Ischemic heart disease (IHD), also known as coronary artery disease (CAD), is a leading cause of morbidity and mortality worldwide, resulting from an imbalance between myocardial oxygen supply and demand due to atherosclerotic plaque formation in the coronary arteries [1]. The pathophysiology of IHD involves a complex interplay between lipid metabolism, endothelial dysfunction, inflammation, and thrombosis. Among the numerous biomarkers implicated in atherosclerosis and cardiovascular disease, adiponectin has emerged as a critical adipocytokine with potential protective cardiovascular properties.

Adiponectin is a 30-kDa protein secreted predominantly by adipocytes and is abundant in the systemic circulation [2]. It exists in various multimedia forms and is involved in regulating glucose levels and fatty acid breakdown. Contrary to most adipokines that exhibit pro-inflammatory effects, adiponectin exerts anti-inflammatory, anti-atherogenic, and insulin-sensitizing actions [3]. Low serum adiponectin levels have been associated with metabolic syndrome, type 2 diabetes mellitus, and increased cardiovascular risk [4].

The inverse relationship between adiponectin levels and obesity, particularly visceral adiposity, is well established, making it a paradoxical adipocyte since it decreases with increasing adipose tissue mass [5]. Hypoadiponectinemia is thought to contribute to endothelial dysfunction by reducing nitric oxide bioavailability, increasing oxidative stress, and promoting vascular smooth muscle cell proliferation and foam cell formation, thereby accelerating the atherogenic process [6].

Several epidemiological and clinical studies have demonstrated an inverse correlation between serum adiponectin concentrations and the prevalence or severity of IHD. Patients with established coronary artery disease often present with lower adiponectin levels than age- and sex-matched controls [7]. Furthermore, low adiponectin has been shown to predict future cardiovascular events independently of traditional risk factors such as hypertension, hyperlipidemia, and smoking [8]. These findings suggest that adiponectin could serve both as a biomarker and a therapeutic target in the management of ischemic heart disease.

The cardioprotective mechanisms of adiponectin are multifactorial. It modulates inflammatory pathways by inhibiting tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), enhances endothelial cell function, and suppresses the expression of adhesion molecules like VCAM-1 and ICAM-1 on vascular endothelium [9]. In addition, adiponectin activates AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor-alpha (PPAR-α), which play crucial roles in myocardial energy metabolism and protection against ischemia-reperfusion injury [10].

Given the growing interest in adiponectin as a novel cardiovascular biomarker, further understanding of its correlation with ischemic heart disease is of immense clinical significance. It could potentially aid in early risk stratification, enhance diagnostic accuracy, and offer new avenues for therapeutic intervention. This study aims to assess the correlation between circulating adiponectin levels and the presence or severity of ischemic heart disease, contributing to the expanding knowledge on metabolic and inflammatory determinants of atherosclerosis.

Study Design: A cross-sectional observational study was conducted to assess the correlation between serum adiponectin levels and ischemic heart disease.

Study Site: The study was carried out in the Department of Biochemistry, BGS Medical College and Hospital, Bangalore.

Study Duration: The study was conducted over a period of one year.

Sample Size: A total of 100 participants were enrolled in the study.

Cases (n = 50): Diagnosed patients of ischemic heart disease (confirmed by ECG, cardiac biomarkers, or angiography).

Controls (n = 50): Age- and sex-matched healthy individuals without clinical or laboratory evidence of IHD.

Inclusion Criteria

• Individuals aged 30–70 years.
• Patients with a confirmed diagnosis of ischemic heart disease.
• Willingness to provide informed written consent.

Exclusion Criteria

Patients with:

• Diabetes mellitus
• Chronic kidney disease
• Liver disorders
• Autoimmune or inflammatory diseases
• Malignancy
• Recent infections (within 4 weeks)

Sample Collection

A total of 100 participants were enrolled in the study, including 50 patients diagnosed with ischemic heart disease (IHD) and 50 age- and sex-matched healthy controls. After obtaining informed consent, 3–5 mL of venous blood was collected from each participant in a plain vacutainer. Blood samples were obtained in the morning hours after an overnight fast of 8–12 hours to minimize diurnal variation in adiponectin levels.

Data Collection

A detailed clinical history and demographic data were recorded, including age, sex, body mass index (BMI), history of hypertension, diabetes mellitus, dyslipidemia, smoking status, and medication use. For IHD patients, diagnosis was based on clinical presentation, ECG changes, cardiac enzyme levels, and/or coronary angiography findings. Control participants had no history of cardiovascular disease and normal ECG and lipid profiles.

Laboratory Analysis

Collected blood samples were allowed to clot at room temperature and centrifuged at 3000 rpm for 10 minutes to separate serum. The serum was aliquoted and stored at –80°C until further analysis.

Serum adiponectin levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (e.g., R&D Systems, USA), based on a sandwich ELISA principle. The assay was performed according to the manufacturer’s instructions. Optical density was measured at 450 nm using a microplate reader. Adiponectin concentrations were calculated from a standard curve derived from known concentrations provided in the kit. All samples were analyzed in duplicate to ensure reproducibility, and the intra-assay and inter-assay coefficients of variation were <10%.

Reference Ranges

Normal reference ranges for serum adiponectin levels vary based on sex and BMI. In general, values are considered normal in the following ranges:

• Men: 4–10 µg/mL
• Women: 5–15 µg/mL

Values below these ranges are associated with an increased risk of metabolic syndrome and cardiovascular disease.

Venous blood samples were collected from all study participants after overnight fasting. The serum was separated and stored appropriately until analysis. Adiponectin levels were measured using enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer’s instructions. In addition, fasting blood sugar (FBS) and lipid profile (including total cholesterol, triglycerides, HDL-C, and LDL-C) were also analyzed using standard automated biochemical methods in the hospital laboratory.

Statistical Analysis: -

For statistical analysis, data were initially entered into a Microsoft Excel spreadsheet and then analyzed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and Graph Pad Prism (version 5). Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests were used to compare independent groups, while paired t-tests accounted for correlations in paired data. Chi-square tests (including Fisher’s exact test for small sample sizes) were used for categorical data comparisons. P-values ≤ 0.05 were considered statistically significant.

Table 1: Demographic and Clinical Characteristics of Study Population

Table 2: Comparison of Biochemical Parameters between Cases and Controls

Table 3: Serum Adiponectin Levels in Cases and Controls

Table 4: Correlation between Adiponectin and Lipid Profile in All Participants (n=100)

Table 5: Logistic Regression Analysis – Predictors of Ischemic Heart Disease

A total of 100 participants were included in the study, comprising 50 ischemic heart disease (IHD) patients and 50 healthy controls. The mean age of the cases was 58.4 ± 8.6 years, while that of the controls was 57.2 ± 9.1 years; the difference was not statistically significant (p = 0.43). The gender distribution was comparable, with 72% males in the case group and 70% in the control group (p = 0.83).

The mean Body Mass Index (BMI) was significantly higher in IHD patients (27.5 ± 3.2 kg/m²) compared to controls (25.8 ± 2.9 kg/m²), with a p-value of 0.01, indicating a statistically significant difference. Systolic blood pressure was notably elevated in the case group (142 ± 12 mmHg) compared to the controls (126 ± 10 mmHg), and this difference was highly significant (p < 0.001). Similarly, diastolic blood pressure was higher in the IHD group (88 ± 8 mmHg) than in the control group (80 ± 6 mmHg), also showing a statistically significant difference (p < 0.001).

Biochemical analysis revealed significant differences between ischemic heart disease (IHD) patients and healthy controls. The mean fasting glucose level was significantly elevated in the IHD group (112.3 ± 18.7 mg/dL) compared to the controls (97.4 ± 14.2 mg/dL), with a p-value of <0.001. Total cholesterol levels were also higher among the cases (210.2 ± 30.1 mg/dL) than in the controls (180.6 ± 28.4 mg/dL), which was statistically significant (p < 0.001).

Low-density lipoprotein cholesterol (LDL-C), a major atherogenic component, was significantly elevated in IHD patients (134.4 ± 25.6 mg/dL) compared to controls (110.2 ± 22.7 mg/dL), with p < 0.001. Conversely, high-density lipoprotein cholesterol (HDL-C), known for its cardioprotective role, was markedly reduced in cases (37.8 ± 6.1 mg/dL) as compared to controls (48.2 ± 7.2 mg/dL), and the difference was highly significant (p < 0.001).

Furthermore, triglyceride levels were significantly higher in the case group (178.5 ± 40.6 mg/dL) than in the control group (140.3 ± 35.7 mg/dL), with a p-value < 0.001.

A statistically significant difference was observed in the mean serum adiponectin levels between ischemic heart disease (IHD) patients and healthy controls. The mean adiponectin concentration in the IHD group was 3.6 ± 1.3 µg/mL, which was significantly lower than the control group, where the mean level was 8.2 ± 1.7 µg/mL (p < 0.001).

Correlation analysis between serum adiponectin levels and lipid profile parameters revealed statistically significant associations. A moderate negative correlation was observed between adiponectin and total cholesterol (r = –0.45, p < 0.001), as well as low-density lipoprotein cholesterol (LDL-C) (r = –0.48, p < 0.001). This indicates that higher cholesterol and LDL-C levels are associated with lower adiponectin concentrations.

Conversely, a positive correlation was found between adiponectin and high-density lipoprotein cholesterol (HDL-C) (r = +0.39, p < 0.001), suggesting a cardioprotective link. Additionally, triglyceride levels exhibited a significant inverse correlation with adiponectin (r = –0.41, p < 0.001).

Logistic regression analysis was performed to identify independent risk factors associated with ischemic heart disease (IHD). The analysis revealed that low adiponectin levels were a significant and strong independent predictor of IHD, with an odds ratio (OR) of 3.96 (95% CI: 1.8–8.5, p < 0.001), suggesting that individuals with lower adiponectin had nearly four times greater odds of developing IHD.

Additionally, high LDL-C was significantly associated with IHD, showing an OR of 2.73 (1.3–5.9, p = 0.008). Low HDL-C also increased the risk, with an OR of 2.11 (1.1–4.0, p = 0.02). Elevated triglyceride levels were another significant predictor, with an OR of 1.89 (1.0–3.6, p = 0.04). Although high BMI showed a mild association with IHD (OR = 1.56), it was not statistically significant (p = 0.11).

The present study underscores a robust association between various metabolic and cardiovascular risk factors and ischemic heart disease (IHD), particularly highlighting the inverse relationship between serum adiponectin levels and lipid parameters. The significantly lower adiponectin levels in IHD patients (3.6 ± 1.3 µg/mL) compared to controls (8.2 ± 1.7 µg/mL, p < 0.001) corroborate findings from previous literature. For instance, Kumada et al. demonstrated that low adiponectin levels were significantly associated with coronary artery disease (CAD), suggesting an anti-inflammatory and anti-atherogenic role for this adipokine [11]. Similar results were reported by Zoccali et al., who found a strong inverse association between adiponectin and cardiovascular morbidity in dialysis patients [12].

The moderate negative correlation observed between adiponectin and LDL-C (r = –0.48) and total cholesterol (r = –0.45) in our study aligns with the work of Arita et al., who first identified the inverse relationship between adiponectin and serum lipid levels, thus establishing its protective role against atherosclerosis [13]. Moreover, the positive correlation with HDL-C (r = +0.39) reinforces the notion of adiponectin as a beneficial cardiovascular marker, consistent with the findings of Kadowaki and Yamauchi, who reported similar associations in both experimental and clinical settings [14].

Biochemical parameters such as fasting glucose, total cholesterol, LDL-C, and triglycerides were markedly elevated in the IHD group, while HDL-C was significantly reduced—findings that are in agreement with earlier studies by Chandalia et al. and Pischon et al., which highlighted the interrelationship between dyslipidemia, insulin resistance, and adiponectin deficiency in the pathogenesis of cardiovascular disease [15,16]. The logistic regression analysis in our study further affirms these associations, with low adiponectin emerging as a significant independent risk factor for IHD (OR = 3.96, 95% CI: 1.8–8.5, p < 0.001). Comparable results were obtained in the study by Li et al., where low adiponectin levels independently predicted coronary events, even after adjusting for traditional risk factors [17].

Additionally, elevated LDL-C and triglyceride levels and reduced HDL-C were found to significantly increase IHD risk, in line with the INTERHEART study, which identified abnormal lipids as one of the leading contributors to myocardial infarction globally [18]. Our findings also mirror those of Yadav et al., who demonstrated that Indian patients with IHD had significantly higher triglycerides and lower HDL-C, often accompanied by low adiponectin concentrations [19]. Although high BMI was mildly associated with IHD (OR = 1.56, p = 0.11), it did not achieve statistical significance, possibly due to the relatively small sample size. Nevertheless, studies like that of Matsuzawa et al. have shown a strong link between visceral obesity, reduced adiponectin, and a higher prevalence of metabolic syndrome and cardiovascular disease [20].

Collectively, these results affirm the multifactorial nature of IHD, emphasizing the interplay between adiponectin deficiency and dyslipidemia. This reinforces the growing consensus that adiponectin is not merely a biomarker but potentially a therapeutic target in the prevention and management of cardiovascular diseases.

The present study clearly highlights significant differences in clinical, anthropometric, and biochemical parameters between ischemic heart disease (IHD) patients and healthy controls. Elevated body mass index, blood pressure, fasting glucose, and adverse lipid profile parameters were all significantly associated with IHD. Most notably, serum adiponectin levels were markedly reduced in IHD patients and demonstrated significant inverse correlations with total cholesterol, LDL-C, and triglycerides, while showing a positive correlation with HDL-C. Logistic regression analysis confirmed that low adiponectin levels, high LDL-C, low HDL-C, and elevated triglycerides are independent and significant risk factors for IHD. Among these, low adiponectin emerged as the strongest predictor, nearly quadrupling the risk of IHD. These findings suggest that serum adiponectin, due to its strong inverse association with atherogenic lipids and its predictive power, may serve as a valuable biomarker for cardiovascular risk stratification. Early identification and modification of these risk factors, especially targeting adiponectin-linked pathways, could be crucial in the prevention and management of ischemic heart disease.

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