This study proposed a new idea of constructing the death risk prediction model of stroke patients based on the idea of Stacking integration. Four single models with good forecasting efficiency (XGboost, Catboost, GBDT, MLP) were selected and the Stacking models were integrated. Previous studies have shown that the four models have good performance in predicting stroke death [18]. In this study, the AUC values of these four models for predicting stroke death in the test set were 0.786, 0.777, 0.78 and 0.829, respectively. However, in order to further improve the performance of the algorithm and improve the accuracy and generalization ability of the model on this basis, this study combined the advantages of various model algorithms. Different single models with good forecasting efficiency are merged into Stacking models. The AUC values of the Stacking model in the training set and the test set were 0.878 and 0.871, respectively. To further validate the Stacking model’s performance in an independent dataset, data from 88 patients were prospectively collected from January 2023 to June 2023. The Stacking model demonstrated higher prospective prediction accuracy and AUC value compared to the other eight algorithms. This indicates that the Stacking prediction model has stronger accuracy and effectiveness in predicting mortality among ICU stroke patients.
In this study, the researchers found that the risk of poor prognosis in patients with acute stroke was significantly positively associated with elevated serum creatinine levels, increased blood neutrophil counts, increased serum sodium concentrations, increased total bilirubin levels, increased international normalized ratio (INR), older age at presentation, decreased platelet counts, decreased low-density lipoprotein levels, and higher NIHSS scores at admission. In addition, the risk of death was also increased if patients had pulmonary infections, coma, hypertension, or atrial fibrillation during hospitalization. Studies have shown a significant correlation between renal insufficiency and mortality in patients with ischemic stroke [19]. Aryandhito Widhi Nugroho and used multivariate logistic regression analysis to find that low EGFR based on creatinine level was closely related to in-hospital and discharge deaths [20]. In addition, studies have also revealed that traditional cardiovascular risk factors may lead to similar vascular damage in the kidney and cerebrovascular, so doctors can use serum creatinine to predict the risk of death in patients with stroke [21]. Lili Cui's research showed that patients with neutrophil counts exceeding 7.79×10^9/L havd a higher risk of death [22]. A meta-analysis by Lu Wang of 10,371 stroke patients showed that a higher neutrophil ratio was positively associated with bleeding conversion after stroke and the risk of death within three months [23]. By releasing reactive oxygen species, proteases, cytokines and chemokines, neutrophils are involved in destroying the blood-brain barrier, exacerbating ischemic injury and edema, which may aggravate cerebral infarction and even lead to cerebral hernia [24–25]. Amit Akirov found that abnormal serum sodium levels on admission were significantly associated with short and long-term mortality. Patients with hypernatremia are at higher risk of death than those with hyponatremia [26]. In the hypertonic state of hypernatremia, brain cell dehydration may cause brain atrophy, which may lead to vascular rupture, triggering intracerebral hemorrhage, subarachnoid hemorrhage, and permanent neurological impairment or severe fatal outcomes [27]. In an animal experiment, excess bilirubin was found to be significantly toxic to the nervous system and cause a large number of neuronal death [28]. Patients with acute stroke who have higher bilirubin levels may face more extensive cerebral infarction, more significant brain edema, and more severe reperfusion injury [29], which combined to significantly increase the risk of death in stroke patients.Xuewei Xie found that a high INR on admission was highly correlated with poor stroke outcomes in patients with acute ischemic stroke who did not receive anticoagulant therapy [30]. This correlation may be due to the hemorrhagic transformation of intracranial cerebral infarction lesions or hemorrhagic enlargement of cerebral hemorrhage lesions caused by elevated INR, which exacerbates the deterioration and even death of stroke patients. In an analysis of 1233 patients with acute ischemic stroke, Jason J. Sico and colleagues showed that a decreased platelet count was associated with higher mortality [31]. In stroke patients, thrombocytopenia may increase mortality by increasing the area of ischemic infarction [32], meanwhile, studies have shown that thrombocytopenia increases the risk of post-infectious intracerebral hemorrhage and death [33].In addition, the study by Gang Lv showed that the risk of poor outcome of stroke increased by 46.2% for every 1 mmol/L decrease in low-density lipoprotein cholesterol (LDL-C) level [34]. Bang found that LDL cholesterol levels were independently associated with abnormal permeability of the blood-brain barrier [35], suggesting that reduced lipids may compromise vascular integrity and cause blood to leak between unstable cerebrovascular endothelial cells [36], which increases the likelihood of bleeding transitions after stroke.
The NIHSS score at the time of admission not only has predictive value for the prognosis of cerebral infarction, but also has guiding significance for the prognosis of cerebral hemorrhage. C. M. Cheung used the NIHSS score at admission to predict 30-day mortality in patients with intracerebral hemorrhage, with sensitivity and specificity of 81% and 90%, respectively [37]. Studies on the relationship between the Glasgow Coma Scale (GCS) and the prediction of stroke death indicate that the GCS score is an independent predictor of the risk of death in stroke patients [38, 39]. Aspiration pneumonia is the most common type of pulmonary infection in stroke patients and one of the direct causes of death from stroke. Based on an analysis of 2,424,379 death certificates, Chia-Yu Chang pointed out that 5% of stroke patients died from aspiration pneumonia [40]. Lijuan Zhang found that stroke patients infected with the acute respiratory syndrome coronavirus were more likely to die [41]. Pulmonary infections can trigger a systemic inflammatory response, worsening brain edema and brain injury, and may lead to complications such as sepsis, which has a high mortality rate. Severe pulmonary infections interfere with normal pulmonary ventilation, resulting in inadequate oxygenation of the brain and the body, which leads to brain cell damage and death. In addition, hypertension and atrial fibrillation are considered to be important causes of stroke, and they also have important clinical significance in predicting mortality in patients with stroke. According to a meta-analysis of 61 prospective studies by Sarah Lewington, about 60% of stroke deaths worldwide are associated with high systolic blood pressure, and effective control of blood pressure has been identified as one of the most critical interventions for stroke prevention [42]. The study by Daniele Massera revealed an independent correlation between newly-onset atrial fibrillation and increased incidence and mortality of stroke in hospitalized patients. The patients involved had significantly increased mortality within 30 days and 1 year after admission [43]. These conditions may be related to factors such as cardiac embolism, fatal arrhythmias, myocardial ischemia, and myocardial infarction caused by atrial fibrillation. Besides, the prediction model constructed in this study takes the preliminary assessment, laboratory and diagnostic results of patients admitted to ICU as the inclusion indexes, so as to rapidly predict the early prognosis of patients in a short time, assist clinicians to evaluate the condition and make corresponding clinical diagnosis.
In summary, this study successfully constructed an in-hospital death prediction model for ICU acute stroke patients based on the Stacking integration algorithm. The model demonstrated strong prediction accuracy and effectiveness in the testing and validation of data from 1882 patients. By comparing the AUC values of the four base learners, the Stacking model outperforms a single model on both the training and test sets, highlighting the strong potential of the Stacking integration algorithm in the field of healthcare prediction. In addition, this study revealed biomarkers with significant predictive value for patients’ mortality risk, such as blood creatinine, blood neutrophils, serum sodium, total bilirubin, and INR, by using the SHAP feature interpretation method. The comprehensive analysis of these biomarkers and clinical characteristics provides clinicians with evidence-based recommendations for feasible interventions, and provides a strong scientific basis for reducing the risk of death in ICU acute stroke patients. The application of this predictive model helps clinicians to rapidly assess the risk of death at the time of patient admission and take targeted early interventions.
Nonetheless, there are some limitations to this study. For example, the data used in this study were all from the same hospital, and data from multiple hospitals can be added for comparison and validation in the future. In addition, more features can be added and new machine learning algorithms can be used to further improve the prediction effect during the process of feature screening and prediction model construction. In subsequent studies, the model can be gradually adjusted and optimized to cope with data updates and continuously improve the prediction performance to provide more effective clinical reference and support.