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J Diabetes Complications. 2015 Mar;29(2):180-5. doi: 10.1016/j.jdiacomp.2014.11.008. Epub 2014 Nov 25.

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

Author information

1
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research.
2
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research; Department of Medicine, Johns Hopkins University School of Medicine.
3
Division of Epidemiology and Community Health, School of Public Health, University of Minnesota.
4
Departments of Medicine and Population Health Sciences, University of Wisconsin School of Medicine and Public Health.
5
Department of Medicine, Section of Cardiovascular Research, Baylor College of Medicine and Houston Methodist DeBakey Heart and Vascular Center.
6
Epidemiological Cardiology Research Center (EPICARE), Department of Epidemiology and Prevention, and Department of Internal Medicine-Cardiology, Wake Forest School of Medicine.
7
Cardiovascular Division, Department of Medicine, University of Minnesota Medical School.
8
Department of Pathology, Johns Hopkins University School of Medicine.
9
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health and the Welch Center for Prevention, Epidemiology and Clinical Research; Department of Medicine, Johns Hopkins University School of Medicine. Electronic address: eselvin@jhu.edu.

Abstract

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.

KEYWORDS:

Advanced glycation end products; Atrial fibrillation; C-reactive protein; Epidemiology; Inflammation

PMID:
25499973
PMCID:
PMC4333077
DOI:
10.1016/j.jdiacomp.2014.11.008
[Indexed for MEDLINE]
Free PMC Article

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