Sharma Tania, Maehara Akiko, Maeng Michael, Kjøller-Hansen Lars, Engstrøm Thomas, Ben-Yehuda Ori, Matsumura Mitsuaki, Fröbert Ole, Persson Jonas, Wiseth Rune, Larsen Alf Inge, Koul Sasha, Rylance Rebecca, Mintz Gary S, Ali Ziad A, James Stefan K, Stone Gregg W, Erlinge David
Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden.
New York-Presbyterian Hospital and Columbia University Irving Medical Center, New York, NY, USA.
Int J Cardiol Cardiovasc Risk Prev. 2025 May 24;26:200440. doi: 10.1016/j.ijcrp.2025.200440. eCollection 2025 Sep.
In the PROSPECT-II study, near infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) was used to characterize atherosclerotic plaques in the coronary arteries. NIRS-derived lipid core burden index (LCBI) and IVUS-derived plaque burden (PB) were able to identify plaques strongly associated with adverse cardiovascular events.
Our aim was to identify biomarkers associated with LCBI or PB in the coronary arteries.
898 patients with recent myocardial infarction underwent percutaneous coronary intervention. Blood samples to analyze plasma levels of 179 proteins associated with cardiovascular disease were procured and a combined NIRS-IVUS catheter was used to analyze the coronary arteries. Adjusted linear regression models were calculated between the biomarkers and the outcomes of interest, adjusted for multiplicity testing. Kaplan-Meier survival curves of biomarkers divided by median were assessed with the log-rank test. Adjusted Cox proportional models were calculated for major adverse cardiovascular events.
A total of 24 proteins were associated with PB and 28 proteins with LCBI. Eight of these biomarkers were associated with both increased pan-coronary LCBI and PB; IL-18R1, CSF-1, VEGFA, EN-RAGE, cathepsin D, PCSK9, transferrin receptor protein 1 and OPN. After adjusting for multiplicity, angiopoietin like 3 (ANGPTL3) retained its association with LCBI, and IL-18R1 and CSF-1 retained their association with PB.
We were able to identify distinct biomarker patterns associated with PB and LCBI. IL-18R1 and CSF-1 had a strong relationship with PB. ANGPTL3 was associated with lipid rich plaques but not with PB, supporting its role in lipid accumulation and development of vulnerable plaques.
在PROSPECT-II研究中，近红外光谱（NIRS）和血管内超声（IVUS）被用于表征冠状动脉中的动脉粥样硬化斑块。NIRS衍生的脂质核心负担指数（LCBI）和IVUS衍生的斑块负担（PB）能够识别与不良心血管事件密切相关的斑块。
我们的目的是识别与冠状动脉中LCBI或PB相关的生物标志物。
898例近期发生心肌梗死的患者接受了经皮冠状动脉介入治疗。采集血样以分析与心血管疾病相关的179种蛋白质的血浆水平，并使用联合NIRS-IVUS导管分析冠状动脉。计算生物标志物与感兴趣结局之间的校正线性回归模型，并针对多重检验进行校正。采用对数秩检验评估按中位数划分的生物标志物的Kaplan-Meier生存曲线。计算主要不良心血管事件的校正Cox比例模型。
共有24种蛋白质与PB相关，28种蛋白质与LCBI相关。其中8种生物标志物与全冠状动脉LCBI和PB的增加均相关；白细胞介素18受体1（IL-18R1）、集落刺激因子1（CSF-1）、血管内皮生长因子A（VEGFA）、晚期糖基化终末产物特异性受体（EN-RAGE）、组织蛋白酶D、前蛋白转化酶枯草溶菌素9（PCSK9）、转铁蛋白受体蛋白1和骨桥蛋白（OPN）。在对多重性进行校正后，血管生成素样蛋白3（ANGPTL3）与LCBI的相关性依然存在，IL-18R1和CSF-1与PB的相关性依然存在。
我们能够识别与PB和LCBI相关的不同生物标志物模式。IL-18R1和CSF-1与PB关系密切。ANGPTL3与富含脂质的斑块相关，但与PB无关，这支持了其在脂质积聚和易损斑块形成中的作用。
