High hemoglobin A1c associated with increased adverse limb events in peripheral arterial disease patients undergoing revascularization

Objective: Diabetes and peripheral arterial disease (PAD) are independently associated with increased risk of amputation. However, the effect of poor glycemic control on adverse limb events has not been studied. We examined the effects of poor glycemic control (high hemoglobin A(1c) level) on the risk of amputation and modified major adverse limb events (mMALEs) after lower extremity revascularization. Methods: Patients undergoing PAD revascularization who had hemoglobin A(1c) (HbA(1c)) levels available within 6 months were identified in the Veterans Affairs database of 2003 to 2014 (N = 26,799). The diagnosis of preoperative diabetes mellitus (PreopDM) was defined using diabetes diagnosis codes and evidence of treatment. Amputation and mMALE risk was compared for HbA(1c) levels using Kaplan-Meier analysis. Cox proportional hazards models were created to assess the effect of high HbA(1c) levels on amputation and mMALE (adjusted for age, gender, race, socioeconomic status, comorbidities, cholesterol levels, creatinine concentration, suprainguinal or infrainguinal procedure, open or endovascular procedure, severity of PAD, year of cohort entry, and medications) for all patients and stratified by PreopDM. Results: High HbA(1c) levels were present in 33.2% of the cohort, whereas 59.9% had PreopDM. Amputations occurred in 4359 (16.3%) patients, and 10,580 (39.5%) had mMALE. Kaplan-Meier curves showed the worst outcomes in patient with PreopDM and high HbA(1c) levels. In the Cox model, incremental HbA(1c) levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8% were associated with 26% (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.15-1.39), 53% (HR, 1.53; 95% CI, 1.37-1.7), and 105% (HR, 2.05; 95% CI, 1.87-2.26) higher risk of amputation, respectively. Similarly, the risk of mMALE also increased by 5% (HR, 1.05; 95% CI, 0.99-1.11), 21% (HR, 1.21; 95% CI, 1.13-1.29), and 33% (HR, 1.33, 95% CI, 1.25-1.42) with worsening HbA(1c) levels of 6.1% to 7.0%, 7.1% to 8.0%, and >8%, respectively (vs HbA(1c) <= 6.0%). In stratified analysis by established PreopDM, the relative risk of amputation or mMALE was much higher with poor glycemic control (HbA(1c) >7.0%) in patients without PreopDM. Conclusions: PAD patients with worse perioperative glycemic control have a significantly higher risk of amputation and mMALE. Incremental increases in HbA(1c) levels are associated with higher hazards of adverse limb outcomes independent of PreopDM status. Poor glycemic control (HbA(1c) > 7.0%) in patients without a PreopDM diagnosis carries twice the relative risk of amputation and mMALE than in those with good glycemic control. These results suggest that screening of diabetic status and better management of glycemic control could be a target for improvement of perioperative and long-term outcomes in PAD patients.