Detecting coronary artery inflammation by imaging the surrounding fat, and its association with coronary artery disease

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Atherosclerosis is the build-up of cholesterol deposits (plaque) within the walls of the coronary arteries which are the blood vessels supplying heart muscle. If the plaque ruptures, it can cause a reaction and block off the vessel causing a heart attack. Vessel inflammation is a major contributor to both plaque formation and rupture. The fat (adipose tissue) surrounding the coronary arteries is a rich source of inflammatory chemical messengers, many of which are the same as those found in plaques, and in particular plaques considered to be vulnerable to rupture, called high risk plaques (HRP). Computed tomography coronary angiography (CTCA) is a widely used investigation for the assessment of plaque as well as HRP. Inflammation of the coronary arteries, however, is not as easily assessed. Specialised imaging methods are limited by cost, availability and image resolution. Circulating blood markers of inflammation do not reflect what happens at the level of the vessel. Therefore, the ability to measure a regional marker of inflammation is highly desirable and may improve risk prediction beyond the current measures that CTCA provides. Pericoronary adipose tissue (PCAT) is the layer of fat immediately adjacent to the coronary artery wall. It has been demonstrated that inflammatory chemical messengers cross between the vessel and adjacent fat in both directions. Therefore, PCAT may act as a sensor of vessel inflammation, as well as a driver of plaque formation. A recent seminal scientific study showed that exposure to inflammatory chemical messengers stops fat cells from maturing. The density (attenuation) of PCAT can be accurately assessed on CTCA, and has been validated as a marker of inflammation. A more negative fat attenuation represents less inflammation (fat-rich tissue) whereas higher values suggest greater inflammation (less fat maturation). With increasing evidence of the benefits of anti-inflammatory medications to reduce cardiovascular events, the use of CTCA to detect vascular inflammation as well as its established role in plaque analysis represent an ideal tool for a single, non-invasive imaging test to guide future research into coronary plaque formation and vulnerability. Our hypotheses are: 1. Patients with heart attacks will demonstrate lower PCAT attenuation than stable and asymptomatic patients. 2. Persisting high PCAT attenuation predicts plaque progression and vulnerability. 3. The baseline PCAT attenuation at sites of HRP predicts future heart attacks. This study aims to demonstrate that PCAT attenuation will exhibit a gradient of increasing inflammation from normal vessel to HRP. We will aim to define a threshold at which PCAT attenuation predicts HRP presence and progression, to then guide future studies using anti-inflammatory medications. The long-term goal is the ability to detect inflammation in normal vessels free of plaque and therefore are at risk of accelerated plaque progression.

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