Skin Autofluorescence as a Measure of Advanced Glycation End Products Deposition Is Elevated in Peripheral Artery Disease

Abstract

Evidence for an important role of advanced glycation end products (AGEs) in the development of atherosclerosis and cardiovascular disease beyond diabetes mellitus and renal disease is growing. Skin autofluorescence (SAF) is a validated noninvasive measure of tissue AGEs. We hypothesized that SAF is elevated in peripheral artery disease (PAD). A case-control study was performed in 492 patients with PAD and 164 controls, matched for age (mean 66 ± 10 years) and presence of diabetes mellitus. Cardiovascular risk factors and comorbidity (coronary artery disease, cerebrovascular disease, abdominal aortic aneurysm) were assessed. SAF was measured with the AGE Reader. SAF was higher in patients compared with controls: geometric mean 2.77 (95% confidence interval [CI], 2.71-2.83) versus 2.44 (95% CI, 2.35-2.53) arbitrary units, P=0.4×10(-8). In logistic regression, the adjusted odds ratio for the presence of PAD was 2.47 (95% CI, 1.66-3.69) per 1 unit increase of SAF. PAD patients with cardiovascular comorbidity had a higher SAF compared with those without: geometric mean 2.93 (95% CI, 2.85-3.02) versus 2.63 (95% CI, 2.55-2.71) arbitrary units, P=0.4×10(-6), also after correction for confounders. Regression analysis showed that age, smoking, diabetes mellitus, chronic kidney disease, and a history of cerebrovascular disease or abdominal aortic aneurysm were independently associated with SAF in the patients with PAD. Accumulation of tissue AGEs is increased in patients with PAD, independent of cardiovascular risk factors and comorbidity, although these conditions are associated with a further increase. These findings underscore the importance of AGEs in PAD, irrespective of the presence of diabetes mellitus and renal insufficiency.