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

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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.

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