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

Mahmoud Al Rifai, Andrea L C Schneider, Alvaro Alonso, Nisa Maruthur, Christina M. Parrinello, Brad C. Astor, Ron C. Hoogeveen, Elsayed Z. Soliman, Lin Y. Chen, Christie M. Ballantyne, Marc K Halushka, Elizabeth Selvin

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)180-185
Number of pages6
JournalJournal of Diabetes and its Complications
Volume29
Issue number2
DOIs
StatePublished - Mar 1 2015

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Atrial Fibrillation
Atherosclerosis
Inflammation
Transferases
C-Reactive Protein
Advanced Glycosylation End Products
Leukocyte Count
Electrocardiography
Hospitalization
Cardiovascular Diseases

Keywords

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

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

SRAGE, inflammation, and risk of atrial fibrillation : Results from the Atherosclerosis Risk in Communities (ARIC) Study. / Al Rifai, Mahmoud; Schneider, Andrea L C; Alonso, Alvaro; Maruthur, Nisa; Parrinello, Christina M.; Astor, Brad C.; Hoogeveen, Ron C.; Soliman, Elsayed Z.; Chen, Lin Y.; Ballantyne, Christie M.; Halushka, Marc K; Selvin, Elizabeth.

In: Journal of Diabetes and its Complications, Vol. 29, No. 2, 01.03.2015, p. 180-185.

Research output: Contribution to journalArticle

Al Rifai, Mahmoud ; Schneider, Andrea L C ; Alonso, Alvaro ; Maruthur, Nisa ; Parrinello, Christina M. ; Astor, Brad C. ; Hoogeveen, Ron C. ; Soliman, Elsayed Z. ; Chen, Lin Y. ; Ballantyne, Christie M. ; Halushka, Marc K ; Selvin, Elizabeth. / SRAGE, inflammation, and risk of atrial fibrillation : Results from the Atherosclerosis Risk in Communities (ARIC) Study. In: Journal of Diabetes and its Complications. 2015 ; Vol. 29, No. 2. pp. 180-185.
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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",
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T1 - SRAGE, inflammation, and risk of atrial fibrillation

T2 - Results from the Atherosclerosis Risk in Communities (ARIC) Study

AU - Al Rifai, Mahmoud

AU - Schneider, Andrea L C

AU - Alonso, Alvaro

AU - Maruthur, Nisa

AU - Parrinello, Christina M.

AU - Astor, Brad C.

AU - Hoogeveen, Ron C.

AU - Soliman, Elsayed Z.

AU - Chen, Lin Y.

AU - Ballantyne, Christie M.

AU - Halushka, Marc K

AU - Selvin, Elizabeth

PY - 2015/3/1

Y1 - 2015/3/1

N2 - 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.

AB - 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.

KW - Advanced glycation end products

KW - Atrial fibrillation

KW - C-reactive protein

KW - Epidemiology

KW - Inflammation

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