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Peer-reviewedCC BY-NC-ND 4.0Cardiovascular Diabetology

Stress-hyperglycemia ratio, frailty index, and their product in relation to incident cardiometabolic multimorbidity comprising diabetes, heart disease, and stroke: a longitudinal analysis of CHARLS

  1. 1Jiangxi Key Laboratory of Neurological Diseases, Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi China
  2. 2Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, Jiangxi China

Abstract

Background: Cardiometabolic multimorbidity (CMM), encompassing the co-occurrence of major cardiometabolic conditions such as diabetes, heart disease, and stroke, is a major source of disability and premature mortality in ageing populations. The stress-hyperglycemia ratio (SHR) captures glycemic dysregulation relative to long-term glycemic exposure, whereas the frailty index (FI) quantifies accumulated health deficits. We evaluated whether SHR, FI, and their composite product (SHR-FI), assessed at baseline and across two survey waves, were associated with incident CMM.

Methods: We conducted a prospective analysis of 6,096 participants from the China Health and Retirement Longitudinal Study who were free of CMM at baseline. SHR, FI, and SHR-FI were assessed at Waves 1 and 3. Time-weighted two-wave summaries and data-derived two-time-point longitudinal patterns were evaluated; cumulative and pattern analyses used Wave 3 as a landmark. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline, subgroup, receiver operating characteristic, decision-curve, joint-model, landmark, and sensitivity analyses were performed.

Results: During the Wave 1-anchored follow-up, 527 participants developed CMM. In fully adjusted models, each SD increase in baseline SHR, FI, and SHR-FI was associated with HRs of 1.09 (95% CI, 1.01–1.18), 1.36 (1.26–1.48), and 1.35 (1.26–1.45), respectively. Associations were stronger for cumulative FI and cumulative SHR-FI: the HRs per SD increase were 1.60 (1.48–1.73) and 1.55 (1.44–1.66). The AUCs were 0.68 for baseline FI and SHR-FI and 0.72 and 0.73 for cumulative FI and SHR-FI, respectively. FI accounted for most of the observed discrimination, while SHR-FI showed a modest complementary signal. Landmark analyses beginning at Wave 3 produced directionally consistent cumulative FI and SHR-FI associations.

Conclusions: Higher SHR, greater FI, and a higher SHR-FI product were associated with incident CMM. FI provided most of the observed discrimination, and SHR-FI offered limited additional information in this cohort. Two-wave cumulative summaries and longitudinal patterns may support research-oriented risk stratification, but their clinical value requires calibration, internal validation, and external validation.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12933-026-03414-7.

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BibTeX
@article{liu2026stresshyperglycemia,
  title = {{Stress-hyperglycemia ratio, frailty index, and their product in relation to incident cardiometabolic multimorbidity comprising diabetes, heart disease, and stroke: a longitudinal analysis of CHARLS}},
  author = {Shuheng Liu and Guangbin Xie and Yi Lei and Wenqiang Xin},
  journal = {Cardiovascular Diabetology},
  year = {2026},
  month = oct,
  doi = {10.1186/s12933-026-03414-7},
  url = {https://doi.org/10.1186/s12933-026-03414-7},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Stress-hyperglycemia ratio, frailty index, and their product in relation to incident cardiometabolic multimorbidity comprising diabetes, heart disease, and stroke: a longitudinal analysis of CHARLS
AU  - Shuheng Liu
AU  - Guangbin Xie
AU  - Yi Lei
AU  - Wenqiang Xin
PY  - 2026
DA  - 2026/10/20
JO  - Cardiovascular Diabetology
DO  - 10.1186/s12933-026-03414-7
UR  - https://doi.org/10.1186/s12933-026-03414-7
AB  - Background: Cardiometabolic multimorbidity (CMM), encompassing the co-occurrence of major cardiometabolic conditions such as diabetes, heart disease, and stroke, is a major source of disability and premature mortality in ageing populations. The stress-hyperglycemia ratio (SHR) captures glycemic dysregulation relative to long-term glycemic exposure, whereas the frailty index (FI) quantifies accumulated health deficits. We evaluated whether SHR, FI, and their composite product (SHR-FI), assessed at baseline and across two survey waves, were associated with incident CMM.  Methods: We conducted a prospective analysis of 6,096 participants from the China Health and Retirement Longitudinal Study who were free of CMM at baseline. SHR, FI, and SHR-FI were assessed at Waves 1 and 3. Time-weighted two-wave summaries and data-derived two-time-point longitudinal patterns were evaluated; cumulative and pattern analyses used Wave 3 as a landmark. Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs). Restricted cubic spline, subgroup, receiver operating characteristic, decision-curve, joint-model, landmark, and sensitivity analyses were performed.  Results: During the Wave 1-anchored follow-up, 527 participants developed CMM. In fully adjusted models, each SD increase in baseline SHR, FI, and SHR-FI was associated with HRs of 1.09 (95% CI, 1.01–1.18), 1.36 (1.26–1.48), and 1.35 (1.26–1.45), respectively. Associations were stronger for cumulative FI and cumulative SHR-FI: the HRs per SD increase were 1.60 (1.48–1.73) and 1.55 (1.44–1.66). The AUCs were 0.68 for baseline FI and SHR-FI and 0.72 and 0.73 for cumulative FI and SHR-FI, respectively. FI accounted for most of the observed discrimination, while SHR-FI showed a modest complementary signal. Landmark analyses beginning at Wave 3 produced directionally consistent cumulative FI and SHR-FI associations.  Conclusions: Higher SHR, greater FI, and a higher SHR-FI product were associated with incident CMM. FI provided most of the observed discrimination, and SHR-FI offered limited additional information in this cohort. Two-wave cumulative summaries and longitudinal patterns may support research-oriented risk stratification, but their clinical value requires calibration, internal validation, and external validation.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12933-026-03414-7.
SN  - 1475-2840
ER  -