Soluble receptor for advanced glycation end products is associated with in-stent restenosis in patients with type 2 diabetes with drug-eluting coronary stents

Background: The levels of soluble receptor for advanced glycation end products (sRAGE) may reflect the activity of the advanced glycation end products-RAGE axis, which has been proposed as a potential mechanism of vascular inflammation in patients with type 2 diabetes (T2D). However, the role of sRAGE in in-stent restenosis (ISR) is not yet known in patients with T2D with drug-eluting stent (DES) implantation. Methods and Results: We enrolled 35 patients with T2D with ISR (T2D-ISR) and 35 patients with age-matched T2D without ISR (T2D-control) at the time of follow-up coronary angiography after DES implantation. Plasma levels of glycosylated hemoglobin (HbA_1c), C-reactive protein (CRP), insulin-like growth factor-1 (IGF-1), and sRAGE were measured in blood samples obtained at the time of the index procedure. Baseline characteristics showed no difference between the groups. Plasma levels of sRAGE were significantly higher in the T2D-ISR group than in the T2D-control group (7.29±2.91 vs. 5.36±2.20 ng/ml, P=0.003), but levels of HbA1c (7.65±1.59% vs. 7.60±1.65%, P=0.89), CRP (8.15±13.82 vs. 5.59±7.68 mg/l, P=0.34), and IGF-1 (0.93±0.37 vs. 0.99±0.30 ng/ml, P=0.42) did not differ significantly between the two study groups. In multivariate logistic regression analysis, elevated plasma level of sRAGE (above the median) was a significant predictor of ISR [odds ratio (OR): 4.33, 95% confidence interval (CI): 1.38-13.59, P=0.01], followed by mean stent diameter less than 3.0 mm (OR: 3.35, CI: 0.98-11.46, P=0.05). Conclusion: Plasma level of sRAGE may be positively associated with ISR and RAGE-dependent inflammatory responses may contribute more to ISR development than IGF-1-dependent proliferative responses in patients with T2D with DES implantation.