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
TL;DR
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.
Abstract
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.