title: 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.
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.
authors.affiliation: Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC. Electronic address: Deepak.voora@duke.edu.
authors.forename: Deepak
authors.initials: D
authors.lastname: Voora
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Adrian
authors.initials: A
authors.lastname: Coles
authors.affiliation: Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: Lee
authors.affiliation: Massachusetts General Hospital, Harvard Medical School, Boston, MA.
authors.forename: Udo
authors.initials: U
authors.lastname: Hoffmann
authors.affiliation: CardioDx, Inc., Redwood City, CA.
authors.forename: James A
authors.initials: JA
authors.lastname: Wingrove
authors.affiliation: CardioDx, Inc., Redwood City, CA.
authors.forename: Brian
authors.initials: B
authors.lastname: Rhees
authors.affiliation: CardioDx, Inc., Redwood City, CA.
authors.forename: Lin
authors.initials: L
authors.lastname: Huang
authors.affiliation: CardioDx, Inc., Redwood City, CA.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Daniels
authors.affiliation: CardioDx, Inc., Redwood City, CA.
authors.forename: Mark
authors.initials: M
authors.lastname: Monane
authors.affiliation: CardioDx, Inc., Redwood City, CA.
authors.forename: Steven
authors.initials: S
authors.lastname: Rosenberg
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Svati H
authors.initials: SH
authors.lastname: Shah
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: William E
authors.initials: WE
authors.lastname: Kraus
authors.affiliation: Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC.
authors.forename: Geoffrey S
authors.initials: GS
authors.lastname: Ginsburg
authors.affiliation: Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Douglas
mesh_terms: D000367:Age Factors; D000368:Aged; D000072226:Computed Tomography Angiography; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics* / Q000601:surgery; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009204:Myocardial Revascularization / Q000706:statistics & numerical data*; D016017:Odds Ratio; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D018570:Risk Assessment; D012737:Sex Factors; D059467:Transcriptome / Q000235:genetics*
chemical_list: D012333:RNA, Messenger