Polygenic Risk Scores and Digital Devices for Primary Cardiovascular Prevention: INNOPREV Trial

Background The INNOPREV (INNOvative approaches for personalized cardiovascular PREVention) trial is a multicentre RCT evaluating prevention strategies integrating Polygenic Risk Scores (PRS) and digital health technologies for primary cardiovascular disease (CVD) prevention. Methods Participants were enrolled across three Italian centres (Rome, Catania and Palermo) and randomized into four groups: usual care, digital, genetic (PRS-based) and combined intervention (digital and genetic). Follow-up occurred over 12 months (baseline T0; 6-month T1; 12-month T2). Recruitment is finished while follow-up is still on-going. Study endpoints concern lifestyle changes, assessed through Life’s Essential 8 (LE8) questionnaire, reflecting cardiovascular health (CVH) profiles, SCORE2 and lipid profile changes. Analyses were conducted using linear mixed effects models (LMM) to evaluate the marginal effect of adding at least one intervention or both with respect to usual care. Results 1032 participants were enrolled, 813 (79%) completed T1, 687 participants (67%) completed T2, while 132 (13%) participants withdrew from the study. At T0, CVH was low, intermediate, and high in 10%, 83%, and 7% of participants; PRS risk was normal, intermediate, and high in 76%, 22%, and 2%, respectively. No significant association was observed between CVH categories and PRS risk. LE8 scores increased by + 2.3 points at T1 (p < 0.05) and +2.6 points at T2 (p < 0.05) compared to T0 among all participants. No significant differences emerged between intervention arms at either timepoint. SCORE2 showed no significant changes at T2. Total cholesterol remained unchanged across arms, while initiation of lipid-lowering therapy was associated with a significant reduction at T2 (−23.3 mg/dL; p < 0.001). Conclusions A modest but significant improvement in lifestyle was observed at 6 and 12 months among all participants, regardless of any intervention assignment. Funded by NextGenerationEU. CUP: C53C22001100007. Key messages • Genetic-digital strategies did not outperform usual care in this RCT, highlighting the need to optimize implementation to unlock the full potential of personalized CVD prevention. • Genetic predisposition and cardiovascular health profile are not correlated, supporting their combined use for a more complete risk assessment.