Diabetes Research and Clinical Practice · Nov 7, 2026

Relation of advanced cardiovascular-kidney-metabolic syndrome with mortality risk in cancer survivors: joint effect and mediating role of PhenoAge acceleration

By Wu J, Kang Z, Wu D et al.

Aims We assessed mortality associations of advanced cardiovascular-kidney-metabolic syndrome (CKM) and PhenoAge acceleration (PAA), individually and jointly, among cancer survivors. Outcomes were all-cause, cancer-specific, and cardiovascular mortality; mediation by PAA was also evaluated. Methods We analyzed 2,781 cancer survivors from NHANES 1999–2010 and 2015–2018 using Cox regression, restricted cubic splines, joint exposure, additive interaction, subgroup, and mediation analyses. Results Advanced CKM was associated with all-cause, cancer-specific, and cardiovascular mortality (HRs 2.319 [95% CI 1.926–2.793], 1.627 [1.215–2.181], and 4.469 [2.695–7.410], respectively). After adjusting for continuous age, these associations were attenuated, and the association with cancer-specific mortality was no longer significant. Compared with neither exposure, coexisting advanced CKM and PAA conferred the highest cardiovascular mortality risk (HR 9.026 [95% CI 5.505–14.800]). A positive additive interaction was observed for cardiovascular mortality (RERI 4.36 [1.42–7.30]; AP 0.48 [0.29–0.67]; SI 2.19 [1.38–3.48]). The indirect effects via PAA accounted for 17.0% and 4.7% of the associations of advanced CKM with all-cause and cardiovascular mortality, respectively (both P < 0.05). Conclusions 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.

doi.org/10.1016/j.diabres.2026.113647PubMed 42998724Populations