Genetics, coronary artery disease, and myocardial revascularization: will novel genetic risk scores bring new answers?

ABSTRACT

Both percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are options for revascularization in multi-vessel coronary artery disease (CAD). However, the best form of revascularization remains controversial. Results from clinical trials (FREEDOM, SYNTAX, NOBLE, EXCEL) have identified factors related to CAD severity such as diabetes and SYNTAX score as indicators that patients may have better outcomes with CABG compared to PCI. Nevertheless, the discovery of other predictors of optimal revascularization therapy is necessary to improve decision-making and personalize the treatment of multi-vessel CAD. Genome-wide association studies have identified numerous previously unknown DNA variants that increase predisposition for CAD. Recently, a composite polygenic risk score has been developed to better assess the relative contribution of multiple SNPs and quantify overall genetic risk for CAD. High polygenic risk score is associated with increased coronary events and greater benefit from statin therapy in large observational studies. This effect is independent from traditional cardiovascular risk factors. At the same time, randomized clinical trials have shown that CAD severity is a determinant of optimal revascularization treatment. It remains unknown whether polygenic risk score is robustly associated with increased CAD severity at presentation, and whether this score can be used to identify patients who will show greater benefit from revascularization with CABG or with PCI.