Relation of advanced cardiovascular-kidney-metabolic syndrome with mortality risk in cancer survivors: joint effect and mediating role of PhenoAge acceleration
Main finding · All-cause mortalityResult — go to the resultHazard ratio 2.319 95% CI 1.926–2.793Authors' conclusion
Advanced CKM and PAA were independently associated with mortality, while their coexistence further increased cardiovascular mortality. Joint assessment may improve cardiometabolic risk stratification and preventive care.
Study context
- Population
- Cancer survivors from NHANES 1999–2010 and 2015–2018cancer survivors analyzed
- Participants
- 2,781 survivors
- Exposure
- Advanced CKM and PhenoAge acceleration (PAA), individually and jointly, in relation to mortality
- Outcome
- All-cause mortality
Methodological detailsCox regression, restricted cubic splines, joint exposure, additive interaction, subgroup analyses, mediation analyses
- Cox regression
- Restricted cubic splines
- Joint exposure
- Additive interaction
- Subgroup analyses
- Mediation analyses
Main finding
As reported in the abstract
Hazard ratio
2.319
95% CI 1.926–2.793
Advanced CKMvs Neither exposure
HR 2.319 (95% CI 1.926–2.793)
Observational data: associations, not effects.
Further findings
| Outcome | HR (95% CI) | |
|---|---|---|
| Cancer-specific mortalityAdvanced CKMvs Neither exposureNo longer significant after adjusting for continuous age | 1.627 (1.215–2.181) | |
| Cardiovascular mortalityAdvanced CKMvs Neither exposureAttenuated after adjusting for continuous age | 4.469 (2.695–7.410) | |
| Cardiovascular mortality, joint exposureCoexisting advanced CKM and PAAvs Neither exposureHighest cardiovascular mortality risk | 9.026 (5.505–14.800) | |
| 0.050.21520Hazard ratio (log scale) |
Additive interaction for cardiovascular mortality
- RERI
- 4.36 [1.42-7.30]
- AP
- 0.48 [0.29-0.67]
- SI
- 2.19 [1.38-3.48]
- A positive additive interaction was observed
Mediation by PAA
- Proportion of association of advanced CKM with all-cause mortality via PAA
- 17.0%
- Proportion of association of advanced CKM with cardiovascular mortality via PAA
- 4.7%
- Both P < 0.05
Original publication
Relation of advanced cardiovascular-kidney-metabolic syndrome with mortality risk in cancer survivors: joint effect and mediating role of PhenoAge acceleration. Diabetes Res Clin Pract. Published 7 November 2026. doi:10.
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