An integrated approach to coronary heart disease diagnosis and clinical management

Abstract

The major issue in coronary heart disease (CHD) diagnosis and management is that symptoms onset in an advanced state of disease. Despite the availability of several clinical risk scores, the prediction of cardiovascular events is lacking, and many patients at risk are not well stratified according to the canonical risk factors alone. Therefore, adequate risk assessment remains the most challenging issue. Recently, the integration of imaging data with biochemical markers in a radiogenomic framework has been proposed in many fields of medicine as well as in cardiology. Multimodal imaging and advanced processing techniques can provide both direct (e.g., remodeling index, calcium score, total plaque volume, plaque burden) and indirect (e.g., myocardial perfusion index, coronary flow reserve) imaging features of CHD. Furthermore, the identification of novel non-invasive biochemical markers, mainly focused on plasma and/or serum samples, has increased the specificity of findings, reflecting several pathophysiological pathways of atherosclerosis, the principal actor in CHD. In this context, a multifaced approach, derived from the strengths of all these modalities, appears promising for finer risk stratification and treatment strategies, facilitating the decision-making and clinical management of patients. This review underlines the role of different imaging modalities in the quantification of coronary atherosclerosis and describes novel blood-based markers that could improve diagnosis and have a better predictive value in CHD.

Keywords: Atherosclerosis; biomarkers; coronary heart disease; imaging.

Figure 1

Integrated diagnostic approach in coronary heart disease. The figure shows the imaging modalities for direct assessment of coronaries and the diversity of circulating biomarkers that could be associated with the diagnosis, outcome prediction and risk assessment in coronary heart disease (CHD). The left panel represents X-ray angiography (XRA), coronary computed tomography angiography (CTCA) and intravascular ultrasound (IVUS) in coronary imaging and respective parameters. For XRA: luminal narrowing, blood flow and fractional flow reserve (FFR); for CTCA: coronary artery calcium (CAC), remodeling index (RI), plaque features, plaque burden and FFR CT; for IVUS: lumen, RI, vessel structure, external elastic membrane (EEM) and plaque features. The right panel depicts markers that can be analyzed in serum/plasma or whole blood and reflect coronary artery alterations: cellular: peripheral blood mononuclear cells (PBMCs), neutrophils, lymphocytes, endothelial progenitors cells (EPCs), CD31+ cells; biochemical markers: inflammatory pathways, cytokines, adhesion molecules, enzymes and metabolites; epigenetic markers: DNA methylation levels and differential expression of circulating non-coding RNAs (ncRNAs); and transcriptional markers: genes coding for pro-and antioxidant molecules, cell motility proteins, signaling receptors, transcription factors, inflammatory and metabolic mediators.