title: Circulating transforming growth factor-β as a prognostic biomarker in Marfan syndrome.
abstract: BACKGROUND
  Patients with Marfan syndrome (MFS) are at risk for cardiovascular disease. Marfan associated mutations in the FBN1 gene lead to increased transforming growth factor-β (TGF-β) activation. The aim of this study was to investigate the role of plasma TGF-β as a biomarker for progressive aortic root dilatation and dissection.
  
  
  METHODS
  Plasma TGF-β level and aortic root diameter by means of echocardiography were assessed in 99 MFS patients. After 38 months of follow-up measurement of the aortic root was repeated and individual aortic root growth curves were constructed. Clinical events were evaluated. The primary composite endpoint was defined as aortic dissection and prophylactic aortic root replacement.
  
  
  RESULTS
  TGF-β levels were higher in MFS patients as compared to healthy controls (109 pg/ml versus 54 pg/ml, p<0.001). Higher plasma TGF-β levels correlated with larger aortic root dimensions (r=0.26, p=0.027), previous aortic root surgery (161 pg/ml versus 88 pg/ml, p=0.007) and faster aortic root growth rate (r=0.42, p<0.001). During 38 months of follow-up, 17 events were observed (four type B dissections and 13 aortic root replacements). Patients with TGF-β levels above 140 pg/ml had a 6.5 times higher risk of experiencing the composite endpoint compared to patients with TGF-β levels below 140 pg/ml (95% CI: 2.1 to 20.1, p=0.001) with 65% sensitivity and 78% specificity.
  
  
  CONCLUSIONS
  Elevated TGF-β level in patients with Marfan syndrome is correlated with larger aortic root diameters and faster aortic root growth. Level of plasma TGF-β predicts cardiovascular events and might serve as a prognostic biomarker in MFS.
authors.affiliation: Department of Cardiology, Academic Medical Center Amsterdam, The Netherlands; Interuniversity Cardiology Institute of the Netherlands, The Netherlands.
authors.forename: Romy
authors.initials: R
authors.lastname: Franken
authors.forename: Alexander W
authors.initials: AW
authors.lastname: den Hartog
authors.forename: Vivian
authors.initials: V
authors.lastname: de Waard
authors.forename: Leo
authors.initials: L
authors.lastname: Engele
authors.forename: Teodora
authors.initials: T
authors.lastname: Radonic
authors.forename: Rene
authors.initials: R
authors.lastname: Lutter
authors.forename: Janneke
authors.initials: J
authors.lastname: Timmermans
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Scholte
authors.forename: Maarten P
authors.initials: MP
authors.lastname: van den Berg
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.forename: Maarten
authors.initials: M
authors.lastname: Groenink
authors.forename: Barbara J M
authors.initials: BJ
authors.lastname: Mulder
mesh_terms: D000293:Adolescent; D000328:Adult; D001018:Aortic Diseases / Q000097:blood* / Q000209:etiology*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000097:blood* / Q000150:complications*; D008875:Middle Aged; D011379:Prognosis; D016212:Transforming Growth Factor beta / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016212:Transforming Growth Factor beta
keywords: Aortic dissection; Aortic root growth; Biomarker; Clinical events; Marfan syndrome; Transforming growth factor beta (TGF-β)