| Title: | Proteomic Profiling Captures Residual Cardiovascular Risk Beyond the PREVENT Model in Individuals With Cardiovascular-Kidney-Metabolic Syndrome Stages 2-3 |
| Journal: | Diabetes Obesity and Metabolism |
| Published: | 1 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42225325/ |
| DOI: | https://doi.org/10.1111/dom.70933 |
Publication 19818
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Abstract
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome reflects complex pathobiological interactions among metabolic disorders, kidney injury, and cardiovascular disease (CVD). Stages 2 and 3 represent critical phases of disease progression characterised by high pathological heterogeneity. This study aimed to develop a CVD protein risk score (PRS) for this population and evaluate its incremental predictive value over the PREVENT model.</p>
METHODS: This study included 24 017 participants with CKM Stages 2-3 from the UK Biobank. Using 2923 plasma proteins measured via the Olink platform, a PRS was developed in a training set (n = 19 218) using the LASSO method. In the validation set (n = 4799), the incremental predictive performance of this score over the PREVENT model was assessed using Harrell's C-statistic, net reclassification improvement (NRI) and integrated discrimination improvement (IDI).</p>
RESULTS: A risk score comprising 63 proteins was constructed, primarily reflecting inflammation, kidney injury and matrix remodelling. Key proteins included growth differentiation factor 15 (GDF15), hepatitis A virus cellular receptor 1 (HAVCR1), matrix metallopeptidase 12 (MMP12) and NT-proBNP. In the validation set, after adjusting for PREVENT risk factors, individuals in the high PRS group had a 2.56-fold higher risk of CVD compared to those in the low score group (HR: 2.56, 95% CI: 1.96-3.37). Integrating the score into the PREVENT model improved the C-statistic by 0.034 (0.672-0.706) and achieved a 10-year NRI of 15.8% (95% CI: 9.5%-20.9%) and an IDI of 2.2% (95% CI: 1.3%-3.3%).</p>
CONCLUSION: Combining the PREVENT model with the PRS developed in this study enhances the prediction of future CVD events in the CKM Stages 2-3 population. This approach facilitates the capture of residual risk and supports precision risk stratification and management for this high-risk group.</p>
5 Authors
- Xuefei Han
- Jiacheng Ding
- Jingqian Li
- Yiyin Gao
- Yunqian Li
1 Application
| Application ID | Title |
|---|---|
| 629227 | Multifactorial Influences on Women's Health and related diseases. |
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