Background and aim: Cardiovascular disease (CVD) is the major cause of death in patients with type 2 diabetes mellitus (T2DM), making it of interest to attain efficient methods for prognostic purposes. We aimed to prospectively investigate the association between plasma copeptin and cardiovascular disease (CVD) in individuals with type 2 diabetes mellitus (T2DM), adjusting for mean 24-h ambulatory blood pressure, left ventricular mass index, and traditional cardio-metabolic risk factors.

Methods and results: A cohort of 523 patients with T2DM with complete data on copeptin, age, sex, body mass index (BMI), smoking, total cholesterol, eGFR, HbA1c, 24-h ambulatory systolic blood pressure (24-h SBP), and left ventricular mass index (LVMI) was derived from the Cardiovascular Risk Factors in Patients with Diabetes - a Prospective Study in Primary Care (CARDIPP) study. The incidence of major adverse cardiovascular events (MACE) and all-cause mortality were obtained from the Swedish Cause of Death Registry and the Inpatient Register. A Cox-proportional hazard analysis was conducted. Over 15 years, 120 patients had MACE, while 122 died of any cause. Patients with a copeptin level of ≥5.6 pmol/L exhibited a 2.05 hazard ratio (HR) for MACE (95 % CI 1.24-3.37, p < 0.005). However, after adjustment, no significant association with all-cause mortality (HR 1.30, 95 % CI 0.84-2.02, p = 0.238) was noted. These findings were independent of traditional cardio-metabolic risk factors, 24-h SBP, and LVMI.

Conclusions: Elevated copeptin levels (≥5.6 pmol/L) in patients with T2DM were independently associated with an increased risk of MACE. Measuring plasma copeptin may help identify high-risk T2DM patients.