| Title: | Cardiovascular health factors and altered proteomic landscapes in the progression of cardiovascular-kidney-metabolic syndrome: Evidence from multi-cohorts in China, the UK, and the US |
| Journal: | Metabolism |
| Published: | 1 Mar 2026 |
| DOI: | https://doi.org/10.1016/j.metabol.2026.156596 |
Publication 17556
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Abstract
Background The role of cardiovascular health (CVH) factors and their associated proteomic profiles in the progression and prognosis of cardiovascular-kidney-metabolic (CKM) syndrome among individuals at stages 0-3 remains unclear. Methods This study analyzed data from 10,351 Chinese adults (China Health and Retirement Longitudinal Study [CHARLS]), 224,352 British adults (UK Biobank [UKB]), and 20,726 American adults (National Health and Nutrition Examination Survey [NHANES]). Cox proportional hazards models were used to assess the associations of CVH score and proteomic panel with incident CVD and in CKM stages 0-3 individuals. Results The median follow-up periods were 13.6 years in UKB, 9.4 years in CHARLS, and 7.5 years in NHANES. Among individuals with CKM stages 0-3, those with optimal CVH had reduced risks of overall CVD compared with those with low CVH (UKB, HR = 0.58, 95% CI: 0.55-0.62; CHARLS, HR = 0.77, 95% CI: 0.64-0.92), and all-cause mortality (UKB, HR = 0.45, 95% CI: 0.42-0.49; CHARLS, HR = 0.60, 95% CI: 0.47-0.76; NHANES, HR = 0.34, 95% CI: 0.26-0.44). These protective associations were similarly observed across CVD subtypes and cause-specific mortality. An ENM-selected panel of 722 proteins was associated with 41% lower overall CVD risk and 54% lower all-cause mortality. Meanwhile, circulating proteins mediated the associations between CVH score and CKM syndrome progression and prognosis, particularly ALPP. Conclusions Optimal cardiovascular health behaviors and factors are key to halting the progression and improving the prognosis of CKM syndrome, with the associated proteins potentially serving as biomarkers and molecular targets for interventions.</p>
8 Authors
- Erxu Xue
- Jianhui Zhao
- Bowen Chen
- Jingyu Ye
- Jingjie Wu
- Jing Shao
- Xue Li
- Zhihong Ye
Enabling scientific discoveries that improve human health