Experimental design
Research objects
This article is a hospital-based retrospective study of patients with acute ischemic stroke who were admitted to the Neurosurgery Department of Hospital A between April 2021 and April 2022 based on a unified clinical registry.
Inclusion criteria: over 18 years of age; and according to the diagnostic criteria determined by the 2021 “China AIDS diagnosis and Treatment Standards”; 24 h or more, signs of local neurological loss; Head CT or MRI was performed within 72 h of hospitalization, and the corresponding cerebral infarction was found.
Exclusion criteria: Suffering from other neurological diseases that significantly affect the research results, such as brain tumors, brain injuries, etc.; Patients with severe cardiovascular disease, liver and kidney dysfunction, or other important organ dysfunction.
Subject conditions: hospitalization 72 h after onset; fatal brain stem infarction; incomplete clinical or laboratory data.
Of the 951 eligible patients, 14 patients with a lack of laboratory data, 116 patients with 72 h of onset, 5 patients with severe and fatal brain stem infarction and 13 patients with missing follow-up data were excluded, and 803 patients were eligible for inclusion.
Collecting clinical data
All patients used a standard clinical registration form to collect relevant data such as age, sex, medical history, and clinical characteristics at the time of admission, during hospitalization, and after discharge.
The diagnosis is based mainly on the following: the main basis for the diagnosis of hypertension: multiple measurements of the patient’s right upper extremity or the healthy side, diastolic blood pressure greater than 90 mmHg, the use of antihypertensive drugs or a history of hypertension;
The condition of a smoking history is smoking or regular smoking (20 cigarettes per day for more than 1 year).
History of drinking: more than 50 g per day or 500 g per week.
There was a history of cerebral infarction, cerebral hemorrhage, etc., without any sequelae.
Clinical characteristics: NIHSS was used to evaluate neurological function scores at the time of hospitalization. The modified Rankin Scale (mRS) was used to evaluate the prognosis of patients after discharge.
In the laboratory test, 2 ml of venous blood was collected by an EDTA-k2 anticoagulation vacuum tube, mixed with an automatic blood cell analyzer XE-5000 production line to measure the number of leukocytes and monocytes, and 5 ml of venous blood was taken on an empty stomach the next morning after hospitalization. All patients were tested 24 h after hospitalization.
According to the grading criteria of the Online Certificate Status Protocol (OCSP), patients were included in head CT or magnetic resonance imaging within 72 h and divided into 4 categories according to clinical manifestations: total anterior circulation infarction (TACI); partial anterior circulation infarction (PACI); posterior circulation infarction (POCI); lacunar infarction (LACI).
Results
The severity of the stroke was determined mainly by the NIHSS score at the time of hospitalization, and the NIHSS score of 0–3 belonged to mild cerebral infarction.
2.
Diagnostic criteria for pulmonary infections
Post-stroke pulmonary infection is based on the diagnostic criteria for stroke-related pneumonia in 2021.
The details are as follows: At least one condition is met: body temperature > 38 °C for no other reason; decreased white blood cell count (< 4 × 109/L) or increased white blood cell count (> 11 × 109/L).
Combined X-ray or lung CT: New or evolving exudate, consolidation, or hole.
4.
Evaluation of prognostic effects
Poor prognosis at discharge: When a patient is discharged, if mRS < 2, the patient has a good prognosis, while mRS > 2 indicates a poor prognosis.
5.
Confirmation of death cases
For 90 days, phone or face-to-face tracking of all deaths, deaths need to wait for confirmation from family members, colleagues, or death certificates, medical records, etc.
Discussion
The results showed that MHR and monocyte counts at admission were not associated with neurological severity at admission, poor prognosis at discharge, and death within 90 days. There was a weak correlation between HDL and neurological severity at hospitalization, and MHR and monocyte count at hospitalization had a certain relationship with the appearance of poststroke-related pneumonia. Inflammation is a key factor in the occurrence and development of ischemic stroke [
31]. Inflammation not only accelerates the occurrence of stroke but also worsens the condition of stroke. In the occurrence and development of most strokes, inflammation is also involved in most strokes.
Endothelial dysfunction is the first stage of atherosclerosis, and when endothelial function is abnormal, activated monocytes interact with damaged endothelial cells. Existing studies have shown that the enhanced activity of MMPA can accelerate the destruction of the vascular elastic membrane, thereby causing plaque rupture. Monocytes, a specific type of atherosclerosis, interact with vascular endothelial cells and platelets to cause vascular inflammation, endothelial dysfunction, and vascular occlusion, which can predict plaque development [
32]. Our findings suggest that high monocyte counts are associated with plaque formation in ST-segment elevation myocardial infarction. At the same time, the number of monocytes also has a certain relationship with the severity, prognosis, and mortality of coronary heart disease, stroke, and other related diseases. Animal experiments showed that 12 h after intracerebral hemorrhage, monocytes invaded and surrounded the hematoma, reaching a maximum value in 5 days.
Several recent studies have confirmed that high monocyte counts are strongly associated with mortality at 30 days from intracerebral hemorrhage [
33]. A study in the United States showed that high monocyte counts at the time of hospitalization were not associated with the number of hematomas in cerebral hemorrhage, but were not associated with 30-day mortality. Patients with high monocyte counts at admission had a significantly higher 30-day mortality rate. However, some studies have indicated that after acute cerebral infarction after 3 months, monocyte count is not associated with a poor prognosis.
In recent years, several experiments have shown that there is a close relationship between HDL and monocytes, and HDL can regulate the activation, adhesion, and migration of monocytes [
34]. Studies have shown that HDL can inhibit the migration of monocytes to the inner layer. Subsequently, HDL and its main protein component, apolipoprotein A-1, can inhibit the activity of CD11b, thus inhibiting the inflammatory response of human monocytes. Furthermore, HDL may also increase indirect effects such as anti-inflammatory and antioxidant, thus enhancing antioxidant capacity. Several recent studies have shown a new view that HDL is anti-inflammatory. HDL plays an anti-inflammatory role in the hematopoietic system, it can promote the proliferation of hematopoietic stem cells, and it can inhibit the production of monocytes.
More clinical studies have shown that high HDL can reduce the area of ischemic stroke damage and reduce the severity of the disease, thus improving the prognosis of patients. Therefore, the high-density lipoprotein content and its associated monocyte count are of great significance in the occurrence, development, severity, and prognosis of stroke. MHR can be used as a new indicator to reflect the inflammatory response, and multiple studies have shown that there is a strong link between high MHR and the occurrence and death of cardiovascular events. 513 cases of acute ST-segment elevation myocardial infarction and percutaneous coronary intervention (PCI) were analyzed. The results showed that there is a certain correlation between high MHR and serious adverse cardiovascular events (MACEs) and death after PCI. A survey of patients preparing for coronary angiography showed that an increase in MHR was associated with a 2.03-fold increase in the incidence of MACE. Recently, a new study has shown that high MHR is strongly associated with the prognosis and mortality of cerebral infarction. The team in this article found that elevated MHR was strongly associated with patient discharge, prognosis, and death 3 months later [
35]. In patients with ischemic cerebral infarction, high MHR is an independent predictor. However, we found only a weak association between HDL in the hospital and neurological severity in the hospital, and no associations between monocyte count and MHR with severity in the hospital, discharge outcomes, and death within 90 days.
The function of monocytes after cerebral ischemia is bidirectional and the mechanism is closely related to the type of monocyte. Because the experiment only counted monocytes, not monocytes, the relationship between monocyte severity at hospitalization, hospital discharge, and 90-day mortality was not available. In this article, monocytes will be classified and their functions analyzed.
Dynamic changes in monocytes after ischemic cerebral ischemia may be related to the time when monocytes and macrophages invade brain damage after cerebral ischemia. Several studies have shown that neutrophils in peripheral blood enter brain tissue in about 1 day, while monocytes and macrophages in peripheral blood are more abundant in 3 to 7 days. All patients included in this study were in 72 h and the monocytes in the peripheral blood probably did not change. According to the dynamic characteristics of monocytes, the relationship between the two can be obtained by appropriately prolonging the onset time of selected patients.
The results of this paper suggest the appearance of immunosuppressive syndrome after stroke. In the acute phase of cerebral infarction, due to the activity of sympathetic nerves, the number of immune cells decreases and also stimulates the increase in inflammatory cells such as neutrophils and monocytes, resulting in the secretion of glucocorticoids and the onset of SAP. At the same time, after acute cerebral infarction, parasympathetic and pituitary-adrenal axis abnormalities also occur. Activation of parasympathetic nerves, in particular, induces cholinergic activity, which leads to the production of systemic applications and products (SAP). Therefore, by detecting the monocyte count and MHR of patients during hospitalization, the risk of stroke-related pneumonia can be better judged, and the basis for the early diagnosis and treatment of post-stroke pneumonia can be provided.
This article is primarily a single-center retrospective study and, although some study-relevant factors were identified in the multivariate analysis, other unmeasured or inappropriate factors could not be completely ruled out.
This article focuses on the Chinese population, but caution should be exercised for populations with other genetic backgrounds. At the same time, some patients with monocyte and HDL deficiency were excluded from the included cases, which would also cause inconsistent results.
Research limitations and future research directions
This paper has a small sample size, but there are sample selection biases and limitations. Furthermore, there is a lack of long-term monitoring and observation data to evaluate the long-term impact of Cmmi-MHR combined with thromboelastography parameters on the prognosis of acute cerebral infarction. There are still certain technical limitations and standardization deficiencies in thromboelastography technology and Cmmi MHR calculation methods.
In future research, we will consider increasing the sample size, conducting long-term tracking studies, and delving into the stability and persistence of these parameters in prognosis prediction. We will also strive for technological improvements to improve image resolution and data accuracy, to further reveal the potential value of Cmmi-MHR combined with thromboelastography parameters in predicting acute cerebral infarction.