European Journal of Cardiovascular Medicine

Coronary artery disease (CAD) is a major global health problem and the leading cause of morbidity and mortality worldwide. It is primarily caused by atherosclerosis, a chronic inflammatory and lipid-driven process that leads to progressive narrowing of the coronary arteries and subsequent myocardial ischemia (1). The burden of CAD is increasing rapidly in developing countries, including India, due to lifestyle changes, urbanization, and the growing prevalence of metabolic disorders such as diabetes mellitus, obesity, and dyslipidaemia (2).

Conventionally, lipid parameters such as total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides are used to assess the risk of CAD. However, several studies have shown that these traditional lipid measures may not fully capture the complexity of lipid metabolism or accurately predict coronary events, especially when discordance exists between LDL-C levels and the number of atherogenic particles (3,4).

Apolipoproteins, which are the structural and functional protein components of lipoproteins, have emerged as superior indicators of cardiovascular risk. Apolipoprotein B (ApoB) is the main apolipoprotein of atherogenic lipoproteins—LDL, VLDL, and IDL—and represents the total number of potentially atherogenic particles in circulation. Elevated ApoB levels have been shown to correlate strongly with increased risk of atherosclerotic cardiovascular events, even in patients with normal LDL-C (5,6). Conversely, Apolipoprotein A-I (ApoA-I), the major protein component of HDL, plays a protective role by mediating reverse cholesterol transport and exerting antioxidant, anti-inflammatory, and endothelial-stabilizing effects. Low ApoA-I levels are associated with impaired HDL function and increased CAD risk (7,8).

The ApoB/ApoA-I ratio integrates both atherogenic and anti-atherogenic lipoprotein profiles, reflecting the balance between cholesterol deposition and removal. Large-scale studies, including the AMORIS and INTERHEART studies, have established the ApoB/ApoA-I ratio as a stronger predictor of myocardial infarction and cardiovascular mortality than traditional lipid ratios such as LDL/HDL cholesterol (9,10). Despite this, the measurement of apolipoproteins is not yet routinely incorporated into risk assessment protocols in many clinical settings, particularly in developing countries.

Given these findings, evaluating the association between apolipoproteins and CAD can provide valuable insights into their diagnostic and prognostic utility and may guide better risk stratification and management strategies.

Aim and Objectives

Aim:

To study the association between apolipoproteins and coronary artery disease.

Objectives:

To estimate serum levels of Apolipoprotein B (ApoB) and Apolipoprotein A-I (ApoA-I) in patients with coronary artery disease and healthy controls.

To determine the ApoB/ApoA-I ratio in both groups and assess its correlation with the severity of coronary artery disease.

To compare the predictive value of apolipoproteins and conventional lipid parameters in identifying CAD risk.

Study Design and Setting This study was designed as a case–control observational study conducted in the Department of Medicine and Department of Medicine and Cardiology at Konaseema institute of medical sciences Amalapuram AP India a tertiary care teaching hospital, between November 2018 and March 2020. The study was approved by the Institutional Ethics Committee, and written informed consent was obtained from all participants prior to enrolment. Study Population A total of 100 participants were included in the study, comprising 50 patients with angiographically proven coronary artery disease (CAD) and 50 age- and sex-matched healthy controls without clinical or electrocardiographic evidence of CAD. Inclusion Criteria Patients aged 30–70 years. Individuals with CAD confirmed by coronary angiography (≥50% stenosis in at least one major coronary artery). Patients willing to provide written informed consent. Exclusion Criteria Patients with secondary dyslipidemia (due to hypothyroidism, nephrotic syndrome, chronic liver disease). History of chronic kidney disease, diabetes mellitus, or acute infections. Individuals on lipid-lowering therapy or antioxidant supplementation. Smokers and alcoholics were excluded to minimize confounding variables. Data Collection A detailed clinical history was recorded, including demographic details, cardiovascular risk factors, and medication history. Physical examination included measurement of height, weight, and blood pressure. Body mass index (BMI) was calculated as weight (kg)/height (m²). Sample Collection and Laboratory Investigations Venous blood samples were collected from all participants after an overnight fast of 10–12 hours. Serum was separated and stored at –20°C until analysis. The following investigations were performed: Lipid profile: Total cholesterol, triglycerides, HDL-C, and LDL-C were measured using enzymatic colorimetric methods on an automated analyzer. Apolipoprotein assay: Serum Apolipoprotein A-I (ApoA-I) and Apolipoprotein B (ApoB) levels were estimated using immunoturbidimetric method with commercially available reagent kits. The ApoB/ApoA-I ratio was calculated for each subject. Quality control sera were run with each batch of samples to ensure analytical accuracy and precision. Assessment of Coronary Artery Disease Severity In CAD patients, the severity of coronary lesions was graded based on coronary angiography findings, and classified as: Single-vessel disease (SVD), Double-vessel disease (DVD), or Triple-vessel disease (TVD), depending on the number of major arteries involved. Statistical Analysis Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 25.0 (IBM Corp., USA). Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables as frequencies and percentages. Comparison between cases and controls was performed using the student’s t-test for continuous variables and the Chi-square test for categorical variables. Correlation between apolipoproteins and lipid parameters was assessed using Pearson’s correlation coefficient. The ApoB/ApoA-I ratio was compared across CAD severity groups using one-way ANOVA followed by post hoc analysis. A p-value < 0.05 was considered statistically significant.

A total of 100 subjects were studied, comprising 50 patients with coronary artery disease (CAD) and 50 age- and sex-matched healthy controls. The mean age of CAD patients was 55.8 ± 8.4 years, and that of controls was 54.2 ± 7.9 years. The male-to-female ratio was 3:1 in both groups, showing no significant sex difference between cases and controls (p > 0.05).

Table 1: Baseline characteristics of study participants

p < 0.05 considered statistically significant

CAD patients had significantly higher mean BMI and blood pressure compared to controls.

Table 2: Comparison of lipid profile between CAD patients and controls

*Significant at p < 0.05

Patients with CAD had significantly higher total cholesterol, triglycerides, and LDL-C levels, and significantly lower HDL-C levels compared with controls.

Table 3:- Comparison of Apolipoprotein levels and ApoB/ApoA-I ratio

*Significant at p < 0.05

CAD patients had significantly higher mean ApoB levels and ApoB/ApoA-I ratio, and significantly lower ApoA-I levels compared to healthy controls.

Table 4: ApoB/ApoA-I ratio in relation to severity of CAD

p-value                 <0.001*

A significant positive trend was observed between ApoB/ApoA-I ratio and the severity of CAD (p < 0.001, ANOVA).

Correlation Analysis

Pearson’s correlation analysis showed that ApoB correlated positively with total cholesterol (r = 0.62, p < 0.001) and LDL-C (r = 0.69, p < 0.001), whereas ApoA-I showed a positive correlation with HDL-C (r = 0.71, p < 0.001) and an inverse correlation with triglycerides (r = –0.43, p = 0.002).

In the present study, patients with coronary artery disease showed a distinctly more atherogenic lipid profile than healthy controls, characterized by higher total cholesterol, triglycerides, LDL-C, and ApoB levels, together with lower HDL-C and ApoA-I levels. The ApoB/ApoA-I ratio was also significantly elevated in CAD patients and increased with angiographic severity, suggesting that this index may better reflect the balance between pro-atherogenic and anti-atherogenic lipoprotein pathways than conventional lipid parameters alone.

These findings are in agreement with earlier large epidemiological investigations. In the AMORIS study, Walldius et al. demonstrated that high ApoB and low ApoA-I were strongly associated with fatal myocardial infarction, emphasizing the clinical value of combining these two apolipoproteins into a single risk indicator [9]. Likewise, the INTERHEART study showed that apolipoprotein-based measures, particularly the ApoB/ApoA-I ratio, had strong associations with myocardial infarction across diverse populations and were at least as informative, and in many settings more informative, than traditional lipid indices [10]. The present findings therefore support the relevance of apolipoprotein assessment in identifying individuals with established coronary risk.

The higher ApoB concentrations observed in our CAD group indicate an increased number of circulating atherogenic lipoprotein particles. Since each atherogenic particle contains one ApoB molecule, serum ApoB provides a direct estimate of particle burden, which may explain its closer relation to atherosclerotic risk than LDL-C concentration alone. This concept is supported by discordance analyses showing that ApoB can identify residual cardiovascular risk even when conventional cholesterol measures appear less abnormal [11]. Thus, patients with apparently acceptable LDL-C values may still harbor a substantial burden of atherogenic particles, which remains clinically important.

In contrast, ApoA-I represents the principal structural and functional apolipoprotein of HDL and plays a central role in reverse cholesterol transport. Beyond cholesterol efflux, HDL and ApoA-I exert anti-inflammatory, antioxidant, and endothelial protective effects. Kontush and Chapman highlighted that dysfunctional HDL may lose these vasoprotective properties, thereby contributing to atherosclerotic progression [7]. Consistent with this concept, Rohatgi et al. reported that impaired HDL cholesterol efflux capacity was associated with incident cardiovascular events, reinforcing the view that reduced ApoA-I and impaired HDL function may be closely linked to CAD pathogenesis [8]. The lower ApoA-I levels in our CAD patients may therefore reflect not only reduced HDL quantity but also compromised anti-atherogenic function.

An important observation in the present study was the progressive rise in the ApoB/ApoA-I ratio from less extensive to more severe coronary involvement. This suggests that the ratio may have value not only in identifying CAD but also in reflecting disease burden. Because it integrates the concentration of atherogenic particles and the opposing protective HDL-related component, the ApoB/ApoA-I ratio provides a biologically meaningful summary of lipid-related risk. This interpretation is consistent with previous work indicating that apolipoprotein-based measures are robust markers of coronary risk across clinical settings [9,10,11].

The association of ApoB with other conventional lipid abnormalities in our study further supports its metabolic relevance. Talmud et al. showed that ApoB, particularly in conjunction with triglyceride-related abnormalities, predicted coronary heart disease risk in middle-aged men [12]. This is especially relevant in patients with hypertriglyceridemia, insulin resistance, or mixed dyslipidemia, in whom LDL-C alone may underestimate the true atherogenic burden. In such settings, ApoB and the ApoB/ApoA-I ratio may provide a more precise indication of underlying lipoprotein-mediated risk.

Overall, the present study adds to the growing body of evidence supporting the clinical usefulness of apolipoprotein measurements in CAD. Our results indicate that ApoB is elevated, ApoA-I is reduced, and the ApoB/ApoA-I ratio is significantly higher in CAD patients and correlates with angiographic severity. These findings suggest that apolipoprotein-based markers may complement conventional lipid testing and improve cardiovascular risk stratification, particularly in individuals in whom standard lipid parameters do not fully capture the extent of atherogenic risk [9-12].

Limitations

The study was limited by a relatively small sample size and its cross-sectional design, which precludes causal inference. Additionally, the study did not account for genetic polymorphisms or dietary factors influencing apolipoprotein levels. Larger prospective studies across diverse populations are warranted to validate these findings and establish apolipoprotein-based cut-offs for CAD risk prediction in the Indian population.

The present study demonstrates that serum ApoB and ApoA-I levels, and particularly the ApoB/ApoA-I ratio, are strongly associated with the presence and severity of coronary artery disease. The ApoB/ApoA-I ratio serves as a more reliable and sensitive marker of atherogenic risk than conventional lipid parameters, highlighting its potential clinical utility in early detection and management of CAD.

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