Impact of DNA‐Methylation Age Acceleration on Long‐Term Mortality Among US Adults With Cardiovascular‐Kidney‐Metabolic Syndrome

Shuang Wu 1
, 
Jun Zhu 1
, 
Siqi Lyu 1
, 
Juan Wang 1
, 
Xinghui Shao 1
, 
Han Zhang 1
, 
Ziyi Zhong 2, 3
, 
Hongyu Liu 2, 4
, 
Lihui Zheng 1
, 
Yang Chen 2, 3
1
 
2
 
3
 
4
 
Publication type: Journal Article
Publication date: 2025-03-21
Ovid Technologies (Wolters Kluwer Health)
scimago Q1
wos Q1
SJR: 2.189
CiteScore: 8.5
Impact factor: 5.3
ISSN: 20479980
Abstract
Background
The association between DNA methylation age acceleration (DNAmAA) and cardiovascular‐kidney‐metabolic (CKM) syndrome stages and long‐term mortality in the population with CKM syndrome remains unclear.
Methods and Results
This cohort study included 1889 participants from the National Health and Nutrition Examination Survey (1999–2002) with CKM stages and DNA methylation age data. DNAmAA was calculated as residuals from the regression of DNA methylation age on chronological age. The primary outcome was all‐cause mortality, with cardiovascular and noncardiovascular mortality as secondary outcomes. Proportional odds models assessed the associations between DNAmAAs and CKM stages, and Cox proportional hazards regression models estimated the associations between DNAmAAs and mortality. Significant associations were found between DNAmAAs and advanced CKM stages, particularly for GrimAge2Mort acceleration (GrimAA) (odds ratio [OR], 1.547 [95% CI, 1.316–1.819]). Over an average follow‐up of 14 years, 1015 deaths occurred. Each 5‐unit increase in GrimAA was associated with a 50% increase in all‐cause mortality (95% CI, 1.39–1.63), a 77% increase in cardiovascular mortality (95% CI, 1.46–2.15), and a 42% increase in noncardiovascular mortality (95% CI, 1.27–1.59). With the lowest GrimAA tertile as a reference, the highest GrimAA tertile showed hazard ratios of 1.95 (95% CI, 1.56–2.45) for all‐cause mortality, 3.06 (95% CI, 2.13–4.40) for cardiovascular mortality, and 1.65 (95% CI, 1.20–2.29) for noncardiovascular mortality. Mediation analysis indicated that GrimAA mediates the association between various exposures (including physical activity, Healthy Eating Index‐2015 score, hemoglobin A1c, etc.) and mortality.
Conclusions
GrimAA may serve as a valuable biomarker for assessing CKM stages and mortality risk in individuals with CKM syndrome, thereby informing personalized management strategies.
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Wu S. et al. Impact of DNA‐Methylation Age Acceleration on Long‐Term Mortality Among US Adults With Cardiovascular‐Kidney‐Metabolic Syndrome // Journal of the American Heart Association. 2025.
GOST all authors (up to 50) Copy
Wu S., Zhu J., Lyu S., Wang J., Shao X., Zhang H., Zhong Z., Liu H., Zheng L., Chen Y. Impact of DNA‐Methylation Age Acceleration on Long‐Term Mortality Among US Adults With Cardiovascular‐Kidney‐Metabolic Syndrome // Journal of the American Heart Association. 2025.
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RIS Copy
TY - JOUR
DO - 10.1161/jaha.124.039751
UR - https://www.ahajournals.org/doi/10.1161/JAHA.124.039751
TI - Impact of DNA‐Methylation Age Acceleration on Long‐Term Mortality Among US Adults With Cardiovascular‐Kidney‐Metabolic Syndrome
T2 - Journal of the American Heart Association
AU - Wu, Shuang
AU - Zhu, Jun
AU - Lyu, Siqi
AU - Wang, Juan
AU - Shao, Xinghui
AU - Zhang, Han
AU - Zhong, Ziyi
AU - Liu, Hongyu
AU - Zheng, Lihui
AU - Chen, Yang
PY - 2025
DA - 2025/03/21
PB - Ovid Technologies (Wolters Kluwer Health)
SN - 2047-9980
ER -
BibTex
Cite this
BibTex (up to 50 authors) Copy
@article{2025_Wu,
author = {Shuang Wu and Jun Zhu and Siqi Lyu and Juan Wang and Xinghui Shao and Han Zhang and Ziyi Zhong and Hongyu Liu and Lihui Zheng and Yang Chen},
title = {Impact of DNA‐Methylation Age Acceleration on Long‐Term Mortality Among US Adults With Cardiovascular‐Kidney‐Metabolic Syndrome},
journal = {Journal of the American Heart Association},
year = {2025},
publisher = {Ovid Technologies (Wolters Kluwer Health)},
month = {mar},
url = {https://www.ahajournals.org/doi/10.1161/JAHA.124.039751},
doi = {10.1161/jaha.124.039751}
}