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: Danielle Potgieter, Dale Simmers, Lisa Ryan, Bruce M Biccard, Giovanna A Lurati-Buse, Daniela M Cardinale, Carol P W Chong, Miloslaw Cnotliwy, Sylvia I Farzi, Radmilo J Jankovic, Wen Kwang Lim, Elisabeth Mahla, Ramaswamy Manikandan, Anna Oscarsson, Michael P Phy, Sriram Rajagopalan, William J Van Gaal, Marek Waliszek, Reitze N Rodseth
• Journal: Anesthesiology (Anesthesiology) Vol. 123 Issue 2 Pg. 264-71 (Aug 2015) ISSN: 1528-1175 [Electronic] United States
• PMID: 26200179 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't, Review, Systematic Review)

Chemical References

• Biomarkers
• Peptide Fragments
• pro-brain natriuretic peptide (1-76)
• Natriuretic Peptide, Brain

Topics

• Biomarkers (blood)
• Heart Diseases (blood, diagnosis)
• Humans
• Natriuretic Peptide, Brain (blood)
• Peptide Fragments (blood)
• Prognosis