Circulating soluble receptor for advanced glycation end product identifies patients with bicuspid aortic valve and associated aortopathies

Arterioscler Thromb Vasc Biol. 2014 Oct;34(10):2349-57. doi: 10.1161/ATVBAHA.114.303784. Epub 2014 Aug 14.

Abstract

Objective: A total of 30% to 50% of patients with bicuspid aortic valve (BAV) require surgery for aortic valve replacement (AVR), ascending aortic replacement (AA), or both. To prevent adverse aortic events, they are risk stratified using imperfect criteria based on imaging modalities. As a result, a significant number of dissections occur outside of the parameters suggested by the guidelines. Advanced glycation end products (AGEs) are associated with valve and vascular remodeling and trigger the release of a soluble receptor (soluble receptor for advanced glycation end product [sRAGE]). This study aims to characterize sRAGE as a diagnostic and risk-stratification tool for patients with BAV referred for surgery.

Approach and results: sRAGE was measured in 135 patients (BAV, n=74; tricuspid aortic valve, n=61) meeting inclusion criteria from 338 enrolled patients undergoing AVR and AA. Univariate and multivariate analyses were performed. sRAGE level was significantly associated with the presence of BAV, independent of age, sex, and common risk factors for vascular disease (P<0.001). Within the BAV cohort, patients referred for AA and AVR had higher sRAGE values than patients undergoing AVR only (P=0.002). Patients with BAV <60 years of age, presenting with both valve and aortic diseases (fast progressors), had higher sRAGE than older patients who only needed AVR (slow progressors). Histological analysis showed that sRAGE correlates with dysfunctional aortic microstructure and does not correlate with aortic diameter (R(2)=0.007; P=0.51) or diameter/body surface area (R(2)=0.011; P=0.42).

Conclusions: These results show that elevated level of circulating sRAGE is associated with the presence of BAV and associated aortopathies, independent of aortic diameter.

Keywords: advanced glyosylation end-product receptor; aortic aneurysm, thoracic; bicuspid aortic valve.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aortic Diseases / blood*
  • Aortic Diseases / diagnosis
  • Aortic Diseases / etiology
  • Aortic Diseases / surgery
  • Aortic Valve / abnormalities*
  • Aortic Valve / surgery
  • Bicuspid Aortic Valve Disease
  • Biomarkers / blood
  • Blood Vessel Prosthesis Implantation
  • Female
  • Heart Valve Diseases / blood*
  • Heart Valve Diseases / complications
  • Heart Valve Diseases / diagnosis
  • Heart Valve Diseases / surgery
  • Heart Valve Prosthesis Implantation
  • Humans
  • Linear Models
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Prognosis
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / blood*
  • Retrospective Studies
  • Risk Factors
  • Up-Regulation

Substances

  • Biomarkers
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic