European Journal of Cardiovascular Medicine

Cardiovascular disease (CVD) throughout the world is considered as major factor reducing the quality of life (1). Global burden of cardiovascular disease estimated by world health organization is about 10% and is considered as primary cause of death (2, 3). Coronary artery disease is obstruction in coronary artery & stenosis (≥ 50%) occurs in one or more coronary vessels and its prevention and treatment includes removing of obstruction for treating angina and preventing MI (4). Atherosclerosis, one of the major risk factor for CVD propagates on exposure to risk factors related to CVDs (5). Chronic inflammation and plaques deposition within arteries leads to atherosclerosis and these plaques stimulates inflammations that results in disturbed blood flow contributing to atherosclerotic cardiovascular disease (6). Hypertension is also a risk factor for CVDs, and arterial hypertension increases risk for cardiovascular diseases linked with atherosclerosis (7). Another study reports that hypertension for long time promotes atherosclerotic plaques formation leads to increasing prevalence of myocardial infarction and mortality associated with MI (8).

Coronary computed tomography angiography (CCTA) is non-invasive technique to determine coronary atherosclerotic disease hence CAD (9).  Mollet et al (2005) in their study reported that the degree of calcification and total occlusion is best assessed by CT and it is more accurate predictor than invasive angiography (10).

T-cadherin is a protein which is a third receptor for high molecular weight adiponectin. According to Genome-wide association study (GWAS), circulatory T-cadherin effects glucose metabolism and is associated with CAD (11). In atherosclerosis T-cadherin level is elevated in human aorta, carotid artery, smooth muscle cells and endothelium (12). Altered T-cadherin level can effect insulin sensitivity, contractile activity of vascular smooth muscle cells, extra cellular matrix, activity of nitric oxide synthase in endothelium etc (13). Khan et al (2023) in their study demonstrated that patients having atherosclerosis have greater circulatory T-cadherin when compared with healthy individuals (14). Elevation in Circulatory T-cadherin in plasma during CVDs and complications involved in CVDs indicating it as marker for early screening of atherosclerosis and CAD (15). Present study is design to predict coronary artery disease and risk for MI, assess with CTA and circulatory T-cadherin.

In this study, Total 140 subjects (70 cases and 70 controls) were enrolled from Hospital, University Medical College, IIMS&R, Lucknow after approval from Institutional Ethical Committee (IEC) and followed all the ethical standards with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All the subjects were enrolled in the study after taking complete history and informed consent. Cases were included, those having age in between 30-70 years, Referred for CTA with complain of heaviness in chest & breathlessness. Patients with CKD, hyperthyroidism, auto-immune disorders & pregnant women were excluded from the study. Healthy subjects having age in between 30-70 years were included as controls.

CTA was done on 128 slice Multi-detector computed tomography (MDCT). Coronary segments were visualized and the analysis was done to interpret the degree of stenosis. Significant stenosis was defined if the visualized lumen diameter found to reduce more than 50% otherwise the segment was considered non-diagnostic. CCTA was analyzed to interpret single vessel, double vessel and triple vessel involvement in CAD.

Major anthropometric and clinical parameters as risk factors for CVD are also estimated. Obesity was estimated measuring the waist circumference (WC) in both male and female patients, WC ≥ 90 cm for men and ≥ 80 cm for women was considered as obese. (16). Hypertension was measured using sphygmomanometer, blood pressure (BP) ≥ 140 mmHg (systolic) and/or ≥ 90 mmHg (diastolic) was considered as hypertension (17).

Among the clinical parameters, fasting blood glucose (FBS) and lipid profile was estimated using commercially available kits on fully automatic biochemistry analyzer. FBS ≥ 126 mg/dl were considered as T2DM (18) and total cholesterol (TC) > 200 mg/dl, High density lipoprotein cholesterol (HDL-C) < 40 mg/dl and Triglyceride (TG) > 150 mg/dl were considered having dyslipidemia (19). Circulatory level of T-cadherin was estimated using Enzyme linked Immune sorbent assay (ELISA). On the basis of CT angiography patients were categorized into three categories, single vessel involvement, double vessels involvement and three vessels involvement. After this categorization, circulatory T-cadherin was estimated in all the three groups and value was recorded. Statistical analysis was done using IBM SPSS 20.0 (Armonk, NY, USA). Values are represented as mean ± SD. ANOVA – analysis of variance or unpaired t-test was used wherever required. p- Value< 0.05 was considered as statistically significant..

When the demographic characteristics were analyzed, this was found that 28(40%) females and 42(60%) males were enrolled as cases in the study. This was observed among the cases that 20(28.5%) were in between 30-40 years of age, 18(25.7%) in between 41-50 years, 25(35.7%) in between 51-60 years and 07(10%) were in between 61-70 years of age. Among enrolled cases, total of 25(35.7%) were obese, 38(54.2%) were T2DM, 32(45.7%) having hyperlipidemia and 40(57.1%) were hypertensive those are associated with risk factors for CAD. Clinical signs and symptoms of acute chest pain were seen in 52(74.2%), Heaviness in chest in 55(78.5%) and difficulty in breathing was seen in 30(42.8%) individuals those were advised for CT angiography shown in Table 1 given below.

Table 1: Demographic characteristics of cases.

Multidetector computed tomography (MDCT) findings of coronary artery among cases are given in Table 2. It was observed that 15(21.4%) having single vessels blockage, 20(28.5%) having two vessels blockage and 35(50.0%) individuals have three vessels blockage.

Table 2: Multidetector computed tomography (MDCT) findings of coronary artery among cases.

When Circulatory T-cadherin level in plasma was estimated, the mean of T-cadherin was observed significantly high in cases when compared to controls (p<0.01) shown in Table 3.

Table 3: Comparison of  circulatory T-cadherin among cases & controls.

** Statistical significant at 0.01 level (2-tailed), p<0.01

*Statistical significant at 0.05 level (2-tailed), p<0.05

Circulatory T-cadherin levels were also estimated in all the individuals having single vessel blockage, two vessel blockage and three vessels blockage. This was observed that, mean of T-cadherin in patients having three vessels blockage was highest (7.79±0.73), when compared to two vessels blockage (7.33±0.76) and single vessel blockage (7.15±0.56). This overall difference in means of all three types of patients was statistically significant (p=0.007, p<0.05) shown in Table 4 below.

Table 4: Comparison of Circulatory T-cadherin among cases on the basis of MDCT findings.

** Statistical significant at 0.01 level (2-tailed), p<0.01

*Statistical significant at 0.05 level (2-tailed), p<0.05

Demographic analysis in this study among cases shows maximum patients having coronary artery disease (CAD) were in between 51-60 years of age. Lin et al. (2020) concluded the same risk factors of Mets that takes part in progression of CAD (20). Another study conducted by Kumar et al. (2024) gave the demographic characteristics of patients in which 16% were obese, 46% had hypertension, 28% had T2DM and 36% were of hyperlipidemia (21). Khan et al. (2023) in their study reported that individuals having greater abdominal obesity are at higher risk of developing T2DM and coronary artery disease and Asian Indians are more susceptible (22). In this study we found 35.7% with obesity, 54.2% were T2DM, 45.7% were having hyperlipidemia and 57.1% were hypertensive.

Adiponectin (APN) is a protein having T-cadherin as one of its receptor, binding of APN with T-cadherin enhances exosome biogenesis which in turn provide cardio-protective role of  both the protein together. In this present study levels of T-cadherin in cases (7.12±0.60) was found higher when compared to controls (1.01±0.32) and the difference was statistically significant (p< 0.01) the same conclusion was achieved by Khan et al. (2023) indicating Circulatory T-cadherin can be used as tool for early screening for T2DM and CVD risk factors (14).

Coronary computed tomography angiography (CCTA) has given worldwide acceptance as a suggestive non-invasive cardiac imaging technique (23). MDCT imaging increases the visualization of coronary artery and its anatomy that leads to originate CCTA which is used for detecting stenosis in coronary artery. It also provides information about plaque formation, composition, burden and its involved risk factors (24). Multicenter prospective studies conducted in United States (EVINCI) and Europe (PICTURE) concluded that the diagnostic accuracy of CCTA for detecting coronary stenosis is excellent when compared with functional imaging modalities (25). Adverse cardiovascular events and increased risk of death due to extensive obstructive or non-obstructive coronary atherosclerosis can be predicted by coronary computed tomography Angiography (CCTA) (26). In this study with the help of CT, obstructed vessels were determined and the patients were categorized accordingly. It was found and observed that patients having three vessels blockage have highest levels of circulatory T-cadherin when compared to double and single vessels. Hence this could be concluded that level of circulatory T-cadherin can be used to predict the level of coronary artery blockage and progression of cardiovascular complications i.e. greater the level of T-cadherin, greater will be chances of atherosclerosis and coronary obstruction. This conclusion is similar to the results obtained by Khan et al. (2022) (12).

This study concludes that the estimation of Circulatory T-cadherin and CTA evaluation can be used to predict the complications due to coronary obstruction. They can be used for the prognosis during the treatment of   CVDs and its complications. Increased level of T-cadherin can give early indication of involved cardiac pathology that can be evaluated with the help of CTA, hence both can be used in determination, treatment, prognosis and in reducing the mortality rate due to CAD.

Conflict of Interest – Authors have no conflict of interest.

Funding – None.

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