title: N-terminal pro-B-type Natriuretic Peptides' Prognostic Utility Is Overestimated in Meta-analyses Using Study-specific Optimal Diagnostic Thresholds.
abstract: BACKGROUND
  N-terminal fragment B-type natriuretic peptide (NT-proBNP) prognostic utility is commonly determined post hoc by identifying a single optimal discrimination threshold tailored to the individual study population. The authors aimed to determine how using these study-specific post hoc thresholds impacts meta-analysis results.
  
  
  METHODS
  The authors conducted a systematic review of studies reporting the ability of preoperative NT-proBNP measurements to predict the composite outcome of all-cause mortality and nonfatal myocardial infarction at 30 days after noncardiac surgery. Individual patient-level data NT-proBNP thresholds were determined using two different methodologies. First, a single combined NT-proBNP threshold was determined for the entire cohort of patients, and a meta-analysis conducted using this single threshold. Second, study-specific thresholds were determined for each individual study, with meta-analysis being conducted using these study-specific thresholds.
  
  
  RESULTS
  The authors obtained individual patient data from 14 studies (n = 2,196). Using a single NT-proBNP cohort threshold, the odds ratio (OR) associated with an increased NT-proBNP measurement was 3.43 (95% CI, 2.08 to 5.64). Using individual study-specific thresholds, the OR associated with an increased NT-proBNP measurement was 6.45 (95% CI, 3.98 to 10.46). In smaller studies (<100 patients) a single cohort threshold was associated with an OR of 5.4 (95% CI, 2.27 to 12.84) as compared with an OR of 14.38 (95% CI, 6.08 to 34.01) for study-specific thresholds.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Department of Anaesthesia, University of Kwa-Zulu Natal, Inkosi Albert Luthuli Central Hospital, Durban, South Africa (D.P., D.S.); Department of Anaesthesia, Greys Hospital, Pietermaritzburg, South Africa (L.R.); Department of Anaesthetics, Inkosi Albert Luthuli Central Hospital, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa (B.M.B.); Department of Anaesthesia and Intensive Care Medicine, University Hospital Basel, Basel, Switzerland (G.A.L.-B.); Cardioncology Unit, European Institute of Oncology, Milan, Italy (D.M.C.); Departments of Aged Care, Northern Clinical Research Centre, The Northern Hospital, Epping, Victoria, Australia, and Department of Medicine, Austin and Northern Health, The University of Melbourne, Victoria, Australia (C.P.W.C., K.W.L.); Department of Vascular and General Surgery and Angiology, Pomeranian Medical University, Szczecin, Poland (M.C.); Department of Anaesthesiology and Intensive Care Medicine, Medical University of Graz, Graz, Austria (S.I.F., E.M.); Department for Anesthesia and Intensive Care, Clinic for Cardiovascular and Thoracic Surgery, Clinical Center Nis, School of Medicine, University of Nis, Nis, Serbia (R.J.J.); Departments of Urology, Stepping Hill Hospital, Stockport and Wrightington, Wigan, and Leigh NHS Foundation Trust, Wigan, United Kingdom (R.M.); Department of Medicine and Health, Linköping University and Department of Anaesthesiology and Intensive Care, Linköping University Hospital, Linköping, Sweden (A.O.); Department of General Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas (M.P.P.); Department of Vascular Surgery, University of Aberdeen and Aberdeen Royal Infirmary, NHS Grampian, Foresterhill, Aberdeen, United Kingdom (S.R.); Department of Cardio logy, University of Melbourne, Northern Health, Epping, Victoria, Australia (W.J.V.G.); Cardiac Diagnostics Unit, M. Pirogow Provincial Specialist Hospital, Lodz, Poland (M.W.); and D
authors.forename: Danielle
authors.initials: D
authors.lastname: Potgieter
authors.forename: Dale
authors.initials: D
authors.lastname: Simmers
authors.forename: Lisa
authors.initials: L
authors.lastname: Ryan
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Biccard
authors.forename: Giovanna A
authors.initials: GA
authors.lastname: Lurati-Buse
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Cardinale
authors.forename: Carol P W
authors.initials: CP
authors.lastname: Chong
authors.forename: Miloslaw
authors.initials: M
authors.lastname: Cnotliwy
authors.forename: Sylvia I
authors.initials: SI
authors.lastname: Farzi
authors.forename: Radmilo J
authors.initials: RJ
authors.lastname: Jankovic
authors.forename: Wen Kwang
authors.initials: WK
authors.lastname: Lim
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mahla
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Manikandan
authors.forename: Anna
authors.initials: A
authors.lastname: Oscarsson
authors.forename: Michael P
authors.initials: MP
authors.lastname: Phy
authors.forename: Sriram
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: William J
authors.initials: WJ
authors.lastname: Van Gaal
authors.forename: Marek
authors.initials: M
authors.lastname: Waliszek
authors.forename: Reitze N
authors.initials: RN
authors.lastname: Rodseth
mesh_terms: D015415:Biomarkers / Q000097:blood; D006331:Heart Diseases / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D011379:Prognosis
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain