title: Thoracic aortic aneurysm frequency and dissection are associated with fibrillin-1 fragment concentrations in circulation.
abstract: BACKGROUND
  Mutations in fibrillin-1 are associated with thoracic aortic aneurysm (TAA) in Marfan syndrome. Genome-wide association studies also implicate fibrillin-1 in sporadic TAA. Fragmentation of the aortic elastic lamellae is characteristic of TAA.
  
  
  OBJECTIVE
  Immunoassays were generated to test whether circulating fragments of fibrillin-1, or other microfibril fragments, are associated with TAA and dissection.
  
  
  RESULTS
  Plasma samples were obtained from 1265 patients with aortic aneurysm or dissection and from 125 control subjects. Concentrations of fibrillin-1, fibrillin-2, and fibulin-4 were measured with novel immunoassays. One hundred and seventy-four patients (13%) had aneurysms with only abdominal aortic involvement (abdominal aortic aneurysm), and 1091 (86%) had TAA. Of those with TAA, 300 patients (27%) had chronic dissection and 109 (10%) had acute or subacute dissection. Associations of fragment concentrations with TAA (versus abdominal aortic aneurysm) or with dissection (versus no dissection) were estimated with odds ratios (OR) and 95% confidence intervals (CI) adjusted for age, sex, and smoking. Compared with controls, significantly higher percentages of aneurysm patients had detectable levels of fibrillin fragments. TAA was significantly more common (than abdominal aortic aneurysm) in the highest compared with lowest quartile of fibrillin-1 concentration (OR=2.9; 95% CI, 1.6-5.0). Relative to TAA without dissection, acute or subacute dissection (OR=2.9; 95% CI, 1.6-5.3), but not chronic dissection, was more frequent in the highest compared with lowest quartile of fibrillin-1 concentration. Neither TAA nor dissection was associated with fibrillin-2 or fibulin-4.
  
  
  CONCLUSIONS
  Circulating fibrillin-1 fragments represent a new potential biomarker for TAA and acute aortic dissection.
authors.affiliation: From the Departments of Orthopedics and Rehabilitation.
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Marshall
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Carlson
authors.forename: Jean
authors.initials: J
authors.lastname: O'Malley
authors.forename: Caryn K
authors.initials: CK
authors.lastname: Snyder
authors.forename: Noe L
authors.initials: NL
authors.lastname: Charbonneau
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Hayflick
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Coselli
authors.forename: Scott A
authors.initials: SA
authors.lastname: Lemaire
authors.forename: Lynn Y
authors.initials: LY
authors.lastname: Sakai
mesh_terms: D000368:Aged; D000784:Aortic Dissection / Q000097:blood* / Q000453:epidemiology*; D017544:Aortic Aneurysm, Abdominal / Q000097:blood / Q000453:epidemiology; D017545:Aortic Aneurysm, Thoracic / Q000097:blood* / Q000453:epidemiology*; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D006801:Humans; D015994:Incidence; D008297:Male; D008840:Microfilament Proteins / Q000097:blood*; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D054392:Adipokines
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D000071838:Fibrillin-1; D000071840:Fibrillin-2; D000071837:Fibrillins; D008840:Microfilament Proteins; C403672:EFEMP2 protein, human; C000605722:FBN1 protein, human; D054392:Adipokines; C000605723:FBN2 protein, human
keywords: Marfan Syndrome; aneurysm; dissection; fibrillin; microfibrils