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

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.

Author information

1
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.
2
Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
3
Massachusetts General Hospital, Harvard Medical School, Boston, MA.
4
CardioDx, Inc., Redwood City, CA.
5
Department of Medicine, Duke University School of Medicine, Durham, NC; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.
6
Department of Medicine, Duke University School of Medicine, Durham, NC.
7
Duke Center for Applied Genomics & Precision Medicine, Duke University School of Medicine, Durham, NC; Department of Medicine, Duke University School of Medicine, Durham, NC.

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.

PMID:
28224927
DOI:
10.1016/j.ahj.2016.11.004
[Indexed for MEDLINE]
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