Mosaic Chromosomal Alterations, Frailty and Cardiovascular Disease Mortality: A Population-based Cohort Study Among Chinese Adults
Abstract Body: Background Mosaic chromosomal alterations (mCAs), representing a group of large-scale structural alterations detected in a fraction of peripheral leukocytes, serve as an indicator of genomic aging. We aim to investigate the association between expanded mCAs (cell fraction ≥10%) and cardiovascular disease (CVD) mortality, and examine whether combining mCAs with frailty index (FI), an indicator of phenotipic aging, contribute to the prediction of CVD mortality. Methods A total of 100,297 genotyped participants aged 30-79 years from China Kadoorie Biobank were included, whose baseline information were collected from 2004-2008 and followed till Dec 31, 2023. MoChA pipeline was used to detect expanded mCAs events, including mCAs on autosomes, and the loss of X and Y chromosomes. FI was calculated using a previously validated equation using 28 health-related variables, which categorized participants into three groups: robust (FI≤0.1), prefrail (0.1Results After a median follow-up of 17.2 years (IQR: 15.7-18.2), 13,655 deaths from CVD diseases were recorded. Expanded mCAs were associated with an increased risk of CVD mortality independent of FI (hazard ratio [HR] and 95% confidence interval [CI]=1.24 [1.13, 1.36]), including deaths from ischaemic heart diseases (IHD, 1.24 [1.08, 1.42]), from strokes (1.20 [1.03, 1.39]) and from pulmonary heart diseases (PHD, 2.20 [1.03, 4.68]). Compared with robust participants without expanded mCAs, frail participants with expanded mCAs had around three-times increased risks of CVD mortality (2.98 [2.17, 4.07]), deaths from IHD (3.18 [2.03, 4.96]), and death from strokes (2.79 [1.64, 4.74]), and had sixteen-times increased risks of PHD mortality (16.51 [3.63, 75.01]). Conclusion Combining expanded mCAs, a novel pre-symptomatic marker, with frailty index might increase the prediction of death from multiple CVD diseases.
Song, Mingyu
( Peking university
, Beijing, China
, China
)
Chen, Yiping
( Nuffield Dept of Population Health
, Oxford
, United Kingdom
)
Du, Huaidong
( Nuffield Dept of Population Health
, Oxford
, United Kingdom
)
Yang, Xiaoming
( Nuffield Dept of Population Health
, Oxford
, United Kingdom
)
Chen, Junshi
( China National Center for Food Safety Risk Assessment
, Beijing
, China
)
Chen, Zhengming
( Nuffield Dept of Population Health
, Oxford
, United Kingdom
)
Genovese, Giulio
( Broad Institute of MIT and Harvard
, Cambridge
, Massachusetts
, United States
)
Terao, Chikashi
( RIKEN Center for Integrative Medical Sciences
, Kanagawa
, Japan
)
Li, Liming
( Peking University
, Beijing
, China
)
Sun, Dianjianyi
( Peking University
, Beijing
, China
)
Zhao, Yuxuan
( Peking university
, Beijing, China
, China
)
Han, Yuting
( Peking University
, Beijing
, China
)
Lv, Jun
( Peking university
, Beijing, China
, China
)
Yu, Canqing
( Peking University
, Beijing
, China
)
Pei, Pei
( Peking University Center for Public Health and Epidemic Preparedness & Response
, Beijing
, China
)
Yang, Ling
( Nuffield Dept of Population Health
, Oxford
, United Kingdom
)
Millwood, Iona
( Nuffield Dept of Population Health
, Oxford
, United Kingdom
)
Walters, Robin
( Nuffield Dept of Population Health
, Oxford
, United Kingdom
)
Author Disclosures:
Mingyu Song:DO NOT have relevant financial relationships
| Yiping Chen:No Answer
| Huaidong Du:No Answer
| Xiaoming Yang:No Answer
| Junshi Chen:DO NOT have relevant financial relationships
| Zhengming Chen:No Answer
| Giulio Genovese:No Answer
| Chikashi Terao:No Answer
| Liming Li:No Answer
| Dianjianyi Sun:DO NOT have relevant financial relationships
| Yuxuan Zhao:No Answer
| Yuting Han:DO NOT have relevant financial relationships
| Jun Lv:No Answer
| Canqing YU:No Answer
| pei pei:No Answer
| Ling Yang:No Answer
| Iona Millwood:No Answer
| Robin Walters:No Answer
Li Aolin, Yang Xiaoming, Chen Junshi, Chen Zhengming, Lv Jun, Li Liming, Sun Dianjianyi, Gong Shuo, Yu Canqing, Pei Pei, Yang Ling, Millwood Iona, Walters Robin, Chen Yiping, Du Huaidong
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