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Research Article: 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

Date Published: 2026-09-09

Abstract:
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. 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). 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 (?C-index?=?0.018 for mortality and 0.016 for MACCEs), exceeding those of the evaluated biomarker models. Sensitivity analyses generally supported the primary findings. 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.

Introduction:
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…

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