The present invention relates to biomarker signatures and associated methods for identifying patients that are not likely to manifest significant coronary artery disease. It is based, at least in part, on a study performed on serum samples of 239 patients with clinical symptoms of cardiac distress, some of whom required invasive intervention (stent placement or bypass graft surgery). A set of biomarkers was identified as exhibiting different levels of expression in subjects that did, or did not, require invasive intervention. Further, an algorithm was developed which, using serum levels of these biomarkers, assigned a score to a given patient that was indicative of whether that patient required invasive intervention.