|Year : 2021 | Volume
| Issue : 3 | Page : 141-149
A literature survey on the biomarkers of cardiovascular disease
Ravindran Pavithra1, Thangavelu Sangeetha1, Shanmugam Velayuthaprabhu2, Arumugam Vijaya Anand1
1 Department of Human Genetics and Molecular Biology, Medical Genetics and Epigenetics Laboratory, Bharathiar University, Coimbatore, Tamil Nadu, India
2 Department of Biotechnology, Bharathiar University, Coimbatore, Tamil Nadu, India
|Date of Submission||23-Jun-2020|
|Date of Acceptance||15-Jan-2021|
|Date of Web Publication||28-Sep-2021|
Dr. Arumugam Vijaya Anand
Department of Human Genetics and Molecular Biology, Medical Genetics and Epigenetics Laboratory, Bharathiar University, Coimbatore - 641 046, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Biomarkers of any condition will help in predicting the disease that can help in improvised treatment and medication. Due to lack of symptoms and precursors, cardiovascular disease (CVD) is one of the leading reasons for death in population all over the world. To reduce the death rate and improve the therapeutic approach, biomarkers related to CVD can be helpful. The study of the levels of biomarkers in the body can help in predicting the chances of CVD. The literature study of biomarkers of CVD is to analyze the biomarkers and their role and levels in causing CVD. Among the various analyzed lipid-related markers like apolipoprotein B, apolipoprotein A1, lipoprotein (a), high-sensitivity cardiac troponin, high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A2, coronary artery calcification, cystatin C, it has been identified that the cystatin C is the biomarker for not only the chronic kidney disease but also a predictor of major CVD events.
The following core competencies are addressed in this article: Medical knowledge, Patient care, Systems-based practice.
Keywords: Biomarkers, cardiovascular disease, chronic kidney disease, cystatin C, therapeutics
|How to cite this article:|
Pavithra R, Sangeetha T, Velayuthaprabhu S, Anand AV. A literature survey on the biomarkers of cardiovascular disease. Int J Acad Med 2021;7:141-9
|How to cite this URL:|
Pavithra R, Sangeetha T, Velayuthaprabhu S, Anand AV. A literature survey on the biomarkers of cardiovascular disease. Int J Acad Med [serial online] 2021 [cited 2021 Nov 27];7:141-9. Available from: https://www.ijam-web.org/text.asp?2021/7/3/141/326820
| Introduction|| |
Cardiovascular disease (CVD) refers to the condition that affects the heart or blood vessels. CVD includes diseases like coronary artery disease, cerebrovascular disease, rheumatic heart disease, hypersensitive heart disease, etc., the risk of CVD may be increased by smoking, high blood pressure, high cholesterol, high glucose, unhealthy diet, lack of physical activity, and obesity. CVD is the leading cause of global death in the past few years., According to the World Health Organization (WHO) report, 17.9 million people die each year from CVDs, which accounts for 31% of all deaths globally. In India, the age-adjusted CVD mortality rates are 349/1,00,000 in men and 265/1,00,000 in women.
| Risk Stratification|| |
The WHO reported that CVD is the source of great morbidity and mortality. The risk of developing CVD will increase with the number of risk factors nonheritable. Normally, the risk factors for CVD can be separated into nonmodifiable and modifiable risk factors. Nonmodifiable risk factors are included age, gender, and case history. Many studies have shown that the prevalence of CVD will increase with age wherever every decade of life above the age of 40 years showed an increase in any vascular disease. The main modifiable risk factors are health conditions and lifestyle factors. The health conditions embrace high blood pressure, dyslipidemia, diabetes mellitus, and chronic kidney disease (CKD). A way of lifestyle factor includes cigarette, smoking, diet, exercise, obesity, and psychosocial factors. The main risk stratification as high blood pressure has an abundant quantity of evidence to support its role as a risk factor thinks about developing CVD.
| Risk Factors of Cardiovascular Disease|| |
The use of ancient cardiovascular risk factors emprises and predicts about one-half of future cardiovascular events. The risk factors related to CVD are unit modifiable and nonmodifiable. The modifiable risk factors are physical inactivity, overwhelming tobacco, smoking, unhealthy diet, blood lipids, high blood pressure, and obesity. The WHO suggested that more than 60% of the global population is sufficiently inactive. If the individual becomes physically inactive, the lifespan could decrease and will additionally pave the manner for the enhancement of any chronic health issues including any type of CVD.
Tobacco smoking could be a leading reason for CVD morbidity and mortality. The study prompt that tobacco may be considered the increasing risk issue of CVD area unit highest in current and up to date smokers, compared to never smokers and those who have quit in the more distant past. Tobacco smoking promotes CVD through damaging the epithelial tissue, increasing fatty deposits within the arteries, will increase coagulation, raises rarity compound protein low-density lipoprotein (LDL) steroid alcohol, and reduces high-density compound protein high-density lipoprotein (HDL) steroid alcohol. Some smokers possess a gene that increases the risk of CVD. Women who smoke and additionally intake the alcohol increase the chance of CVD, heart condition, and stroke than men who smoke. High blood pressure additionally will increase the risk of CVD. Patients with high blood pressure and diabetes with accompanied dyslipidemia are targets cardiovascular events. The elevated levels of lipids within the blood area unit related to risk for CVD and stroke.
Nonmodifiable risk factors are case history, overweight, and obesity. Approximately two-thirds of adults are overweight or obese, and even modest excess body weight is related to a significantly increased risk of CVD connected mortality. Lifestyle interventions to promote weight loss reduce the chance of CVD related illness for patients to sustain over long periods of your time. The increased incidence of obesity has additionally contributed to important will increase within the prevalence of alternative vital CVD risk factors, including high blood pressure, dyslipidemia, endocrine resistance, and type 2 diabetes mellitus.
Type 2 diabetes patients are being found to be more susceptible to CVD in comparison with healthy people. Booth et al. suggested that the individuals that suffer from physical inactivity and weight gain predisposes to CVD a lot of often within the people with spinal cord injury than within the general population. Another study has additionally suggested that the presence of high compound protein A, environmental and lifestyle factors, higher levels of insulin resistance, hyperinsulinemia, type 2 diabetes, impaired glucose tolerance, dyslipidemia, high blood pressure, obesity, low high-density compound protein levels characterized by the metabolic syndrome are another vital reason for increased CVD incidence in Indian population.
| Biomarkers of Cardiovascular Disease|| |
The discussed risk factors perform well to predict the risk of CVD but do not perfectly predict the future risk of CVD. Thus, the discovery of biomarkers associated with CVD risk has been done. Such markers include lipid-related markers as apolipoprotein A-1, apolipoprotein B-100, lipoprotein A, lipoprotein-associated phospholipase A2 (Lp-PLA2), natriuretic peptides (NP), high-sensitivity troponin T, high-sensitivity troponin I, high-sensitivity c-reactive protein (hs-CRP), coronary artery calcium, and Cystatin C. These biomarkers have become important diagnostic tools to predict cardiovascular risk and are discussed below in this review and have been diagrammatically represented in [Figure 1].
| Lipid-Related Markers|| |
Apolipoprotein B and apolipoprotein A1
Apolipoprotein B is the primary apolipoprotein of chylomicrons, very-LDL, intermediate-density lipoprotein, and LDL particles. The study suggests that the concentrations of apolipoprotein B have been found to be associated with heart disease and risk prediction of CVD. Increased concentrations of HDL cholesterol have been closely associated with the decreased risk of future CVD. A study has suggested that the apolipoprotein A1 is the major protein component of HDL and it helps in predicting the risk of future CVD.
A study suggested that the lipid-related markers as apolipoprotein B and apolipoprotein A1 are structural and functional components of lipoprotein particles that serve as transporters of cholesterol. The ratio of apolipoprotein B and apolipoprotein A1 reflects the cholesterol transport and is shown strongly associated with the risk of CVD. Many studies reported that apolipoprotein B/apolipoprotein A1 ratio is related to a CVD risk. Lu et al. compared the samples of coronary heart disease (CHD) patients and healthy individuals who were overweight or obese to predict the risk of CVD. Based on the receiver operating characteristic curve analysis, it has resulted that the apolipoprotein B and apolipoprotein A1 ratio levels are associated in predicting the risk of CVD events that were overweight or obese.
Malaguarnera et al. have performed a study, which involved the determining of lipoprotein (a) values to predict the risk of cardiovascular events. Maranhão et al. suggested that lipoprotein (a) can be considered as a genetic risk factor of CVD. The study has found that the lipoprotein (a) has been positively associated with CVD risk. Normally, lipoprotein (a) is a LDL particle bound to glycoprotein lipoprotein (a). They also suggest that lipoprotein (a) plays a role in the prothrombotic or antifibrinolytic effects or through accelerated atherogenesis and elevation in the levels of lipoprotein (a) is associated with increases in the risk of CVD.
A study suggests that the lipoprotein (a) plays a critical role in the pro-inflammatory reaction as inhibition of the activation of plasminogen; inhibition of the activation of tumor growth factor-beta; activation of acute inflammation; induction of the expression of adhesion molecules; elevation of the production of cytokines are associated with risk of CVD events. Another study has used a Mendelian randomization approach to predict the association of lipoprotein (a) with CVD. Based on the cross-sectional general population study in more than 29,000 individuals, the elevated lipoprotein (a) levels were associated with an increased risk of CVD events.
| Lipoprotein-Associated Phospholipase A2|| |
A study indicates that the Lp-PLA2 is an associate accelerator secreted by the inflammatory cells that circulate and bind in the main to beta-lipoprotein that is taken into account as a marker for CVD risk. A study examined Lp-PLA2 and determined that the mass of Lp-PLA2 will increase related to the danger of major CVD events. A study investigated the link between Lp-PLA2 and markers of CVD risk, and it has been measured that Lp-PLA2 was within the high CVD risk class and may be pictured as an early biomarker of CVD risk events.
A study by Cook et al. has prompt that Lp-PLA2 has the properties of proatherogenic-associated antiatherogenic role and analyzed that elevated levels of Lp-PLA2 are related to an enhanced risk of vessel events. Lp-PLA2 is the associate accelerator that conjointly exhibits unhealthy property which has been related to the danger of vessel events.
| Natriuretic Peptides|| |
The NPs, including brain-type natriuretic peptide (BNP) or N-terminal prohormone of BNP (NT-pro BNP), are biomarkers that are strongly associated with the risk of CVD events. Several studies suggest that elevated BNP and NT-pro BNP levels increased the risk of total CVD, CHD, and stroke. In general populations, the levels of BNP and NT-pro BNP are higher in women than in men. Hence, the increase in BNP or NT-pro BNP may be used for the prediction of CVD risk.
The NPs include three characterized hormones as atrial natriuretic peptide (ANP), BNP, and C-type NP which are mainly involved in cardiovascular events. Normally, ANP and BNP are synthesized mainly in the heart, and BNP is mainly produced by endothelial cells. Due to natriuretic, antiproliferative, and antiapoptotic effects, they are involved in the pathogenic mechanisms leading to major CVD like heart failure, coronary artery disease, hypertension, and cerebrovascular accidents.
| High-Sensitivity Cardiac Troponin|| |
High-sensitivity cardiac troponin T, high-sensitivity cardiac troponin I has been used as a specific marker for diagnosis and risk stratification of CVD. When the levels are compared in the general population, the high-sensitivity cardiac troponin T and high-sensitivity cardiac troponin I levels are significantly higher in men than in women. A study by Welsh et al. indicates that the elevations in high-sensitivity cardiac troponin T or high-sensitivity cardiac troponin I levels are strongly associated with the risk of CVD events. A study suggests that an increase in high-sensitivity cardiac troponin is associated with a higher risk of CVD. The high sensitivity cardiac troponin T has been found to be individually associated with the CVD events in a study conducted by Tehrani et al.
A study has suggested that the elevated levels on the measurement of the cardiac troponin as cardiac troponin T and cardiac troponin I are associated with the risk of CVD events by comparing with normal healthy individuals. Among the 19,501 individuals, the Scottish health study reveals that CVD risk events are strongly associated with cardiac troponin T and cardiac troponin I. They identified as five loci (53 individual single nucleotide polymorphisms (SNPs)) that had GWAS (genome-wide association study) in cardiac troponin I and a different set of four loci (SNPs) for cardiac troponin T noted as elevations of these are strongly associated with CVD events.
| High-Sensitivity C-Reactive Protein|| |
A study reported that hs-CRP is associated with CVD. CRP is mainly produced by the liver as an acute phase reactant and is strongly regulated by interleukin-6 concentrations. The blood concentrations of hs-CRP have been used to assess the risk of CVD, heart attack, and stroke as well as cholesterol levels. A study found that elevated levels of CRP were associated with three times the greater risk of CVD. CRP may increase in CVD in response to infectious agents, including the inflammatory reactions in the coronary vessels. The circulating CRP levels were analyzed in the CVD patients and has been observed to be associated with CVD, with or without myocardial tissue damage. The hs–CRP has been investigated extensively as a marker of inflammatory response that is useful in predicting the risk of CVD. The study described that the measurement of hs–CRP in CVD patients with diabetes and hypertension may prove to be an even better marker of risk response.
A study by Wallace et al. indicates that the CRP can be a screening tool for prediction of CVD. Based on the Framingham risk score, positive associations between elevated CRP levels and incident CVD has been observed. A case-cohort study assessed the association of CRP with incident CHD and suggested a positive association. Therefore, the basic risk factor model, which includes age, sex, total and HDL cholesterol levels, blood pressure, and elevated CRP levels, may predict the risk of CHD. A study by and Joseph et al. suggested the positive effects of atorvastatin on CRP and lipid profile in patients with stroke, as information on atorvastatin may predict the risk of cerebrovascular morbidity and mortality.
| Coronary Artery Calcification|| |
A study indicated that coronary artery calcification (CAC) is a strong predictor of CVD risk events and mortality. CAC is a highly specific feature of coronary atherosclerosis. The concentration of CAC performed by computer tomography increases the levels of CAC are associated with the risk of CVD. The studies performed by Orimoloye et al. determine the risk of CVD events based on CAC scores. Among the study population of 6764 participants analyzed, the CAC scores positively correlate with the risk of CVD.
The prospective cohort study indicates that the higher levels of CAC are strongly associated with risk factors of CVD, myocardial infarction, heart failure, all-cause mortality. Among the study population of 1541 participants aged 35–60 years analyzed, the inclusion of CAC score for predicting CVD risk factors overall of all the above mentioned. The study determines the relationship between CAC scores and cardiovascular events. Using the computer tomography to measure the CAC in 1205 participants and analyzed that increase the scores of CAC associated with an increase in the risk of cardiovascular events and mortality.,
| Cystatin C|| |
The Framingham heart study targeted a high range of proteins through the proteomic platform by separation, quantification, and characterization in the biological system using the two-dimensional electrophoresis.,suggested that cystatin C biomarker has been associated with the incidence of CVD using multivariate Cox models. The normal concentration of serum cystatin C ranges from 0.6 to 1 mg/L. The risk of CVD increases with the increase in cystatin C concentration. Higher the concentration of protein increases the risk factors of CVD as age, sex, body mass index, LDL and HDL cholesterol, and smoking. Higher the level of cystatin C increases the risk of kidney function, hypertension, and dyslipidemia.
The study investigated the cystatin C levels to predict ischemic stroke risk and CVD events. Based on the samples analyzed in China using cohort study and decision free model, the levels of cystatin C and risk of stroke resulted that the high levels of cystatin C are highly associated with risk of ischemic stroke and CVD events. The study investigated the cystatin C for risk stratification in patients after an acute coronary syndrome by estimated glomerular filtration rate (eGFR), a strong correlation with creatinine and moderate correlation with fibroblast growth factor, and weak correlation with BNP. Studies have also shown that the higher concentration of cystatin C increases the risk of CVD and Heart failure. Hence, cystatin C is found to be associated with CVD and its risk.
The biomarkers discussed so far in the current study have a notable role in other clinical condition diagnoses apart from CVD, and the same is shown in [Table 1].
| Diseases Involved in Cardiovascular Disease|| |
A meta-analysis reported the major diseases which are strongly and directly related to cardiovascular mortality. Dyslipidemia is shown to be independently associated with CVD through disturbances in the lipid metabolism as elevated with the levels of total cholesterol, LDL cholesterol, low HDL cholesterol. Diabetes mellitus is associated with CVD; equally, it is also associated with a similar risk of myocardial infarction. Therefore CKD is also considered as commonly associated with increased in all-cause and cardiovascular mortality events through decreased glomerular filtration rate and increased proteinuria.
| Selection Criteria and Importance of the Study|| |
The current literature survey mainly focuses on the biomarkers related to the prediction of CVD, and the outline of the selection criteria followed for the study is shown in [Figure 2]. The current literature survey has been aimed at analyzing the various biomarkers, which has a notable role in the diagnosis of CVD. The identification of possible biomarkers for the diagnosis of an important clinical condition paves a significant way for the discovery of drugs and treatment of the condition at the earliest stage possible. The CVD is one of the fatal diseases that may be asymptomatic till a certain stage. The biomarkers considered for the study are very common molecules that have a diagnostic role in other clinical conditions simultaneously, and hence, the analysis of these biomarkers in comparison to CVD as well as another clinical condition seems to be an effective diagnostic process in case of significant positive results.
| Conclusion|| |
Prediction of biomarkers associated with CVD helps to monitor and prevent the risks for CVD. The CVD biomarkers are used as diagnostic, prognostic, and predictive biomarkers. The biomarkers may also be the targets for drug delivery and development. Other than these biomarkers osteoprotegerin, neopterin, cardiotrophin, and glycoprotein are also used, which are associated with the risk of CVD events. Here, high-sensitivity cardiac troponin T and high-sensitivity cardiac troponin I is the specific inflammatory marker to predict the risk of myocardial injury. Then, the hs-CRP biomarker acts as a predictor of CVD events. Lp-PLA2, secretory phospholipase A2, and elevated levels of NP and galectin-3 predict the risk of cardiovascular events. The cystatin C has been identified as not only as a biomarker of CVD but also a predictor of major events in CKD.
From the observed analysis of available literature, the CVD can be predicted at the earlier stages using troponin T as a biomarker. Though other biomarkers have an efficient prediction of the clinical condition, troponin T plays its role as a chief. Although hs-CRP can also be considered a major biomarker, it can be found in other related inflammatory conditions too, and hence, this literature recommends the troponin T as chief and predominant indicators of CVD at its earliest stage, followed by the other biomarkers.
The authors acknowledge the institutional authorities and the laboratory fellows for rendering their help during the preparation of manuscripts.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
Ravindran Pavithra have designed the manuscript. Thangavelu Sangeetha reviewed and structured the manuscript. Shanmugam Velayuthaprabhu reviewed and edited the manuscript. Arumugam Vijaya Anand have corrected and finalised the manuscript. All the authors have contributed to the structuring and framing the concept of the manuscript.
Ethical conduct of research
The authors of this manuscript declare that this scientific work complies with reporting quality, formatting, and reproducibility guidelines set forth by the EQUATOR Network (http://www.equator-network.org). The authors also attest that because there was no clinical investigation carried out, the Institutional Review Board/Ethics Committee approval was not required.
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