Association of triglyceride–glucose and obesity-derived indices with the risk of aortic stenosis among individuals in cardiovascular–kidney–metabolic syndrome stages 0–3: a prospective cohort study from the UK Biobank

Q: What are the key findings of this study?

Elevated triglyceride-glucose-related indices, particularly TyG-WHtR, were independently associated with a 65% increased risk of incident aortic stenosis (HR 1.65) in the highest versus lowest tertile.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 (n=363907). Intervention: Triglyceride-glucose (TyG) and obesity-related indices (particularly TyG-WHtR) vs. Lowest tertile of TyG-related indices. Primary outcome: Incident aortic stenosis (HR 1.65, 95% CI 1.49-1.83, p=<0.001).

Q: What does this research mean for the field?

Triglyceride-glucose (TyG) and its obesity-related indices, particularly TyG-WHtR, are independently associated with an increased risk of incident aortic stenosis in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the prospective associations between triglyceride-glucose (TyG) and obesity-derived indices with the risk of incident aortic stenosis across stages 0–3 of cardiovascular–kidney–metabolic syndrome.

Jiacheng Ding; Xinyu Cai; Li J; Yiyin Gao

doi:10.3389/fendo.2026.1844215

July 7, 2026Frontiers in EndocrinologyOpen Access

Association of triglyceride–glucose and obesity-derived indices with the risk of aortic stenosis among individuals in cardiovascular–kidney–metabolic syndrome stages 0–3: a prospective cohort study from the UK Biobank

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Key result

Elevated triglyceride-glucose indices, especially TyG-WHtR, are linked to ~65% higher aortic stenosis risk.

HR 1.65
95% CI 1.49-1.83
P<0.001
n=363,907

Figures

Why the study?

The association between triglyceride-glucose and its obesity-related derivatives and the risk of aortic stenosis in cardiovascular-kidney-metabolic syndrome stages 0-3 remains unclear.

Do elevated triglyceride-glucose and obesity-derived indices increase the risk of incident aortic stenosis in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3?

Key Points

To evaluate the prospective associations between triglyceride-glucose (TyG) and obesity-derived indices with the risk of incident aortic stenosis across stages 0–3 of cardiovascular–kidney–metabolic syndrome.
Prospective cohort study analyzing 363,907 individuals with CKM stages 0–3 from the UK Biobank over a median follow-up of 15.25 years.
Evaluated six TyG-related indices (TyG, TyG-BMI, TyG-Waist, TyG-WHR, TyG-WHtR, and TyG-ABSI) using Cox proportional hazards and competing risk models.
Performed mediation analysis to examine the contribution of systolic blood pressure and calculated C-index and net reclassification improvement to assess predictive value.
Across 15.25 years of follow-up, 3,326 incident aortic stenosis events occurred, with each 1-SD increment in indices increasing risk by 8% to 24% in competing risk models (TyG: 8%, 95% CI: 4–11%; TyG-BMI: 24%, 95% CI: 20–27%; TyG-WHtR: 21%, 95% CI: 17–25%).
Compared to the lowest tertile, the highest tertile conferred significant risk elevations: TyG (HR 1.21, 95% CI: 1.11–1.32), TyG-BMI (HR 1.77, 95% CI: 1.61–1.95), TyG-Waist (HR 1.67, 95% CI: 1.50–1.86), TyG-WHR (HR 1.44, 95% CI: 1.29–1.61), TyG-WHtR (HR 1.65, 95% CI: 1.49–1.83), and TyG-ABSI (HR 1.13, 95% CI: 1.02–1.25).
Systolic blood pressure mediated 12.1% to 18.1% of the observed associations, while TyG-WHtR provided the greatest predictive enhancement (C-index: 0.806, 95% CI: 0.800–0.811; NRI: 0.308, 95% CI: 0.198–0.354).

Study Design

Type

Cohort (n=363,907)

Multicenter

Yes

Structured PICO

Do elevated triglyceride-glucose and obesity-derived indices increase the risk of incident aortic stenosis in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3?

P

Population

363,907 adults aged 40-69 years with cardiovascular-kidney-metabolic syndrome stages 0-3 from the UK Biobank, free of prior valvular disease, followed for a median of 15.25 years.

E

Exposure

Higher levels of six triglyceride-glucose (TyG)-related indices (TyG, TyG-BMI, TyG-Waist, TyG-WHR, TyG-WHtR, and TyG-ABSI) evaluated continuously (per 1-SD increment) and categorically (highest tertiles).

C

Comparator

Lowest tertile of the respective TyG-related indices.

O

Outcome

Incident aortic stenosis (AS) ascertained using hospital diagnosis records linked to ICD-10 codes I35.0 and I35.2.hard clinical

Main Result

Hazard Ratio: 1.65 (95% CI 1.49–1.83)

p-value: p=<0.001

Elevated triglyceride-glucose and obesity-derived indices, particularly TyG-WHtR, are independently associated with an increased risk of incident aortic stenosis in individuals with early-stage cardiovascular-kidney-metabolic syndrome.

Limitations

Observational study design cannot establish causality
Potential for residual confounding despite extensive adjustments

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Implication

TyG-WHtR may aid risk stratification in CKM syndrome; extends TyG markers to aortic stenosis but remains hypothesis-generating.

Abstract

Background Cardiovascular-kidney-metabolic (CKM) syndrome emphasizes the interplay between metabolic dysfunction, kidney injury, and cardiovascular abnormalities. The triglyceride-glucose (TyG) and its obesity-related derivatives have emerged as simple biomarkers for insulin resistance, yet their association with aortic stenosis (AS) risk in CKM syndrome stages 0–3 remains unclear. Methods This prospective cohort study included 363,907 participants with CKM stages 0–3 from the UK Biobank. We calculated six TyG-related indices (TyG, TyG-BMI, TyG-Waist, TyG-WHR, TyG-WHtR, and TyG-ABSI) 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), and incremental predictive value was evaluated using C-index and net reclassification index (NRI). Results During 15.25 years of follow-up, 3,326 AS cases occurred. After full adjustment, each 1-SD increment in TyG-related indices was associated with 8-24% increased AS risk. Compared with the lowest tertile, the highest tertile showed 1.13-1.77-fold increased risk. All indices demonstrated linear dose-response relationships with AS. SBP mediated 12.1-18.1% of these associations. TyG-WHtR showed the greatest predictive improvement (C-index: 0.806; NRI: 0.308). Conclusions TyG-related indices, particularly TyG-WHtR, are independently associated with AS risk in CKM syndrome stages 0-3, offering potential for early risk stratification and targeted prevention strategies.

Discussion

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Cite This Study

Ding et al. (2026) conducted a cohort in Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 (n=363,907). Triglyceride-glucose (TyG) and obesity-related indices (particularly TyG-WHtR) vs. Lowest tertile of TyG-related indices was evaluated on Incident aortic stenosis (HR 1.65, 95% CI 1.49-1.83, p=<0.001). Elevated triglyceride-glucose-related indices, particularly TyG-WHtR, were independently associated with a 65% increased risk of incident aortic stenosis (HR 1.65) in the highest versus lowest tertile.

synapsesocial.com/papers/6a556b224f0a0bb1c9a1c0dc https://doi.org/10.3389/fendo.2026.1844215

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Association of triglyceride–glucose and obesity-derived indices with the risk of aortic stenosis among individuals in cardiovascular–kidney–metabolic syndrome stages 0–3: a prospective cohort study from the UK Biobank

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Association of triglyceride–glucose and obesity-derived indices with the risk of aortic stenosis among individuals in cardiovascular–kidney–metabolic syndrome stages 0–3: a prospective cohort study from the UK Biobank

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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