Cardiac marker

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Cardiac marker
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Kinetics of cardiac markers Troponin and CK-MB in myocardial infarction with or without reperfusion treatment.
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Cardiac markers are biomarkers measured to evaluate heart function. They can be useful in the early prediction or diagnosis of disease. [1] Although they are often discussed in the context of myocardial infarction, other conditions can lead to an elevation in cardiac marker level. [2] [3]

Contents

Cardiac markers are used for the diagnosis and risk stratification of patients with chest pain and suspected acute coronary syndrome and for management and prognosis in patients with diseases like acute heart failure.

Most of the early markers identified were enzymes, and as a result, the term "cardiac enzymes" is sometimes used. However, not all of the markers currently used are enzymes. For example, in formal usage, troponin would not be listed as a cardiac enzyme. [4]

Applications of measurement

Measuring cardiac biomarkers can be a step toward making a diagnosis for a condition. Whereas cardiac imaging often confirms a diagnosis, simpler and less expensive cardiac biomarker measurements can advise a physician whether more complicated or invasive procedures are warranted. In many cases medical societies advise doctors to make biomarker measurements an initial testing strategy especially for patients at low risk of cardiac death. [5] [6]

Many acute cardiac marker IVD products are targeted at nontraditional markets, e.g., the hospital ER instead of traditional hospital or clinical laboratory environments. Competition in the development of cardiac marker diagnostic products and their expansion into new markets is intense. [7]

Recently, the intentional destruction of myocardium by alcohol septal ablation has led to the identification of additional potential markers. [8]

Types

Types of cardiac markers include the following:

Test Sensitivity and specificity Approximate peakDescription
Troponin test The most sensitive and specific test for myocardial damage. Because it has increased specificity compared with CK-MB, troponin is composed of 3 proteins- Troponin C, Cardic troponin I, and Cardiac troponin T. Troponin I especially has a high affinity for myocardial injury.12 hoursTroponin is released during MI from the cytosolic pool of the myocytes. Its subsequent release is prolonged with degradation of actin and myosin filaments. Isoforms of the protein, T and I, are specific to myocardium. Differential diagnosis of troponin elevation includes acute infarction, severe pulmonary embolism causing acute right heart overload, heart failure, myocarditis. Troponins can also calculate infarct size but the peak must be measured in the 3rd day. After myocyte injury, troponin is released in 2–4 hours and persists for up to 7 days.

Normal value are - Troponin I <0.3 ng/ml and Troponin T <0.2 ng/ml. In patients with non-severe asymptomatic aortic valve stenosis and no overt coronary artery disease, the increased troponin T (above 14 pg/mL) was found associated with an increased 5-year event rate of ischemic cardiac events (myocardial infarction, percutaneous coronary intervention, or coronary artery bypass surgery). [2]

Creatine Kinase (CK-MB) test It is relatively specific when skeletal muscle damage is not present.10–24 hoursThe CK-MB isoform of creatine kinase is expressed in heart muscle. It resides in the cytosol and facilitates movement of high energy phosphates into and out of mitochondria. Since it has a short duration, it cannot be used for late diagnosis of acute MI but can be used to suggest infarct extension if levels rise again. This is usually back to normal within 2–3 days. Normal range - 2-6 ng/ml
Lactate dehydrogenase (LDH)LDH is not as specific as troponin.72 hoursLactate dehydrogenase catalyses the conversion of pyruvate to lactate. LDH-1 isozyme is normally found in the heart muscle and LDH-2 is found predominantly in blood serum. A high LDH-1 level to LDH-2 suggest MI. LDH levels are also high in tissue breakdown or hemolysis. It can mean cancer, meningitis, encephalitis, or HIV. This is usually back to normal 10–14 days.
Aspartate transaminase (AST)This was the first used. [9] It is not specific for heart damage, and it is also one of the liver transaminases.
Myoglobin (Mb)low specificity for myocardial infarction 2 hoursMyoglobin is used less than the other markers. Myoglobin is the primary oxygen-carrying pigment of muscle tissue. It is high when muscle tissue is damaged but it lacks specificity. It has the advantage of responding very rapidly, [10] rising and falling earlier than CK-MB or troponin. It also has been used in assessing reperfusion after thrombolysis. [11]
Ischemia-modified albumin (IMA)low specificityIMA can be detected via the albumin cobalt binding (ACB) test, a limited available FDA approved assay. Myocardial ischemia alters the N-terminus of albumin reducing the ability of cobalt to bind to albumin. IMA measures ischemia in the blood vessels and thus returns results in minutes rather than traditional markers of necrosis that take hours. ACB test has low specificity therefore generating high number of false positives and must be used in conjunction with typical acute approaches such as ECG and physical exam. Additional studies are required.
Pro-brain natriuretic peptide This is increased in patients with heart failure. It has been approved as a marker for acute congestive heart failure. Patients with < 80 have a much higher rate of symptom-free survival within a year. Generally, pt with CHF will have > 100. In patients with non-severe asymptomatic aortic valve stenosis, increased age- and sex-adjusted N-terminal pro-brain natriuretic peptide (NT-proBNP) levels alone and combined with a 50% or greater increase from baseline had been found associated with increased event rates of aortic valve stenosis related events (cardiovascular death, hospitalization with heart failure due to progression of aortic valve stenosis, or aortic valve replacement surgery). [3]
Glycogen phosphorylase isoenzyme BB 0.854 and 0.767 [12] 7 hours

Glycogen phosphorylase isoenzyme BB (abbreviation: GPBB) is one of the three isoforms of glycogen phosphorylase. This isoform of the enzyme exists in cardiac (heart) and brain tissue. Because of the blood–brain barrier, GP-BB can be seen as being specific to heart muscle. GP-BB is one of the "new cardiac markers" which are considered to improve early diagnosis in acute coronary syndrome. During the process of ischemia, GP-BB is converted into a soluble form and is released into the blood. A rapid rise in blood levels can be seen in myocardial infarction and unstable angina. GP-BB is elevated 1–3 hours after process of ischemia.

Limitations

Reference ranges for blood tests, measured in units, including several cardiac markers. Reference ranges for blood tests - by units.png
Reference ranges for blood tests, measured in units, including several cardiac markers.

Depending on the marker, it can take between 2 and 24 hours for the level to increase in the blood. Additionally, determining the levels of cardiac markers in the laboratory - like many other lab measurements - takes substantial time. Cardiac markers are therefore not useful in diagnosing a myocardial infarction in the acute phase. The clinical presentation and results from an ECG are more appropriate in the acute situation.[ citation needed ]

However, in 2010, research at the Baylor College of Medicine revealed that, using diagnostic nanochips and a swab of the cheek, cardiac biomarker readings from saliva can, with the ECG readings, determine within minutes whether someone is likely to have had a heart attack[ citation needed ].

See also

Related Research Articles

<span class="mw-page-title-main">Coronary artery disease</span> Reduction of blood flow to the heart

Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the cardiac muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, and myocardial infarction.

<span class="mw-page-title-main">Angina</span> Chest discomfort that is generally brought on by inadequate blood flow to the cardiac muscle

Angina, also known as angina pectoris, is chest pain or pressure, usually caused by insufficient blood flow to the heart muscle (myocardium). It is most commonly a symptom of coronary artery disease.

<span class="mw-page-title-main">Troponin</span> Protein complex

Troponin, or the troponin complex, is a complex of three regulatory proteins that are integral to muscle contraction in skeletal muscle and cardiac muscle, but not smooth muscle. Measurements of cardiac-specific troponins I and T are extensively used as diagnostic and prognostic indicators in the management of myocardial infarction and acute coronary syndrome. Blood troponin levels may be used as a diagnostic marker for stroke or other myocardial injury that is ongoing, although the sensitivity of this measurement is low.

<span class="mw-page-title-main">Acute coronary syndrome</span> Medical condition

Acute coronary syndrome (ACS) is a syndrome due to decreased blood flow in the coronary arteries such that part of the heart muscle is unable to function properly or dies. The most common symptom is centrally located pressure-like chest pain, often radiating to the left shoulder or angle of the jaw, and associated with nausea and sweating. Many people with acute coronary syndromes present with symptoms other than chest pain, particularly women, older people, and people with diabetes mellitus.

<span class="mw-page-title-main">Unstable angina</span> Medical condition

Unstable angina is a type of angina pectoris that is irregular or more easily provoked. It is classified as a type of acute coronary syndrome.

P2Y<sub>12</sub> Protein-coding gene in the species Homo sapiens

P2Y12 is a chemoreceptor for adenosine diphosphate (ADP) that belongs to the Gi class of a group of G protein-coupled (GPCR) purinergic receptors. This P2Y receptor family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. The P2Y12 receptor is involved in platelet aggregation and is thus a biological target for the treatment of thromboembolisms and other clotting disorders. Two transcript variants encoding the same isoform have been identified for this gene.

<span class="mw-page-title-main">Troponin T</span> Protein family

Troponin T is a part of the troponin complex, which are proteins integral to the contraction of skeletal and heart muscles. They are expressed in skeletal and cardiac myocytes. Troponin T binds to tropomyosin and helps position it on actin, and together with the rest of the troponin complex, modulates contraction of striated muscle. The cardiac subtype of troponin T is especially useful in the laboratory diagnosis of heart attack because it is released into the blood-stream when damage to heart muscle occurs. It was discovered by the German physician Hugo A. Katus at the University of Heidelberg, who also developed the troponin T assay.

<span class="mw-page-title-main">Troponin I</span> Muscle protein

Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack. It occurs in different plasma concentration but the same circumstances as troponin T - either test can be performed for confirmation of cardiac muscle damage and laboratories usually offer one test or the other.

<span class="mw-page-title-main">Myocardial perfusion imaging</span> Nuclear medicine imaging method

Myocardial perfusion imaging or scanning is a nuclear medicine procedure that illustrates the function of the heart muscle (myocardium).

Avijit Lahiri is a researcher in cardiology in the UK.

The ST2 cardiac biomarker is a protein biomarker of cardiac stress encoded by the IL1RL1 gene. ST2 signals the presence and severity of adverse cardiac remodeling and tissue fibrosis, which occurs in response to myocardial infarction, acute coronary syndrome, or worsening heart failure.

<span class="mw-page-title-main">Myocardial infarction</span> Interruption of cardiac blood supply

A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction to the heart muscle. The most common symptom is retrosternal chest pain or discomfort that classically radiates to the left shoulder, arm, or jaw. The pain may occasionally feel like heartburn.

<span class="mw-page-title-main">Heart-type fatty acid binding protein</span> Protein-coding gene in the species Homo sapiens

Heart-type fatty acid binding protein (hFABP) also known as mammary-derived growth inhibitor is a protein that in humans is encoded by the FABP3 gene.

The N-terminal prohormone of brain natriuretic peptide is a prohormone with a 76 amino acid N-terminal inactive protein that is cleaved from the molecule to release brain natriuretic peptide 32.

A diagnosis of myocardial infarction is created by integrating the history of the presenting illness and physical examination with electrocardiogram findings and cardiac markers. A coronary angiogram allows visualization of narrowings or obstructions on the heart vessels, and therapeutic measures can follow immediately. At autopsy, a pathologist can diagnose a myocardial infarction based on anatomopathological findings.

<span class="mw-page-title-main">Management of acute coronary syndrome</span>

Management of acute coronary syndrome is targeted against the effects of reduced blood flow to the affected area of the heart muscle, usually because of a blood clot in one of the coronary arteries, the vessels that supply oxygenated blood to the myocardium. This is achieved with urgent hospitalization and medical therapy, including drugs that relieve chest pain and reduce the size of the infarct, and drugs that inhibit clot formation; for a subset of patients invasive measures are also employed. Basic principles of management are the same for all types of acute coronary syndrome. However, some important aspects of treatment depend on the presence or absence of elevation of the ST segment on the electrocardiogram, which classifies cases upon presentation to either ST segment elevation myocardial infarction (STEMI) or non-ST elevation acute coronary syndrome (NST-ACS); the latter includes unstable angina and non-ST elevation myocardial infarction (NSTEMI). Treatment is generally more aggressive for STEMI patients, and reperfusion therapy is more often reserved for them. Long-term therapy is necessary for prevention of recurrent events and complications.

Copeptin is a 39-amino acid-long peptide derived from the C-terminus of pre-pro-hormone of arginine vasopressin, neurophysin II and copeptin. Arginine vasopressin (AVP), also known as the antidiuretic hormone (ADH), is encoded by the AVP gene and is involved in multiple cardiovascular and renal pathways and abnormal level of AVP are associated with various diseases. Hence measurement of AVP would be useful, but is not commonly carried out in clinical practice because of its very short half-life making it difficult to quantify. In contrast, copeptin can be immunologically tested with ease and therefore can be used as a vasopressin surrogate marker.

Kounis syndrome is defined as acute coronary syndrome caused by an allergic reaction or a strong immune reaction to a drug or other substance. It is a rare syndrome with authentic cases reported in 130 males and 45 females, as reviewed in 2017; however, the disorder is suspected of being commonly overlooked and therefore much more prevalent. Mast cell activation and release of inflammatory cytokines as well as other inflammatory agents from the reaction leads to spasm of the arteries leading to the heart muscle or a plaque breaking free and blocking one or more of those arteries.

Remote ischemic conditioning (RIC) is an experimental medical procedure that aims to reduce the severity of ischaemic injury to an organ such as the heart or the brain, most commonly in the situation of a heart attack or a stroke, or during procedures such as heart surgery when the heart may temporary suffer ischaemia during the operation, by triggering the body's natural protection against tissue injury. Although noted to have some benefits in experimental models in animals, this is still an experimental procedure in humans and initial evidence from small studies have not been replicated in larger clinical trials. Successive clinical trials have failed to identify evidence supporting a protective role in humans.

Arthur Mark Richards is a New Zealand physician, academic and medical researcher. He is a professor of cardiology and director of the Cardiovascular Research Institute at the National University of Singapore, and a professor of medicine and founder of the Christchurch Heart Institute at the University of Otago, Christchurch, New Zealand, where he holds the National Heart Foundation (NZ) Chair of Cardiovascular Studies.

References

  1. ↑ Rao SP, Miller S, Rosenbaum R, Lakier JB (2019). "Opportunities for microRNAs in the Crowded Field of Cardiovascular Biomarkers". Annual Review of Pathology: Mechanisms of Disease. 14: 211–238. doi:10.1146/annurev-pathmechdis-012418-012827. PMC   6442682 . PMID   30332561.
  2. 1 2 Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesäniemi YA, Nienaber CA, Ray SG, Rossebø AB, Wachtell K, Nielsen OW (April 2023). "Association of high-sensitivity troponin T with outcomes in asymptomatic non-severe aortic stenosis: a post-hoc substudy of the SEAS trial". eClinicalMedicine. 58: 101875. doi:10.1016/j.eclinm.2023.101875. ISSN   2589-5370. PMC   10006443 . PMID   36915288.
  3. 1 2 Hadziselimovic E, Greve AM, Sajadieh A, Olsen MH, Kesäniemi YA, Nienaber CA, Ray SG, Rossebø AB, Willenheimer R, Wachtell K, Nielsen OW (2022-04-01). "Association of Annual N-Terminal Pro-Brain Natriuretic Peptide Measurements With Clinical Events in Patients With Asymptomatic Nonsevere Aortic Stenosis: A Post Hoc Substudy of the SEAS Trial". JAMA Cardiology. 7 (4): 435–444. doi:10.1001/jamacardio.2021.5916. ISSN   2380-6583. PMC   8851368 . PMID   35171199.
  4. ↑ Rao SP, Miller S, Rosenbaum R, Lakier JB (August 1999). "Cardiac troponin I and cardiac enzymes after electrophysiologic studies, ablations, and defibrillator implantations". Am. J. Cardiol. 84 (4): 470, A9. doi:10.1016/S0002-9149(99)00337-9. PMID   10468091.
  5. ↑ American Society of Nuclear Cardiology, "Five Things Physicians and Patients Should Question" (PDF), Choosing Wisely: an initiative of the ABIM Foundation , American Society of Nuclear Cardiology, archived from the original (PDF) on 2012-04-16, retrieved August 17, 2012
  6. ↑ Hendel RC, Berman DS, Di Carli MF, Heidenreich PA, Henkin RE, Pellikka PA, Pohost GM, Williams KA, American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Nuclear Cardiology, American College Of R, American Heart A, American Society of Echocardiology, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, Society Of Nuclear M (2009). "ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging". Journal of the American College of Cardiology. 53 (23): 2201–2229. doi:10.1016/j.jacc.2009.02.013. PMID   19497454.
  7. ↑ "Cardiac Marker Diagnostic Testing Markets". TriMark Publications, LLC. November 2011.
  8. ↑ Lewis GD, Wei R, Liu E, et al. (October 2008). "Metabolite profiling of blood from individuals undergoing planned myocardial infarction reveals early markers of myocardial injury". J. Clin. Invest. 118 (10): 3503–12. doi:10.1172/JCI35111. PMC   2525696 . PMID   18769631.
  9. ↑ NISSEN NI, RANLOV P, WEIS-FOGH J (July 1965). "Evaluation of Four Different Serum Enzymes in the Diagnosis of Acute Myocardial Infarction". Br Heart J. 27 (4): 520–6. doi:10.1136/hrt.27.4.520. PMC   503341 . PMID   14324110.
  10. ↑ "Use of Cardiac Markers in the Emergency Department: - eMedicine" . Retrieved 2009-01-06.
  11. ↑ Christenson RH, Ohman EM, Topol EJ, et al. (September 1997). "Assessment of coronary reperfusion after thrombolysis with a model combining myoglobin, creatine kinase-MB, and clinical variables. TAMI-7 Study Group. Thrombolysis and Angioplasty in Myocardial Infarction-7". Circulation. 96 (6): 1776–82. doi:10.1161/01.cir.96.6.1776. PMID   9323061.
  12. ↑ Lippi G, Mattiuzzi C, Comelli I, Cervellin G (2013). "Glycogen phosphorylase isoenzyme BB in the diagnosis of acute myocardial infarction: a meta-analysis". Biochem Med (Zagreb). 23 (1): 78–82. doi:10.11613/bm.2013.010. PMC   3900091 . PMID   23457768.

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