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与早期类风湿关节炎患者心血管疾病相关的生物标志物。

Biomarkers associated with cardiovascular disease in patients with early rheumatoid arthritis.

机构信息

Department of Public Health and Clinical Medicine/Rheumatology, University of Umeå, Umeå, Sweden.

Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, Umeå, Sweden.

出版信息

PLoS One. 2019 Aug 5;14(8):e0220531. doi: 10.1371/journal.pone.0220531. eCollection 2019.

Abstract

OBJECTIVES

Patients with rheumatoid arthritis (RA) have an increased mortality and morbidity due to cardiovascular disease (CVD). In this prospective 5-year follow up of patients with RA, we analysed several biomarkers, known to be associated with atherosclerosis and/or inflammation in the general population. The aim of this study was to find out whether the RA-disease per se affect these biomarkers and if those could be associated with the progression of atherosclerosis, as measured by intima media thickness (IMT) among patients with early RA.

METHODS

Patients from northern Sweden diagnosed with early RA, are consecutively recruited into an ongoing prospective study on CVD comorbidity. A subgroup of patients, aged ≤60 years (n = 71) was included for ultrasound measurements of IMT at inclusion (T0) and after 5 years (T5) together with age-sex-matched controls (n = 40). The patients were clinically assessed. Blood was analysed for lipids, ESR and CRP and several biomarkers known to be associated with atherosclerosis in the general population.

RESULTS

At T0, the patients with RA had significantly lower levels of MIF and significantly higher levels of interleukin (IL)-18 and MIC-1 compared with controls. At T5, the patients with RA had significantly higher levels of pentraxin3, MIC-1, TNF-R2, ICAM-1, VCAM-1 and endostatin compared with controls. At T0 the levels of MPO correlated with DAS28, sCD40L with CRP and IL-18 with systolic blood pressure and Reynolds risk score. Using PLSR on a CVD-panel analysed with multiplex immunoassay, the patients with RA could be correctly classified into those who had a worsening in their IMT over the five years or not. Here, MMP3 was identified as influential.

CONCLUSIONS

This study indicates that the RA disease itself could affect several of the biomarkers in this study, and possibly also the processes involved in the development of atherosclerosis.

摘要

目的

类风湿关节炎(RA)患者由于心血管疾病(CVD)而导致死亡率和发病率增加。在这项对 RA 患者进行的为期 5 年的前瞻性随访中,我们分析了几种生物标志物,这些标志物已知与一般人群中的动脉粥样硬化和/或炎症有关。本研究的目的是确定 RA 疾病本身是否会影响这些生物标志物,以及这些生物标志物是否与早期 RA 患者动脉粥样硬化的进展有关,如内膜中层厚度(IMT)测量所示。

方法

瑞典北部连续确诊为早期 RA 的患者被招募到一项关于 CVD 合并症的正在进行的前瞻性研究中。年龄≤60 岁的患者亚组(n=71)包括在内膜中层厚度(IMT)测量的纳入(T0)和 5 年后(T5),并与年龄性别匹配的对照组(n=40)一起。患者进行了临床评估。分析血液中的血脂、红细胞沉降率和 C 反应蛋白以及几种已知与一般人群中的动脉粥样硬化有关的生物标志物。

结果

在 T0 时,与对照组相比,RA 患者的 MIF 水平显著降低,白细胞介素(IL)-18 和 MIC-1 水平显著升高。在 T5 时,RA 患者的 pentraxin3、MIC-1、TNF-R2、ICAM-1、VCAM-1 和内皮抑素水平明显高于对照组。在 T0 时,MPO 水平与 DAS28 相关,sCD40L 与 CRP 相关,IL-18 与收缩压和雷诺兹风险评分相关。使用多重免疫测定分析的 CVD 面板上的 PLSR,RA 患者可以正确分类为在五年内 IMT 恶化或不恶化的患者。在这里,MMP3 被确定为有影响的。

结论

这项研究表明,RA 疾病本身可能会影响本研究中的几种生物标志物,并且可能还会影响动脉粥样硬化发展过程中涉及的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c4a/6681963/a9f347dd6b7a/pone.0220531.g001.jpg

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