P5510High plasma sRAGE is associated with slower carotid intima media thickness progression and lower risk for first-time coronary events and mortality

Abstract

Abstract Background/Introduction The receptor for advanced glycation end products (RAGE) and the extracellular matrix metalloproteinase inducer (EMMPRIN) are immune receptors for pro-inflammatory mediators. These receptors can also be found in a soluble form in the circulation. Soluble RAGE (sRAGE) has shown atheroprotective properties in animal studies, by acting as a decoy receptor for its ligands. Whether sEMMPRIN has similar roles is unknown. Purpose The purpose of our study was to investigate the associations between sRAGE and sEMMPRIN in plasma and the progression of vascular disease, incident coronary events and mortality in the general population. Methods We measured baseline sRAGE and sEMMPRIN in 4612 cardiovascular disease-free middle aged individuals from a population-based cohort. Measurements of intima media thickness (IMT) in the common carotid artery were performed at inclusion and after a median of 16.5 years. Incident major adverse coronary events (MACE) and mortality were recorded during a follow-up period of 21 years. Results sRAGE was negatively correlated with the progression of carotid IMT, independently of traditional cardiovascular risk factors, kidney function and hsCRP. Additionally, sRAGE was associated with decreased risk for MACE [HR=0.91 (0.83–0.99); p=0.031] and total mortality [HR=0.92 (0.87–0.99); p=0.017] in multivariate Cox regression analyses. We found no correlations between EMMPRIN, IMT progression or prognosis. Conclusion We show that individuals with high levels of circulating sRAGE have a slower rate of carotid artery disease progression, and a lower risk for coronary events and mortality. These findings support further research into the potential atheroprotective properties of sRAGE. Acknowledgement/Funding This study was supported by grants from the Swedish Research Council, Marianne and Marcus Wallenberg Foundation, Swedish Heart and Lung Foundation