Abstract 195: Peripheral Blood S100A8 and S100A12 Gene Expression Correlate with Coronary Calcium Score and Percent Diameter Stenosis in Patients by CT-Angiography
Background— Coronary artery disease (CAD) can vary by coronary artery calcification (CAC) and extent of stenosis. A previously described peripheral blood 23-gene expression score (GES) was validated for discrimination of obstructive CAD and shown to correlate with maximum % diameter stenosis (%DS), however, its relation to CAC has not been analyzed in detail. S100A12, a component of the score, has been correlated with calcification in a transgenic mouse model.
Methods— A total of 398 patients from the COMPASS trial (NCT01117506) had both core-lab analyzed CT-angiography (CTA) and GES. CAC was determined as whole-heart Agatston score and per-patient maximum %DS by CTA. GES was measured by RT-PCR according to Corus CAD protocols (CardioDx, Palo Alto, CA). Individual gene expression levels were analyzed for significance relative to CAC and %DS by age and sex-adjusted logistic regression.
Results— Patients were 50% male; 50/398 had obstructive CAD (≥50% stenosis by core-lab CTA). Both CAC and %DS were highly correlated with overall GES (p< 10-16). Genes significantly associated with %DS were expressed predominantly in either lymphocyte or myeloid cells (circles and squares in figure respectively, bottom quadrants) whereas no lymphocyte genes and a larger set of myeloid-specific genes were associated with CAC (squares in figure, left quadrants); S100A8 and S100A12 showed the strongest associations with CAC (p = 0.006).
Conclusion— Gene expression significance for %DS appears to reflect increased neutrophil to lymphocyte ratio whereas neutrophil gene up-regulation appears correlated with CAC, the strongest association being seen with S100A8 and S100A12.
- © 2012 by American Heart Association, Inc.