Cardiometabolic & kidneyCohort study

Cardiovascular-Kidney-Metabolic Syndrome Staging and Cancer Risk

JACC CardioOncolPublished

  • Prospective cohort study
  • multiomics mediation analysis

Authors' conclusion

CKM staging is associated with incremental cancer risk and stage-specific immune-metabolic pathways, highlighting potential prevention targets.

Study context

Population
UK Biobank participants
Exposure
Cardiovascular-kidney-metabolic (CKM) stages 1–4 vs stage 0
Outcome
Overall cancer incidence

Main finding

As reported in the abstract

Overall cancer risk
  • Overall cancer risk increased stepwise from CKM stages 1 to 3, with slight attenuation but persistent elevation in stage 4

Observational data: associations, not effects.

Further findings

Stage-specific proteomic mediators and mechanisms

Stage 1: leukocyte/lymphocyte activation and cell-cell adhesion
Stage 2: T cell-related immunity and emerging immune tolerance induction
Stage 3: emerging natural killer (NK) cell tolerance induction and respiratory burst in the inflammatory response
Stage 4: dominant NK cell tolerance induction and tissue-resident chronic pathology

Metabolomic mediation

Dominant metabolomic mediation evolved from high-density lipoproteins (HDLs) and triglyceride-rich lipoproteins (TRLs) to low-density lipoproteins (LDLs)

Original publication

Cardiovascular-Kidney-Metabolic Syndrome Staging and Cancer Risk. JACC CardioOncol. Published 14 July 2026. doi:10.1016/j.jaccao.2026.05.012

Summarised from the published abstract; every number is checked against it