Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study

Background Cardiovascular autonomic neuropathy (CAN) is a severe complication of type 2 diabetes. Significant sex‐related differences have been observed in type 2 diabetes consequences such as mortality. However, the effect of sex on the association between CAN and mortality in patients with type 2...

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Main Authors: Ziwei Zhou, Yiquan Huang, Xiaodong Zhuang, Yue Guo, Peihan Xie, Zhenyu Xiong, Menghui Liu, Wenjing Zhang, Junqi Zhong, Yi Li, Xinxue Liao
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.034626
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author Ziwei Zhou
Yiquan Huang
Xiaodong Zhuang
Yue Guo
Peihan Xie
Zhenyu Xiong
Menghui Liu
Wenjing Zhang
Junqi Zhong
Yi Li
Xinxue Liao
author_facet Ziwei Zhou
Yiquan Huang
Xiaodong Zhuang
Yue Guo
Peihan Xie
Zhenyu Xiong
Menghui Liu
Wenjing Zhang
Junqi Zhong
Yi Li
Xinxue Liao
author_sort Ziwei Zhou
collection DOAJ
description Background Cardiovascular autonomic neuropathy (CAN) is a severe complication of type 2 diabetes. Significant sex‐related differences have been observed in type 2 diabetes consequences such as mortality. However, the effect of sex on the association between CAN and mortality in patients with type 2 diabetes is currently unknown. Methods and Results We assessed 7866 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, including 4730 men and 3136 women. CAN was diagnosed using a combination of heart rate variability and QT interval index, which has 3 different definitions. There were 1364 cases of all‐cause mortality and 452 cases of cardiovascular disease mortality during a median follow‐up of 9.7 years. We used multivariable Cox regression models to assess the association between different CAN definitions and mortality. In women, various CAN measures were statistically significant associated with an increased risk of all‐cause mortality (CAN1: hazard ratio [HR], 1.64 [95% CI, 1.28–2.09]; CAN2: HR, 1.58 [95% CI, 1.17–2.15]; CAN3: HR, 1.78 [95% CI, 1.20–2.65]) and mortality (CAN1: HR, 2.25 [95% CI, 1.44–3.52]; CAN 2: HR, 2.22 [95% CI, 1.28–3.87]; CAN3: HR, 3.31 [95% CI, 1.67–6.57]). CAN was not significantly associated with mortality in men. A significant multiplicative interaction of CAN and sex was observed on both mortality outcomes (P<0.01). Conclusions Significant sex‐related differences were observed in CAN and its associated mortality. In terms of mortality risk prevention, CAN should be given greater consideration in women with type 2 diabetes.
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spelling doaj-art-335f4201d3544eaead82c02ecc09820c2025-08-20T03:24:48ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-01-0114210.1161/JAHA.124.034626Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD StudyZiwei Zhou0Yiquan Huang1Xiaodong Zhuang2Yue Guo3Peihan Xie4Zhenyu Xiong5Menghui Liu6Wenjing Zhang7Junqi Zhong8Yi Li9Xinxue Liao10Department of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaDepartment of Cardiology The First Affiliated Hospital of Sun Yat‐sen University Guangzhou ChinaBackground Cardiovascular autonomic neuropathy (CAN) is a severe complication of type 2 diabetes. Significant sex‐related differences have been observed in type 2 diabetes consequences such as mortality. However, the effect of sex on the association between CAN and mortality in patients with type 2 diabetes is currently unknown. Methods and Results We assessed 7866 participants in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, including 4730 men and 3136 women. CAN was diagnosed using a combination of heart rate variability and QT interval index, which has 3 different definitions. There were 1364 cases of all‐cause mortality and 452 cases of cardiovascular disease mortality during a median follow‐up of 9.7 years. We used multivariable Cox regression models to assess the association between different CAN definitions and mortality. In women, various CAN measures were statistically significant associated with an increased risk of all‐cause mortality (CAN1: hazard ratio [HR], 1.64 [95% CI, 1.28–2.09]; CAN2: HR, 1.58 [95% CI, 1.17–2.15]; CAN3: HR, 1.78 [95% CI, 1.20–2.65]) and mortality (CAN1: HR, 2.25 [95% CI, 1.44–3.52]; CAN 2: HR, 2.22 [95% CI, 1.28–3.87]; CAN3: HR, 3.31 [95% CI, 1.67–6.57]). CAN was not significantly associated with mortality in men. A significant multiplicative interaction of CAN and sex was observed on both mortality outcomes (P<0.01). Conclusions Significant sex‐related differences were observed in CAN and its associated mortality. In terms of mortality risk prevention, CAN should be given greater consideration in women with type 2 diabetes.https://www.ahajournals.org/doi/10.1161/JAHA.124.034626cardiac autonomic neuropathymortalityrisksex differencestype 2 diabetes
spellingShingle Ziwei Zhou
Yiquan Huang
Xiaodong Zhuang
Yue Guo
Peihan Xie
Zhenyu Xiong
Menghui Liu
Wenjing Zhang
Junqi Zhong
Yi Li
Xinxue Liao
Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cardiac autonomic neuropathy
mortality
risk
sex differences
type 2 diabetes
title Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study
title_full Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study
title_fullStr Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study
title_full_unstemmed Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study
title_short Sex Differences in the Association Between Cardiovascular Autonomic Neuropathy and Mortality in Patients With Type 2 Diabetes: The ACCORD Study
title_sort sex differences in the association between cardiovascular autonomic neuropathy and mortality in patients with type 2 diabetes the accord study
topic cardiac autonomic neuropathy
mortality
risk
sex differences
type 2 diabetes
url https://www.ahajournals.org/doi/10.1161/JAHA.124.034626
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