In this issue of the journal, Long et al. describe a close association of epicardial adipose tissue (EAT) and pericardial adipose tissue with the presence and severity of systemic sclerosis (SSc). The authors looked at a large cohort of patients with SSc (202 patients, 134 without pulmonary hypertension and 68 with SSc-associated pulmonary hypertension) and found that an increased EAT volume is associated with the presence and severity of SSc, independent of cardiovascular risk factors and interstitial lung disease. Further, the association between EAT and SSc-associated pulmonary arterial hypertension highlights a new potential imaging biomarker that may be used for both detecting the presence of and stratifying PAH severity in patients with SSc.
The interest in EAT was born out of observations of visceral abdominal adiposity demonstrating increased associations with atherosclerosis, inflammation, and poor outcome . Mazurek et al demonstrated that the EAT of patients undergoing coronary artery bypass surgery expressed significantly higher concentrations of inflammatory markers than the subcutaneous fat of the same individuals. Further, epicardial fat demonstrated an increased number T-lymphocytes, macrophages, and mast cells that were not present in the subcutaneous fat of the same patients. Since that time, EAT has been demonstrated to be associated with increased levels of coronary artery calcium , increased vascular stiffness , and worsened cardiovascular outcomes .
In the report by Long et al. , however, further evidence is provided that an increase in EAT is a marker of cardiovascular risk in a highly select population. In fact, Long et al. reported that the larger the EAT volume, the greater the presence and the severity of SSc. Given the patient selection, these findings cannot automatically be extended to the general population; however, further evaluation of Long et al.’s finding that those with pulmonary hypertension had more EAT deserves further attention in this very high-risk cohort. It is not intuitively obvious why EAT would be associated with pulmonary hypertension, but if an association can be made, this may have significant implications for those stricken with this deadly complication, and potentially provide future therapies in pulmonary arterial hypertension that have yet to be explored.
Interestingly, coronary artery calcification (CAC) was not independently associated with SSc in the current study. This lack of an association may represent either shortcomings in their methodology or a unique cofounder in patients with severe inflammation, such as those with SSc. The authors have two methodological limitations that may explain the lack of association with CAC. There was no information regarding the presence of diabetes. Diabetes is a well-known cofounder for EAT and CAC; however, the authors did not adjust for it in the logistic model. It is presumed that diabetes may not have been common in this cohort, but given the strength of the association (probably through metabolic syndrome-related inflammation), this needed to be controlled. Further, if the authors want to show a significant relationship between SSc, SSc with PAH, and EAT, they should have three groups, including SSc alone, SSc with PAH, and a larger number of controls derived from a consecutive cohort, not a selected population. This method would allow further control for age, gender, and risk factors, including body mass index and diabetes in the 3 groups. The use of only 63 controls severely limits the confidence of the observations. Normal controls should be at least a 1:1 control, if not 2:1, so inclusion of 202 or 404 normal controls would give much more confidence that these findings are more specific to the SSc and not some other underlying mechanism (like higher inflammatory levels, presence of diabetes or metabolic syndrome, or incomplete matching for cardiovascular risk). Controls are rarely limited in availability in any center compared to rare diseases SSc or SSc with associated pulmonary hypertension.
Regardless, the observations made related to epicardial fat and potential associations provide important preliminary data in the potential for better identification and risk stratification of these high-risk individuals, and is relatively easy to measure on existing computed tomographic scans, whether obtained for cardiac (computed tomography angiography or coronary artery calcium) or nongated (lung evaluation) indications. EAT can be accurately measured on both types of scans with high precision . This opens the door for potential ways to treat EAT, and perhaps the underlying disease. We now understand that this fat depot represents inflamed and metabolically active tissue, which has been associated with atherosclerosis and cardiovascular disease independent of other risk factors. Several studies have demonstrated the ability to reduce the fat burden with different therapies. Nakazato et al. demonstrated that the EAT volume regressed in persons who lost over 5% of their weight during a 4-year follow-up period. Alexopoulos et al. reported that the EAT volume regressed by 3% after intense statin therapy in 194 hyperlipidemic women, which may reflect the well-known ability of statins to decrease systemic inflammation, among other antiatherosclerotic effects.
Finally, the current study supports other observations made in similar chronic inflammatory states, whereby increased EAT is present in those persons with both rheumatoid arthritis and systemic lupus erythematosus . This consistent relationship of inflammatory conditions and increased visceral fat should be heeded. Studies are now needed to evaluate if different drug therapies for the underlying rheumatologic disease (ie, disease-modifying drugs as compared to steroids and anti-inflammatories) will have different effects on long-term outcomes, and whether this will be modulated through cardiovascular risk. Visceral fat is easily identified on all computed tomographic scans performed, and this population (ie, SSc) undergoes imaging of the underlying lung at some point in their evaluation. If a simple marker can be used to alert the clinician to increased cardiovascular risk (or risk of pulmonary hypertension), these observations by Long et al. may prove very useful to the rheumatologic community.
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