A higher PAD polygenic risk score was associated with a 30% increased risk of major adverse limb events per 1-SD increase (HR 1.30; 95% CI 1.19-1.42; P<.0001) beyond clinical risk factors.
Cohort (n=68,816)
Yes
Does a PAD polygenic risk score predict prevalent PAD and incident major adverse limb events independent of clinical risk factors in patients with cardiometabolic disease?
A PAD polygenic risk score independently predicts prevalent PAD and incident major adverse limb events in patients with cardiometabolic disease, though its incremental discriminative value over clinical risk factors is modest.
Effect estimate: HR 1.30 (95% CI 1.19-1.42)
p-value: p=< .0001
BACKGROUND AND AIMS: Large-scale genome-wide association studies have identified common genetic variants that predict the risk of peripheral artery disease (PAD). This study assessed whether a polygenic risk score (PRS) is associated with PAD and the incidence of major adverse limb events (MALE) independent of clinical risk factors in patients with established cardiometabolic disease. METHODS: A genetic analysis was performed, pooling individual patient-level data from six TIMI trials. The association of a recently validated PAD PRS with prevalent PAD and the incidence of MALE (acute limb ischaemia, chronic limb-threatening ischaemia, major amputation, or peripheral revascularization) was assessed. RESULTS: A total of 68 816 patients were included in this analysis, with a median follow-up of 2.6 years. Of these, 5986 (8.7%) had known PAD at baseline. After adjusting for clinical risk factors, a higher PAD PRS was independently associated with a 15% greater odds of prevalent PAD (adjusted odds ratio per 1-SD: 1.15 95% confidence interval 1.12-1.18, P < .0001), a magnitude of risk as strong as established clinical risk factors. A total of 577 patients experienced MALE during follow-up. A higher PAD PRS was associated with a 30% increased risk of MALE (adjusted hazard ratio per 1-SD: 1.30 1.19-1.42, P < .0001). Adding the PAD PRS to clinical risk factors resulted in a statistically significant but modest improvement in discrimination (area under the curve went from 0.651 to 0.662 P < .0001). CONCLUSIONS: 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.
Said et al. (Wed,) conducted a cohort in Established cardiometabolic disease (n=68,816). Polygenic risk score (PRS) for peripheral artery disease vs. Clinical risk factors alone was evaluated on Incidence of major adverse limb events (MALE) (HR 1.30, 95% CI 1.19-1.42, p=< .0001). A higher PAD polygenic risk score was associated with a 30% increased risk of major adverse limb events per 1-SD increase (HR 1.30; 95% CI 1.19-1.42; P<.0001) beyond clinical risk factors.