A peripheral blood gene expression score is associated with plaque volume and phenotype by intravascular ultrasound with radiofrequency backscatter analysis: results from the ATLANTA study

Parag H. Joshi, Sarah Rinehart, Gustavo Vazquez, Zhen Qian, Abhinav Sharma, Hunt Anderson, Laura Murrieta, Nancy Flockhart, Dimitri Karmpaliotis, Anna Kalynych, Bela Asztalos, Michael R. Elashoff, John Blanchard, Steven Rosenberg, Charles Brown III, Szilard Voros


Background: A composite, peripheral gene expression score based on quantitative RNA-measurements has been validated for detecting stenosis against invasive coronary X-ray angiography. IVUS/VH has been validated for quantitative measurements of coronary plaque volume and composition and has been shown to be predictive of outcomes and treatment effects. The correlation between peripheral gene expression and coronary plaque composition by intravascular ultrasound with radiofrequency backscatter (IVUS/VH) is unknown.
Methods: Peripheral blood gene expression score (GES) was prospectively measured in 18 patients undergoing IVUS/VH. Plaque volume and composition [fibrous tissue (FI), fibro-fatty tissue (FF), necrotic core (NC) and dense calcium (DC)] were quantified in 3 dimensions in all plaques within the entire pullback. The relationship to GES was assessed by Spearman rank correlation.
Results: Mean age was 61.1±8.6 years; 67% were male. 1,158 mm of coronary anatomy was imaged by IVUS/VH. Using a validated scale of 1-40, mean GES was 21.6±9.4. GES was associated with plaque volume (R2=0.55; P=0.018), NC volume (R2=0.56; P=0.015), DC volume (R2=0.60; P=0.007), and non-calcified plaque volume (R2=0.50; P=0.036) by Spearman rank correlation.
Conclusions: In this preliminary report, increased GES was associated with higher plaque volume and a more vulnerable plaque phenotype as evidenced by NC and DC. This composite GES is not only associated with obstructive coronary disease, but also with higher plaque volume and vulnerable phenotype.