Whole-Blood Transcriptional Profiles Enable Early Prediction of the Presence of Coronary Atherosclerosis and High-Risk Plaque Features at Coronary CT Angiography

Abstract

Existing tools to estimate cardiovascular (CV) risk have sub-optimal predictive capacities. In this setting, non-invasive imaging techniques and omics biomarkers could improve risk-prediction models for CV events. This study aimed to identify gene expression patterns in whole blood that could differentiate patients with severe coronary atherosclerosis from subjects with a complete absence of detectable coronary artery disease and to assess associations of gene expression patterns with plaque features in coronary CT angiography (CCTA). Patients undergoing CCTA for suspected coronary artery disease (CAD) were enrolled. Coronary stenosis was quantified and CCTA plaque features were assessed. The whole-blood transcriptome was analyzed with RNA sequencing. We detected highly significant differences in the circulating transcriptome between patients with high-degree coronary stenosis (≥70%) in the CCTA and subjects with an absence of coronary plaque. Notably, regression analysis revealed expression signatures associated with the Leaman score, the segment involved score, the segment stenosis score, and plaque volume with density <150 HU at CCTA. This pilot study shows that patients with significant coronary stenosis are characterized by whole-blood transcriptome profiles that may discriminate them from patients without CAD. Furthermore, our results suggest that whole-blood transcriptional profiles may predict plaque characteristics.

Identification of novel prognostic targets in coronary artery disease and related complications using bioinformatics and next generation sequencing data analysis

“…NGS dataset was downloaded from the GEO database. GSE202625 [30] dataset includes 76 CAD samples and 62 normal control samples. The GSE202625 dataset based on GPL23934 Ion Torrent S5 (Homo sapiens).…”

“…In the current investigation, we downloaded NGS dataset, namely, GSE202625 [30] from the NCBI Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/) [31], including NGS data. We identified DEGs using the DESeq2 package in R bioconductor.…”

The Mediating Role of IDL Particles in the Relationship between Primary Hypertension and Cardiovascular Diseases: Insights from Mendelian Randomization and Multi-Omics Analysis

“…Speci cally, for primary hypertension, we utilized the GSE234085 dataset 18 , comprising peripheral blood lymphocyte expression data from 6 healthy controls and 6 patients with primary hypertension. For coronary artery disease (CAD), we utilized two datasets: GSE202625 19 , consisting of whole blood expression data from 25 healthy controls and 27 CAD patients, and GSE242046 20 , comprising feces and blood expression data from 20 healthy controls and 30 CAD patients. For peripheral arterial disease (PA), we utilized the GSE100927 dataset 21 , which includes carotid artery expression data from 12 healthy controls and 29 PA patients.…”

Computed tomography and nuclear medicine for the assessment of coronary inflammation: clinical applications and perspectives

“…In patients with stable angina, there is evidence that circulating levels of high-sensitivity C-reactive protein (hs-CRP) or interleukin-6 (IL-6) predict functionally significant CAD and high-risk coronary anatomy at CCTA 22,51 . Moreover, whole-blood transcriptional profiles, including genes involved in the inflammatory response, have been shown to discriminate patients with significant coronary stenoses and predict adverse plaque characteristics 52 . Circulating levels of IL-6 are associated with the risk of cardiovascular death, myocardial infarction (MI) and hospitalization for heart failure in patients with stable CAD under optimal medical treatment and serum hs-CRP levels appear to be higher in patients with acute MI than in those with stable CAD 53,54 .…”

“…22,51 Moreover, whole-blood transcriptional profiles, including genes involved in the inflammatory response, have been shown to discriminate patients with significant coronary stenoses and predict adverse plaque characteristics. 52 Circulating levels of IL-6 are associated with the risk of cardiovascular death, myocardial infarction (MI) and hospitalization for heart failure in patients with stable CAD under optimal medical treatment and serum hs-CRP levels appear to be higher in patients with acute MI than in those with stable CAD. 53,54 Although these are excellent biomarkers of systemic inflammation, they are not specific for coronary inflammation and provide little information on local vascular biological processes.…”