Abstract
Introduction: Ankle-brachial index (ABI) ≤ 0.9 is used to define lower-extremity peripheral artery disease (PAD). However, the association between ABI and severe ischemic leg outcomes in the general population has not been investigated. Hypothesis: Lower ABI is independently associated with risk of severe ischemic leg outcomes. Methods: We studied 13,742 ARIC participants (median age 54 [SD 5.75] years, 45% males) without intermittent claudication or a history of revascularization for PAD at baseline (1987-89). We quantified the association of ABI with risk of severe ischemic leg outcomes using Cox regression. ABI was modeled as a restricted cubic spline allowing for potentially non-linear associations. Severe ischemic leg outcomes were ascertained through ICD codes and included critical limb ischemia (CLI) (defined as PAD with rest pain or tissue loss) and ischemic leg amputation (amputations with PAD diagnosis). Results: Over a median of 28 years of follow-up, there were 221 and 129 events of CLI and ischemic leg amputation, respectively. Lower ABI was linearly associated with both CLI and ischemic leg amputation (Figure). With ABI 1.25 as the reference, adjusted hazard ratios of CLI were 2.48 (95% CI 1.15-5.36) at ABI 0.7, 1.97 (1.30-2.99) at ABI 0.9, and 1.73 (1.18-2.54) at ABI 1.0. The corresponding hazard ratios of ischemic leg amputation were 3.57 (1.44-8.81), 2.63 (1.54-4.48), and 2.23 (1.34-3.70), respectively. The association was largely consistent in demographic and clinical subgroups, although the results were less evident in younger and female participants compared to their counterparts. Conclusions: In middle-aged adults without clinical PAD, lower ABI was independently and linearly associated with higher risk of severe ischemic leg outcomes. Our results support the value of ABI as an indicator for leg vascular condition and also indicate that ABI 0.9-1.1 should not be considered normal for ischemic leg prognosis.
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