Journal of NeuroEngineering and Rehabilitation

and 55 secondary to trauma or cancer. Mean age at ampu- tation was 75.7 ± 11.3 years for those with dysvascular dis- ease and 32.5 ± 20.8 years for those with TFA due to trauma or cancer ( p < 0.001). Men with dysvascular TFA were significantly younger at time of amputation than fe- males with dysvascular TFA ( p = 0.020, Table 1 ) . Those with dysvascular amputations had a significantly higher mortality rate at 1 and 5 years compared to those with TFA second- ary to trauma or cancer ( p < 0.001, Table 1 ) . Patients with a dysvascular TFA were more likely to have MACE compared to patients with amputations due to trauma or cancer, with the exception of coronary stent placement (Table 2 ) . Both the patients with a TFA due to dysvascular etiology and those due to either trauma or cancer had greater rates of myocardial infarctions when compared to their respective matched non-TFA cohorts. Overall, however, patients with TFA were no more likely to experience a MACE than their respective controls. Dysvascular TFA, N = 107 The early and later risk of mortality appeared to change around 2.5 years following an dysvascular TFA as observed in the initial Kaplan-Meir curves (Fig. 1 ) , therefore a time dependent variable was added to account for this change and satisfy the proportional hazard assumption. Having a dysvascular TFA was associated with an approximately four-fold increase in experiencing a cardiac event both prior to and after 2.5 years of undergoing an amputation (Hazard Ratio (HR) 3.78, 95% CI: 3.07 – 4.49; HR 4.17, 95% CI: 3.46 – 4.86). There was also an increased risk for non-cardiac mortality both prior to and after 2.5 years (HR 6.27, 95% CI: 6.11 – 6.58; HR 3.03, 95% CI: 2.60 – 3.46) (Fig. 1 ) . TFA due to trauma or cancer, N = 55 The early and later risk of mortality appeared to change around 10 years following an trauma or cancer related TFA as observed in the initial Kaplan-Meir curves (Fig. 2 ) , therefore a time dependent variable was added to account for this change and satisfy the proportional hazard assumption. Those with a TFA had no significant increase in experiencing a cardiac event within 10 years or beyond 10 years relative to the controls (HR 1.30, 95% CI: 0.30 – 5.85; HR 1.60, 95% CI: 0.67 – 3.80). Adjusted non-cardiac mortality risks did not appear to differ from the controls (HR 1.94, 95% CI: 0.54 – 6.91; HR 1.45, 95%CI: 0.72 – 2.93). Individuals with a TFA do not differ in risk of MACE or death compared to control subjects. TFA (Dysvascular and trauma/Cancer) with prosthesis, N = 70 Those receiving a prosthesis had almost a 60% reduction in risk of death (HR 0.40, 95% CI: 0.26 – 0.64). There was no difference in risk of experiencing a major cardiac event for those with or without a prosthesis (HR 1.20, 95% CI: 0.55 – 2.62) (Fig. 3 ) . The only covariates associated with an increased risk of MACE were age at time of amputation (HR 1.02, 95% CI: 1.01 – 1.03) and a higher Charlson Comorbidity index (HR 1.25, 95% CI: 1.17 – 1.33). Discussion This study determined the longitudinal risk of major cardio- vascular events (MACE) in patients with an transfemoral amputation. Unlike previous studies, which only evaluated cardiovascular events throughout the perioperative time period or up to 5 years post amputation [ 9 , 10 , 23 ] , this study uniquely calculated the risk as a function of time over a 30 year time span in a well characterized population-based observational study. This unique, population-based study suggests that the high risk of initial mortality stemming from an amputation event may preclude many amputees from progression of cardiovascular disease. Mortality rate among individuals with dysvascular TFA in our study was 28% at 1 year and 45% at 5 years, which is lower than previously re- ported ranges of 43 – 54% mortality at 1 year and 40 – 90% at 5 years [ 11 , 24 , 25 ] . Those with dysvascular amputations had a higher all-cause mortality rate than those with TFA secondary to trauma or cancer, which is also consistent with the literature. [ 5 , 23 , 25 – 27 ] Etiology of the amputation is also an important factor, as MACE were more likely among patients with a dysvascular TFA. Dysvascular disease progression and need for amputation is a significant risk factor for MACE, and studies show that level of amputation is also important. Mohammedi et al. followed 11,140 patients with diabetes over a median time period of 9.9 years and found that compared to those with- out peripheral artery disease, those with lower extremity ul- ceration and or amputation were at a significantly higher risk of cardiovascular death, myocardial infarction, and all-cause mortality (HR 1.91, 1.50, and 1.39 respectively). [ 28 ] They did not perform separate risk analyses for Table 1 Demographic information Amputation Etiology Total Men (number (%)) Mean Age at Amputation Years (SD) Mortality Rate (%) p value Men Women 1 year 5 year Dysvascular 107 55 (51.4%) 73.27 (10.7) 78.33 (11.4) 28% 45% 0.020 Trauma/Cancer 55 39 (70.9%) 31.57 (19.3) 34.57 (24.6) 2% 2% 0.631 All 162 94 (58.0%) 55.97 (25.4) 68.04 (24.2) 19% 30% 0.003 Mundell et al. Journal of NeuroEngineering and Rehabilitation 2018, 15 (Suppl 1):58 Page 5 of 72