Cardiovascular-kidney-metabolic syndrome stages and risk of diverse gastrointestinal diseases: a prospective cohort study and integrative proteomic analysis
Main finding · Overall GI disease riskResult — go to the resultAdjusted hazard ratio 1.91 95% CI 1.84–2.00Authors' conclusion
Advanced CKM stages significantly elevate the risk of diverse GI diseases. Specific circulating proteomic signatures underlie these systemic associations. Integrating cardiometabolic profiling into GI risk stratification holds early preventive potential, requiring external validation before clinical implementation.
Study context
- Population
- UK Biobank participants (cardiovascular-kidney-metabolic (CKM) stages 0–4) free of baseline gastrointestinal (GI) diseasesproteomics n = 38,031
- Participants
- 354,444 participants
- Exposure
- CKM stages 1-4 vs stage 0
- Outcome
- Incident functional, inflammatory and malignant GI diseases
- Follow-up
- Median 13.2 years
Methodological detailsintegrative proteomic analysis, mediation modeling
- Integrative proteomic analysis
- Mediation modeling
Main finding
Overall GI disease risk
Adjusted hazard ratio
1.91
95% CI 1.84–2.00
Stage 4vs Stage 0
adjusted HR 1.91 (95% CI 1.84–2.00)
As reported in the abstract
- GI cases
- 81,168
- Population attributable fraction of CKM stages 1-4
- 27.1%
Observational data: associations, not effects.
Further findings
Subgroups by sex and age
- Associations stronger in females and individuals < 60 years, except higher male susceptibility to colorectal cancer
Proteomic mediation
- Immune-inflammatory networks underpinned functional and inflammatory diseases; GI cancers enriched in pro-proliferative pathways
- HGF, GDF15 and PLAUR emerged as core shared targets
Original publication
Cardiovascular-kidney-metabolic syndrome stages and risk of diverse gastrointestinal diseases: a prospective cohort study and integrative proteomic analysis. Diabetes Res Clin Pract. Published 16 April 2026. doi:10.
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