Comparative Analysis of Biomarkers in CAD: Evaluating Homocysteine, Lipid HS-CRP, Apo A, and ADMA

ABSTRACT

Introduction:

Coronary artery disease (CAD), resulting from the narrowing of coronary arteries that supply oxygen to the heart, poses a significant global health challenge.

Materials and Methods:

To compare the levels of homocysteine, lipid profile, lipid ratios, HS-CRP, ADMA, and apolipoproteins in CAD patients with controls, this chapter analyzes risk factors, biomarkers, and clinical traits linked to coronary artery disease (CAD) through a case–control study involving 200 participants (100 CAD cases and 100 controls). The investigation focuses on demographic variables, traditional risk factors (e.g., hypertension, smoking, alcohol intake), and essential biochemical markers such as lipid profiles, homocysteine, and emerging biomarkers like HS-CRP, ADMA, and apolipoproteins (Apo A1 and Apo B).

Results and Conclusion:

The findings underscore the interplay between traditional and emerging risk factors in CAD progression. LDL, homocysteine, and TC/HDL ratio emerge as robust predictors of CAD risk. The regression model’s high explanatory power (R^² =97.2%) validates these indicators for effective risk assessment.

INTRODUCTION

Coronary artery disease (CAD), resulting from the narrowing of coronary arteries that supply oxygen to the heart, poses a significant global health challenge. Unstable angina, a severe manifestation, highlights the urgency of timely intervention. Cardiovascular diseases (CVDs), including CAD, remain leading causes of morbidity and mortality globally. Traditional risk factors like dyslipidemia—characterized by high LDL cholesterol and low HDL cholesterol—are compounded by novel factors such as hyperhomocysteinemia (HHcy).[1] The metabolism of homocysteine primarily involves two pathways—remethylation and transsulfuration—both requiring essential cofactors like vitamin B6, B9, and B12. Disruptions in these pathways lead to increased plasma homocysteine levels, adversely affecting cardiovascular health.[2] Studies highlight an inverse relationship between homocysteine and HDL cholesterol, emphasizing the metabolic interplay influencing cardiovascular outcomes.[3]

A systematic review and meta-analysis revealed significant variations in homocysteine levels between CAD patients and controls, with stronger associations observed in Asian populations.[4] Highlighted the interplay between hyperhomocysteinemia and coronary artery disease (CAD). Low vitamin D levels were inversely correlated with homocysteine, influencing disease severity.[5] NCEP demonstrated the compound effect of elevated homocysteine levels and dyslipidemia on cardiovascular risk.[6] Guo et al. (2017)[7] showed that folic acid supplementation significantly reduces homocysteine levels and improves endothelial function, offering potential preventive benefits against atherosclerosis. Schaffer et al. (2014)[8] confirmed the independent association between elevated homocysteine levels and CAD severity, underscoring its role as a reliable biomarker for disease progression. Nelson (2013).[9] The correlation between cardiovascular disease and elevated blood lipid levels has been recognized for quite some time. Adults with hyperlipidemia are classified and treated according to NCEP recommendations.

AIM AND OBJECTIVES

• To compare the levels of homocysteine, lipid profile, lipid ratios, HS-CRP, ADMA, and apolipoproteins in CAD patients with controls

• To evaluate how hyperhomocysteinemia is associated with lipid profiles and lipid ratios in patients with coronary artery disease.

MATERIAL AND METHODS

Sampling technique

A non-probability purposive sampling method will be used. The sample size will comprise 200 participants, including 100 newly diagnosed CAD patients and 100 controls from hospitals in Maharashtra.

Inclusion Criteria:

• Newly diagnosed cardiac or hypertensive patients.

Exclusion Criteria:

• Patients with liver or kidney diseases.

• Patients undergoing extensive medical treatment or on lipid-lowering drugs.

Data collection and preparation

Venous blood samples (5 mL) will be drawn from participants under aseptic conditions and analyzed for the following parameters:

Serum homocysteine, total cholesterol, triglycerides, HDL-C, LDL-C, VLDL-C, HS-CRP, ADMA, Apo A1.

Data analysis

Statistical analysis will be conducted using SPSS (version 26.0).

RESULTS

This chapter analyzes risk factors, biomarkers, and clinical traits linked to coronary artery disease (CAD) through a case–control study involving 200 participants (100 CAD cases and 100 controls). The investigation focuses on demographic variables, traditional risk factors (e.g., hypertension, smoking, alcohol intake), and essential biochemical markers such as lipid profiles, homocysteine, and emerging biomarkers like HS-CRP, ADMA, and apolipoproteins (Apo A1 and Apo B). Additionally, critical lipid ratios, including HDL/LDL and TC/HDL, are evaluated to enhance cardiovascular risk assessments.

Regression analysis

The study employs multiple regression analysis to identify predictors of CAD:

• Predictive Strength: LDL, homocysteine, and TC/HDL ratio are the strongest predictors of CAD. These factors have significant relationships with CAD risk.

• Statistical Indicators:

  • R = 0.986: Strong correlation between predictors and CAD.

  • R^² = 0.972: 97.2% of CAD likelihood variance is explained by predictors.

  • Adjusted R^² = 0.971: Ensures robust model reliability.

  • P value <0.05: Confirms model’s statistical significance as shown in Table 1.

• Lipid Ratios: TC/HDL and HDL/LDL ratios are critical in assessing CAD risk.

Table 1.

Multiple regression analysis to identify predictors of CAD

Coefficientsa
Model		“Unstandardized Coefficients”		“Standardized Coefficients Beta	t-test	Sig.
		B	Std. Error
1	Parameters	1.801	0.354		5.089	0.000
	Total cholesterol (mg/dL)	-0.044	0.009	-1.005	-4.643	0.000
	Triglycerides (mg/dL)	-0.010	0.002	-0.239	-4.057	0.000
	LDL (mg/dL)	0.051	0.014	0.973	3.641	0.000
	HDL (mg/dL)	0.039	0.011	0.407	3.558	0.000
	Homocysteine levels (μmol/L)	0.061	0.002	0.724	27.387	0.000
	HS-CRP Levels (mg/L)	-0.013	0.010	-0.022	-1.285	0.002
	ADMA Levels (μmol/L)	0.106	0.065	0.048	1.632	0.004
	Apo A1 (mg/dL)	0.001	0.000	0.021	1.305	0.094
	Apo B (mg/dL)	-0.004	0.001	-0.200	-5.746	0.000
	HDL/LDL Ratio	-2.171	0.433	-2.003	-5.011	0.000
	TC/HDL Ratio	1.444	0.281	1.901	5.134	0.000

a=Dependent variable: Group

The findings emphasize monitoring lipid indicators and homocysteine levels to mitigate CAD risk and improve clinical strategies.

DISCUSSION

In our study, gender distribution indicates a predominance of men among both cases and controls, with a greater male prevalence of 65% among CAD patients, while a study done by (Santos et al., 2023)[10] found that the male sex exhibited a higher prevalence of CAD than the female sex (21% vs. 12%). In our study, age distribution reveals that CAD is most common in the 56–65 age group, highlighting age as a critical risk factor. Another study done by (Reibis et al., 2012)[11] found that a large-scale survey conducted in German cardiac rehabilitation centers found that 37% of men and women under the age of 55 and 65 had CAD, whereas 67% of men and women over the age of 55 and 65 had CAD.

Another study done by (Aggarwal et al., 2021)[12] found “that non-high density lipoprotein cholesterol and Apo B” have been established as more accurate indicators of CAD risk. A study suggested that non-high-density lipoprotein cholesterol (non-HDL-C) and other lipid indicators could be potential markers for coronary artery disease risk.[13]

CONCLUSION

The findings underscore the interplay between traditional and emerging risk factors in CAD progression. LDL, homocysteine, and TC/HDL ratio emerge as robust predictors of CAD risk. The regression model’s high explanatory power (R^² = 97.2%) validates these indicators for effective risk assessment. Homocysteine’s correlations with lipid profiles highlight its potential as a biomarker for CAD, complementing traditional measures like LDL cholesterol.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.