sRAGE, inflammation, and risk of atrial fibrillation: results from the Atherosclerosis Risk in Communities (ARIC) Study

Objective: Advanced glycation end products (AGEs) may cause inflammation by binding to their cellular receptors (RAGE). Soluble RAGE (sRAGE) acts as a decoy receptor for AGEs and may prevent inflammation. Chronic low-grade inflammation is a risk factor for cardiovascular disease, including atrial fibrillation (AF). Methods: We studied 1,068 participants in a subsample of the Atherosclerosis Risk in Communities (ARIC) Study who had baseline measurements of sRAGE (mean age 56, 60% female, 21% Black). Inflammation was assessed using measurements of high sensitivity C-reactive protein (hsCRP), fibrinogen, gamma-glutamyl transferase (GGT) and white blood cell (WBC) count. AF events were identified using ECG data, hospitalization discharge codes, and linkage to the National Death Index. Results: Compared to the highest quartile (>1272.4 pg/mL), the lowest quartile of sRAGE (<714 pg/mL) was associated with higher baseline levels of inflammation (hsCRP >= 3 mg/L: OR = 2.21 [95% CI 1.41-3.49], fibrinogen >= 400 mg/dL: OR = 4.31 [95% CI 1.50-12.41], GGT >= 36 U/L in women and >= 61 U/L in men: OR = 5.22 [95% CI 2.66-10.22], WBC >6.2 x 10(9)/L: OR = 238 [95% CI 1.52-3.72]). sRAGE was not prospectively associated with 6-year change in inflammatory markers (hsCRP or GGT). There was no significant association of sRAGE and risk of AF (HR 1.49 [95% CI: 0.80-2.78] for the 1st vs. 4th quartile of sRAGE). Conclusions: sRAGE was strongly inversely associated with markers of inflammation at baseline, but not prospectively. sRAGE was not significantly associated with incident AR This supports a role for sRAGE in attenuating current inflammation, but it remains unclear whether sRAGE plays a role in the development of AF. (C) 2015 Elsevier Inc. All rights reserved.