Biological and Analytical Stability of a Peripheral Blood Gene Expression Score for Obstructive Coronary Artery Disease in the PREDICT and COMPASS Studies

Abstract

A gene expression score (GES) for obstructive coronary artery disease (CAD) has been validated in two multicenter studies. Receiver-operating characteristics (ROC) analysis of the GES on an expanded Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) cohort (NCT no. 00500617) with CAD defined by quantitative coronary angiography (QCA) or clinical reads yielded similar performance (area under the curve (AUC) = 0.70, N = 1,502) to the original validation cohort (AUC = 0.70, N = 526). Analysis of 138 non-Caucasian and 1,364 Caucasian patients showed very similar performance (AUCs = 0.72 vs. 0.70). To assess analytic stability, stored samples of the original validation cohort (N = 526) was re-tested after 5 years, and the mean score changed from 20.3 to 19.8 after 5 years (N = 501, 95%). To assess patient scores over time, GES was determined on samples from 173 Coronary Obstruction Detection by Molecular Personalized Gene Expression (COMPASS) study (NCT no. 01117506) patients at approximately 1 year post-enrollment. Mean scores increased slightly from 15.9 to 17.3, corresponding to a 2.5% increase in obstructive CAD likelihood. Changes in cardiovascular medications did not show a significant change in GES.