Triglyceride-glucose index combined with DAS28-ESR predicts cardiovascular disease risk in patients with rheumatoid arthritis: a national multicenter cohort study

Patients with rheumatoid arthritis (RA) face a significantly increased risk of cardiovascular disease (CVD). This study aimed to evaluate the combined association of systemic inflammatory activity and glucose-lipid metabolic abnormalities on long-term CVD outcomes in RA patients and to elucidate the dynamic trajectories of these factors during follow-up and their prognostic implications. This prospective longitudinal cohort study included 4,902 RA patients without baseline CVD. Baseline and follow-up status matrices (G1–G4 groups) were constructed using the triglyceride-glucose (TyG) index and DAS28-ESR score. Multistage nested Cox proportional hazards regression models were employed to assess the adjusted association of combined status and dynamic trajectories on incident CVD. Restricted cubic splines (RCS) quantified nonlinear associations, and the Delta method was used to estimate additive interaction measures. During a maximum 6-year follow-up, 355 incident CVD events occurred (7.24%). In the fully adjusted multifactorial model (Model 3), the baseline dual-high immune-metabolic status group (G4) showed significantly elevated incident CVD risk compared to the dual-low control group (G1) (HR 9.46, 95% CI 3.90–22.96, P < 0.001). Additive interaction analysis indicated a positive additive interaction (relative excess risk due to interaction [RERI] of 3.55; 95% CI, 0.46–6.64), with an AP of 0.38 (95% CI 0.16–0.60), supporting a positive departure from additivity on the relative hazard scale. RCS analysis showed nonlinear associations between both continuous variables and CVD risk ( P < 0.05). Dynamic trajectory analysis showed that persistent dual-high status (G4 → G4) during follow-up was associated with a higher risk of incident CVD (HR 6.95, 95% CI 2.06–23.41, P < 0.001), whereas the G2 → G3 trajectory showed a nonsignificant trend toward an increased risk of CVD (HR 1.24, 95% CI 0.28–5.48; P > 0.05). Baseline dual-high immune-metabolic status and adverse longitudinal trajectories were associated with incident CVD events in patients with RA after multivariable adjustment, with a positive additive interaction observed between high TyG and high DAS28-ESR. These findings support moving beyond an approach focused solely on inflammatory control by jointly considering inflammatory and metabolic status in CVD risk assessment and management.