title: The relationship of fibroblast growth factor 21 with cardiovascular outcome events in the Fenofibrate Intervention and Event Lowering in Diabetes study.
abstract: OBJECTIVE
  Circulating fibroblast growth factor 21 (FGF21) levels are often elevated in obesity, dyslipidaemia, insulin resistance and type 2 diabetes. This study investigated the relationship of plasma FGF21 levels with cardiovascular events in patients with type 2 diabetes.
  
  
  METHODS
  Plasma FGF21 levels were measured by ELISA at baseline in 9,697 individuals with type 2 diabetes participating in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. We assessed the association of FGF21 levels with the incidence of different cardiovascular outcomes over 5 years. The primary outcome was total cardiovascular disease (CVD) events and the secondary outcomes were the four individual components: coronary heart disease events, total stroke, CVD mortality and coronary and carotid revascularisation. The tertiary outcome was hospitalisation for angina pectoris.
  
  
  RESULTS
  Higher baseline FGF21 levels were associated with higher risks of all cardiovascular outcome events after adjusting for the study treatment allocation (all p < 0.01). The associations remained significant for total CVD events and for coronary and carotid revascularisation after further adjusting for confounding factors, with the HR (95% CI) being 1.28 (1.10, 1.50) and 1.26 (1.01, 1.56), respectively, for the highest tertile compared with the lowest tertile (overall effect p = 0.002 and 0.007, respectively). The addition of FGF21 levels to a model including established CVD risk factors predicting total CVD events led to a non-significant increase in the C-statistic but there was a significant improvement in integrated discrimination and net reclassification.
  
  
  CONCLUSIONS
  Higher baseline plasma FGF21 levels were associated with higher risk of cardiovascular events in patients with type 2 diabetes.
  
  
  BACKGROUND
  ISRCTN64783481.
authors.affiliation: Lipid Research Group, Heart Research Institute, Sydney, NSW, Australia, oklws@yahoo.com.hk.
authors.forename: Kwok-Leung
authors.initials: KL
authors.lastname: Ong
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Januszewski
authors.forename: Rachel
authors.initials: R
authors.lastname: O'Connell
authors.forename: Alicia J
authors.initials: AJ
authors.lastname: Jenkins
authors.forename: Aimin
authors.initials: A
authors.lastname: Xu
authors.forename: David R
authors.initials: DR
authors.lastname: Sullivan
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Barter
authors.forename: Wei-Ting
authors.initials: WT
authors.lastname: Hung
authors.forename: Russell S
authors.initials: RS
authors.lastname: Scott
authors.forename: Marja-Riitta
authors.initials: MR
authors.lastname: Taskinen
authors.forename: Anthony C
authors.initials: AC
authors.lastname: Keech
authors.forename: Kerry-Anne
authors.initials: KA
authors.lastname: Rye
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D005346:Fibroblast Growth Factors / Q000097:blood*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D020521:Stroke / Q000097:blood
chemical_list: D000960:Hypolipidemic Agents; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D011345:Fenofibrate