Uncovering Hidden Risk: Polygenic Scores for Personalized Prevention

Abstract Polygenic Risk Scores (PRS) are attracting growing interest as a tool to enhance precision in primary prevention strategies, particularly for complex, multifactorial diseases such as cardiovascular diseases (CVDs). By aggregating numerous genetic variants, PRS allows early identification of individuals at elevated genetic risk and enables tailored interventions, potentially preventing or delaying disease onset. In CVDs, where much of the burden is linked to modifiable risk factors, PRS adds value beyond traditional models based on age, blood pressure, cholesterol, or lifestyle, offering a more personalized layer of information to guide clinical and behavioral decisions. This may help identify high-risk individuals often missed by conventional screening. Evidence on the effectiveness and real-world feasibility of PRS-based prevention is still emerging. This presentation will include ongoing studies such as the the INNOPREV clinical trial (INNOvative personalized cardiovascular disease PREVention in high-risk adults), which evaluates the clinical efficacy of integrating PRS and digital health technologies in primary cardiovascular prevention. In parallel, the FItPreV pilot randomized trial (Feasibility of Innovative Approaches for Personalized Cardiovascular Prevention) is assessing the practical implementation of PRS-based strategies and wearable health devices within the Italian National Health System. Together, these trials illustrate how PRS can be operationalized in real-world settings and highlight the importance of addressing key implementation challenges, such as acceptability, demand, and integration into routine care. Beyond cardiovascular health, PRS is also being explored in oncology. Brief references will be made to emerging studies in ovarian, pancreatic, and breast cancer, illustrating the broader potential of PRS in supporting personalized prevention across disease areas.