Assessing the Correlation Between Inter-Leg Ankle-Brachial Index Asymmetry and Peripheral Artery Disease Outcomes

Peripheral artery disease (PAD) remains underdiagnosed and suboptimally treated, with limited disease awareness and underutilization of available diagnostic strategies representing important contributing factors. The ankle-brachial index (ABI) is the gold-standard screening test for PAD and has been shown to correlate with limb outcomes. However, the current interpretation of ABIs does not account for clinically significant differences between legs, which may reflect asymmetric disease burden and have an impact on limb outcomes. The association between inter-leg ABI asymmetry and PAD outcomes is unclear and requires further study. Thus, we assessed the prognostic importance of a clinically significant difference in left and right ABI values (≥0.15) on limb outcomes in patients with PAD.

A total of 3313 patients with PAD who received outpatient vascular care at a single institution were retrospectively analyzed. At baseline, ABIs were measured in a certified vascular laboratory by dividing the higher of the dorsalis pedis or posterior tibial artery systolic pressures in each leg by the higher brachial systolic pressure. Inter-leg ABI asymmetry was defined by an absolute difference between left and right ABI values ≥ 0.15, which has been shown to be clinically significant. The primary outcome was major adverse limb event (MALE) over 2 years of follow-up. MALE was defined as the need for vascular intervention (either open or endovascular lower extremity revascularization) or major lower extremity amputation above the ankle. The association between inter-leg ABI asymmetry and 2-year MALE was evaluated using univariable and multivariable logistic regression models adjusted for age, sex, body mass index (BMI), and ABI-defined hemodynamic severity.

The mean participant age was 58.4 years (SD 12.9), 966 (29.2%) participants were female, and the mean BMI was 28.8 kg/m² (SD 5.7). There were 666 (20.1%) patients who had inter-leg ABI asymmetry. The mean inter-leg ABI difference was 0.38 (SD 0.29) in the inter-leg ABI asymmetry group and 0.04 (SD 0.02) in the no inter-leg ABI asymmetry group (p < 0.001). Patients with inter-leg ABI asymmetry were more likely to have moderate PAD (36.0% vs. 6.5%, p < 0.001) and severe PAD (6.2% vs. 0.7%, p < 0.001), and less likely to have mild PAD (57.8% vs. 92.8%, p < 0.001), compared to patients with no inter-leg ABI asymmetry. Over the median follow-up period of 2 years, 304 (9.2%) participants experienced MALE. The 2-year MALE rate was significantly higher in patients with inter-leg ABI asymmetry compared to those without (26.0% vs. 4.9%, p < 0.001). Similarly, patients with inter-leg ABI asymmetry had a higher rate of the need for revascularization (21.5% vs. 4.1%, p < 0.001) and major amputation (10.2% vs. 1.8%, p < 0.001). Multivariable logistic regression controlling for age, sex, BMI, and ABI-defined hemodynamic severity showed that inter-leg ABI asymmetry was independently associated with 2-year MALE (adjusted OR 3.70, 95% CI 2.80-4.91, p < 0.001).

In this study, over 20% of patients with PAD had clinically significant inter-leg ABI asymmetry, which was independently associated with a nearly four times higher odds of 2-year MALE, including the need for revascularization and major amputation. Our results suggest that inter-leg ABI asymmetry may represent a readily available prognostic marker of adverse limb outcomes in patients with PAD. Further external validation and prospective studies are needed to determine whether incorporating inter-leg ABI asymmetry into clinical assessment improves risk stratification or clinical outcomes.