Serial Changes in Epicardial Adipose Tissue Attenuation Identify Residual Atherosclerotic Risk Independent of LDL Lowering: A Post Hoc Analysis of the CAUGHT-CAD Trial.

BACKGROUND

Coronary plaque progression persists in some patients despite effective low-density lipoprotein cholesterol (LDL-C) lowering. Epicardial adipose tissue (EAT) is a metabolically active visceral fat depot that may influence coronary atherosclerosis through inflammatory signaling. The authors hypothesized that longitudinal changes in EAT would influence plaque progression.

METHODS

Plaque and EAT quantification with paired baseline and follow-up coronary computed tomography angiography was attainable in 313 asymptomatic, statin-naive participants (aged 58.8 ± 6.8 years, 44% female) in the CAUGHT-CAD (Coronary Artery calcium score: Use to Guide management of Hereditary Coronary Artery Disease) trial. Associations between longitudinal changes in EAT volume and attenuation (ΔEAT) and coronary plaque outcomes were evaluated using analysis of covariance models, with adjustment for baseline plaque burden, treatment allocation, and changes in cardiometabolic risk factors. Exploratory analyses evaluated the relationship between ΔEAT attenuation and Δ pericoronary adipose tissue (PCAT) attenuation. An LDL-C-based reference model of achieved LDL-C (Reference: <1.4 mmol/L [<55 mg/dL], 1.4-1.8 mmol/L [55-70 mg/dL], and >1.8 mmol/L [>70 mg/dL]) was used, and incremental discrimination with ΔEAT attenuation was assessed using nested model comparison and likelihood ratio testing.

RESULTS

Higher ΔEAT attenuation, but not EAT volume change, remained independently associated with progression of noncalcified plaque (NCP) and adverse plaque remodeling. Per 1-SD increase in ΔEAT attenuation, NCP volume was higher by 4.21 mm3 (95% CI: 0.67-7.74; P = 0.020), fibrous plaque volume by 3.55 mm3 (95% CI: 0.67-6.43; P = 0.016), and NCP percent atheroma volume by 1.08% (95% CI: 0.47-1.69; P < 0.001). In participants with high baseline EAT volume (tertile 3 ≥67.1 cm3), the addition of ΔEAT attenuation to LDL-C-based analysis of covariance models resulted in a statistically significant improvement in model fit (Δ Akaike information criterion -4.8; likelihood ratio test P = 0.012). In exploratory analyses, ΔEAT attenuation was also associated with increasing PCAT attenuation (β = 2.44 HU per SD; P < 0.001), suggesting that changes in PCAT may partly explain the observed association with plaque progression.

CONCLUSIONS

The association of serial changes in EAT attenuation with coronary plaque remodeling, independent of LDL-C lowering, supports a potential mechanistic role for EAT inflammation in residual plaque progression.