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

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.

The use of preoperative B-type natriuretic peptide as a predictor of atrial fibrillation after thoracic surgery: systematic review and meta-analysis.

OBJECTIVE: To determine whether elevated preoperative B-type natriuretic peptide (NP) measurements are an independent predictor of atrial fibrillation (AF) in patients having thoracic surgery. DESIGN: Systematic review and meta-analysis. SETTING: In-hospital and 30 days after thoracic surgery. PARTICIPANTS: The 742 patients who participated in the 5 observational studies. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: EMBASE, OVID Health Star, Ovid Medline, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses A&I databases were searched for all studies of noncardiac thoracic surgery patients in whom a preoperative NP was measured up to 1 month before surgery, and that measured the incidence of postoperative AF. Studies were included regardless of their language, sample size, publication status, or study design. Study quality was evaluated using the Newcastle Ottowa Scale. The combined incidence of postoperative AF was 14.5% (n=108/742), and the NP thresholds used to predict AF varied among studies. An elevated preoperative NP measurement was associated with an OR of 3.13 (95% CI 1.38-7.12; I2=87%) for postoperative AF, with the sensitivity analysis reporting an OR of 9.51 (95% CI 4.66-19.40; I2=0). CONCLUSION: Patients with an elevated preoperative NP measurement are at an increased risk of postoperative AF. There may be value in incorporating NP measurement into existing AF risk prediction models.