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).
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 rulingoutan MI (if the myoglobin is not elevated, you can be quite sure your patient hasn’t had an MI).
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, the LDH will go up, and usually you’ll see that isoenzyme 2 is higher than isoenzyme 1 (this is called a “flipped” pattern, because under normal circumstances, isoenzyme 1 is present in greater amounts than isoenzyme 2). 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!