Circulating cytokines predict severity of rheumatic heart disease
Circulating cytokines predict severity of rheumatic heart disease
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DOI：
10.1016/j.ijcard.2019.04.063
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发表时间：
2019-08-15
影响因子：
3.5
通讯作者：
Nunes, Maria Carmo P.
中科院分区：
文献类型：
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作者：
Diamantino Soares, Adriana C.;Araujo Passos, Livia S.;Nunes, Maria Carmo P.
背景：风湿性心脏病（RHD）与损害心脏瓣膜的炎症有关，通常需要手术干预。参与疾病进展的潜在机制尚未完全了解。本研究旨在评估RHD患者血浆细胞因子水平作为疾病严重程度的可能标志物。方法和结果：89例RHD患者，年龄为41岁+/- 11.5岁，前瞻性入选。RHD严重程度定义为需要侵入性干预（瓣膜修复或置换）的瓣膜功能障碍。从所有患者收集外周血样品用于细胞因子测量。对患者进行随访，观察不良临床事件，定义为需要瓣膜介入或死亡。基线时，64例（71.9%）患者既往接受过瓣膜介入治疗，而25例患者的临床表现稳定。严重RHD患者的炎性细胞因子水平高于病情稳定的患者。聚类分析显示分别基于IL-6/TNF-α和IL-6/IL-17 A的重度和稳定性RHD的分离。IL-6和TNF-α的表达在严重的RHD患者中呈正相关，但在稳定的RHD患者中不相关。在中位随访23个月期间，16例患者（18%）出现不良结局。基线时的IL-10（HR 1.24，95%CI 1.08-1.43，p = 0.003）和IL-4（HR 1.12，95%CI 1.01-1.24，p = 0.041）是随访期间事件的预测因素。结论：高水平的细胞因子与RHD的严重程度相关。IL-6和TNF-α的共调节表达与严重瓣膜功能障碍相关，而高IL-10和IL-4水平预测随后的不良结局。(c)2019爱思唯尔B. V.保留所有权利。
Background: Rheumatic heart disease (RHD) is associated with inflammation that damages cardiac valves, often requiring surgical interventions. The underlying mechanisms involved in the disease progression are not completely understood. This study aimed to evaluate cytokine plasma levels in patients with RHD as possible markers of disease severity.Methods and results: Eighty-nine patients with RHD, age of 41 years +/- 11.5 years, were prospectively enrolled. RHD severity was defined as valve dysfunction that required invasive intervention, either valve repair or replacement. Peripheral blood samples were collected from all patients for cytokine measurements. The patients were followed up to look at adverse clinical events defined as either the need for valve intervention or death. At baseline, 64 (71.9%) patients had previously undergone valve intervention, whereas 25 patients had stable clinical presentation. Patients with severe RHD displayed higher levels of inflammatory cytokines than patients with stable disease. Cluster analysis showed segregation of severe and stable RHD based on IL-6/TNF-alpha and IL6/IL-17A, respectively. IL-6 and TNF-alpha expression were positively correlated in severe but not in stable RHD patients. During a median follow-up of 23 months, 16 patients (18%) had an adverse outcome. IL-10 at baseline (HR 1.24, 95% CI 1.08-1.43, p = 0.003), and IL-4 (HR 1.12, 95% CI 1.01-1.24, p = 0.041) were predictors of events during the follow-up.Conclusions: High levels of cytokines are associatedwith severity of RHD. The co-regulated expression of IL-6 and TNF-alpha is associated with severe valve dysfunction, whereas high IL-10 and IL-4 levels predicted subsequently adverse outcome. (c) 2019 Elsevier B.V. All rights reserved.