Clinical Quick Reference Monthly / January & February 2024 / The Biomarker Revolution
BIOMARKERS IN CARDIOLOGY 2024 EDIT
A biomarker is a term used to describe a wide range of medical symptoms that are objectively measurable and can be gauged from the outside of the patient’s body (biomarkers are also called “biological markers”).
Cardiac Biomarkers
What is a cardiac biomarker?
A cardiac biomarker is a naturally occurring substance that is released into the blood stream when the heart muscle undergoes injury or stress.
History and Basic Review of Cardiac Biomarkers in Modern Medicine
Cardiac enzymes have been in use since the middle of the 20th century.
Clinicians commonly used them in the assessment of acute myocardial infarction (AMI). Modern biomarkers are more sensitive and focused than the biomarkers of the past, as such many from that time have lost clinical relevance.
The first clinical biomarker used in AMI diagnosis was AST. It had been postulated by Ladue et al. in 1954 that AST released from cardiocytes (cells) experiencing necrosis could be helpful in identifying cases of acute myocardial infarction (“heart attack”).
Over time, AST clinical standing diminished. This occurred because AST is not specific to cardiac myocytes.
LDH then emerged as a potential biomarker for detection of MI. LDH increases in the blood 6 to 12 hours after an AMI, peaks within 24 to 72 hours, and returns to normal after 8-14 days.
Studies indicated that LDH was also not a specific marker for cardiocyte damage, and found that it could be elevated in many other conditions. After these findings, LDH also lost clinical standing in myocardial infarction diagnosis.
Myoglobin is a hemoprotein that is found in cardiac and skeletal muscle tissue. Because of its low molecular weight, it can be detected in the blood one hour after myocardial tissue injury. It reaches a maximum in 4–12 hours, and almost immediately returns to baseline. As a result, this protein has diagnostic value when measured together with the cardiac enzyme, CK-MB, for faster detection of acute myocardial infarctions.
Although troponins today have largely replaced myoglobin in AMI detection, myoglobin assays play a role in the diagnosis of rhabodomyolysis (condition where there is injury to striated muscle fibers).
Another marker, known as Heart-type fatty acid-binding protein (H-FABP) has also been studied.
The biomarker is involved in fatty acid metabolism in cardiac myocytes.
In research, the sensitivity of H-FABP in detecting AMI in patients who presented for care within 4 hours of their symptom onset was 60%. This was significantly higher than that of troponin and CK-MB.
Issues with specificity, as noted with other previously used biomarkers, were found when additional clinical research was conducted.
Key Cardiac Biomarkers
The principal cardiac biomarkers currently utilized in the diagnosis of acute myocardial ischemia are troponins. This is a protein found in the cells of the heart muscle.
The troponin complex, is a complex of three proteins. These regulatory proteins (troponin C, troponin I, and troponin T) are essential for muscle contraction.
Troponins rise in the majority of cases of AMI within 2 to 3 hours. A troponin test is ordered to measure levels of troponin T or troponin I proteins in the blood. That is because these proteins are released when the heart muscle has been damaged.
(CK-MB still retains some diagnostic value in both cardiac and noncardiac conditions. The marker can be detected in the serum studies 4 hours after injury. It peaks by 24 hours, and then normalizes in about 48 to 72 hours.)
Analysis and Application--- What Do I Need to Know?
A cardiac troponin test is the first-line serum test for assessing patients with suspected AMI.
These proteins can be identified in both cardiac and skeletal tissues.
Remember that the three subunits that make up the troponin complex are troponin C, troponin I, and troponin T.
The troponin I and troponin T in the cardiac muscle differ structurally from those found in skeletal muscles, making them more specific indicators of damage to cardiac myocytes.
The blood levels of troponin T and troponin I increase as early as 4 hours after the onset of symptoms in AMI. They go on to peak in 24 to 48 hours and can continue to rise for several days. Troponin T and troponin I are quite helpful in identifying first ischemic episodes. In later cases of reinfarction they may lose some reliability.
Clinical Significance
When assessing patients who may have AMI, cardiac troponin evaluation is recommended.
This is directly related to their level of specificity. In the US, an extremely sensitive troponin assay was authorized in 2017.
CK-MB testing should not be the primary diagnostic indicator evaluated in suspected acute myocardial infarction. CK-MB is far less sensitive and specific than cardiac troponins.
In the absence of cardiac troponin tests, CK-MB could be helpful in assessing for myocardial infarction.
It is also important to remember that troponin levels may not be as helpful in assessing for reinfarction as they stay elevated in the patient’s blood for several days following MI.
The fifth-generation Elecsys Troponin T STAT test (Roche), was the first "new generation" troponin assay authorized for use in the US, receiving 510(k) clearance from the US Food and Drug Administration (FDA) in 2021. Many other parts of the world had been using these high-sensitivity assays for years.
In the industrialized world, acute myocardial infarction (AMI) is one of the leading causes of mortality. Over a million individuals die from the disease each year in the United States, where its prevalence is close to 3 million.
Non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI) are the two categories into which AMI falls. And while cases of unstable angina can resemble NSTEMI, it is normal cardiac markers that help distinguish such cases from infarction.
MI Criteria
Per 2023 NIH documentation, MI is diagnosed when 2 of the following criteria are met:
Symptoms of ischemia
New ST-segment changes; or a left bundle branch block (LBBB)
The presence of pathological Q waves on electrocardiogram (ECG)
New regional wall motion abnormality as identified on imaging studies
The presence of an intracoronary thrombus at autopsy/ or angiography
(See more at their point of care site: https://www.statpearls.com/point-of-care/17160).
Every patient presenting with chest discomfort, should receive early and timely care. Women may exhibit unusual symptoms, such as vertigo or stomach discomfort, and may not have chest pain. ECG is an extremely targeted diagnostic tool for evaluating cases of potential MI.
Helpful Videos:
Understanding Unstable Angina and Myocardial Infarction
Troponin Blood Test: Interpret Elevated Troponin Levels , Normal Range & High Sensitive Troponin
High Sensitivity Troponin
Resources:
CDC,
Medline,
NIH.
Cardiac Biomarkers
Saikrishna Patibandla; Kush Gupta; Khalid Alsayouri. Last Update: November 17, 2023.
Point of care site:
Disclaimer:
This study guide resource listing of medications is not intended to be used as medical advice. Note that products used tends to vary from institution to institution. Always pursue and follow the advise of your healthcare provider, facility protocols or supervising agency in matters of health issues or problems. Call 911 in case of emergency.