title: A blood-based gene expression test for obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for myocardial perfusion imaging the COMPASS study.
abstract: 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. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01117506.
authors: Long Beach Memorial Medical Center, Long Beach, CA 90806, USA. gthomas1@memorialcare.org
authors: Gregory S
authors: GS
authors: Thomas
authors: Szilard
authors: S
authors: Voros
authors: John A
authors: JA
authors: McPherson
authors: Alexandra J
authors: AJ
authors: Lansky
authors: Mary E
authors: ME
authors: Winn
authors: Timothy M
authors: TM
authors: Bateman
authors: Michael R
authors: MR
authors: Elashoff
authors: Hsiao D
authors: HD
authors: Lieu
authors: Andrea M
authors: AM
authors: Johnson
authors: Susan E
authors: SE
authors: Daniels
authors: Joseph A
authors: JA
authors: Ladapo
authors: Charles E
authors: CE
authors: Phelps
authors: Pamela S
authors: PS
authors: Douglas
authors: Steven
authors: S
authors: Rosenberg
mesh_terms: D000328:Adult; D000367:Age Factors; D000465:Algorithms; D019540:Area Under Curve; D003251:Constriction, Pathologic; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism; D004311:Double-Blind Method; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D055414:Myocardial Perfusion Imaging; D009504:Neutrophils / Q000378:metabolism; D015995:Prevalence; D011446:Prospective Studies; D012372:ROC Curve; D012737:Sex Factors; D014057:Tomography, X-Ray Computed