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Editor-in-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2]


Troponin is a complex of three proteins that is integral to muscle contraction in skeletal and cardiac muscle, but not smooth muscle. Troponin is attached to the protein tropomyosin and lies within the groove between actin filaments in muscle tissue. In a relaxed muscle, tropomyosin blocks the attachment site for the myosin crossbridge, thus preventing contraction. When the muscle cell is stimulated to contract by an action potential, calcium channels open in the sarcoplasmic reticulum and release calcium into the sarcoplasm. Some of this calcium attaches to troponin, causing a conformational change that moves tropomyosin out of the way so that the cross bridges can attach to actin and produce muscle contraction. Troponin is found in both skeletal muscle and cardiac muscle, but the specific versions of troponin differ between types of muscle. The main difference is that the TnC subunit of troponin in skeletal muscle has four calcium ion binding sites, whereas in cardiac muscle there are only three.

Discussions of troponin often pertain to its functional characteristics and/or to its usefulness as a diagnostic marker for various heart disorders. When cardiac injury occurs (such as in case of an acute MI), these intracellular proteins are then released into the bloodstream. Along with the patient's history and the electrocardiogram, the release of these enzymes forms the basis of the diagnosis of ST elevation myocardial infarction.

Until the 1980s, the enzymes SGOT and LDH were used to assess cardiac injury. In the early 1980s it was found that disproportional elevation of the MB subtype of the enzyme creatine kinase (CK) was very specific for myocardial injury. More recently, troponin sub-units I or T, have been used as an even more specific marker of myonecrosis.[1][2][3] The 2007 Joint ESC/ACCF/AHA/WHF Task Force[4] for the definition of myocardial infarction emphasized the importance of both elevated cardiac biomarkers and clinical evidence for MI.

Physiologic Role of Troponins in the Absence of Disease

Both cardiac and skeletal muscles are controlled by changes in the intracellular calcium concentration. When calcium rises, the muscles contract, and when calcium falls the muscles relax.

Troponin is a component of thin filaments (along with actin and tropomyosin), and is the protein to which calcium binds to accomplish this regulation. Troponin has three subunits, TnC, TnI, and TnT. When calcium is bound to specific sites on TnC, tropomyosin rolls out of the way of the actin filament active sites, so that myosin (a molecular motor organized in muscle thick filaments) can attach to the thin filament and produce force and/or movement. In the absence of calcium, tropomyosin interferes with this action of myosin, and therefore muscles remain relaxed.

Troponin I has also been shown to inhibit angiogenesis in vivo and in vitro.

Individual subunits serve different functions:

  • Troponin C binds to calcium ions to produce a conformational change in TnI
  • Troponin T binds to tropomyosin, interlocking them to form a troponin-tropomyosin complex
  • Troponin I binds to actin in thin myofilaments to hold the troponin-tropomyosin complex in place

Diagnostic Use

See also Acute coronary syndromes Two subtypes of troponin (cardiac troponin I and T) are very sensitive and specific indicators of damage to the heart muscle (myocardium). The agreement between hscTNT and hscTNI measurements is excellent (Cohen's kappa =0.9)[5].

One of the more common uses of troponin is to determine if a patient with chest pain has sustained death of the myocytes (heart muscle cells) as a result of thrombotic (blood clot related) occlusion of a coronary artery which would warrant urgent medical or interventional therapy. The level of troponin is measured in the bloodstream and it is used to differentiate between unstable angina (no elevation of troponin, the myocardium is not irreversibly damaged) versus either non ST elevation MI or ST elevation MI (heart attack) in patients with chest pain. Troponin is a simple yet potent tool for risk stratification. If a patient is troponin positive, and has signs and symptoms of ischemic heart disease (substernal chest pain or pressure, electrocardiographic EKG changes), then an early invasive strategy is warranted. This should be preceded by aggressive antiplatelet and antithrombin therapy (see acute coronary syndromes).

Use of Troponin to "Rule Out" or "Rule In" a Heart Attack

While it is commonly said that a negative troponin "rules out" a non ST elevation MI or ST elevation MI, it should be noted that among those patients who are ultimately found to be troponin positive, approximately 20% will be troponin negative at the time of the initial testing. These patients are sometimes referred to as an "MI in evolution" and form the basis for checking serial or multiple troponins in a monitored setting. A negative troponin on a single test does not exclude the possibility that the patient has ongoing myonecrosis.

On the other hand, a positive troponin does not "rule in" (i.e. does not allow one to conclude) that there is a thrombotic occlusion of the epicardial artery. As shown below, there are a wide variety of other causes for an elevated troponin.

Role of Pre-Test Probability in the Positive Predictive Value of Troponin

If troponin values are checked in a population with a low pre-test probability of disease, then the positive predictive value of the test will drop dramatically. Patients who have a low pre-test probability of an acute coronary syndrome (negative family history, few or absent cardiac risk factors, absent EKG changes, absent ischemic chest pain) do not derive benefit from an early invasive strategy. Identification of an alternate source of the troponin other than an acute coronary syndrome should be sought and the underlying disease treated. Not all troponin positive patients should undergo cardiac catheterization. Indeed, patients with a low pre-test probability of heart disease should not be treated with aggressive antiplatelet therapy, antithrombin therapy, diagnostic catheterization and revascularization.

Absence of Troponin Elevation in the General Population

Among 3,557 individuals in the general population, only 0.7% of patients had a troponin ≥0.01 microg/L, which is > than the 99th percentile of the reference range. The underlying disease state in those individuals with elevated troponins included chronic kidney disease, heart failure, left ventricular hypertrophy and diabetes.[6]

Prognostic Value of an Elevated Troponin in the Absence of Thrombotic Acute Coronary Syndromes

Even in the absence of an acute coronary syndrome, and in the presence of "normal coronary arteries" on diagnostic cardiac catheterization, an elevated troponin is associated with adverse outcomes.[7] There is no data to suggest that aggressive antiplatelet and / or antithrombin strategies improve clinical outcomes in these patients who are often critically ill from non-cardiac conditions. Aspirin is safe to administer to these patients.

General Mechanisms by Which Troponin May be Elevated in Disease

1. Injury or Death of Heart Muscle Cells due to Reduced Oxygen Supply

In these scenarios there is reduced blood flow to the heart muscle:

a. Epicardial Vessel Occlusion:
This is the cause of an acute coronary syndrome and should be the trigger for an early invasive strategy. This form of myonecrosis is classified as a Type I MI in the new universal definition of MI proposed by the 2007 Joint European Society of Cardiology/American College of Cardiology/American Heart Association/World Health Federation (ESC/ACCF/AHA/WHF). [8]
b. Epicardial vessel spasm
c. Microvascular obstruction:
Microvascular disease, cocaine abuse, stress cardiomyopathy, subarachnoid hemmorhage, transplant vasculopathy, and hypertrophic cardiomyopathy may all lead to troponin elevations due to small vessel disease or spasm.
d. Hypoperfusion:
Heart block and hypotension may lead to hypoperfusion of the myocardium.

2. Injury or Death of the Heart Muscle Cells due to Increased Demands for Oxygen

Classic example of this would the patient with tachycardia and strenuous exercise such as a marathon or the patient with new onset atrial fibrillation and a rapid ventricular response.[9] This form of myonecrosis is classified as a Type II MI in the new universal definition of MI proposed by the 2007 Joint European Society of Cardiology/American College of Cardiology/American Heart Association/World Health Federation (ESC/ACCF/AHA/WHF). [10] Demand can be increased due to tachycardia, increased oxygen consumption and changes in loading conditions. Sepsis is associated with troponin elevations in part due to this mechanism, and in part due to the increased permeability of myocytes during sepsis.[11] [12][13]

3. Injury or Death of the Myocytes due to Increased Stretch of the Cells

Patients with congestive heart failure, pulmonary hypertension and acute valvular disorders such as aortic insufficiency often have dilated hearts. Both subendocardial ischemia and excess stretch due to the dilation may damage the myocytes. Increase demand due to tachycardia and subendocardial ischemia may play a role as well.

4. Direct Injury of the Heart Muscle Cells

a. Inflammation and Infection
Classic examples of this would be inflammatory diseases such as pericarditis, myocarditis, Kawasaki's disease and inflitrative diseases such as amyloidosis, hemochromatosis, sarcoidosis, and scleroderma.
b. Trauma to the Heart Muscle Cells
Classic examples of this would be ablation, blunt trauma, cardiac surgery, cardioversion, defibrillation, endomyocardial biopsy.

5. Drug toxicity or toxins

Drug toxicity such as high-dose chemotherapy and compounds such as adriamycin, 5-flurouracil, herceptin, snake venom

6. Leakage of Troponin from the Heart Muscle Cells

A classic example is sepsis. [14] [15][16]

7. Reduced Clearance of Troponin from the Bloodstream

A classic example of this would include renal failure.

"False Positive" Troponin Elevations That Are Not Due to Thrombotic Coronary Occlusion

Again, it should be re-emphasized that while a troponin elevation reflects myocardial injury, thrombotic occlusion of an epicardial coronary artery is just one of many causes of myocardial injury. Non-thrombotic causes of an elevated troponin are often referred to as "false positive" causes of a troponin elevation. [17] [18] [19] Troponin release in the context of coronary thrombosis and vessel occlusion is due to irreversible damage (myocyte necrosis or cell death) with the release of the intracardiac enzymes into the bloodstream as the myocyte's cell membranes break down. However, in the absence of thrombotic occlusion of a coronary artery, troponin can also be released from myocytes in the absence of necrosis or cell death. This release can occur as a result of changes in the permeability of the cell membrane. Sepsis for instance can cause the breakdown of troponin to lower-molecular-weight fragments that can then leak into the bloodstream through a myocyte membrane that is also rendered more porous by sepsis. [20] The fact that patients who survive sepsis do not have an irreversible decline in LV function supports this mechanism as well. [21] Among patients who have an elevated troponin and a normal angiogram, a very small study of 21 patients identified the following as the underlying causes [22]:

Non-Thrombotic Cardiac Causes of Troponin Elevation

Non-cardiac Causes of Troponin Elevation

Technical Aspects

Cardiac troponin T (cTnT) and I (cTnI) are measured by immunoassay methods. A single manufacturer distributes cTnT but a host of diagnostic companies make cTnI methods available on many different immunoassay platforms.[24]

Drug-induced cardiotoxicity is common to all classes of therapeutic drugs. It is essential that cardiotoxicity is detected with a high degree of sensitivity and specificity. The newly developed troponins are especially useful in this context[25]

Troponin Elevation During Pregnancy

  • Troponin is validated for the diagnosis of AMI in pregnancy.[26][27][28][29]
  • After normal delivery, troponin concentration may slightly increase. The increase may be above or below the upper limit of normal.[26]
  • More prominent troponin concentration elevation is observed among women with pre-eclampsia or gestational hypertension.[28][29]
  • To view changes in CK and CK-MB concentrations during labor and delivery, click here.


  1. Eisenman A (2006) Troponin assays for the diagnosis of myocardial infarction and acute coronary syndrome: where do we stand? Expert Rev Cardiovasc Ther 4 (4):509-14. DOI:10.1586/14779072.4.4.509 PMID: 16918269
  2. Aviles RJ, Askari AT, Lindahl B, Wallentin L, Jia G, Ohman EM et al. (2002) Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med 346 (26):2047-52. DOI:10.1056/NEJMoa013456 PMID: 12087140
  3. Chen BH (2002) Cardiac troponin T levels in patients with renal failure. CMAJ 167 (6):671. PMID: 12358205
  4. Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction (2007) Universal definition of myocardial infarction. Eur Heart J 28 (20):2525-38. DOI:10.1093/eurheartj/ehm355 PMID: 17951287
  5. van der Linden N, Wildi K, Twerenbold R, Pickering JW, Than M, Cullen L; et al. (2018). "Combining High-Sensitivity Cardiac Troponin I and Cardiac Troponin T in the Early Diagnosis of Acute Myocardial Infarction". Circulation. 138 (10): 989–999. doi:10.1161/CIRCULATIONAHA.117.032003. PMID 29691270.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  6. Wallace, TW, Abdullah, SM, Drazner, MH, et al. Prevalence and determinants of troponin T elevation in the general population. Circulation 2006; 113:1958.
  7. Wright, RS, Williams, BA, Cramner, H, et al. Elevations of cardiac troponin I are associated with increased short-term mortality in noncardiac critically ill emergency department patients. Am J Cardiol 2002; 90:634.
  8. Thygesen, K, Alpert, JS, White, HD, et al. Universal definition of myocardial infarction: Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Eur Heart J 2007; 28:2525.
  9. Zellweger, MJ, Schaer, BA, Cron, TA, et al. Elevated troponin levels in absence of coronary artery disease after supraventricular tachycardia. Swiss Med Wkly 2003; 133:439.
  10. Thygesen, K, Alpert, JS, White, HD, et al. Universal definition of myocardial infarction: Kristian Thygesen, Joseph S. Alpert and Harvey D. White on behalf of the Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Eur Heart J 2007; 28:2525.
  11. Wu, AH. Increased troponin in patients with sepsis and septic shock: myocardial necrosis or reversible myocardial depression?. Intensive Care Med 2001; 27:959.
  12. Parrillo, JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993; 328:1471.
  13. Ammann, P, Fehr, T, Minder, EI, et al. Elevation of troponin I in sepsis and septic shock. Intensive Care Med 2001; 27:965.
  14. Wu, AH. Increased troponin in patients with sepsis and septic shock: myocardial necrosis or reversible myocardial depression?. Intensive Care Med 2001; 27:959.
  15. Parrillo, JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993; 328:1471.
  16. Ammann, P, Fehr, T, Minder, EI, et al. Elevation of troponin I in sepsis and septic shock. Intensive Care Med 2001; 27:965.
  17. Jeremias A, Gibson CM (2005). "Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded". Ann. Intern. Med. 142 (9): 786–91. PMID 15867411. Unknown parameter |month= ignored (help)<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  18. Ammann P, Pfisterer M, Fehr T, Rickli H. Raised cardiac troponins. BMJ 2004;328:1028-9. PMID 15117768.
  19. Higgins, JP, Higgins, JA. Elevation of cardiac troponin I indicates more than myocardial ischemia. Clin Invest Med 2003; 26:133.
  20. Wu, AH. Increased troponin in patients with sepsis and septic shock: myocardial necrosis or reversible myocardial depression?. Intensive Care Med 2001; 27:959.
  21. Parrillo, JE. Pathogenetic mechanisms of septic shock. N Engl J Med 1993; 328:1471.
  22. Bakshi, TK, Choo, MK, Edwards, CC, et al. Causes of elevated troponin I with a normal coronary angiogram. Intern Med J 2002; 32:520
  23. Kim, M, Kim, K. Elevation of cardiac troponin I in the acute stage of Kawasaki disease. Pediatr Cardiol 1999; 20:184.
  24. Collinson PO, Boa FG, Gaze DC. Measurement of cardiac troponin. Ann Clin Biochem 2001;38:423-449. PMID 11587122.
  25. Gaze DC, Collinson PO. Cardiac troponins as biomarkers of drug- and toxin-induced cardiac toxicity and cardioprotection. Expert Opin Drug Metab Toxicol 2005;1:715-725. PMID 16863435.
  26. 26.0 26.1 Shade GH, Ross G, Bever FN, Uddin Z, Devireddy L, Gardin JM (2002). "Troponin I in the diagnosis of acute myocardial infarction in pregnancy, labor, and post partum". Am J Obstet Gynecol. 187 (6): 1719–20. PMID 12501092.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  27. Shivvers SA, Wians FH, Keffer JH, Ramin SM (1999). "Maternal cardiac troponin I levels during normal labor and delivery". Am J Obstet Gynecol. 180 (1 Pt 1): 122. PMID 9914590.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  28. 28.0 28.1 Fleming SM, O'Gorman T, Finn J, Grimes H, Daly K, Morrison JJ (2000). "Cardiac troponin I in pre-eclampsia and gestational hypertension". BJOG. 107 (11): 1417–20. PMID 11117772.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>
  29. 29.0 29.1 Atalay C, Erden G, Turhan T, Yildiran G, Saraçoglu OF, Koca Y (2005). "The effect of magnesium sulfate treatment on serum cardiac troponin I levels in preeclamptic women". Acta Obstet Gynecol Scand. 84 (7): 617–21. doi:10.1111/j.0001-6349.2005.00667.x. PMID 15954868.<templatestyles src="Module:Citation/CS1/styles.css"></templatestyles>

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