Nick S. Nurmohamed et al. Catherine Cantlay Alfateh Sidahmed Andrew D. Choi
Atherosclerotic cardiovascular disease (ASCVD) is a systemic disease initiated by an endothelial influx of lipid particles, including low-density lipoproteins (LDL), with subsequent endothelial activation via local recruitment of inflammatory cells. This local process – elicited by age-determined exposure to genetic, environmental, and lifestyle ASCVD risk factors – is the first step of a process that will lead to a chronic, low-grade systemic inflammatory state. Prolonged exposure of the endothelium to ASCVD risk factors and this inflammatory state will increase the number of vulnerable plaques and may eventually lead to plaque rupture resulting in ASCVD events.
Multiple efforts have focused on measuring systemic and endothelial inflammation. Ridker et al. showed that C-reactive protein (CRP) levels were positively associated with future ASCVD events. Subsequent trials, including the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), proved the existence of a targetable, important residual inflammation component (later denoted as the NLRP3 inflammasome) through treatment with rosuvastatin. On the imaging side, investigators from the Framingham Heart Study, were the first to show that pericardial and visceral fat volumes from non-contrast CT scans were associated with increased levels of inflammatory markers such as CRP and IL-6 as independent risk factors for ASCVD. Using coronary CT angiography (CCTA), it was discovered that measurement of pericoronary adipose tissue (PCAT) density – resembling perivascular fat inflammation – provided additional discriminatory value for predicting ASCVD events, independent from inflammatory high-risk plaque features.
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