Cardiovascular disease (CVD) is the leading cause of death on a global scale due to the consistent rise in mortality rates. As such, biomarkers are the utmost priority within the medical domain for discerning early warning signs of CVDs and delivering an evidence-based delineation of heart failure. This overview highlights the variety of promising biomarkers that provide the need for risk stratification, diagnosis, prognostication, and decision-making regarding the management of cardiovascular diseases.
Cardiovascular disorders (CVDs), including peripheral vascular disease, ischemic heart disease, and stroke, are the leading causes of death globally, contributing to 17.9 million deaths in 2016. Recently, it has been predicted that 23.6 million people would have died from CVD, with heart disease and stroke accounting for the majority of deaths by 2030. Though non-pharmacological prevention of CVD is important for public health initiatives to avoid the onset and consequences of CVD, the use of pharmaceutical therapies is still a fundamental pillar for preventing and managing CVD. This is supported by a notable increase in drug development for CVD between 1995 and 2020. However, the major concerns in the advancement of novel medications are lack of efficacy and safety, which account for 52 per cent and 24 per cent of drug failures, respectively. In this context, biomarkers could serve as a powerful tool for the enhanced identification of high-risk patients, thereby facilitating prompt and precise diagnoses of diseases and effectively prognosticating and treating patients.
Biomarkers are specific molecules or substances found in the body that can indicate the presence of risk or progression of a disease. Technically biomarkers are observable characteristics that possess the capability of being objectively evaluated and furnish measurable indications pertaining to physiological, pathological and pharmacological responses to an intervention. Investigating the role of biomarkers in causing disease manifestation can (i) Impart etiological knowledge, which can enhance our comprehensive understanding of the molecular mechanisms of disease pathology (ii) provide the comparative role of altered traits implicated in disease etiology during therapeutic intervention and (iii) contribute to the development of public health strategies in response to environmental exposure.
Cardiac biomarkers refer to biomolecular constituents released into circulation following cardiac injury or strain. These biomarkers aid in assessing an individual's susceptibility to cardiac diseases and serve as a means for monitoring and treating individuals suspected of suffering from various CVDs. In this context, this write up provides an overview of existing biomarkers that consistently aid in the prognosis of early CVD.
Cardiac Troponin
The regulation of cardiac troponin is a calcium-dependent process that governs the contraction and relaxation of the heart muscle. They are widely utilised as the gold standard biomarker for myocardial infarction (MI). Troponin T (TNT), troponin I (TNI), and troponin C (TNC) are the three components that make up the cardiac troponin complex, which are currently used to detect the cardiacspecific TNT and cardiac-specific TNI by immunoassays utilising monoclonal antibodies.
Brain natriuretic peptide (BNP and NT-pro BNP)
BNP and NT-proBNP have been shown in studies to be higher in patients with heart failure, making them an important biomarker for CVDs. BNP is also involved in the renin-angiotensin-aldosterone system and has been linked to a number of physiological processes, such as diuresis, natriuresis, vasodilation, and the inhibition of the sympathetic nervous system. Furthermore, a mid-regional sequence of pro-a-type natriuretic peptide has been shown to be a useful biomarker for the diagnosis and prognosis of acute heart failure in clinical settings.
Glycogen phosphorylase BB (GPBB)
Because of high oxygen demand, the heart is particularly sensitive to carbon monoxide (CO)-induced hypoxia. For this reason, patients with cardiovascular issues may not be diagnosed with CO poisoning or receive treatment due to absence of obvious symptoms or distinct electrocardiogram alteration. Nevertheless, glycogen phosphorylase BB isoenzyme (GPBB) is one of the emerging and potential prognostic biomarkers for myocardial hypoxia. Moreover, investigations have shown that GPBB may be a useful cardiac marker in the diagnosis of acute coronary syndrome and myocardial ischemia.
Soluble CD40 Ligand (sCD40L)
TNF superfamily member CD40L is found in a variety of cellular types, including immune cells (lymphocytes, dendritic cells, neutrophils, and macrophages) and nonimmune cells (endothelial cells, vascular smooth muscle cells, and epithelial cells). Further, the interaction between CD40L and the receptor CD40 is crucial for immunomodulatory properties and is associated with atherosclerosis and plaque instability. Clinical trials have demonstrated the predictive capacity of sCD40L as a biomarker for determining CVD risk in patients with CAD. Another trial demonstrated that elevated levels of sCD40L could reliably predict the risk of stroke in patients who had previously experienced a minor stroke or transient ischemic attack.
Heart-fatty acid binding protein (H-FABP) is a diminutive cytosolic protein found in cardiac tissues that serves as a mediator for the transportation of fatty acids from the plasma membrane to oxidation sites in both mitochondria and peroxisomes. Recently, studies have observed a rise in serum levels of H-FABP as soon as 30 min after MI. Additionally, H-FABP is widely employed as a prognostic biomarker for HF mortality.
Growth differentiation factor-15 (GDF-15) is primarily generated by the placenta and plays a significant role in the activation of pathways linked to apoptosis, inflammation, and tissue damage. Prior research has demonstrated that raised GDF- 15 levels above a particular threshold may serve as a reliable marker for identifying individuals who are at a high risk of heart disease. Furthermore, in individuals with chronic heart failure, increased levels of GDG-15 have been linked to adverse remodelling and hypertrophy.
Lp-PLA2 is mostly produced by monocytes and macrophages and is a member of the phospholipase A2 superfamily, also known as platelet-activating factor acetylhydrolase. Fascinatingly, the first report from the West Scotland Coronary Prevention Study presented the main evidence supporting a link between elevated Lp-PLA2 levels and cardiovascular events. Also, further studies have demonstrated that Lp-PLA2 activity may function as a stand-alone predictor of CAD and stroke in the general population.
Apart from the commonly available proteins described above, some of the potential biomarkers that are associated with CVD are listed in Table 1
Though the existence of emerging and innovative biomarkers in clinical these markers into clinical practice. For instance, (i) the functions and physiological CAD, as well as their clinical usefulness, have to be thoroughly explained; (ii) he be defined; and (iii) since CVD is a multi-factorial disease, further multicentric and well as to understand the molecular pathology of CVD. Addressing these may lead to management of CVD.
Agiesh kumar Balakrishna Pillai received his Ph.D. in Biotechnology in 2008 from Pondicherry University, Puducherry. His postdoctoral research was conducted in virology (arboviral) at the University of Georgia and the Texas Tech University. His academic career continued with position as Senior Scientist and Associate professor at the Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth. Currently, he is actively involved in various research projects in the field of arboviral disease, respiratory infection and heart failure.
Vignesh Mariappan recently received his Ph.D. in Interdisciplinary Research from Sri Balaji Vidyapeeth. During this period, he worked in dengue disease pathogenesis with a special focus on characterisation and validation of endothelial and macrophage released molecules for the early prognosis of dengue disease outcome.
S R Rao, former Senior Advisor in the Department of Biotechnology (Govt. of India), is a renowned expert in promoting R&D across various fields of biotechnology. Currently, he is serving as the Vice President of Sri Balaji Vidyapeeth University Pondicherry and committed to promoting research, innovation, and development ecosystems. Also, he is the founder of the Global Alliance for Pandemic Preparedness and Response and the RISAsian Biotechnology Development Review.
