Use of FGF21 in the preparation of a product for the assessment of the risk of suffering from or prognosis of retinal artery occlusion

Abstract

The present invention discloses the use of FGF21 in the preparation of products for the assessment of the risk of suffering from or prognosis of retinal artery occlusion. The present invention finds that the level of FGF21 in serum is related to the prevalence of RAO, and is also related to the risk of concurrent ischemic stroke in RAO patients, and is further related to the degree of visual improvement in RAO patients. Based on this, the present invention provides the application of the level of fibroblast growth factor 21 in the preparation of products for the assessment of the risk of suffering from retinal artery occlusion in a subject, the assessment of the risk of suffering from concurrent ischemic stroke in retinal artery occlusion, and the assessment of the prognosis risk of retinal artery occlusion patients, which has great application potential in the early diagnosis and treatment of RAO, the assessment of the risk of suffering from concurrent ischemic stroke in retinal artery occlusion, and the assessment of the visual prognosis of retinal artery occlusion.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and particularly to the use of circulating serum fibroblast growth factor 21 (FGF21) in the preparation of a product for assessing the risk of retinal artery occlusion in a subject, in a product for assessing the risk of concurrent ischemic stroke in a patient with retinal artery occlusion, and in a product for assessing the visual prognosis of a patient with retinal artery occlusion. Background Art

[0002] Retinal artery occlusion (RAO) is an ophthalmic emergency characterized by irreversible severe visual impairment. According to a consensus statement published by the American Heart Association, RAO is defined as a variant of acute ischemic stroke. Although the prevalence of acute RAO is estimated to be 2 - 3 per 100,000 people, the visual prognosis of most patients is below functional vision, and the risk of stroke is high, posing a major threat to the health of the elderly. Currently, the diagnosis of RAO mainly relies on the clinical manifestations of monocular vision loss and the typical funduscopic findings of retinal edema and cherry - red spot, without additional existing specific tools for early prediction and diagnosis. Therefore, early detection of RAO patients has become crucial. A variety of treatment methods for RAO have been developed, including tissue - type plasminogen activator administration, anterior chamber paracentesis, and hyperbaric oxygen chamber treatment. However, according to current clinical evidence, the above - mentioned treatment methods rarely show good treatment effects. Summary of the Invention

[0003] The present invention discovers that the level of FGF21 in serum is related to the prevalence of RAO, and is related to the risk of concurrent ischemic stroke in RAO patients, and is also related to the degree of visual improvement in RAO patients. One objective of the present invention is to develop a product for assessing the risk of retinal artery occlusion for subjects without clinical manifestations, another objective is to develop a product for assessing the risk of ischemic stroke complications for patients already diagnosed with retinal artery occlusion, and another purpose is to develop a product for assessing the visual prognosis risk for patients already diagnosed with retinal artery occlusion.

[0004] In a first aspect, the present invention provides the use of a biomarker in the preparation of a product for the diagnosis, treatment, risk assessment of retinal artery occlusion, and risk assessment of complications, wherein the biomarker comprises fibroblast growth factor 21.

[0005] In one embodiment, the biomarker is a combination of fibroblast growth factor 21, glucose, triglyceride, high - density lipoprotein cholesterol, and monocytes.

[0006] In one embodiment, the products for the diagnosis of retinal artery occlusion, assessment of the risk of disease, and assessment of the risk of complications are one or more of reagents, kits, chips, systems, and instruments; the reagents, kits, and chips target fibroblast growth factor 21, or a combination of fibroblast growth factor 21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes for detection. The products for the treatment of retinal artery occlusion include drugs for treating retinal artery occlusion. The treatment includes treatment for those already suffering from the disease, preventive treatment, and preventive measures. Treatment for those already suffering from the disease and preventive treatment include administering drugs that reduce the level of FGF21 in the blood, and preventive measures include changing exercise activities, changing lifestyle, and changing diet to reduce the level of fibroblast growth factor 21 in the blood.

[0007] In a second aspect, the present invention provides the use of a reagent for detecting a biomarker in the preparation of a kit for assessing the risk of developing retinal artery occlusion or the risk of its concurrent ischemic stroke. The reagent for detecting the biomarker includes a reagent for detecting the level of fibroblast growth factor 21 in serum.

[0008] In one embodiment, the reagent for detecting the biomarker is a reagent combination of fibroblast growth factor 21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes.

[0009] In one embodiment, the kit for the diagnosis or prognosis assessment of retinal artery occlusion is used to detect the level of fibroblast growth factor 21 in serum, and compare the statistical result of the level of fibroblast growth factor 21 in the serum of the subject with the statistical result of the level of fibroblast growth factor 21 in the serum of healthy individuals. When there is a significant difference between the statistical results of the level of fibroblast growth factor 21 in the serum of the subject and the level of fibroblast growth factor 21 in the serum of healthy individuals, it is determined that the subject has a high risk of developing retinal artery occlusion or a high risk of concurrent ischemic stroke.

[0010] In one embodiment, the serum is preferably the serum of circulating blood.

[0011] In a third aspect, for subjects who have not been diagnosed with retinal artery occlusion and do not have retinal artery occlusion, the present invention provides a system for assessing the risk of developing retinal artery occlusion, including:

[0012] An acquisition module for acquiring the level of a biomarker in the serum of the subject; the biomarker includes fibroblast growth factor 21;

[0013] An evaluation module, configured to evaluate the risk of a subject (i) suffering from retinal artery occlusion, (ii) suffering from retinal artery occlusion complicated with ischemic stroke, or (iii) visual prognosis according to the level of the biomarker, and output a risk evaluation result;

[0014] Wherein, the acquisition module and the evaluation module are connected by wireless and / or wired means.

[0015] In a fourth aspect, for a subject who has been diagnosed with retinal artery occlusion, the present invention provides a risk assessment system for a patient with retinal artery occlusion complicated with ischemic stroke, including:

[0016] An acquisition module, configured to acquire the level of a biomarker in the serum of the subject; the biomarker includes fibroblast growth factor 21;

[0017] An evaluation module, configured to evaluate the risk of a subject (i) suffering from retinal artery occlusion, (ii) suffering from retinal artery occlusion complicated with ischemic stroke, or (iii) visual prognosis according to the level of the biomarker, and output a risk evaluation result;

[0018] Wherein, the acquisition module and the evaluation module are connected by wireless and / or wired means.

[0019] In a fifth aspect, for a subject who has been diagnosed with retinal artery occlusion, the present invention provides a risk assessment system for the prognosis of a patient with retinal artery occlusion, including:

[0020] An acquisition module, configured to acquire the level of a biomarker in the serum of the subject; the biomarker includes fibroblast growth factor 21;

[0021] An evaluation module, configured to evaluate the risk of a subject (i) suffering from retinal artery occlusion, (ii) suffering from retinal artery occlusion complicated with ischemic stroke, or (iii) visual prognosis according to the level of the biomarker, and output a risk evaluation result;

[0022] Wherein, the acquisition module and the evaluation module are connected by wireless and / or wired means.

[0023] In a specific embodiment of the above risk assessment system of the present invention, when the absolute concentration of fibroblast growth factor 21 ≥ 192.67 pg / mL, the risk assessment result output by the evaluation module is that the subject is prone to suffer from retinal artery occlusion complicated with ischemic stroke.

[0024] In the specific implementation manner of the above risk assessment system of the present invention, the level of fibroblast growth factor 21 in the subject's serum refers to the absolute concentration of fibroblast growth factor 21 in the subject's serum, or the relative concentration of fibroblast growth factor 21 in the subject's serum. The relative concentration refers to the ratio of the absolute concentration of fibroblast growth factor 21 in the subject's serum to the statistical result of the absolute concentration of fibroblast growth factor 21 in the serum of healthy people.

[0025] In the specific implementation manner of the above risk assessment system of the present invention, the evaluation module is used to perform a risk assessment on the level of fibroblast growth factor 21 obtained by the acquisition module and output a risk assessment result. The evaluation module includes a risk assessment model, and the formula of the risk assessment model is: Logit(P) = -1.457 + 0.007 * FGF21 level, where P represents the probability of RAO onset.

[0026] In the specific implementation manner of the above risk assessment system of the present invention, the biomarker is a combination of fibroblast growth factor 21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes. The evaluation module is used to perform a risk assessment on the levels of fibroblast growth factor 21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes obtained by the acquisition module and output a risk assessment result. The evaluation module includes a risk assessment model, and the formula of the risk assessment model is:

[0027] Logit(P) = -7.027 + 0.006 * FGF21 level + 1.266 * glucose level + 1.159 * triglyceride level - 3.026 * high-density lipoprotein cholesterol level + 2.457 * monocyte count, where P represents the probability of RAO onset.

[0028] The risk assessment system is a tangible medium that stores a risk assessment method. In one embodiment, the test is performed by using a software program executed by a suitable processor. In certain embodiments, the program is embodied in software stored on a tangible medium. In certain other embodiments, the tangible medium is selected from a flash drive, a CD-ROM, a floppy disk, a hard disk drive, a DVD, and a memory associated with the processor.

[0029] In one embodiment, the acquisition module detects the level of fibroblast growth factor 21 in the serum by one or more of the following methods: chromatography, spectroscopy, mass spectrometry, chemical analysis.

[0030] In a sixth aspect, the present invention provides an auxiliary diagnostic instrument, including the above risk assessment system.

[0031] Compared with the prior art, the beneficial effects of the present invention are:

[0032] The present invention is particularly valuable in evaluating the risk of retinal artery occlusion (RAO) in subjects and the risk of concurrent ischemic stroke in patients with RAO, and has great application potential in the early diagnosis and treatment of RAO and the risk assessment of concurrent ischemic stroke and visual prognosis in patients with RAO. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the following will briefly introduce the drawings required for the description of the embodiments. Obviously, the drawings in the following description are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on these drawings.

[0034] Figure 1 : ROC curve of serum FGF21 level in patients with RAO.

[0035] Figure 2 : ROC curve of serum FGF21 level combined with other blood indexes in patients with RAO.

[0036] Figure 3 : Restricted cubic spline analysis shows a positive correlation between the prevalence of RAO and the serum FGF21 level. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0037] To make the objectives, technical solutions and advantages of the present invention clearer, the following will clearly and completely describe the technical solutions of the present invention in combination with the embodiments of the present invention. Obviously, the described embodiments are some, but not all, of the embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

[0038] The term "treatment" refers to therapeutic and prophylactic or preventive measures, where the aim is to prevent or slow down (mitigate) the target pathological condition or disorder. Persons in need of treatment include those who already have the disease, those who are susceptible to the disease or those who want to prevent the disease.

[0039] The term "level" refers to the absolute concentration.

[0040] The term "high risk" means a high prevalence in the prevalence statistics. The terms "prevalence", "incidence probability" and "disease risk" have the same meaning.

[0041] The term "stroke" refers to ischemic stroke, which is manifested as an ischemic lesion in the brain.

[0042] In the formula of the risk assessment model, Logit(P)=log(P / 1 - P), where P is the incidence probability of RAO.

[0043] Fibroblast growth factor 21 (FGF21) plays an important role in regulating energy balance and glycolipid homeostasis. It has been considered a potential risk factor for various metabolic diseases such as type 2 diabetes and cardiovascular diseases. It can also improve the neurological outcomes in mice with ischemic stroke and has an anti-atherosclerotic effect in vitro. In addition, FGF21 analogs are emerging therapeutic targets for type 2 diabetes and diabetic retinopathy. Currently, there is no research report on the relationship between FGF21 and the risk of retinal artery occlusion (RAO) or the co-occurrence of ischemic stroke in RAO patients.

[0044] In this invention, the relationship between the level of FGF21 in serum and the prevalence of RAO, the prevalence of ischemic stroke in RAO patients, and the degree of vision improvement in RAO patients was studied by statistical methods. It was found that the level of FGF21 in serum was significantly correlated with the increased risk of RAO. The higher the level of FGF21, the higher the risk of RAO. The results of logistic regression analysis showed that the odds ratio (95% confidence interval) of the fourth quartile (highest) to the first quartile (lowest) of the FGF21 level was 9.672 (2.573, 36.359). Moreover, when the level of FGF21 in serum ≥ 192.67 pg / mL, the prevalence of ischemic stroke in RAO patients was as high as 60%, and only 31.25% of the patients had improved vision.

[0045] The risk assessment system provided by this invention mainly evaluates the risk of retinal artery occlusion in subjects, the risk of co-occurrence of ischemic stroke in retinal artery occlusion patients, and the prognosis of retinal artery occlusion patients through the level of fibroblast growth factor 21 in the serum of subjects. Further, indicators such as glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes can be combined for risk assessment of disease occurrence or prognosis risk assessment. In the optimized model of this invention, fibroblast growth factor 21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes are used as biomarkers for combined evaluation. See Figure 2 , and the accuracy of combined evaluation is higher.

[0046] The experimental methods in the following examples are all conventional methods unless otherwise specified, and are carried out according to the techniques or conditions described in the literature in this field or according to the product instructions. The materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified.

[0047] Example

[0048] (1) Detection of FGF21

[0049] In participants without a diagnosis of retinal artery occlusion (RAO) and those without RAO, blood samples were collected after a 12-hour fast using standard venipuncture techniques. Serum FGF21 levels were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) kit (R&D Systems, USA, catalog number: DY2539). The colorimetric system of the sandwich ELISA kit included streptavidin-HRP, hydrogen peroxide, and tetramethylbenzidine. The coefficients of variation within and between batches were 2.9%-3.9% and 5.2%-10.9%, respectively.

[0050] (2) Measurement of visual prognosis in RAO patients

[0051] All RAO patients were evaluated by experienced ophthalmologists upon admission and before discharge. Visual acuity (VA) was evaluated using a standard logarithmic visual acuity chart, and the results were converted to the logarithm of the minimum angle of resolution (logMAR) according to the formula logMAR = lg(1 / decimal VA). Additionally, for low visual acuity categories such as "counting fingers", "hand movement", "light perception", and "no light perception", the corresponding logMAR values were determined to be 2.0, 2.3, 2.6, and 2.9, respectively. The criterion for a significant improvement in visual acuity was a reduction in logMAR of ≥0.3 in the discharge vision relative to the admission vision.

[0052] (3) Measurement of concurrent ischemic stroke in RAO patients

[0053] The primary outcome of RAO was the occurrence of concurrent ischemic stroke. All RAO patients underwent brain magnetic resonance imaging (MRI) within 7 days after the onset of RAO, and all images were evaluated by a certified neurologist for the presence of acute ischemic lesions. MRI was performed on a magnetic resonance imaging system (1.5T - GE Signa; GE Medical Systems, Milwaukee, Wisconsin). High signal intensity on diffusion-weighted imaging (DWI) and low signal intensity on the apparent diffusion coefficient (ADC) map, or low signal intensity on T1-weighted imaging 16 hours after the initial stroke and high signal intensity on T2-weighted imaging 8 hours after the initial stroke were considered acute ischemic lesions.

[0054] (4) Statistical analysis

[0055] Continuous variables were described as the median and interquartile range. The Mann-Whitney test was used for between-group comparison of continuous data. Categorical variables were presented as numbers and percentages. The chi-square test was performed to compare categorical data. Logistic regression analysis in the statistical software IBM SPSS (version number 26) was used to evaluate the association between the ln-transformed serum FGF21 level and the occurrence of RAO and its visual and concurrent ischemic stroke outcomes. Restricted cubic regression splines in R software (version number 4.2.3) were used to evaluate the potential non-linear relationship between FGF21 levels and the prevalence of RAO. A two-sided p-value < 0.05 was considered statistically significant.

[0056] (5) Diagnosis and prediction

[0057] (5.1) Analyze the correlation between serum FGF21 levels and the prevalence of RAO

[0058] As shown in Table 1, the present invention divided the FGF21 levels into quartiles, and the FGF21 levels in serum samples were divided into quartiles. The first quartile (level 1) was the lowest level, ≤ 119.561 pg / mL, which was used as the baseline for evaluating the odds ratio of RAO (Table 1). It was found that with the increase in FGF21 levels in different models, the odds ratio of the occurrence risk of RAO increased significantly:

[0059] In the crude model and model 1 (adjusted according to clinical data such as gender, age, diabetes, and hypertension), there was a positive correlation between serum FGF21 levels and the prevalence of RAO. After additional adjustment of variables such as neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, glutamic oxaloacetic transaminase, triglycerides, high-density lipoprotein cholesterol, glomerular filtration rate, and glucose in model 2, the correlation between serum FGF21 levels and the prevalence of RAO was still statistically significant. In the fully adjusted model 2, the odds ratio (95% confidence interval) of level 4 (the highest) of serum FGF21 levels compared to level 1 (the lowest) was 9.672 (2.573, 36.359). Similarly, after adjusting for confounding factors including neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, glutamic oxaloacetic transaminase, triglycerides, high-density lipoprotein cholesterol, glomerular filtration rate, and glucose, the correlation between serum FGF21 levels and the prevalence of RAO was still significant, as shown in Table 2.

[0060] Table 1 Logistic regression analysis of transformed serum FGF21 levels on RAO

[0061]

[0062]

[0063] Crude model: No adjustment.

[0064] Model 1: Adjusted for sex, age, hypertension, and diabetes.

[0065] Model 2: Adjusted for the same variables as Model 1 and variables such as neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, glutamic oxaloacetic transaminase, triglycerides, high-density lipoprotein cholesterol, glomerular filtration rate, and glucose.

[0066] Table 2 Logistic regression analysis of serum FGF21 levels and the risk of RAO

[0067]

[0068] Crude model: No adjustment.

[0069] Model 1: Adjusted for sex, age, hypertension, and diabetes.

[0070] Model 2: Adjusted for the same variables as Model 1 and variables such as neutrophils, lymphocytes, neutrophil-to-lymphocyte ratio, monocytes, glutamic oxaloacetic transaminase, triglycerides, high-density lipoprotein cholesterol, glomerular filtration rate, and glucose.

[0071] Restricted cubic spline analysis of the fully adjusted data also showed a positive correlation between the prevalence of RAO and serum FGF21. As Figure 3 shown, the curve shows that the threshold for the ln-transformed FGF21 level (equivalent to an FGF21 level of 192.67 pg / mL) used to predict the risk of RAO is approximately 5.26, and beyond this threshold, the odds ratio increases.

[0072] As Figure 1 shown, the single-factor Logistics risk prediction model for fibroblast growth factor 21 level in serum is: Logit(P) = -1.457 + 0.007 * FGF21 level. The area under the curve (AUC) of FGF21 is 0.715 ([95% CI] = [0.647, 0.783]), the sensitivity is 81.13%, the specificity is 50.09%, and the Youden index is 0.3207. This indicates that the FGF21 level has a certain degree of accuracy in predicting the probability of RAO occurrence.

[0073] As Figure 2As shown in the figure, when the levels of FGF21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes in serum are used for combined evaluation, the Logistics risk prediction model is: Logit(P) = -7.027 + 0.006 * FGF21 level + 1.266 * glucose level + 1.159 * triglyceride level - 3.026 * high-density lipoprotein cholesterol level + 2.457 * monocyte count. The area under the curve is 0.877, ([95% CI] = [0.829, 0.925]), the sensitivity is 77.23%, the specificity is 86.79%, and the Youden index is 0.6402. This indicates that the combination of FGF21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes has higher accuracy in predicting the prevalence of RAO.

[0074] Table 3 ROC curve analysis of FGF21 combined with laboratory indicators for the diagnosis of RAO

[0075]

[0076]

[0077] As shown in Table 4, in terms of the percentage of improvement in visual acuity (VA), the trend of decreasing percentage with the increase in FGF21 level remains consistent. The overall FGF21 level is negatively correlated with the prognosis of RAO patients. There is no significant difference after stratified analysis, which may be due to insufficient sample size.

[0078] Table 4 Relationship between serum FGF21 level and visual acuity improvement in RAO patients

[0079]

[0080] (5.2) Analyze the correlation between serum FGF21 level and ischemic stroke

[0081] As shown in Table 5, after adjusting for age, gender, hypertension, diabetes, hyperlipidemia, smoking, and alcohol consumption, the incidence of ischemic stroke is positively correlated with the ln-transformed FGF21 level (OR [95% CI] = 1.944 [1.029, 3.672], P = 0.04). An increase in the serum FGF21 level is associated with an increased risk of ischemic stroke in RAO patients. In the stratified analysis according to the serum FGF21 level, for participants with a serum FGF21 level ≥ 192.67 pg / mL, this association remains statistically significant, and the prevalence of ischemic stroke in RAO patients is 60%. However, for participants with a serum FGF21 level < 192.67 pg / mL, this association is not significant, and the prevalence of ischemic stroke in RAO patients is 46.34%.

[0082] Table 5 Relationship between Serum FGF21 Level and Concurrent Ischemic Stroke in Patients with RAO

[0083]

[0084] In the description of this specification, the description with reference to terms such as "one embodiment / way", "some embodiments / ways", "example", "specific example" or "some examples" means that the specific features, structures, materials or characteristics described in connection with the embodiment / way or example are included in at least one embodiment / way or example of the present invention. In this specification, the schematic expressions of the above terms do not necessarily refer to the same embodiment / way or example. Moreover, the specific features, structures, materials or characteristics described can be combined in a suitable manner in any one or more embodiments / ways or examples. In addition, without contradiction, those skilled in the art can combine and combine the different embodiments / ways or examples described in this specification and the features of different embodiments / ways or examples.

[0085] It should be noted that in the present invention, relational terms such as "first" and "second" are only used to distinguish one entity or operation from another entity or operation, and do not necessarily require or imply any such actual relationship or order between these entities or operations. Moreover, the term "comprising", "including" or any other variant thereof is intended to cover a non-exclusive inclusion, so that a process, method, article or device comprising a series of elements includes not only those elements but also other elements not expressly listed, or also includes elements inherent to such process, method, article or device. Without further limitation, an element defined by the statement "comprising one..." does not exclude the existence of additional identical elements in the process, method, article or device comprising the element. In the present invention, the meaning of "a plurality" is at least two, such as two, three, etc., unless otherwise specifically defined.

[0086] The above are only specific embodiments of the present invention, enabling those skilled in the art to understand or implement the present invention. Various modifications to these embodiments will be obvious to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to these embodiments shown herein, but rather to the broadest scope consistent with the principles and novel features claimed herein.

Claims

1. Use of a reagent for detecting the level of biomarkers in serum in the preparation of a product for diagnosing retinal artery occlusion or assessing the risk of disease, characterized in that: The biomarkers include fibroblast growth factor 21.

2. The use according to claim 1, characterized in that: The biomarker is a combination of fibroblast growth factor 21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes.

3. The use according to claim 1 or 2, characterized in that: The product used for diagnosing retinal artery occlusion or assessing the risk of disease is one or more of a reagent, a kit, a chip, a system, or an instrument.

4. A risk assessment system, characterized in that: include: An acquisition module, used to obtain the level of biomarkers in the serum of the subject; the biomarkers include fibroblast growth factor 21; An assessment module, used to assess the risk of the subject suffering from retinal artery occlusion according to the level of the biomarker and output a risk assessment result; Wherein, the acquisition module and the evaluation module are connected wirelessly and / or wiredly.

5. The risk assessment system according to claim 4, characterized in that: The biomarker is a combination of fibroblast growth factor 21, glucose, triglyceride, high-density lipoprotein cholesterol, and monocytes.

6. The risk assessment system according to claim 5, characterized in that: The evaluation module includes a risk evaluation model, and the formula of the risk evaluation model is: Logit (P) = -7.027 + 0.006 * FGF21 level + 1.266 * glucose level + 1.159 * triglyceride level - 3.026 * high-density lipoprotein cholesterol level + 2.457 * monocyte count, P represents the probability of RAO.

7. An auxiliary diagnostic instrument, characterized in that: A risk assessment system comprising the risk assessment system described in any one of claims 4 to 6.

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