Our study indicates that computer-aided quantification of PFV and TFV can be performed from non-contrast coronary calcium scans with TFV being performed almost automatically with high reproducibility and PFV requiring moderate user interaction. We have previously demonstrated the accuracy of the semi-automated quantitation, TFV, showing excellent agreement with QFAT and expert manual processing 7
. “Pericardiac fat” in the previous paper actually equates to TFV in the current manuscript; we revised this term to TFV to correctly differentiate it from PFV and to be more consistent with subsequent publications on this topic 3, 9
. PFV is essentially manual measurement by drawing closed pericardial contours, followed by fat quantitation using standard preset fat thresholds. PFV measurement was not available in QFAT at the time of our previous publication7
; this is its first description. To our knowledge, this is the first report of a tool which allows fast quantification of both PFV and TFV from the non-contrast CT scan at the same time; such a tool could potentially advance existing techniques for cardiovascular risk assessment, both in clinical research and in clinical practice. We showed that PFV and TFV correlate similarly with CCS, and both PFV and TFV are strongly associated with the presence of coronary calcium, unlike standard risk factors. Additionally, PFV and TFV are strongly associated with METS and combined METS and diabetes, unlike standard risk factors and CCS. Compared to PFV, TFV has the advantage of automatic quantification as soon as simple limits of the heart are chosen, which results in lower observer variability.
TFV correlated with low adiponectin and low HDL levels and with high glucose and triglyceride levels. It has been shown that human epicardial adipose tissue expresses adiponectin and that adiponectin expression is significantly higher in epicardial fat from subjects with normal coronary arteries than in patients with severe coronary artery disease 1
. Interestingly, there was no correlation with CRP. However, CRP is a non-specific marker of inflammation and plasma inflammatory biomarkers may not adequately reflect local tissue inflammation in all patients 22
. High-sensitivity CRP values were not available in our patient population.
Although semi-automated quantitation of thoracic fat have been described 7, 23
, to our knowledge, ours is the first report of fast, simultaneous quantitation PFV and TFV from non-contrast CT, and subsequent direct comparison of these measures. Our reproducibility was lower than that recently reported by Grief et al who reported inter-observer variability of 15% for PFV and 8% for TFV from manual quantification of coronary CT Angiography scans 21
. Our study adds to several recent studies underscoring the clinical importance of pericardial fat. Ding et al have also shown that pericardial fat, quantified manually from a 45 mm thick slab around the origin of the left main artery, was independently associated with calcified coronary plaque in 159 individuals from the MESA study, they did not, however, quantify TFV from the same slices 5
. Grief et al, manually quantified TFV from contrast-enhanced coronary CT angiography (CCTA) scans from 286 consecutive patients and found that patients with atherosclerotic coronary plaque on CCTA had significantly larger TFV than patients without plaque, and elevated TFV strongly predicted the presence of coronary atherosclerosis as imaged by CCTA and were correlated with hypoadiponectimia 21
. Rosito et al found that pericardial and intra-thoracic fat volume, quantified manually in 1155 participants of the Framingham Heart Study, were associated with vascular calcification, suggesting that these fat depots may exert local toxic effects on the vasculature 3
. Interestingly, the same group has recently reported that pericardial fat, but not thoracic fat, was independently associated with cardiovascular events 9
. Since our automated algorithm quantifies TFV within a bounding box about the heart, and excludes posterior fat 7
, it centers more on the heart than previously-described methods 3, 9
. While the patients in this study were a consecutive cohort of 201 patients without cardiovascular event information, we have recently completed an outcome analysis of 232 matched patients from 2751 asymptomatic patients without known CAD (enrolled in the EISNER study), with prospective 4-year post-scan follow-up for major adverse cardiovascular events (MACE); the MACE events were cardiac death, myocardial infarction, stroke, and late revascularization24
. We compared 58 cases who experienced MACE to 174 event-free controls (1:3 MACE-to-control ratio), matched by gender and propensity score to account for age, traditional risk factors and coronary calcium score. PFV and TFV were measured in these 232 patients as described in this manuscript. Our results showed that MACE patients had significantly higher mean PFV, higher mean TFV and higher frequencies of PFV > 125 cm3
and TFV > 250 cm3
. In multivariable regression analysis, doubling of PFV and TFV were both associated with MACE (odds ratio 1.74, p = 0.038 for log2
(PFV); odds ratio 1.78, p = 0.047 for log2
Our study had several limitations. We used CCS as the reference marker for CAD and did not have invasive angiographic data in these patients to further describe coronary artery disease severity. Our algorithm for quantifying PFV and TFV was not completely automatic and still required user interaction. Our patient sample size was small (201). Single-slice abdominal CT is an additional CT scan, and was available only for a subset of the 201 patients; however, conclusive results could be reached in this subgroup. Additionally, blood serum was only available in a subset of the 201 patients. Our patient population was at an intermediate clinical risk for CAD, with intermediate-to-high Framingham Risk Scores and high CCS. In our study population without prior cardiovascular disease, it was not possible to compare PFV or TFV to other modalities, such as echocardiography, Magnetic Resonance Imaging (MRI), or to contrast-enhanced CT coronary angiography. Prognostic studies with event follow-up are needed to prove the incremental predictive impact of PFV and TFV over CCS and standard risk factors.