Prognostic role of the preoperative neutrophil-to-lymphocyte ratio and albumin for 30-day mortality in patients with postoperative acute pulmonary embolism

We performed a single-center, retrospective and case-control study. The medical records of consecutive patients who were diagnosed with pulmonary embolism from September 1, 2012, to March 31, 2019, in our hospital were reviewed, and patients who were diagnosed with acute pulmonary embolism within 90 days postoperatively were included in this study. In the present study, only patients with pulmonary embolism confirmed by computed tomography pulmonary angiography (CTPA) were defined as pulmonary embolism patients, and patients with suspected but unconfirmed pulmonary embolism by examination were not defined as pulmonary embolism patients. Patients were excluded if they underwent cardiac surgery, did not have complete data, had received blood transfusion within 1 month preoperatively, had comorbid infection, and had comorbid hematological disease or received immunosuppressive therapy within 1 month preoperatively. Finally, 101 patients met our inclusion criteria. All patients with PAPE met the diagnostic criteria of the 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism [17].

Data were extracted from the hospital electronic database by two independent doctors. If controversial data were encountered, the two doctors who collected the data underwent discussion to reach an agreement. All patients’ characteristics (sex, age, BMI, smoking history and drinking history), comorbidities (hypertension, diabetes, respiratory diseases, chronic coronary heart disease, chronic arrhythmia, history of stroke and chronic renal failure), surgical information (surgical type and ASA level), admission examination data (neutrophil-to-lymphocyte ratio; platelet-to-lymphocyte ratio; monocyte-to-lymphocyte ratio; hemoglobin; white blood cell; platelet; mean platelet volume; platelet distribution width; red cell distribution width; glucose; neutrophil; lymphocyte; creatinine and albumin) and the situation within 30 days after PAPE were obtained through our electronic medical recording system and follow-up. Complete blood counts (CBCs), blood glucose levels, and albumin assessments were carried out at the biochemistry laboratory of our hospital. The NLR was obtained by dividing the absolute neutrophil counts by the absolute lymphocyte counts from the same blood sample, the PLR was obtained by dividing the absolute platelet counts by the absolute lymphocyte counts from the same blood sample, and the MLR was obtained by dividing the absolute monocyte counts by the absolute lymphocyte counts from the same blood samples. All test results were obtained from the same blood sample test within 3 days before surgery.

Data analysis was performed using the Statistical Package for the Social Sciences version 25.0 for Windows (IBM, Chicago, IL, USA). Data with a normal distribution are represented as the mean ± standard deviation, and Student’s t-test was used to compare two groups. The data with an abnormal distribution are represented as medians (interquartile ranges), and the Mann-Whitney U test was used to compare two groups. Categorical variables are represented as numbers or percentages, and the χ² test or Fisher’s exact test was performed for categorical variables. Based on the univariate analysis, variables with a P value < 0.05 were included in the multivariate logistic regression analysis to confirm the independent risk factors. Forward logistic regression analysis was conducted to estimate the OR and 95% CI for 30-day mortality of the NLR, albumin and other parameters after adjusting for potential confounding factors. The receiver operating characteristic (ROC) curve was used to examine the performance of independent risk factors in predicting 30-day mortality. The area under the curve (AUC) was derived from the ROC curve, which ranged from 0.5 to 1.0 – with higher values indicating higher discriminatory ability, and the Youden Index (maximum [sensitivity +specificity] minus 1) was adopted to define the optimal cut-off value. Afterwards, a nomogram based on the independent predictors was established, and the calibration curve and decision curve analysis (DCA) were generated to evaluate the nomogram. In addition, the AUC of the nomogram was calculated, and the differences in the AUC between the nomogram and independent predictors were compared by the pROC package in R software (version 3.6.1). All P values < 0.05 were accepted as statistically significant.

During the study period, 125 patients were diagnosed with pulmonary embolism within 90 days after noncardiac surgery. Twenty-four patients were excluded because they did not meet our criteria for hematological disease (2 cases), received blood transfusion within 1 month preoperatively (13 cases), had an infection (2 cases), received immunosuppressive therapy within 1 month preoperatively (1 case) and had missing data (6 cases). Finally, 101 patients with PAPE following noncardiac surgery met our inclusion criteria and were included in this study, which included 41 males and 60 females, and the median age was 64 years (interquartile range: 57.50–71.00 years). For 101 patients, the median time of PAPE was 3 days (interquartile range: 1–5 days). Seven patients were diagnosed with massive pulmonary embolism: ten patients received fibrinolytic therapy, and the remaining patients received anticoagulant therapy. The demographic data and clinical data of deaths and survivors are listed in Table 1.

Twenty-four patients died within 30 days, corresponding to a 30-day mortality rate of 23.8%. There were no significant differences in terms of age, sex, BMI, smoking history, drinking history, admission systolic blood pressure, surgical type or ASA level (all P values>0.05). There were no significant differences in terms of hypertension, diabetes, respiratory diseases, coronary heart disease, arrhythmia, history of stroke or renal failure (all P values>0.05). The baseline characteristics and comorbidities of the patients are shown in Table 1. The preoperative laboratory parameters are presented in Table 2. The NLR, neutrophil count and creatinine level were significantly higher in those who died than in survivors with PAPE (all P values < 0.05), and the albumin level was significantly lower in those who died than in survivors after PAPE (P = 0.008). There were no significant differences in the other parameters included in our research (Table 2).

To further confirm the independent risk factors for mortality after PAPE, multivariate logistic analysis was performed. The NLR, MLR, WBC, neutrophil, lymphocyte, creatinine, and albumin (all P values<0.05) were included in the multivariate analysis, and the results indicated that both the NLR and albumin were independent predictors of 30-day mortality in patients with PAPE. The probability of death increased by approximately 17.1% (OR = 1.171, 95% CI: 1.073–1.277, P = 0.000) with a one-unit increase in the NLR, and the probability of death decreased by approximately 15.4% (OR = 0.846, 95% CI: 0.762c–0.939, P = 0.002) with a one-unit increase in albumin (Table 3). In addition, the results indicated that creatinine, the MLR, neutrophil, lymphocyte and WBC were no longer independent predictors in multivariate analysis (all P values > 0.05).

Based on the independent predictors, a nomogram was established to predict 30-day mortality in PAPE patients (Fig. 1). The AUC of the nomogram was 0.888 (95% CI: 0.812–0.964), which was significantly higher than that of any single predictor (P value< 0.05) (Table 4 and Figs. 2 and 3a). Moreover, the calibration curve is shown in Fig. 2b, and the results indicated that the prediction by the nomogram was highly consistent with the actual observations. In addition, the DCA indicated that if the threshold probability of a patient and a doctor was between 5 and 75%, this nomogram predicted 30-day mortality with more benefit than the scheme(Fig. 2c).