Association between Fundus Atherosclerosis and Carotid Arterial Atherosclerosis ()
1. Introduction
Atherosclerosis, especially carotid atherosclerosis, is closely related to the occurrence, development and recurrence of cerebral infarction, and is the most important cause and risk factor of cerebral infarction [1] . Insufficient perfusion of the carotid artery will inevitably cause blood supply disorders to the retina, retrobulbar artery, and posterior ciliary artery, resulting in impaired circulation within the optic disc. The eyeground artery is the only artery that can be directly observed from the body surface through an ophthalmoscope or fundus camera. The degree of its atherosclerotic lesions can be used as a window to reflect systemic arteriosclerosis and is closely related to the onset of cardiovascular and cerebrovascular diseases [2] [3] . The carotid artery is an important branch of the human aorta, while the ophthalmic artery mostly originates from the internal carotid artery. Plaque-like lesions in the carotid artery can cause thickening of the intima-media, leading to arterial stenosis, hemodynamic changes, and blood microcirculation disorders, leading to ischemic eye diseases [4] . In addition, an increasing number of studies have confirmed that patients with carotid artery stenosis often have ischemic eye lesions, which often appear as the first symptom of internal carotid artery stenosis [5] . This study is intended to help clinical patients objectively evaluate the presence and severity of atherosclerosis in different individuals through non-invasive examinations such as ophthalmoscope or fundus camera by observing the correlation between eyeground arteriosclerosis and carotid atherosclerosis, and guide clinical patients to better prevent stroke at the first level.
2. Research Object and Method
2.1. Research Subjects
516 individuals aged ≥ 40 years who underwent neck vascular ultrasound and color fundus photography simultaneously at the physical examination center of Deyang People’s Hospital in Sichuan Province from June 2020 to December 2022 using a random sampling method. Among them, there are 257 males and 259 females, aged 40 - 80 years, with an average age of 54.6 ± 16.3 years.
2.2. Method
1) Evaluate the traditional risk factors of the enrolled patients, including age, gender, hypertension, diabetes, coronary heart disease and other medical history; Fasting venous blood was collected to measure blood glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and homocysteine.
2) Fundus examination: Using the CR-2 fundus camera from CANON Company in Japan, the examination is completed in a dark room. According to Keith Wagner’s classification of the presence and severity of retinal arteriosclerosis [6] [7] : 0 level: no retinal arteriosclerosis; Grade I: Mild extensive thinning of retinal arteries with enhanced reflective bands; Grade II: Retinal artery stenosis and widened reflective band, arteriovenous compression; Level III: On the basis of the above level II, accompanied by retinal hemorrhage or exudation; Grade IV: On the basis of Grade III retinal fundus changes, optic nerve papillary edema appears. The above examinations and results are determined by two qualified clinical physicians. If the grading of the fundus examination of both eyes is inconsistent, the one with higher grading will be counted.
3) Carotid artery examination method and observation indicators: The Philips EPIQ7 color ultrasound diagnostic instrument and 7.5 MHz linear array probe were used to detect the bilateral carotid arteries of the subject. Sampling location: Common carotid artery (1.0 - 1.5 cm from the bifurcation); the bifurcation of the common carotid artery and the internal carotid artery (1.0 to 1.5 cm from the bifurcation). Observation indicators: a) Intima media thickness (IMT) of the common carotid artery, defined as IMT thickening when IMT ≥ 1.0 mm; b) presence or absence of carotid plaques, whether carotid plaques are vulnerable or stable. Carotid artery plaques are defined as those with IMT ≥ 1.5 mm. For patients with carotid artery plaques, the plaques can be further divided into: (i) hypoechoic lipid soft plaques; (ii) Fibrous flat plaques with moderate echogenicity and rich collagen tissue; (iii) Ulcerative mixed type plaques with varying echogenicity; (iv) A calcified hard plaque with strong echoes and echogenic shadows. Define types (i), (ii), and (iii) of plaques as vulnerable plaques, and type (iv) of plaques as stable plaques. The plaque score method was used to score the plaque [8] , that is, without calculating the length of each plaque, only the maximum thickness (mm) of each isolated carotid atherosclerotic plaque on the same side was added to obtain the carotid plaque score on that side, and the sum of the carotid plaque scores on both sides was the total plaque score of the patient. The total plaque score of 1.1 - 5.0 is mild carotid atherosclerosis; 5.1 - 10.0 are moderate carotid atherosclerosis 10.0 is severe carotid atherosclerosis; c) The presence and severity of carotid artery stenosis: The location of the largest plaque is evaluated based on the ultrasound blood velocity of the carotid artery and the cross-sectional area of the residual cavity to determine the presence and severity of carotid artery stenosis. Based on this, the research subjects were divided into: normal or carotid artery stenosis group (vascular stenosis degree < 50%), moderate carotid artery stenosis group (stenosis degree 50% - 69%), and severe carotid artery stenosis group (stenosis degree 70% - 99%) [8] [9] .
2.3. Statistical Analysis
Statistical analysis was conducted using SPSS 23.0 statistical software. Counting data is expressed in terms of rate, and inter group comparisons are made using X2. The measurement data are expressed as mean ± standard deviation. The comparison of measurement data of normal distribution is performed by analysis of variance or t-test, otherwise, the rank sum test is used. Spearman rank correlation analysis of the correlation between fundus arteriosclerosis and age. Use logistic regression to analyze the risk factors of fundus arteriosclerosis and carotid arteriosclerosis. P < 0.05 indicates a statistically significant difference.
3. Results
3.1. Comparison of General Conditions and Risk Factors among Different Grades of Fundus Arteriosclerosis
Among the 516 physical examination patients, 198 (38.4%) had normal fundus examination, and 318 (61.6%) had fundus arteriosclerosis. Among them, 166 cases were of grade I (32.2%), 86 cases were of grade II (16.7%), and 66 cases were of grade III (12.8%). No grade IV lesions were found in this group of data. Compared with those with normal fundus examination, those with grade II and III fundus arteriosclerosis were older, had a history of hypertension and diabetes, and other general conditions and risk factors were not statistically significant between the two groups (see Table 1). Spearman correlation analysis found a correlation between the degree of fundus arteriosclerosis and age (r = 0.422).
3.2. Single Factor Analysis of the Correlation between the Grading of Eyeground Arteriosclerosis and Carotid Atherosclerosis
Among 516 physical examinees, 286 (55.4%) had no carotid atherosclerotic plaque, 201 (38.9%) had carotid atherosclerotic plaque, of which 58 (11.2%) were vulnerable plaque, 172 (33.3%) were stable plaque; There were 33 cases (6.4%) with carotid artery stenosis, including 23 cases (4.5%) with <50% stenosis and 10 cases (1.9%) with 50% - 69% stenosis. No stenosis ≥ 70% was found in this group of data. The IMT thickness of bilateral common carotid arteries, the incidence of carotid plaques and vulnerable plaques, the score of carotid plaques, and the presence of carotid stenosis in patients with fundus arteriosclerosis were significantly higher than those with normal fundus examination, with statistical significance (P < 0.05, see Table 1). Vascular elastic function is related to the degree of arteriolar wall sclerosis, expandability and lumen size, which are all affected by atherosclerosis. The first affected part of arteriosclerosis is the intima
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Table 1. Correlation factors of different grades of eyeground arteriosclerosis and their relationship with carotid atherosclerosis.
and media, and vascular elastic function is mainly maintained by the elastic fibers of the media. When hardening occurs, the media is damaged, and then the arterial elastic function decreases, thereby affecting the vascular volume, resulting in hemodynamic changes [10] .
3.3. Multifactor Analysis of the Correlation between the Grading of Eyeground Arteriosclerosis and Carotid atherosclerosis
With eyeground arteriosclerosis II and III as dependent variables, the parameters with statistical significance between different grades of eyeground arteriosclerosis in the above univariate analysis as independent variables, including age, hypertension, diabetes, carotid atherosclerotic plaque, vulnerable carotid atherosclerotic plaque, carotid stenosis, bilateral common carotid artery IMT thickness and carotid plaque score, etc., Fundus arteriosclerosis was independently correlated with age, hypertension, vulnerable plaque of carotid atherosclerosis, carotid stenosis, IMT of common carotid artery, and carotid plaque score, with statistical significance (P < 0.05, see Table 2). Evidence-based medicine confirms that the occurrence of arteriosclerosis is influenced by age, blood pressure, blood lipids, diabetes, uric acid, obesity, smoking and diet habits, and the influence of various risk factors such as genetics. Fundus arteriosclerosis is a type of slow Sexual vascular disease that is one of the indications for target organ and peripheral arterial sclerosis, which is Aging manifestations of the vascular system around the body; Fundus artery microvascular abnormalities and heart. The occurrence, development, and prognosis of cerebrovascular diseases are closely related; Vascular lesions. It is systemic and can predict systemic arterial stiffness simultaneously with an increase in pulse pressure [11] .
4. Discussion
Atherosclerosis is a chronic and progressive systemic arterial disease, which is characterized by the accumulation of lipids and complex sugars, bleeding and
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Table 2. Multiple analyses of the main risk factors for vulnerable plaques.
OR: Odds ratio; CI: Confidence interval.
thrombosis, followed by fibrous tissue hyperplasia and calcification, and the gradual degeneration and calcification of the middle layer of the artery, leading to thickening and hardening of the arterial wall and narrowing of the vascular lumen, which are the main reasons for clinical cardiovascular and cerebrovascular events [2] [8] [12] . Carotid atherosclerosis is closely related to the occurrence, development and recurrence of cerebral infarction, and is the most important cause and risk factor of cerebral infarction [1] . Atherosclerosis screening is beneficial for early detection of atherosclerosis patients and early intervention of atherosclerosis, which is of great significance in preventing cardiovascular and cerebrovascular diseases [13] .
Carotid atherosclerosis inspection methods include carotid color Doppler ultrasound, CT angiography (CTA), magnetic resonance angiography (MRA) and cerebral angiography [14] , but these inspection methods are expensive, some are invasive inspection methods, which is not conducive to carotid atherosclerosis screening. The retinal artery of the fundus is a branch of the internal carotid artery and is one of the few small arteries in clinical practice that can be directly observed in morphology in vivo. With the popularization of digital technology, fundus digital photography technology can provide objective and standardized manifestations of retinal arteriole abnormalities [6] [7] , which is a simple, easy-to-implement, low-cost, non-invasive, and easily accepted examination method for patients. Multiple studies have found that the degree of fundus arteriosclerosis is related to cerebral small vessel disease, suggesting that fundus arteriosclerosis can serve as a clinical observation window for cerebral small vessel disease [15] . The correlation between fundus retinal angiopathy and cervical atherosclerosis has been confirmed by some studies. Studies have found that carotid artery IMT is associated with retinal arteriovenous diameter and arterial/venous ratio [16] . In addition, the severity of retinal microvascular lesions is related to the degree of extracranial carotid artery stenosis and the area of carotid artery plaques [17] . The results of this study found that eyeground arteriosclerosis was independently related to vulnerable carotid atherosclerotic plaque, carotid stenosis, common carotid artery IMT, and carotid plaque score, which was consistent with the above results. The results suggest that eyeground atherosclerosis can be used as one of the indicators to judge the presence and severity of carotid atherosclerosis.
This study found that eyeground arteriosclerosis is related to age, hypertension and diabetes, and age and hypertension are independently related to the severity of eyeground arteriosclerosis, which is consistent with previous research results [2] [7] . Therefore, for patients with these risk factors, timely change of bad lifestyle and active intervention of hypertension and diabetes may reduce the incidence of atherosclerosis, and thus reduce the incidence of cardiovascular and cerebrovascular diseases.
To sum up, carotid artery disease is closely related to the degree of eyeground arteriosclerosis. Fundus photography is a simple, easy, non-invasive and easy-to-accept inspection method. Its results are helpful to judge whether carotid atherosclerosis is present and serious, guide clinical early detection and intervention of atherosclerosis, and reduce the incidence of cardiovascular and cerebrovascular diseases.
5. Limitations and Future Directions
This study is a cross-sectional study and cannot explain the sequence of occurrence of fundus arteriosclerosis and carotid arteriosclerosis. However, existing studies have shown that carotid arteriosclerosis occurs earlier than fundus arteriosclerosis. In the future, further experiments on improving arteriosclerosis can be conducted to improve the accuracy of predicting changes in the carotid artery in the fundus arteries.