Clinical Biochemistry: Cardiac Biomarkers (PDF)

Faculty of Nursing and Health Sciences Department of Laboratory Sciences 3rd Year – English Session Clinical Biochemistry Chapter 5: Cardiac biomarkers Dr Lina Ismaiil 2024-2025 1 ...

Faculty of Nursing and Health Sciences Department of Laboratory Sciences 3rd Year – English Session Clinical Biochemistry Chapter 5: Cardiac biomarkers Dr Lina Ismaiil 2024-2025 1  Chapter 5 What is heart disease? Heart disease is a broad term that includes many types of heart problems. It is also called cardiovascular disease, that is, disease of the heart and blood vessels. There are many types of heart disease. Some you may be born with, called congenital heart defects. Other types develop over the course of your life. Coronary heart disease (also called cardiovascular disease) is the most common type of heart disease. This happens slowly over time when a sticky substance called plaque builds up in the arteries that supply blood to your heart muscle. Clinical Biochemistry / 2024-2025 2  Chapter 5 Cardiac profile test Ischemic heart disease: Coronary blood supply to the myocardium is insufficient relative to its demand. ✓The most common cause is atherosclerosis. ✓Congenital anomalies of the coronary arteries. ✓Coronary emboli of various types coming from different sources: 1. Vegetation of bacterial endocarditis. Endocarditis is due to the proliferation on the internal lining of the heart (endocardium) of bacteria, sometimes banal, or fungi (for example yeast). This overgrowth can lead to the formation of ulcers or perforations, or the appearance of a small growth that “hangs” (a “vegetation”). Clinical Biochemistry / 2024-2025 3  Chapter 5 Cardiac profile test Ischemic heart disease 2. Atheromatous plaque of the great coronary artery. Atheromatosis is an arterial disease characterized by a buildup of cholesterol plaques in the arterial wall. Coronary atheroma: lipid deposit in an intimal tunic of the coronary arteries. ✓ Narrowing of the lumen ✓ Decreased blood supply to the myocardium ✓ Thrombus formation in the coronary arteries ✓ Complete occlusion - Infarction/necrosis Clinical Biochemistry / 2024-2025 4  Chapter 5 Cardiac profile test Ischemic heart disease 2. Atheromatous plaque of the great coronary artery. Clinical Biochemistry / 2024-2025 5  Chapter 5 Cardiac profile test Ischemic heart disease 3. Reduced blood supply due to paroxysmal tachycardia Paroxysmal supraventricular tachycardia is a rapid, regular heart rhythm (160 to 220 beats per minute) that starts and stops abruptly and originates in heart tissue other than the ventricles. Clinical Biochemistry / 2024-2025 6  Chapter 5 Cardiac profile test Ischemic heart disease 4. Severe anemia, CO2 poisoning and decreased O2 supply to the myocardium. Clinical Biochemistry / 2024-2025 7  Chapter 5 Coronary atheroma Modifiable risk factors for heart disease: Hyperlipidemia Diabetes mellitus Smoking Hypertension Stress Obesity physical inactivity poor nutrition Clinical Biochemistry / 2024-2025 8  Chapter 5 Coronary atheroma Non-modifiable risk factors for heart disease: ✓Heredity: individuals more susceptible to premature atherosclerosis ✓Age: After middle age, increased incidence of atherosclerosis. ✓Gender: man > woman risk of atherosclerosis. Clinical Biochemistry / 2024-2025 9  Chapter 5 Biomarkers It is a substance used as an indicator of a biological state. It is characteristic and found only in the tissue of interest. It is objectively measured. It is evaluated as an indicator of normal biological processes, pathogenic processes or pharmacological responses to therapeutic intervention. Detection of the marker should enable intervention that prevents or minimizes the effects of the disease. Clinical Biochemistry / 2024-2025 10  Chapter 5 Cardiac biomarkers Intracellular macromolecules (proteins) released by a heart muscle when it is damaged following a myocardial infarction (MI). They are found in the blood. They are normally present at all times; however, they are significantly elevated during damage to the heart muscle. These include: Aspartate transaminase (AST or SGOT), Troponin I and T (TnI, TnT), Creatine phosphate kinase MB (CK-MB), Myoglobin (Mb), Lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), Myeloperoxidase (MPO) Ischemic modified albumin (IMA). Clinical Biochemistry / 2024-2025 11  Chapter 5 Classification of cardiac biomarkers according to the type of heart problem Cardiac markers could be classified as: Markers of myocardial injury (myocardial infarction ): ✓ Myocardial necrosis markers: CK-MB, myoglobin and troponin. ✓Myocardial ischemia markers: IMA and H-FABP. Hemodynamic stress markers: natriuretic peptides. Inflammatory and prognostic markers: hs-CRP, sCD40l and homocysteine Clinical Biochemistry / 2024-2025 12  Chapter 5 Aspartate Transaminase (AST) Also called glutamic oxaloacetic transaminase (GOT or SGOT, like serum GOT). It is widely distributed in tissues, but the highest levels are found in the liver, heart, skeletal muscles and red blood cells. o Normal value (-20 U/L) o Increased from 6 to 8 hours o Peak 18-24 hours o Return to normal in 4 to 5 days Clinical Biochemistry / 2024-2025 13  Chapter 5 Lactate Dehydrogenase (LDH) - Isoenzyme LDH is an enzyme found in almost all tissues of the body, but only a small amount is usually detectable in the blood. It is released into the bloodstream from destroyed or damaged cells, which is used as a general marker of cell damage. Clinical Biochemistry / 2024-2025 14  Chapter 5 Lactate Dehydrogenase (LDH) - Isoenzyme LDH functions as a tetramer and is composed of two types of subunits, H and M, each encoded by a different gene. This results in 5 different isoenzymes. The M subunit is found primarily in anaerobic tissues, including skeletal muscle and liver. The H subunit is most commonly found in tissues with a ready source of O2 and that metabolize lactate, including the heart and brain. 1. LDH-1 (4H) – in the heart 2. LDH-2 (3H1M) – in the reticuloendothelial system 3. LDH-3 (2H2M) – in the lungs 4. LDH-4 (1H3M) – in the kidney 5. LDH-5 (M4) – in the liver LDH-2 is generally the predominant form in serum. An LDH-1 level higher than the LDH-2 level suggests myocardial infarction. Clinical Biochemistry / 2024-2025 15  Chapter 5 Lactate Dehydrogenase (LDH) - Isoenzyme Clinical Biochemistry / 2024-2025 16  Chapter 5 Interpretation of results - LDH Heart diseases: ✓Following a myocardial infarction, LDH levels increase within 24-48 hours, peak at 3-4 days, and remain elevated for up to 10 days. ✓The level of LDH is directly proportional to the size of the infarction. ✓LDH level may be elevated in other heart diseases such as myocardial and rheumatic fever. Clinical Biochemistry / 2024-2025 17  Chapter 5 Interpretation of results - LDH Non-cardiac diseases: ❖High LDH levels in: ✓ Hemolytic and pernicious anemias ✓ Liver disease: LDH increases in liver diseases such as hepatitis and carcinoma (mainly LD4 and LD5). ✓ Muscular dystrophy ✓ Certain cancers (in particular lymphomas and leukemias). Clinical Biochemistry / 2024-2025 18  Chapter 5 Cardiac troponins Troponin is a complex of three regulatory proteins and is integral to non-smooth muscle contraction of skeletal and cardiac muscles. Troponin is attached to tropomyosin located in the groove between actin filaments in muscle tissue Troponin has three subunits: TnC, TnT and TnI: ✓Troponin -C: has calcium binding capacity and has no diagnostic value ✓Troponin -T: attaches the troponin complex to tropomyosin and actin ✓Troponin -I: is an inhibitory protein Clinical Biochemistry / 2024-2025 19  Chapter 5 Cardiac troponins Clinical Biochemistry / 2024-2025 20  Chapter 5 Cardiac troponins Clinical Biochemistry / 2024-2025 21  Chapter 5 Cardiac troponins Cardiac troponin I (cTnI) is a heart muscle protein with a molecular weight of 24 KD. The additional amino acid residues cTnI on its N- terminus which do not exist in the skeletal form. The half-life of TnI (2-4) hours. Increase in serum (2-8) hours. Troponin levels begin to increase 2 to 3 hours after the onset of myocardial injury. Elevated troponin-I and troponin-T may persist for up to 10 days after myocardial infarction. Clinical Biochemistry / 2024-2025 22  Chapter 5 Cardiac troponins Troponins T and I are not detected in healthy individuals. A significant increase in troponins reflects myocardial necrosis Troponin T dosage ranges: 0.01- 0.025 ng/ml Reference limits based on the 99th percentile for a healthy population are: 0.01 ng/ml (troponin T) 0.04 ng/ml (troponin I) Clinical Biochemistry / 2024-2025 23  Chapter 5 Total Creatine Kinase (CK) Creatine kinase (CK) known as creatine phosphokinase (CPK) is an enzyme expressed by various tissues and cell types. Creatine is produced by the liver, kidneys and pancreas. CK catalyzes the conversion of creatine and consumes adenosinetriphosphate (ATP) to create phosphocreatine (CP) and adenosine diphosphate (ADP). CP is a reserve of ATP Clinical Biochemistry / 2024-2025 24  Chapter 5 Total Creatine Kinase (CK) In cells, the CK enzyme consists of two subunits, which can be either B (brain type) or M (muscle type). There are three different isozymes: CK-MM, (CK3), CK-BB (CK1) and CK MB (CK2). Clinical Biochemistry / 2024-2025 25  Chapter 5 Meaning of CK-MB CK-MB is a cardiac marker released into the bloodstream when there is damage (necrosis) to the heart muscles. The release of CK-MB into the bloodstream is detected within 6 to 18 hours after the onset of acute myocardial infarction. Due to the protein breakdown mechanism that removes CK-MB from the bloodstream. Due to this short window, the peak level of CK-MB may be missed. Clinical Biochemistry / 2024-2025 26  Chapter 5 Meaning of CK-MB CK-MB begins to increase 3 to 6 hours after the onset of acute myocardial infarction (AMI). The peak is between 12 and 24 hours. It returns to normal in 24 to 48 hours. After 72 hours of AMI, 2/3 of patients show an increase in CK-MB. Clinical Biochemistry / 2024-2025 27  Chapter 5 Myoglobin Small heme proteins found in all tissues primarily help in oxygen transport. It is freed from all damaged tissues (non-specific) Increases often occur more rapidly than CK. Freed from damaged tissues in 1 hour (anterior marker). Normal value: 17.4-105.7 ng/ml. Clinical Biochemistry / 2024-2025 28  Chapter 5 Myoglobin Timing: At the earliest: 1 to 3 hours Peak: 6-9 hours Return to normal: 12h Increased myoglobin in - AMI, - skeletal muscle damage, - renal failure, - shock and trauma. Clinical Biochemistry / 2024-2025 29  Chapter 5 Cardiac biomarkers Clinical Biochemistry / 2024-2025 30  Chapter 5 High sensitivity C-reactive protein (hs-CRP) C-reactive protein (CRP) is a protein produced by the liver that increases in the blood during inflammation and infection and following a heart attack, surgery, or 'a trauma. CRP test: is a blood test marker for inflammation in the body. The high-sensitivity CRP (hs-CRP) test measures low levels of CRP in the blood to identify low levels of inflammation associated with the risk of developing cardiovascular disease (CVD). Clinical Biochemistry / 2024-2025 31  Chapter 5 Natriuretic Peptides Brain natriuretic peptide, or B-type natriuretic peptide, or BNP (“brain natriuretic peptide”), is one of the natriuretic peptides, that is to say, causing the excretion of sodium by the kidneys. The term B (for English: brain) is, in fact, a reminder that the messenger RNA for this protein was first identified in the brain. BNP and its N-terminal part (NT-proBNP) are secreted as protein hormones excreted mainly by the myocardium, also by the endothelium, and the kidneys Clinical Biochemistry / 2024-2025 34  Chapter 5 Natriuretic Peptides ANP is stored as secretory granules in the cytosol of atrial cardiomyocytes. BNP and NT-proBNP dosages in particular are used as indicators of the heart's inability to pump and as a sign of activation of one of the basic neurohumoral systems regulating cardiac performance. Its triggering is immediate, of the order of a few tens of seconds to a few minutes. Clinical Biochemistry / 2024-2025 35  Chapter 5 The role of natriuretic peptides in people with risk factors for heart failure In patients at risk of developing heart failure, natriuretic peptides can be used to screen patients for specialized care and aggressive cardiovascular treatment. This strategy reduces the development of left ventricular systolic dysfunction or new-onset heart failure. BNP = B-type natriuretic peptide; CAD = coronary artery disease; CV = cardiovascular; NP = natriuretic peptide; NT-proBNP = N-terminal pro-B type natriuretic peptide. Clinical Biochemistry / 2024-2025 36  Chapter 5 Heart failure and natriuretic peptide Clinical Biochemistry / 2024-2025 37  Chapter 5 Other biomarkers: Ischemia-modified albumin (IMA) It measures the changes that occur in albumin in the presence of ischemia, giving it the advantage of being able to detect ischemia before the heart is damaged. Free radical formation that occurs during tissue ischemia is thought to alter albumin within minutes of ischemia and lasts for approximately 6 hours. IMA is not specific for cardiac lesions; it has a Clinical sensitivity effect for acute coronary syndrome (ACS) of 50% to 90%. IMA is used in the early diagnosis of ACS; its use will complement, not replace, troponin and CK- MB detection. Clinical Biochemistry / 2024-2025 39  Chapter 5 Other biomarkers Homocysteine Homocysteine is a sulfur-containing amino acid formed in plasma from the metabolic demethylation of methionine, derived from dietary proteins. Normal total plasma homocysteine ranges from 5 to 15 μmol/L, moderate is 16 to 30 μmol/L, intermediate is 31 to 100 μmol/L, And severe hyperhomocysteinemia is greater than 100 μmol/L (>13.5 mg/L) which indicates CVD. Clinical Biochemistry / 2024-2025 40  Chapter 5 Other biomarkers sCD40 ligand sCD40 Ligand is a transmembrane protein related to tissue necrosis factor (TNF) alpha. It has multiple prothrombotic and proatherogenic effects. Assays are usually designed to measure the circulating soluble form o the receptor, which has been shown to be a predictor o events after acute Acute Coronary Syndrome (ACS) presentations. Clinical Biochemistry / 2024-2025 41  Chapter 5 Other biomarkers Myeloperoxidase MPO MPO is released when neutrophils aggregate. Its release may indicate an active inflammatory response in blood vessels. It is elevated chronically when chronic Coronary Artery Disease (CAD) is present. Also, it is increased when patients present with ACS. A multi-biomarker study has shown that MPO as a prognostic tool was dependent on the outcomes studied (cardiac death) and the demographics of the patient population enrolled. Clinical Biochemistry / 2024-2025 42  Chapter 5 Biochemical cardiac markers Clinical Biochemistry / 2024-2025 43