In the present study, the value of the modified A2DS2 scoring system (combining the conventional A2DS2 scoring system with hyperglycemia) for predicting SAP was investigated. It was found that fasting hyperglycemia is an independent risk factor of SAP, which may be a valuable indicator for predicting SAP. Moreover, the predictive value of the modified A2DS2 scoring system is better than that of the conventional A2DS2 scoring system.
In present clinical practice, evaluating the risk of SAP remains challenging. The A2DS2 scoring system, in which scoring items include age, gender, atrial fibrillation, dysphagia and severity of stroke, has been proven to be a simple and reliable scoring scale. However, in literature, hyperglycemia has also been reported as a potential risk factor of SAP, although the evidence remains controversial. Hoffman et al. found that the history of diabetes was not an independent risk factor for SAP [6]. It is noteworthy that the history of diabetes cannot represent an abnormal blood glucose level, and temporary hyperglycemia may indicate stress hyperglycemia, rather than diabetes. In addition, diabetic patients with poor blood glucose control would most likely suffer from cerebral infarction. Thus, the correlation between hyperglycemia and SAP, as well as the value of hyperglycemia for predicting SAP, were investigated.
According to the international diagnosis and treatment guidelines for acute stroke, blood glucose level is recommended as a routine screening index for all patients. In the present study, the random blood glucose level after the onset of stroke represented stress hyperglycemia. Fasting hyperglycemia represented diabetes with poor glycemic control or newly-onset diabetes. Random or fasting hyperglycemia represented an increased blood glucose level caused by different causes. After statistical comparisons, merely fasting hyperglycemia entered the logistic regression model. It was speculated that stress hyperglycemia may be not an independent risk factor for SAP, and occasional transient hyperglycemia cannot increase the risk of SAP. Patients with fasting hyperglycemia (diabetes with poor glycemic control or newly-onset diabetes) are more likely to have SAP, which is consistent with previous findings [5, 13, 14].
The present study indicated that fasting hyperglycemia is an independent risk factor for SAP. Acute ischemic stroke can cause hyperglycemia mainly through the following mechanisms: the activation of the sympathetic and parasympathetic nervous system [15-17], and the immune response of the hypothalamic-pituitary-adrenal axis [16-18]. Hyperglycemia can reduce the bactericidal ability of leukocytes, increasing the likelihood of pulmonary infection [19, 20]. The study conducted by Obiako et al. revealed that the proportion of hyperglycemia was greater than that of diabetes in patients with acute stroke [21], suggesting that the poor prognosis of acute stroke may be attributed to hyperglycemia induced by stress reaction, rather than diabetes.
A number of studies have shown that hyperglycemia is significantly correlated with the occurrence of pneumonia and the poor outcome of acute ischemic stroke, especially in patients without diabetes. Dziedzic et al. noted that the incidence of pneumonia was higher in non-diabetic patients with fasting hyperglycemia. Nevertheless, the multivariate analysis revealed that fasting hyperglycemia was not significantly associated with pneumonia [22]. Hirata et al. reported that the mortality of pneumonia was significantly correlated with hyperglycemia during hospitalization, but was not correlated to the history of diabetes [23]. It was speculated that hyperglycemia may be associated with the severity and poor prognosis of acute stroke in non-diabetic patients, and diabetic patients may have adapted to the long-term hyperglycemia, which can protect the brain tissue against acute blood glucose increase.
The management of hyperglycemia should be highlighted during hospitalization for reducing the risks of SAP. Blood glucose level is correlated to the functions of various intracranial systems, such as the cerebrovascular system, inflammatory system, and metabolic system [24]. Appropriate blood glucose control can improve immunosuppression and decrease the incidence and severity of infection. The optimal treatment of hyperglycemia in patients with acute stroke remains to be well-elucidated.
Furthermore, the average age of patients in the present study was lower than that reported in the study conducted by Hoffman et al. (61.9 ± 12.7 vs. 71.2 ± 13.1) [6]. This discrepancy may indicate a different age distribution between China and Germany. ROC curve analysis has been widely used for making the best diagnostic criteria, and determining the best critical value, while the area under curve can represent the efficiency of the prediction. In the present study, the area under curve of the modified A2DS2 scoring system was significantly higher than that of the conventional A2DS2 scoring system, suggesting that the modified system (including the item of hyperglycemia) is more effective for predicting SAP. This modified A2DS2 scoring system may help in the early identification of stroke with high SAP risks, allowing timely prophylactic treatment, such as antibiotic therapy and the prophylactic use of aspiration.
The present study has some strengths. At present, reliable tools for predicting the risk of SAP include the A2DS2 scoring system and AIS-APS scale [5, 6]. In the present study, the former one was utilized, since it was more simple and practical. In addition, the inclusion and exclusion criteria were strict in the present study, and all researchers were uniformly trained [1]. The novelty of the present study was the combination of the A2DS2 scoring system and evaluation of hyperglycemia. The present findings may improve the predictive value of the A2DS2 scoring system.
There were still some limitations in the present study. First, the dynamic changes of the blood glucose levels of patients were not monitored throughout hospitalization, and only the random blood glucose level on admission was assessed. Second, the single-center and retrospective design was an inherent defect of the present study. In the future research, more external verifications are needed to arrive at a definitive conclusion.
Conclusion
Fasting hyperglycemia is an independent risk factor for predicting SAP. The predictive value of the modified A2DS2 score (combined A2DS2 score and fasting hyperglycemia) is higher than that of the A2DS2 score.