Q. I have been studying for boards and have run into an issue. I am wondering what markers are used to test if a patient has had an MI. Robbins says that troponin is the best overall but creatine kinase MB is also good. The Dental Decks say that myoglobin is the first to show. Another boards book says that troponin is the first to show up in the blood. I am wondering what you know from a clinical standpoint and if you know the truth behind this issue.
A. There are several laboratory tests (or “markers”) that can be used to detect myocardial infarction. They vary in sensitivity and specificity (especially in the first few hours after an infarct), and you have to correlate them with the patient’s symptoms and other co-existing medical conditions (as well as EKG and angiogram findings).
Here is a list of the tests with some pertinent facts about each:
1. Creatine kinase (total)
Creatine kinase (CK) is an enzyme present in cardiac and skeletal muscle that is released into the blood when cells are injured. An elevation in total CK means you either have skeletal muscle or cardiac muscle injury (in other words, it’s not specific for MI). This is a easy, cheap, widely-available test.
2. Creatine kinase (MB fraction)
CK has three isoenzymes: MM, MB, and BB. CK-MM and CK-MB are both found in cardiac and skeletal muscle, but CK-MB is much more specific for cardiac muscle. CK-BB is found in brain, bowel, and bladder.
CK-MB is a very good test for acute myocardial injury. It’s very specific (you don’t see elevations in CK-MB in other conditions very often), and it goes up very quickly and dramatically after MI (within 2-8 hours). It returns to normal within 1-3 days, which makes it a good test to use in diagnosing re-infarction.
Sometimes the CK total and CK-MB are reported in the form of a “cardiac index”, which is the ratio of total CK to CK-MB. This is a sensitive indicator of early MI.
Just to make things more complicated, it turns out there are two isoforms of CK-MB, conveniently called 1 and 2. CK-MB isoform 2 goes up even before the regular old CK-MB does. The results are usually reported as a ratio of isoform 2 to isoform 1; a ratio of 1.5 or more is a great indicator for early MI. However, to detect these isoforms, you have to do electrophoresis (which is a time-intensive test that has to be performed by skilled people), so the results take a while to get back.
3. Troponin I and T
Troponins are components of cardiac muscle that are released into the blood when myocardial cells are injured. They are very, very specific for myocardial muscle – even more specific than CK-MB. Troponins go up within 3-12 hours after the onset of MI (though the rise is more gradual than the steep bump you see with CK-MB). They remain elevated for a long time (5-9 days for troponin I and up to a couple weeks for troponin T), which means they’re great for diagnosing MI in the recent past (even up to a couple weeks previous to the test) but not so great for diagnosing re-infarction (unless the first infarction was over a few weeks ago). Troponin I is more specific than troponin T (which can be elevated rarely in skeletal muscle injury or renal failure).
4. Myoglobin
Myoglobin is a protein present in both skeletal and cardiac muscle that is released when cells are damaged. It’s a very sensitive indicator of muscle injury, and it’s also the first marker to go up in a myocardial infarction (even before CK-MB). It’s not specific for cardiac muscle, so you wouldn’t want to do this test as your only marker for ruling in an MI (because if the myoglobin is elevated, you wouldn’t know if it was due to an MI or a skeletal muscle injury). It is a good marker, though, for ruling out an MI (if the myoglobin is not elevated, you can be quite sure your patient hasn’t had an MI).
5. Lactate dehydrogenase
Lactate dehydrogenase (LDH) is an enzyme present in many different cells. There are 5 isoenzymes (1-5), each with different specificities for different types of tissue. In the case of cardiac injury, LDH isoenzyme 1 will go up, and usually you’ll see that isoenzyme 1 is higher than isoenzyme 2 (this is called a “flipped” pattern, because under normal circumstances, isoenzyme 2 is present in greater amounts than isoenzyme 1). The LDH starts going up in 12-24 hours following an MI, and it dissipates within a week or two. This test has been supplanted by the other markers discussed above – but you might still see older texts (or board questions, heaven forbid) that discuss this test as a marker for cardiac injury.
So, back to your question. Robbins and the Dental Decks are both correct, in a sense. Robbins is correct in saying that troponins are the best overall markers; they have the best combination of sensitivity, specificity, and ease of test performance of all the markers. CK-MB is second best, and might be the test to do if your lab doesn’t yet do troponins (although most labs do perform troponin assays now). The Dental Decks are also correct in saying that the first marker to go up is myoglobin (although they don’t mention the lack of specificity of this marker, which means that it’s not a good test to use for ruling in MI). The other boards book that says troponin is the first marker to go up is wrong; myoglobin is the first, followed by CK-MB (within 2-8 hours) and the troponins (within 3-12 hours). When in doubt, trust Robbins!
Photo credit: CarbonNYC (http://www.flickr.com/photos/carbonnyc/132922595/)
excellent knowledge,thnx
Thats some great info packed into just a few paragraphs!
Thank you!
Thanks! Glad you found it useful!!
Thank you for sharing your idea! I find it hard too in choosing between CK-MB and troponin
thank you very much,,, it helps a lot@_@
thankyou thankyou…
im surely going to pass my finals.
pathology student rocks my world!!!!!!!!
Another super helpful post. Thanks for making this crystal clear.
Thanks so much, I’m studying pharmacy so really helpful synopsis!
I agree I’m still having a hard time.
Almost all books say that troponin assay is the gold standard when suspecting an MI in the first 24 hours, other books say in the first 8 hours. But in reality when you are having a patient in emergency that is having a heart attack or unstable angina (chest pain) you order the lab to do troponin, Ck-MB, total CK, LDH ratio, myoglobin and PCR and total homocysteine the moment the person arrives. Because the labs take about 30-60 minutes to reveal the results, the best way to start treatment inmediately is EKG with cardiac symptoms (including tachycardia, additional S4 sound, diaphoretic, increased respiration rate, oxugen saturation and chest pain), familial history of CAD, hypercholesterolemia, age, smoking, homocystenuria is reason enough to start treament. You have to start treating them with aspirin/nitroglycerin and oxygen, then antithrombolitic therapy. The best chance of survival is within the first 4 hours after beginning of pain. In reality the cardiac enzymes just establishes the timeline of cardiac injury or the beginning of another infarction and confirms the diagnostic. you don’t wait for the results you do EKG plus symptoms to treat.
Thanks Michael! I really appreciate your clinical input on emergency treatment of MI/angina. We focus on the pathology/laboratory side of things here – so it’s really helpful to get a clinical perspective from a person who actually treats these patients. Nicely written too – your last two sentences sum up your discussion perfectly.
You are most welcome Kristine. But I still have confounding problems with what boards books state about cardiac enzymes. All board books just put troponin as the best marker which is true but with what I don’t agree and what most books state is that troponin is the best marker in the first 8 hours and it is the first one to peak.Troponin in some books states 3-6 hours, others put troponin 4-8 hours, others put it as 3-12 hours. I read 5 recent medical journal articles(2009-2017) that state that neither CK-MB nor Troponin are as good indicators for MI in the first 6 hours. Why? Because it takes 4-12 hours for heart tissue to show necrosis. The presence of cardiac markers in blood is as sign of tissue death and inflammation (this is the difference between apoptosis and necrosis), but if it takes 4-8 hours for troponin to start increasing and remember to asses a myocardial infarction properly you have to have the enzyme levels above the 99th percentile once and in the case of CK-MB show rise and fall pattern. A person could be having a heart attack with no enzyme elevation less than 6 hours after presentation of chest pain. So this is why troponin test and CK-MB are not useful in the first 6 hours of onset of ischaemia symptoms and that is why almost all books are wrong. This is why you do 3 separate cardiac enzyme test in a span of 24 hours. At the beginning, 6 hours later and at 24 hours(the American cardiology Association states every 6 hours in a 24 hour period). In reality as well stated above, myoglobin is the first to peak (2-3 hours), other books state as early as 1.5 hour. My first aid book ignores myoglobin completely. Myoglobin rise only indicates muscle damage and that is reason enough to include myocardial infarction as a possible presumptive diagnosis not definitive but presumptive. A person who does not have myoglobin levels up is most likely to not having an MI, but that is why you do another test after 6 hours of management and treatment. There is a lot of discusion about another marker called heart type fatty acid binding protein which rises 1-2 hour after heart damage, but it has not been discussed extensively. My other problem I have is the initial timeline when comparing biomarkers CK-MB and troponin. Some state that Ck-MB rises first (3-6 hours)and troponin starts second (4-8 hours), other state that they started about the same (3-8 hours) and other put troponin first (3-6) and CK-MB (4-8_ later. This is a problem. For all intented purposes if you get an exam question asking for the first marker rising or 6 hours after onset until 24 hours troponin is the best cardiac biomaker(close to 95% sensitivity and 90% specificity). Between 24-48 hours Ck-MB is the best marker.