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

To quantify the association between cardiovascular autonomic neuropathy (CAN) and heart failure (HF) in individuals with type 2 diabetes (T2D).

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.

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.

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.