MR-proANP, but Not Copeptin, Predicts Cardiovascular Events and Mortality in Type 1 Diabetes: A Prospective Cohort Study

Background/Objectives: MR-proANP and copeptin are biomarkers of cardiovascular stress and individuals with type 1 diabetes are at increased cardiovascular risk. We aimed to investigate the associations of MR-proANP and copeptin with major adverse cardiovascular events (MACEs) and all-cause mortality in individuals with type 1 diabetes and in controls. Methods: MR-proANP and copeptin were measured in 576 individuals with type 1 diabetes and 513 controls enrolled in the LeDIG cohort. Participants were followed for a median of 10.7 and 10.2 years, respectively. Major adverse cardiovascular events (MACEs) and all-cause mortality were ascertained through linkage to the national Cause of Death and Inpatient Registries. Associations with outcomes were evaluated using Cox proportional hazards regression with adjustment for established cardiovascular risk factors. Non-linear associations were assessed using restricted cubic splines, and Kaplan–Meier analyses were performed across tertiles of MR-proANP. Results: In type 1 diabetes, higher MR-proANP levels were independently associated with increased risk of both MACE (HR 1.005, 95% CI 1.001–1.009; p = 0.010) and all-cause mortality (HR 1.008, 95% CI 1.003–1.012; p < 0.001) after multivariable adjustment. Individuals with type 1 diabetes had higher risks of MACE (HR 2.22, 95% CI 1.41–3.50; p < 0.001) and all-cause mortality (HR 4.36, 95% CI 2.13–8.90; p < 0.001) compared with controls. The association with MACE was attenuated and became statistically nonsignificant after additional adjustment for previous myocardial infarction or stroke (p = 0.086), but remained significant after exclusion of such individuals. Copeptin was not independently associated with outcomes after adjustment. In controls, MR-proANP was associated with mortality but not MACE. Conclusions: MR-proANP was independently associated with long-term risk of cardiovascular events and all-cause mortality in individuals with type 1 diabetes. MR-proANP may reflect established cardiovascular disease but also be associated with future cardiovascular risk in individuals without previous events. In contrast, copeptin was not independently associated with these outcomes.