title: Circulating soluble receptor for advanced glycation end product identifies patients with bicuspid aortic valve and associated aortopathies.
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.
  
  
  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.
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Emanuela
authors.initials: E
authors.lastname: Branchetti
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Bavaria
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Juan B
authors.initials: JB
authors.lastname: Grau
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Richard E
authors.initials: RE
authors.lastname: Shaw
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Paolo
authors.initials: P
authors.lastname: Poggio
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Eric K
authors.initials: EK
authors.lastname: Lai
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Nimesh D
authors.initials: ND
authors.lastname: Desai
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Gorman
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.).
authors.forename: Robert C
authors.initials: RC
authors.lastname: Gorman
authors.affiliation: From the Department of Surgery, Thoracic Aortic Program, Perelman School of Medicine at University of Pennsylvania, Philadelphia (E.B., J.E.B., J.B.G., P.P., E.K.L., N.D.D., J.H.G., R.C.G., G.F.); and Department of Surgery, Valley Hospital, Columbia University, Ridgewood, NJ (R.E.S.). Giovanni.Ferrari@uphs.upenn.edu.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ferrari
mesh_terms: D000328:Adult; D000368:Aged; D001018:Aortic Diseases / Q000097:blood* / Q000175:diagnosis / Q000209:etiology / Q000601:surgery; D001021:Aortic Valve / Q000002:abnormalities* / Q000601:surgery; D000082882:Bicuspid Aortic Valve Disease; D015415:Biomarkers / Q000097:blood; D019917:Blood Vessel Prosthesis Implantation; D005260:Female; D006349:Heart Valve Diseases / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000601:surgery; D019918:Heart Valve Prosthesis Implantation; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D011379:Prognosis; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012189:Retrospective Studies; D012307:Risk Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic
keywords: advanced glyosylation end-product receptor; aortic aneurysm, thoracic; bicuspid aortic valve