Study participants and baseline characteristics
The data of a total of 6,616 AMI patients were extracted from the database. Patients without data for BUN (n=328) or Cr(n=50) levels were excluded from the study. Patients with an eGRF<60mL/min/per 1.73 m2were excluded. A total of 3,831 (57.9%) patients were included in the statistical analyses. The ICU admission rate of patients without a BUN or Cr level was 5.7% (378 out of 6,616 patients), and the overall in-hospital mortality rate was 3.71% (142 out of 3,831patients). The mean BUN/Cr ratio was 18.6±8.2. A flow chart of the study is shown in Fig.1.
The baseline data of the study population are given in Table1. According to the BUN/Cr ratio, 1271, 1274, and 1286 patients fell into the first (<14.6), second (≥14.7 and <19.8), and third (≥20.0) tertiles, respectively. In general, the patients’ mean age was 62.2±12.4 years, and 2,689(70.2%) patients were male patients. No statistically significant differences were detected between the groups in terms of the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), international normalized ratio (INR), heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), capillary blood glucose (CABG),and incidence of percutaneous coronary intervention (PCI) between the different groups (all p values > 0.05). Factors observed among participants with high BUN/Cr ratio levels included having an older age, being a Caucasian, having a longer hospital stay, and having higher WBC, RDW, HDL, and potassium values(all p values<0.05). The opposite was observed for body mass index (BMI), red blood cell (RBC) count, levels of platelets, (total cholesterol)TC, triglycerides (TG), and low-density lipoprotein (LDL), heart rate (HR), and history of diabetes and hypertension (all p values<0.05).
We illustrated the in-hospital mortality of the two groups in supplementary Fig.1.The mortality rate of non-STEMI patients was 4.9%,which was significantly higher than that of the STEMI group (2.8%, p=0.001).
Kaplan–Meier Survival Curves of the BUN/Cr Ratio for Predicting the In-Hospital Mortality Among Patients with AMI
The Kaplan–Meier curve for the tertiles of the BUN/Cr ratio is shown in Fig.2. The figure indicated that survival rates were highest when the BUN/Cr ratio was ≤15.12 and lowest when the BUN/Cr ratio was ≥19.41 after adjustment for age, sex, and ethnicity (log-rank test p <0.001). The BUN/Cr ratio was used to distinguish between different survival statuses. It had good discrimination.
The BUN/Cr ratio as a Predictor of In-hospital Mortality
We constructed three different models to analyze the independent effects of the BUN/Cr ratio on the in-hospital mortality of critically ill patients with AMI grouped according to the BUN/Cr ratio tertiles. As shown in Table2, in model I, after adjustment for age, sex, and ethnicity, a higher BUN/Cr ratio was associated with an increased risk of in-hospital mortality compared with those in the first tertile. In model II, after adjusting for more confounding factors, the BUN/Cr ratio was found to be an independent predictor of in-hospital mortality in critically ill patients with AMI as well (tertile 3 vs.tertile 1: adjusted HR, 2.14; 95% CI, 1.16–3.97; p for trend<0.05).
Analyses of the nonlinear relationship between the BUN/Cr ratio and in-hospital mortality
It is essential to analyze the nonlinear relationships among continuous variables. In this study (Fig.3), we detected a nonlinear relationship between the BUN/Cr ratio and in-hospital mortality after adjusting for age, sex, and ethnicity. Using the two-piecewise linear regression model, we calculated the inflection point as 18. The HR (95%CI) and p values were 1.31 (1.15, 1.49) and <0.0001, respectively, on the right of the inflection point. However, on the left of the inflection point, the BUN/Cr ratio–mortality relationship was insignificant (HR = 0.99,95% CI: 0.91, 1.07; p = 0.7299; Table3).
Subgroup analyses
The results of the subgroup analyses are presented in Table4. After adjusting for potential confounders, we found that the test for the interaction was statistically significant for history of CHF (p for interaction<0.0001) and the AMI category (p for interaction=0.0002). However, statistical significance was not observed for age, sex, BMI, history of diabetes, history of hypertension, PCI, CABG, glucose, heart rate, and LDL. We also found evidence of BUN/Cr–AMI category interactions. The effect of the BUN/Cr ratio on in-hospital mortality significantly differed among patients with different AMI categories. The BUN/Cr ratio was positively correlated with in-hospital mortality (HR = 1.25,95% CI: [1.14, 1.37]) in patients with non-ST-segment elevation myocardial infarction(non-STEMI). However, there was no significant relationship between the BUN/Cr ratio and the in-hospital mortality in patients with ST-segment elevation myocardial infarction (STEMI). Moreover, we observed that the BUN/Cr ratio was positively correlated with the in-hospital mortality if the BUN/Cr ratio was > 18.
Prediction of in-hospital mortality
The ROC curves generated using the indicated variables(BUN/Cr plus APACHE scores and APACHE scores) are plotted in Supplementary Fig. 2.The AUCs for the APACHE scores were 0.859 and 0.861 for BUN/Cr plus APACHE scores (all p <0.001).