Joint association of Insulin resistance and frailty index with incident atherosclerotic cardiovascular disease (ASCVD) and major adverse cardiovascular events (MACE) in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3: a multi-cohort study
Authors' conclusion
The IR-FI are significantly associated with the incidence of cardiovascular events, an association that appears to be mediated through systemic inflammatory pathways.
Study context
- Population
- Individuals with Cardiovascular-Kidney-Metabolic (CKM) syndrome stages 0–3 from the UK Biobank and the China Health and Retirement Longitudinal Study (CHARLS)259,714 UK Biobank (UKB)
- Exposure
- Higher vs lower composite IR-FI indices
- Outcome
- UKB: incident ASCVD and MACE (co-primary)
Methodological detailsUK Biobank and CHARLS cohorts
- UK Biobank and CHARLS cohorts
Main finding
As reported in the abstract
ASCVD and MACE (UKB)
- Elevated IR-FI associated with increased risks of ASCVD and MACE in the UKB
- Significant positive nonlinear relationships of METS-IR-FI and eGDR-FI with CV outcomes
Observational data: associations, not effects.
Secondary outcomes
CVD, heart disease and stroke (CHARLS)
- Consistent findings for CVD, heart disease and stroke in the CHARLS
Mediation by inflammatory markers
- C-reactive protein, neutrophils and leucocytes partially mediated the associations (ratio range)
- 1.5-12%
Proteomic analyses
- Cytokine-cytokine receptor interaction identified as primary regulatory hub; leukocyte migration, chemotaxis and neutrophil degranulation as central pathological mechanisms
Original publication
Joint association of Insulin resistance and frailty index with incident ASCVD and MACE in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3: a multi-cohort study. Cardiovasc Diabetol. Published 6 July 2026. doi:10.
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