Implications of Modest Reductions in ABI Measurements for Risk of Major Adverse Limb Events Among 223,350 Veterans

Low resting ankle-brachial index (ABI) is a marker of poor cardiovascular outcomes. Whether modest decrements in ABI translate into higher risks of major adverse limb events (MALE) is unclear because prior studies are small or lack racial diversity and incident outcomes.

The purpose of this study was to assess the association between the full range of ABI measures and incident MALE in a large, diverse cohort.

Using data from the Veterans Aging Cohort Study-National Cohort, we analyzed a prospective, longitudinal cohort of veterans free of prevalent peripheral artery disease (PAD). Participants were enrolled beginning January 1, 2000, and followed through September 30, 2021. The exposure was resting ABI (continuous and categorical), and the primary outcome was MALE, defined as amputation or revascularization using administrative codes. Secondary outcomes included total amputation, major amputation, or revascularization. Cox proportional hazards models assessed the overall association between ABI and MALE and stratified by sex or race. Models were adjusted for demographics and PAD risk factors.

The analysis included 223,350 people, including 8,207 women and 42,173 Black individuals. There were 28,191 MALE. Risk of MALE followed an inverse j-shaped distribution across the continuous ABI spectrum. Compared with a categorical ABI of 1.11 to 1.20, borderline ABI values (range 0.91-1.00) were associated with an increased risk of MALE in the total population as well as sex/race subgroups: total population: HR: 1.53 (95% CI: 1.43-1.64); men: HR: 1.53 (95% CI: 1.43-1.64); women: HR: 2.00 (95% CI: 1.18-3.38); White individuals: HR: 1.60 (95% CI: 1.48-1.73); Black individuals: HR: 1.39 (95% CI: 1.18-1.64). Similar associations were demonstrated for major amputation (HR: 1.34 [95% CI: 1.17-1.54]), total amputation (HR: 1.22 [95% CI: 1.12-1.33]), and revascularization (HR: 2.05 [95% CI: 1.87-2.26]) in the full cohort. ABI was a stronger marker of MALE risk than established risk factors, including current smoking and prevalent cardiovascular disease.

In a large, diverse cohort free of prior PAD, ABI values across the full spectrum were associated with an increased risk of incident MALE, suggesting that treating the ABI as a binary measure does not adequately capture clinical risk. Further studies are needed to better understand why MALE occurs despite near-normal ABI values.