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

心血管疾病是工业化国家最常见的死亡原因，其中冠状动脉疾病（CAD）是最常见的形式。最新的2019年欧洲心脏病学会指南推荐冠状动脉计算机断层扫描血管造影（cCTA）作为疑似CAD患者和低至中等临床可能性患者的一线诊断测试。常规cCTA包括冠状动脉狭窄严重程度和斑块范围的定性评估。此外，cCTA可以可视化斑块组成和表型，包括高危斑块特征，如正重构、低衰减核心和餐巾环征象，这些特征对预测主要心脏不良事件（MACE）具有独立和增加的价值。炎症被怀疑与冠状动脉粥样硬化的病理生理有关。系统性炎症生物标志物与冠状动脉斑块负荷相关，并与动脉粥样硬化斑块破裂和急性冠状动脉综合征的风险增加相关。虽然cCTA不能直接检测血管炎症，但CT可以显示冠状动脉周围脂肪组织（PCAT），这可能反映局部血管炎症变化的替代品，正如先前的研究表明，PCAT衰减与高风险斑块患者冠状动脉周围18f -氟化钠摄取有关。ccta衍生的PCAT衰减、MACE和全身炎症生物标志物之间的潜在关系是新的，尚未被研究。PROMISE试验队列提供了独特的机会来探索稳定胸痛患者的PCAT衰减，深入的冠状动脉斑块特征，炎症生物标志物，以及前瞻性收集的独立判定的MACE。因此，本研究的目的是(1)将PCAT衰减与CAD的定性和定量CT测量相关联，(2)评估MACE在传统心血管危险因素和已建立的CAD CT测量之外的预后价值。(3)另一个新颖的方面是对病理生理背景的评估，将PCAT衰减与全身炎症生物标志物和临床危险因素联系起来。(4)利用客座机构在机器学习方面的经验，我们将探索PCAT的放射学特征，以识别与冠状动脉斑块、炎症生物标志物和MACE相关的新的不利CAD表型。如果成功，该结果将为冠状动脉粥样硬化的病理生理学提供新的见解，即阐明作为血管炎症标志物的PCAT衰减、高危冠状动脉斑块表型和MACE之间的关系。此外，这些结果可能为未来更广泛的前瞻性随机试验奠定基础，其中PCAT衰减可能作为炎症的替代品来评估抗炎药物的疗效。

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.