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



A 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.



We 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).



Elevated 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.
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass; Department of Surgery, George Washington University Medical Center, Washington, D.C.
Sara L
SL
Zettervall
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.
Peter A
PA
Soden
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.
Klaas H J
KH
Ultee
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.
Crystal
C
Seldon
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.
Jinhee
J
Oh
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.
Kevin
K
McGann
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass.
Marc L
ML
Schermerhorn
Division of Vascular and Endovascular Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Mass. Electronic address: rjguzman@bidmc.harvard.edu.
Raul J
RJ
Guzman
D000368:Aged; D000369:Aged, 80 and over; D000671:Amputation, Surgical; D015415:Biomarkers / Q000097:blood; D001900:Boston; D016638:Critical Illness; D018572:Disease-Free Survival; D057510:Endovascular Procedures / Q000009:adverse effects / Q000401:mortality; D005260:Female; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D007511:Ischemia / Q000150:complications / Q000000981:diagnostic imaging / Q000401:mortality / Q000628:therapy*; D053208:Kaplan-Meier Estimate; D023821:Limb Salvage; D008297:Male; D008875:Middle Aged; D010710:Phosphates / Q000097:blood*; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D015854:Up-Regulation; D014656:Vascular Surgical Procedures / Q000009:adverse effects / Q000401:mortality
D015415:Biomarkers; D010710:Phosphates
Clin J Am Soc Nephrol. 2009 Jun;4(6):1136-9
19423568
Source Code Biol Med. 2008 Dec 16;3:17
19087314
Arterioscler Thromb Vasc Biol. 1996 Aug;16(8):978-83
8696962
Adv Chronic Kidney Dis. 2011 Mar;18(2):113-9
21406296
Am J Kidney Dis. 2003 Oct;42(4 Suppl 3):S1-201
14520607
Circulation. 2005 Oct 25;112(17):2627-33
16246962
Clin J Am Soc Nephrol. 2009 Mar;4(3):609-15
19211667
J Am Coll Cardiol. 1998 Jan;31(1):126-33
9426030
J Am Soc Nephrol. 2001 Oct;12(10):2131-8
11562412
Circulation. 2012 Aug 28;126(9):1127-38
22927475
Eur J Vasc Endovasc Surg. 2012 Jan;43(1):55-61
22001150
Crit Care. 2010;14(4):R147
20682049
J Vasc Surg. 2015 Jan;61(1):162-9
25073577
J Am Soc Nephrol. 2005 Feb;16(2):520-8
15615819
Nat Clin Pract Nephrol. 2006 Mar;2(3):136-48
16932412
J Vasc Surg. 2014 Jan;59(1):220-34.e1-2
24126108
J Am Coll Cardiol. 2008 May 20;51(20):1967-74
18482666
Arch Intern Med. 2007 May 14;167(9):879-85
17502528
Nephrol Dial Transplant. 2003 Sep;18(9):1731-40
12937218
J Vasc Surg. 2000 Jan;31(1 Pt 2):S1-S296
10666287
Am J Kidney Dis. 1998 Apr;31(4):607-17
9531176
Clin J Am Soc Nephrol. 2011 Feb;6(2):440-6
21292848
Br J Clin Pharmacol. 2014 Jan;77(1):39-54
23506202
Kidney Int. 2009 May;75(9):890-7
19145240
J Vasc Surg. 2009 Aug;50(2):299-304, 304.e1-4
19631864
Cochrane Database Syst Rev. 2011 Feb 16;(2):CD006023
21328279
Stroke. 2003 Oct;34(10 ):2367-72
12958327