Whole blood gene expression testing for coronary artery disease in nondiabetic patients: major adverse cardiovascular events and interventions in the PREDICT trial

Abstract

The majority of first-time angiography patients are without obstructive coronary artery disease (CAD). A blood gene expression score (GES) for obstructive CAD likelihood was validated in the PREDICT study, but its relation to major adverse cardiovascular events (MACE) and revascularization was not assessed. Patients (N = 1,160) were followed up for MACE and revascularization 1 year post-index angiography and GES, with 1,116 completing follow-up. The 30-day event rate was 23% and a further 2.2% at 12 months. The GES was associated with MACE/revascularizations (p < 0.001) and added to clinical risk scores. Patients with GES >15 trended towards increased >30 days MACE/revascularization likelihood (odds ratio = 2.59, 95% confidence interval = 0.89-9.14, p = 0.082). MACE incidence overall was 1.5% (17 of 1,116) and 3 of 17 patients had GES ≤ 15. For the total low GES group (N = 396), negative predictive value was 90% for MACE/revascularization and >99% for MACE alone, identifying a group of patients without obstructive CAD and highly unlikely to suffer MACE within 12 months.

Trial registration: ClinicalTrials.gov NCT00500617.

Conflict of interest statement

This work was funded by CardioDx, Inc.; MRE, BB, and SR are employees and have equity interests and/or stock options in CardioDx, Inc. HDL is a consultant employee at CardioDx, Inc. WEK, RSS, SV, and SGE report research support, JM reports minor consulting income, and AL reports funding for QCA studies all from CardioDx, Inc. EJT is supported in part by the Scripps Translational Science Institute Clinical Translational Science Award from the National Institutes of Health (NIHU54RR02504-01). RW reports no conflicts of interest with respect to this manuscript.

Figures

Fig. 1

Schematic of patient flow and endpoint summary. A total of 1,166 patients from the algorithm development and validation cohorts were followed up. There were 6 late clinical exclusions, resulting in a final cohort of 1,160 of whom follow-up data was available for 1,143 (96%). A total of 267 had interventional procedures or events associated with their index angiographic procedure (within 30 days). The remaining 850 patients had a total of 25 endpoints (14 interventional procedures and 11 adverse events) in the subsequent follow-up period, for a total of 292 endpoints (25%) over 1 year

Fig. 2

a Dependence of event and interventional procedure likelihood on GES in 1 year. The percentage of patients who had interventional procedures or events within 1 year of the index catheterization are shown stratified by GES. GES are divided into low (1–15), medium (16–27), and high (28–40) categories as described in the text. Results are shown for the entire cohort of 1,160 patients. b Dependence of MACE likelihood on GES in 1 year. The percentage of patients who had MACE within 1 year of index catheterization are shown stratified by GES (striped bars). The percentage of patients with revascularization or MACE >30 days post-index catheterization are shown stratified by GES (solid bars). Scores are divided as in a. There were 3, 9, and 5 events for MACE alone (striped bars) and 4, 11, and 4 revascularizations and MACE (solid bars) in the low, medium, and high GES categories