Personalised HeartCare Trial: Preliminary Results on Genomic Literacy and PRS Psychological Impact

Background

Primary prevention of cardiovascular diseases (CVD) represents a priority given the growing disease burden. Polygenic risk scores (PRS) may have the potential of improving behaviors especially among individuals at high PRS-risk. The Personalised HeartCare (PHC) trial aims to assess the effect of PRS disclosure on lifestyle behaviors.

Methods

PHC is a single-arm monocentric trial conducted at Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, enrolling healthy ≥40 years adults with low 10-year CVD risk (ClinicalTrials.gov NCT06888466). Primary endpoint is change in CardioVascular Health (CVH) assessed by Life’s Essential 8 (LE8, 0-100) at 12 months. At baseline, PRS testing was performed and genomic literacy was assessed using Vanderbilt PRS-Knowledge Scale (PRS‑KS:0 to 7, with 0-2=low). One month after PRS disclosure(T1), psychological responses were measured with FACToR questionnaire (negativity, uncertainty, privacy 0-12; positivity 0-16).Recruitment is finalized while follow-up is still ongoing.

Results

434 participants were enrolled (60% female, mean age 56±7.2). Mean LE8 score was 65.5±10.6, with 83% classified as intermediate CVH. Among 432 genotyped participants, 56 (13%) had high PRS and 376 (87%) non-high. Genomic literacy, assessed in 406 participants, showed mean PRS‑KS score of 4.6 ± 1.5, with no differences between PRS groups. At T1, mean FACToR scores across all participants were: negativity 1.3±1.8, uncertainty 2.0±2.2, privacy 1.0±1.5, positivity 9.6±3.4. High PRS recipients showed significantly greater negativity and uncertainty, and lower positivity compared with non-high PRS (all p < 0.001).

Conclusions

Baseline findings from the PHC trial describe a population with intermediate CVH and good Genomic literacy. Preliminary results show that high PRS disclosure is associated with emotional distress and uncertainty. Ongoing follow-up will clarify whether PRS disclosure influences lifestyle change.

Thanks to DARE-CUP:B53C22006320001

Key messages

• High PRS disclosure for CVD is associated with significantly greater negativity and uncertainty in a pilot study in Italy, highlighting the need for tailored communication strategies.

• Most participants had intermediate cardiovascular health at baseline, suggesting room for lifestyle improvement through PRS-based personalized prevention.