A total of 2224 incident PD patients were enrolled in the present study, of whom ten patients younger than 18 years, 84 patients on PD <3 months, 35 with current drinking, 279 with a history of CVD, 134 with chronic liver disease, 77 without baseline AST/ALT ratio, and 26 with AST or ALT values ≥two times higher than normal values were excluded. The remaining 1579 patients with baseline AST/ALT ratio were eligible for the present analysis (Figure 1). Of 1579 patients with CCI of 3.87±1.66, the mean age was 49.3±14.6 years, 55.4% were male sex, 18.1% had diabetes, 64.2% had hypertension, and 16.2% had hyperlipidemia.
In ROC curve analysis, the AST/ALT ratio (area under curve = 0.75, 95% CI 0.72-0.77; p < 0.001) was found to be a significant predictor of CVD mortality with a sensitivity (79.4%) and specificity (75.8%). The cut-off of the AST/ALT ratio for CVD mortality was 1.0 in the cohort population. A total of 1210 (76.6%) patients were in the high group and 369 (23.4%) patients in the normal group. The baseline characteristics of the study population are shown in Table 1. Patients with high AST/ALT ratio were older (P<0.001), likely to be female sex (P<0.001), had higher frequency of hyperlipidemia (P=0.029) and statin use (P=0.037), had higher CCI (P<0.001) and LDL (P=0.038), and had a lower ALT values (P<0.001) as compared to their counterparts.
The high AST/ALT ratio
The prevalence of the high AST/ALT ratio was 76.6% (74.5%-78.7%) in the cohort population (Figure 2). Univariate Logistic analysis found that age (P<0.001), female sex (P<0.001), CCI (P<0.001), hyperlipidemia (P=0.026), statin use (P=0.035) and LDL (P=0.039) were associated with high AST/ALT ratio (Table 2). Multivariate Logistic analysis showed that older age (increased pre one year, HR=1.02, 95%CI 1.01-1.03, P<0.001) and female (HR=3.04, 95%CI 2.31-4.06, P<0.001) were independently associated with the high AST/ALT ratio.
Baseline AST/ALT ratio and endpoints
The median follow-up period was 4659.6 patient-years. By the end of this study, 316 (20.0%) patients had died, 106 (6.7%) patients had undergone renal transplantation, 247 (15.6%) patients had transferred to hemodialysis, 18 (1.1%) patients had transferred to other PD centers, and 60 (3.8%) patients had been lost to follow-up; the remaining 832 (52.7%) patients were still followed at these PD centers. Of 316 deaths, 193 (61.1%) deaths were caused by CVD episodes. The CVD mortality incidence was 13.1% (95%CI 11.2%-15.0%) and 9.2% (95%CI 6.2%-12.2%) in the high and normal groups, respectively (P=0.024, Figure 3 A), and the all-cause mortality rates was 21.4% (95%CI 19.1%-23.7%) and 15.4% (95%CI 11.7%-19.2%) in the high and normal groups, respectively (P=0.001, Figure 3 B). The Kaplan-Meier estimates showed that the cumulative CVD and all-cause mortality incidence were significantly different between two AST/ALT ratio groups (HR=1.50, 95%CI 1.09-2.07, and HR=1.53, 95%CI 1.16-1.93, Figure 4 A and Figure 5 A). At the end of 1, 3, and 5 years in this study, the incidence of CVD mortality was 8.1%, 15.8%, and 24.5% in the high group, and 6.1%, 10.2%, and 15.2% in the normal group, respectively. The incidence of all-cause mortality was 12.7%, 26.7%, and 32.6% in the normal group, and 9.8%, 17.8%, and 20.7% in the high group, respectively.
The association between the baseline AST/ALT ratio and CVD and all-cause mortality is shown in Table 3. Crude Cox model analysis showed that a high AST/ALT ratio was associated with an increased risk of CVD and all-cause mortality (HR=1.63, 95% CI 1.13-2.27; HR=1.58, 95%CI 1.18-2.10, Model 1). Multivariate Cox model analysis found that patients with a high AST/ALT ratio carried a higher risk of CVD and all-cause mortality (HR=1.43, 95% CI 1.08-2.41, and HR=1.45, 95% CI 1.13-2.37, Model 3), even after adjusting for confounding factors.
The prevalence of high AST/ALT ratio ranged from 68.4% (95%CI 65.3%-71.5%) to 86.9% (95%CI 84.3%-89.3%) among all subgroups (Figure 2). The prevalence of high AST/ALT ratio was significant difference between females and males (P<0.001), those aged ≥65 years and <65 years (P<0.001), and hyperlipidemia and non-hyperlipidemia (P=0.029). The incidence of CVD and all-cause mortality among subgroups were shown in Figure 3 A, and B. Male and non-hyperlipidemia with high a AST/ALT ratio had a significantly higher CVD mortality than their counterparts (P=0.031 and P=0.013). Non-diabetes, hypertension, and non-hyperlipidemia with a high AST/ALT ratio had a significantly higher all-cause mortality than their counterparts (P=0.010, P=0.001, and P=0.001). Survival analysis showed that the cumulative CVD mortality incidence between high and normal groups was a significant difference in the male and non-hyperlipidemia subgroups (Figure 4 B and C). The cumulative all-cause mortality incidence between high and normal groups was a significant difference in the non-diabetes, hypertension, and non-hyperlipidemia subgroups (Figure 5 B, C, and D). Adjusted HRs for CVD mortality were conducted in the male and non-hyperlipidemia subgroups, and for all-cause mortality in the non-diabetes, hypertension, and non-hyperlipidemia subgroups by the Cox regression models (Figure 6).