title: Copeptin, a surrogate marker for arginine vasopressin, is associated with cardiovascular and all-cause mortality in patients with type 2 diabetes (ZODIAC-31).
abstract: OBJECTIVE
  Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim was to investigate whether copeptin is associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care.
  
  
  METHODS
  Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationship of baseline copeptin with CV and all-cause mortality.
  
  
  RESULTS
  We included 1,195 patients (age 67±12 years, 44% male). Median baseline copeptin concentration was 5.4 (interquartile range [IQR] 3.1-9.6) pmol/L. After a median follow-up of 5.9 (IQR 3.2-10.1) years, 345 patients died (29%), with 148 CV deaths (12%). Log2 copeptin was associated with CV (hazard ratio 1.17 [95% CI 0.99-1.39]; P=0.068) and all-cause mortality (1.22 [1.09-1.36]; P=0.001) after adjustment for age, sex, BMI, smoking, systolic blood pressure, total cholesterol to HDL ratio, duration of diabetes, HbA1c, treatment with ACE inhibitors and angiotensin receptor blockers, history of CV diseases, log serum creatinine, and log albumin to creatinine ratio; however, copeptin did not substantially improve risk prediction for CV (integrated discrimination improvement 0.14% [IQR -0.27 to 0.55%]) and all-cause mortality (0.77% [0.17-1.37%]) beyond currently used clinical markers.
  
  
  CONCLUSIONS
  We found copeptin to be associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. Intervention studies should show whether the high CV risk in type 2 diabetes can be reduced by suppression of vasopressin, for example by reducing salt intake.
authors.affiliation: Corresponding author: Ineke J. Riphagen, i.j.riphagen@umcg.nl.
authors.forename: Ineke J
authors.initials: IJ
authors.lastname: Riphagen
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Boertien
authors.forename: Alaa
authors.initials: A
authors.lastname: Alkhalaf
authors.forename: Nanne
authors.initials: N
authors.lastname: Kleefstra
authors.forename: Ron T
authors.initials: RT
authors.lastname: Gansevoort
authors.forename: Klaas H
authors.initials: KH
authors.lastname: Groenier
authors.forename: Kornelis J J
authors.initials: KJ
authors.lastname: van Hateren
authors.forename: Joachim
authors.initials: J
authors.lastname: Struck
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Henk J G
authors.initials: HJ
authors.lastname: Bilo
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D000368:Aged; D001127:Arginine Vasopressin / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000401:mortality*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000401:mortality*; D005260:Female; D006020:Glycopeptides / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012737:Sex Factors
chemical_list: D015415:Biomarkers; D006020:Glycopeptides; C048197:copeptins; D001127:Arginine Vasopressin