Much confusion exists about troponin values and their implications including the meaning and significance of the 99th percentile level. Let’s start with the 99th percentile.
Percentiles of a lab test tell us how likely the test result is truly abnormal. At the 50th percentile, the test result has only a 50/50 chance of being truly abnormal; at the 95th percentile there is a 95% probability the result is truly abnormal; at the 99th percentile the result has a 99% chance of being truly abnormal and conversely only a 1% chance that it is “normal” for that particular patient. For troponin, a result higher than the 99th percentile of the test has been selected as “abnormal”, indicating myocardial injury.
Troponin is a cardiac protein that is released when myocardial tissue is damaged from any cause. Myocardial infarction is just one of many causes and due to ischemia. Other causes not due to ischemia include heart failure and non-cardiac causes include sepsis. See “Causes of Elevated Troponins” below.
Troponin exists in two forms: troponin I (cTnI) and troponin T (cTnT), the test for the former being more accurate than the latter. The “c” stands for cardiac. Because troponin levels differ between men and women, the result should be reported by gender.
High-sensitivity troponins (hs-cTn) are recommended since myocardial infarction can be rapidly ruled out within 1-2 hours of presentation so they can be discharged from the ED earlier than with standard troponins which can take up to 6 hours. Both hs-Troponin I and T tests perform similarly in the acute care setting.
There are currently eight FDA-approved manufacturers each with its own “normal” range and the 99th percentile level. The enhanced sensitivity of high-sensitivity troponins has resulted in more “positive” results than with standard troponins.
What is considered significant? Troponin levels are much different than other lab tests, for example electrolytes such as sodium. If a patient has a higher or lower sodium than the normal reference range, it usually indicates hyper- or hyponatremia.
Not so with troponins. Although levels higher than the 99th percentile upper reference limit indicate “myocardial injury”, this does not equate to myocardial infarction.
The higher the troponin levels above the 99th percentile URL, the greater likelihood of myocardial infarction. For example, the manufacturer’s suggested reference range (gender-specific) for one of the high-sensitivity troponin tests is:
Therefore, 21 and above is the upper reference limit (URL) and the 99th percentile for males, and 15 and above is the URL and the 99th percentile for females.
For this particular hs-troponin, the critical action values (also gender-specific) are:
The troponin CAV (critical action value) usually means that lab calls the patient care area and verbally reports the result to a licensed professional. Does a CAV always equate to myocardial infarction? No. Significantly elevated troponins are associated with causes not due to myocardial infarction, such as acute heart failure, myocarditis, and other non-ischemic causes. Elevated troponins due to non-ischemic causes would be considered acute or chronic “myocardial injury” only.
There is no single troponin value above the 99th percentile that indicates myocardial infarction—the clinical context is critical to the interpretation. Elevated troponin is only one component of diagnosing myocardial infarction and is only used as part of the total clinical picture for the provider who is making the diagnosis. Other factors to be considered are specific symptoms, patient’s age, existence or risk of coronary artery disease, EKG abnormalities, positive cardiac imaging or additional studies or workup, and co-existing non-ischemic and non-cardiac causes.
Treatment for type 1 myocardial infarctions (that do not require coronary intervention) typically include aspirin, beta blockers, ace inhibitors, anticoagulants or antithrombotics, while treatment for type 2 myocardial infarctions is correction of the underlying cause.
Query for myocardial infarction? It would be inappropriate to query a provider for myocardial infarction for elevated troponins only. It is important to review the entire record for evidence of ischemia considering the clinical context. For example, it would be inappropriate to query if the provider addresses the elevated troponins and documents for example: “Troponins flat” (indicates chronic myocardial injury) or “no ischemic changes” based on the EKG and cardiac studies. Or, if the clinical picture supports a non-ischemic diagnosis as the probable cause (see below table).
In summary, elevated troponin levels above the 99th percentile indicate myocardial “injury” only. Acute myocardial infarction would be indicated if the values are significantly elevated with rise/fall AND the clinical picture includes indicators of ischemia as evidenced by symptoms, EKG abnormalities, or positive cardiac studies.
|Due to Ischemia = Myocardial Infarction
|1. Myocardial infarction (Type 1):
due to coronary artery disease and obstruction/ thrombus
|2. Myocardial infarction (Type 2) due to oxygen imbalance caused by:
· Severe anemia
· Atrial fibrillation
· Sustained tachyarrhythmia
· Severe bradycardia
· Severe hypertension
· Coronary artery spasm
· Coronary embolism
|Not due to ischemia = Myocardial Injury only
|1. Cardiac Causes:
· Heart failure
· Cardiomyopathy (any type)
· Takotsubo (stress) syndrome
· Coronary revascularization
· Cardiac procedure, other
· Catheter ablation
· Defibrillator shocks
· Cardiac contusion
|2. Non-Cardiac (Systemic) Causes:
· Chronic kidney disease
· Pulmonary hypertension
· Amyloidosis, sarcoidosis
· Chemotherapy agents
· Pulmonary embolism
· Critically ill patients
· Strenuous exercise
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