INNOPREV trial: Polygenic Risk Scores and digital tools in personalized cardiovascular prevention

Abstract Background The INNOvative approaches for personalized cardiovascular PREVention (INNOPREV) is a multicenter randomized controlled trial (RCT) designed to evaluate prevention strategies that integrate Polygenic Risk Scores (PRS) and digital health technologies for the primary prevention of cardiovascular diseases (CVDs). Methods We enrolled 1020 participants across three Italian centers (Rome, Catania, and Palermo) and randomized into four groups: usual care, digital intervention, genetic intervention (PRS-based), combined intervention (digital tools and PRS). Participants are followed for 12 months with assessments at baseline (T0), 6 months (T1), 12 months (T2). Primary endpoints include lifestyle changes, assessed via the Life's Essential 8 (LE8) questionnaire, reflecting cardiovascular health (CVH) levels. Enrollment was finished in March 2025 and participants are undergoing T1 follow-up. We conducted preliminary analysis on changes in LE8 scores and body mass index (BMI) using paired t-tests. Results In total 560 participants completed both T0 and T1 assessments. At baseline, 74% had a low, 16% intermediate and 10% high PRS. CVH levels were low in 10%, intermediate in 83%, and high in 7% of participants. From T0 to T1, the mean LE8 score increased from 64.1(SD 11.1) to 65.5(SD 10.6) in the overall population (p = 0.0002). Notably, subgroup analyses by intervention arm showed mean LE8 increased from 63.6(SD 11.5) to 65.4(SD 10.9) in the usual care group (p = 0.03) and 63(SD 10.8) to 64.9(SD 10.4) in combined intervention (p = 0.01). Similarly, the mean BMI decreased from 25.7(SD 4.1) to 25.6(SD 3.9) kg/m² in the overall population (p = 0.02), with comparable trends observed across intervention groups. Conclusions Preliminary results show encouraging trends toward improved lifestyle behaviors and BMI across all intervention arms, suggesting a potential benefit of integrating PRS and digital tools in CVDs prevention. Thanks to NextGenerationEU. CUP: C53C22001100007. Key messages • The integration of PRS and digital tools shows promising potential in improving cardiovascular health behaviors. • Public health intervention at a population level may benefit of innovative approaches, including genetic and digital, for more effective cardiovascular disease prevention strategies.