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建议将冠状动脉计算机断层扫描血管造影术（cCTA）作为疑似CAD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允许斑块组成和表型的可视化，包括高风险斑块特征，如正性重塑、低衰减核心和napkin-ring征，这些特征具有预测主要不良心脏事件（MACE）的独立和增量价值。 炎症被怀疑是冠状动脉粥样硬化的病理生理学原因。全身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允许冠状动脉周围脂肪组织（PCAT）可视化，这可能反映了局部血管炎症变化的替代，如先前将PCAT衰减与高危斑块患者的冠状动脉周围18 F-氟化钠摄取联系起来的研究所示。 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，尚未进行研究。 PROMISE试验队列提供了独特的机会，可以在具有稳定性胸痛、深入冠状动脉斑块特征、炎症生物标志物和前瞻性收集的独立裁定MACE的大型患者队列中探索PCAT衰减。因此，当前研究的目的是（1）将PCAT衰减与CAD的定性和定量CT测量相关联，（2）评估MACE的预后价值，超越传统的心血管风险因素和CAD的既定CT测量。(3)另一个新的方面是评估病理生理学背景，将PCAT衰减与全身炎症生物标志物和临床风险因素相关联。(4)利用客座机构在机器学习方面的经验，我们将探索PCAT的放射组学特征，以识别与冠状动脉斑块、炎症生物标志物和MACE相关的不良新CAD表型。 如果成功，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PCAT衰减作为血管炎症，高危冠状动脉斑块表型和MACE的标志物之间的关系。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物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.