Abstract
Perivascular adipose tissue (PVAT) surrounding the human coronary arteries, secretes a wide range of adipocytokines affecting the biology of the adjacent vascular wall in a paracrine way. However, we have recently found that PVAT also behaves as a sensor of signals coming from the vascular wall, to which it reacts by changing its morphology and secretory profile. Indeed, vascular inflammation, a key feature of vascular disease pathogenesis, leads to the release of inflammatory signals that disseminate into local fat, inducing local lipolysis and inhibiting adipogenesis. This ability of PVAT to sense inflammatory signals from the vascular wall, can be used as a “thermometer” of the vascular wall, allowing for non-invasive detection of coronary inflammation. Vascular inflammation induces a shift of PVAT's composition from lipid to aqueous phase, resulting into increased computed tomography (CT) attenuation around the inflamed artery, forming a gradient with increasing attenuation closer to the inflamed coronary artery wall. These spatial changes in PVAT's attenuation are easily detected around culprit lesions during acute coronary syndromes. A new biomarker designed to captured these spatial changes in PVAT's attenuation around the human coronary arteries, the Fat Attenuation Index (FAI), has additional predictive value in stable patients for cardiac mortality and non-fatal heart attacks, above the prediction provided by the current state of the art that includes risk factors, calcium score and presence of high risk plaque features. The use of perivascular FAI in clinical practice may change the way we interpret cardiovascular CT angiography, as it is applicable to any coronary CT angiogram, and it offers dynamic information about the inflammatory burden of the coronary arteries, providing potential guidance for preventive measures and invasive treatments.
Highlights
Ischemic heart disease remains the leading cause of death in uppermiddle and high income economies.[1]
We have shown that the secretome of Perivascular adipose tissue (PVAT) contains anti-inflammatory and antioxidant substances like adiponectin, and it may host defense mechanisms for the vascular wall.[21,22]
We have recently shown that the inflamed human vascular wall releases inflammatory cytokines like TNFα, IL-6 and IFNγ, which diffuse into the perivascular space, triggering a local “cachexia-type” response by the adipocytes within PVAT.[17]
Summary
Ischemic heart disease remains the leading cause of death in uppermiddle and high income economies.[1]. It is time to consider developing “companion diagnostics”, i.e. tests that will allow us to tailor deployment of these new and expensive therapeutics in well-defined populations who can derive maximum benefit, entering the era of personalized (or precision) medicine. New diagnostic tests allowing detection of the “vulnerable patient” will enable application of targeted treatments in primary or secondary prevention, to prevent the development of clinical cardiovascular disease, including myocardial infarction. These tests might allow identification of patients with severe but stable CAD in whom unnecessary invasive therapy might be avoided. Understanding the potential implications of these new diagnostic tests requires knowledge of the factors behind “residual cardiovascular risk”, not currently captured by the clinical or biochemical risk scores
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