Research article
A polygenic risk score for peripheral artery disease and major adverse limb events
- Genetic analysis of pooled individual patient-level data from six TIMI trials
Authors' conclusion
In a broad spectrum of patients with cardiometabolic disease, the PAD PRS is associated with an increased risk of PAD and the incidence of MALE beyond clinical risk factors; however, the improvement in discrimination was statistically significant but clinically modest.
Study context
- Population
- Patients with established cardiometabolic disease in six TIMI trials
- Participants
- 68,816 patients · 6 TIMI trials
- Comparison
- Higher vs lower peripheral artery disease (PAD) polygenic risk score
- Outcome
- Prevalent PAD and incident MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation or peripheral revascularization)
- Follow-up
- Median 2.6 years
Main finding
As reported in the abstract
PAD PRS per 1-SDEstimateP value
prevalent PAD
adjusted OR 1.15(95% CI 1.12–1.18)
P < 0.0001incident MALE
adjusted HR 1.30(CI 1.19–1.42)
P < 0.0001Per 1-SD, as printed
- Known PAD at baseline
- 5986 (8.7%)
- Patients with major adverse limb events (MALE) during follow-up
- 577
Further findings
Discrimination (AUC) on adding PAD polygenic risk score (PRS) to clinical risk factors
- AUC clinical risk factors
- 0.651
- AUC with PAD PRS
- 0.662
- P < .0001
- statistically significant but modest improvement
Original publication
A polygenic risk score for peripheral artery disease and major adverse limb events. Eur Heart J. Published 28 November 2025. doi:10.1093/eurheartj/ehaf891
Summarised from the published abstract; every number is checked against it