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.