Abstract of the day - Does combining polygenic risk scores with ESC and ACC/AHA risk models improve prevention prediction?

Polygenic risk scores (PRS) predict the risk of developing atherosclerotic CVD (ASCVD), but do they add value to clinical risk scores?

Today, Doctor Roxane de La Harpe (University Hospital Centre Vaudois [CHUV] - Lausanne, Switzerland) presents a two-part study that firstly validated four different PRS in a Swiss population-based cohort, then assessed the benefit of combining the most predictive PRS with two clinical risk scores.

In the first part of the study, data from 4,215 individuals (53% women; mean age 54 years), including 357 patients with ASCVD, were analysed. The researchers found that the PRS developed by Inouye et al¹ – comprising >1.6 million variants – demonstrated the best predictive capacity, with an area under the receiver operating characteristic curve (AUC ROC) of 0.77. The AUC ROC was 0.76 for the PRS developed by Khera et al² and by Mars et al³ and 0.765 for the PRS developed by Elliott et al.⁴

The PRS by Inouye et al was used in the second part of the study, which analysed data from 3,390 individuals (mean follow­-up of 12.0 years), with 188 incident ASCVD cases. Individuals in the top 20% of the PRS distribution were found to have the same magnitude of association with ASCVD as current smokers or patients with diabetes.

Combining the PRS by Inouye et al with the Systematic COronary Risk Evaluation 2 (SCORE2) led to a reclassification of 5.3% (95% CI −1.9 to 12.4) of subjects overall; however, this rose to 17.1% (95% CI 4.7 to 29.5) for subjects in the intermediate-risk category. Similar findings were observed when the PRS was combined with the Pooled Cohort Equations – the net reclassification index was 19.2% (95% CI 4.8 to 22.4) in the intermediate-risk category.

When subgroups of the intermediate-risk category were considered, adding the PRS to SCORE2 appeared to increase reclassification more commonly in women than in men (27.8% versus 14.3%) and in individuals aged <55 years than ≥55 years (28.6% versus 11.1%).

The authors conclude that, based on their analysis in a Swiss population-based cohort, the PRS allows good prediction of CV risk, which could help identify high-risk individuals at an early age to enable the introduction of preventive measures before the development of irreparable lesions. Introducing PRS into clinical practice may also help refine CV prevention for subgroups of patients in whom prevention strategies are uncertain.