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Introduction: Pericoronary adipose tissue (PCAT) attenuation on coronary computed tomography angiography (CCTA) is an emerging noninvasive marker of coronary inflammation. Prior studies suggest statin therapy may be associated with lower PCAT attenuation, but this relationship remains incompletely characterized in contemporary trial populations. We therefore evaluated the association between baseline statin use and CCTA-derived PCAT attenuation in T-PLAQUE trial participants.

Methods: We performed a baseline cross-sectional analysis of data from participants in T-PLAQUE, a multicenter, double-blind, randomized, placebo-controlled phase IV trial evaluating the effect of tirzepatide on coronary atherosclerosis progression. PCAT attenuation was quantified on baseline contrast-enhanced CCTA scans by independent readers blinded to clinical data using Medis QAngio Suite. Using validated methods, proximal 40-mm segments of the left anterior descending (LAD), left circumflex (LCx), and right coronary arteries (RCA) were analyzed, with LAD and LCx segments defined immediately distal to the left main bifurcation and RCA segments 10 mm distal to the ostium. Voxels from -190 to -30 Hounsfield units (HU) within a radial distance equal to the vessel diameter were included, excluding the first 1 mm adjacent to the vessel wall to minimize partial volume artifact. Mean PCAT attenuation across the LAD, LCx, and RCA was analyzed, and multivariable linear regression was performed to evaluate its association with baseline statin use.

Results: PCAT attenuation was evaluable in 102 participants (mean age, 61.8±7.8 years; 65% male). Mean PCAT attenuation averaged across the LAD, LCx, and RCA was -75.1±9.4 HU, and 25 participants (25%) had a mean PCAT attenuation greater than the prespecified clinical threshold of -70 HU. Mean LAD-LCx-RCA PCAT attenuation was significantly higher among participants not receiving statin therapy (n=34) than among those receiving statins (n=68) (-69.9±9.4 HU vs. -77.7±8.2 HU, respectively; p<0.001). In multivariable linear regression adjusting for age, sex, diabetes mellitus, hypertension, and prior smoking, baseline statin therapy was independently associated with a 9-HU lower PCAT attenuation (p<0.001).

Conclusions: In this baseline cross-sectional analysis of data from the T-PLAQUE trial, statin use was independently associated with lower PCAT attenuation after adjustment for major cardiovascular risk factors, consistent with a less inflamed pericoronary environment. These findings suggest that PCAT attenuation may have utility as a noninvasive imaging marker of the anti-inflammatory effects of therapies.