Systematic review, meta-analysis and economic modelling of ...

Assessment of diagnostic and prognostic accuracyTABLE 17 Sensitivity and specificity of other biomarkersStudy Biomarker Threshold Sensitivity (95% CI) Specificity (95% CI)Bassan 2005 56 BNP 100 pg/ml 0.71 (0.67 to 0.74) 0.69 (0.65 to 0.72)Body 2011 57 BNP 73 ng/ml 0.35 (0.26 to 0.44) 0.85 (0.82 to 0.88)Apple 2009 55 CD40L 1.08 ng/l 0.72 (0.51 to 0.88) 0.23 (0.19 to 0.27)Body 2011 46 CD40L 17.2 ng/l 0.67 (0.58 to 0.75) 0.25 (0.21 to 0.28)Keller 2010 71 Copeptin 9.8 pmol/l13 pmol/l18.9 pmol/lReichlin2009 80 Copeptin 9 pmol/l14 pmol/l20 pmol/l24 pmol/lApple 2009 55 CRP 125 ng/l age < 75 years,450 ng/l age > 75 years0.66 (0.6 to 0.71)0.57 (0.52 to 0.63)0.49 (0.43 to 0.55)Reported only incombination with troponin0.79 (0.54 to 0.94)0.50 (0.12 to 0.88)0.70 (0.67 to 0.73)0.78 (0.75 to 0.8)0.84 (0.82 to 0.87)Reported only in combinationwith troponin0.47 (0.42 to 0.53)0.28 (0.17 to 0.40)Potsch 2006 51 CRP 1.0 mg/l 0.30 (0.22 to 0.38) 0.80 (0.78 to 0.83)Apple 2009 55 MMP9 125 µg/l 0.96 (0.80 to 0.99) 0.19 (0.15 to 0.23)Apple 2009 55 MPO 233 µg/l 0.76 (0.55 to 0.91) 0.38 (0.34 to 0.43)Body 2011 57 MPO 510 pM 0.60 (0.51 to 0.68) 0.58 (0.54 to 0.62)Esporcatte MPO ≥100 pM 0.92 (0.67 to 1.0) 0.40 (0.32 to 0.49)2007 65Rudolph MPO Sample median 0.80 (0.76 to 0.84) 0.68 (0.65 to 0.71)2010 81Apple 2009 55 NT-pro-BNP 1.0 mg/l3.0 mg/l0.80 (0.59 to 0.93)0.88 (0.69 to 0.97)0.39 (0.35 to 0.46)0.19 (0.15 to 0.23)Body 2011 46 PAPP-A 4.4 µg/l 0.49 (0.4 to 0.58) 0.67 (0.63 to 0.71)Brown 2007 47 ST2 NR NR a NRAUROC, area under receiver operating characteristic; NR, not reported.a AUROC for MI was 0.636.troponin and the alternative biomarker were combined by classifying the combination as positive if eithertest was positive. However, the study by Apple et al. 55 classified the combination as positive only if bothtests were positive. Thus, in most studies the combination had higher sensitivity and lower specificitythan troponin alone, whereas the combinations tested by Apple et al. 55 had lower sensitivity and higherspecificity than troponin alone.These studies show that combining troponin with another biomarker at presentation, with elevationof either biomarker producing a positive test, results in markedly improved sensitivity but with a loss inspecificity that can be substantial. None of these analyses uses a high-sensitivity troponin assay. The resultsof the troponin meta-analysis suggest that a similar improvement in sensitivity at the expense of specificitycan be achieved if a lower threshold for troponin positivity is used.Summary of the findings of the diagnostic biomarker reviewThe sensitivity and specificity of troponin measurement at presentation depends on the assay used andthe threshold for positivity. High-sensitivity assays using the 99th percentile as the threshold for positivity54NIHR Journals Library