A Blood Based Gene Expression Test for Obstructive Coronary Artery Disease Tested in Symptomatic Non-Diabetic Patients Referred for Myocardial Perfusion Imaging: The COMPASS Study
Background—Obstructive coronary artery disease (CAD) diagnosis in symptomatic patients often involves non-invasive testing before invasive coronary angiography (ICA). A blood-based gene expression score (GES) was previously validated in non-diabetic patients referred for ICA but not in symptomatic patients referred for myocardial perfusion imaging (MPI).
Methods and Results—This prospective multi-center study obtained peripheral blood samples for GES before MPI in 537 consecutive patients. Patients with abnormal MPI usually underwent ICA; all others had research coronary CT-angiography (CTA), with core laboratories defining coronary anatomy. A total of 431 patients completed GES, coronary imaging (ICA or CTA), and MPI. Mean age was 56±10 (48% women). The pre-specified primary endpoint was GES receiver-operator characteristics (ROC) analysis to discriminate ≥50% stenosis (15% prevalence by core laboratory analysis). ROC curve area (AUC) for GES was 0.79 (95% CI 0.73-0.84, p<.001), with sensitivity, specificity, and negative predictive value (NPV) of 89%, 52%, and 96%, respectively, at a pre-specified threshold of ≤15 with 46% of patients below this score. The GES outperformed clinical factors by ROC and reclassification analysis and also showed significant correlation with maximum percent stenosis. Six-month follow-up on 97% of patients showed that 27/28 patients with adverse cardiovascular events or revascularization had GES >15. Site and core-lab MPI had AUCs of 0.59 and 0.63, respectively, significantly less than GES.
Conclusions—A GES has high sensitivity and NPV for obstructive CAD. In this population clinically referred for MPI, the GES outperformed clinical factors and MPI.
Clinical Trial Registration Information—www.clinicaltrials.gov; Identifier: NCT01117506.
- gene expression
- myocardial perfusion imaging
- computed tomography angiography
- coronary angiography
- Received June 6, 2012.
- Revision received January 15, 2013.
- Accepted February 5, 2013.
- Copyright © 2013, Circulation: Cardiovascular Genetics