Hoshino Shinsuke, Jain Sonia, Shimizu Chisato, Roberts Samantha, He Feng, Daniels Lori B, Kahn Andrew M, Tremoulet Adriana H, Gordon John B, Burns Jane C
Dept. of Pediatrics, University of California San Diego, La Jolla, CA, United States.
Dept. of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, United States.
Int J Cardiol Heart Vasc. 2021 Sep 1;36:100863. doi: 10.1016/j.ijcha.2021.100863. eCollection 2021 Oct.
Myocardial histology from autopsies of young adults with giant coronary artery aneurysms following Kawasaki disease (KD) shows bridging fibrosis beyond the territories supplied by the aneurysmal arteries. The etiology of this fibrosis is unknown, but persistent, low-level myocardial inflammation and microcirculatory ischemia are both possible contributing factors. To investigate the possibility of subclinical myocardial inflammation or fibrosis, we measured validated biomarkers in young adults with a remote history of KD.
We measured plasma calprotectin, galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and serum procollagen type 1C-terminal propeptide (P1CP) in 91 otherwise healthy young adults with a remote history of KD and in 88 age-similar, healthy controls. KD subjects were stratified by coronary artery aneurysm (CAA) status and history of remote myocardial infarction (MI).
After correction for multiple testing, calprotectin, Gal-3, and GDF-15 levels were significantly higher in subjects with persistent CAA (n = 26) compared with KD subjects with remodeled CAA (n = 20, p = 0.005, 0.001, 0.0036, respectively). In a multivariable regression model with CA status as the main predictor and adjusting for sex, MI history, and interval from KD onset, CA status was a significant predictor (Persistent CAA vs KD Normal CA) of calprotectin, Gal-3, GDF-15 and sST2 levels (p = 0.004, <0.001, 0.007, and 0.049, respectively).
These results suggest that ongoing inflammation and fibrosis may be occurring in individuals with persistent CAA. Longitudinal follow-up is needed to clarify the clinical significance of these elevated biomarker levels in this patient population that requires life-long monitoring.
对川崎病（KD）后患有巨大冠状动脉瘤的年轻成年人进行尸检，其心肌组织学显示，动脉瘤动脉供血区域以外存在桥接纤维化。这种纤维化的病因尚不清楚，但持续性的低水平心肌炎症和微循环缺血均可能是促成因素。为了研究亚临床心肌炎症或纤维化的可能性，我们对有KD远期病史的年轻成年人进行了经过验证的生物标志物检测。
我们对91名有KD远期病史的健康年轻成年人以及88名年龄相仿的健康对照者测量了血浆钙卫蛋白、半乳糖凝集素-3（Gal-3）、生长分化因子-15（GDF-15）、可溶性ST2（sST2）以及血清Ⅰ型前胶原C端前肽（P1CP）。KD受试者根据冠状动脉瘤（CAA）状态和远期心肌梗死（MI）病史进行分层。
在进行多重检验校正后，与CAA已重塑的KD受试者（n = 20）相比，持续性CAA受试者（n = 26）的钙卫蛋白、Gal-3和GDF-15水平显著更高（分别为p = 0.005、0.001、0.0036）。在以CAA状态作为主要预测指标并对性别、MI病史以及自KD发病起的时间间隔进行校正的多变量回归模型中，CAA状态是钙卫蛋白、Gal-3、GDF-15和sST2水平的显著预测指标（持续性CAA与KD正常CAA相比）（分别为p = 0.004、<0.001、0.007和0.049）。
这些结果表明，持续性CAA个体可能正在发生持续的炎症和纤维化。需要进行纵向随访，以阐明这些生物标志物水平升高在这一需要终身监测的患者群体中的临床意义。
