A Blood-Based Gene Expression Test for Obstructive Coronary Artery Disease Tested in Symptomatic Nondiabetic Patients Referred for Myocardial Perfusion Imaging The COMPASS StudyClinical Perspective
Background—Obstructive coronary artery disease diagnosis in symptomatic patients often involves noninvasive testing before invasive coronary angiography. A blood-based gene expression score (GES) was previously validated in nondiabetic patients referred for invasive coronary angiography but not in symptomatic patients referred for myocardial perfusion imaging (MPI).
Methods and Results—This prospective, multicenter study obtained peripheral blood samples for GES before MPI in 537 consecutive patients. Patients with abnormal MPI usually underwent invasive coronary angiography; all others had research coronary computed tomographic angiography, with core laboratories defining coronary anatomy. A total of 431 patients completed GES, coronary imaging (invasive coronary angiography or computed tomographic angiography), and MPI. Mean age was 56±10 years (48% women). The prespecified primary end point was GES receiver-operating characteristics analysis to discriminate ≥50% stenosis (15% prevalence by core laboratory analysis). Area under the receiver-operating characteristics curve for GES was 0.79 (95% confidence interval, 0.73–0.84; P<0.001), with sensitivity, specificity, and negative predictive value of 89%, 52%, and 96%, respectively, at a prespecified threshold of ≤15 with 46% of patients below this score. The GES outperformed clinical factors by receiver-operating characteristics and reclassification analysis and showed significant correlation with maximum percent stenosis. Six-month follow-up on 97% of patients showed that 27 of 28 patients with adverse cardiovascular events or revascularization had GES >15. Site and core-laboratory MPI had areas under the curve of 0.59 and 0.63, respectively, significantly less than GES.
Conclusions—GES has high sensitivity and negative predictive value for obstructive coronary artery disease. In this population clinically referred for MPI, the GES outperformed clinical factors and MPI.
- computed tomography angiography
- coronary angiography
- gene expression
- myocardial perfusion imaging
- Received June 6, 2012.
- Accepted February 5, 2013.
- © 2013 American Heart Association, Inc.