Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies

J Cardiovasc Transl Res. 2014 Oct;7(7):615-22. doi: 10.1007/s12265-014-9583-3. Epub 2014 Aug 14.

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.

Trial registration: ClinicalTrials.gov NCT00500617 NCT01117506.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Area Under Curve
  • Coronary Angiography / methods
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / ethnology
  • Coronary Artery Disease / genetics*
  • Coronary Stenosis / blood
  • Coronary Stenosis / diagnostic imaging
  • Coronary Stenosis / ethnology
  • Coronary Stenosis / genetics*
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation
  • Genetic Markers
  • Genetic Testing / methods*
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • RNA Stability
  • ROC Curve
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Time Factors
  • Tomography, X-Ray Computed
  • White People / genetics

Substances

  • Genetic Markers

Associated data

  • ClinicalTrials.gov/NCT00500617
  • ClinicalTrials.gov/NCT01117506