Elevated serum phosphate levels are associated with decreased amputation-free survival after interventions for critical limb ischemia

Abstract

ObjectiveElevated serum phosphate levels have been associated with increased risks of cardiovascular events and death in several patient populations. The effects of serum phosphate on outcomes in patients with critical limb ischemia (CLI) have not been evaluated. In this study, we assessed the effect of abnormal phosphate levels on mortality and major limb events after surgical intervention for CLI. MethodsA retrospective review was undertaken to identify all patients at a single institution who underwent a first-time open or endovascular intervention for CLI between 2005 and 2014. Patients without recorded postoperative phosphate levels were excluded. Postoperative phosphate levels ≤30 days of the initial operation were recorded, and the mean was calculated. Patients were stratified according to mean phosphate levels (low: <2.5 mg/dL, normal: 2.5-4.5 mg/dL, and high: >4.5 mg/dL). Patient demographics, comorbidities, and operative details were compared in univariate analysis. Multivariable regression and Cox proportional hazard modeling were used to account for patient demographics and comorbid conditions. ResultsWe identified 941 patients, including 42 (5%) with low phosphate, 768 (82%) with normal phosphate, and 131 (14%) with high phosphate. Patients with elevated phosphate were younger and had higher rates of congestive heart failure, diabetes, and dialysis dependence. Bypass was more common among patients with normal phosphate compared with high or low phosphate levels. There was no difference in the Wound, ischemia, and Foot infection (WiFi) classification or TransAtlantic Inter-Society Consensus classification among the cohorts. There were significant differences in 1-year mortality (low: 19%, normal: 17%, high: 33%; P < .01) and 3-year mortality (low: 38%, normal: 34%, high: 56%; P < .01) between phosphate cohorts. Major amputation (low: 12%, normal: 12%, high: 15%) and restenosis (low: 21%, normal: 24%, high: 28%) tended toward worse outcomes among patients with elevated phosphate levels but did not reach statistical significance. After adjustment for baseline characteristics, mortality was higher (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.3-2.2) and amputation-free survival was lower (HR, 1.5; 95% CI, 1.2-1.9) among patients with elevated compared with normal phosphate levels. A subgroup analysis was then performed to assess dialysis and nondialysis patients separately. Patients with elevated serum phosphate levels maintained a significantly higher risk of mortality in each group (dialysis: HR, 1.8; 95% CI, 1.2-2.6; nondialysis: HR, 1.5; 95% CI, 1.04-2.10). ConclusionsElevated phosphate levels are associated with increased mortality and decreased amputation-free survival after interventions for CLI. Future studies evaluating the effects of phosphate reduction in patients with CLI are warranted.