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成年幼年特发性关节炎持续缓解患者的亚临床心血管风险迹象。

Subclinical cardiovascular risk signs in adults with juvenile idiopathic arthritis in sustained remission.

机构信息

Rheumatology Department, IMIBIC/Reina Sofía University Hospital/University of Cordoba, Cordoba, Spain.

Medicine Department, University of Cordoba/IMIBIC/Reina Sofía University Hospital, Cordoba, Spain.

出版信息

Pediatr Rheumatol Online J. 2020 Jul 14;18(1):59. doi: 10.1186/s12969-020-00448-3.

Abstract

BACKGROUND

Juvenile Idiopathic Arthritis (JIA) is one of the most common chronic diseases of childhood that often persists into adulthood and can result in significant long-term morbidity. As a long lasting chronic inflammatory disease, concern has been raised regarding the risk of premature development of cardiovascular disease (CVD) in JIA. This study aims to determine whether adults with JIA in clinical remission display clinical and subclinical signs of CVD risk: inflammatory mediators, adipokines, endothelial dysfunction and oxidative stress markers.

METHODS

This is a cross-sectional study including 25 patients diagnosed with JIA according to the International League of Associations for Rheumatology criteria (ILAR 2001) and 25 age- and sex-matched controls. Remission was determined by JADAS10 < 1 and according to Wallace criteria. The presence of traditional CVD risk factors was analyzed. An extensive clinical analysis including body mass index (BMI), lipid profile, homeostatic model assessment - insulin resistance (HOMA-IR) and arterial blood pressure was performed. Intima media thickness of the common carotid artery (CIMT) was measured as a marker of subclinical atherosclerosis. Several proinflammatory cytokines, molecules involved in the endothelial dysfunction, oxidative stress and adipokines were quantified on serum by ELISA and on peripheral blood mononuclear cells (PBMCs) by RT-PCR. In vitro studies were carried out in healthy PBMCs, adipocytes and endothelial cells which were treated with serum from JIA patients under sustained remission.

RESULTS

Mean duration of the disease was 13.47 ± 5.47 years. Mean age was 25.11 ± 7.21. Time in remission was 3.52 ± 3.33 years. Patients were in remission with no treatment (40%) and with treatments (60%). CVD risk factors and CIMT were similar in JIA patients and controls. However, cholesterol levels were significantly elevated in JIA patients. Levels of adipocytokines, oxidative stress and endothelial activation markers were elevated in serum and PBMCs from JIA patients. Serum of those JIA patients induced the activation of adipocytes, endothelial cells and healthy PBMCs.

CONCLUSIONS

JIA adult patients in remission have subclinical signs of inflammation and CVD risk, showed by an increase in the levels of inflammatory cytokines, endothelial activation and oxidative stress markers and adipokines, molecules closely involved in the alteration of the vascular system.

摘要

背景

幼年特发性关节炎(JIA)是儿童中最常见的慢性疾病之一,通常会持续到成年期,并导致严重的长期发病。作为一种长期持续的慢性炎症性疾病,人们对 JIA 患者心血管疾病(CVD)发病风险的增加表示关注。本研究旨在确定处于临床缓解期的 JIA 成年患者是否存在 CVD 风险的临床和亚临床迹象:炎症介质、脂肪因子、内皮功能障碍和氧化应激标志物。

方法

这是一项横断面研究,纳入了 25 名根据国际风湿病联盟协会标准(ILAR 2001)诊断为 JIA 的患者和 25 名年龄和性别匹配的对照者。通过 JADAS10<1 和 Wallace 标准来确定缓解状态。分析了传统 CVD 危险因素的存在情况。进行了广泛的临床分析,包括体重指数(BMI)、血脂谱、稳态模型评估-胰岛素抵抗(HOMA-IR)和动脉血压。测量颈总动脉内膜中层厚度(CIMT)作为亚临床动脉粥样硬化的标志物。通过 ELISA 检测血清中和通过 RT-PCR 检测外周血单个核细胞(PBMC)中几种促炎细胞因子、参与内皮功能障碍、氧化应激和脂肪因子的分子。将 JIA 患者的血清在体外处理健康的 PBMC、脂肪细胞和内皮细胞,以进行体外研究。

结果

疾病的平均病程为 13.47±5.47 年。平均年龄为 25.11±7.21 岁。缓解时间为 3.52±3.33 年。患者处于缓解期,其中无治疗(40%)和有治疗(60%)。JIA 患者和对照组的 CVD 危险因素和 CIMT 相似。然而,JIA 患者的胆固醇水平明显升高。JIA 患者的血清和 PBMC 中的脂肪因子、氧化应激和内皮激活标志物水平升高。这些 JIA 患者的血清诱导脂肪细胞、内皮细胞和健康 PBMC 的激活。

结论

处于缓解期的 JIA 成年患者存在亚临床炎症和 CVD 风险迹象,表现为炎症细胞因子、内皮激活和氧化应激标志物以及脂肪因子水平升高,这些因子与血管系统的改变密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/864c/7362625/8d4bb0f254ef/12969_2020_448_Fig1_HTML.jpg

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