Reevaluating the mortality impact of lower extremity amputations in diabetes-related foot disease

Diabetes-related foot disease-associated lower extremity amputation (LEA) is associated with substantial mortality. This raises a more relevant question: "Can reducing lower extremity amputations decrease mortality associated with diabetic foot ulcers (DFU)?." The findings from the study by Chen et al. highlighted cardiovascular disease accounts for nearly half (46.6%; 95% CI 33.5%-59.7%) of the total deaths in individuals with DFD-related LEA and an adjusted pooled hazard ratio of post-amputation mortality rates of 2.415 (95% CI 1.323-4.408), suggesting amputations as an independent factor for mortality. The findings are substantiated from observational studies carried out in individuals with post-traumatic LEA. Hrubec et al. reported that veterans with proximal amputation had a higher risk for all-cause (RR, 1.29; 90% CI 1.18-1.41; p < 0.001) and cardiovascular (CV) mortality (RR, 1.44; 90% CI 1.26-1.64; p < 0.001). A part of the increased CV mortality is attributed to the hemodynamic changes that occur after an LEA, leading to an increase in shear stress from increased peripheral flow resistance, causing an increase in the magnitude and number of reflective pulse waves. Considering this, we hypothesize that the post-LEA hemodynamic changes in individuals with diabetes can potentially accelerate the occurrence of CV events by causing an atherosclerotic plaque rupture. While definitive evidence regarding the causal relationship between amputation and mortality remains elusive, the findings presented provide some support for considering LEA as an independent risk factor for mortality and to consider it as an independent cardiovascular risk factor.