Copeptin, a Surrogate Marker for Arginine Vasopressin, Is Associated With Cardiovascular and All-Cause Mortality in Patients With Type 2 Diabetes (ZODIAC-31)

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. RESEARCH DESIGN AND 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%). Log(2) 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, HbA(1c), 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.