Full Text

Review Article

Biochemical Markers for Early Detection of Cardiovascular Diseases


Abstract

Biochemical indicators are critical for the early detection, evaluation and prognosis of cardiovascular disorders (CVD). The clinical uses and functions of both established and developing indicators were examined. Additionally, B-type natriuretic peptide (BNP) and troponins are recognized biomarkers used to diagnose heart failure and myocardial infarction. Emerging biomarkers that are considered as promise markers for CVD disease in pathways and risk stratification interpretation include high sensitivity troponins, galectin-3 and microRNAs. Although these markers are helpful for CVD, there are many problems including assay uniformity, interindividual variability and specificity. The use of sensitive assays and customized medicine techniques and the use of biomarker for a more thorough risk assessment are the main future prospects. New and conventional markers are included into recent clinical standards to improve patient care. This oversite of the potential of biochemical markers to change cardiovascular outcomes further exemplifies the revolutionary possibility of such markers in healthcare.

 

Keywords: Atherosclerosis, Cardiovascular disease, Heart failure, Hypertension, Lipoprotein

 

1. Introduction

Cardiovascular diseases (CVD) will always be the primary cause of high death rates on all of the world's continents, which emphasizes the need of early identification and management techniques. Early diagnosis is essential for predicting patient outcomes and for enabling early care, which can reduce major issues. Biomarkers have become the most common surrogates for CVD diagnosis and prognosis because these markers provide crucial information about the history of pathophysiological CVD1,2. In order to deliver more targeted, precise therapy, recent advancements in biomarker research have broadened the understanding of CVD beyond traditional risk factors.

 

Biomarkers provide important information about the early detection and prognosis of CVD. In order to identify acute cardiac events and assess the risk of heart failure, conventional markers such as troponins and natriuretic peptides have been widely used. But recently, more precise and sensitive biomarkers have been used3,4.

 

CVD molecular pathways understanding is affected by these advancements. By incorporating these new insights into existing clinical practice, healthcare practitioners may be able to better stratify individuals at risk, more precisely modify treatment plans and improve patient outcomes.

 

This review will focus on the diagnostic and prognostic potential of biochemical markers for CVD. problems and future potential in biomarker research will also talk about, as well as technology advancements in marker detection to improve early intervention strategies and optimize patient care.

 

2. Pathophysiology of Cardiovascular Diseases

The major cause of morbidity and death worldwide is still CVD, which is mediated by several pathophysiological mechanisms, despite substantial research efforts. Thus, it is essential to comprehend these pathways for early detection and treatment strategies.

 

2.1. Atherosclerosis

Atherosclerosis is a degenerative disease in which the walls of the arteries accumulate fibrous debris, inflammatory cells and lipids. This has to do with endothelial dysfunction, a critical early event characterized by decreased nitric oxide production and increased permeability. Endothelium is independently infiltrated by lipoproteins, particularly low-density lipoprotein (LDL) which is then oxidized and elicited inflammation. Oxidized LDL is consumed by macrophages to become foam cells and fatty streaks, turning into fibrous plaques. Eventually they become unstable over time and rupture and thrombosis are the primary causes of myocardial infarction and stroke5-7.

 

2.2. Hypertension

Hypertension, arterial walls subjected to mechanical stress under hypertension, such as hypertensive patients, will undergo endothelial injury and will develop atherosclerosis. chronic hypertension is associated with left ventricular hypertrophy, increased myocardial oxygen demand and eventual heart failure. Aside from accelerating arteriosclerosis, it also increases the risk of cardiovascular event8,9.

 

2.3. Inflammation

CVD pathogenesis is characterized by fundamental inflammation. Plaque formation and instability also have a role played by inflammatory cytokines and cells such as C-reactive protein and interleukins. Further endothelial dysfunction is promoted and atherosclerosis progresses, as a consequence of the chronic inflammatory state6,10-12.

 

2.4. Thrombosis

Blood clots that form in vessels, causing obstruction of blood flow, is called thrombosis. Thrombogenic material becomes exposed to the bloodstream in case of plaque rupture, triggering platelet activation and the coagulation cascade. If the resulting thrombus occludes coronary arteries, the result can be acute coronary syndromes13-15.

 

2.5. Myocardial infarction

Reduced blood flow to the heart muscle (myocardial ischemia) may result from obstruction of a coronary artery. Myocardial infarction, the prolongation of ischemia, may cause irreversible cardiac tissue damage. Minimization of the myocardial loss requires rapid intervention16.

 

2.6. Heart failure

Heart failure is a complex syndrome in which the heart cannot pump blood adequately. Myocardial infarction, chronic hypertension or valvular disease of the heart may lead to it. Neurohormonal activation, fluid retention and cardiac structural change in heart failure result in the associated symptoms of congestion and decreased heart output17-19.

 

2.7. Genetic factors

CVD risk is heavily affected by genetic predisposition. It has been identified that variants that affect the metabolism of lipid, blood pressure and coagulation pathways exist (Table 1). Therefore, knowing these genetic factors is essential for making personalized medicine approaches in CVD management20,21.

 

Table 1: Pathophysiological Mechanisms in Cardiovascular Diseases.

Mechanism

Description

Impact on Cardiovascular System

Atherosclerosis

Accumulation of lipids and inflammatory cells in arterial walls

Leads to plaque formation, vessel narrowing and potential rupture

Hypertension

Persistent high blood pressure

Causes endothelial damage, left ventricular hypertrophy and heart failure

Inflammation

Chronic immune response affecting vascular health

Promotes plaque instability and progression of atherosclerosis

Thrombosis

Formation of blood clots within vessels

Can result in vessel occlusion, myocardial infarction or stroke

Myocardial Ischemia

Reduced blood supply to the heart muscle

Causes tissue damage and, if prolonged, leads to myocardial infarction

Heart Failure

Inability of the heart to pump effectively

Results in fluid retention, decreased cardiac output and congestion

Genetic Factors

Inherited predispositions affecting cardiovascular risk

Influence lipid metabolism, blood pressure regulation and thrombosis

 

3. Current Biochemical Markers

Biochemical markers play important roles in diagnosis and prediction of cardiovascular disease management in the world. C-reactive protein (CRP), Troponins and B-type natriuretic peptide (BNP), are some of traditional biomarkers, that gives an information about the health of heart. (Figure 1) is a schematic show effect of certain CVD conditions on the current biochemical markers.



Figure 1:
The effect of certain CVD conditions on the current biochemical markers.

 

3.1. Troponins

Troponins, that are proteins released into the bloodstream when cardiovascular muscle is injured, are considered to be the typical diagnostic for myocardial infarction or heart attack, because of their high specificity and sensitivity. Elevated troponin levels indicate myocardial injury, enabling timely diagnosis and therapy22,23.

 

3.2. C-reactive protein (CRP)

CRP is a marker of systemic inflammation and has been associated with CVD. High-sensitivity CRP (hs-CRP) tests provide a more accurate evaluation that helps identify people who are more likely to develop cardiovascular diseases even in the absence of traditional risk factors24,25.

 

3.3. B-type natriuretic peptide (BNP)

Heart stress is indicated by BNP and its inactive fragment NT-proBNP, especially in heart failure. Ventricular strain and pressure overload cause the release of these peptides. Measuring BNP levels helps assess the severity of heart failure, guide treatment decisions and predict patient outcomes26,27.

 

3.4. Lipid profile

How to lower cholesterol levels, including LDL and high-density lipoprotein (HDL) cholesterol, is still important in assessing the role of cardiovascular risk. HDL cholesterol is considered protective and primary contributor of atherosclerosis is elevated LDL cholesterol. A regular monitoring helps in the risk stratification and management strategies28.

 

3.5. D-dimer

Fibrin degradation product D-dimer is used in evaluating thrombotic activity such as in coronavirus-19 (COVID-19) patients helping to identify those with severe conditions29. A cardiovascular diseases concern, elevated levels are indicative of increased clot formation and breakdown, making them helpful in helping assess conditions such as deep vein thrombosis or pulmonary embolism, but they are not specific to the disease30.

 

Table 2: Key Biochemical Markers in Cardiovascular Diseases.

Biochemical Marker

Associated Condition

Function/Role

Clinical Utility

Troponins

Myocardial Infarction

Indicator of cardiac muscle injury

Diagnosis of acute coronary syndrome

C-reactive Protein (CRP)

Atherosclerosis/Inflammation

Marker of systemic inflammation

Evaluates risk of cardiovascular events

B-type Natriuretic Peptide (BNP)

Heart Failure

Reflects heart strain and fluid overload

Assess severity of heart failure

LDL Cholesterol

Atherosclerosis

Major contributor to plaque formation

Risk assessment for coronary artery disease

D-dimer

Thrombosis

Degradation product of fibrin clots

Evaluation of thrombotic conditions

High-sensitivity C-reactive Protein (hs-CRP)

Cardiovascular Disease Risk

Sensitive marker of inflammation

Predicts future cardiovascular events

Lipoprotein(a)

Atherosclerosis/Thrombosis

Genetic risk factor for CVD

Risk stratification in high-risk patients

 

4. Emerging Biochemical Markers

New markers first discovered in the field of CVD diagnostics are changing the landscape of CVD diagnostics. These emerging markers show promise in the development of improved early detection, risk stratification and personalized treatment targets.

 

4.1. High-sensitivity troponins

High sensitivity troponins have been developed with assay sensitivity so high that even minor cardiac injuries can be detected. These markers can diagnose earlier myocardial infarction and identify patients who are at risk for future cardiovascular events earlier31.

 

4.2. Galectin-3

Galectin-3 is a marker of fibrosis and inflammation and a contributor to heart failure progression. Heart failure patients with elevated levels are worse outcomes and it is a potential target for therapeutic intervention and a prognostic parameter32.

 

4.3. Soluble ST2 (sST2)

It is a marker of cardiac stress and remodeling of the interleukin-33 receptor family. Prognostic information beyond conventional markers such as BNP is provided by high levels of Soluble ST2 (sST2), which are also associated with increased mortality and heart failure hospitalization33.

 

4.4. Growth differentiation factor-15 (GDF-15)

Growth Differentiation Factor-15 (GDF-15) is a stress-responsive cytokine associated with inflammation and oxidative stress. It has demonstrated potential in predicting unfavorable cardiovascular outcomes, especially in those with heart failure and acute coronary syndromes34.

 

4.5. MicroRNAs

Because of their persistence in circulation, these tiny, non-coding RNAs control gene expression and have become promising biomarkers. Certain microRNA profiles can reveal information on the processes behind heart failure, atherosclerosis and myocardial damage35.

 

4.6. Lipoprotein(a)

Elevated lipoprotein(a) levels, that can be hereditary, are linked to thrombosis and atherosclerosis. It acts as a stand-alone risk factor for CVD, especially in people who have a family history of early-onset illness36.

 

4.7. Adiponectin

This adipokine has a role in the breakdown of fatty acids and the control of glucose. Its potential in risk assessment is highlighted by lower levels (Table 3), which are linked to higher CV risk, especially in metabolic syndrome and type 2 diabetes37,38.

 

Table 3: Emerging Biochemical Markers in Cardiovascular Diseases.

Marker

Associated Role

Clinical Significance

High-Sensitivity Troponins

Early detection of myocardial injury

Earlier diagnosis and risk assessment for myocardial infarction

Galectin-3

Fibrosis and inflammation

Prognostic marker in heart failure; potential therapeutic target

Soluble ST2 (sST2)

Cardiac stress and remodelling

Predicts mortality and hospitalization in heart failure

Growth Differentiation Factor-15 (GDF-15)

Inflammation and oxidative stress

Predicts adverse outcomes in acute coronary syndromes and heart failure

MicroRNAs

Gene expression regulation

Biomarkers for myocardial injury, atherosclerosis and heart failure

Lipoprotein(a)

Atherosclerosis and thrombosis risk

Independent risk factor for CVD, especially with familial predisposition

Adiponectin

Glucose regulation and lipid metabolism

Risk assessment in metabolic syndrome and type 2 diabetes

 

5. Comparison of Biochemical Markers

In order to diagnose and treat CVD, biochemical markers are crucial. Clinical decision-making is aided by highlighting the advantages and disadvantages of both existing and novel markers (Table 4).

 

Table 4: Comparison of Biochemical Markers in Cardiovascular Diseases.

Marker

Sensitivity/Specificity

Prognostic Value

Clinical Utility

Limitations

Troponins

High for myocardial infarction

Predicts future cardiac events

Acute coronary syndrome diagnosis

May rise in non-cardiac conditions

BNP/NT-proBNP

Sensitive for heart failure

Correlates with heart failure severity

Guides heart failure management

Affected by age and renal function

CRP/hs-CRP

Moderate specificity

Long-term risk of CVD events

Inflammation assessment

Not specific to CVD

sST2

Moderate

Predicts mortality/hospitalization

Heart failure prognosis

Limited availability in routine labs

Galectin-3

Moderate

Heart failure outcomes

Potential therapeutic target

Requires further validation

Lipoprotein(a)

Low sensitivity, high genetic linkage

Genetic risk for atherosclerosis

Risk stratification in high-risk patients

Less routine use

MicroRNAs

Varies

Insights into disease mechanisms

Experimental; potential biomarkers

Requires validation and standardization

GDF-15

Emerging

Adverse outcomes in acute settings

Prognosis in acute coronary syndromes

Limited clinical integration

 

6. Clinical Applications and Guidelines

Diagnosis, risk assessment and therapy selection are among the primary functions of biochemical indicators in the clinical management of CVD. This is how they are incorporated into practice:

 

7. Limitations and Challenges

Although the use of biochemical indicators for cardiovascular disorders has advanced, there are still a number of obstacles, restrictions and potential future paths that are outlined in (Table 5).

 

Table 5: Challenges, Limitations and Future Directions in Biochemical Markers for Cardiovascular Diseases.

Aspect

Limitations and Challenges

Future Directions

Specificity

Specificity lack in some markers like CRP

Making more precise and targeted markers

Interindividual Variability

Influence of age, sex and comorbidities

Methods for personalized healthcare that include genetic data

Standardization

Methods assay variability

Worldwide uniformity of biomarker assays

Access and Cost

high cost and limited availability of new biomarkers

Establishing accessible and reasonably priced diagnostic instruments

Integration into Practice

Slow use of new biomarkers

Quick conversion of research findings into therapeutic recommendations

Technological Advancements

Limited use of advanced technologies

Predictive analytics using machine learning and large data

Comprehensive Risk Assessment

Limitations of single biomarker

Biomarker panel implementation for comprehensive risk assessment

 

8. Conclusion

Effective biochemical indicators are crucial for managing cardiovascular disease because they allow for early detection, precise diagnosis and precise risk assessment. While well-known indicators like BNP and troponins have all shown their clinical value, there are also novel theories that might improve our knowledge of and ability to treat CVD. By incorporating these indicators into conventional clinical practice, current issues like specificity and uniformity will be resolved. Continued study about the emerging guidelines to impact better patient outcomes in cardiovascular care will further promote the usage of biochemical markers currently used for cardiovascular care.

 

9. Declarations

9.1. Conflicts of interest

There are no conflicts of Interest in this manuscript.

 

9.2. Ethics approval and consent to participate

Not applicable.

 

9.3. Consent for publication

Not applicable.

 

9.4. Funding

There is no funding to be declare.

 

10. References

  1. Roth GA, Mensah GA, Johnson CO, et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update from the GBD 2019 Study. J Am Coll Cardiol, 2020;76(25): 2982-3021.
  2. Ramic-Catak A, Mesihović-Dinarevic S, Prnjavorac B. Public Health Dimensions of CVD Prevention and Control - Global Perspectives and Current Situation in the Federation of BiH. Mater Sociomed, 2023;35(2): 88-93.
  3. Omran F, Kyrou I, Osman F, et al. Cardiovascular Biomarkers: Lessons of the Past and Prospects for the Future. Int J Mol Sci, 2022;23(10).
  4. Wang XY, Zhang F, Zhang C, et al. The Biomarkers for Acute Myocardial Infarction and Heart Failure. Biomed Res Int, 2020;2020: 2018035.
  5. Liang ZY, Qian, CW, Lan, TH, et al. Regulatory T Cells: A New Target of Chinese Medicine in Treatment of Atherosclerosis. Chin. J. Integr. Med, 2021;27: 867-873.
  6. Dutta S, Singhal AK, Suryan V, et al. Obesity: An Impact with Cardiovascular and Cerebrovascular Diseases. Ind J Clin Biochem, 2024;39: 168-178.
  7. Marchio P, Guerra-Ojeda S, Vila JM, et al. Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation. Oxidative Medicine and Cellular Longevity, 2019;2019(1): 8563845.
  8. Kim HL. Arterial stiffness and hypertension. Clin Hypertens, 2023;29(1): 31.
  9. Poznyak AV, Sadykhov NK, Kartuesov AG, et al. Hypertension as a risk factor for atherosclerosis: Cardiovascular risk assessment. Front Cardiovasc Med, 2022;9: 959285.
  10. Liu YZ, Wang YX, Jiang CL. Inflammation: The Common Pathway of Stress-Related Diseases. Front Hum Neurosci, 2017;11: 316.
  11. Henein MY, Vancheri S, Longo G, et al. The Role of Inflammation in Cardiovascular Disease. Int J Mol Sci, 2022;23(21).
  12. Alfaddagh A, Martin SS, Leucker TM, et al. Inflammation and cardiovascular disease: From mechanisms to therapeutics. Am J Prev Cardiol, 2020;4: 100130.
  13. Lai H, Tu Y, Zhang S, et al. Association of inflammation and abnormal lipid metabolism with risk of thrombosis and thrombosis progression in patients with polycythemia vera: a retrospective study. Ann Hematol, 2023;102: 3413-3426.
  14. Beura SK, Panigrahi AR, Yadav P, et al. Role of Thrombosis in Neurodegenerative Diseases: An Intricate Mechanism of Neurovascular Complications. Mol Neurobiol, 2025;62: 4802-4836.
  15. Samanta J, Dhar J, Gupta P, et al. Venous Thrombosis in Acute Pancreatitis: What to and Not to Do? Dig Dis Sci, 2024;69: 1537-1550.
  16. Buja LM. Pathobiology of Myocardial Ischemia and Reperfusion Injury: Models, Modes, Molecular Mechanisms, Modulation and Clinical Applications. Cardiol Rev, 2023;31(5): 252-264.
  17. Zhou B, Tian R. Mitochondrial dysfunction in pathophysiology of heart failure. J Clin Invest, 2018;128(9): 3716-3726.
  18. Schwinger RHG. Pathophysiology of heart failure. Cardiovasc Diagn Ther, 2021;11(1): 263-276.
  19. Chiatto LM, Corallo F, Calabrò RS, et al. A systematic review about the importance of neuropsychological features in heart failure: is at heart the only failure? Neurol Sci, 2024;45: 3611-3624.
  20. Vrablik M, Dlouha D, Todorovova V, et al. Genetics of Cardiovascular Disease: How Far Are We from Personalized CVD Risk Prediction and Management? Int J Mol Sci, 2021;22(8).
  21. Ordovas JM. Genetic influences on blood lipids and cardiovascular disease risk: tools for primary prevention. Am J Clin Nutr, 2009;89(5): 1509-1517.
  22. Potter JM, Hickman PE, Cullen L. Troponins in myocardial infarction and injury. Aust Prescr, 2022;45(2): 53-7.
  23. Park KC, Gaze DC, Collinson PO, et al. Cardiac troponins: from myocardial infarction to chronic disease. Cardiovasc Res, 2017;113(14): 1708-1718.
  24. Kamath DY, Xavier D, Sigamani A, et al. High sensitivity C-reactive protein (hsCRP) & cardiovascular disease: An Indian perspective. Indian J Med Res, 2015;142(3): 261-268.
  25. Banait T, Wanjari A, Danade V, et al. Role of High-Sensitivity C-reactive Protein (Hs-CRP) in Non-communicable Diseases: A Review. Cureus, 2022;14(10): 30225.
  26. Weber M, Hamm C. Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine. Heart, 2006;92(6): 843-849.
  27. Cao Z, Jia Y, Zhu B. BNP and NT-proBNP as Diagnostic Biomarkers for Cardiac Dysfunction in Both Clinical and Forensic Medicine. Int J Mol Sci, 2019;20(8).
  28. Sucato V ortello A, Comparato F, et al. Cholesterol-Lowering Strategies for Cardiovascular Disease Prevention: The Importance of Intensive Treatment and the Simplification of Medical Therapy. J Clin Med, 2024;13(7).
  29. Al-Hashimi NH, Al-Hindawi MS, Mohsen AM, et al. Enoxaparin Effect on Interleukin-10 Levels in Iraqi Patients with COVID-19: A Case–Control Study. Front. Biosci. (Schol Ed), 2024;16(2): 9.
  30. Ikeda N, Wada H, Ichikawa Y, et al. D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases. Clin Appl Thromb Hemost, 2022;28.
  31. Lazar DR, Lazar FL, Homorodean C, et al. High-Sensitivity Troponin: A Review on Characteristics, Assessment and Clinical Implications. Dis Markers, 2022;2022: 9713326.
  32. Hara A, Niwa M, Kanayama T, et al. Galectin-3: A Potential Prognostic and Diagnostic Marker for Heart Disease and Detection of Early-Stage Pathology. Biomolecules, 2020;10(9).
  33. Sciatti E, Merlo A, Scangiuzzi C, et al. Prognostic Value of sST2 in Heart Failure. J Clin Med, 2023;12(12).
  34. Li M, Duan L, Cai YL, et al. Growth differentiation factor-15 is associated with cardiovascular outcomes in patients with coronary artery disease. Cardiovasc Diabetol, 2020;19(1): 120.
  35. Feinberg MW, Moore KJ. MicroRNA Regulation of Atherosclerosis. Circ Res, 2016;118(4): 703-20.
  36. Vinci P, Di Girolamo FG, Panizon E, et al. Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives. Int J Environ Res Public Health, 2023;20(18).
  37. Clemente-Suárez VJ, Redondo-Flórez L, Beltrán-Velasco AI, et al. The Role of Adipokines in Health and Disease. Biomedicines, 2023;11(5).
  38. Feijóo-Bandín S, Aragón-Herrera A, Moraña-Fernández S, et al. Adipokines and Inflammation: Focus on Cardiovascular Diseases. Int J Mol Sci, 2020;21(20).