Polygenic Risk Score: Clinically Useful Tool for Prediction of Cardiovascular Disease and Benefit from Lipid-Lowering Therapy?

Improvement in risk prediction of atherosclerotic cardiovascular disease (ASCVD) using information on the genetic predisposition at an individual level might offer new possibilities for the successful management of such complex trait. Latest developments in genetic research with the conduction of genome-wide association studies have facilitated a broader utility of polygenic risk score (PRS) as a potent risk prognosticator, being strongly associated with future cardiovascular events. Although its discriminative ability beyond traditional risk factors is still a matter of controversy, PRS possesses at least comparable risk information to that provided by traditional risk tools. More importantly, increased genetic risk for ASCVD might be discovered at younger ages, much longer before conventional risk factors become manifest, thereby providing a potent instrument for aggressive primordial and primary prevention in those at high risk. Furthermore, there is strong evidence that inherited risk may be successfully modulated by a healthy lifestyle or medication use (e.g., statins or PCSK-9 inhibitors). Here, we provide a short overview of the current research related to the possible application of PRS in clinical routine and critically discuss existing pitfalls, which still limit a widespread utility of PRS outside a research setting.