Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson St, Torrance, CA, 90502, USA.
David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, 90095, USA.
J Cardiovasc Comput Tomogr. 2020 Jul-Aug;14(4):343-348. doi: 10.1016/j.jcct.2019.12.033. Epub 2020 Jan 17.
The association between inflammation and atherosclerosis has been well described in the literature. There is now mounting evidence in support of adipose tissue as a reservoir for inflammatory markers. Epicardial adipose tissue (EAT) has been shown to associate with coronary atherosclerosis and found to be a predictor of future adverse cardiovascular events. This study, VIA-EAT, assesses the change in epicardial fat volume (EFV) after treatment with an investigational anti-inflammatory agent (VIA-2291) in a cohort of post-acute coronary syndrome (ACS) patients.
This study is derived from a post-hoc analysis of a previously conducted randomized clinical trial (NCT00358826). Patients were recruited for a prospective, double-blind, multi-center randomized trial of a 5-lipooxygenase inhibitor or placebo in a 3:1 randomization, including doses of placebo, and 25 mg, 50 mg and 100 mg of active treatment. Cardiac computed tomography was performed at baseline and at 24 weeks after treatment with VIA-2291. EAT and pericardial adipose tissue (PAT) were measured using previously published methodology. A Pearson correlation test was used to determine the relationship between change in epicardial fat and change in plaque composition.
We analyzed 54 pre- and post-treatment scans. There were no major differences between traditional cardiovascular risk factors among the 4 randomized study arms. There was a significant decrease in EAT and PAT in patients in the treatment arms vs. placebo, -3.0 ± 8.2mm3 and -3.9 ± 10.9mm3 vs. 1.7 ± 7.5mm3 and 1.4 ± 10.7mm3 (p = 0.001), respectively. The changes in EAT and PAT were more pronounced in patients taking 100 mg of the drug vs. placebo: 4.2 ± 9.6mm3, -7.6 ± 8.5mm3, p = 0.0001, respectively. In a subgroup analysis, reduction in epicardial fat volume correlated with reduction in total atherosclerotic plaque volume across all VIA treatment groups, r = 0.52 (p = 0.004).
After adjustment for traditional cardiovascular risk factors including age, gender, body mass index, dyslipidemia and smoking, VIA-2291 decreases EAT and PAT in individuals with recent ACS. Treatment with the drug also appears to alter plaque volume and composition.
文献中已经充分描述了炎症与动脉粥样硬化之间的关联。越来越多的证据支持脂肪组织是炎症标志物的储存库。心外膜脂肪组织（EAT）与冠状动脉粥样硬化有关，并且是未来不良心血管事件的预测指标。这项名为 VIA-EAT 的研究评估了在急性冠脉综合征（ACS）后患者中使用一种研究性抗炎药物（VIA-2291）治疗后心外膜脂肪量（EFV）的变化。
这是一项先前进行的随机临床试验（NCT00358826）的事后分析研究。患者被纳入一项前瞻性、双盲、多中心、随机试验，以 3:1 的比例随机接受 5-脂氧合酶抑制剂或安慰剂治疗，包括安慰剂、25mg、50mg 和 100mg 活性治疗。在接受 VIA-2291 治疗后 24 周时进行心脏计算机断层扫描。使用先前发表的方法测量心外膜脂肪和心包脂肪组织（PAT）。采用 Pearson 相关检验确定心外膜脂肪变化与斑块成分变化之间的关系。
我们分析了 54 例治疗前后的扫描。在 4 个随机研究臂中，传统心血管危险因素之间没有显著差异。与安慰剂相比，治疗组患者的心外膜脂肪和心包脂肪组织显著减少，分别为-3.0±8.2mm3 和-3.9±10.9mm3，与 1.7±7.5mm3 和 1.4±10.7mm3（p=0.001）。与安慰剂相比，服用 100mg 药物的患者心外膜脂肪和心包脂肪组织的变化更为明显：4.2±9.6mm3 和-7.6±8.5mm3，p=0.0001。在亚组分析中，在心外膜脂肪体积减少方面，所有 VIA 治疗组之间均与总动脉粥样硬化斑块体积减少相关，r=0.52（p=0.004）。
在调整了包括年龄、性别、体重指数、血脂异常和吸烟在内的传统心血管危险因素后，VIA-2291 可降低近期 ACS 患者的心外膜脂肪和心包脂肪组织。该药物治疗似乎还可以改变斑块体积和成分。
