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Background <p>Previous studies have revealed the relationships of separated C-reactive protein-triglyceride glucose (CTI) levels and the frailty index (FI) with stroke. However, the impact of combined CTI and FI (CTI-FI) on stroke incidence is unclear, especially among those with cardiovascular kidney metabolic (CKM) syndrome stages 0–3.</p> Objective <p>This research aimed to validate the associations between different CTI-FI dimensions (baseline CTI-FI, cumulative CTI-FI (cuCTI-FI), and dynamic trajectories of CTI-FI (traCTI-FI)) and stroke risk among individuals with CKM syndrome stages 0–3.</p> Methods <p>The enrolled participants and the utilized data were derived from five waves of the China Health and Retirement Longitudinal Study. K-means clustering was used to categorize participants into an appropriate number of clusters. Cox regression analysis, restricted cubic spline (RCS) curves, and Kaplan-Meier (K-M) survival curves were used to evaluate the relationships between different CTI-FI dimensions and stroke risk. Receiver operating characteristic (ROC) curves and the DeLong test were constructed to assess the performance of various dimensions of CTI-FI in predicting stroke.</p> Results <p>In this study, the mean age of the 5293 participants was 57.94 years, and 53.45% were female. During the nearly 9-year follow-up period, 540 (10.20%) stroke events occurred. A 61% and 41% increase in stroke risk was associated with each 1-unit increase in the baseline CTI-FI and cuCTI-FI, respectively. The RCS modeling further revealed significant positive nonlinear associations between baseline CTI-FI (<i>P</i><sub>overall</sub> &lt; 0.001, <i>P</i><sub>nonlinear</sub> = 0.049) and cuCTI (<i>P</i><sub>overall</sub> &lt; 0.001, <i>P</i><sub>nonlinear</sub> = 0.047) and stroke incidence. Compared with the lowest different dimensions CTI-FI level groups, the highest level groups had a greater stroke risk. The fully adjusted HRs (95% CIs) were as follows: baseline CTI-FI (Q4 vs. Q1), 2.36 (1.76, 3.15); cuCTI-FI (Q3 vs. Q1), 4.75 (2.73, 8.27); and traCTI-FI (Cluster 3 vs. Cluster 1), 6.24 (3.72, 10.46). In terms of predicting stroke risk, baseline CTI-FI, cuCTI-FI, and traCTI-FI performed better than CTI and FI, and cuCTI-FI and traCTI-FI performed significantly better than baseline CTI-FI (<i>P</i> &lt; 0.001 and = 0.022, respectively).</p> Conclusion <p>Persistently high CTI-FI is associated with increased stroke risk. CTI-FI, especially cuCTI-FI and traCTI-FI, are potent predictors of stroke. Long-term surveillance of CTI-FI alterations and maintenance of its low levels is clinically important for early stroke detection and prevention in patients with stages 0–3 CKM syndrome.</p> Graphical abstract <p></p>

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Associations of the combined C-reactive protein-triglyceride glucose index and frailty index in different dimensions with incident stroke among individuals with stages 0–3 cardiovascular-kidney-metabolic syndrome

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  • 发表日期：

    2026年5月26日

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  • Honglin Zheng,
  • Yao Zhang,
  • Li Li,
  • Mingye Zhu,
  • Wei Kong,
  • Jialin Wang,
  • Ruxi Liu,
  • Fang Wang

摘要

Background

Previous studies have revealed the relationships of separated C-reactive protein-triglyceride glucose (CTI) levels and the frailty index (FI) with stroke. However, the impact of combined CTI and FI (CTI-FI) on stroke incidence is unclear, especially among those with cardiovascular kidney metabolic (CKM) syndrome stages 0–3.

Objective

This research aimed to validate the associations between different CTI-FI dimensions (baseline CTI-FI, cumulative CTI-FI (cuCTI-FI), and dynamic trajectories of CTI-FI (traCTI-FI)) and stroke risk among individuals with CKM syndrome stages 0–3.

Methods

The enrolled participants and the utilized data were derived from five waves of the China Health and Retirement Longitudinal Study. K-means clustering was used to categorize participants into an appropriate number of clusters. Cox regression analysis, restricted cubic spline (RCS) curves, and Kaplan-Meier (K-M) survival curves were used to evaluate the relationships between different CTI-FI dimensions and stroke risk. Receiver operating characteristic (ROC) curves and the DeLong test were constructed to assess the performance of various dimensions of CTI-FI in predicting stroke.

Results

In this study, the mean age of the 5293 participants was 57.94 years, and 53.45% were female. During the nearly 9-year follow-up period, 540 (10.20%) stroke events occurred. A 61% and 41% increase in stroke risk was associated with each 1-unit increase in the baseline CTI-FI and cuCTI-FI, respectively. The RCS modeling further revealed significant positive nonlinear associations between baseline CTI-FI (Poverall < 0.001, Pnonlinear = 0.049) and cuCTI (Poverall < 0.001, Pnonlinear = 0.047) and stroke incidence. Compared with the lowest different dimensions CTI-FI level groups, the highest level groups had a greater stroke risk. The fully adjusted HRs (95% CIs) were as follows: baseline CTI-FI (Q4 vs. Q1), 2.36 (1.76, 3.15); cuCTI-FI (Q3 vs. Q1), 4.75 (2.73, 8.27); and traCTI-FI (Cluster 3 vs. Cluster 1), 6.24 (3.72, 10.46). In terms of predicting stroke risk, baseline CTI-FI, cuCTI-FI, and traCTI-FI performed better than CTI and FI, and cuCTI-FI and traCTI-FI performed significantly better than baseline CTI-FI (P < 0.001 and = 0.022, respectively).

Conclusion

Persistently high CTI-FI is associated with increased stroke risk. CTI-FI, especially cuCTI-FI and traCTI-FI, are potent predictors of stroke. Long-term surveillance of CTI-FI alterations and maintenance of its low levels is clinically important for early stroke detection and prevention in patients with stages 0–3 CKM syndrome.

Graphical abstract