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

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. 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. 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. 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). 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.