title: Plasma COOH-terminal proendothelin-1: a marker of fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in type 2 diabetes? (ZODIAC-29).
abstract: OBJECTIVE
  The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes.
  
  
  METHODS
  A total of 1,225 patients with type 2 diabetes participated in this prospective observational study of two combined cohorts. Three clinical end points were studied: fatal cardiovascular events, all-cause mortality, and new-onset albuminuria. After a median follow-up of 3 or 10 years, Cox proportional hazard modeling was used to investigate the association between CT-proET-1 and the end points. Harrell C statistic, the Groennesby and Borgan test, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) were used to evaluate whether CT-proET-1 is of additional value compared with classic cardiovascular and renal risk factors.
  
  
  RESULTS
  During follow-up, 364 (30%) patients died, 150 (42%) of whom died of cardiovascular disease; 182 (26.7%) of 688 patients with normoalbuminuria at baseline developed albuminuria. CT-proET-1 was associated with fatal cardiovascular events, all-cause mortality, and new-onset albuminuria with hazard ratios of 1.59 (95% CI 1.15-2.20), 1.41 (95% CI 1.14-1.74), and 1.48 (95% CI 1.10-2.01), respectively. Addition of CT-proET-1 to a model containing traditional risk factors leads only to improved prediction of fatal cardiovascular events. The IDI appeared significant for fatal cardiovascular events (0.82 [0.1-1.54]) and all-cause mortality (0.4 [0.05-0.92]), but not for new-onset albuminuria.
  
  
  CONCLUSIONS
  CT-proET-1 has additional value for the prediction of fatal cardiovascular events and new-onset albuminuria in patients with type 2 diabetes, compared with conventional risk factors, but not for all-cause mortality.
authors: Diabetes Centre, Isala Clinics, Zwolle, The Netherlands. i.drion@isala.nl
authors: Iefke
authors: I
authors: Drion
authors: Nanne
authors: N
authors: Kleefstra
authors: Gijs W D
authors: GW
authors: Landman
authors: Alaa
authors: A
authors: Alkhalaf
authors: Joachim
authors: J
authors: Struck
authors: Klaas H
authors: KH
authors: Groenier
authors: Stephan J L
authors: SJ
authors: Bakker
authors: Henk J G
authors: HJ
authors: Bilo
mesh_terms: D000328:Adult; D000419:Albuminuria / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000401:mortality; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D015415:Biomarkers; C557077:C-terminal proendothelin-1; D019332:Endothelin-1; D010446:Peptide Fragments