|Home | About | Journals | Submit | Contact Us | Français|
As a component of the metabolic syndrome, abdominal obesity has been more closely associated with both cardiovascular events (1–3) and acute coronary syndrome (4) than standard measures of adiposity such as body mass index and waist circumference (5). Abdominal visceral adipose tissue (VAT) is a specific measurement of abdominal obesity. Abdominal VAT has been linked to insulin resistance and hepatic production of inflammatory factors, potentially through direct hepatic drainage of its metabolites (6).
Computed tomography (CT) is recognized as a highly effective, accurate, and reproducible technique for measuring VAT by detecting the characteristic low Hounsfield units of fat (7,8). On non-contrast CT, abdominal VAT has been linked to development of myocardial infarction (9). In this issue of iJACC, Ohashi et al. (10) report further evidence of the relationship between abdominal VAT and the pathogenesis of coronary atherosclerosis and acute coronary syndrome. In 427 patients with known or suspected coronary artery disease who underwent coronary computed tomography angiography (CTA), the authors report the relationships between axially imaged abdominal VAT area and noncalcified coronary plaques on coronary CTA. Increased abdominal VAT area was significantly associated with both the presence and extent of noncalcified plaques, whereas other body composition measures (subcutaneous adipose tissue, body mass index, waist circumference) were not. The most striking new observation was that increased VAT area was also independently associated with the presence of 3 plaque characteristics previously shown to be related to an increased risk of acute plaque rupture: positive remodeling, low-attenuation plaque, and adjacent spotty calcification (11,12). These findings represent another step toward gaining insight into the mechanism by which VAT is associated with acute coronary syndrome and support the hypothesis that VAT contributes to the instability of coronary arterial plaques.
Noticeably absent from this work, however, are data regarding pericardial fat (visceral fat around the heart) and pericoronary fat (fat immediately adjacent to the coronary artery). While pericardial fat correlates strongly with abdominal VAT (13,14), paracrine effects of the pericardial and pericoronary fat beds may be more potent determinants of coronary plaque development and progression than VAT.
Mazurek et al. (15) studied adipose tissue adjacent to the right coronary artery removed during surgical bypass surgery and found it to contain significantly higher levels of inflammatory markers than subcutaneous fat. This finding has been substantiated in subsequent publications (16,17) and suggests that proximity of pericardial fat to the coronary arteries amplifies its paracrine role in promoting inflammation, resulting in a local toxic effect on the coronary arteries. Evidence that the pericardial fat may directly affect plaque development has also been provided by a 3-dimensional ultrasound study that demonstrated eccentric atherosclerotic plaques develop with a spatial orientation suggestive of a relationship with pericardial fat (18). Further, autopsy evidence has shown that coronary arteries with large necrotic cores have more macrophages in the periadventitial fat than in vessels without a lipid core (19).
Pericardial fat can be quantified by cardiac CT, and multiple publications have implicated its role in the pathophysiology of coronary atherosclerosis. In a report from the Multi-Ethnic Study of Atherosclerosis (MESA) study, Ding et al. (20) showed that pericardial fat on noncontrast CT was associated with increased coronary calcium burden. Mahabadi et al. (21) recently described a strong association between pericoronary fat volume on noncontrast CT and the presence of calcified plaque in the underlying coronary segment. Alexopoulos et al. (22) observed on coronary CTA a significant increase in adipose tissue volume within the pericardial sac (epicardial adipose tissue) with increasing severity of coronary luminal stenosis. In this last study, epicardial adipose tissue volume was larger in patients with mixed or noncalcified plaques, prompting the authors to suggest that epicardial adipose tissue may be associated with the “most dangerous” plaques.
Pericardial fat has also been linked to the development of major adverse cardiac events (MACE). Mahabadi et al. (23) studied the associations between pericardial fat and visceral VAT on noncontrast CT with subsequent cardiovascular events in asymptomatic participants of the Framingham Heart Study (23). In this study, after adjustment for standard clinical measures including body mass index and waist circumference, pericardial fat was more strongly associated with subsequent events than abdominal VAT. Interestingly, pericardial fat was predominantly associated with MACE, whereas only abdominal VAT was associated with stroke. These findings suggest the two fat beds may impact atherogenesis differently, with abdominal VAT having a more systemic effect and pericardial fat a more local effect on the coronary arteries (24). In a case-control study in which pericardial fat was measured from noncontrast coronary calcium CT by a semiautomated method, we found that asymptomatic patients who experienced MACE exhibited a greater pericardial fat volume when compared with event-free control subjects (24). The addition of pericardial fat volume to conventional clinical risk stratification and coronary artery calcium score improved the prediction of MACE in this population. In a subsequent case-control study of patients who underwent myocardial perfusion imaging within 6 months of noncontrast CT, we have shown that, after adjusting for the coronary calcium score, pericardial fat volume was strongly associated with ischemia (25).
The findings of Ohashi et al. (10) provide important information regarding the relationship between abdominal VAT and the genesis of acute coronary syndromes. However, existing literature continues to speak strongly for an even more important role for the fat around the heart. As evidence supporting the relationship between increased pericardial fat, coronary atherosclerosis, and adverse coronary events continues to mount, measurement of pericardial fat from cardiac CT appears primed to ultimately become a routine complement to the information gained from plaque evaluation. This assessment could generate CT information regarding the activity of the atherosclerotic process, potentially adding meaningfully to clinical risk assessment.
This work was supported in part by grants from the Eisner Foundation, the Glazer Foundation, the Lincy Foundation, and the National Institute of Biomedical Imaging and Bioengineering (R21EB006829 to Dr. Dey).
*Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.