IN THE PAST 2 DECADES, more blood tests have been developed for cardiac biomarkers, which have a role in diagnosis, prognosis, and intervention.1 (See Testing serum cardiac biomarkers.) Troponin is currently the selected biomarker for detecting cardiac injury, because it's involved in the interaction between actin and myosin and a resulting cardiac contraction. In myocardial injury, troponin is released from the bonds of these contractile proteins and becomes detected in the circulation.
Troponin, a three-protein complex consisting of troponins I, T, and C, is found in cardiac and skeletal muscle. Most of these proteins stored in myofibrils (bound) are key for calcium-regulated cardiac and skeletal contraction.2 Some troponin is also found in the cytosol (unbound). Troponins I (cTnI) and T (cTnT) are cardiac tissue-specific, but troponin C (cTnC) isn't.3 Injured cardiac muscle releases troponin into the bloodstream. Thus, increased levels of cardiac troponin may suggest myocardial injury.2 Troponin released after cardiac injury usually remains elevated (its half-life is about 2 hours), leading to better identification of cardiac injury.2 Monoclonal antibodies can now detect cardiac troponins, resulting in immunoassays for blood measurement.
The quality of assays available for measuring troponin has improved since the first tests were developed. The newer assays are more sensitive-the test has a low rate of false negatives-so more patients are identified with elevated troponin levels. Assays to measure either cTnT or cTnI are equal in specificity (the tests have a low rate of false positives).2 The specific assay used and the cut-off values for positive results vary across laboratories. You need to identify the reference ranges for your hospital or lab to accurately interpret test results. These reference range variations also makes comparing troponin values from other hospitals difficult.
The amount of cardiac troponin in the blood initially rises in about 4 to 6 hours. Peak concentrations appear at 18 to 24 hours after symptoms begin.2 Because of this pattern, obtain samples on admission and then repeat testing 6 to 9 hours later. Troponin can remain elevated for 10 days after the injury.3 Prolonged elevation makes diagnosing cardiac injury in a patient who doesn't seek treatment for more than 24 hours easier, because other cardiac biomarkers in these patients, such as creatine kinase (CK-MB), may be normal.
Troponin in various populations
Acute coronary syndromes (ACS) is the term used to describe the group of clinical syndromes that includes acute myocardial infarction (MI) and unstable angina. Troponin levels can help in the diagnosis and prognosis of ACS.1
Myocardial infarction can be diagnosed based on pathological findings or on the typical rise and fall of myocardial necrosis biomarkers and the presence of at least one of the following: signs and symptoms of myocardial ischemia, ECG indications of ischemia or necrosis, or a coronary artery intervention.4 Cardiac troponins are the preferred biomarker for MI because they have a higher level of sensitivity and specificity than other available biomarkers.4 Early diagnosis and treatment of MI can reduce the degree of myocardial injury.
Elevated troponin levels can be prognostic in the ACS patient. The risk of short-term mortality is increased in patients with ST-segment elevation MI (STEMI), although the risk of death and repeat MI is higher in patients with non-ST-segment elevation MI (NSTEMI) when troponin levels are elevated, compared with those patients without elevations.1 Troponin elevations have also helped clinicians detect reinfarctions and estimate infarct size.2 Levels of troponin aren't elevated in unstable angina.4
Although ACS can cause elevated troponin levels, so can other conditions. For example, in cardiac surgery patients, myocardial damage is inescapable due to many factors, including cross-clamping and cardiopulmonary bypass use. Biomarkers can't identify the specific cause of injury, but some research has suggested that the more elevated the level is postoperatively, the greater the damage and the more grave the prognosis.2
Critically ill patients
Because troponin levels are being tested more frequently, we've learned that cardiac injury occurs often. However, many unknown factors contribute to increased troponin levels. Elevated cardiac troponin has been found in critically ill patients without a cardiac diagnosis.5 Critically ill patients with sepsis often have increased troponin levels, although the reason is unclear. The elevated troponin could be related to underlying coronary artery disease, or the release of toxins in sepsis (such as tumor necrosis factor) that can injure the heart and cause increased troponin levels.2
Patients with renal failure may have elevated troponin levels, possibly due to skeletal injury. But because these patients are at high risk for cardiovascular disease, obtain a baseline troponin value that can be used as a comparison in future acute cardiac events.2
Patients with heart failure also have increased levels of cardiac troponins, both in acute and chronic phases with and without coronary artery disease. In patients with ventricular hypertrophy (left or right), the ventricular wall stress or oxygen imbalances could cause troponin elevations.2 Similarly, right ventricular strain and increased pulmonary vascular resistance may explain increased troponin levels in patients with acute pulmonary embolism (PE). The troponin elevation in PE resolves in 40 hours or less.2
Direct damage to the heart, such as from blunt cardiac trauma, is another cause of elevated troponin levels. Also, therapies such as electrical cardioversion or defibrillation may injure the heart. Elective cardioversion usually doesn't raise troponin levels, but levels are more likely to be elevated after defibrillation or prolonged resuscitation.
With the current state of troponin testing, you must know the patient's history to accurately interpret results. The diagnostic and prognostic value of elevated troponin levels has strong evidence in some populations, but can be uncertain in others. Further diagnostic studies to confirm cardiac injury are indicated in at-risk patients. Rule out other causes of elevated troponin levels, especially in critically ill patients-elevated levels have been linked to increased mortality and negative patient outcomes.5 Finally, to correctly evaluate troponin values, you'll need to be familiar with the specific assays and normal reference ranges used in the lab where blood samples are obtained.
Suppose you're caring for Nick Giovannazzo, 72, who was involved in a head-on car crash. Although he was wearing a seat belt, he suffered a cardiac contusion and multiple fractures. After undergoing surgery to repair the fractures, he was admitted to the trauma intensive care unit, where his postoperative ECG and general lab tests were normal. However, he complained of generalized chest discomfort, and a cardiac marker analysis revealed an elevated troponin level.
A second ECG showed no changes from the initial 12-lead ECG. He was given an analgesic to alleviate his pain, had no further complaints of discomfort, and remained stable.
Mr. Giovannazzo's medical history included asthma and renal insufficiency, which can falsely elevate troponin levels without a cardiac event.
By understanding troponin levels, you can help your patient get the best possible care.[black small square]
Testing serum cardiac biomarkers
Before the use of troponin, total creatine kinase (CK) and CK-MB had been used to diagnose acute myocardial infarction (AMI). Creatine kinase is an enzyme found in heart and skeletal muscle and the brain, and CK-MB is an isoenzyme of CK found mainly, but not exclusively, in the cardiac tissue.3 Conditions such as myocardial contusion, skeletal trauma, or defibrillation can cause elevated CK-MB levels.3
Creatine kinase and CK-MB have limitations for diagnosing AMI because the blood elevations occur late in the course of an AMI. Furthermore, the distribution of CK and CK-MB in skeletal muscle may result in falsely elevated levels due to noncardiac injury, thus leading to an incorrect AMI diagnosis. For these reasons, CK and CK-MB aren't considered the standard for diagnosing AMI. Serial CK-MB measurements (noting the characteristic rise and fall) can be useful when other cardiac biomarkers such as troponin aren't available.1
1. Maisel AS, Bhalla V, Braunwald E. Cardiac biomarkers: A contemporary status report. Nature Clinical Practice Cardiovascular Medicine. 3(1):24-34, January 2006. [Context Link]
2. Casey PE. Markers of myocardial injury and dysfunction. AACN Clinical Issues. 15(4):547-557, October-December 2004. [Context Link]
3. Babuin L, Jaffe AS. Troponin: the biomarker of choice for the detection of cardiac injury. CMAJ. 173(10):1191-1202, November 2005. [Context Link]
4. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined: a consensus document of the Joint European Society of Cardiology/American College of Cardiology committee for the redefinition of myocardial infarction. Journal of the American College of Cardiology, 36(3):959-969, September 2000. [Context Link]
5. Lim W, Qushmaq I, Devereaux P, et al. Elevated cardiac troponin measurements in critically ill patients. Archives of Internal Medicine, 166(22):2446-2454, December 11-25, 2006. [Context Link]