Introduction
Cardiovascular disease (CVD) concerns continue to increase worldwide compared to previous years because of the aging population. Atherosclerotic (plaque build-up in arteries) heart disease starts at an earlier age and progresses in time. Therefore, it allows an adequate period for disease screening and early detection. The primary prevention of CVD depends on identifying high-risk individuals before the disease becomes apparent. Cardiac biomarkers aid in early detection, risk assessment, diagnosis, prognosis, and decision-making regarding CVD treatment. They are also useful in the preliminary assessment of the disease to determine if an urgent treatment is needed.
What Are the Cardiac Biomarkers and Their Significance?
Biomarkers are molecules in the blood, circulatory fluids, or tissues signifying normal or abnormal conditions. Biomarkers can detect how the body responds to a treatment of the disease. Biomarkers must be accurate and specific and assess the therapeutic impact of early intervention. Cardiac biomarkers appear in the blood after the heart has been under stress and becomes injured due to a lack of oxygen. The levels of biomarkers quickly find out the significance of the heart injury. Many cardiac markers have been employed in CVD diagnosis and management.
However, no single method can test a novel cardiac biomarker for its clinical use. It is because it is a disease progressing over years from a subclinical stage to a clinical disease due to various risk factors. Therefore, the prediction of CVD risk involves risk factor assessment such as age, gender, blood pressure, serum cholesterol, smoking status, and history of diabetes mellitus.
In general, individual biomarkers have failed to predict CVD risk over standard risk factors. Hence, investigators are exploring multiple biomarkers and traditional risk factors to examine the individual’s CVD risk.
What Are the Various Cardiac Biomarkers Used for Cardiovascular Diseases?
A CVD diagnosis is critical to administer the therapy at the earliest and reverse heart injury. The various biomarkers are enzymes, proteins, peptides (smaller proteins), and other molecules.
1. Biomarkers of Heart Injury:
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Cardiac Troponins: Troponins are contractile proteins found in muscle cells. They are the most frequently utilized biomarkers with the highest sensitivity (detecting the disease correctly). They enter the bloodstream from the injured heart tissue after a short time. Further, they stay in the bloodstream for days even after all other biomarkers reach normal levels. Cardiac Troponin (cTn) I and troponin T are the two cardiac muscle-specific isoforms for heart disease detection. cTn I increase in about six hours, peaks at twelve hours, and returns to baseline in ten days. On the contrary, cTn T remains elevated for about three days and reaches the normal range in ten days. Troponins are diagnostic of myocardial infarction (MI, also called heart attack). Also, cTn testing is an essential part of the diagnostic tests and treatment of acute coronary syndrome (an umbrella term for MI and unstable angina).
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Creatine Kinase: It is an enzyme present in high amounts in skeletal muscle, myocardium (heart muscle), and brain. Creatine kinase (CK) can be measured several times a day. The value becomes double in myocardial damage and heart attack. However, it is non-specific as the levels can increase in various conditions.
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Creatine Kinase- MB: A subtype of CK, Creatine kinase- MB (CK-MB) is more sensitive to heart damage. CK-MB increases about four to six hours after a heart attack. CK-MB is more specific to the myocardium and has quickly replaced CK as the gold standard. CK-MB forms about 30 percent of CK, and an increase of more than five percent of the total CK activity suggests heart muscle damage. CK-MB peaks between ten and twelve hours after MI. One must note that the best time for its detection is between six hours and three days.
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Myoglobin: Myoglobin is a small storage protein for oxygen measured in heart disease. It is sometimes calculated in addition to cTn for diagnosing MI. Myoglobin is released within an hour following heart injury and increases more rapidly than cTn or CK-MB. Moreover, it peaks in nearly eight to ten hours and returns to normal levels within a day. As it is non-specific to the myocardium, it is a negative predictor of heart damage. If serum myoglobin levels do not rise in samples analyzed two to four hours apart, MI is ruled out.
2. Biomarkers of Inflammation and Prognosis:
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C-Reactive Protein: A protein manufactured by the liver, C-reactive protein (CRP) is stimulated by interleukin (IL-6, an inflammatory mediator) in tissue injury and inflammation. CRP levels increase in acute illness and differ between age and gender. CRP levels of more than ten milligrams/liter (mg/L) denote acute inflammation. For risk assessment, more than three mg/L indicates an increased risk, one to three mg/L is a moderate risk, and less than one mg/L indicates a low risk. Hence, CRP levels are a predictor of prognosis and disease extent. Furthermore, new CRP assays are increasingly used for heart disease risk assessment.
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Fibrinogen: Fibrinogen is a protein produced in the liver with increased levels during acute inflammation. Furthermore, it plays a central role in blood clot formation. Raised fibrinogen levels correlate with an increased risk of CVD. Fibrinogen comprises Aα, Bβ, and γ polypeptide chains. Recently, a study showed a positive correlation of γ fibrinogen with coronary artery disease (CAD), stroke, and cardiovascular deaths. Hence, this observation suggests that γ fibrinogen is a risk factor for CVD.
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Uric Acid: Recent studies show an independent positive association between uric acid (UA) and cardiovascular death. Also, a high UA is related to an adverse prognosis. Positive associations for people at high risk for CVD are found with conditions such as type 2 diabetes mellitus, hypertension, or CAD patients.
3. Biomarkers of Myocardial Stress:
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Natriuretic Peptides: The natriuretic peptides (NPs) are a peptide family for sodium and water balance in the body. The atrial natriuretic peptide (ANP) and brain-natriuretic peptide (BNP) are produced primarily in the heart muscle cells. The BNP gene induction produces a prohormone called N-terminal pro–B-type natriuretic peptide (NT-proBNP), independently associated with heart failure (HF), that improves acute and chronic heart failure risk prediction.
Conclusion
Advances in biomarker research related to CVD have led to more sensitive screening methods, early detection and diagnosis, and improved treatments. All of these result in a favorable prognosis for patients. However, biomarkers for different CVD conditions remain an underexplored research area, with many new developments. Though biomarkers have improved care delivery, one must remember that all biomarkers work together with a proper history, physical, laboratory, and radiographic findings.
