Participants
A total of 2,114 participants were included in the study, with 290 deaths observed during the follow-up period (Figure 1). The median age of participants was 64 years (IQR: 55–73), with 54.5% (n = 1,160) being female. table 1 We summarize patient demographics, vital signs, laboratory results, and comorbidities across tertiles at ACC level. Patients with the highest tartiles were generally older and showed higher WBC and platelet counts compared to the lowest BC, which showed lower WBC and platelet counts.
Among the total cohort, missing covariates were ethnicity (13, 0.61%), comorbidities (27, 1.28%), heart rate (27, 1.28%), MAP (28, 1.32%), respiratory rate (33, 1.56%), temperature (143, 6.76%), serum catasium (3, 0.14%), 0.05% (143, 6.76%), Bunine (143, 6.76%), (5, 0.24%), WBC (62, 2.93%), RBC (62, 2.93%), hemoglobin (51, 2.41%), platelets (73, 3.45%), and Apache-IV score (257, 12.15%).
Hospital mortality rate 28 days
The in-hospital mortality rate over the 28-day period was 14.52% (290/2114). The mortality rates stratified by ACC treatment were 10.37%, 13.91% and 16.81% for the lowest, middle and highest tertiles, respectively (in the table) 1).
Unadjusted association between baseline variables and 28-day mortality rates
Univariate analysis identified several factors significantly associated with 28-day mortality (table) 2). The mean ACC was 9.36±0.82 mg/dL. An increase in mortality was observed due to increased calcium levels. p= 0.0433) and highlands (OR 1.75, 95%CI 1.28–2.38, p = 0.0004). Older age was a strong independent risk factor (or 2.17, 95% CI 1.56–3.02; p<0.0001). Additional significant risk factors include increased heart rate (or 2.10, 95% CI 1.54–2.87; p<0.0001), infection (OR 1.71, 95% CI 1.31–2.23, p<0.0001), and High Apache-IV (or 8.83, p<0.0001) and sofa (or 5.84, p<0.0001) Score.
Relationship between ACC and 28-day in-hospital mortality in different models.
Multivariable models confirmed the association between ACC levels and the risk of death (table) 3). In the unadjusted model, an increase in each unit of ACC was associated with a higher risk of death (OR 1.27, 95% CI 1.09–1.48). p= 0.0024). This relationship persisted after adjusting for confounding factors (adjusted model I: or 1.29, 95% CI 1.10–1.51; p= 0.0020; Adjusted Model II: or 1.24, 95% CI 1.05–1.47, p= 0.0129).
Stratified analysis revealed a significant increase in the risk of death in the high calcium group. In Model II, the tertile of high calcium was OR 1.69 (95% CI 1.09–2.53; p= 0.0032). Elevated ACC levels were significantly associated with in-hospital mortality over the 28-day period, and results remained robust even after adjusting for multiple confounding factors.
Subgroup analysis of the relationship between ACC and 28-day mortality
Subgroup analysis assessed the corrective effects of demographics and clinical variables on the relationship between ACC levels and mortality (Figure 2). Age emerged as a significant effect modifier (p-interaction = 0.0239). In younger patients (<65 years), increased calcium levels significantly increased the risk of death (OR 1.49, 95% CI 1.17–1.89; p= 0.0013), no significant association was observed in older patients (≥65 years, or 1.03, 95% CI 0.83–1.27; p= 0.8149). Male patients showed moderately increased risk (OR 1.27, 95% CI 1.00–1.62; p= 0.0477). Patients without CHF (or 1.26; p= 0.0070) or diabetes (or 1.30, p= 0.0119) significantly increased risk. An increased risk of death was also observed in patients with sepsis (or 1.40; p= 0.0126), low albumin (or 1.37, p= 0.0171), and low phosphate levels (or 1.48; p= 0.0317). Results show that younger age, male gender, intermediate BMI, lack of chronic comorbidities, lower albumin levels, and reduced disease severity are associated with stronger effects. This underscores the importance of individualized risk assessments in clinical practice.
Nonlinear relationship between ACC and 28-day mortality rates
A nonlinear dose-response relationship was observed between ACC and mortality (Figure 3 and the table 4). A nonlinear association between ACC and 28-day mortality was detected using GAM (table 4). Comparing the linear regression model with the two-piece linear linear regression model, pThe log-likelihood ratio test value was 0.020. This result shows that a two-piece linear regression model is more appropriate for characterizing relationships.
For ACC levels below 8.04 mg/dL, mortality was reduced at adjusted or 0.44 (95% CI 0.20–0.98,). p= 0.0438) for every 1 mg/dL increase in ACC. Effect size was 1.36 (95% CI 1.13–1.64, with ACC levels above 8.04 mg/dL p=0.0011), and the risk of in-hospital mortality for 28 days increased by 36% for every 1 mg/dL increase in ACC levels.
Dose-response relationships were observed in a clear pattern based on age (Supplementary Figure) 1). In younger patients, linear relationships were more appropriate (p= 0.121), the piecewise linear model was more appropriate in older patients (p= 0.020) (Supplementary Table 1).