title: Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community: The Framingham Heart Study.
abstract: OBJECTIVE
  Growth differentiation factor-15 (GDF-15), soluble (s)ST2, and high-sensitivity troponin-I (hs-TnI) are associated with incident cardiovascular disease (CVD) including heart failure, yet the underlying mechanisms are not fully understood. We investigated if GDF-15, sST2, and hs-TnI are related to subclinical vascular dysfunction in the community, which may explain the relations of these biomarkers with CVD.
  
  
  METHODS
  We evaluated 1823 Framingham Study participants (mean age 61 ± 10 years, 54% women) who underwent routine assessment of vascular function. We related circulating GDF-15, sST2, and hs-TnI concentrations to measures of arterial stiffness (carotid-femoral pulse wave velocity, CFPWV; augmentation index; and forward pressure wave amplitude, FW), endothelial-dependent vasodilation (flow-mediated dilation, FMD), and baseline and hyperemic brachial flow velocities using linear regression adjusting for standard risk factors.
  
  
  RESULTS
  After multivariable adjustment, GDF-15 levels were positively associated with CFPWV (0.044 [95% confidence interval 0.007-0.081] standard deviation [SD] change per SD increase in loge[GDF-15], p = 0.02) and FW (0.076 [0.026-0.126] SD change per SD increase in loge[GDF-15], p = 0.003) and inversely related to FMD (-0.051 [-0.101-0.0003] SD change per SD increase in loge[GDF-15], p = 0.048). sST2 was positively associated with CFPWV (0.032 [0.0005-0.063] SD change per SD increase in loge[sST2], p = 0.046), and hs-TnI inversely associated with hyperemic flow velocity (-0.041 [-0.082-0.0004] SD change per SD increase in loge[hs-TnI], p = 0.048).
  
  
  CONCLUSIONS
  In our community-based investigation, individual cardiac stress biomarkers were differentially related to select aspects of vascular function. These findings may contribute to the associations of circulating GDF-15, sST2, and hs-TnI with incident CVD and heart failure.
authors.affiliation: The Boston University's and National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA, USA. Electronic address: ca@heart.dk.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Andersson
authors.affiliation: Department of Biostatistics, Boston University, MA, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Enserro
authors.affiliation: Department of Biostatistics, Boston University, MA, USA.
authors.forename: Lisa
authors.initials: L
authors.lastname: Sullivan
authors.affiliation: The Boston University's and National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA, USA; Division of Cardiovascular Medicine, Vanderbilt University, Nashville, TN, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Januzzi
authors.affiliation: The Boston University's and National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA, USA; Sections of Preventive Medicine and Cardiology, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Emelia J
authors.initials: EJ
authors.lastname: Benjamin
authors.affiliation: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Vita
authors.affiliation: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Naomi M
authors.initials: NM
authors.lastname: Hamburg
authors.affiliation: The Boston University's and National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA, USA.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.affiliation: Cardiovascular Engineering, Inc., Norwood, MA, USA.
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.affiliation: The Boston University's and National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA, USA; Sections of Preventive Medicine and Cardiology, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood*; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006333:Heart Failure / Q000097:blood; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012044:Regression Analysis; D012307:Risk Factors; D019210:Troponin I / Q000097:blood*; D059289:Vascular Stiffness
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D019210:Troponin I; D003404:Creatinine
keywords: Biomarkers; Endothelial function; GDF-15; General population; ST2; Troponin I; Vascular stiffness