Multi-omics Circulating Biomarker Profiling for Early Diagnosis of Coronary Artery Disease

Multi-omics Circulating Biomarker Profiling for Early Diagnosis of Coronary Artery Disease

Abstract
Cardiovascular diseases (CVD) are the major cause of death worldwide and comprise several conditions affecting the heart and blood vessel system. Coronary artery disease (CAD), one example of CVDs, involves impairment of blood flow through the coronary arteries, most commonly by atherosclerotic plaques, which cause the narrowing of coronary arteries (also termed stenosis) and subsequently decrease the heart’s blood and oxygen supply. If left untreated, this oxygen shortage leads to damaged heart muscle tissue and cardiac dysfunction and can cause acute events such as a myocardial infarction.
Coronary angiography (CA) is the state-of-the art diagnostic procedure to visualize and diagnose stenosis, which is achieved by injecting contrast agent into coronary arteries via a catheter and performing X-ray imaging. Aim of this study was to develop novel, minimally invasive multi-omics biomarkers for stenosis prediction and thereby not only circumvent the given radiation exposure and invasiveness of CA but most importantly also reduce unnecessary CAs as right now 40% of patients undergoing CA do not display stenosis in the end.
We recruited 146 patients who had undergone coronary angiography and of which 77 were found to display significant stenosis (defined as > 50% lumen narrowing in at least one coronary artery) 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 (1) genome-wide DNA methylation profiling from whole blood via Illumina EPIC microarrays, (2) proteome-wide antibody profiling from plasma on in-house produced high density protein microarrays and (3) small RNA sequencing from plasma and cell-free saliva derived extracellular vesicles. We identified a variety of statistically significant differences in DNA-methylation-, small RNA and autoantibody 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.