Skin autofluorescence as a measure of advanced glycation end products deposition predicts 5-year amputation in patients with peripheral artery disease

Arterioscler Thromb Vasc Biol. 2015 Jun;35(6):1532-7. doi: 10.1161/ATVBAHA.115.305407. Epub 2015 Apr 16.


Objective: Patients with peripheral artery disease are at risk for critical limb ischemia and amputation. Accumulation of advanced glycation end products is increased and predictive for coronary and cerebrovascular events in several high cardiovascular risk groups. We hypothesized that accumulation of tissue advanced glycation end products, measured by skin autofluorescence (SAF), predicts amputation in patients with peripheral artery disease.

Approach and results: Between October 2007 and June 2008, 252 patients with peripheral artery disease were included at the outpatient clinic. During a 5-year follow-up, 22 (9%) had an amputation because of critical limb ischemia. Competing risks regression analysis showed a subproportional hazard ratio of 3.05 (95% confidence interval [CI], 1.87-4.96); P<0.0001 for amputation per unit incease of SAF. After correction for diabetes mellitus and Fontaine stage, subproportional hazard ratio was 2.72 (95% CI, 1.38-5.39); P=0.004. In patients with Fontaine stage I and II only (n=215), SAF was the only predictor for amputation, subproportional hazard ratio 4.05 (95% CI, 2.09-7.83); P<0.0001. Fontaine stage multiplied by SAF resulted in a significant increase of the area under the curve for prediction of amputation when compared with Fontaine stage only: area under the curve increased from 0.74 (95% CI, 0.63-0.86) to 0.83 (95% CI, 0.74-0.92); P=0.003.

Conclusions: Skin autofluorescence, as a measure of tissue advanced glycation end products deposition, predicts amputation in patients with peripheral artery disease during a 5-year follow-up, independent from the presence of diabetes mellitus and Fontaine stage. Even at lower Fontaine stage (I or II), SAF is a strong predictor of amputation. The multiplication of Fontaine stage by SAF results in a good prediction model of amputation.

Keywords: advanced glycation end products; peripheral artery disease.

MeSH terms

  • Aged
  • Amputation*
  • Diabetes Mellitus / blood
  • Diabetic Angiopathies / blood
  • Diabetic Angiopathies / surgery
  • Extremities / blood supply*
  • Female
  • Follow-Up Studies
  • Glycation End Products, Advanced / blood*
  • Humans
  • Ischemia / etiology
  • Ischemia / surgery
  • Male
  • Middle Aged
  • Optical Imaging*
  • Peripheral Arterial Disease / blood*
  • Peripheral Arterial Disease / complications
  • Peripheral Arterial Disease / surgery*
  • Prospective Studies
  • Risk Factors
  • Skin / blood supply*


  • Glycation End Products, Advanced