Major amputations and the compound risk of peripheral arterial disease following minor amputation

Introduction Foot ulcers and minor amputations represent notable complications of peripheral arterial disease (PAD), and this risk is further heightened by concomitant diabetes. Comprehensive assessment should account for comorbid conditions, vascular status, and prior surgical interventions to inform optimal treatment strategies. The present study evaluates the impact of PAD and revascularization on the probability of major amputation following an initial minor amputation. Methods We conducted a retrospective cohort study of patients undergoing minor lower extremity amputation at a single tertiary referral center between 2017 and 2023. Limbs were identified using five Current Procedural Terminology (CPT) codes and followed for up to one year after the index procedure. Data collected included demographics, comorbidities, wound characteristics, Wound, Ischemia, and foot Infection (WIfI) stage when available, and attempted revascularization categorized as endovascular, open, or diagnostic-only.The primary exposure was peripheral arterial disease (PAD). Primary outcomes were major amputation at 30 days, 6 months, and 1 year, and 1-year all-cause mortality. Kaplan-Meier analysis estimated 1-year amputation-free survival with comparisons by log-rank test. Time to major amputation was evaluated using Cox proportional hazards models. Multivariable logistic regression and limb-level generalized estimating equation (GEE) models accounting for within-patient clustering were performed as secondary analyses . Results A total of 973 limbs from 861 patients who underwent minor lower extremity amputation were included (mean age 60.2 ± 13.3 years, 32.8% female) with PAD present in 46.0% of limbs. Progression to major amputation occurred in 11.5% of limbs during follow-up, and 1-year all-cause mortality was 10.8% among limbs with known survival status.Limbs with PAD had higher crude major amputation rates compared with non-PAD limbs (16.3% vs. 7.3%, p < 0.001). Kaplan–Meier analysis demonstrated shorter amputation-free survival among limbs with PAD (324 ± 5 vs. 348 ± 3 days, log-rank p < 0.001).In multivariable Cox analysis, PAD was independently associated with increased hazard of major amputation (HR 2.03, 95% CI 1.31–3.16, p=0.002), along with dialysis-dependent end-stage renal disease (HR 2.71, 95% CI 1.64–4.47, p < 0.001), thrombophilia (HR 2.48, 95% CI 1.21–5.07, p=0.013), and Black race (HR 1.68, 95% CI 1.09–2.59, p=0.019). Atrial fibrillation was independently associated with a reduced hazard of major amputation (HR 0.37, 95% CI 0.16–0.89, p=0.026).Revascularization was attempted in 280 limbs (61.8% endovascular, 26.8% open, 11.4% diagnostic-only). Major amputation rates did not differ by revascularization strategy (p = 0.199). The limb-level generalized estimating equation (GEE) model confirmed these findings, with PAD (p = 0.004), dialysis-dependent end-stage renal disease (p < 0.001), and thrombophilia (p = 0.016) remaining significant. Other covariates, including age, coronary artery disease, hypertension, smoking status, and revascularization were not associated with major amputation. Conclusion Peripheral arterial disease significantly increases the risk of major amputation following a minor foot amputation. Dialysis dependence, thrombophilia, and cerebrovascular disease further contribute to this heightened risk. Notably, the specific revascularization method performed did not affect outcomes. These findings emphasize the paramount importance of assessing PAD status and comorbidity profile during patient counseling.