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Derivation and External Validation of a High-Sensitivity Cardiac Troponin-Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease.

ABSTRACT: Background Current noninvasive modalities to diagnose coronary artery disease (CAD) have several limitations. We sought to derive and externally validate a hs-cTn (high-sensitivity cardiac troponin)-based proteomic model to diagnose obstructive coronary artery disease. Methods and Results In a derivation cohort of 636 patients referred for coronary angiography, predictors of ?70% coronary stenosis were identified from 6 clinical variables and 109 biomarkers. The final model was first internally validated on a separate cohort (n=275) and then externally validated on a cohort of 241 patients presenting to the ED with suspected acute myocardial infarction where ?50% coronary stenosis was considered significant. The resulting model consisted of 3 clinical variables (male sex, age, and previous percutaneous coronary intervention) and 3 biomarkers (hs-cTnI [high-sensitivity cardiac troponin I], adiponectin, and kidney injury molecule-1). In the internal validation cohort, the model yielded an area under the receiver operating characteristic curve of 0.85 for coronary stenosis ?70% (P<0.001). At the optimal cutoff, we observed 80% sensitivity, 71% specificity, a positive predictive value of 83%, and negative predictive value of 66% for ?70% stenosis. Partitioning the score result into 5 levels resulted in a positive predictive value of 97% and a negative predictive value of 89% at the highest and lowest levels, respectively. In the external validation cohort, the score performed similarly well. Notably, in patients who had myocardial infarction neither ruled in nor ruled out via hs-cTnI testing ("indeterminate zone," n=65), the score had an area under the receiver operating characteristic curve of 0.88 (P<0.001). Conclusions A model including hs-cTnI can predict the presence of obstructive coronary artery disease with high accuracy including in those with indeterminate hs-cTnI concentrations.

SUBMITTER: McCarthy CP

PROVIDER: S-EPMC7660799 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Derivation and External Validation of a High-Sensitivity Cardiac Troponin-Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease.

McCarthy Cian P CP Neumann Johannes T JT Michelhaugh Sam A SA Ibrahim Nasrien E NE Gaggin Hanna K HK Sörensen Nils A NA Schäefer Sarina S Zeller Tanja T Magaret Craig A CA Barnes Grady G Rhyne Rhonda F RF Westermann Dirk D Januzzi James L JL

Journal of the American Heart Association 20200806 16

Background Current noninvasive modalities to diagnose coronary artery disease (CAD) have several limitations. We sought to derive and externally validate a hs-cTn (high-sensitivity cardiac troponin)-based proteomic model to diagnose obstructive coronary artery disease. Methods and Results In a derivation cohort of 636 patients referred for coronary angiography, predictors of ≥70% coronary stenosis were identified from 6 clinical variables and 109 biomarkers. The final model was first internally ...[more]

PMID: 32757795

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Project description:IntroductionTroponin elevation is an independent risk factor for mortality, but the prognosis of patients with troponin elevation and non-obstructive coronary artery disease (CAD) is unknown. Recent data have suggested an increased risk of mortality. This study was performed to further investigate the outcomes of troponin-positive patients with obstructive and non-obstructive CAD.MethodsA retrospective cohort analysis was performed of all patients with raised troponin presenting to Kettering General Hospital (January 2010 to December 2011, n = 1,351). The patients who had angiograms were stratified anatomically into obstructive CAD and non-obstructive CAD (?50% stenosis). The obstructive CAD group (O-CAD) was sub-analyzed by management strategy: emergency re-vascularization (<12 h), urgent, delayed, and medically managed. Patients with non-obstructive CAD were grouped by the cause of the raised troponin if this could be identified (NO-CAD-I) or cause remained unidentified (NO-CAD-U). The major adverse cardiac and cerebrovascular event (MACCE) and mortality rates were calculated at 30 days and 1-year follow-up.ResultsThere was a preponderance of hypertension and severe renal impairment in the non-obstructive CAD group. The patients with NO-CAD-U were a low-risk group (MACCE at 1-year follow-up = 0). The remaining NO-CAD-I group had a similar risk to the O-CAD group for MACCE and mortality at 30 days and 1-year follow-up. In fact, at 1-year follow-up, the NO-CAD-I patients when compared with the subgroups of O-CAD, had higher MACCE rates and mortality compared with the emergency re-vascularized group [MACCE: relative risk (RR) (95% CI) = 2.27 (1.29-3.40), P = 0.0047; mortality: RR (95% CI) = 2.08 (1.10-3.93), P = 0.024]. This was driven by higher risk non-cardiac death [RR (95% CI) = 4.10 (1.53-10.99), P = 0.005].ConclusionPatients with identified cause for raised troponin and non-obstructive CAD are at equivalent risk of MACCE and mortality at 30 days and 1-year follow-up compared to those with obstructive CAD.

Project description:BackgroundWe determined whether high-sensitivity cardiac troponin I can improve the estimation of the pretest probability for obstructive coronary artery disease (CAD) in patients with suspected stable angina.Methods and resultsIn a prespecified substudy of the SCOT-HEART trial (Scottish Computed Tomography of the Heart), plasma cardiac troponin was measured using a high-sensitivity single-molecule counting assay in 943 adults with suspected stable angina who had undergone coronary computed tomographic angiography. Rates of obstructive CAD were compared with the pretest probability determined by the CAD Consortium risk model with and without cardiac troponin concentrations. External validation was undertaken in an independent study population from Denmark comprising 487 patients with suspected stable angina. Higher cardiac troponin concentrations were associated with obstructive CAD with a 5-fold increase across quintiles (9%-48%; P<0.001) independent of known cardiovascular risk factors (odds ratio, 1.35; 95% confidence interval, 1.25-1.46 per doubling of troponin). Cardiac troponin concentrations improved the discrimination and calibration of the CAD Consortium model for identifying obstructive CAD (C statistic, 0.788-0.800; P=0.004; χ2=16.8 [P=0.032] to 14.3 [P=0.074]). The updated model also improved classification of the American College of Cardiology/American Heart Association pretest probability risk categories (net reclassification improvement, 0.062; 95% confidence interval, 0.035-0.089). The revised model achieved similar improvements in discrimination and calibration when applied in the external validation cohort.ConclusionsHigh-sensitivity cardiac troponin I concentration is an independent predictor of obstructive CAD in patients with suspected stable angina. Use of this test may improve the selection of patients for further investigation and treatment.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT01149590.

Dataset Information

Derivation and External Validation of a High-Sensitivity Cardiac Troponin-Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease.

Publications

Derivation and External Validation of a High-Sensitivity Cardiac Troponin-Based Proteomic Model to Predict the Presence of Obstructive Coronary Artery Disease.

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