An age- and sex-specific gene expression score is associated with revascularization and coronary artery disease: Insights from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial

Am Heart J. 2017 Feb:184:133-140. doi: 10.1016/j.ahj.2016.11.004. Epub 2016 Nov 15.

Abstract

Background: Identifying predictors of coronary artery disease (CAD)-related procedures and events remains a priority.

Methods: We measured an age- and sex-specific gene expression score (ASGES) previously validated to detect obstructive CAD (oCAD) in symptomatic nondiabetic patients in the PROMISE trial. The outcomes were oCAD (≥70% stenosis in ≥1 vessel or ≥50% left main stenosis on CT angiography [CTA]) and a composite endpoint of death, myocardial infarction, revascularization, or unstable angina.

Results: The ASGES was determined in 2370 nondiabetic participants (47.5% male, median age 59.5 years, median follow-up 25 months), including 1137 with CTA data. An ASGES >15 was associated with oCAD (odds ratio 2.5 [95% CI 1.6-3.8], P<.001) and the composite endpoint (hazard ratio [HR] 2.6 [95% CI 1.8-3.9], P<.001) in unadjusted analyses. After adjustment for Framingham risk, an ASGES >15 remained associated with the composite endpoint (P=.02); the only component that was associated was revascularization (adjusted HR 2.69 [95% CI 1.52-4.79], P<.001). Compared to noninvasive testing, the ASGES improved prediction for the composite (increase in c-statistic=0.036; continuous net reclassification index=43.2%). Patients with an ASGES ≤15 had a composite endpoint rate no different from those with negative noninvasive test results (3.2% vs. 2.6%, P=.29).

Conclusions: A blood-based genomic test for detecting oCAD significantly predicts near-term revascularization procedures, but not non-revascularization events. Larger studies will be needed to clarify the risk with non-revascularization events.

Publication types

  • Multicenter Study

MeSH terms

  • Age Factors
  • Aged
  • Computed Tomography Angiography
  • Coronary Angiography
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / genetics*
  • Coronary Artery Disease / surgery
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Revascularization / statistics & numerical data*
  • Odds Ratio
  • Proportional Hazards Models
  • Prospective Studies
  • RNA, Messenger / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Risk Assessment
  • Sex Factors
  • Transcriptome / genetics*

Substances

  • RNA, Messenger