005;330:625
5. Mega JL, Morrow DA, De Lemos JA, Sabatine MS, Murphy SA, Rifai N, Gibson CM, Antman EM, Braunwald E. B-type natriuretic peptide at presentation and prognosis in patients with ST-segment elevation myocardial infarction: an ENTIRE-TIMI-23 substudy. J Am Coll Cardiol 2004;44:335–9
6. Mangano DT. Perioperative cardiac morbidity. Anesthesiology 1990;72:153–84
7. Weiser TG, Regenbogen SE, Thompson KD, Haynes AB, Lipsitz SR, Berry WR, Gawande AA. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet 2008;372:139–44
8. Devereaux PJ, Goldman L, Cook DJ, Gilbert K, Leslie K, Guyatt GH. Perioperative cardiac events in patients undergoing noncardiac surgery: a review of the magnitude of the problem, the pathophysiology of the events and methods to estimate and communicate risk. CMAJ 2005;173:627–34
9. Lee TH, Marcantonio ER, Mangione CM, Thomas EJ, Polanczyk CA, Cook EF, Sugarbaker DJ, Donaldson MC, Poss R, Ho KK, Ludwig LE, Pedan A, Goldman L. Derivation and prospective validation of a simple index for prediction of cardiac risk of major noncardiac surgery. Circulation 1999;100:1043–9
10. Fleisher LA, Beckman JA, Brown KA, Calkins H, Chaikof E, Fleischmann KE, Freeman WK, Froehlich JB, Kasper EK, Kersten JR, Riegel B, Robb JF, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Antman EM, Buller CE, Creager MA, Ettinger SM, Faxon DP, Fuster V, Halperin JL, Hiratzka LF, Hunt SA, Lytle BW, Nishimura R, Ornato JP, Page RL, Tarkington LG, Yancy CW. ACC/AHA 2007 guidelines on perioperative cardiovascular evaluation and care for noncardiac surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery): developed in collaboration with the American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Rhythm Society, Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, Society for Vascular Medicine and Biology, and Society for Vascular Surgery. Circulation 2007;116:e418–99
11. Rodseth RN, Padayachee L, Biccard BM. A meta-analysis of the utility of pre-operative brain natriuretic peptide in predicting early and intermediate-term mortality and major adverse cardiac events in vascular surgical patients. Anaesthesia 2008;63:1226–33
12. Karthikeyan G, Moncur RA, Levine O, Heels-Ansdell D, Chan MT, Alonso-Coello P, Yusuf S, Sessler D, Villar JC, Berwanger O, McQueen M, Mathew A, Hill S, Gibson S, Berry C, Yeh HM, Devereaux PJ. Is a pre-operative brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide measurement an independent predictor of adverse cardiovascular outcomes within 30 days of noncardiac surgery? A systematic review and meta-analysis of observational studies. J Am Coll Cardiol 2009;54:1599–606
13. Ryding AD, Kumar S, Worthington AM, Burgess D. Prognostic value of brain natriuretic peptide in noncardiac surgery: a meta-analysis. Anesthesiology 2009;111:311–9
14. Lurati Buse GA, Koller MT, Burkhart C, Seeberger MD, Miodrag F. Predictive value of preoperative natriuretic peptide concentrations in adults undergoing surgery: systematic review and meta-analysis. Anesth Analg 2011;112:1019–33
15. Chien TI, Chen HH, Kao JT. Comparison of Abbott AxSYM and Roche Elecsys 2010 for measurement of BNP and NT-proBNP. Clin Chim Acta 2006;369:95–9
16. Apple FS, Wu AH, Jaffe AS, Panteghini M, Christenson RH. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medical Practice Guidelines: analytical issues for biomarkers of heart failure. Clin Biochem 2008;41:222–6
17. Fox AA, Shernan SK, Collard CD, Liu KY, Aranki SF, DeSantis SM, Jarolim P, Body SC. Preoperative B-type natriuretic peptide is an independent predictor of ventricular dysfunction and mortality after primary coronary artery bypass grafting. J Thorac Cardiovasc Surg 2008;136:452–61
18. Pedrazzini GB, Masson S, Latini R, Klersy C, Rossi MG, Pasotti E, Faletra FF, Siclari F, Minervini F, Moccetti T, Auricchio A. Comparison of brain natriuretic peptide plasma levels versus logistic EuroSCORE in predicting in-hospital and late postoperative mortality in patients undergoing aortic valve replacement for symptomatic aortic stenosis. Am J Cardiol 2008;102:749–54
19. Fox AA, Muehlschlegel JD, Body SC, Shernan SK, Liu KY, Perry TE, Aranki SF, Cook EF, Marcantonio ER, Collard CD. Comparison of the utility of preoperative versus postoperative B-type natriuretic peptide for predicting hospital length of stay and mortality after primary coronary artery bypass grafting. Anesthesiology 2010;112:842–51
20. Fellahi JL, Hanouz JL, Manach YL, Gue X, Monier E, Guillou L, Riou B. Simultaneous measurement of cardiac troponin I, B-type natriuretic peptide, and C-reactive protein for the prediction of long-term cardiac outcome after cardiac surgery. Anesthesiology 2009;111:250–7
21. Daniels LB, Clopton P, Iqbal N, Tran K, Maisel AS. Association of ST2 levels with cardiac structure and function and mortality in outpatients. Am Heart J 2010;160:721–8
22. Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008;27:157–72
23. Pfisterer M, Buser P, Rickli H, Gutmann M, Erne P, Rickenbacher P, Vuillomenet A, Jeker U, Dubach P, Beer H, Yoon SI, Suter T, Osterhues HH, Schieber MM, Hilti P, Schindler R, Brunner-La Rocca HP. BNP-guided vs. symptom-guided heart failure therapy: the trial of intensified vs. standard medical therapy in elderly patients with congestive heart failure (TIME–CHF) randomized trial. JAMA 2009;301:383–92
24. Jourdain P, Jondeau G, Funck F, Gueffet P, Le Helloco A, Donal E, Aupetit JF, Aumont MC, Galinier M, Eicher JC, Cohen-Solal A, Juilliere Y. Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS–BNP multicenter study. J Am Coll Cardiol 2007;49:1733–9
25. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM. Treatment of heart failure guided by plasma aminoterminal brain natriuretic peptide (N-BNP) concentrations. Lancet 2000;355:1126–30
© 2011 International Anesthesia Research Society