Acute ischemic stroke (AIS) is a disorder of blood flow supply to brain tissue caused by various reasons, which is characterized by high morbidity, disability, and mortality (1). According to statistics, the number of deaths due to ischemic stroke (IS) in the world ranks first in the number of deaths from cardiovascular and cerebrovascular diseases. It is one of the third leading causes of death in the world. China is a country with a high incidence of stroke. The incidence of stroke was 170/100,000 and 620/100,000 in males and females, respectively, and the prevalence rate was 620/100,000.

There are many pathogenic factors and complex pathological mechanisms of AIS. At present, it is generally believed that the occurrence of AIS is caused by atherosclerosis. Oxidative stress and vascular endothelial dysfunction are the primary pathogenesis of atherosclerosis. In recent years, with the deepening of research, people have found that the renin-angiotensin system (RAS) activation is closely related to AIS, which can directly or indirectly induce the occurrence and influence the development of AIS.

RAS is an endocrine regulatory system composed of peptide hormones and corresponding enzymes as the main components. It comprises six parts: renin, angiotensinogen, angiotensin, angiotensin-converting enzyme, angiotensin receptor, and aldosterone. Renin is an acid-hydrolytic protease produced by the juxtaglomerular cells of the kidney. Sodium depletion, sympathetic excitation, and decreased renal blood flow stimulate the release of renin, which acts on the hepatic production of angiotensinogen to convert it to angiotensin I (Ang I). Ang I has no biological activity and is further hydrolyzed to angiotensin II (Ang II) by the action of angiotensin-converting enzyme I. Ang II can be further decomposed into angiotensin (1–7) and angiotensin III and angiotensin IV by the step of angiotensin-converting enzyme II and aminopeptidase A, respectively (2).

Over-activation of RAS can produce a series of pathophysiological effects. At present, it is believed that circulating RAS mainly acts through the following two axes: (1) angiotensin-converting enzyme 1-Ang II-AT1R axis: the binding of Ang I-IV to AT1R leads to vasoconstriction, tissue cell fibrosis, and oxidative stress; (2) Angiotensin-converting enzyme 2-Ang (1–7)-Mas receptor axis: The binding of angiotensin domain with AT2R and Ang (1–7) with Mas receptor can resist the pathological effects of AT1R, dilate blood vessels, anti-inflammation, anti-tissue cell fibrosis, reduce cell apoptosis, and have protective effects on heart, brain, kidney, blood vessels and other organs (2). Studies on the pathological mechanism of RAS causing AIS mainly focus on Ang II, and the relationship between other components of RAS and AIS is relatively few.

The preferred treatment for AIS is intravenous thrombolysis within the time window. Still, due to the strict time window, the proportion of patients who can benefit from it is relatively low, and the treatment effect is poor (3). In recent years, with the continuous development of various endovascular therapy (EVT) devices and techniques, EVT has shown a good application prospect in treating AIS. Some domestic and foreign AIS treatment guidelines (4) recommend EVT as the first choice of treatment when intravenous thrombolysis is contraindicated or ineffective. Studies have shown that the overexpression of inflammatory factors and abnormal secretion of neurohormones in the pathogenesis of AIS aggravates the degree of neurological impairment and affects the prognosis of patients (5).

At present, the content of clinical evaluation of the development and prognosis of AIS mainly includes serological indicators and imaging examinations, among which serological indicators have the advantages of being simple, fast, and highly accurate and have become an essential means to guide clinical diagnosis and treatment. The primary objective of this study is to analyze the risk factors related to the occurrence of AIS, and the secondary aim is to explore the role of serum indicators such as neurohormones, blood routine, liver and kidney function, electrolytes, and coagulation function in the prognosis of patients undergoing endovascular thrombectomy (EVT).

In this retrospective study, univariate and multivariate logistic regression were used to analyze the risk factors for AIS. Consistent with previous studies, advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors for acute ischemic AIS. We also found that the increase of white blood cells and the increase of neutrophil ratio in blood routine examination also have specific suggestive significance. In addition, we found that the higher Ang I was, the lower the risk of AIS was. The level of Ang I was higher in the good prognosis group. Significant differences existed in the expression of globulin, AGR, ALT, K+, and prothrombin activity between the good and the poor prognosis group. As previously mentioned, our study found that Ang I and AGR had a non-negligible impact on the prognosis of patients with AIS, so we developed a nomogram to evaluate its ability to predict the prognosis of AIS.

Risk factors for AIS include age, smoking, obesity, atrial fibrillation, hypertension, diabetes, etc. (6), of which hypertension is the most critical risk factor. Excluding other risk factors for AIS, a 10mmHg increase in systolic blood pressure was associated with a 49% increased risk of AIS, and a 5mmHg rise in diastolic blood pressure was associated with a 46% increased risk of AIS (7). Experimental results showed that the vascular shear stress was increased in hypertensive patients compared with normal people, which caused vascular endothelial damage (8). At the same time, endothelial injury also affects NO activity and increases the synthesis and release of endothelin and Ang II, resulting in vasomotor dysfunction (8). Wallace et al. found that after endothelial injury, endothelial cells will release a large number of active substances, including adenosine triphosphate, 5-hydroxytryptamine, etc., which can promote the synthesis and release of endothelin, increasing blood pressure, and then damage endothelial cells again, forming a vicious circle (9). The primary pathogenesis of AIS is as follows: The damage of vascular endothelial cells leads to atherosclerosis, which leads to occlusion of cerebral arteries and cerebral ischemia. Neurons in the ischemic center release the injury-related molecular pattern to activate the immune response (10–12).

Hyperactivation of the local renin-angiotensin-aldosterone system (RAAS) in hypertensive patients is also an important reason for vascular endothelial injury (13). RAAS is an essential regulatory system to maintain the body’s balance of water and electrolyte. Its dysfunction will lead to vasoconstriction and aggravate the degree of ischemic injury in cerebrovascular diseases. And affect the rate of vascular recanalization after treatment (14, 15). The mechanism of RAAS activation is as follows: firstly, angiotensinogen is converted into Ang I under the stimulation of renin, and then Ang I is converted into Ang II by ACE. Ang II increases aldosterone secretion through the sympathetic nervous system, resulting in water and sodium retention and increasing blood pressure (16).

Some studies have shown that the serum Ang II level of patients after intravenous thrombolysis or EVT treatment is significantly lower than that before treatment, and the serum Ang II level of patients in the EVT group is lower than that in intravenous thrombolysis group, suggesting that EVT can significantly reduce the neurohormone level of AIS patients (17–22). How does the level of Ang I change? Our study focused on the changes of Ang I.

Our study found that Ang I levels were lower in AIS patients than in controls and higher in the group with a good prognosis. One study had similar results to ours. The level of Ang I decreased while the level of Ang II remained unchanged, accompanied by an increase in ACE activity. This phenomenon can be explained by the decrease in renin caused by the negative feedback after the rise in blood pressure. Increased ACE activity can convert all available Ang I to Ang II (16). Another reason for maintaining a steady Ang II concentration may be the up-regulation of local AT1 and AT2 receptors in and around the infarct area. Animal experiments have also confirmed that RAAS promotes brain oxidative stress response, further promoting RAAS and sympathetic nervous system activation to mobilize peripheral organ responses (23).

Nomograms are highly effective in areas such as diagnosis and prediction. Compared with traditional scoring systems for IS (24, 25), the nomogram model can estimate the probability of adverse outcomes after EVT, which often provides a better-personalized assessment to help management decisions. In addition, the graph has higher accuracy and better-discriminating ability and is more convenient to use. Several studies have predicted poor outcomes in patients with IS. Zhang et al. established a nomogram model to predict the 3-month risk of death in IS patients with anterior circulation arterial occlusion who successfully received endovascular thrombolysis, composed of age, pretreatment collateral status, baseline blood glucose level, symptomatic intracranial hemorrhage, and baseline National Institutes of Health Stroke Scale score (26). Du et al. determined that age, baseline National Institutes of Health Stroke Scale score, collateral circulation, rapid blood glucose levels, and recirculation were independent predictors of malignant cerebral edema after EVT (27). A study from Japan also focused on whether imaging technology, low relative diffusion-weighted imaging (DWI) signal intensity, can predict good clinical outcomes after EVT in patients with acute IS. Forty-nine patients were included in the analysis, and the results showed that the relative DWI signal intensity of the group with a good prognosis was significantly lower than that of the group with a poor prognosis. Low relative DWI signal intensity was associated with a good prognosis after EVT (28). In this study, Ang I and AGR, two readily available variables, have good discriminative ability, and the AUC value of the combined ROC model is 0.859. Therefore, the combined Ang I and AGR model can predict the prognosis of AIS patients, thus achieving a more accurate therapeutic effect and better serving the patient population.

The small sample size limits our study, and the sample size will be expanded. This is a retrospective single-center study, and the results must be further prospectively verified in multiple centers. Our study has established the role of Ang I in the prognosis of patients undergoing EVT. Still, there was no study of the other components, including angiotensinogen and Ang II, so further studies are needed to explore the mechanisms and other parts of the RAAS system.

The study’s findings suggested advanced age, high blood glucose, high D-dimer, and high prothrombin activity are risk factors in patients with AIS. The higher the ANG I and AGR, the better the prognosis of AIS surgery. Furthermore, the combined ANG I and AGR model has a good predictive ability for the prognosis of patients undergoing arterial thrombectomy.

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding authors.

The studies involving humans were approved by The institutional review board of the First People’s Hospital of Lianyungang. The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.

SY: Conceptualization, Data curation, Formal Analysis, Writing – original draft. KL: Methodology, Software, Visualization, Writing – review & editing. ZH: Validation, Writing – review & editing. YX: Validation, Writing – review & editing. JL: Validation, Writing – review & editing. YS: Funding acquisition, Investigation, Resources, Supervision, Writing – review & editing. AL: Conceptualization, Project administration, Supervision, Writing – review & editing.