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Atherosclerosis. 2014 Mar;233(1):284-90. doi: 10.1016/j.atherosclerosis.2013.12.045. Epub 2014 Jan 20.

A peripheral blood gene expression score is associated with atherosclerotic Plaque Burden and Stenosis by cardiovascular CT-angiography: results from the PREDICT and COMPASS studies.

Author information

1
Stony Brook University, Stony Brook, NY, USA.
2
CardioDx, Inc., 2500 Faber Place, Palo Alto, CA 94303, USA.
3
Harbor UCLA Medical Center, Torrance, CA, USA.
4
Long Beach Memorial Medical Center, Long Beach, CA, USA; University of California, Irvine, Orange, CA, USA.
5
CardioDx, Inc., 2500 Faber Place, Palo Alto, CA 94303, USA. Electronic address: srosenberg@cardiodx.com.

Abstract

OBJECTIVE:

We previously validated a gene expression score (GES) based on age, sex and peripheral blood cell expression levels of 23 genes measured by quantitative real-time PCR (qRT-PCR) for diagnosis of obstructive coronary artery disease (CAD) (≥ 50% luminal diameter stenosis). In this study we sought to determine the association between the GES and coronary arterial Plaque Burden and Stenosis by CT-angiography.

METHODS:

A total of 610 patients (mean age: 57 ± 11; 50% male) from the PREDICT and COMPASS studies from 59 centers were analyzed. Coronary artery calcium (CAC) scoring, CT angiography (CTA)-based plaque and stenosis and GES measurements were performed. CAC was expressed as Agatston score and CTA evaluated for stenosis severity: 0. None; 1. Minimal, 2. Mild, 3. Moderate, 4. Severe and 5. Occluded. Correlation analysis, one-way analysis of variance (ANOVA) and receiver operating characteristics (ROC) analyses were performed.

RESULTS:

GES was significantly associated with plaque burden by CAC (r = 0.50; p < 0.001) and CTA (segment involvement score index: r = 0.37, p < 0.001); a low score (≤ 15) had sensitivity of 0.71 and a high score (≥ 28) a specificity of 0.97 for the prediction of zero vs. non-zero CAC. Increasing GES was associated with a greater degree of categorical stenosis by ANOVA (p < 0.001); GES significantly correlated with maximum luminal stenosis (r = 0.41; p < 0.01) and segment stenosis score index (r = 0.38; p < 0.01). A low score had sensitivity of 0.90 and a high score a specificity of 0.87 for ≥ 70% stenosis.

CONCLUSIONS:

A previously validated GES is significantly associated with Plaque Burden and Stenosis by CT.

CLINICAL TRIAL REGISTRATION:

(PREDICT [NCT00500617] and COMPASS [NCT01117506]), www.clinicaltrials.gov.

KEYWORDS:

CT-angiography; Calcium score; Coronary artery disease; Gene expression; Plaque burden

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