Short-term trajectories of TyG-WHtR and hs-CRP and their joint impact on stroke risk in early CKM syndrome: evidence from Chinese national cohort

Stroke is a major outcome of cardiovascular–kidney–metabolic (CKM) syndrome, but evidence on the longitudinal interplay between metabolic dysfunction and systemic inflammation remains limited. We analyzed 4,614 participants with early-stage CKM syndrome from the China Health and Retirement Longitudinal Study (CHARLS). The triglyceride–glucose waist-to-height ratio (TyG-WHtR) and high-sensitivity C-reactive protein (hs-CRP) were measured in 2011 and 2015. Latent class mixed models identified distinct short-term trajectories, and Cox regression estimated hazard ratios (HRs) for incident stroke and all-cause mortality from 2015 to 2020. During follow-up, 445 strokes and 164 deaths occurred. Higher baseline TyG-WHtR (HR, 1.57; 95% CI, 1.26–1.97) and hs-CRP (HR for Q4 vs. Q1, 1.67; 95% CI, 1.06–2.64) predicted greater stroke risk, while associations with mortality were weaker. Participants with both markers elevated had the highest stroke risk (HR, 1.83; 95% CI, 1.38–2.44). Trajectory analyses identified three distinct patterns for each biomarker. Compared with the low-stable group, high TyG-WHtR (HR, 1.87; 95% CI, 1.32–2.63) and high hs-CRP (HR, 1.49; 95% CI, 1.15–1.91) trajectories conferred significantly increased stroke risk. Joint trajectory analysis showed that participants with persistently elevated hs-CRP and historically high TyG-WHtR (Class 3) had the greatest risk (HR, 1.66; 95% CI, 1.22–2.26), whereas Class 2 (moderate and rising levels) did not differ significantly from the low-risk group. No trajectory was significantly associated with mortality. Both baseline and unfavorable short-term trajectories of TyG-WHtR and hs-CRP independently predict stroke but not all-cause mortality in early CKM populations. Concurrent metabolic and inflammatory burden markedly amplifies cerebrovascular risk, underscoring the importance of dynamic biomarker monitoring for early risk stratification and precision prevention.