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 Materials and MethodsMaterials and Methods are available in the online-only Data Supplement.In short, we performed a single-center prospective cohort study of 252 patients with established PAD. Deposition of tissue AGEs was noninvasively measured by skin autofluorescence with the AGE Reader. Five-year follow-up data were analyzed. The end point was defined as amputation caused by critical limb ischemia. Amputationfree survival was analyzed by Kaplan-Meier plot with log-rank test, according to the optimal cutoff value of SAF (generated by the receiver operating characteristics curve) and to subdivision into 4 groups, based on Fontaine stage (I-II versus III-IV) and SAF below or above the cutoff value. Subproportional hazard ratios (sHR) for amputation risk with 95% confidence interval (CI) were calculated by competing risks regression analysis, with death as the competing risk. Additional log-rank and competing risks regression analyses were performed in patients with Fontaine stage I and II. Receiver operating characteristics analysis was performed, with Fontaine stage and Fontaine stage multiplied by SAF. The study was approved by the local institutional review board, and all participating patients gave informed consent. Results Patients Characteristics and SAFA total of 267 patients were willing to participate. Fifteen patients were excluded because of hemodialysis (n=4), kidney transplantation (n=8), a recent myocardial infarction (n=1), and a recent stroke (n=2). Baseline characteristics of the 252 patients with PAD (mean age, 66±11 years) are shown in Table 1. In 38 (15%) patients, ankle-brachial index was not measured because PAD had already been established by imaging of the lower arteries (n=12) or a revascularization procedure (n=26) was performed directly. Sixty-six (26%) patients were classified as Fontaine stage I, 149 (59%) as Fontaine stage II, 21 (8%) as Fontaine stage III, and 16 (7%) patients as Fontaine stage IV. Mean anklebrachial index was 0.57±0.15. At baseline, 152 (60%) patients had an intervention for their PAD, including 21 (8%) amputations because of critical limb ischemia. Of the patients with current Fontaine stage I or II, 127 (59%) patients had a history of intervention whereas 88 (41%) had not. Of the patients with current Fontaine stage III and IV, 25 (68%) had a history intervention whereas 12 (32%) had not. Seventy-four (29%) patients had diabetes mellitus. Mean SAF was 2.76±0.66 arbitary units. Five-Year Follow-UpMedian follow-up duration was 5.3 (interquartile range, 4.7-5.7) years. Of the 252 patients who ...

IntroductionDiabetes mellitus is a well-defined risk factor for peripheral artery disease (PAD), but protects against the development and growth of abdominal aortic aneurysm (AAA). Diabetes mellitus is associated with arterial stiffening and peripheral arterial media sclerosis. Advanced glycation end-products (AGEs) are increased in diabetes mellitus and cardiovascular disease. AGEs are known to form cross-links between proteins and are associated with arterial stiffness. Whether AGEs contribute to the protective effects of diabetes mellitus in AAA is unknown. Therefore, the ARTERY (Advanced glycation end-pRoducts in patients with peripheral arTery disEase and abdominal aoRtic aneurYsm) study is designed to evaluate the role of AGEs in the diverging effects of diabetes mellitus on AAA and PAD.Methods and analysisThis cross-sectional multicentre study will compare the amount, type and location of AGEs in the arterial wall in a total of 120 patients with AAA or PAD with and without diabetes mellitus (n=30 per subgroup). Also, local and systemic vascular parameters, including pulse wave velocity, will be measured to evaluate the association between arterial stiffness and AGEs. Finally, AGEs will be measured in serum, urine, and assessed in skin with skin autofluorescence using the AGE Reader.Ethics and disseminationThis study is approved by the Medical Ethics committees of University Medical Center Groningen, Martini Hospital and Medisch Spectrum Twente, the Netherlands. Study results will be disseminated through peer-reviewed journals and scientific events.Trial registration numbertrialregister.nl NTR 5363.

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