How is it used?

Troponin tests are primarily ordered to evaluate people who have chest pain to see if they have had a heart attack or other damage to their heart. Either a cardiac-specific troponin I or troponin T test can be performed; usually a laboratory will offer one test or the other. Troponin tests are sometimes ordered along with other cardiac biomarkers, such as CKMB ormyoglobin. However, troponins are the preferred tests for a suspected heart attack because they are more specific for heart injury than other tests (which may become positive in skeletal muscle injury) and remain elevated for a longer period of time. The troponin test is used to help diagnose a heart attack, to detect and evaluate mild to severe heart injury, and to distinguish chest pain that may be due to other causes. In those who experience heart-related chest pain, discomfort, or other symptoms and do not seek medical attention for a day or more, the troponin test will still be positive if the symptoms are due to heart damage. ^ Back to top

When is it ordered?
A cardiac-specific troponin I or T test will usually be ordered when a person with a suspected heart attack first comes into the emergency room, followed by a series of troponin tests performed over several hours. It is sometimes ordered along with other tests such as CK, CKMB, or myoglobin. In people with stable angina, a troponin test may be ordered when:

Symptoms worsen Symptoms occur when a person is at rest Symptoms are no longer eased with treatment

These are all signs that the angina is becoming unstable, which increases the risk of a heart attack or other serious heart problem in the near future. ^ Back to top

What does the test result mean?

Because troponin is specific to the heart, even slight elevations may indicate some degree of damage to the heart. When a person has significantly elevated troponin levels and, in particular, a rise and/or fall in the results from a series of tests done over several hours, then it is likely that the person has had a heart attack or some other form of damage to the heart. When someone with chest pain and/or known stable angina has normal troponin values in a series of measurements over several hours, then it is unlikely that their heart has been injured. Troponin values can remain high for one to two weeks after a heart attack. The test is not affected by damage to other muscles, so injections, accidents, and drugs that can damage muscle do not affect cardiac troponin levels. Troponin may rise following strenuous exercise, although in the absence of signs and symptoms of heart disease, it is usually of no medical significance.

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Is there anything else I should know?

Increased troponin concentrations should not be used by themselves to diagnose or rule out a heart attack. A physical exam, clinical history, and ECG are also important as is whether the troponin levels from a series of tests are stably elevated or show a rise and/or fall over several hours. Very rarely, people who have a heart attack will have normal troponin concentrations, and some people with increased troponin concentrations have no apparent heart injury. Troponin levels may also be elevated with acute or chronic conditions such as myocarditis (heart inflammation), congestive heart failure, severe infections, kidney disease, and certain chronic inflammatory conditions of muscles and skin.

Troponin I is a part of the troponin complex. It binds to actin in thin myofilaments to hold the actintropomyosin complex in place. Because of it myosin cannot bind actin in relaxed muscle. When calcium binds to the Troponin C it causes conformational changes which lead to dislocation of troponin I and finally tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its inhibitory character. The tissue specific subtypes are: Slow-twitch skeletal muscle isoform troponin I, TNNI1 (1q31.3, 191042) Fast-twitch skeletal muscle isoform troponin I, TNNI2 (11p15.5, 191043) Cardiac troponin I, TNNI3 (19q13.4, 191044)

cTnI
Human troponin I is presented in cardiac muscle tissue by a single isoform with molecular weight 23876 Da and it consists of 209 amino acid residues. The theoretical pI of cTnI is 9.87. cTnI molecule contains two serines in the 22 and 23 positions. Both amino acid residues can be phosphorylated in vivo by protein kinase A, so four forms of protein one dephospho, two monophospho and one bisphospho can coexist in the cell. Phosphorylation of cTnI changes the conformation of the protein and modifies its interaction with other troponins as well as the interaction with anti-TnI antibodies. According to the latest [1] findings significant part of cTnI released into the patients blood stream is phosphorylated. For more than 15 years cTnI has been known as a reliable marker of cardiac muscle tissue injury. It is considered to be more sensitive and significantly more specific in diagnosis of the myocardial infarction than the golden marker of last decades CKMB, as well as myoglobin and LDH isoenzymes. HyTest Ltd holds patents for Method and kit for the diagnosis of troponin I (US7285418 and EP0938678).
Cardiac Troponins

Troponins are protein components of striated muscle. There are three different troponins: troponin C, troponin T and troponin I. Troponins T and I are only found in cardiac muscle o Troponin T (1) 84% sensitivity for myocardial infarction 8 hours after onset of symptoms (1); 81% specificity (1) low specificity - 22% for unstable angina advantages highly sensitive for detecting myocardial ischaemia

levels may help to stratify risk afterward Troponin I 90% sensitivity for myocardial infarction 8 hours after onset of symptoms (1); 95% specificity (1) low specificity for unstable angina - 36% - note however that there is evidence that (2)
troponin I elevation is useful for predicting in-hospital risk for unstable angina patients admitted to a community hospital. The association of ECG changes and high troponin I identifies a population at very high risk; however, the absence of both variables in patients with a diagnosis of unstable angina does not preclude the development of events

rises after 3-6 hours (1) peaks at about 20 hours (1) general advantages (3) o troponin T (cTnT) and troponin I (cTnI) are released only following cardiac damage CK and CK-MB are found in skeletal muscle as well as cardiac muscle therefore if there is damage to skeletal muscle, elevations of CK and CK-MB will occur and can make the diagnosis of myocardial infarction difficult. In such a situation levels of cTnT and/or cTnI will not rise unless myocardial infarction has occurred o troponin T and I are present for, and remain elevated, a long time unlike CK and CK-MB, cTnT and cTnI are released for much longer with cTnI detectable in the blood for up to 5 days and cTnT for 7-10 days following MI. This allows an MI to be detected if the patient presents late. For example, if a patient comes to the surgery with a history of chest pain 2-3 days ago, measurement of cTnT or cTnI will allow the diagnosis or exclusion of MI as a cause of the chest pain o troponin T and I are very sensitive there is always a low level release of CK and CK-MB from skeletal muscle at a low level all the time so there is always a background value. This is not the case for the cardiac structural proteins such as cTnT and cTnI and therefore, they are very sensitive. Studies have revealed that about one third of patients admitted with unstable angina, in whom MI was apparently excluded by CK and CK-MB measurement, have raised levels of cTnT and cTnI. Follow up studies have revealed that these patients are at significantly greater risk of death, subsequent MI or readmission with unstable angina than patients who did not have detectable levels cTnT or cTnI general disadvantages (3) o elevation of cTnT or TnI is absolutely indicative of cardiac damage, but this can occur as a result of causes other than MI e.g. myocarditis, coronary artery spasm from cocaine, severe cardiac failure,cardiac trauma from surgery or road traffic accident, and pulmonary embolus can cause cardiac damage with an accompanying elevation of cardiac troponin(s) o failure to show a rise in cTnT or cTnI does not exclude the diagnosis of ischaemic heart disease o both cTnT and cTnI may be elevated in patients with chronic renal failure and indicate a higher long-term risk of death. They can be distinguished from changes due to myocardial infarction by repeating the tests. Myocardial infarction causes a rise and fall in cTnT or cTnI, but in renal failure the elevated levels are sustained o reference ranges may vary between laboratories and are dependent on methods of measurement used

Troponin I is the inhibitory subunit of troponin, the thin filament regulatory complex which confers calciumsensitivity to striated muscle actomyosin ATPase activity. Subunit structure Post-translational modification

Binds to actin and tropomyosin. Interacts with TRIM63. Interacts with

Phosphorylated at Ser-42 and Ser-44 by PRKCE; phosphorylation in Ser-23 and Ser-24 by PRKD1; phosphorylation reduces myofilamen by STK4/MST1 alters its binding affinity to TNNC1 (cardiac Tn-C) an

Involvement in disease

Defects in TNNI3 are the cause of familial hypertrophic cardiomyopa hereditary heart disorder characterized by ventricular hypertrophy, w symptoms include dyspnea, syncope, collapse, palpitations, and che intrafamilial variability ranging from benign to malignant forms with h death. Ref.13 Ref.14 Ref.16 Ref.18 Ref.20 Defects in TNNI3 are the cause of familial restrictive cardiomyopathy characterized by impaired filling of the ventricles with reduced diasto function. Ref.15 Defects in TNNI3 are the cause of cardiomyopathy dilated type 2A (C ventricular dilation and impaired systolic function, resulting in conges Defects in TNNI3 are the cause of cardiomyopathy dilated type 1FF by ventricular dilation and impaired systolic function, resulting in con