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Cardiac Adipose Tissue and Pericoronary Inflammation

Summary

Two cardiac fat depots are often conflated but are mechanistically and genetically different. Epicardial/pericardial adipose tissue (EPAT) is a bulk fat depot around the heart whose genetics turns out to be largely that of generic visceral adiposity — so an EPAT polygenic score is a visceral-adiposity axis, not a heart-specific one. Pericoronary adipose tissue (PCAT) attenuation on CT, by contrast, is a marker of local coronary inflammation, dissociates from adipose volume, and has essentially no published GWAS — making it the more mechanistically-specific, and still-unmapped, target.

Epicardial/Pericardial Adiposity Is Genetically Visceral Fat: Rämö et al. 2024

Rämö et al. trained a deep-learning model to quantify EPAT area from four-chamber cardiac MRI in 44,475 UK Biobank participants, ran a GWAS, and validated a polygenic score (PGS) in 453,733 FinnGen participants.[1] The EPAT PGS was associated with type 2 diabetes (OR 1.06 per SD), heart failure (1.05), CAD (1.04), atrial fibrillation (1.04), and stroke (1.02).[1] But two results argue against treating it as a coronary- or inflammation-specific axis:

  • The 7 GWAS loci implicate generic adipocyte/visceral-fat biology — transcriptional regulators of adipocyte morphology and brown adipogenesis (EBF1, EBF2, CEBPA) and regulators of visceral adiposity (WARS2, TRIB2).[1]
  • EPAT's prospective associations with incident HF, T2D, and CAD were no longer significant after adjustment for abdominal visceral adipose tissue (VAT).[1] The authors conclude EPAT "may largely reflect a metabolically unhealthy adiposity phenotype similar to abdominal visceral adiposity."[1]

Lab interpretation: the practical consequence for CVD subtyping is that the EPAT PGS should be used as the visceral-adiposity axis to adjust for — a covariate/negative control that establishes whether a putative coronary-inflammatory effect is independent of generic ectopic fat — not as the inflammation signal itself. Using it as a "cardiac fat/inflammation" axis would misattribute a VAT effect.

Pericoronary Adipose Tissue Attenuation Is Inflammation, and Dissociates from Volume: Yuvaraj et al. 2023

PCAT lies directly against the coronary adventitia; increased CT attenuation of this depot reflects inflammatory signals diffusing from the vessel wall (adipocyte-morphology change), and is an established surrogate of coronary inflammation linked to vulnerable plaque.[2] In a matched CCTA cohort of 108 patients (54 Indigenous Australian, 54 non-Indigenous), PCAT attenuation (PCAT-a) and PCAT volume (PCAT-v) behaved differently:[2]

  • PCAT-a (inflammation) was higher in males (−86.7 vs −91.3 HU, P=0.003) and in obstructive CAD (P=0.030), but was not correlated with plaque burden (SIS r=0.14, P=0.18).[2]
  • PCAT-v (adiposity) was correlated with plaque burden (SIS r=0.29, P=0.003), age, hypertension, and obesity (P<0.001), and was higher in Indigenous participants.[2]

The dissociation is the key point: pericoronary "fat" resolves into an inflammatory attenuation signal and an adiposity volume signal that must not be conflated. The Indigenous-Australian and male-sex associations also flag population and sex heterogeneity in coronary inflammation.[2]

PCAT Radiomics Captures MI-Relevant Biology Beyond Mean Attenuation: Lin et al. 2020

Beyond a single mean-attenuation number, radiomic (texture/spatial) phenotyping of PCAT distinguished patients with acute myocardial infarction from stable/control CCTA scans, indicating that higher-dimensional PCAT phenotypes carry MI-relevant information that mean attenuation alone misses.[3] This supports using a radiomic PCAT signature — not just the fat attenuation index — as an imaging endophenotype.

The Open Gap: PCAT-Attenuation Genetics

Open question: unlike coronary artery calcium and CCTA plaque burden (which have well-powered GWAS — see Genetics of Subclinical Coronary Atherosclerosis Imaging) and unlike EPAT (Rämö et al. 2024), pericoronary adipose tissue attenuation has no published GWAS or polygenic score identified in this vault's discovery pass (2026-07-21). It is the most inflammation-specific coronary imaging endophenotype and its genetic architecture is unmapped — a candidate discovery target, albeit one that requires large genotyped-CCTA samples.

See Also

Citations

[1] Rämö, J. T., Kany, S., Hou, C. R., Friedman, S. F., Roselli, C., Nauffal, V., Koyama, S., Karjalainen, J., FinnGen, Maddah, M., Palotie, A., Ellinor, P. T., & Pirruccello, J. P. (2024). Cardiovascular Significance and Genetics of Epicardial and Pericardial Adiposity. JAMA Cardiology, 9(5), 418–427. DOI: 10.1001/jamacardio.2024.0080. Source: jamacardiology_rm_2024_oi_240006_1714486932.70443.pdf. Supports: UKB/FinnGen sample sizes, EPAT PGS disease ORs, the 7 adipogenesis/visceral-fat loci, and the VAT-adjustment attenuation and conclusion above. Location: Full text — Abstract and Results. Verified 2026-07-21.

[2] Yuvaraj, J., Lim, E., Vo, T., Huynh, D., Rocco, C., Nerlekar, N., Cheng, K., Lin, A., Dey, D., Nicholls, S. J., Kangaharan, N., & Wong, D. T. L. (2023). Pericoronary adipose tissue attenuation on coronary computed tomography angiography associates with male sex and Indigenous Australian status. Scientific Reports, 13, 15509. DOI: 10.1038/s41598-023-41341-9. Source: 41598_2023_Article_41341.pdf. Supports: PCAT-a vs PCAT-v dissociation, sex/CAD/plaque-burden correlations, and Indigenous-Australian association above. Location: Full text — Results. Verified 2026-07-21.

[3] Lin, A., Kolossváry, M., Yuvaraj, J., Cadet, S., McElhinney, P. A., Jiang, C., Nerlekar, N., Nicholls, S. J., Slomka, P. J., Maurovich-Horvat, P., Wong, D. T. L., & Dey, D. (2020). Myocardial Infarction Associates With a Distinct Pericoronary Adipose Tissue Radiomic Phenotype. JACC: Cardiovascular Imaging, 13(11), 2371–2383. DOI: 10.1016/j.jcmg.2020.06.033. Source: lin-et-al-2020-myocardial-infarction-associates-with-a-distinct-pericoronary-adipose-tissue-radiomic-phenotype.pdf. Supports: radiomic PCAT phenotype distinguishing MI above. Location: Full text — Abstract and Results. Verified 2026-07-21.