Abstract 17577: Peripheral Blood Gene Expression in Acute Coronary Syndrome Reflects Acute Inflammatory Responses and Correlates With Residual Inflammation at Follow-up

Abstract

Introduction: Previous research showed that peripheral blood gene expression profiles correlate with the extent of coronary artery disease (CAD) in stable non-diabetic patients. It remains unknown how these expression profiles change during an acute coronary syndrome (ACS), and whether they relate to residual inflammation at 30-days follow-up. Methods: Peripheral blood samples were prospectively collected from 34 unselected ACS patients (mean age 62 years, 20 STEMI and 14 NSTEMI) on admission and after 30 days. Total RNA was extracted from whole blood at both time points and micro-array analysis was performed (Affymetrix). The results were validated with qRT-PCR and correlated to clinical characteristics and biomarkers. Results: On admission, 170 inflammatory transcripts were differentially expressed when compared to 30 days after the event. Pathway analysis revealed IL-1ß and TNF-α as common upstream regulators of these transcripts. From the top 10 genes, we selected 4 significantly upregulated genes on admission for qRT-PCR validation: CLEC4E (fold change 2.2, p <0.001), FKBP5 (fold change 2.3, p <0.001), IL18RAP (fold change 1.6, p =0.002) and the inflammasome-related NLRC4 (fold change 1.8, p <0.001). These findings were consistent in STEMI and NSTEMI. The gene expression levels on admission were inversely related to hsCRP levels at 30 days. Patients with a high gene expression score on admission had a mean hsCRP of 0.56±0.11mg/l at 30-day follow-up, vs. 2.44±0.75mg/l in patients with a low gene expression score ( p =0.035, figure 1). This difference was independent of peak troponin T or peak CRP. Conclusion: Peripheral blood gene expression profiles reflect acute inflammatory responses in ACS. Lower baseline gene expression levels, but not infarct size or peak CRP, were associated with higher hsCRP at 30 days, an important marker of residual cardiovascular risk. Whether these expression profiles correlate with outcome needs further investigation.