Abstract
BACKGROUND: Heart failure (HF) is a clinical syndrome with high global incidence and mortality, imposing a substantial economic burden. While creatinine (Cr) and body weight (BW) individually influence HF progression, the prognostic role of the creatinine-to-body weight ratio (CWR) remains unclear. This study investigates the association between CWR and mortality in HF patients, aiming to identify high-risk individuals and inform prognosis. METHODS: Patient data were extracted from the MIMIC-IV database. Participants were first stratified into CWR index quartiles to categorize the cohort. The primary endpoints were 30- and 365-day all-cause mortality, while secondary endpoints included 90- and 180-day mortality. Kaplan-Meier curves with log-rank tests were then used to compare survival across quartiles. Next, Cox proportional hazards regression (with sequential model adjustment) and restricted cubic spline (RCS) analysis assessed the association between CWR and prognosis. Sensitivity analyses were subsequently conducted to examine the robustness of the non-linear relationship, and subgroup analyses explored potential effect modifications. Finally, time-dependent receiver operating characteristic (ROC) curve analyses compared the predictive performance of CWR against traditional markers. RESULTS: Among 4,371 participants (median age: 75 years; 54.8% male), higher CWR index values were significantly associated with increased all-cause mortality risks at 30, 90, 180, and 365 days, as demonstrated by Kaplan-Meier survival curves (log-rank P < 0.01). Building on these results, Cox regression analysis further revealed that individuals in the highest CWR index quartile had an elevated risk of death compared to those in lower quartiles. Additionally, restricted cubic spline (RCS) analysis showed a robust biphasic nonlinear association between the CWR index and mortality, identifying 0.05 as a key threshold where the risk relationship changes. Specifically, for most patients (CWR ≤ 0.05), mortality risk increases with rising CWR values until it plateaus, whereas for those with CWR > 0.05 (n = 320), a distinct pathophysiological state may emerge, marked by a sharp increase in risk. The underlying mechanisms require further investigation. CONCLUSION: CWR demonstrates a robust biphasic association with mortality, identifying 0.05 as a critical threshold separating a risk-plateau phase from extreme high-risk. Its stable prognostic value suggests CWR may integrate acute hemodynamic and chronic metabolic stress, though prospective validation is warranted.