C-reactive protein-triglyceride-glucose index and diabetes status for risk stratification in stage 4 cardiovascular-kidney-metabolic syndrome with acute decompensated heart failure: a retrospective cohort study.

BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome integrates metabolic dysfunction, kidney disease, and cardiovascular disease. In stage 4 CKM syndrome with acute decompensated heart failure (ADHF), prognosis may be influenced by dysglycaemia, triglyceride-related metabolic disturbance, systemic inflammation, and adiposity-related risk, yet risk stratification remains challenging. We evaluated whether the C-reactive protein-triglyceride-glucose index (CTI), a routinely available inflammatory-metabolic marker, refines risk stratification beyond diabetes status and related inflammatory-metabolic biomarkers in patients with stage 4 CKM syndrome and ADHF. METHODS: This single-centre retrospective cohort included 2,000 eligible patients hospitalized for ADHF with CKM stage 4. CTI was calculated as 0.412 × ln[CRP (mg/L)] + ln[TG (mg/dL) × FPG (mg/dL) / 2]. High CTI was defined using the cohort-specific upper-tertile threshold (CTI ≥ 9.50). Patients were categorized as non-DM + low CTI, non-DM + high CTI, DM + low CTI, or DM + high CTI. Outcomes were all-cause mortality and major adverse cardiac and cerebrovascular events (MACCEs). RESULTS: During a median follow-up of 532 days, 366 deaths (18.3%) and 551 MACCEs (27.6%) occurred. Compared with non-DM + low CTI, non-DM + high CTI was associated with higher risks of all-cause mortality (HR 1.54, 95% CI 1.15-2.06) and MACCEs (HR 1.37, 95% CI 1.08-1.75). DM + low CTI was not significantly associated with either outcome, whereas DM + high CTI had the highest risks of all-cause mortality (HR 1.95, 95% CI 1.47-2.58) and MACCEs (HR 1.91, 95% CI 1.51-2.41). CTI showed approximately linear associations with both outcomes, without significant interaction by diabetes status. Adding CTI to the clinical model plus diabetes status yielded modest improvements in discrimination (ΔC-index = 0.018 for mortality and 0.016 for MACCEs), exceeding those of the evaluated biomarker models. Sensitivity analyses generally supported the primary findings. CONCLUSION: In patients with stage 4 CKM syndrome hospitalized for ADHF, elevated CTI was associated with higher risks of all-cause mortality and MACCEs, with the greatest risk in patients with both diabetes and high CTI. CTI may be a candidate adjunctive marker for risk refinement; external validation is required before clinical implementation.