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Peer-reviewedCC BY-NC-NDCardiovascular diabetology

Associations of baseline levels, cumulative exposure, and two-wave patterns of the combined triglyceride-glucose index and frailty index with progression from cardiovascular-kidney-metabolic syndrome stages 0-2 to stages 3-4 and stage 4: a prospective cohort study from CHARLS.

  • Hailan Xiong1
  • Yushan Lei2,3
  • Jing Zhou4
  • Jiawang Zou5,6
6 affiliations
  1. 1Department of Cardiology, Jiujiang City Key Laboratoryof Cell Therapy, JiuJiang NO.1 People's Hospital, Jiujiang, Jiangxi, 332000, China.
  2. 2Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107 Yan Jiang West Road, Guangzhou, 510120, China.
  3. 3The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, 510120, China.
  4. 4Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107 Yan Jiang West Road, Guangzhou, 510120, China. [email protected].
  5. 5Department of Cardiology, Jiujiang City Key Laboratoryof Cell Therapy, JiuJiang NO.1 People's Hospital, Jiujiang, Jiangxi, 332000, China. [email protected].
  6. 6Department of Endocrinology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No.107 Yan Jiang West Road, Guangzhou, 510120, China. [email protected].
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Abstract

Background

The triglyceride-glucose index (TyG) and frailty index (FI) reflect metabolic dysregulation and multisystem vulnerability, respectively. However, the associations of the combined triglyceride-glucose index and frailty index (TyG-FI), its cumulative exposure, and two-wave patterns with progression from cardiovascular-kidney-metabolic (CKM) syndrome stages 0-2 to stages 3-4 and stage 4 remain unclear.Methods

This CHARLS cohort study included 3,473 adults with CKM stages 0-2 at Wave 1 and repeat exposure and outcome assessments at Wave 3. TyG-FI was calculated as TyG × FI. Estimated cumulative TyG-FI combined the two measurements and their time interval; K-means clustering identified three two-wave patterns. Cox regression evaluated baseline TyG-FI, and logistic regression evaluated cumulative exposure and two-wave patterns. Discrimination, internal K-fold cross-validation, and sensitivity analyses were assessed.Results

At Wave 3, 319 participants met CKM stage 4 criteria and 975 met CKM stages 3-4 criteria. In fully adjusted models, baseline TyG-FI was associated with stage 4 (HR per SD, 1.33; 95% CI, 1.20-1.47) and stages 3-4 (HR, 1.10; 95% CI, 1.03-1.18). The corresponding ORs for estimated cumulative TyG-FI were 1.83 (95% CI, 1.62-2.06) and 1.42 (95% CI, 1.29-1.56); highest-versus-lowest-tertile ORs were 12.40 (95% CI, 7.43-20.67) and 2.38 (95% CI, 1.86-3.04). TyG-FI pattern Class 3 was associated with stage 4 (OR, 5.93; 95% CI, 3.88-9.07) and stages 3-4 (OR, 2.30; 95% CI, 1.67-3.17). Spline associations were nonlinear. Baseline TyG-FI AUCs were 0.67 and 0.57 for the respective endpoints, with similar performance to FI.Conclusions

Higher baseline TyG-FI was associated with subsequent CKM progression, while cumulative TyG-FI and two-wave patterns were associated with progression status at follow-up. TyG-FI may provide an accessible composite measure for identifying individuals with early CKM syndrome who are at increased risk of advanced-stage progression.

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Cite

BibTeXRIS
BibTeX
@article{xiong2026associations,
  title = {{Associations of baseline levels, cumulative exposure, and two-wave patterns of the combined triglyceride-glucose index and frailty index with progression from cardiovascular-kidney-metabolic syndrome stages 0-2 to stages 3-4 and stage 4: a prospective cohort study from CHARLS.}},
  author = {Hailan Xiong and Yushan Lei and Jing Zhou and Jiawang Zou},
  journal = {Cardiovascular diabetology},
  year = {2026},
  month = oct,
  doi = {10.1186/s12933-026-03411-w},
  url = {https://europepmc.org/article/MED/42958256},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Associations of baseline levels, cumulative exposure, and two-wave patterns of the combined triglyceride-glucose index and frailty index with progression from cardiovascular-kidney-metabolic syndrome stages 0-2 to stages 3-4 and stage 4: a prospective cohort study from CHARLS.
AU  - Hailan Xiong
AU  - Yushan Lei
AU  - Jing Zhou
AU  - Jiawang Zou
PY  - 2026
DA  - 2026/10/16
JO  - Cardiovascular diabetology
DO  - 10.1186/s12933-026-03411-w
UR  - https://europepmc.org/article/MED/42958256
AB  - Background  The triglyceride-glucose index (TyG) and frailty index (FI) reflect metabolic dysregulation and multisystem vulnerability, respectively. However, the associations of the combined triglyceride-glucose index and frailty index (TyG-FI), its cumulative exposure, and two-wave patterns with progression from cardiovascular-kidney-metabolic (CKM) syndrome stages 0-2 to stages 3-4 and stage 4 remain unclear.Methods  This CHARLS cohort study included 3,473 adults with CKM stages 0-2 at Wave 1 and repeat exposure and outcome assessments at Wave 3. TyG-FI was calculated as TyG × FI. Estimated cumulative TyG-FI combined the two measurements and their time interval; K-means clustering identified three two-wave patterns. Cox regression evaluated baseline TyG-FI, and logistic regression evaluated cumulative exposure and two-wave patterns. Discrimination, internal K-fold cross-validation, and sensitivity analyses were assessed.Results  At Wave 3, 319 participants met CKM stage 4 criteria and 975 met CKM stages 3-4 criteria. In fully adjusted models, baseline TyG-FI was associated with stage 4 (HR per SD, 1.33; 95% CI, 1.20-1.47) and stages 3-4 (HR, 1.10; 95% CI, 1.03-1.18). The corresponding ORs for estimated cumulative TyG-FI were 1.83 (95% CI, 1.62-2.06) and 1.42 (95% CI, 1.29-1.56); highest-versus-lowest-tertile ORs were 12.40 (95% CI, 7.43-20.67) and 2.38 (95% CI, 1.86-3.04). TyG-FI pattern Class 3 was associated with stage 4 (OR, 5.93; 95% CI, 3.88-9.07) and stages 3-4 (OR, 2.30; 95% CI, 1.67-3.17). Spline associations were nonlinear. Baseline TyG-FI AUCs were 0.67 and 0.57 for the respective endpoints, with similar performance to FI.Conclusions  Higher baseline TyG-FI was associated with subsequent CKM progression, while cumulative TyG-FI and two-wave patterns were associated with progression status at follow-up. TyG-FI may provide an accessible composite measure for identifying individuals with early CKM syndrome who are at increased risk of advanced-stage progression.
SN  - 1475-2840
ER  -