Epicardial Fat Shows Promise as a Clinical Risk Factor for CAD

People with more epicardial adipose tissue (EAT) seem to have more coronary plaque and greater progression of their coronary artery disease, according to data from the PARADIGM registry.

While EAT volume (EATv), as measured by coronary computed tomography angiography (CCTA), was not independently associated with major adverse cardiovascular events in the analysis, increased fat volume was associated with both any plaque progression (PP) and rapid plaque progression (RPP). These in turn were tied to more MACE over 10 years.

“Our findings add a new layer to the importance of EAT as a risk marker for not only plaque presence but also plaque progression,” senior author Leandro Slipczuk, MD, PhD (Montefiore Health System/Albert Einstein College of Medicine, Bronx, NY), told TCTMD in an email. While it is not routinely measured in clinical practice today, “accumulating evidence supports its association with the presence of CAD, a relationship we and others have demonstrated across diverse patient populations.”

But it’s the progression of CAD that is “arguably a more critical determinant of outcomes” and deserves more study, he argued.

The study, published online this week in JACC: Cardiovascular Imaging with first author Annalisa Filtz, MD (Montefiore Health System/Albert Einstein College of Medicine), included 773 patients (mean age 62 years; 43% women) who underwent serial CCTA imaging. Among them, 76% had CAD. Patients were stratified into tertiles of EATv: low (≤ 77 cm³), moderate (77-113 cm³), and high (> 113 cm³).

Higher mean EATv was observed in men compared with women (96.0 vs 89.5 cm³; P = 0.021) and in those with versus without CAD (95.0 vs 83.5 cm³; P < 0.001). Notably, as EATv increased, so did body mass index, smoking, creatinine, and triglycerides (P < 0.02 for all).

Over 8 years of follow-up, 83.7% of patients had PP, including 31.2% with RPP (defined as an annualized increase in percent atheroma volume [PAV] ≥ 1%); new plaque was found in 33.3% of those without baseline plaque. Progression of plaque volume, PAV, and calcified and noncalcified plaque were consistently higher among those in the highest EATv tertile (P < 0.03 for all). Additionally, rates of PP (78.9% vs 83.9% vs 88.5%; P = 0.013) and RPP (25.2% vs 32.3% vs 36.4%; P = 0.021) increased across EATv tertiles.

On multivariate analysis adjusted for age, sex, body mass index, diabetes, dyslipidemia, hypertension, hypertriglyceridemia, smoking, and statin therapy, high EATv was an independent predictor of plaque, PP, and RPP, but not MACE. Still, those with PP and RPP reported lower rates of MACE-free survival over 10 years (P < 0.01 for both).

As EAT can be quantified from either noncontrast or contrast-enhanced CT images using artificial intelligence (AI), it’s poised to become a more prevalent clinical risk marker, according to Slipczuk. “In this study, we used an extensively validated platform (QFat) that enables rapid, automated segmentation,” he said. “Importantly, EATv appears to be a modifiable target of therapies such as statins and GLP-1 receptor agonists, suggesting it may represent a potentially clinically actionable biomarker.”

More research is needed in this regard, Slipczuk said. Emerging cardiac CT technology driven by AI tools “enables a comprehensive phenotypic characterization of coronary atherosclerosis that extends far beyond luminal stenosis,” he said, adding, “While some of these features—such as plaque quantification and FFR-CT—are already reimbursed, widely available, and integrated into clinical practice, others remain largely confined to research settings or expert centers. We hope that our findings will help advance EAT toward clinical practice.”

Commenting on the study for TCTMD, Ron Waksman, MD (MedStar Washington Hospital Center, Washington, DC), who has done research on EATv, said the findings are interesting but aren’t enough to yet convince him that this will be a useful tool. “We have a plethora of imaging markers that show the same thing,” he said. “I wonder in what way this one is giving you a better predictability than existing imaging markers that have been described before.”

Coronary artery calcium is a well-established risk tool, not to mention assessing plaque burden by IVUS and OCT as well as measuring lipid rich plaque with NIRS, Waksman said. It’s helpful that EATv is a noninvasive measurement, he added, but it’s not clear whether it will become standard.

As far as next steps, Waksman would like to see more work examining using imaging to predict future events as well as to detect disease progression without any intervention. “I wish we had more methods to confirm halting this progression or rapid progression,” he said.

Also, studies should “look at measuring the effect of therapy,” Waksman added. “Just telling someone they have a marker is not good enough because it’s a longitudinal thing. And today we are reacting to most of the findings that we have. So, if we see a high LDL, if we see lipid-rich plaque, we apply therapy to those patients. You want to see that you can see some regression of those findings by applying the therapy.”