N-terminal pro-B-type Natriuretic Peptides’ Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds

Potgieter, D.; Simmers, Dale; Ryan, Lisa; Biccard, Bruce; Buse, Giovanna Lurati; Cardinale, Daniela; Chong, Carol P; Cnotliwy, Miłosław; Farzi, Sylvia; Janković, Radmilo; Lim, Wen Kwang; Mahla, Elisabeth; Manikandan, Ramaswamy; Oscarsson, Anna; Phy, Michael; Rajagopalan, Sriram; Gaal, William J. van; Waliszek, Marek; Rodseth, Reitze

doi:10.1097/aln.0000000000000728

Cited by 18 publications

(11 citation statements)

References 26 publications

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“…(28) In perioperative medicine, several studies have shown that preoperative BNP and NT-proBNP values are associated with postoperative cardiac events after major non-cardiac surgery. (15–18,20,21,29–32) High-sensitivity cardiac troponin assays now allow the detection of more subtle episodes of cardiac injury. (9,11) Baseline hs-cTn is a strong predictor of cardiac morbidity and mortality in the general adult population.…”

Section: Discussionmentioning

confidence: 99%

“…(8–13) We have recently reported that hs-cTnT improves preoperative risk prediction. (14) We now sought to investigate whether NT-proBNP(15–21) and hs-cTnT augment the accuracy of standard risk indices such as RCRI and ASA physical status to predict postoperative MI. Accordingly, we conducted a nested cohort study within the completed Vitamins in Nitrous Oxide (VINO) Trial.…”

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Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP

Kopec

Duma

Helwani

et al. 2017

Anesthesia &Amp; Analgesia

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Background This study sought to determine if preoperatively measured high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) improve cardiac risk prediction in patients undergoing major non-cardiac surgery when compared to standard risk indices. Methods In this ancillary study to the Vitamins in Nitrous Oxide (VINO) trial, patients were included who had preoperative hs-cTnT and NT-proBNP measured (n=572). Study outcome was the incidence of postoperative myocardial infarction (MI) within the first three postoperative days. hs-cTn was considered elevated if >14 ng/L and NT-proBNP if >300 ng/L. Additional cutoff values were investigated based on ROC statistics. Biomarker risk prediction was compared to Lee’s Revised Cardiac Risk Index (RCRI) using standard methods and net reclassification index (NRI). Results The addition of hs-cTnT (>14 ng/L) and NT-proBNP (>300 ng/L) to RCRI significantly improved the prediction of postoperative MI (event rate 30/572 (5.2%), AUC ROC increased from 0.590 to 0.716 with a 0.66 NRI [95% CI 0.32 – 0.99] p<0.001). Using 108 ng/L as cutoff for NT-proBNP improved sensitivity compared to 300 ng/L (0.87 vs. 0.53). Sensitivity, specificity, positive and negative predictive value for hs-cTnT were 0.70, 0.60, 0.09 and 0.97, and 0.53, 0.68, 0.08, 0.96 for NT-proBNP. Conclusions The addition of cardiac biomarkers hs-cTnT and NT-proBNP to RCRI improves prediction of adverse cardiac events in the immediate postoperative period after major non-cardiac surgery. The high negative predictive value of preoperative hs-cTnT and NT-proBNP suggest usefulness as a “rule-out” test to confirm low risk of postoperative MI.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP

Kopec

Duma

Helwani

et al. 2017

Anesthesia &Amp; Analgesia

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“…Patients with preoperatively increased cardiac integrity markers (e. g. troponin; N-terminal pro B-type natriuretic peptide, NT-proBNP) have more perioperative cardiovascular complications [19][20][21]. Whether routine preoperative measurement of cardiac integrity markers in cardiovascular risk patients can contribute to reducing perioperative morbidity has not yet been clarified and this is thus not recommended.…”

Section: A31 Blood Analysesmentioning

confidence: 99%

Preoperative evaluation of adult patients before elective, noncardiothoracic surgery

Zwißler

2017

Anaesthesist

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“…In this issue of ANEsTHEsIology, Potgieter et al 6 provide an elegant comparison of two different approaches to meta-analysis of 14 studies of noncardiac surgical patients (n = 2,196) that assess the association between elevated preoperative NT-proBNP and the composite outcome of 30-day postoperative mortality or nonfatal myocardial infarction (MI). B-type natriuretic peptide (BNP) is secreted primarily by cardiac ventricular myocytes in response to increased ventricular wall stress induced by volume expansion, pressure overload, or ischemia.…”

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confidence: 99%

“…1 BNP protein formation begins with intracellular translation into a large preprohormone that is processed to pro-brain natriuretic peptide (proBNP) and then is cleaved and released into the circulation as active BNP and biologically inactive N-terminal proBNP (NT-proBNP) fragment. In this issue of ANEsTHEsIology, Potgieter et al 6 provide an elegant comparison of two different approaches to meta-analysis of 14 studies of noncardiac surgical patients (n = 2,196) that assess the association between elevated preoperative NT-proBNP and the composite outcome of 30-day postoperative mortality or nonfatal myocardial infarction (MI). Although BNP has known compensatory natriuretic, diuretic, and vasodilatory properties, studies of both ambulatory and surgical patients have found that elevations of circulating BNP or NT-proBNP significantly associate with increased adverse cardiac events.…”

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confidence: 99%

Perioperative B-type Natriuretic Peptide/N-terminal pro-B-type Natriuretic Peptide

Fox

2015

Anesthesiology

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T HE heart is not only a pumping organ but also an endocrine organ. B-type natriuretic peptide (BNP) is secreted primarily by cardiac ventricular myocytes in response to increased ventricular wall stress induced by volume expansion, pressure overload, or ischemia. 1 BNP protein formation begins with intracellular translation into a large preprohormone that is processed to pro-brain natriuretic peptide (proBNP) and then is cleaved and released into the circulation as active BNP and biologically inactive N-terminal proBNP (NT-proBNP) fragment. 1 Commercial assays are available to measure circulating BNP and NT-proBNP. Although BNP has known compensatory natriuretic, diuretic, and vasodilatory properties, studies of both ambulatory and surgical patients have found that elevations of circulating BNP or NT-proBNP significantly associate with increased adverse cardiac events. 1-3 Worldwide, approximately 200 million noncardiac surgeries are performed every year, with 30-day postoperative mortality estimated at approximately 2%. 4,5 A number of studies therefore have evaluated whether elevations in preoperative BNP or NT-proBNP predict cardiac morbidity and mortality after noncardiac surgeries. In this issue of ANEsTHEsIology, Potgieter et al. 6 provide an elegant comparison of two different approaches to meta-analysis of 14 studies of noncardiac surgical patients (n = 2,196) that assess the association between elevated preoperative NT-proBNP and the composite outcome of 30-day postoperative mortality or nonfatal myocardial infarction (MI). The authors report that meta-analysis that aggregates study findings using the different optimal cut-points and corresponding odd ratios (oRs) established for each individual study cohort (i.e., aggregate data approach) results in a substantially inflated reported oR for association between NT-proBNP and 30-day postoperative outcome when compared with meta-analysis that combines individual-level data across all studies to define one optimal NT-proBNP cut-point to be used across all study cohorts (i.e., individual patient-level data approach). These findings provide an important warning regarding likely overestimation of effect size reported in aggregate data metaanalyses of biomarker studies. However, although the results of the individual patient-level data meta-analysis by Potgieter et al. demonstrate a marked shrinkage in resulting oR from the oR identified using aggregate data meta-analysis, their findings still highlight a clinically relevant effect size (oR for association between NT-proBNP >367.15 pg/ml and 30-day outcome = 3.61; 95% CI, 2.73 to 4.78). Thus, the question remains regarding what next studies and steps can be undertaken to determine whether perioperative NT-proBNP or BNP assessments can be used in clinical practice to predict and mitigate postoperative morbidity and mortality.A key impediment to moving evaluation of perioperative BNP or NT-proBNP into routine clinical practice for risk stratification and management of surgical patients is the lack of clarity from...

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N-terminal pro-B-type Natriuretic Peptides’ Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds

Abstract: Post hoc identification of study-specific prognostic biomarker thresholds artificially maximizes biomarker predictive power, resulting in an amplification or overestimation during meta-analysis of these results. This effect is accentuated in small studies.

Cited by 18 publications

References 26 publications

Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP

Improving Prediction of Postoperative Myocardial Infarction With High-Sensitivity Cardiac Troponin T and NT-proBNP

Preoperative evaluation of adult patients before elective, noncardiothoracic surgery

Perioperative B-type Natriuretic Peptide/N-terminal pro-B-type Natriuretic Peptide

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