Cardiac Biomarkers, Cardiac Enzymes, and Heart Disease

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Cardiac enzymes (the old name), or cardiac biomarkers (the new name), are blood tests that are used to detect damage to heart muscle cells. These tests are most useful in diagnosing myocardial infarctions (heart attacks), but they are now also being used to detect heart cell damage from other causes, as well — such as from traumatic injury or myocarditis

Cardiac biomarkers are proteins from heart muscle cells that have leaked out into the bloodstream after an injury to the cardiac muscle.

Creatine kinase and troponin are the two proteins currently measured in biomarker tests.

How the ”Cardiac Enzyme Test" Became the “Cardiac Biomarker Test"

Because creatine kinase was the first cardiac protein widely used by doctors to help diagnose heart attacks, and because creatine kinase is an enzyme, blood tests for diagnosing heart attacks were originally known as cardiac enzyme tests. (An enzyme is a protein that helps bring about a specific biochemical reaction.)

However, troponin has become the more important blood protein used for detecting heart cell damage, and troponin is not an enzyme. Rather, it is a complex of regulatory proteins important to the contraction of cardiac muscle. When troponin in found the bloodstream, it is a reliable indicator that heart cell damage has occurred. This is why most doctors now refer to “biomarker tests” instead of “enzyme tests.”

How are Biomarker Tests Used?

Measuring biomarkers is usually an important early step in diagnosing a heart attack.

Today, troponin is the preferred biomarker used for this purpose, because it is a more specific marker (and also a more sensitive marker) for heart muscle damage than creatine kinase. Most doctors will still measure both troponin and creatine kinase levels when a heart attack is suspected — but whether the creatine kinase measurement still adds much to clinical care is questionable.

When a heart attack occurs, the release of heart cell proteins into the bloodstream usually follows a typical pattern over a period of hours. So, confirming that a heart attack has occurred often requires several biomarker blood tests over a period of time, demonstrating a typical rise and fall of the biomarkers.

Creatine kinase is released into the bloodstream 4 to 6 hours after heart cell damage occurs, and peak blood levels of creatine kinase are seen after 24 hours. Elevated creatine kinase levels usually, but not always, indicate heart muscle damage. Creatine kinase levels sometimes can be increased with damage to other kinds of cells as well, since it is also present in non-cardiac muscle cells.

Troponin is released into the bloodstream 2 to 6 hours after heart cell damage, and blood levels peak in 12 to 26 hours. Elevated levels of troponin are regarded as a more reliable indicator of heart muscle damage than elevated creatine kinase levels.

Because troponin is an "earlier" marker of cardiac cell damage than creatine kinase, and because it is more accurate at indicating heart cell damage than creatine kinase, troponin is the preferred marker today for diagnosing heart attacks.

When Are Biomarkers Most Helpful?

When a patient has a typical myocardial infarction with ST-segment elevation on the ECG (a "STEMI"), the ECG pattern itself, along with clinical symptoms, are usually enough to make the correct diagnosis.

So with STEMI it is generally not necessary for the doctor to wait for the results of the biomarker test before initiating treatment.

Biomarkers are more helpful in people with acute heart attacks who do not have a typical STEMI, that is, in people who are having an "NSTEMI". With an NSTEMI the ECG changes tend to be relatively non-specific, so that it is much more difficult to make the correct diagnosis based on the ECG and symptoms alone. Here, the biomarker test is often critical in deciding whether acute therapy for a heart attack is required.

In people having an NSTEMI, the initial biomarker blood test may be in the "indeterminate" range.

In this case, a second blood test a few hours later will reveal whether troponin levels (or creatine kinase levels) are displaying the typical rise-and-fall pattern seen with heart attacks.

In recent years, a high-sensitivity troponin assay has been developed that, in many people having an NSTEMI, allows the diagnosis to be made a single blood test, thus permitting treatment to begin earlier than otherwise might be advisable.

What Causes “False” Elevation of Biomarkers?

Not all elevations in cardiac biomarkers indicate a heart attack.

Creatine kinase levels can become elevated with any muscle injury, or with damage to the brain or lungs, or with liver or kidney disease.

Elevations in the troponin blood level is really quite specific for cardiac cell damage, so strictly speaking, there is no such thing as a “false” elevation of troponin. However, damage to cardiac cells can occur for reasons other than an acute heart attack. These conditions may include heart failure, myocarditis, rapid atrial fibrillationsepsiscoronary artery spasmaortic dissectionstress cardiomyopathy, or severe pulmonary embolus.

This is why the diagnosis of a heart attack relies not on a single blood test, but also on clinical symptoms, ECG changes, and (often) on a pattern of biomarker elevations suggesting acute heart cell injury.

Sources:

Mills NL, Churchhouse AM, Lee KK, et al. Implementation of a Sensitive Troponin I Assay and Risk of Recurrent Myocardial Infarction and Death in Patients with Suspected Acute Coronary Syndrome. JAMA 2011; 305:1210.

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.

Thygesen K, Mair J, Katus H, et al. Recommendations for the Use of Cardiac Troponin Measurement in Acute Cardiac Care. Eur Heart J 2010; 31:2197.

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