Multidisciplinary evaluation of Polygenic Risk Score and Digital Health in Cardiovascular Prevention

Background

Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality, requiring continuing efforts in prevention. Polygenic risk scores (PRS) and digital health technologies (DHTs) may improve risk stratification and patient engagement, but evidence supporting their adoption in health systems remains limited. The project INNOPREV (PNRR-MAD-2022-12375795), funded by the Italian Ministry of Health, evaluated the efficacy, cost-effectiveness, and implementation feasibility of PRS and DHTs for primary CVD prevention in the Italian NHS.

Methods

A multicentre randomised controlled trial compared standard of care, PRS, DHT, and PRS+DHT in adults aged 40–69 years with medium-high cardiovascular risk (SCORE2 2.5–10%) in three Italian centres. SCORE2 trajectories informed a 10-year decision-tree cost-utility model relied on national costs and utilities. Implementation feasibility was explored through two scoping reviews and a Delphi panel for identifying barriers and facilitators and by administering questionnaire to trial participants for evaluating risk perception, technology acceptance, and PRS knowledge.

Results

1,019 participants were enrolled. No improvement in SCORE2 was observed in any intervention arm. From the economic viewpoints, all strategies were dominated by the standard of care. Scoping reviews and the Delphi panel identified regulatory, economic, infrastructural, and cybersecurity barriers for DHTs, alongside limited genomic literacy and trust barriers for PRS. Questionnaires revealed low perceived CVD risk, positive attitudes towards prevention and DHTs, and low PRS literacy with socioeconomic gradients.

Conclusions

PRS and DHTs did not improve cardiovascular risk trajectories nor demonstrate cost-effectiveness compared with standard of care. New evidence needs to be generated to better disentangle their potential role in CVD prevention also in consideration of equity-relevant literacy gaps and implementation barriers.

Key messages

• In a multicentre RCT, neither PRS nor DHTs improved cardiovascular risk trajectories or demonstrated cost-effectiveness versus standard care in high-risk Italian adults aged 40–69.

• Implementation barriers and equity-relevant literacy gaps in PRS and DHTs suggest further research is needed before large-scale adoption within the Italian NHS and similar health systems.