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

Background Cardiac stress testing, particularly with imaging, has been the focus of debates about rising health care costs, inappropriate use, and patient safety in the context of radiation exposure. Objective To determine whether U.S. trends in cardiac stress test use may be attributable to population shifts in demographics, risk factors, and provider characteristics and evaluate whether racial/ethnic disparities exist in physician decision making. Design Analyses of repeated cross-sectional data. Setting National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (1993 to 2010). Patients Adults without coronary heart disease. Measurements Cardiac stress test referrals and inappropriate use. Results Between 1993 to 1995 and 2008 to 2010, the annual number of U.S. ambulatory visits in which a cardiac stress test was ordered or performed increased from 28 per 10 000 visits to 45 per 10 000 visits. No trend was found toward more frequent testing after adjustment for patient characteristics, risk factors, and provider characteristics (P = 0.134). Cardiac stress tests with imaging comprised a growing portion of all tests, increasing from 59% in 1993 to 1995 to 87% in 2008 to 2010. At least 34.6% were probably inappropriate, with associated annual costs and harms of $501 million and 491 future cases of cancer. Authors found no evidence of a lower likelihood of black patients receiving a cardiac stress test (odds ratio, 0.91 [95% CI, 0.69 to 1.21]) than white patients, although some evidence of disparity in Hispanic patients was found (odds ratio, 0.75 [CI, 0.55 to 1.02]). Limitations Cross-sectional design with limited clinical data. Conclusion National growth in cardiac stress test use can largely be explained by population and provider characteristics, but use of imaging cannot. Physician decision making about cardiac stress test use does not seem to contribute to racial/ethnic disparities in cardiovascular disease.