Abstract

Advanced glycation end-products (AGEs) activate specific receptors (RAGE) promoting inflammation and oxidative stress. The lungs, with high RAGE expression, may be particularly susceptible to AGE-related injury. This study assessed whether baseline skin AGE levels, measured by skin autofluorescence (SAF), predict pulmonary function decline in middle-aged adults with cardiovascular risk factors. This ancillary analysis of the ILERVAS cohort included adults aged 45-70 years with cardiovascular risk factors but without diabetes or chronic kidney disease. Baseline data included demographics, lifestyle, and fasting blood tests. SAF was measured using AGE Reader (TM), and spirometry performed at baseline and after a median follow-up of 4 years. Associations between baseline SAF and annual declines in FEV1, FVC, and FEV1/FVC were analysed using adjusted models and generalized additive models, stratified by smoking status. Among 658 participants (median age 56 years, 48% female), median baseline SAF was 1.90 AU [1.60; 2.20]. Baseline lung function was preserved, with median FEV1, FVC and FEV1/FVC of 2795 mL [2270; 3,341], 3,525 mL [2870; 4300], and 78.6% [74.4; 82.8]. Annual declines were - 81.9 mL [- 120.6; - 43.3] for FEV1, - 99.6 mL [- 159.3; - 37.9] for FVC, and - 0.04% [- 0.85; 0.70] for FEV1/FVC. No significant associations were found between SAF and spirometry changes. Results were consistent across smoking subgroups. Baseline skin AGE levels did not predict pulmonary function decline over four years in middle-aged adults with cardiovascular risk factors. While SAF reflects cumulative AGE exposure, it has limited prognostic value for lung function in this population.