Cardiovascular Autonomic Neuropathy Raises Mortality Risk in Women With Type 2 Diabetes, Study Finds

The study, which examined data from the ACCORD and ACCORDION trials, found that CAN was linked to a higher risk of all-cause and cardiovascular mortality in women but not in men. These findings highlight the need for greater clinical attention to CAN in women to improve long-term health outcomes.

With the prevalence of type 2 diabetes on the rise and cases expected to reach 552 million by 2030, its complications pose a growing concern. Among them, cardiovascular autonomic neuropathy stands out as a severe condition affecting up to 60% of patients, significantly increasing the risk of mortality. Studies indicate that CAN nearly doubles the five-year mortality risk in individuals with diabetes and remains a strong predictor of cardiovascular mortality. Notably, sex-related differences have been observed, particularly in heart rate variability and cardiovascular risk.

Against the above background, Xinxue Liao, NHC Key Laboratory of Assisted Circulation Sun Yat‐sen University Guangzhou China, and colleagues aimed to examine the link between CAN and mortality in T2D patients, with a specific focus on sex-related differences in prognosis.

For this purpose, the researchers analyzed data from 7,866 ACCORD trial participants (4,730 men and 3,136 women). CAN was diagnosed using heart rate variability and QT interval index based on three definitions. Over a 9.7-year median follow-up, 1,364 all-cause and 452 cardiovascular mortality cases were recorded. Multivariable Cox regression models were used to assess the impact of CAN on mortality.

The study led to the following findings:

• In women, different measures of CAN were significantly linked to a higher risk of all-cause mortality (HR ranging from 1.58 to 1.78).
• CAN was also associated with an increased risk of cardiovascular mortality in women (HR ranging from 2.22 to 3.31).
• There was no significant association between CAN and mortality in men.
• A significant interaction between CAN and sex was observed for both mortality outcomes, highlighting sex-related differences in risk.

The study revealed significant sex-related differences in the association between cardiovascular autonomic neuropathy (CAN) and mortality in individuals with type 2 diabetes. CAN was linked to a higher risk of mortality in women, while there was no such association in men.

"These findings highlight the need for greater clinical attention to CAN in women, as its progression may lead to a worse prognosis. Early identification and management of CAN could be crucial in improving long-term outcomes for women with type 2 diabetes," the authors concluded.

Reference:

Zhou Z, Huang Y, Zhuang X, Guo Y, Xie P, Xiong Z, Liu M, Zhang W, Zhong J, Li Y, Liao X. Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study. J Am Heart Assoc. 2025 Jan 21;14(2):e034626. doi: 10.1161/JAHA.124.034626. Epub 2025 Jan 10. PMID: 39791396.