Polygenic Risk Score’s Predictive Value in CAD

A UK longitudinal cohort study suggested that the predictive ability of a polygenic risk score (PRS) for coronary artery disease (CAD) was greater in younger individuals and could be used to better identify patients with borderline and intermediate clinical risk who should initiate statin therapy. Polygenic risk for CAD was defined as low (bottom 20%), intermediate, and high (top 20%) using a CAD PRS including 241 genome-wide significant single-nucleotide variations (SNVs). A total of 330 201 patients (median age, 57 years; females 57%) were included from the UK Biobank. Over 10-year follow-up, 4454 individuals had a myocardial infarction (MI). The CAD PRS was significantly associated with the risk of MI in all age groups but had significantly stronger risk prediction at younger ages (age <50 years: hazard ratio [HR] per 1 SD of PRS, 1.72; age 50-60 years: HR, 1.46; age >60 years: HR, 1.42; P for interaction <.001). In patients younger than 50 years, those with high PRS had a 3- to 4-fold increased MI risk compared with those in the low PRS category. A significant interaction between CAD PRS and age was also replicated in an analysis in Biobank Japan. When CAD PRS testing was added to the clinical atherosclerotic cardiovascular disease risk score in individuals younger than 50 years, 591 of 4373 patients with borderline (5-<7.5%) risk were risk stratified into intermediate (7.5-<20%) risk, warranting initiation of statin therapy, and 3198 of 7477 patients with borderline or intermediate risk were stratified as low (<5%) risk, thus not warranting therapy. The findings suggest targeted CAD PRS testing may help guide preventive strategies such as statin initiation in younger adults with borderline to intermediate cardiovascular risk. Source: https://jamanetwork.com/