Interplay between pericoronary adipose tissue, CT-derived high risk coronary plaque phenotype, systemic inflammation, and major cardiac events in patients with stable chest pain

• Applicant: Dr. Marcel Langenbach
• Subject Area: Nuclear Medicine, Radiotherapy, Radiobiology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 502109212

Cardiovascular disease is the most frequent cause of death in industrialized countries, with coronary artery disease (CAD) as the most common form. The latest 2019 European Society of Cardiology guidelines recommend coronary computed tomography angiography (cCTA) as the first-line diagnostic test in patients with suspected CAD and a low to intermediate clinical likelihood. Routine cCTA comprises a qualitative assessment of coronary artery stenosis severity and extent of plaque. In addition, cCTA allows for visualization of plaque composition and phenotype, including high-risk plaque features like positive remodeling, low-attenuation core, and the napkin-ring sign that have independent and incremental value to predict a major adverse cardiac event (MACE). Inflammation is suspected to contribute to the pathophysiology of coronary atherosclerosis. Systemic inflammatory biomarkers correlate with the coronary artery plaque burden and are associated with an increased risk of atherosclerotic plaque rupture and acute coronary syndrome. While cCTA cannot detect vascular inflammation directly, CT allows visualization of pericoronary adipose tissue (PCAT), which may reflect a surrogate of local vascular inflammatory changes, as suggested by previous studies linking PCAT attenuation to pericoronary 18F-sodium-fluoride uptake in patients with high-risk plaques. The potential relationship between cCTA-derived PCAT attenuation, MACE, and systemic inflammatory biomarkers is novel and has not been investigated yet. The PROMISE trial cohort provides the unique opportunity to explore PCAT attenuation in a large cohort of patients with stable chest pain, in-depth coronary plaque characterization, inflammatory biomarkers, and prospectively collected independently adjudicated MACE. Therefore, the aims of the current study are (1) to associate PCAT attenuation with qualitative and quantitative CT measures of CAD, (2) to assess prognostic value for MACE beyond traditional cardiovascular risk factors and established CT measures of CAD. (3) Another novel aspect is the assessment of the pathophysiological background, correlating PCAT attenuation with systemic inflammatory biomarkers and clinical risk factors. (4) Leveraging the guest institution’s experience in machine learning, we will explore radiomic features of PCAT to identify adverse new CAD phenotypes, related to coronary plaques, inflammatory biomarkers, and MACE. If successful, the results will provide new insights into the pathophysiology of coronary atherosclerosis, namely elucidating the relationship between PCAT attenuation as a marker of vascular inflammation, high-risk coronary plaque phenotype, and MACE. Moreover, these results may build a base for future more extensive prospective randomized trials, where PCAT attenuation may function as a surrogate of inflammation to evaluate the efficacy of anti-inflammatory drugs.

• DFG Programme: WBP Fellowship
• International Connection: USA
• Host: Dr. Borek Foldyna