{"paper_id":"39c63249-1a61-4438-b60f-83f7d9d83e66","body_text":"Association of fibrinogen/albumin ratio and Castelli risk index 2 (CI2 = LDL-C/HDL-C) with severity of coronary artery disease and carotid atherosclerosis in different glucose metabolism states | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Association of fibrinogen/albumin ratio and Castelli risk index 2 (CI2 = LDL-C/HDL-C) with severity of coronary artery disease and carotid atherosclerosis in different glucose metabolism states Yue Liu, Xiandu Jin, Wenjun Jia, Xiuju Guan, Hao Wu, Jiao Li, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5827255/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The fibrinogen to albumin ratio (FAR) is a novel inflammatory indicator correlating with the severity of coronary artery disease. An indicator of atherosclerosis is the Castelli Risk Index 2 (CI2 = LDL-C/HDL-C). Yet, little research has focused on the link between both of indicators and coronary artery disease (CAD) and carotid atherosclerotic lesions in distinct glucose metabolic states. Thus, the aim of this investigation was to look into the link involving these two indicators and atherosclerotic lesions of the coronary and carotid arteries in patients with CAD who were in distinct glucose metabolic states. Method: In this investigation, coronary angiography and carotid Doppler ultrasonography were performed about 2825 individuals suffering from symptomatic CAD at Tianjin Union Medical Center from 2016 to 2023.The number of stenotic arteries in the coronary arteries was counted. Both the Carotid intima-media thickness and the Gensini score were taken into account or computed. Normal glucose regulation (NGR), pre-diabetes mellitus (Pre-DM), and diabetes mellitus (DM) were the three categories of glucose status according to the WHO diabetes guidelines. Patients were also divided into FAR index and Castelli risk index 2 quartiles to look into the link between FAR index and Castelli risk index 2 and coronary or carotid artery lesions in CAD patients with different glucose metabolic states. Receiver operating characteristic (ROC) curves were constructed to analyse the predictive value of the FAR index and Castelli risk index for coronary artery severity and carotid artery lesions. Result According to logistic regression analysis, the FAR index and Castelli risk index 2 were statistically associated with coronary artery disease and carotid plaques ( P < 0.05). The FAR index was linked with CAD severity regardless of glucose metabolism states ( P < 0.05). It was also substantially associated with carotid lesions in the NGR and Pre-DM stages ( P < 0.05), but not in the DM state ( P < 0.05). The Castelli risk index 2 was strongly linked with CAD severity and carotid artery lesions in both NGR and DM status ( P < 0.05). Yet, there was no statistical significance in Pre-DM states. ( P > 0.05). The FAR index and Castelli risk index 2 exhibited higher regions underneath the ROC curve in forecasting coronary artery lesions and carotid atherosclerosis. Conclusion The FAR index and Castelli risk index 2 were significantly associated with coronary and carotid atherosclerosis in different glucose metabolic states. FAR index and Castelli risk index 2 have predictive value for coronary artery lesions and carotid plaques. Fibrinogen/albumin ratio Castelli risk index 2 (CI2 = LDL-C/HDL-C) coronary artery disease Coronary artery disease severity Carotid atherosclerosis glucose metabolic state Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction A chronic cardiac condition identified as coronary artery disease (CAD) is brought by varying degrees of coronary artery stenosis. the incidence of which is increasing year by year, and the burden of CAD is growing and has become a major public health problem [ 1 , 2 ]. Inflammation plays an important role in the development and progression of atherosclerotic CAD [ 3 ]. In clinical practice, invasive coronary angiography (CAG) is considered as the most commonly used technique for detecting CAD, allowing precise assessment of the extent of coronary artery stenosis and the number of lesions. Based on the results of CAG, CAD is diagnosed in patients with ≥ 50% coronary lumen constriction [ 4 ]. In addition, the severity of CAD is related to the number of stenotic vessels. The higher the number of stenotic vessels in the coronary artery, the higher the risk of poor prognosis [ 5 ]. Most patients do not undergo CAG in a timely manner in the early stages of the disease, considering that CAG is invasive. In addition, populations with cardiovascular risk factors, especially those with type 2 diabetes mellitus (T2DM), have a higher risk of recurrence of CAD [ 6 ]. Therefore, in order to better reduce the incidence and mortality of CAD in patients, it is clinically important to identify and intervene in high-risk patients with CAD in a timely manner. Albumin is a 65 kDa protein that constitutes more than half of human serum proteins and is mainly synthesised in the liver with anti-inflammatory, antioxidant, anticoagulant and antiplatelet physiological properties [ 7 ]. Studies have shown that there is a correlation between plasma albumin levels and the prevalence, severity and mortality of CAD [ 8 ]. Fibrinogen, a plasma protein produced by the liver, plays an important role in the inflammatory response and coagulation system and is associated with the severity of CAD [ 9 ]. Recent studies have shown that fibrinogen to albumin ratio (FAR), reported as a new inflammatory marker, assesses the risk of prognosis in several cancer diseases [ 10 , 11 ]. In addition, the new inflammatory index FAR was significantly associated with CAD severity in patients with CAD [ 12 ]. The most prominent pathophysiological manifestation in the T2DM population is insulin resistance (IR), which fosters an inflammatory state, vascular endothelial dysfunction and lipid disorders, IR could potentially be the primary mechanism leading to atherosclerosis [ 13 ]. The main factor of death among developed nations is cardiovascular disease, which is made more likely by atherosclerosis and dyslipidemia. Castelli risk index 2, the ratio of low-density lipoprotein (LDL-C) to high-density lipoprotein cholesterol (HDL-C), is a parameter for assessing plasma atherosclerosis, and has been shown to be a better predictor of cardiovascular risk [14.15]. Both fibrinogen to albumin ratio (FAR) and Castelli risk index 2 have been associated with cardiovascular occurrences. Yet, little research on the link of FAR index and Castelli risk index 2 with CAD severity and carotid artery lesions in distinct glucose metabolic states. Thus, the aim of this investigation was to look into the link involving FAR index and Castelli risk index 2 with CAD severity and carotid artery lesions in distinct glucose metabolic states. Study population Patients who were admitted to the Department of Cardiology at Tianjin Union Medical Center and underwent coronary angiography and carotid Doppler ultrasonography from 2016 to 2023; The exclusion criteria were as follows: (1) Patients with insufficient data; (2) Patients with severe hepatic and renal insufficiency, malignant tumors and so on. A total of 2825 individuals (male = 1353, female = 1472) were enrolled, including 2805 undergoing carotid Doppler ultrasonography. The enrolled population was separated into CAD (n = 2166) and non-CAD (n = 659). Furthermore, the CAD group was separated into single-vessel (n = 740), double-vessels (n = 645), and triple-vessels (n = 781) CAD groups. The study protocol was approved by the Ethical Committee of Tianjin Union Medical Center (IRB number:2021-C03) and was conducted in accordance with the principles of the Declaration of Helsinki. As this was a retrospective study with no additional interventions, all patient data were anonymized to ensure confidentiality. Therefore, informed consent is not required. Data Collection Patient data were obtained from the digital medical record system and included key demographic characteristics, clinical background, blood analysis results and relevant medical imaging records. Demographic characteristics included age, gender, weight, height, blood pressure, smoking and drinking habits. Clinical history included history of hypertension and diabetes and treatment status. Medication included antihypertensive, antidiabetic and antilipidemic drugs. Blood samples were obtained by skilled healthcare professionals by collecting fasting venous blood in the morning. Albumin (ALB), HDL-C, aspartate aminotransferase (AST), low-density lipoprotein cholesterol (LDL-C), fibrinogen (FIB), glycated hemoglobin (HbA1c) were measured on an automated hematology analyser, and fasting venous blood samples were used to measure total cholesterol (TC), TG, white blood cells (WBC). Catheter-based invasive CAG was performed using percutaneous radial or femoral arteriography. The angiographic equipment used was versatile enough to accurately diagnose all manifestations of the coronary arteries. Physicians with backgrounds in radiology and cardiology monitored the findings of coronary angiography and carotid Doppler ultrasonography. The severity of the coronary artery lesions is defined by figuring the Gensini score. Participants undergoing carotid Doppler ultrasonography had their carotid intima-media thickness (IMT) and plaque thickness checked. Definition. CAD is defined as ≥50% luminal narrowing of one primary coronary artery [16].The severity of CAD is determined by the number of stenotic coronary arteries. A left aortic stenosis of ≥50% is designated multivessel CAD [16]. The severity of CAD is determined by the number of diseased vessels and the Gensini score (GS), which takes into account the degree of luminal stenosis and the importance of its location in the following way: obstruction of less than 25% is scored as 1 point, 26-50% obstruction is scored as 2 points, 51-75% obstruction is scored as 4 points, 8 points 76-90% obstruction is scored as 16 points and 91-99% obstruction is scored as 16 points. Complete obstruction (100 per cent) is given a score of 32. The score is then multiplied by a coefficient that depends on the functional importance of the area provided by the segment.5 for the left main coronary artery, 2.5 for the proximal segment of the left anterior descending or circumflex artery, and 1.5 for the middle segment of the left anterior descending branch[17] . FAR was calculated as (FIB [mg/dL] × ALB [g/L]) [18]. Castelli risk index 2 was calculated as (LDL-C [mol/L]/HDL-C [mol/L]) [9]. The WHO guidelines for diabetes mellitus [19] define diabetes mellitus (DM) as FPG > 7.0 mmol/L, 2-hour plasma glucose level ≥ 11.1 mmol/L based on an oral glucose tolerance test, HbA1c ≥ 6.5%, or a history of T2DM. Normoglycaemic regulation (NGR) is characterized by an FPG < 6.1 mmol/L and a 2-hour plasma glucose level < 7.8 mmol/L. Pre-diabetes mellitus (Pre-DM) should be examined in those who have high plasma glucose levels but fail to match the diagnostic categories as T2DM [20]. Statistical analyses Continuous variables were reported as mean ± SD or median and interquartile range. Differences between groups were analyzed using the independent samples t-test or Mann-Whitney U-test for normally and non-normally distributed data, respectively. Categorical variables were reported as numbers (percentages) and compared using the chi-square test. The link between the FAR index and the Castelli risk index 2 and the data from coronary angiography and carotid Doppler ultrasound in the different groups was analysed using multivariate logistic regression; additionally, the logistic regression analysis was used to analyse the relationship between the examined FAR index and the Castelli risk index 2 and the data from coronary angiography and carotid Doppler ultrasound in the different glycemic states. Statistical analysis was conducted using SPSS software version 26.0 (SPSS, Inc., Chicago, IL, USA).and GraphPad Prism 8 (GraphPad Software, USA). P-values < 0.05 were considered significant. Results Baseline and clinical characteristics This study comprised 2825 patients who had coronary angiography following hospitalization; their average age was 63.18 years, and 47.8% were male. Patients were divided into four groups based on the number of diseased vessels in the coronary arteries. There was a significant difference in gender, age, weight, SBP, history of smoking, drinking, hypertension, diabetes mellitus, stroke, and medication use ( p < 0.05), but no difference in DBP, family history of coronary artery disease, or history of hyperlipidemia ( p > 0.05). As shown in Table 1. Laboratory parameters in the four groups Table 2 displays the laboratory parameters for each of the four patient groups. Within the four subject groups, there were no appreciable variations in PDW, MPV, TC, or TP ( P > 0.05). The Triple-vessels CAD group had greater levels of WBC, RBC, NEUT, MON, UA, Glucose, HbA1c, CR, TG, LDL-C, VLDL-C, AIP, AST, FIB, FAR index, and Castelli risk index 2 levels ( P < 0.05), whereas HDL-C and ALB levels dropped ( P < 0.05). Relationship between FAR index and number and severity of coronary lesions In order to investigate the relationship between the FAR index and the number and severity of coronary lesions in patients, we divided the patients into three groups according to the quartiles of the FAR index level in the study (Quartile 1: < 0.07; Quartile 2: 0.07-0.09; Quartile 3: > 0.09), and as shown in Table 3 , The number of arterial lesions, hypertension, diabetes, and Gensini scores all rose in tandem with an increase in the FAR index values.( P < 0.05).As the FAR index quartiles increased, so did the levels of WBC, NEUT, MON, Glucose, AIP, FIB, and Castelli risk index 2 ( P < 0.05). Patients with higher FAR index quartiles had lower levels of RBC, HDL-C, ALB, and TP ( P < 0.05). In addition, statistically substantial variations were demonstrated in Gender, Age, Height, Weight, Smoking, Drinking and ALT level among these three groups. ( P < 0.05); and there were no statistically significant variations in terms of SBP.DBP, Hyperlipidemia, Antihyperlipidemic drugs, PDW, LYMP, MPV, UA, Glucose, CR, TC, TG, LDL-Cand AST ( P > 0.05)（ Table 3 ）. Since TC, TG, and LDL-C are known to be risk factors for coronary heart disease, they were included in the following statistical model even though there was no discernible variation in their levels. We additionally performed a interaction investigation between FAR index and CHD risk variables as demonstrated in Figure 1 . FAR index was positively correlated with Age, Hypertension, Diabetes, Stroke, Antihypertensive drugs, Antiglycemic drugs, WBC, NEUT, MON , FIB, AIP, HbA1c, Castelli risk index 2 and Gensini scores, and negatively correlated with Antilipidemic drugs, RBC, TP and HDL-C ( P < 0.05). Multivariate Logistic Regression Analysis of the Number of Coronary Artery Lesions by FAR Index Quartiles As indicated in Table 4, the study's findings demonstrated a strong statistical relationship between the quartile 3 group of the FAR index and a greater risk level for the number of diseased coronary arteries ( P < 0.05). Additionally, FAR index level was still significantly notably associated with the risk level for the number of diseased coronary arteries, even after controlling for confounders in the multiple regression analysis, such as hypertension, diabetes, hyperlipidemia, smoking, drinking, total cholesterol, triglycerides, HDL-C, LDL-C, and glucose. The number of diseased coronary arteries in quartile 3 group of the FAR index was 1.357 times higher than that of the group in the first quartile group (95% CI 1.220-1.509, P < 0.05). as shown in Table 4. Multivariate Logistic Regression Analysis of Coronary Artery Lesion Severity by the FAR Index Based on the quartiles of the Gensini score, the patients were divided into three groups: mild (quartile 1: Gensini scores < 24), moderate (quartile 2: Gensini scores in the range of 25–45), and severe coronary artery lesions (quartile 3: Gensini scores ≥ 45).As indicated in Table5, the study's findings demonstrated a strong correlation between the FAR index and the degree of CAD severity ( P < 0.05). Furthermore, the severity of coronary arteries was 1.802 times higher in the quartile 3 group of the FAR index than in the quartile 1 group (95% CI 1.220-1.509, P < 0.05), following confusions adjustment such as hypertension, diabetes, hyperlipidemia, coronary artery disease, smoking, drinking, total cholesterol, triglycerides, HDL-c, LDL-c, AIP, and glucose in the multivariate regression analyses. as shown in Table 5. Association between FAR index and number and severity of coronary lesions To gain insight into the link between the FAR index and the number and severity of coronary lesions, the number of coronary lesions and Gensini scores in CAD patients grouped by quartiles of the FAR index showed that the number of coronary lesions and Gensini scores were significantly higher in quartile 3 group compared with quartile 1 and quartile 2 group ( P < 0.05) (Figure 2A.B). FAR index determined by Gensini scores and the number of coronary lesion vessels. The group with triple vessels had a significantly higher FAR index than the group with single and double vessels; The group with severe coronary artery lesions (Gensini score quartile 3 group) had a significantly higher FAR index than the group with mild and moderate coronary artery lesions ( P < 0.05)( Figure 2C.D). Association of Castelli Risk Index 2 (CI2 = LDL-C/HDL-C) Levels With Number and Severity of Lesioned Coronary Arteries In order to clarify the correlation between the number of diseased coronary arteries and Castelli risk index 2, we separated the patients into four groups based on the study's Castelli index 2 quartiles (T1: < 1.94; T 2: 1.94-2.50; T 3: 2.50-3.15, and T 4 > 3.15). Table 6 indicates that the T 4 group with Castelli index 2 was significantly associated with a higher level of risk for the number of diseased coronary arteries ( P < 0.05). Furthermore, Table 6 indicates that even after controlling for confounding variables like smoking, drinking, ALB, glucose, HbA1c, diabetes, hypertension, and coronary artery disease in the multivariate regression analyses, the levels of the Castelli risk index 2 were still linked to the risk level of the amount of diseased coronary branches. The severity of the diseased coronary arteries was also 1.384 times higher in the T4 group than in the T1 group for Castelli risk index 2 [OR = 1.384 (95% CI 1.228-1.562)] ( P < 0.05). Multivariate Logistic Regression Analysis of Severity of Coronary Arteries by Castelli Risk Index 2 According to Table 7, the study's findings demonstrated a significant relationship between the level of coronary severity and the Castelli Risk Index 2. ( P < 0.05)；Additionally, as demonstrated in Table 7, the severity of coronary arteries was 1.613 times higher in the T4 group than in the T 1 group for the Castelli index 2[OR = 1.613 (95% CI 1.347, 1.930)] ( P < 0.05), after controlling for confounders such as hypertension, diabetes, hyperlipidemia, coronary artery disease, smoking, drinking, ALB, glucose, and HbA1c in the multivariate regression analyses. Association between the Castelli Risk Index 2 and the number and severity of coronary lesions In order to further assess the relationship between the Castelli Risk Index 2 and the number and severity of coronary lesions. The number of branches of coronary lesions and the Gensini score, which is derived from the quartiles of the Castelli Risk Index 2 grouped by the number of coronary lesions, were significantly higher in the T4 group when compared with the T1, T2, and T3 group ( P < 0.05) (Fig. 3A.B); The Castelli Risk Index 2 derived from the number of coronary diseased vessels and Gensini score quartiles. The Castelli Risk Index 2 displayed substantially greater level in the triple vessels group than in the single and double vessels group; The Castelli Risk Index 2 displayed substantially greater level in the group with severe coronary artery lesions (Gensini score quartile 3 group) than in the group with mild coronary artery lesions ( P < 0.05) (Fig. 3C.D). Association between FAR index and carotid artery disease Each individual was subjected to carotid Doppler ultrasonography and categorized based on intima-media thickness (IMT), which was defined as carotid intima-media thickening with an IMT more than 1.0mm. Table 8 summarizes the clinical features of individuals who had a carotid ultrasonography. Patients with increased IMT had considerably greater levels of age, SBP, HbA1c (%), LDL-C, FIB, FAR, and CI2 compared to those with normal IMT. However, HDL-C and ALB levels were significantly lower ( P < 0.05). Comparison of height, weight, hypertension, diabetes mellitus, stroke, smoking, drinking, antihypertensive and antiglycaemic drug use between the two groups was statistically significant ( P < 0.05). However, there were no significant differences in blood glucose, TC, TG, hyperlipidemia or use of antilipidemic drugs. ( P > 0.05). Analysis of the connection between carotid artery lesions and FAR index in CAD patients, the result demonstrated that FAR index was substantially higher in the IMT increased group than the IMT normal group ( P < 0.05) (Figure 4A) . Furthermore, the IMT increased group was separated into two groups: carotid atherosclerosis (IMT of more than 1.0 mm) and carotid plaque development ( IMT of not less than 1.5 mm). The FAR index was considerably higher in the carotid plaque group compared to the other groups ( P < 0.05) (Figure 4B). The frequency of individuals with carotid plaques was highest in the FAR index quartile 3 group ( P < 0.05) (Figure 4C). Assessment of plaque thickness in the carotid atherosclerotic plaque group showed that plaques in the highest FAR quartile were much thicker than those in the lowest quartile ( P < 0.05) (Figure 4D). Multivariate Logistic Regression Analysis of Carotid Atherosclerotic Lesions by FAR Index Quartiles Table 9 demonstrates a strong link between the fourth FAR index quartile and carotid atherosclerotic lesions. In comparison to individuals with normal carotid arteries, the risk of carotid plaque in the Q3 group was 1.514 times greater than the Q1 group. [OR = 1.514 (95% CI 1.258, 1.823)] ( P < 0.05). regardless of sex, age，smoking, hypertension, diabetes. Association between Castelli risk index 2 index and carotid artery lesions Analysis the relationship between carotid artery lesions and Castelli risk index 2 in CAD patients, the results showed that Castelli risk index 2 had a considerably greater in the IMT increased group than in the IMT normal group ( P < 0.05) (Figure. 5A) . Furthermore, the IMT increased group was separated into two groups: carotid atherosclerosis (IMT of more than 1.0 mm) and carotid plaque development ( IMT of not less than 1.5 mm). The Castelli risk index 2 was s considerably higher in the carotid plaque group compared to the other groups ( P < 0.05) (Figure 5B). The group with the Castelli risk index 2 quartile 4 had the highest percentage of patients with carotid plaque (Figure 5C). Evaluation of the carotid atherosclerotic plaque group's plaque thickness exhibited no discernible change between plaques in the top Castelli risk index 2 quartile compared with plaque thickness in the lowest quartile (Figure 5D). Multivariate Logistic Regression Analysis of Carotid Atherosclerotic Lesions in Castelli risk index 2 Quartiles Table 10 demonstrates a substantial link between the fourth Castelli risk index 2 quartile and carotid atherosclerotic lesions. The risk of carotid plaque was 1.355 times higher in the T4 group compared to the T1 group in participants with normal carotid arteries. irrespective of age, sex, smoking, diabetes, or hypertension. [OR = 1.355 (95% CI 1.108, 1.657)] ( P < 0.05). Association of the FAR index and Castelli risk index 2 with the number and severity of coronary lesions in subgroups of different glucose metabolic states As shown in Table 11 , there was a statistically significant relationship between FAR index and CAD severity regardless of glucose metabolic status ( P < 0.05). Similarly, Castelli risk index 2 was significantly associated with CAD severity in NGR patients and DM patients ( P < 0.05). However, there was no statistically significant relationship between Castelli risk index 2 and the severity of CAD in Pre-DM patients ( P > 0.05 Table 12); Association of FAR index and Castelli risk index 2 index with carotid artery lesions in subgroups of different glucose metabolic states Table 13 indicates that there was a statistically significant link between the FAR index and carotid artery lesions in NGR patients and Pre-DM patients ( P < 0.05), but there was no statistically significant relationship between FAR index and carotid artery lesions in DM patients ( P >0.05); In both NGR and DM patients, there was a significant correlation between Castelli risk index 2 and carotid artery lesions. Nonetheless, in individuals with Pre-DM, there existed no substantial link between Castelli risk index 2 and carotid artery disease. ( P > 0.05 Table 14). Predictive value of the FAR index and Castelli risk index 2 for coronary lesion severity and carotid lesions The ROC curve analysis of the FAR index and Castelli Risk Index 2 for coronary lesion severity and carotid lesion prediction is shown in Figure 6AB, In the ROC curve analysis, the FAR index and Castelli risk index 2 predicted CAD severity with an AUC of 0.572(95% CI 0.548-0.596)and 0.584(95% CI 0.561-0.607) ( P < 0.001), the FAR index and Castelli risk index 2 predicted carotid lesion with an AUC of 0.573(95% CI 0.550-0.596)and 0.555(95% CI 0.531-0.578), ( P < 0.001),as shown in Table 15. Discussion The FAR index and Castelli Risk Index 2 were initially assessed in connection with coronary and carotid artery disease in this study. The findings demonstrated a significant correlation between FAR index and Castelli Risk Index 2 and the severity of both carotid artery disease and coronary artery disease; Additionally, individuals with more severe carotid artery plaques and coronary artery disease had higher FAR and Castelli Risk Index 2 levels, and elevated levels of these indexes were also predictive of more severe carotid artery disease and coronary artery disease in patients; The relationship of FAR and Castelli Risk Index 2 with CAD severity and carotid artery lesions was then investigated in different glucose metabolic states. The severity of CAD turns out to be statistically strongly linked with the FAR index regardless of glucose metabolic states; the FAR index was significantly associated with carotid artery lesions in NGR and Pre-DM states, The Castelli Risk Index 2 was substantially linked with CAD severity and carotid artery lesions in both the NGR and DM states. However, there was no statistically meaningful link between Castelli risk index 2 and CAD severity or carotid artery lesions in the Pre-DM state. Furthermore, with comparable predictive values, the FAR index and Castelli risk index 2 are potential biomarkers for predicting the severity of lesions in the coronary and carotid arteries. Research has demonstrated that inflammation is a determinant of the onset of atherosclerosis at all stages, including the rupture, progression, and thrombosis that result in an acute myocardial infarction [ 21 ]. In addition to having a strong correlation with the number and severity of diseased coronary vessels, plasma levels of inflammatory biomarkers are crucial for the initiation and advancement of atherosclerotic plaques [ 22 ]. Recent studies have applied lipid-related biomarkers to assess coronary artery lesions and carotid artery lesions [ 23 ]. A significant part of the pathophysiology of atherosclerosis and vascular inflammation is played by fibrinogen, a major glycoprotein produced by the liver [ 18 ]. Furthermore, fibrinogen has a role in the coagulation and hemorrhagic systems of the body [ 24 , 25 ]. Apart from its predictive power for thrombotic status, recent research has demonstrated that plasma fibrinogen levels are independently associated with the severity of coronary atherosclerosis and the degree of stable coronary atherosclerosis in patients with CAD [12.26]. Our findings revealed a substantial difference in fibrinogen levels between coronary and carotid lesions, indicating that fibrinogen levels can be used to predict coronary and carotid atherosclerosis risk. Albumin is a major protein in the body that serves as a biomarker of inflammation and a mediator of platelet-induced atherosclerosis [ 22 ]. Serum albumin and involvement in the progression of atherogenesis have been reported in the literature. Hypoalbuminemia is associated with an increased incidence of various cardiovascular diseases including ischaemic heart disease [ 27 ]. Our investigation found substantial changes in albumin levels between distinct coronary and carotid lesions, indicating a link between ALB and the severity of coronary stenosis and carotid lesions in individuals. Although both plasma fibrinogen and albumin have been correlated with cardiovascular disease, previous studies have shown that there is limited evidence to examine the correlation between these organisational inflammatory biomarkers independently and the severity of coronary artery lesions and carotid lesions. The FAR index, which is made up of two significant inflammatory biomarkers, may be a more accurate indicator for those with inflammatory conditions. According to recent research, the FAR index is a more accurate predictor of the risk of cardiovascular disease than fibrinogen and albumin alone [ 28 ]. According to research by Sirui Yang et al., the FAR index was an independent predictor of death in patients with different types of HF; the greater a patient's FAR index level, the higher their overall death rate [ 29 ]. Xinsheng Li et al. found that greater FAR index levels were linked with all-cause mortality and MACCE in TVD patients [ 25 ].Our research revealed a correlation between FAR and both carotid and coronary artery disease in CAD patients. Furthermore, the Gensini score and carotid intima-media thickness were computed or scrutinized in order to examine the correlation between FAR, coronary artery severity, and carotid artery lesions. Our research demonstrated a substantial correlation between FAR levels and both the severity of coronary artery disease and carotid artery lesions in individuals, indicating that this combination of biomarkers may be more useful in detecting the number and severity of coronary lesions. Furthermore, we found a correlation between FAR index and CAD severity regardless of glucose metabolism status. Our research also illustrated a substantial link between FAR index and carotid artery lesions in NGR and Pre-DM status, but not in the DM population. Dyslipidemia is a common risk factor for cardiovascular disease and a key factor in the development and progression of coronary atherosclerosis [ 30 ]. Atherosclerosis is a complex multifactorial disease influenced by a variety of factors, and the Castelli Risk Index 2, the ratio of LDL-C/HDL-C, has been shown to be a better predictor of cardiovascular risk compared with a single lipid [ 31 ]. In addition, Po Gao showed a significant correlation between the LDL-C/HDL-C ratio and the severity of coronary heart disease in STEMI patients [ 15 ]. In this study, we observed that the Castelli risk index 2 is associated with both coronary and carotid artery lesions in CAD patients. Furthermore, we examined the link between the Castelli risk index 2 and coronary artery severity, as well as carotid artery lesions. Our findings showed that Castelli risk index 2 was strongly associated with CAD severity and carotid artery lesions in both the NGR and DM groups. In the Pre-DM group, Castelli risk index 2 was not associated with CAD severity or carotid artery disease. One symptom of systemic atherosclerosis is carotid plaque. Arterial ischemia symptoms can be caused by extensive plaque development and considerable lumen constriction; in severe situations, A stroke could come about from that. Monitoring the formation of carotid plaques is necessary to determine the extent of systemic atherosclerosis.[ 32 ]. We utilized carotid ultrasonography on individuals and used carotid intima-media thickness and plaque thickness to study the association between FAR index and Castelli risk index 2 and carotid artery lesions. The association between FAR index and Castelli risk index 2 and carotid artery disease in different glucose metabolic states was also investigated. As far as we are aware, there are few studies on the association of FAR index and Castelli risk index 2 with carotid and coronary atherosclerosis in patients with CAD. Previous studies have shown that the FAR index and Castelli Risk Index 2 can predict CAD independently [28.33]. According to our current research, there are few studies on the predictive value of specifically comparing these two indices for the diagnosis of CAD in terms of the severity of coronary lesions and carotid artery disease. Chinese patients admitted to Tianjin Union Medical Center with symptomatic cardiovascular disease were recruited in the present investigation. We noticed that the FAR index and Castelli Risk Index 2 correlated with the severity of CAD coronary lesions and carotid artery disease. When accounting for sex, age, smoking, drinking, hypertension, diabetes and antihyperlipidemic and hypoglycemic medications, the risk of coronary artery lesions and carotid artery disease increased with the increase in FAR index and Castelli Risk Index 2. The highest quartile (quartile 4) was associated with a higher incidence of coronary artery lesions and carotid artery disease compared with the lowest FAR index and Castelli Risk Index 2 quartile. Both coronary artery severity and carotid artery disease were substantially and favorably linked with the FAR index and Castelli Risk Index 2. Despite varying glucose metabolic conditions, the FAR index and Castelli Risk Index 2 are correlated with the severity of coronary artery disease and carotid artery disease. The FAR index and Castelli Risk Index 2 have the potential to serve as simple biomarkers with the purpose of timely detection of CAD risk individuals and more targeted treatment or prevention. The present study also has some limitations. First, the FAR index and Castelli Risk Index 2 were determined from baseline data, and their ongoing interactions with CVD risk over time cloud not be assessed with time. Second, the possible consequences of persistent of antihypertensive, hypoglycemic, and hypolipidemic medications on lipid and glucose measurements as well as the occurrence of coronary heart disease could not be excluded. Third, other confounders, including employment category and exercise routines, were not accounted for. Fourth, we were unable to alter for nutritional structure, which would have affected protein and blood finger levels. Finally, An admission bias may arise from this single-center investigation involving a Chinese population. and the insights may not be applicable to a wider population. Additional massive, forward-looking, multicenter randomized investigations could strengthen the validity of our discoveries. To increase the credibility and precision of the discoveries., these elements should be taken into account in subsequent studies. Conclusion The FAR index and Castelli Risk Index 2 are closely related to the severity of coronary artery disease and carotid artery disease as well as being good markers for predicting the number and severity of coronary artery lesions. These two indices can be widely used in clinical practice to identify high-risk groups for CAD at an early stage and provide new preventive strategies for clinical management. Declarations Ethics approval and consent to participate The study protocol was approved by the Ethics Committee of Tianjin Union Medical Center (IRB number:2021-C03). This study was conducted in compliance with the Declaration of Helsinki. As this was a retrospective study with no additional interventions, all patient data were anonymized to ensure confidentiality. Therefore, informed consent is not required. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding information Supported by Tianjin administration of traditional Chinese medicine(grant no.2021155)、 The Cooperation Project of Beijing, Tianjin and Hebei (grant no. 19JCZDJC63900) and Foundation of Tianjin Union Medical Center (grant no. 2020YJ014). Authors' contributions LW and XQ designed the experiments. XJ and YL drafted the manuscript. XJ analysed the data and generated the figures. WJ, XG, HW, QJ, MC and HZ collected data. All authors have read and approved the final version of the manuscript. Acknowledgements Not applicable. Author details 1.School of Medicine, Nankai University, No. 94, Weijin Road, Nankai District, Tianjin, P.R. China, 300071 ；2. Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, No.190 Jieyuan Road, Hongqiao District, Tianjin 300121, P. R. China. 3. School of Graduate Studies, Tianjin University of Traditional Chinese Medicine, Tianjin, China . References Ma L-Y, Chen W-W, Gao R-L, et al. China cardiovascular diseases report 2018: an updated summary[J]. Journal of Geriatric Cardiology : JGC, 2020, 17(1): 1–8. Bergmark B A, Mathenge N, Merlini P A, et al. Acute coronary syndromes[J]. Lancet (London, England), 2022, 399(10332): 1347–1358. Jebari-Benslaiman S, Galicia-García U, Larrea-Sebal A, et al. Pathophysiology of Atherosclerosis[J]. International Journal of Molecular Sciences, 2022, 23(6): 3346. Wang X, Xu W, Song Q, et al. Association between the triglyceride–glucose index and severity of coronary artery disease[J]. Cardiovascular Diabetology, 2022, 21: 168. Hanson C A, Lu E, Ghumman S S, et al. Long‐term outcomes in patients with normal coronary arteries, nonobstructive, or obstructive coronary artery disease on invasive coronary angiography[J]. Clinical Cardiology, 2021, 44(9): 1286–1295. Liu H, Wang L, Wang H, et al. The association of triglyceride–glucose index with major adverse cardiovascular and cerebrovascular events after acute myocardial infarction: a meta-analysis of cohort studies[J]. Nutrition & Diabetes, 2024, 14: 39. Arques S. Albumine sérique et maladies cardiovasculaires : une revue approfondie de la littérature[J]. Annales de Cardiologie et d’Angéiologie, 2018, 67(2): 82–90. Arques S. Human serum albumin in cardiovascular diseases[J]. European Journal of Internal Medicine, 2018, 52: 8–12. Yang S, Cui Y, Hou J, et al. Assessment of the relationship between plasma fibrinogen-to-albumin ratio and slow coronary flow phenomenon in patients without obstructive coronary artery disease[J]. BMC Cardiovascular Disorders, 2023, 23: 540. Zhang D, Chen S, Cao W, et al. 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European Heart Journal, 2020, 41(2): 255–323. Wu X, Qiu W, Yang H, et al. Associations of the triglyceride-glucose index and atherogenic index of plasma with the severity of new-onset coronary artery disease in different glucose metabolic states[J]. Cardiovascular Diabetology, 2024, 23: 76. Liu Y, Dai M. Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis[J]. Mediators of Inflammation, 2020, 2020: 4634172. Gao J, Lu J, Sha W, et al. Relationship between the neutrophil to high-density lipoprotein cholesterol ratio and severity of coronary artery disease in patients with stable coronary artery disease[J]. Frontiers in Cardiovascular Medicine, Frontiers Media SA, 2022, 9. Guo J, Chen M, Hong Y, et al. Comparison of the Predicting Value of Neutrophil to high-Density Lipoprotein Cholesterol Ratio and Monocyte to high-Density Lipoprotein Cholesterol Ratio for in-Hospital Prognosis and Severe Coronary Artery Stenosis in Patients with ST-Segment Elevation Acute Myocardial Infarction Following Percutaneous Coronary Intervention: A Retrospective Study[J]. Journal of Inflammation Research, 2023, 16: 4541–4557. Litvinov R I, Pieters M, de Lange-Loots Z, et al. Fibrinogen and Fibrin[J]. Sub-Cellular Biochemistry, 2021, 96: 471–501. Li X, Wang Z, Zhu Y, et al. Prognostic Value of Fibrinogen-to-Albumin Ratio in Coronary Three-Vessel Disease[J]. Journal of Inflammation Research, 2023, 16: 5767–5777. Celebi S, Ozcan Celebi O, Berkalp B, et al. The association between the fibrinogen-to-albumin ratio and coronary artery disease severity in patients with stable coronary artery disease[J]. Coronary Artery Disease, 2020, 31(6): 512. Cheng C-W, Lee C-W, Chien S-C, et al. Serum Albumin was Associated with a Long Term Cardiovascular Mortality among Elderly Patients with Stable Coronary Artery Disease[J]. Acta Cardiologica Sinica, 2024, 40(1): 87–96. Zhu Y, Tao S, Zhang D, et al. Association between fibrinogen/albumin ratio and severity of coronary artery calcification in patients with chronic kidney disease: a retrospective study[J]. PeerJ, 2022, 10: e13550. Yang S, Pi J, Ma W, et al. Prognostic value of the fibrinogen-to-albumin ratio (FAR) in patients with chronic heart failure across the different ejection fraction spectrum[J]. The Libyan Journal of Medicine, , 19(1): 2309757. Wilson P W F, Polonsky T S, Miedema M D, et al. Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines[J]. Journal of the American College of Cardiology, 2019, 73(24): 3210–3227. Kou H, Wang H, Liu P, et al. Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study[J]. BMC cardiovascular disorders, 2024, 24(1): 144. Li J, Dong Z, Wu H, et al. The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia[J]. Cardiovascular Diabetology, 2023, 22: 224. Liu X, Yang Y, Kang F, et al. Cardiovascular Disease Risk Across a Spectrum of Adverse Plasma Lipid Combinations by Gender and Glycemic Status[J]. The American Journal of Cardiology, 2019, 124(5): 702–708. Tables Tables 1 to 15 are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files GraphicalAbstract.docx Highlights.docx Tables.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-5827255\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Research Article\",\"associatedPublications\":[],\"authors\":[{\"id\":403498942,\"identity\":\"30c26577-49ab-4fb4-ae6f-a0d8b0effd40\",\"order_by\":0,\"name\":\"Yue Liu\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Tianjin Union Medical Center, Nankai University Affiliated Hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Yue\",\"middleName\":\"\",\"lastName\":\"Liu\",\"suffix\":\"\"},{\"id\":403498943,\"identity\":\"1b4c049b-c7a8-4041-8ba9-91a8d576e8b7\",\"order_by\":1,\"name\":\"Xiandu 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UA\\u003c/em\\u003e: uric acid; \\u003cem\\u003eHbA1c\\u003c/em\\u003e: glycosylated hemoglobin; \\u003cem\\u003eCR\\u003c/em\\u003e :creatinine; \\u003cem\\u003eTC\\u003c/em\\u003e :total cholesterol; \\u003cem\\u003eTG:\\u003c/em\\u003e triglyceride; \\u003cem\\u003eHDL-C\\u003c/em\\u003e: high-density lipoprotein cholesterol; \\u003cem\\u003eLDL-C\\u003c/em\\u003e: low-density lipoprotein cholesterol; \\u003cem\\u003eAIP\\u003c/em\\u003e: atherosclerosis index of plasma; \\u003cem\\u003eTP\\u003c/em\\u003e: total protein; \\u003cem\\u003eALB\\u003c/em\\u003e: albumin; \\u003cem\\u003eALT\\u003c/em\\u003e: alanine aminotransferase; \\u003cem\\u003eAST\\u003c/em\\u003e: aspartate aminotransferase; \\u003cem\\u003eFIB\\u003c/em\\u003e: fibrinogen; \\u003cem\\u003eFAR\\u003c/em\\u003e: The fibrinogen to albumin ratio;\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"1.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5827255/v1/6c9cf1e3e99d4b600b6be9bf.png\"},{\"id\":74244132,\"identity\":\"b3677f40-6fc6-4b29-9f24-2b37e1a829a0\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 09:49:43\",\"extension\":\"png\",\"order_by\":2,\"title\":\"Figure 2\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":44936,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eRelationship between the number of vascular lesions and Gensini scores and FAR index in patients with CAD, A:The number of vascular lesions by FAR index quartiles, B: Gensini score by FAR index quartiles; C: FAR index by number of vascular lesions; D: FAR index by Gensini score. #:\\u003cem\\u003e p\\u003c/em\\u003e \\u0026lt; 0.05.\\u003cem\\u003e Quartile 1\\u003c/em\\u003e: the first FAR index quartile; \\u003cem\\u003eQuartile 3\\u003c/em\\u003e: the fourth FAR index quartile,\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"2.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5827255/v1/06e05ad31f33dee913abfe52.png\"},{\"id\":74244166,\"identity\":\"c114df70-8a40-4e92-8539-ae6f1e822ef7\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 09:49:44\",\"extension\":\"png\",\"order_by\":3,\"title\":\"Figure 3\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":40646,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eRelationship between the number of vascular lesions and Gensini score with Castelli Risk Index 2 in CAD patients, A: number of vascular lesions by Castelli Risk Index 2 quartiles, B: Gensini score by by Castelli Risk Index 2 quartiles; C: Castelli Risk Index 2 by number of vascular lesions; D: Castelli Risk Index 2 by Gensini score. #: \\u003cem\\u003ep\\u003c/em\\u003e \\u0026lt; 0.05; \\u003cem\\u003eT 1\\u003c/em\\u003e: the first Castelli risk index 2 quartile; \\u003cem\\u003eT4\\u003c/em\\u003e: the fourth Castelli risk index 2 quartile,\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"3.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5827255/v1/b3a7f7259d91ad8a51fb9754.png\"},{\"id\":74246895,\"identity\":\"1ef14b8a-5573-409a-afcb-262f3de768e0\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 09:57:43\",\"extension\":\"png\",\"order_by\":4,\"title\":\"Figure 4\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":82381,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAssociation between carotid artery lesions and FAR index in patients with CAD.A、B ：FAR index in carotid artery lesion group; C：Proportion of carotid ultrasonographic findings by quartiles of the FAR index; D：Plaque thickness by quartiles of the FAR index. * \\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05. Q1: the first FAR index quartile , Q3: the fourth FAR index quartile .\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"4.png\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-5827255/v1/6172aef04f3b5a29467bce2b.png\"},{\"id\":74244130,\"identity\":\"9999799f-be31-4d2e-a551-8dbb455750c7\",\"added_by\":\"auto\",\"created_at\":\"2025-01-20 09:49:43\",\"extension\":\"png\",\"order_by\":5,\"title\":\"Figure 5\",\"display\":\"\",\"copyAsset\":false,\"role\":\"figure\",\"size\":95711,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003eAssociation between carotid artery lesions and Castelli risk index 2 in patients with CAD. A and B: Castelli risk index 2 in carotid artery lesion group; C: Proportion of carotid ultrasonographic findings by Castelli risk index 2 index quartiles; D: Plaque thickness by Castelli risk index 2 index quartiles. \\u003csup\\u003e#\\u003c/sup\\u003e \\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05. 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Inflammation plays an important role in the development and progression of atherosclerotic CAD [\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e]. In clinical practice, invasive coronary angiography (CAG) is considered as the most commonly used technique for detecting CAD, allowing precise assessment of the extent of coronary artery stenosis and the number of lesions. Based on the results of CAG, CAD is diagnosed in patients with \\u0026ge;\\u0026thinsp;50% coronary lumen constriction [\\u003cspan citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e]. In addition, the severity of CAD is related to the number of stenotic vessels. The higher the number of stenotic vessels in the coronary artery, the higher the risk of poor prognosis [\\u003cspan citationid=\\\"CR5\\\" class=\\\"CitationRef\\\"\\u003e5\\u003c/span\\u003e]. Most patients do not undergo CAG in a timely manner in the early stages of the disease, considering that CAG is invasive. In addition, populations with cardiovascular risk factors, especially those with type 2 diabetes mellitus (T2DM), have a higher risk of recurrence of CAD [\\u003cspan citationid=\\\"CR6\\\" class=\\\"CitationRef\\\"\\u003e6\\u003c/span\\u003e]. Therefore, in order to better reduce the incidence and mortality of CAD in patients, it is clinically important to identify and intervene in high-risk patients with CAD in a timely manner.\\u003c/p\\u003e \\u003cp\\u003eAlbumin is a 65 kDa protein that constitutes more than half of human serum proteins and is mainly synthesised in the liver with anti-inflammatory, antioxidant, anticoagulant and antiplatelet physiological properties [\\u003cspan citationid=\\\"CR7\\\" class=\\\"CitationRef\\\"\\u003e7\\u003c/span\\u003e]. Studies have shown that there is a correlation between plasma albumin levels and the prevalence, severity and mortality of CAD [\\u003cspan citationid=\\\"CR8\\\" class=\\\"CitationRef\\\"\\u003e8\\u003c/span\\u003e]. Fibrinogen, a plasma protein produced by the liver, plays an important role in the inflammatory response and coagulation system and is associated with the severity of CAD [\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e]. Recent studies have shown that fibrinogen to albumin ratio (FAR), reported as a new inflammatory marker, assesses the risk of prognosis in several cancer diseases [\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e]. In addition, the new inflammatory index FAR was significantly associated with CAD severity in patients with CAD [\\u003cspan citationid=\\\"CR12\\\" class=\\\"CitationRef\\\"\\u003e12\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eThe most prominent pathophysiological manifestation in the T2DM population is insulin resistance (IR), which fosters an inflammatory state, vascular endothelial dysfunction and lipid disorders, IR could potentially be the primary mechanism leading to atherosclerosis [\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e]. The main factor of death among developed nations is cardiovascular disease, which is made more likely by atherosclerosis and dyslipidemia. Castelli risk index 2, the ratio of low-density lipoprotein (LDL-C) to high-density lipoprotein cholesterol (HDL-C), is a parameter for assessing plasma atherosclerosis, and has been shown to be a better predictor of cardiovascular risk [14.15]. Both fibrinogen to albumin ratio (FAR) and Castelli risk index 2 have been associated with cardiovascular occurrences. Yet, little research on the link of FAR index and Castelli risk index 2 with CAD severity and carotid artery lesions in distinct glucose metabolic states. Thus, the aim of this investigation was to look into the link involving FAR index and Castelli risk index 2 with CAD severity and carotid artery lesions in distinct glucose metabolic states.\\u003c/p\\u003e\"},{\"header\":\"Study population\",\"content\":\"\\u003cp\\u003ePatients who were admitted to the Department of Cardiology at Tianjin Union Medical Center and underwent coronary angiography and carotid Doppler ultrasonography from 2016 to 2023; The exclusion criteria were as follows: (1) Patients with insufficient data; (2) Patients with severe hepatic and renal insufficiency, malignant tumors and so on. A total of 2825 individuals (male = 1353, female = 1472) were enrolled, including 2805 undergoing carotid Doppler ultrasonography. The enrolled population was separated into CAD (n = 2166) and non-CAD (n = 659). Furthermore, the CAD group was separated into single-vessel (n = 740), double-vessels (n = 645), and triple-vessels (n = 781) CAD groups. The study protocol was approved by the Ethical Committee of Tianjin Union Medical Center (IRB number:2021-C03) and was conducted in accordance with the principles of the Declaration of Helsinki. As this was a retrospective study with no additional interventions, all patient data were anonymized to ensure confidentiality. Therefore, informed consent is not required.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eData Collection\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003ePatient data were obtained from the digital medical record system and included key demographic characteristics, clinical background, blood analysis results and relevant medical imaging records. Demographic characteristics included age, gender, weight, height, blood pressure, smoking and drinking habits. Clinical history included history of hypertension and diabetes and treatment status. Medication included antihypertensive, antidiabetic and antilipidemic drugs.\\u003c/p\\u003e\\n\\u003cp\\u003eBlood samples were obtained by skilled healthcare professionals by collecting fasting venous blood in the morning. Albumin (ALB), HDL-C, aspartate aminotransferase (AST), low-density lipoprotein cholesterol (LDL-C), fibrinogen (FIB), glycated hemoglobin (HbA1c) were measured on an automated hematology analyser, and fasting venous blood samples were used to measure total cholesterol (TC), TG, white blood cells (WBC). Catheter-based invasive CAG was performed using percutaneous radial or femoral arteriography. The angiographic equipment used was versatile enough to accurately diagnose all manifestations of the coronary arteries. Physicians with backgrounds in radiology and cardiology monitored the findings of coronary angiography and carotid Doppler ultrasonography. The severity of the coronary artery lesions is defined by figuring the Gensini score. Participants undergoing carotid Doppler ultrasonography had their carotid intima-media thickness (IMT) and plaque thickness checked.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eDefinition.\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eCAD is defined as \\u0026ge;50% luminal narrowing of one primary coronary artery [16].The severity of CAD is determined by the number of stenotic coronary arteries. A left aortic stenosis of \\u0026ge;50% is designated multivessel CAD [16].\\u003c/p\\u003e\\n\\u003cp\\u003eThe severity of CAD is determined by the number of diseased vessels and the Gensini score (GS), which takes into account the degree of luminal stenosis and the importance of its location in the following way: obstruction of less than 25% is scored as 1 point, 26-50% obstruction is scored as 2 points, 51-75% obstruction is scored as 4 points, 8 points 76-90% obstruction is scored as 16 points and 91-99% obstruction is scored as 16 points. Complete obstruction (100 per cent) is given a score of 32. The score is then multiplied by a coefficient that depends on the functional importance of the area provided by the segment.5 for the left main coronary artery, 2.5 for the proximal segment of the left anterior descending or circumflex artery, and 1.5 for the middle segment of the left anterior descending branch[17] .\\u003c/p\\u003e\\n\\u003cp\\u003eFAR was calculated as (FIB [mg/dL] \\u0026times; ALB [g/L]) [18].\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eCastelli risk index 2 was calculated as (LDL-C [mol/L]/HDL-C [mol/L]) [9].\\u003c/p\\u003e\\n\\u003cp\\u003eThe WHO guidelines for diabetes mellitus [19] define diabetes mellitus (DM) as FPG \\u0026gt; 7.0 mmol/L, 2-hour plasma glucose level \\u0026ge; 11.1 mmol/L based on an oral glucose tolerance test, HbA1c \\u0026ge; 6.5%, or a history of T2DM. Normoglycaemic regulation (NGR) is characterized by an FPG \\u0026lt; 6.1 mmol/L and a 2-hour plasma glucose level \\u0026lt; 7.8 mmol/L. Pre-diabetes mellitus (Pre-DM) should be examined in those who have high plasma glucose levels but fail to match the diagnostic categories as T2DM [20].\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStatistical analyses\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eContinuous variables were reported as mean \\u0026plusmn; SD or median and interquartile range. Differences between groups were analyzed using the independent samples t-test or Mann-Whitney U-test for normally and non-normally distributed data, respectively. Categorical variables were reported as numbers (percentages) and compared using the chi-square test. The link between the FAR index and the Castelli risk index 2 and the data from coronary angiography and carotid Doppler ultrasound in the different groups was analysed using multivariate logistic regression; additionally, the logistic regression analysis was used to analyse the relationship between the examined FAR index and the Castelli risk index 2 and the data from coronary angiography and carotid Doppler ultrasound in the different glycemic states. Statistical analysis was conducted using SPSS software version 26.0 (SPSS, Inc., Chicago, IL, USA).and GraphPad Prism 8 (GraphPad Software, USA). P-values \\u0026lt; 0.05 were considered significant.\\u003c/p\\u003e\"},{\"header\":\"Results\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eBaseline and clinical characteristics\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThis study comprised 2825 patients who had coronary angiography following hospitalization; their average age was 63.18 years, and 47.8% were male. Patients were divided into four groups based on the number of diseased vessels in the coronary arteries. There was a significant difference in gender, age, weight, SBP, history of smoking, drinking, hypertension, diabetes mellitus, stroke, and medication use (\\u003cem\\u003ep\\u003c/em\\u003e \\u0026lt; 0.05), but no difference in DBP, family history of coronary artery disease, or history of hyperlipidemia (\\u003cem\\u003ep\\u0026nbsp;\\u003c/em\\u003e\\u0026gt; 0.05). As shown in Table 1.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eLaboratory parameters in the four groups\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTable 2\\u0026nbsp;displays the laboratory parameters for each of the four patient groups. Within the four subject groups, there were no appreciable variations in PDW, MPV, TC, or TP (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026gt; 0.05). The Triple-vessels CAD group had greater levels of WBC, RBC, NEUT, MON, UA, Glucose, HbA1c, CR, TG, LDL-C, VLDL-C, AIP, AST, FIB, FAR index, and Castelli risk index 2 levels (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05), whereas HDL-C and ALB levels dropped (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05).\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eRelationship between FAR index and number and severity of coronary lesions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn order to investigate the relationship between the FAR index and the number and severity of coronary lesions in patients, we divided the patients into three groups according to the quartiles of the FAR index level in the study (Quartile 1: \\u0026lt; 0.07; Quartile 2: 0.07-0.09; Quartile 3: \\u0026gt; 0.09), and as shown in \\u003cstrong\\u003eTable 3\\u003c/strong\\u003e,\\u0026nbsp;The number of arterial lesions, hypertension, diabetes, and Gensini scores all rose in tandem with an increase in the FAR index values.(\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05).As the FAR index quartiles increased, so did the levels of WBC, NEUT, MON, Glucose, AIP, FIB, and Castelli risk index 2 (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). Patients with higher FAR index quartiles had lower levels of RBC, HDL-C, ALB, and TP (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05).\\u003c/p\\u003e\\n\\u003cp\\u003eIn addition, statistically substantial variations were demonstrated in Gender, Age, Height, Weight, Smoking, Drinking and ALT level\\u0026nbsp;among these three groups. (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05);\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003eand there were no statistically significant variations in terms of SBP.DBP, Hyperlipidemia, Antihyperlipidemic drugs, PDW, LYMP, MPV, UA, Glucose, CR, TC, TG, LDL-Cand AST (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026thinsp;\\u0026gt; 0.05)（\\u003cstrong\\u003eTable 3\\u003c/strong\\u003e）. Since TC, TG, and LDL-C are known to be risk factors for coronary heart disease, they were included in the following statistical model even though there was no discernible variation in their levels. We additionally performed a interaction investigation between FAR index and CHD risk variables as demonstrated \\u003cstrong\\u003ein Figure 1\\u003c/strong\\u003e. FAR index was positively correlated with Age, Hypertension, Diabetes, Stroke, Antihypertensive drugs, Antiglycemic drugs, WBC, NEUT, MON , FIB, AIP, HbA1c, Castelli risk index 2 and Gensini scores, and negatively correlated with Antilipidemic drugs, RBC, TP and HDL-C (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMultivariate Logistic Regression Analysis of the Number of Coronary Artery Lesions by FAR Index Quartiles\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAs indicated in\\u0026nbsp;Table 4,\\u0026nbsp;the study\\u0026apos;s findings demonstrated a strong statistical relationship between the quartile 3 group of the FAR index and a greater risk level for the number of diseased coronary arteries (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). Additionally, FAR index level was still significantly notably associated with the risk level for the number of diseased coronary arteries, even after controlling for confounders in the multiple regression analysis, such as hypertension, diabetes, hyperlipidemia, smoking, drinking, total cholesterol, triglycerides, HDL-C, LDL-C, and glucose. The number of diseased coronary arteries in quartile 3 group of the FAR index was 1.357 times higher than that of the group in the first quartile group (95% CI 1.220-1.509, \\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). as shown in Table 4.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMultivariate Logistic Regression Analysis of Coronary Artery Lesion Severity by the FAR Index\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eBased on the quartiles of the Gensini score, the patients were divided into three groups: mild (quartile 1: Gensini scores \\u0026lt; 24), moderate (quartile 2: Gensini scores in the range of 25\\u0026ndash;45), and severe coronary artery lesions (quartile 3: Gensini scores \\u0026ge; 45).As indicated in Table5, the study\\u0026apos;s findings demonstrated a strong correlation \\u0026nbsp;between the FAR index and the degree of CAD severity (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). Furthermore, the severity of coronary arteries was 1.802 times higher in the quartile 3 group of the FAR index than in the quartile 1 group (95% CI 1.220-1.509,\\u003cem\\u003e\\u0026nbsp;P\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05), following confusions adjustment such as hypertension, diabetes, hyperlipidemia, coronary artery disease, smoking, drinking, total cholesterol, triglycerides, HDL-c, LDL-c, AIP, and glucose in the multivariate regression analyses. as shown in Table 5.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssociation between FAR index and number and severity of coronary lesions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTo gain insight into the link between the FAR index and the number and severity of coronary lesions, the number of coronary lesions and Gensini scores in CAD patients grouped by quartiles of the FAR index showed that the number of coronary lesions and Gensini scores were significantly higher in quartile 3 group compared with quartile 1 and quartile 2 group (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05) (Figure 2A.B). FAR index determined by Gensini scores and the number of coronary lesion vessels. The group with triple vessels had a significantly higher FAR index than the group with single and double vessels; The group with severe coronary artery lesions (Gensini score quartile 3 group) had a significantly higher FAR index than the group with mild and moderate coronary artery lesions (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05)( Figure 2C.D).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssociation of Castelli Risk Index 2 (CI2 = LDL-C/HDL-C) Levels With Number and Severity of Lesioned Coronary Arteries\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn order to clarify the correlation between the number of diseased coronary arteries and Castelli risk index 2, we separated the patients into four groups based on the study\\u0026apos;s Castelli index 2 quartiles (T1: \\u0026lt; 1.94; T 2: 1.94-2.50; T 3: 2.50-3.15, and T 4 \\u0026gt; 3.15). Table 6\\u0026nbsp;indicates that the T 4 group with Castelli index 2 was significantly associated with a higher level of risk for the number of diseased coronary arteries (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). Furthermore, Table 6 indicates that even after controlling for confounding variables like smoking, drinking, ALB, glucose, HbA1c, diabetes, hypertension, and coronary artery disease in the multivariate regression analyses, the levels of the Castelli risk index 2 were still linked to the risk level of the amount of diseased coronary branches. The severity of the diseased coronary arteries was also 1.384 times higher in the T4 group than in the T1 group for Castelli risk index 2 [OR\\u0026thinsp;=\\u0026thinsp;1.384 (95% CI 1.228-1.562)] (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMultivariate Logistic Regression Analysis of Severity of Coronary Arteries by\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eCastelli Risk Index 2\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAccording to\\u0026nbsp;Table 7, the study\\u0026apos;s findings demonstrated a significant relationship between the level of coronary severity and the Castelli Risk Index 2. (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05)；Additionally, as demonstrated in\\u0026nbsp;Table 7, the severity of coronary arteries was 1.613 times higher in the T4 group than in the T 1 group for the Castelli index 2[OR\\u0026thinsp;=\\u0026thinsp;1.613 (95% CI 1.347, 1.930)]\\u0026nbsp;(\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05), after controlling for confounders such as hypertension, diabetes, hyperlipidemia, coronary artery disease, smoking, drinking, ALB, glucose, and HbA1c in the multivariate regression analyses.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssociation between the\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eCastelli Risk Index 2\\u0026nbsp;\\u003c/strong\\u003e\\u003cstrong\\u003eand the number and severity of coronary lesions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn order to further assess the relationship between the Castelli Risk Index 2 and the number and severity of coronary lesions. The number of branches of coronary lesions and the Gensini score, which is derived from the quartiles of the Castelli Risk Index 2 grouped by the number of coronary lesions, were significantly higher in the T4 group when compared with the T1, T2, and T3 group (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05)\\u0026nbsp;(Fig. 3A.B);\\u0026nbsp;The Castelli Risk Index 2 derived from the number of coronary diseased vessels and Gensini score quartiles. The Castelli Risk Index 2 displayed substantially greater level in the triple vessels group than in the single and double vessels group; The Castelli Risk Index 2 displayed substantially greater level in the group with severe coronary artery lesions (Gensini score quartile 3 group) than in the group with mild coronary artery lesions (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05) (Fig. 3C.D).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssociation between FAR index and carotid artery disease\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eEach individual was subjected to carotid Doppler ultrasonography and categorized based on intima-media thickness (IMT), which was defined as carotid intima-media thickening with an IMT more than 1.0mm. Table 8 summarizes the clinical features of individuals who had a carotid ultrasonography. Patients with increased IMT had considerably greater levels of age, SBP, HbA1c (%), LDL-C, FIB, FAR, and CI2 compared to those with normal IMT. However, HDL-C and ALB levels were significantly lower (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05). Comparison of height, weight, hypertension, diabetes mellitus, stroke, smoking, drinking, antihypertensive and antiglycaemic drug use between the two groups was statistically significant (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). However, there were no significant differences in blood glucose, TC, TG, hyperlipidemia or use of antilipidemic drugs. (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026gt; 0.05).\\u003c/p\\u003e\\n\\u003cp\\u003eAnalysis of the connection between carotid artery lesions and FAR index in CAD patients, the result demonstrated that FAR index was substantially higher in the IMT increased group than the IMT normal group (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05) (Figure 4A) . Furthermore, the IMT increased group was separated into two groups: carotid atherosclerosis (IMT of more than 1.0 mm) and carotid plaque development ( IMT of not less than 1.5 mm). The FAR index was considerably higher in the carotid plaque group compared to the other groups (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05) (Figure 4B). The frequency of individuals with carotid plaques was highest in the FAR index quartile 3 group (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05) (Figure 4C). Assessment of plaque thickness in the carotid atherosclerotic plaque group showed that plaques in the highest FAR quartile were much thicker than those in the lowest quartile (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05) (Figure 4D).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMultivariate Logistic Regression Analysis of Carotid Atherosclerotic Lesions by FAR Index Quartiles\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTable 9\\u0026nbsp;demonstrates\\u0026nbsp;a strong link between the fourth FAR index quartile and carotid atherosclerotic lesions. In comparison to individuals with normal carotid arteries, the risk of carotid plaque in the Q3 group was 1.514 times greater than the Q1 group.\\u0026nbsp;[OR\\u0026thinsp;=\\u0026thinsp;1.514 (95% CI 1.258, 1.823)] (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05). regardless of sex, age，smoking, hypertension, diabetes.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssociation between Castelli risk index 2 index and carotid artery lesions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAnalysis the relationship between carotid artery lesions and Castelli risk index 2 in CAD patients, the results showed that Castelli risk index 2\\u0026nbsp;had a considerably greater in the IMT increased group than in the IMT normal group (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05) (Figure. 5A) . Furthermore, the IMT increased group was separated into two groups: carotid atherosclerosis (IMT of more than 1.0 mm) and carotid plaque development ( IMT of not less than 1.5 mm). The Castelli risk index 2 was s considerably higher in the carotid plaque group compared to the other groups (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05) (Figure 5B). The group with the Castelli risk index 2 quartile 4 had the highest percentage of patients with carotid plaque (Figure 5C). Evaluation of the carotid atherosclerotic plaque group\\u0026apos;s plaque thickness exhibited no discernible change between plaques in the top Castelli risk index 2 quartile compared with plaque thickness in the lowest quartile (Figure 5D).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMultivariate Logistic Regression Analysis of Carotid Atherosclerotic Lesions in Castelli risk index 2 Quartiles\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTable 10\\u0026nbsp;demonstrates a substantial link between the fourth Castelli risk index 2 quartile and carotid atherosclerotic lesions. The risk of carotid plaque was 1.355 times higher in the T4 group compared to the T1 group in participants with normal carotid arteries. irrespective of age, sex, smoking, diabetes, or hypertension.\\u0026nbsp;[OR\\u0026thinsp;=\\u0026thinsp;1.355 (95% CI 1.108, 1.657)] (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.05).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssociation of the FAR index and Castelli risk index 2 with the number and severity of coronary lesions in subgroups of different glucose metabolic states\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAs shown in\\u0026nbsp;Table 11 ,\\u0026nbsp;there was a statistically significant relationship between FAR index and CAD severity regardless of glucose metabolic status (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). Similarly, Castelli risk index 2 was significantly associated with CAD severity in NGR patients and DM patients (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). However, there was no statistically significant relationship between Castelli risk index 2 and the severity of CAD in Pre-DM patients (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026gt; 0.05\\u0026nbsp;Table 12);\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAssociation of FAR index and Castelli risk index 2 index with carotid artery lesions in subgroups of different glucose metabolic states\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eTable 13\\u0026nbsp;indicates that there was a statistically significant link between the FAR index and carotid artery lesions in NGR patients and Pre-DM patients (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.05), but there was no statistically significant relationship between FAR index and carotid artery lesions in DM patients (\\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026gt;0.05); In both NGR and DM patients, there was a significant correlation between Castelli risk index 2 and carotid artery lesions. Nonetheless, in individuals with Pre-DM,\\u0026nbsp;there existed no substantial link between Castelli risk index 2 and carotid artery disease.\\u0026nbsp;(\\u003cem\\u003eP\\u003c/em\\u003e \\u0026gt; 0.05 Table 14).\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003ePredictive value of the FAR index and Castelli risk index 2 for coronary lesion severity and carotid lesions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe ROC curve analysis of the FAR index and Castelli Risk Index 2 for coronary lesion severity and carotid lesion prediction is shown in Figure 6AB, In the ROC curve analysis, the FAR index and Castelli risk index 2 predicted CAD severity with an AUC of 0.572(95% CI 0.548-0.596)and 0.584(95% CI 0.561-0.607) ( \\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.001), the FAR index and Castelli risk index 2 predicted carotid lesion with an AUC of 0.573(95% CI 0.550-0.596)and 0.555(95% CI 0.531-0.578), ( \\u003cem\\u003eP\\u0026nbsp;\\u003c/em\\u003e\\u0026lt; 0.001),as shown in Table 15.\\u003c/p\\u003e\"},{\"header\":\"Discussion\",\"content\":\"\\u003cp\\u003eThe FAR index and Castelli Risk Index 2 were initially assessed in connection with coronary and carotid artery disease in this study. The findings demonstrated a significant correlation between FAR index and Castelli Risk Index 2 and the severity of both carotid artery disease and coronary artery disease; Additionally, individuals with more severe carotid artery plaques and coronary artery disease had higher FAR and Castelli Risk Index 2 levels, and elevated levels of these indexes were also predictive of more severe carotid artery disease and coronary artery disease in patients;\\u003c/p\\u003e \\u003cp\\u003eThe relationship of FAR and Castelli Risk Index 2 with CAD severity and carotid artery lesions was then investigated in different glucose metabolic states. The severity of CAD turns out to be statistically strongly linked with the FAR index regardless of glucose metabolic states; the FAR index was significantly associated with carotid artery lesions in NGR and Pre-DM states, The Castelli Risk Index 2 was substantially linked with CAD severity and carotid artery lesions in both the NGR and DM states. However, there was no statistically meaningful link between Castelli risk index 2 and CAD severity or carotid artery lesions in the Pre-DM state. Furthermore, with comparable predictive values, the FAR index and Castelli risk index 2 are potential biomarkers for predicting the severity of lesions in the coronary and carotid arteries.\\u003c/p\\u003e \\u003cp\\u003eResearch has demonstrated that inflammation is a determinant of the onset of atherosclerosis at all stages, including the rupture, progression, and thrombosis that result in an acute myocardial infarction [\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e]. In addition to having a strong correlation with the number and severity of diseased coronary vessels, plasma levels of inflammatory biomarkers are crucial for the initiation and advancement of atherosclerotic plaques [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Recent studies have applied lipid-related biomarkers to assess coronary artery lesions and carotid artery lesions [\\u003cspan citationid=\\\"CR23\\\" class=\\\"CitationRef\\\"\\u003e23\\u003c/span\\u003e].\\u003c/p\\u003e \\u003cp\\u003eA significant part of the pathophysiology of atherosclerosis and vascular inflammation is played by fibrinogen, a major glycoprotein produced by the liver [\\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e]. Furthermore, fibrinogen has a role in the coagulation and hemorrhagic systems of the body [\\u003cspan citationid=\\\"CR24\\\" class=\\\"CitationRef\\\"\\u003e24\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e]. Apart from its predictive power for thrombotic status, recent research has demonstrated that plasma fibrinogen levels are independently associated with the severity of coronary atherosclerosis and the degree of stable coronary atherosclerosis in patients with CAD [12.26]. Our findings revealed a substantial difference in fibrinogen levels between coronary and carotid lesions, indicating that fibrinogen levels can be used to predict coronary and carotid atherosclerosis risk. Albumin is a major protein in the body that serves as a biomarker of inflammation and a mediator of platelet-induced atherosclerosis [\\u003cspan citationid=\\\"CR22\\\" class=\\\"CitationRef\\\"\\u003e22\\u003c/span\\u003e]. Serum albumin and involvement in the progression of atherogenesis have been reported in the literature. Hypoalbuminemia is associated with an increased incidence of various cardiovascular diseases including ischaemic heart disease [\\u003cspan citationid=\\\"CR27\\\" class=\\\"CitationRef\\\"\\u003e27\\u003c/span\\u003e]. Our investigation found substantial changes in albumin levels between distinct coronary and carotid lesions, indicating a link between ALB and the severity of coronary stenosis and carotid lesions in individuals.\\u003c/p\\u003e \\u003cp\\u003eAlthough both plasma fibrinogen and albumin have been correlated with cardiovascular disease, previous studies have shown that there is limited evidence to examine the correlation between these organisational inflammatory biomarkers independently and the severity of coronary artery lesions and carotid lesions. The FAR index, which is made up of two significant inflammatory biomarkers, may be a more accurate indicator for those with inflammatory conditions. According to recent research, the FAR index is a more accurate predictor of the risk of cardiovascular disease than fibrinogen and albumin alone [\\u003cspan citationid=\\\"CR28\\\" class=\\\"CitationRef\\\"\\u003e28\\u003c/span\\u003e]. According to research by Sirui Yang et al., the FAR index was an independent predictor of death in patients with different types of HF; the greater a patient's FAR index level, the higher their overall death rate [\\u003cspan citationid=\\\"CR29\\\" class=\\\"CitationRef\\\"\\u003e29\\u003c/span\\u003e]. Xinsheng Li et al. found that greater FAR index levels were linked with all-cause mortality and MACCE in TVD patients [\\u003cspan citationid=\\\"CR25\\\" class=\\\"CitationRef\\\"\\u003e25\\u003c/span\\u003e].Our research revealed a correlation between FAR and both carotid and coronary artery disease in CAD patients. Furthermore, the Gensini score and carotid intima-media thickness were computed or scrutinized in order to examine the correlation between FAR, coronary artery severity, and carotid artery lesions. Our research demonstrated a substantial correlation between FAR levels and both the severity of coronary artery disease and carotid artery lesions in individuals, indicating that this combination of biomarkers may be more useful in detecting the number and severity of coronary lesions. Furthermore, we found a correlation between FAR index and CAD severity regardless of glucose metabolism status. Our research also illustrated a substantial link between FAR index and carotid artery lesions in NGR and Pre-DM status, but not in the DM population.\\u003c/p\\u003e \\u003cp\\u003eDyslipidemia is a common risk factor for cardiovascular disease and a key factor in the development and progression of coronary atherosclerosis [\\u003cspan citationid=\\\"CR30\\\" class=\\\"CitationRef\\\"\\u003e30\\u003c/span\\u003e]. Atherosclerosis is a complex multifactorial disease influenced by a variety of factors, and the Castelli Risk Index 2, the ratio of LDL-C/HDL-C, has been shown to be a better predictor of cardiovascular risk compared with a single lipid [\\u003cspan citationid=\\\"CR31\\\" class=\\\"CitationRef\\\"\\u003e31\\u003c/span\\u003e]. In addition, Po Gao showed a significant correlation between the LDL-C/HDL-C ratio and the severity of coronary heart disease in STEMI patients [\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e]. In this study, we observed that the Castelli risk index 2 is associated with both coronary and carotid artery lesions in CAD patients. Furthermore, we examined the link between the Castelli risk index 2 and coronary artery severity, as well as carotid artery lesions. Our findings showed that Castelli risk index 2 was strongly associated with CAD severity and carotid artery lesions in both the NGR and DM groups. In the Pre-DM group, Castelli risk index 2 was not associated with CAD severity or carotid artery disease.\\u003c/p\\u003e \\u003cp\\u003eOne symptom of systemic atherosclerosis is carotid plaque. Arterial ischemia symptoms can be caused by extensive plaque development and considerable lumen constriction; in severe situations, A stroke could come about from that. Monitoring the formation of carotid plaques is necessary to determine the extent of systemic atherosclerosis.[\\u003cspan citationid=\\\"CR32\\\" class=\\\"CitationRef\\\"\\u003e32\\u003c/span\\u003e]. We utilized carotid ultrasonography on individuals and used carotid intima-media thickness and plaque thickness to study the association between FAR index and Castelli risk index 2 and carotid artery lesions. The association between FAR index and Castelli risk index 2 and carotid artery disease in different glucose metabolic states was also investigated. As far as we are aware, there are few studies on the association of FAR index and Castelli risk index 2 with carotid and coronary atherosclerosis in patients with CAD.\\u003c/p\\u003e \\u003cp\\u003ePrevious studies have shown that the FAR index and Castelli Risk Index 2 can predict CAD independently [28.33]. According to our current research, there are few studies on the predictive value of specifically comparing these two indices for the diagnosis of CAD in terms of the severity of coronary lesions and carotid artery disease. Chinese patients admitted to Tianjin Union Medical Center with symptomatic cardiovascular disease were recruited in the present investigation. We noticed that the FAR index and Castelli Risk Index 2 correlated with the severity of CAD coronary lesions and carotid artery disease. When accounting for sex, age, smoking, drinking, hypertension, diabetes and antihyperlipidemic and hypoglycemic medications, the risk of coronary artery lesions and carotid artery disease increased with the increase in FAR index and Castelli Risk Index 2. The highest quartile (quartile 4) was associated with a higher incidence of coronary artery lesions and carotid artery disease compared with the lowest FAR index and Castelli Risk Index 2 quartile. Both coronary artery severity and carotid artery disease were substantially and favorably linked with the FAR index and Castelli Risk Index 2. Despite varying glucose metabolic conditions, the FAR index and Castelli Risk Index 2 are correlated with the severity of coronary artery disease and carotid artery disease. The FAR index and Castelli Risk Index 2 have the potential to serve as simple biomarkers with the purpose of timely detection of CAD risk individuals and more targeted treatment or prevention.\\u003c/p\\u003e \\u003cp\\u003eThe present study also has some limitations. First, the FAR index and Castelli Risk Index 2 were determined from baseline data, and their ongoing interactions with CVD risk over time cloud not be assessed with time. Second, the possible consequences of persistent of antihypertensive, hypoglycemic, and hypolipidemic medications on lipid and glucose measurements as well as the occurrence of coronary heart disease could not be excluded. Third, other confounders, including employment category and exercise routines, were not accounted for. Fourth, we were unable to alter for nutritional structure, which would have affected protein and blood finger levels. Finally, An admission bias may arise from this single-center investigation involving a Chinese population. and the insights may not be applicable to a wider population. Additional massive, forward-looking, multicenter randomized investigations could strengthen the validity of our discoveries. To increase the credibility and precision of the discoveries., these elements should be taken into account in subsequent studies.\\u003c/p\\u003e\"},{\"header\":\"Conclusion\",\"content\":\"\\u003cp\\u003eThe FAR index and Castelli Risk Index 2 are closely related to the severity of coronary artery disease and carotid artery disease as well as being good markers for predicting the number and severity of coronary artery lesions. These two indices can be widely used in clinical practice to identify high-risk groups for CAD at an early stage and provide new preventive strategies for clinical management.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e\\u003cstrong\\u003eEthics approval and consent to participate\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe study protocol was approved by the Ethics Committee of Tianjin Union Medical Center (IRB number:2021-C03). This study was conducted in compliance with the Declaration of Helsinki. As this was a retrospective study with no additional interventions, all patient data were anonymized to ensure confidentiality. Therefore, informed consent is not required.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConsent for publication\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAvailability of data and materials\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eCompeting interests\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe authors declare that they have no competing interests.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eFunding information\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eSupported by Tianjin administration of traditional Chinese medicine(grant no.2021155)、\\u0026nbsp;The Cooperation Project of Beijing, Tianjin and Hebei (grant no. 19JCZDJC63900) and Foundation of Tianjin Union Medical Center (grant no. 2020YJ014).\\u003c/p\\u003e\\n\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthors\\u0026apos; contributions\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eLW and XQ designed the experiments. XJ and YL drafted the manuscript. XJ analysed the data and generated the figures. WJ, XG, HW, QJ, MC and HZ collected data. All authors have read and approved the final version of the manuscript.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAcknowledgements\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNot applicable.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eAuthor details\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003e1.School of Medicine, Nankai University, No. 94, Weijin Road, Nankai District, Tianjin, P.R. China,\\u0026nbsp;300071\\u0026nbsp;；2. Department of Cardiology, Tianjin Union Medical Center, Nankai University Affiliated Hospital, No.190 Jieyuan Road, Hongqiao District, Tianjin 300121, P. R. China. 3.\\u0026nbsp;School of Graduate Studies, Tianjin University of Traditional Chinese Medicine, Tianjin, China\\u003cstrong\\u003e.\\u003c/strong\\u003e\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\n\\u003cli\\u003eMa L-Y, Chen W-W, Gao R-L, et al. China cardiovascular diseases report 2018: an updated summary[J]. Journal of Geriatric Cardiology : JGC, 2020, 17(1): 1\\u0026ndash;8.\\u003c/li\\u003e\\n\\u003cli\\u003eBergmark B A, Mathenge N, Merlini P A, et al. Acute coronary syndromes[J]. Lancet (London, England), 2022, 399(10332): 1347\\u0026ndash;1358.\\u003c/li\\u003e\\n\\u003cli\\u003eJebari-Benslaiman S, Galicia-Garc\\u0026iacute;a U, Larrea-Sebal A, et al. Pathophysiology of Atherosclerosis[J]. International Journal of Molecular Sciences, 2022, 23(6): 3346.\\u003c/li\\u003e\\n\\u003cli\\u003eWang X, Xu W, Song Q, et al. Association between the triglyceride\\u0026ndash;glucose index and severity of coronary artery disease[J]. Cardiovascular Diabetology, 2022, 21: 168.\\u003c/li\\u003e\\n\\u003cli\\u003eHanson C A, Lu E, Ghumman S S, et al. Long‐term outcomes in patients with normal coronary arteries, nonobstructive, or obstructive coronary artery disease on invasive coronary angiography[J]. Clinical Cardiology, 2021, 44(9): 1286\\u0026ndash;1295.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu H, Wang L, Wang H, et al. The association of triglyceride\\u0026ndash;glucose index with major adverse cardiovascular and cerebrovascular events after acute myocardial infarction: a meta-analysis of cohort studies[J]. Nutrition \\u0026amp; Diabetes, 2024, 14: 39.\\u003c/li\\u003e\\n\\u003cli\\u003eArques S. Albumine s\\u0026eacute;rique et maladies cardiovasculaires : une revue approfondie de la litt\\u0026eacute;rature[J]. Annales de Cardiologie et d\\u0026rsquo;Ang\\u0026eacute;iologie, 2018, 67(2): 82\\u0026ndash;90.\\u003c/li\\u003e\\n\\u003cli\\u003eArques S. Human serum albumin in cardiovascular diseases[J]. European Journal of Internal Medicine, 2018, 52: 8\\u0026ndash;12.\\u003c/li\\u003e\\n\\u003cli\\u003eYang S, Cui Y, Hou J, et al. Assessment of the relationship between plasma fibrinogen-to-albumin ratio and slow coronary flow phenomenon in patients without obstructive coronary artery disease[J]. BMC Cardiovascular Disorders, 2023, 23: 540.\\u003c/li\\u003e\\n\\u003cli\\u003eZhang D, Chen S, Cao W, et al. HALP score based on hemoglobin, albumin, lymphocyte and platelet can predict the prognosis of tongue squamous cell carcinoma patients[J]. Heliyon, 2023, 9(9): e20126.\\u003c/li\\u003e\\n\\u003cli\\u003eHuang L, Mo Z, Hu Z, et al. Diagnostic value of fibrinogen to prealbumin ratio and gamma-glutamyl transpeptidase to platelet ratio in the progression of AFP-negative hepatocellular carcinoma[J]. Cancer Cell International, 2020, 20: 77.\\u003c/li\\u003e\\n\\u003cli\\u003eSurma S, Banach M. Fibrinogen and Atherosclerotic Cardiovascular Diseases-Review of the Literature and Clinical Studies[J]. International Journal of Molecular Sciences, 2021, 23(1): 193.\\u003c/li\\u003e\\n\\u003cli\\u003eLi M, Chi X, Wang Y, et al. Trends in insulin resistance: insights into mechanisms and therapeutic strategy[J]. Signal Transduction and Targeted Therapy, 2022, 7: 216.\\u003c/li\\u003e\\n\\u003cli\\u003eTexis T, Rivera-Manc\\u0026iacute;a S, Col\\u0026iacute;n-Ram\\u0026iacute;rez E, et al. Genetic Determinants of Atherogenic Indexes[J]. Genes, 2023, 14(6): 1214.\\u003c/li\\u003e\\n\\u003cli\\u003eGao P, Wen X, Ou Q, et al. Which one of LDL-C /HDL-C ratio and non-HDL-C can better predict the severity of coronary artery disease in STEMI patients[J]. BMC Cardiovascular Disorders, 2022, 22: 318.\\u003c/li\\u003e\\n\\u003cli\\u003eSu J, Li Z, Huang M, et al. Triglyceride glucose index for the detection of the severity of coronary artery disease in different glucose metabolic states in patients with coronary heart disease: a RCSCD-TCM study in China[J]. Cardiovascular Diabetology, 2022, 21: 96.\\u003c/li\\u003e\\n\\u003cli\\u003eGensini G G. A more meaningful scoring system for determining the severity of coronary heart disease[J]. The American Journal of Cardiology, 1983, 51(3): 606.\\u003c/li\\u003e\\n\\u003cli\\u003eDuan Z, Luo C, Fu B, et al. Association between fibrinogen-to-albumin ratio and the presence and severity of coronary artery disease in patients with acute coronary syndrome[J]. BMC Cardiovascular Disorders, 2021, 21: 588.\\u003c/li\\u003e\\n\\u003cli\\u003eCosentino F, Grant P J, Aboyans V, et al. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD[J]. European Heart Journal, 2020, 41(2): 255\\u0026ndash;323.\\u003c/li\\u003e\\n\\u003cli\\u003eWu X, Qiu W, Yang H, et al. Associations of the triglyceride-glucose index and atherogenic index of plasma with the severity of new-onset coronary artery disease in different glucose metabolic states[J]. Cardiovascular Diabetology, 2024, 23: 76.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu Y, Dai M. Trimethylamine N-Oxide Generated by the Gut Microbiota Is Associated with Vascular Inflammation: New Insights into Atherosclerosis[J]. Mediators of Inflammation, 2020, 2020: 4634172.\\u003c/li\\u003e\\n\\u003cli\\u003eGao J, Lu J, Sha W, et al. Relationship between the neutrophil to high-density lipoprotein cholesterol ratio and severity of coronary artery disease in patients with stable coronary artery disease[J]. Frontiers in Cardiovascular Medicine, Frontiers Media SA, 2022, 9.\\u003c/li\\u003e\\n\\u003cli\\u003eGuo J, Chen M, Hong Y, et al. Comparison of the Predicting Value of Neutrophil to high-Density Lipoprotein Cholesterol Ratio and Monocyte to high-Density Lipoprotein Cholesterol Ratio for in-Hospital Prognosis and Severe Coronary Artery Stenosis in Patients with ST-Segment Elevation Acute Myocardial Infarction Following Percutaneous Coronary Intervention: A Retrospective Study[J]. Journal of Inflammation Research, 2023, 16: 4541\\u0026ndash;4557.\\u003c/li\\u003e\\n\\u003cli\\u003eLitvinov R I, Pieters M, de Lange-Loots Z, et al. Fibrinogen and Fibrin[J]. Sub-Cellular Biochemistry, 2021, 96: 471\\u0026ndash;501.\\u003c/li\\u003e\\n\\u003cli\\u003eLi X, Wang Z, Zhu Y, et al. Prognostic Value of Fibrinogen-to-Albumin Ratio in Coronary Three-Vessel Disease[J]. Journal of Inflammation Research, 2023, 16: 5767\\u0026ndash;5777.\\u003c/li\\u003e\\n\\u003cli\\u003eCelebi S, Ozcan Celebi O, Berkalp B, et al. The association between the fibrinogen-to-albumin ratio and coronary artery disease severity in patients with stable coronary artery disease[J]. Coronary Artery Disease, 2020, 31(6): 512.\\u003c/li\\u003e\\n\\u003cli\\u003eCheng C-W, Lee C-W, Chien S-C, et al. Serum Albumin was Associated with a Long Term Cardiovascular Mortality among Elderly Patients with Stable Coronary Artery Disease[J]. Acta Cardiologica Sinica, 2024, 40(1): 87\\u0026ndash;96.\\u003c/li\\u003e\\n\\u003cli\\u003eZhu Y, Tao S, Zhang D, et al. Association between fibrinogen/albumin ratio and severity of coronary artery calcification in patients with chronic kidney disease: a retrospective study[J]. PeerJ, 2022, 10: e13550.\\u003c/li\\u003e\\n\\u003cli\\u003eYang S, Pi J, Ma W, et al. Prognostic value of the fibrinogen-to-albumin ratio (FAR) in patients with chronic heart failure across the different ejection fraction spectrum[J]. The Libyan Journal of Medicine, , 19(1): 2309757.\\u003c/li\\u003e\\n\\u003cli\\u003eWilson P W F, Polonsky T S, Miedema M D, et al. Systematic Review for the 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines[J]. Journal of the American College of Cardiology, 2019, 73(24): 3210\\u0026ndash;3227.\\u003c/li\\u003e\\n\\u003cli\\u003eKou H, Wang H, Liu P, et al. Prevalence, clinical features and prognosis of familial hypercholesterolemia in Chinese Han patients with acute coronary syndrome after a coronary event: a retrospective observational study[J]. BMC cardiovascular disorders, 2024, 24(1): 144.\\u003c/li\\u003e\\n\\u003cli\\u003eLi J, Dong Z, Wu H, et al. The triglyceride-glucose index is associated with atherosclerosis in patients with symptomatic coronary artery disease, regardless of diabetes mellitus and hyperlipidaemia[J]. Cardiovascular Diabetology, 2023, 22: 224.\\u003c/li\\u003e\\n\\u003cli\\u003eLiu X, Yang Y, Kang F, et al. Cardiovascular Disease Risk Across a Spectrum of Adverse Plasma Lipid Combinations by Gender and Glycemic Status[J]. The American Journal of Cardiology, 2019, 124(5): 702\\u0026ndash;708.\\u003c/li\\u003e\\n\\u003c/ol\\u003e\"},{\"header\":\"Tables\",\"content\":\"\\u003cp\\u003eTables 1 to 15 are available in the Supplementary Files section.\\u003c/p\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"Fibrinogen/albumin ratio, Castelli risk index 2 (CI2 = LDL-C/HDL-C), coronary artery disease, Coronary artery disease severity, Carotid atherosclerosis, glucose metabolic state\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5827255/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5827255/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe fibrinogen to albumin ratio (FAR) is a novel inflammatory indicator correlating with the severity of coronary artery disease. An indicator of atherosclerosis is the Castelli Risk Index 2 (CI2 = LDL-C/HDL-C). Yet, little research has focused on the link between both of indicators and coronary artery disease (CAD) and carotid atherosclerotic lesions in distinct glucose metabolic states. Thus, the aim of this investigation was to look into the link involving these two indicators and atherosclerotic lesions of the coronary and carotid arteries in patients with CAD who were in distinct glucose metabolic states.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eMethod:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eIn this investigation, coronary angiography and carotid Doppler ultrasonography were performed about 2825 individuals suffering from symptomatic CAD at Tianjin Union Medical Center from 2016 to 2023.The number of stenotic arteries in the coronary arteries was counted. Both the Carotid intima-media thickness and the Gensini score were taken into account or computed. Normal glucose regulation (NGR), pre-diabetes mellitus (Pre-DM), and diabetes mellitus (DM) were the three categories of glucose status according to the WHO diabetes guidelines. Patients were also divided into FAR index and Castelli risk index 2 quartiles to look into the link between FAR index and Castelli risk index 2 and coronary or carotid artery lesions in CAD patients with different glucose metabolic states. Receiver operating characteristic (ROC) curves were constructed to analyse the predictive value of the FAR index and Castelli risk index for coronary artery severity and carotid artery lesions.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResult\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eAccording to logistic regression analysis, the FAR index and Castelli risk index 2 were statistically associated with coronary artery disease and carotid plaques (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026lt; 0.05). The FAR index was linked with CAD severity regardless of glucose metabolism states (\\u003cem\\u003eP \\u003c/em\\u003e\\u0026lt; 0.05). It was also substantially associated with carotid lesions in the NGR and Pre-DM stages (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05), but not in the DM state (\\u003cem\\u003eP\\u003c/em\\u003e \\u0026lt; 0.05). The Castelli risk index 2 was strongly linked with CAD severity and carotid artery lesions in both NGR and DM status (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026lt; 0.05). Yet, there was no statistical significance in Pre-DM states. (\\u003cem\\u003eP\\u003c/em\\u003e\\u0026gt; 0.05). The FAR index and Castelli risk index 2 exhibited higher regions underneath the ROC curve in forecasting coronary artery lesions and carotid atherosclerosis.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eThe FAR index and Castelli risk index 2 were significantly associated with coronary and carotid atherosclerosis in different glucose metabolic states. FAR index and Castelli risk index 2 have predictive value for coronary artery lesions and carotid plaques.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Association of fibrinogen/albumin ratio and Castelli risk index 2 (CI2 = LDL-C/HDL-C) with severity of coronary artery disease and carotid atherosclerosis in different glucose metabolism states\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2025-01-20 09:49:37\",\"doi\":\"10.21203/rs.3.rs-5827255/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"e58db552-0d8d-4acc-ab33-6a265a7ec484\",\"owner\":[],\"postedDate\":\"January 20th, 2025\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[],\"tags\":[],\"updatedAt\":\"2025-01-26T13:08:20+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2025-01-20 09:49:37\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5827255\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5827255\",\"identity\":\"rs-5827255\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}