Objective:

To evaluate the association between triglyceride-glucose (TyG) levels, obesity-related metrics, and aortic stenosis (AS) risk in individuals with cardiovascular–kidney–metabolic (CKM) syndrome stages 0–3.

Approach:

• Study Design: Prospective cohort study involving 363,907 participants from the UK Biobank.
• Data Analysis: Calculated six TyG-related indices and evaluated their associations with incident AS using Cox proportional hazards and competing risk models.
• Mediation Analysis: Assessed the role of systolic blood pressure (SBP) in the associations.
• Predictive Value Evaluation: Used C-index and net reclassification index (NRI) to evaluate incremental predictive value.

Key Findings:

• During 15.25 years of follow-up, 3,326 AS cases occurred.
• Each 1-SD increment in TyG-related indices was associated with an 8-24% increased AS risk after full adjustment.
• The highest tertile of TyG-related indices showed a 1.13-1.77-fold increased risk compared to the lowest tertile after full adjustment.
• All indices demonstrated linear dose-response relationships with AS.
• SBP mediated 12.1-18.1% of the associations.
• TyG-WHtR showed the greatest predictive improvement (C-index: 0.806; NRI: 0.308).

Interpretation:

TyG-related indices, particularly TyG-WHtR, are associated with AS risk in CKM syndrome stages 0-3.

Conclusion:

TyG-related indices may offer insights into aortic stenosis risk.