Excess risk of cardiovascular disease and mortality after amputation in type 2 diabetes: a nationwide population study from the Swedish National Diabetes Register

Abstract Background Individuals with diabetes are prone to peripheral angiopathy and neuropathy, predisposing them to diabetic foot ulcers and, ultimately, lower-extremity amputation. The long-term cardiovascular impact of amputation in persons with type 2 diabetes remains insufficiently characterised. The aim of this study was to examine the extent to which lower-extremity amputation in individuals with type 2 diabetes is associated with an increased risk of cardiovascular disease and mortality compared to those with type 2 diabetes without amputation. Methods This was an observational, population-based retrospective cohort study with data from the Swedish National Diabetes Register linked to the National Patient Register and the Cause of Death Register. All individuals with type 2 diabetes who underwent a major or minor lower-extremity amputation between 2006 and 2019 were identified and matched to four controls with type 2 diabetes but without previous amputation on age, sex, and calendar time. Adjusted hazard ratios (aHRs) for cardiovascular events and mortality were estimated using cause-specific Cox proportional hazards regression, accounting for demographic and clinical risk factors. Results A total of 3,485 individuals with type 2 diabetes who had undergone amputation and 13,940 matched controls without previous amputation were included. Individuals undergoing amputation had a markedly increased risk of cardiovascular disease and mortality, with aHRs (95% CI) of 2.46 (2.31–2.61) for all-cause mortality, 2.43 (2.18–2.71) for cardiovascular mortality, 2.13 (1.92–2.36) for heart failure, 1.79 (1.55–2.08) for myocardial infarction, and 1.52 (1.31–1.76) for stroke. The hazard of all-cause mortality was more than threefold higher in the first year after amputation compared with matched controls and remained about 50% higher after five years. Conclusions Lower-extremity amputation in individuals with type 2 diabetes is associated with a substantially increased risk of cardiovascular disease and mortality, independent of pre-existing cardiovascular disease and established risk factors. This underlines the need for intensive cardiovascular risk management both before and after amputation to improve long-term outcomes.