Perivascular Fat Imaging to Predict Coronary Artery Disease Risk

Perivascular fat attenuation index (FAI) measured by CT imaging can be an effective tool to detect and monitor coronary inflammation and risk of coronary artery disease, according to a recent study published by scientists at University of Oxford. The study appeared in Science Translational Medicine.

Perivascular Fat CT Imaging Vs Current Methods To Predict CAD Risk

The authors of the study believe that perivascular fat imaging is superior to currently available methods for the following reasons

• Blood markers such as C-reactive protein and proinflammatory cytokines are not directly involved in the formation of atherosclerotic plaque, or local processes and cannot detect unstable plaques
• Existing noninvasive [computerized tomography angiography (CTA) or 18F-fluorodeoxyglucose (18FFDG)–positron emission tomography (PET)] and invasive (intravascular ultrasound and optical coherence tomography) imaging tools do not provide accurate information on coronary inflammation.
• The only established noninvasive imaging biomarker of predictive value in primary prevention is Coronary calcium scoring (CCS), but it identifies only irreversible changes in the vessel wall that are not altered by interventions to reduce CAD risk, such as statins or lifestyle changes.

To overcome the gaps in the existing tools, the research team has developed an imaging technique that measures the size and quantity of the fat surrounding the coronary arteries and calculate the perivascular fat attenuation index (FAI) that occurred in response to coronary inflammation. Since this tool identifies early CAD, appropriate interventions may help in preventing progression or may even reverse the CAD.

Perivascular Fat Measurement With Histological And PET Validation

• For the study, the team performed perivascular fat CT scans that measured FAI in 453 patients undergoing cardiac surgery, which measured adipocyte content and size.
• On perivascular imaging, higher FAI was found to be associated with greater degree of coronary inflammation (confirmed by FDG uptake on PET).
• Absence of inflammation promotes lipid accumulation within the adipocyte and allows differentiation to more larger and more mature form. This is a good sign and associated with low FAI
• Inflammation reduces lipid accumulation, and slows down differentiation to more mature adipocyte. This is associated with a higher FAI, predisposing to unstable plaques, plaque rupture and cardiac events.
• The above CT findings were validated with samples of arterial tissue obtained during surgery which were sent for histological analysis to confirm the size and fat content of the adipocytes as described above.
• Presence of coronary inflammation was also confirmed by tissue uptake of 18F-fluorodeoxyglucose in positron emission tomography, which is the gold standard method to noninvasively assess tissue inflammation in vivo.
• The team went on to measure FAI in 273 additional patients (156 with and 117 without significant coronary plaques) in a clinical setting and who underwent coronary angiography.

The FAI remained stable in those with stable plaques but increased around unstable lesions preceding a cardiac event.

Another notable finding was that the FAI was much higher immediately adjacent to the inflamed artery and lowered (although still high) a short distance away suggesting that paracrine stimuli from the vessel wall may play a role.

The findings of the study suggest that inflammation reduces perivascular fat accumulation leading to a higher FAI and local vascular stimuli play a part in these processes.

"Our heart arteries are surrounded by fat. The fat detects inflammation, becoming more watery and less fatty as it sits next to an inflamed artery," said Charalambos Antoniades, a senior author on the paper at the University of Oxford.

Inflammation And Atherogenesis (CAD) – A Crucial Link

• Inflammation is a key component in atherogenesis, and any tool that can accurately detect vascular inflammation would be ideal to detect high risk lesions and put in place appropriate interventional measures.
• Inflammation also characterizes unstable atherosclerotic plaques, which may rupture, leading to major cardiovascular events such as heart attacks and strokes.
• Noninvasive and early detection of vascular inflammation will be a game changer in the field of preventive cardiology, which is what this study hopes to have achieved.

Scope of The Study And Perivascular Fat Imaging Test

• The CT scan is a simple non-invasive test that can be done in an outpatient setting and picks up early subclinical CAD.
• Clinicians could detect changes in FAI to determine whether patients are responding to treatment, or make appropriate interventions in people at risk for arterial plaque rupture.

"By detecting those individuals who don't have narrowings, but are in the process of developing them, we may deploy interventions early enough to prevent heart disease. For example, we could deploy [cholesterol-lowering] statins in patients who don't meet the current criteria," Antoniades said.

"The key advantage of this method is to be able to detect early changes in blood vessels that precede cardiovascular disease," said Caitlin Czajka, an associate editor at Science Translational Medicine.

What Does the Future Look Like?

• Clinical follow up studies to establish the predictive accuracy of FAI for cardiac events are ongoing and the authors expect to publish the findings by the end of 2017.
• Currently, although the CT test is in itself simple, the calculation of the FAI from imaging studies is a long drawn out procedure, needing a skilled technician. The authors are working to make their software more user friendly and accessible.

In conclusion, according to Keith Channon, a study author and senior researcher at the University of Oxford, "We are very excited and proud of our findings. This has really been the holy grail of the management of coronary artery disease, which has, up until this point, not been possible."

References:

1. Noninvasive Imaging Gets to the Heart of Cardiac Disease Risk - (https://www.aaas.org/news/noninvasive-imaging-gets-heart-cardiac-disease-risk)

Source-Medindia