At present, the definitive diagnosis of aortic dissection relies on CT scan imaging, which provides detailed views of the aorta. However, these tests are not always readily available, and researchers are also looking for ways to avoid overloading radiology departments with unnecessary scans, especially when a faster, simpler blood test might provide early answers.
Some patients, especially those with inherited risks, may not show visible signs of a problem on a scan. This highlights the need for a blood-based biomarker that can help detect and manage AD earlier and more effectively.
What Are Biomarkers?
Biomarkers are substances found in blood, tissue or other body fluids that can indicate a disease or condition. In aortic dissection, certain biomarkers can reflect the damage to the aortic wall, inflammation, clot formation or genetic changes. Researchers hope these markers can be used to identify people at risk, confirm the diagnosis quickly, guide treatment, and monitor outcomes. A good biomarker would be easy to test, reliable, and specific to AD.
Key Protein Biomarkers
Several proteins have been identified as potentially useful in detecting or predicting AD. Among the most well-known is D-dimer, which rises in the blood when a clot forms. If a patient presents with chest pain and has a normal D-dimer level, AD is unlikely. However, high levels may support the diagnosis, especially if measured within the first 24 hours.
Another promising protein is sST2, which is linked to inflammation. In studies, sST2 levels were significantly higher in people with acute AD compared to those with heart attacks or clots in the lungs. This makes it a strong candidate for ruling in or out AD.
D-dimer is a blood marker that indicates clot formation. High levels can support a diagnosis of AD, especially within the first 24 hours of symptom onset.
sST2 is a protein involved in inflammation. It has shown high accuracy in distinguishing AD from heart attacks and pulmonary embolism.
Adipokines and Cholesterol-Related Markers
Adipokines, such as adiponectin and ANGPTL8, are produced by fat tissue and influence inflammation and blood vessel health. High levels of ANGPTL8, in particular, have been associated with a greater risk of AD, especially when combined with other inflammatory markers.
Lipid-related proteins, such as sLOX-1, are involved in cholesterol metabolism. sLOX-1 is notably higher in AD than in other heart conditions, making it useful in distinguishing AD from other causes of chest pain. LPC (lysophosphatidylcholine), another lipid marker, tends to decrease in AD and may help classify the type and severity of dissection.
Adiponectin and ANGPTL8 are linked to inflammation in blood vessels. They may help identify people at risk before a dissection happens.
sLOX-1 and LPC are involved in cholesterol processing and inflammation. They can help differentiate AD from other heart conditions.
Homocysteine and Smooth Muscle Markers
Homocysteine (Hcy) is a naturally occurring amino acid. Higher levels are associated with damage to blood vessels and have been observed in patients with aortic conditions such as Marfan syndrome. It may also contribute to the weakening of the aortic wall, increasing the risk of dissection.
Markers such as smMHC (smooth muscle myosin heavy chain) and calponin are released when the muscle layer of the aorta is damaged. smMHC, in particular, rises sharply after dissection, especially in cases involving the upper part of the aorta. These markers may help pinpoint the location and timing of the tear.
Homocysteine levels are often raised in people with Marfan syndrome or aortic dilatation, suggesting a higher AD risk.
smMHC (smooth muscle myosin) rises quickly after a dissection, especially in cases where the tear is near the heart.
Creatine kinase-BB and calponin also increase after AD, helping potentially confirm the diagnosis.
Cardiac and Inflammatory Proteins
Biomarkers used in heart disease, such as NT-proBNP and S100A1, could also play a role in AD. NT-proBNP is linked to heart failure and may predict complications during or after surgery for AD. S100A1 is associated with heart muscle damage and is found at higher levels in patients with AD involving the heart valves or lining.
Ischemia-modified albumin (IMA), although not specific to AD, rises when tissues are starved of oxygen and may be useful in identifying patients at risk of poor outcomes, particularly when used alongside other markers.
NT-proBNP, a heart failure marker, and S100A1, related to heart function, can provide information about prognosis.
Ischemia-modified albumin (IMA), though not specific to AD, may predict poor outcomes if levels are high soon after onset.
Markers from the Aortic Wall
The structure of the aortic wall includes proteins like collagen, elastin, and proteoglycans. When a dissection occurs, these substances break down and enter the bloodstream. Matrix metalloproteinases (MMPs), particularly MMP-8 and MMP-9, play a role in breaking down the wall’s structure and are often elevated in AD. Measuring these could give insight into the severity of the dissection.
Soluble elastin fragments (sELAF) indicate that the elastic part of the wall has torn. These levels rise very soon after symptoms begin and can remain elevated for days, making them potentially useful in early diagnosis. Tenascin-C (TNC) and aggrecan are also linked to tissue damage and have shown promise in predicting which patients may have worse outcomes.
Matrix metalloproteinases (MMPs). Higher levels, especially MMP-8 and MMP-9, suggest active damage in AD.
Elastin fragments (sELAF) and Tenascin-C (TNC) are released when the aorta tears. They show promise in identifying AD early and predicting severity.
Aggrecan and vinculin also reflect damage to the structure of the aortic wall.
Genetic and Cell Structure Markers
Proteins such as vinculin, which support the cell’s structure, and TGF-β, which regulates cell growth, are altered in AD. Vinculin levels rise quickly after dissection and may reflect the body’s attempt to repair the vessel wall. TGF-β is especially important in inherited conditions like Marfan syndrome and helps explain why some families are more prone to AD.
Other genetic markers like OPG/TRAIL ratios and β2-GP1 may help predict survival after a dissection and could be used in future risk assessments.
TGF-β, OPG/TRAIL ratio, and β2-GP1 reflect underlying genetic or inflammatory changes and could predict long-term outcomes.
Uric Acid
High levels of uric acid, commonly known in relation to gout, have been found more often in patients with AD. Although it is not specific to AD, it may point to broader metabolic issues that contribute to the weakening of the aorta.
Uric acid, a common marker for gout and kidney issues, may be linked to a higher risk of AD.
RNA-Based Biomarkers
Researchers have discovered that small RNA molecules, called microRNAs (miRNAs), play a role in regulating genes linked to blood vessel structure. Specific miRNAs, such as miR-29, miR-30, and miR-143/145, control proteins in the aortic wall. Their abnormal levels may suggest changes that might lead to dissection.
Panels of multiple miRNAs have shown high accuracy in distinguishing AD from other conditions. Some are elevated, while others are reduced, depending on the stage and location of the dissection. These are currently being studied as potential blood tests.
Specific miRNAs (like miR-29, miR-30, and miR-143/145) are involved in maintaining the aorta’s strength and structure.
DNA Methylation and Cell-Free DNA
In addition to RNA, fragments of cell-free DNA (cfDNA) can be found in the blood of AD patients. These fragments come from damaged cells in the aorta. Researchers have also found differences in DNA methylation patterns, chemical changes that affect how genes are turned on or off, in AD patients. These patterns could help detect the disease early, even before symptoms begin, especially in those with genetic risks.
The charity is currently funding a research project at the University of Cambridge investigating the role of cfDNA methylation in the diagnosis of acute aortic dissection, with the aim of developing a novel biomarker to aid timely and precise diagnosis.
Blood tests detecting changes in DNA methylation could offer a non-invasive way to detect or even predict AD, especially in people with inherited risks.
Inflammatory Markers
Inflammation plays a major role in AD. Proteins like IL-6, IL-10, and C-reactive protein (CRP) rise during the early stages and could help doctors assess how serious the dissection is. IL-6, in particular, has a wide time window for detection and may help monitor patients after treatment.
Ceruloplasmin (CP) is another inflammatory protein that increases in AD and may help distinguish between different forms of the disease. It has shown high accuracy in early studies and may also relate to blood clots within the aorta.
IL-6 and IL-10 are inflammatory proteins that rise during AD and are linked to worse outcomes.
Ceruloplasmin (CP) is another marker that may help identify more serious or complicated dissections.
Summary
While CT remains the gold standard for diagnosing aortic dissection, there is a growing body of research into biomarkers that can improve early detection, guide treatment, and predict outcomes. No single test has yet replaced imaging, but combinations of markers, especially proteins, miRNAs, and cfDNA, are showing great promise.
In the future, a simple blood test may help doctors detect AD sooner and manage it more effectively, especially in people with inherited risk. Until then, awareness of symptoms and timely medical evaluation remain essential. Patients with a family history of aortic disease or genetic conditions like Marfan syndrome should consult their doctor about screening options.
