Circulating epigenetic biomarker profiling for early diagnosis of coronary artery disease

Background/Objectives: Cardiovascular diseases (CVD) are the major cause of death worldwide. In coronary artery disease (CAD), one example of CVDs, typically atherosclerotic plaques are narrowing coronary arteries (stenosis), resulting in an impairment of blood flow which subsequently decreases the heart’s blood and oxygen supply. Untreated, this leads to damaged heart muscle tissue and cardiac dysfunction and can cause acute events like myocardial infarction. Coronary angiography (CA) is the state-of-the art procedure to diagnose stenosis, achieved by injecting contrast agent into coronary arteries and performing X-ray imaging. Aim of this study was to develop novel, minimally invasive epigenetic biomarkers for stenosis prediction to reduce unnecessary invasive CAs as right now 40% of patients undergoing CA do not display stenosis in the end.
Methods: We recruited 146 patients who had undergone coronary angiography, 77 displayed significant stenosis whereas the other 69 did not have stenosis. We collected whole blood, plasma and cell-free saliva from all patients and performed biomarker discovery studies analyzing around 30-40 patients per experimental group and omics layer. These discovery analyses included genome-wide DNA methylation profiling from whole blood via Illumina EPIC microarrays as well as small RNA sequencing from plasma and cell-free saliva derived extracellular vesicles.
Results: We identified a variety of statistically significant differences in DNA-methylation and small RNA profiles between stenosis and non-stenosis patients and will outline the details of the outcome of these multi-omics biomarker discovery studies. We will further present preliminary biomarker verification analysis performed on the total set of 146 patients.