Cardiovascular Autonomic Neuropathy and Indices of Heart Failure in Type 2 Diabetes: The CANCAN Study

Aim To quantify the association between cardiovascular autonomic neuropathy (CAN) and heart failure (HF) in individuals with type 2 diabetes (T2D). Materials and Methods Two hundred T2D individuals were recruited from two Danish outpatient clinics between 2021–2024. CAN was defined by abnormal cardiovascular autonomic reflex test results. HF outcomes included the primary outcome of elevated N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels > 125 pg/mL, WATCH‐DM risk score. Symptomatic HF was defined by New York Heart Association (NYHA) classification score ≥II. We assessed the association between measures of CAN and HF using logistic and linear regressions, adjusting for confounders and testing for effect modification between CAN, NYHA, and WATCH‐DM risk scores. Results Among 176 individuals with NT‐proBNP assessments, the median (interquartile range [IQR]) age was 63 (IQR: 55, 70) years, 61% were men, and median diabetes duration was 17 years (IQR: 11, 24). Among 134 individuals with valid CAN assessment, 40% had CAN and 52% of those had elevated NT‐proBNP compared to 23% of individuals without CAN. In the fully adjusted model, CAN was associated with 6.2 times higher odds (95% CI: 2.1; 20.8) of elevated NT‐proBNP levels compared to individuals without CAN. The association remained statistically significant in asymptomatic individuals, and in individuals with a low‐to‐moderate WATCH‐DM risk score. Conclusion CAN is associated with elevated NT‐proBNP levels in individuals asymptomatic for HF. This suggests that CAN may complement established biomarkers to identify individuals with earlier HF stages, for timelier treatment initiation.