Skin autofluorescence, 5-year mortality, and cardiovascular events in peripheral arterial disease: all that glitters is surely not gold.

T he hunt for predictive biomarkers in diseases of the cardio-, cerebro-, and peripheral vascular systems is an ongoing effort and one whose importance cannot be overstated. The identification of subjects most at risk for death or major adverse cardiovascular events may provide a means to stratify diagnostic and therapeutic interventions based on validated predictive algorithms. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, de Vos et al 1 report that in 252 eligible subjects with documented peripheral arterial disease (PAD) studied at a single center, the measurement of skin autofluorescence (SAF) was independently associated with all-cause mortality and fatal or nonfatal major adverse cardiovascular events after a follow-up period of 5 years. Importantly, the authors excluded subjects with hemodialysis, kidney transplantation, recent myocardial infarction, or recent stroke and report that even after adjustment for cardiovascular risk factors and the use of lipid-lowering drugs, increased SAF remained associated with increased risk for death and major adverse cardiovascular events. A previous report from these authors compared subjects with PAD versus control PAD-free subjects and showed that increased SAF was significantly associated with PAD in a manner independent of traditional cardiovascular risk factors, although such risk factors were associated with further increases in SAF. The AGE reader was used as a biological marker of advanced glycation endproducts (AGEs) in the skin and is usually tested in the forearm. AGEs are the products of nonen-zymatic glycation and oxidation of proteins and lipids. AGEs are increased not only in diabetes mellitus but also in natural aging, oxidative stress, and inflammatory conditions, and in renal failure. 3 AGEs form on lysine and arginine residues and are heterogeneous; some AGEs are associated with crosslink-ing (such as pentosidine), and some AGEs do not fluoresce, such as the carboxy methyl lysine AGEs. Based on defined fluorescent wavelengths of excitation and emission, SAF is reflective of skin levels of AGEs. Although few studies to date have compared directly the measures of SAF with the skin levels of AGEs, Meerwaldt et al 4 measured specific skin AGEs in diabetic and nondiabetic subjects in the same arm as that used to measure the SAF. They reported that SAF correlated with measured levels of collagen-linked fluorescence, pento-sidine, carboxy methyl lysine, and carboxy ethyl lysine AGEs. In a second study, this same group examined specific AGEs in subjects with end-stage renal disease and reported that SAF correlated with measured levels of collagen-linked …