European Journal of Cardiovascular Medicine

One of the most dangerous health issues and one of the main causes of mortality worldwide is cardiovascular disease (CVD). The term "CVD" is frequently used to describe a group of illnesses that affect the heart or blood vessels. Peripheral artery disease, rheumatic heart disease, hypertensive heart disease, heart failure, stroke, and several other vascular and cardiac issues are also included in the illness [1].

In industrialised nations, coronary artery disease (CAD) is the leading cause of both death and morbidity. However, new data revealed that the frequency of coronary artery disease has significantly increased among South Asians [2]. It manifests more severely than in other populations and at a relatively early age [3]. IHD is still one of the biggest dangers to public health, with its total burden rising internationally. As these trends continue, national health systems will need to handle the rising demand for IHD-related preventative and therapeutic interventions due to the significant increase in incident and prevalent IHD cases in the majority of nations.

Since 1990, the prevalence of IHD has increased gradually; in 2019, there were 182 million (95% UI: 170 to 194 million) DALYs and 9.14 million (95% UI: 8.40 to 9.74 million) fatalities due to the disease. A 2019 assessment of the global burden of cardiovascular disease and risk factors put the number of prevalent cases of IHD at 197 million (95% UI: 178 to 220 million) [1]. Young Asian Indians were shown to have a 15-fold higher incidence of CAD than Chinese people, and a 10-fold higher incidence than Malaysian people [4]. Triple valve disease, severe infarcts, and ventricular dysfunction are more common in young Asian Indians, and these conditions translate into higher death rates [5].

The primary cause of cardiovascular disease (CVD) is atherosclerosis [6]. A number of inflammatory markers, such as troponin I, myoglobin, CK-MB, leukocyte count, plasminogen activator, TNF-α, D-dimer, homocysteine, IL-6, C-reactive protein (CRP), fibrinogen, and albumin, are linked to an increased risk of adverse cardiac events in patients with coronary artery disease (CAD), which is a chronic inflammatory state that is involved throughout the pathological course of atherosclerosis [7]. Indians are five to ten years younger than the global population when it comes to coronary artery disease, and this peculiar phenomenon mostly affects the country's working population, which is made up of people between the ages of 35 and 65 [8]. Acute coronary syndrome is most common in India, as evidenced by high incidence and prevalence rates among Indians [8,9]. alterations in way of life and westernisation changes in eating patterns and the rising frequency of diabetes mellitus are all factors in India's rising incidence of acute coronary syndrome [9]. About 20 percent of the world's population now resides in the Indian subcontinent, and the CREATE registry, which has the biggest data set of Indian patients with acute coronary syndrome, shows that the pattern of ACS in this population differs greatly from that in the west. CVD is referred to as the "disease of the elderly" in western nations. Of those under the age of 70, 23% die from CVD, with India accounting for around 52% of these fatalities [10]. Acute coronary syndrome is a collection of clinical conditions that includes STEMI and non-ST elevation acute coronary syndrome.

pathophysiology of susceptible plaque rupture, which is followed by either red or white thrombosis and either partial or total arterial blockage. Large central lipid cores, a high concentration of inflammatory cells, a thin fibrous covering, and a deficiency of smooth muscle cells are the characteristics of the typical plaque [11].

The negatively charged, aglycosylated protein known as serum albumin is made up of 585 amino acids that combine to create a single polypeptide chain with a molecular weight of 66.5 kda [12]. The most prevalent circulatory protein, serum albumin is linked to a number of essential physiological processes, including preserving microvascular integrity and oncotic pressure, controlling metabolic and vascular processes, supplying substance binding ligands, antioxidant activities, and anticoagulant effects. Additionally, serum albumin has an antagonistic relationship with the inflammatory process by modifying neutrophil adhesion and all signalling moieties [13, 14]. Serum albumin [SA] is a key modulator of platelet-induced coronary artery constriction and a significant inhibitor of platelet activation and aggregation [15]. Hypoalbuminemia can induce elevated levels of free lysophosphatidylcholine, which can cause blood viscosity and interfere with endothelial function [16]. It has been discovered that hypoalbuminemia be a risk factor for individuals with coronary artery disease to experience a new myocardial infarction [17]. The liver produces fibrinogen, which is involved in inflammatory reactions on several levels and acts as a procoagulant status indicator [18]. Thus, systemic inflammatory and hemorheological changes are influenced by both fibrinogen and albumin. These two indicators together make up the Fibrinogen–Albumin ratio (FAR), which has been identified as a novel inflammatory measure strongly associated with the severity of coronary artery disease [19, 20].

This study was carried out at the Karnataka Institute of Medical Sciences in Hubli using prospective observational methods. Following clearance from the Institute's Ethical Committee, the study was carried out. Acute coronary syndrome was found in 108 of the study's subjects. Study participants' age, sex, history of diabetes, history of hypertension, and family history of CAD in first-degree relatives were among the risk variables and demographics that were evaluated.

Inclusion criteria:

1. All the patients presenting to KIMS hospital with clinical and ECG features of acute coronary syndrome undergoing angiography included in the study.
2. Age of more than 18years
3. Patients who give consent for the study.

Exclusion criteria:

1. Known Chronic liver disease
2. Known Chronic kidney disease
3. Severe Anaemia
4. Severe malnutrition
5. Known Ischemic heart disease
6. Known Chronic Obstructive pulmonary disease
7. Known Autoimmune disease
8. Known Malignancy
9. Known Ischemic stroke

Method

The study subjects who fulfilled the criteria, underwent coronary angiogram. Based on the coronary angiogram, significant CAD was defined by > 50% luminal stenosis of one of the major vessels (i.e., left anterior descending, circumflex, or right coronary artery) or its branches and insignificant CAD includes luminal stenosis of <50% of the major vessels or its branches. Significant CAD is assessed for the severity with the help of Gensini risk scoring system.

Study subjects were divided into three groups in to low FAR, middle FAR and high FAR based on tertiles. The fibrinogen level is measured based on electromechanical clot detection test with reference range 200 to 400 mg/dl. Patients were examined while wearing an examination gown. Each measurement was carried out twice, with the average being used in the analysis. For height and weight, we utilised the nearest 0.1 units of measurement. The height of the patients was measured with a tape metre in standing position with the shoulders in a normal alignment. Weight was measured using digital electronic weighing scale and rounded to the nearest 100g. BMI is expressed in kg per m² based on corresponding units, i.e., Weight divided by square root of height. The hip circumference is taken at the widest area of the hips at the greatest protuberance of the buttocks, while the waist circumference is taken at midway between the lowest rib and iliac crest. Waist circumference is considered increased in males and females if it is >102cms and >88cms respectively. WHR is calculated by dividing the waist circumference by the hip circumference. A ratio of > 0.9 in males and > 0.8 in women is considered to be abnormal and obese. Blood samples were collected early morning after an overnight fast and immediately centrifuged and stored at -70ºC and assessed according to the following methods, Serum creatinine by modified Jaffe’s, Triglycerides by glycerol phosphate oxidase (GPO) method, total cholesterol by cholesterol oxidase phenol 4-aminoantipyrine peroxidase (CHOD-PAP) method, LDL-C by precipitation method involving polyvinyl sulfonic acid (PVS) and polyethylene- glycol methyl ether (PEGME) complex, and  lipoprotein a by immunoturbidimetry method. According to ATP III criteria for the diagnosis of metabolic syndrome it considers dyslipidaemia, if triglycerides >150 mg/dl, HDL < 40 mg/dl, elevated blood pressure (systolic ≥130mmhg and diastolic ≥85mmhg), fasting blood glucose ≥ 110mg/dl, waist circumference >102 cm in males and >88 cm in females.

Table-1 Age Distribution Among Study Participants

In total, 108 patients were included in the study.  About 34.3% (n=37) were in the age group of 61-70 years, more than one-fourth of the participants were 41-50 years, 7.4% (8) were more than 70 years of age.

Fig-1: Bar Diagram Showing Age Distribution Among Study Participants.

Table-2 Gender Distribution Among Study Participants

Out of all the recruited study participants 70 (64.8%) were male and 38 (35.2%) were female.

Fig: 2- Pie Chart Showing Gender Distribution Among Study Participants

Table-3 HTN And DM Among Study Participants

Of all the 108 study participants, 65 (60.2%) had hypertension, 51 (47.2%) had diabetes mellitus and 7 (6.5%) had family history of coronary artery disease.

Fig 3: Bar Diagram Showing Hypertension, Diabetes And Family History Of CAD Among Study Participants

Table-4 Smoking, alcohol and tobacco use among study participants

Nearly half of the recruited participants had a habit of smoking, 52 (48.2%). About 45% (n=48) had a habit of alcohol use and 53% (n=58) reported that having tobacco use.

Fig-4: Bar Diagram Showing The Participants With Habits Of Smoking, Alcohol And Tobacco Use.

Table-5 Descriptive Statistics Of Study Participants

The mean (SD) total cholesterol was 156.9 (32.7), TGL was 192.2 (69.6), LDL was 108.4 (36.3), HDL was 41.1 (8.9). The median platelet count was 286000. The median GS score was 42 with the minimum of 18 and maximum of 70

The primary aim of this single-center, prospective observational study was to examine the relationship between the serum fibrinogen to albumin ratio and different subsets of patients with coronary artery disease, such as those with myocardial infarction (STEMI), non-ST segment myocardial infarction (NSTEMI), and unstable angina (UA), and how these subsets' angiographic severity was determined using the Gensini risk scoring system. Following coronary angiography, 120 Acute Coronary Syndrome patients were included in the research. Results showed that TVD 7(6.5%), DVD 63(58.3%), and SVD 38(35.2%) were the results. The Gensini risk score method is utilised to evaluate the degree of coronary constriction and the number of arteries implicated. The study subjects were categorised into three groups depending on their FAR levels: low (n = 36), intermediate (n = 36), and high (n = 36). The current study's one-way ANOVA test and Pearson correlation revealed a significant positive association between FAR levels and the Gensini risk rating system-based angiographic severity of coronary artery disease.

The clinical class and severity of CAD may be determined by blood FAR levels, as demonstrated by Karahan et al100's 2016 study. It was quickly shown that FAR is substantially connected with syntax score in predicting severity of CAD in patients with STEMI. The study included 278 participants with STEMI who underwent CAG. The extent and angiographic severity were assessed by SYNTAX score. The goal of Mingkang Li et al101's 2020 study was to assess the relationship between FAR and CAD severity in NSTEMI patients. The study included 1138 consecutive non-STEMI patients from January 2017 to December 2018, categorised into three groups according to FAR tertiles. The Gensini risk rating method is utilised to evaluate the severity of the condition. The study included a prospective arm and Major unfavourable cardiovascular outcomes, such as myocardial infarction, target vessel revascularisation, and all-cause mortality (TVR). The study found that FAR is independently correlated with the prognosis and severity of CAD, which helps to enhance risk classification in non-STEMI cases.

Results showed that FAR is a useful tool to predict intermediate-high SYNTAX score in non-STEMI patients. G. Erddogan et al. (102) conducted a study published in 2021 to look for association between FAR and the extent, severity, and complexity of CAD in non-STEMI patients. The study included 330 patients with non-STEMI who underwent CAG; study groups were divided based on SYNTAX score - Intermediate and High >23 (n = 241) and Low <23 (n = 89). According to multivariate regression analysis, the SYNTAX score may be independently predicted by FAR, LDL, and Troponin I.

Based on the Gensini risk rating method, it was discovered that FAR substantially correlated with the angiographic severity of CAD. The pearson correlation study revealed a substantial positive association between FAR and Gensini score, with a p-value of less than 0.001. The sample size was limited, and as only symptomatic individuals who had coronary angiography were included, it may not be entirely representative of the total population with coronary artery disease. The study was single-centered. Regarding prognostic significance and severity, there was no prospective arm. Additional risk factors that will operate as confounding variables in the development of coronary artery disease include smoking, hypertension, and family history.

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