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Peer-reviewedCC BY 4.0Frontiers in Cardiovascular Medicine

Associations of insulin resistance surrogates with cardiovascular disease in early stage cardiovascular–kidney–metabolic syndrome: a prospective cohort study

  • Ao Li1
  • Shiyu Tian2
  • Jianjun Zhang2,3
  • Dong Zhang4
  • Jie Xu5
  • Xianyun Wang2
  • Hongxuan Yan6
  • Xiaohui Sun2,7
  • Feng Ning1,2,7
  • Lei Zhang8
8 affiliations
  1. 1Department of Epidemiology and Health Statistics, Qingdao Medical College, Qingdao University
  2. 2Qingdao Centers for Disease Control and Prevention
  3. 3Qingdao Municipal Health Big Data Center
  4. 4Huangdao Centers for Disease Control and Prevention
  5. 5Department of Rehabilitation Medicine, Qingdao Municipal Hospital
  6. 6Qingdao Binhai Medical College
  7. 7Qingdao Prevention Medicine Institute
  8. 8Qingdao Endocrine and Diabetes Hospital
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Abstract

Background: The early stages 0–3 of cardiovascular–kidney–metabolic (CKM) syndrome represent a critical window for cardiovascular disease (CVD) prevention. Although insulin resistance (IR) is a key driver of CVD risk, systematic comparisons of IR surrogates in CVD remain limited. This study examined the associations of 12 IR surrogates with CVD in participants with stages 0–3 CKM syndrome.

Methods: This prospective study included 5,625 participants with stages 0–3 CKM syndrome from the Qingdao Diabetes Program. Twelve IR surrogates related to CVD were evaluated using multivariable-adjusted Cox models, restricted cubic splines, sensitivity analyses, and predictive performance analyses, such as triglyceride–glucose index, atherogenic index of plasma, cardiometabolic index, metabolic score for IR (METS-IR), cholesterol-high-density lipoprotein-glucose (CHG) index, CHG plus body mass index, CHG plus waist circumference, CHG plus waist-to-height ratio, CHG plus body roundness index, CHG plus weight-adjusted waist index, CHG plus A body shape index, and CHG plus Chinese visceral adiposity index (CVAI).

Results: Over a median follow-up of 15.2 years, 1,407 incident CVD events occurred. In multivariable-adjusted analyses, all 12 IR surrogates were significantly associated with CVD risk (all P < 0.05), of CHG-CVAI showing the best performance (Q4 vs. Q1: HR = 2.10, 95% CI = 1.74–2.52). Most indices showed nonlinear dose–response relationships. The associations were higher risk for adults aged <60 years and urban residents as compared with counterparts, and sensitivity analyses confirmed the robustness of the primary findings. Furthermore, addition of each IR surrogate improved CVD risk prediction: C-index ranging from 0.669 to 0.674, NRI ranging from 0.089 to 0.205 and IDI ranging from 0.0004 to 0.0032 (all P < 0.001).

Conclusion: All IR surrogates, particularly CHG-CVAI were independently associated with incident CVD in early-stages CKM syndrome. These simple, low-cost indices improved risk stratification and moderately identify CVD individuals in high risk population.

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Cite

BibTeXRIS
BibTeX
@article{li2026associations,
  title = {{Associations of insulin resistance surrogates with cardiovascular disease in early stage cardiovascular–kidney–metabolic syndrome: a prospective cohort study}},
  author = {Ao Li and Shiyu Tian and Jianjun Zhang and Dong Zhang and Jie Xu and Xianyun Wang and Hongxuan Yan and Xiaohui Sun and Feng Ning and Lei Zhang},
  journal = {Frontiers in Cardiovascular Medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fcvm.2026.1876121},
  url = {https://www.frontiersin.org/articles/10.3389/fcvm.2026.1876121/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Associations of insulin resistance surrogates with cardiovascular disease in early stage cardiovascular–kidney–metabolic syndrome: a prospective cohort study
AU  - Ao Li
AU  - Shiyu Tian
AU  - Jianjun Zhang
AU  - Dong Zhang
AU  - Jie Xu
AU  - Xianyun Wang
AU  - Hongxuan Yan
AU  - Xiaohui Sun
AU  - Feng Ning
AU  - Lei Zhang
PY  - 2026
DA  - 2026/10/20
JO  - Frontiers in Cardiovascular Medicine
DO  - 10.3389/fcvm.2026.1876121
UR  - https://www.frontiersin.org/articles/10.3389/fcvm.2026.1876121/full
AB  - Background: The early stages 0–3 of cardiovascular–kidney–metabolic (CKM) syndrome represent a critical window for cardiovascular disease (CVD) prevention. Although insulin resistance (IR) is a key driver of CVD risk, systematic comparisons of IR surrogates in CVD remain limited. This study examined the associations of 12 IR surrogates with CVD in participants with stages 0–3 CKM syndrome.  Methods: This prospective study included 5,625 participants with stages 0–3 CKM syndrome from the Qingdao Diabetes Program. Twelve IR surrogates related to CVD were evaluated using multivariable-adjusted Cox models, restricted cubic splines, sensitivity analyses, and predictive performance analyses, such as triglyceride–glucose index, atherogenic index of plasma, cardiometabolic index, metabolic score for IR (METS-IR), cholesterol-high-density lipoprotein-glucose (CHG) index, CHG plus body mass index, CHG plus waist circumference, CHG plus waist-to-height ratio, CHG plus body roundness index, CHG plus weight-adjusted waist index, CHG plus A body shape index, and CHG plus Chinese visceral adiposity index (CVAI).  Results: Over a median follow-up of 15.2 years, 1,407 incident CVD events occurred. In multivariable-adjusted analyses, all 12 IR surrogates were significantly associated with CVD risk (all P < 0.05), of CHG-CVAI showing the best performance (Q4 vs. Q1: HR = 2.10, 95% CI = 1.74–2.52). Most indices showed nonlinear dose–response relationships. The associations were higher risk for adults aged <60 years and urban residents as compared with counterparts, and sensitivity analyses confirmed the robustness of the primary findings. Furthermore, addition of each IR surrogate improved CVD risk prediction: C-index ranging from 0.669 to 0.674, NRI ranging from 0.089 to 0.205 and IDI ranging from 0.0004 to 0.0032 (all P < 0.001).  Conclusion: All IR surrogates, particularly CHG-CVAI were independently associated with incident CVD in early-stages CKM syndrome. These simple, low-cost indices improved risk stratification and moderately identify CVD individuals in high risk population.
SN  - 2297-055X
ER  -