Should We Use Genetic Scores in the Determination of Treatment Strategies to Control Dyslipidemias?

Abstract

Purpose of Review: Conventional risk stratification algorithms that rely on age, clustered phenotypic traits, and biomarkers under-recognize the sizeable subgroup of individuals at high polygenic risk for atherosclerotic cardiovascular disease (ASCVD). This review provides perspective on the promising role of genetic testing in cardiovascular prevention through the lens of lipid metabolism. Recent Findings: Recent advances in cardiovascular genetics identified a number of common and rare variants affecting ASCVD risk. This genetic susceptibility can be assessed by polygenic risk scores (PRS) which quantify risk conferred by the cumulative impact of common variants. This results in a normally distributed spectrum of risk for coronary artery disease that is present at birth and amplifies the effects of modifiable risk factors including lipids. Summary: Polygenic risk is a significant determinant of ASCVD risk that is below the discrimination level of conventional guideline-based clinical frameworks. Genetic risk scores thus hold potential to refine phenotypic screening in cardiovascular prevention, identify subsets of the population that might derive particular benefit from early lifestyle and pharmaceutical interventions, and guide treatment eligibility. This might pave the way to personalized prevention aimed at reducing the unacceptable global burden of ASCVD.