Post Graduate Programe in Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil; FIPMoc University Center, Montes Claros, Minas Gerais, Brazil.
Laboratory of Cell-Cell Interactions, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Int J Cardiol. 2019 Aug 15;289:107-109. doi: 10.1016/j.ijcard.2019.04.063. Epub 2019 Apr 25.
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.
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-α and IL-6/IL-17A, respectively. IL-6 and TNF-α 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.
High levels of cytokines are associated with severity of RHD. The co-regulated expression of IL-6 and TNF-α is associated with severe valve dysfunction, whereas high IL-10 and IL-4 levels predicted subsequently adverse outcome.
风湿性心脏病（RHD）与炎症有关，炎症会损害心脏瓣膜，通常需要手术干预。疾病进展中涉及的潜在机制尚不完全清楚。本研究旨在评估 RHD 患者的细胞因子血浆水平，作为疾病严重程度的可能标志物。
前瞻性纳入 89 名 RHD 患者，年龄 41 岁±11.5 岁。RHD 严重程度定义为需要侵入性干预的瓣膜功能障碍，包括瓣膜修复或置换。从所有患者采集外周血样进行细胞因子测量。对患者进行随访，观察定义为需要瓣膜干预或死亡的不良临床事件。基线时，64 名（71.9%）患者之前已接受过瓣膜干预，而 25 名患者有稳定的临床表现。重度 RHD 患者的炎症细胞因子水平高于稳定型 RHD 患者。聚类分析显示，基于 IL-6/TNF-α 和 IL-6/IL-17A，重度和稳定型 RHD 患者分别分离。重度 RHD 患者中 IL-6 和 TNF-α 的表达呈正相关，但在稳定型 RHD 患者中则不然。在中位随访 23 个月期间，16 名患者（18%）发生不良结局。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。
高水平的细胞因子与 RHD 的严重程度相关。IL-6 和 TNF-α 的共同调节表达与严重的瓣膜功能障碍相关，而高水平的 IL-10 和 IL-4 则预测随后的不良结局。
