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 × 109/L: OR = 2.38 [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 AF. This supports a role for sRAGE in attenuating current inflammation, but it remains unclear whether sRAGE plays a role in the development of AF.
Bibliographical noteFunding Information:
This research was supported by National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Grant R01 DK076770 and a grant from the American Heart Association to Dr. Selvin. Dr. Schneider and C.M. Parrinello were supported by NIH/NHLBI T32 HL007024. Dr. Alonso was supported by grant 09SDG2280087 from the American Heart Association. The ARIC Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C).
© 2015 Elsevier Inc. All rights reserved.
- Advanced glycation end products
- Atrial fibrillation
- C-reactive protein