Abstract Body (Do not enter title and authors here): Background: Intensive blood pressure (BP) control reduces the risk of cardiovascular (CV) events, yet we recently reported a U-shaped association between BP and limb events in peripheral artery disease (PAD). Whether the involvement of pedal arteries or small vessel disease (SVD), which further compromises lower extremity perfusion, modifies this association is unknown.
Methods: We analyzed the Peripheral Artery Long-term Survival (PEARLS) cohort, a longitudinal registry of ~100,000 US Veterans with incident PAD between 2015-2020. We defined SVD as a low toe-brachial index (TBI≤0.7) with a normal ankle brachial index (ABI >0.9) in any limb, suggesting involvement of distal pedal arteries. Cox regression models, with death as a competing risk, were used to evaluate the association between BP as a time-varying exposure and risk of CV (myocardial infarction, stroke) and limb (chronic limb-threatening ischemia, major amputation) events, adjusted for patient demographics, comorbidities, risk factors, and severity of PAD. Analyses were performed separately in patients with and without SVD, and interaction testing was also performed.
Results: Among 92,909 patients (mean age 70.5 ± 9.3 years; 97% men; 18.5% Black), 35,496 [38.2%] had SVD. Compared to those without, those with SVD only were older, less likely to be Black or current smokers, but had a higher burden of diabetes and chronic kidney disease (Table 1). Baseline BP differences between groups were small. Over a median follow-up of 3.9 years, SVD was associated with a lower crude incidence rate (per-100 patient years) of CV events (4.1 vs. 5.0) and limb events (4.4 vs. 5.6), compared to patients without SVD. In both strata, there was a graded positive association between increasing systolic BP risk of CV events (P for interaction=0.54; Figure 1). Conversely, systolic BP displayed a U-shaped association with limb events, with increased hazard in both low and high BP. This pattern was more pronounced in patients with SVD (P for interaction <0.01; Figure 1). Findings for diastolic blood pressure were similar (Figure 2).
Conclusion: In PAD, higher BP is associated with a higher risk of CV events, whereas the association with limb events was U-shaped. The increased hazard of limb events at both low and high BP is accentuated in patients with SVD. These findings highlight the need for individualized BP targets in PAD, particularly when SVD is present.