Cardiac biomarkers are enzymes, proteins, and hormones that are associated with heart function, damage, or failure. Some of the tests are specific for the heart while others are also elevated with skeletal muscle damage.
Cardiac biomarkers are used for diagnostic and prognostic purposes and are frequently ordered by doctors when someone comes into the emergency room complaining of symptoms such as chest pain, pressure, nausea, and shortness of breath. These tests are ordered along with other laboratory and non-laboratory tests, to detect heart failure and the acute coronary syndromes (ACS) as well as to help determine prognosis for people who have had a heart attack.
The goal with cardiac biomarkers is to be able to detect the presence and severity of an acute heart condition as soon as possible so that appropriate treatment can be initiated. Cardiac biomarkers must be available to the doctor 24 hours a day, 7 days a week with a rapid turn-around-time.
Different biomarkers have different times that their levels rise, peak, and fall within the body, allowing them to be used not only to track the progress of a heart attack but to estimate when it began and to monitor for recurrence. This time of peaking and falling back to normal is referred as the diagnostic window of the biomarker.
There are only a few cardiac biomarkers that are being routinely used by physicians. Some have been phased out because they are not as specific as the marker of choice – troponin. Many other potential cardiac biomarkers are still being researched but their clinical utility has yet to be established.
Commonly used Cardiac Biomarkers
• CK and CK-MB
• Troponin
• Myoglobin (not always used; sometimes ordered with troponin)
• BNP
• LDH
• AST
CREATINE KINASE
Creatine kinase is an enzyme found in the heart, brain, skeletal muscle, and other tissues. Enzymes are proteins that help cells to perform their normal functions. In muscle and heart cells, most of this energy is used when muscles contract.
There are three different forms of CK; they are referred to as isoenzymes:
• CK-MM (found in skeletal muscles and heart)
• CK-MB (found mostly in heart)
• CK-BB (found mostly in brain)
In the first 4 to 6 hours after a heart attack, the concentration of CK in blood begins to rise. It reaches its highest level in 18 to 24 hours and returns to normal within 2 to 3 days. The amount of CK in blood also rises when skeletal muscles are damaged.
CREATINE KINASE – MB
Since a high total CK could indicate damage to either the heart or other muscles, CK–MB helps to distinguish between these two sources.
If the value of CK-MB is elevated and the ratio of CK–MB to total CK (relative index) is more than 2.5–3, it is likely that the heart was damaged. A high CK with a relative index below this value suggests that skeletal muscles were damaged.
TROPONIN
This test measures the concentration of cardiac-specific troponin in your blood. Troponin is a family of proteins found in skeletal and heart muscle fibers; it helps muscles contract. There are three forms of troponin: C, T, and I.
Cardiac troponin T and I are different enough from the troponin T and I found in skeletal muscle that they can be specifically tested for. These types of troponin are normally present in very small quantities in the blood. When there is damage to heart muscle cells, cardiac troponin T and I are released into circulation. The more damage there is, the greater the concentration of troponin T and I.
When a patient has a heart attack, levels of troponin can become elevated in the blood within 3 or 4 hours after injury and may remain elevated for 10 to 14 days.
Troponin tests are primarily ordered for people who have chest pain to see if they have had a heart attack or other damage to their heart.
The troponin test may be ordered by itself or along with other cardiac biomarkers, such as CK, CK– MB, and myoglobin. Troponin I and troponin T tests have begun to replace CK and CK-MB tests because they are more specific for heart injury (versus skeletal muscle injury) and are elevated for a longer period of time.
Troponin will remain high for 1–2 weeks after a heart attack. Troponin is not generally affected by damage to other muscles so that muscle injections, accidents, strenuous exercise, and drugs that can damage muscle do not affect troponin levels.
MYOGLOBIN
Myoglobin is a small oxygen-binding protein found in heart and skeletal muscles. The function of myoglobin is to trap oxygen within muscle cells, which allows them to produce the energy required for muscular contraction. When heart or skeletal muscle is injured, myoglobin is released into the blood, and increased concentrations can be measured within a few hours following injury.
As a cardiac biomarker, myoglobin is used in conjunction with troponin to help diagnose or rule out a heart attack. Myoglobin levels start to rise within 2-3 hours of a heart attack or other muscle injury, reach their highest levels within 8-12 hours, and generally fall back to normal within one day.
Its advantage over other markers is that it turns positive sooner than troponin. However, myoglobin may come from either heart or skeletal muscle, so an increase in serum myoglobin is not specific for damage to the heart. Consequently, a negative myoglobin result effectively rules out a heart attack, but a positive result must be confirmed by testing for troponin.
BNP
These tests measure the concentration of BNP or NT-proBNP in the blood. When the heart is stressed, it produces a precursor, pro-BNP, which is cleaved to release the active hormone BNP and an inactive fragment, NT-proBNP. Both BNP and NT-proBNP are produced mainly in the heart’s left ventricle (the organ’s main pumping chamber). Your heart releases them as a natural response to heart failure, to hypotension (when your heart is not strong enough to pump enough oxygen-rich blood and nutrients to meet your body's needs), when the heart itself does not get enough oxygen (with angina and heart attack), and when the left ventricle has been “stretched” too much (hypertrophy) from the accumulation of blood and fluid.
Another reason for using BNP and NT-proBNP is to evaluate risk in persons who present with chest pain. It has been found that high BNP predicts an increased risk of death or subsequent heart attack in patients with acute coronary syndromes.
Higher-than-normal results suggest that a person is in heart failure, and the level of BNP or NTproBNP in the blood is related to the amount or severity of heart failure. Higher levels of BNP or NT-proBNP also may be associated with a worse outlook for the patient.
LDH
Lactate dehydrogenase (LDH or LD) is an enzyme that is found in almost all body tissues, but only a small amount of it is usually detectable in the blood. Contained within the tissues’ cells, LDH is released into the bloodstream when cells are damaged or destroyed. Because of this, the LDH test can be used as a general marker of injury to cells.
Elevations of LDH may be measured either as a total LDH or as LDH isoenzymes. A total LDH level is an overall measurement of five different LDH isoenzymes. Isoenzymes are slightly different molecular versions of the LDH enzyme. A total LDH level will reflect the presence of tissue damage, but it is not specific. By itself, it cannot be used to identify the underlying cause or its location.
Although there is some overlap, each of the five LDH isoenzymes tends to be concentrated in specific body tissues. Because of this, measurements of the individual LDH isoenzyme levels can be used, along with other tests, to help determine the disease or condition causing cellular damage and to help identify the organs and tissues involved. In general, the isoenzyme locations tend to be:
• LDH-1, heart, red cells, kidney, germ cells
• LDH-2, heart, red blood cells, kidney (lesser amounts than LDH-1)
• LDH-3, lungs and other tissues
• LDH-4, white blood cells, lymph nodes; muscle, liver (lesser amounts than LDH-5)
• LDH-5, liver, skeletal muscle
Elevated levels of LDH may be seen with:
• Cerebrovascular accident (CVA, stroke)
• Drugs: anesthetics, aspirin, narcotics, procainamides, alcohol
• Hemolytic anemias
• Pernicious anemias (megaloblastic anemia)
• Infectious mononucleosis (Mono)
• Intestinal and pulmonary infarction
• Kidney disease
• Liver disease
• Muscular dystrophy
• Pancreatitis
• Lymphoma or other cancers
AST
AST is an enzyme found mostly in the heart and liver, and to a lesser extent in other muscles. When liver or muscle cells are injured, they release AST into the blood. AST is not a specific test for heart muscle damage and is almost always followed up with testing for other biomarkers.
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