Anti-CCP Antibodies, TNF-Antagonists, and Cardiac Function in Rheumatoid Arthriti

类风湿性关节炎中的抗 CCP 抗体、TNF 拮抗剂和心脏功能

基本信息

批准号：
8677689
负责人：
Cesare Russo
金额：
$ 8万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-15 至 2016-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8677689
关键词：
Affect Age Ancillary Study Anti-citrullinated peptide antibody Atherosclerosis Attention Autoimmune Process Autoimmunity Cardiac Cardiovascular Diseases Cardiovascular system Caring Chronic Clinical Cross-Sectional Studies Data Disease Early identification Echocardiography Enrollment Event Exhibits Functional disorder Funding Gender General Population Heart Heart failure Impairment Inflammation Inflammatory Intervention Left Left Ventricular Dysfunction Left Ventricular Function Left Ventricular Mass Left ventricular structure Medical Methods Morbidity - disease rate Myocardial Myocardial dysfunction Myocardial perfusion Myocardium Outcome Parents Pathway interactions Patients Peptide antibodies Perfusion Pharmaceutical Preparations Population Process Randomized Research Design Rheumatoid Arthritis Risk Serum Signs and Symptoms Stratification Subgroup Symptoms TNF gene Techniques Tumor Necrosis Factor Therapy Tumor Necrosis Factor-alpha United States National Institutes of Health Ventricular Work base cyclic citrullinated peptide design effective intervention effective therapy high risk improved mortality prospective public health relevance standard care treatment effect

项目摘要

DESCRIPTION (provided by applicant): Background: Patients with rheumatoid arthritis (RA) are at increased risk of developing heart failure (HF) and cardiovascular (CV) events compared to age- and gender-matched non-RA controls. The widening gap in survival between RA and the general population emphasizes the urgency to understand the causes, and to develop effective interventions to reduce, CV related morbidity and mortality in RA. Rationale: 1) Preliminary data suggest that anti-cyclic citrullinated peptides (-CCP) antibodies may be involved in an autoimmune-based attack to the myocardium in RA. We hypothesize that titers of anti-CCP antibodies may be associated with subclinical myocardial dysfunction in RA patients. If proven, this association may allow the early identification of a subgroup at higher risk of developing HF/CV disease. 2) Antagonists of the tumor necrosis factor-¿ (anti-TNF) are highly effective in treating RA signs and symptoms, however, these drugs proved of no effect or even harmful in advanced HF patients. So far, no studies have directly investigated the effect of anti-TNF therapy on myocardial function in RA. It is crucial to clarify the cardiac effects of these treatment agents in RA, as it may have significant impact on CV outcome in these patients. Objectives: 1) In cross-sectional design, to ascertain whether serum concentrations of anti- CCP antibodies are correlated with subclinical left ventricular (LV) systolic and diastolic dysfunctionin patients with RA and no signs or symptoms of CVD. 2) In prospective design, we will evaluate the effect of treatment with anti-TNF therapy on parameters of LV systolic and diastolic function, compared with usual medical care. Methods: The present study will be an ancillary study of the Escape II Myocardium, an NIH- funded study (P.I. Dr. Joan Bathon) aimed at identifying the correlates of LV structure and perfusion abnormalities in RA patients, and at evaluating the effect of anti-TNF therapy on myocardial perfusion/inflammation. We will analyze myocardial function using speckle-tracking strain echocardiography, a technique able to detect subclinical abnormalities in LV function not detectable using traditional methods. Following the parent study design, a cross-sectional analysis will be performed in 150 RA patients, to assess the correlation of anti-CCP antibody titers with LV systolic/diastolic function by speckle-tracking echocardiography. For aim 2, LV systolic/diastolic function will be assessed in 50 patients with severe RA activity randomized to anti-TNF therapy or standard treatment, and the effect of treatment on cardiac function will be evaluated after 6 months therapy.

描述（由申请人提供）：背景：与年龄和性别匹配的非 RA 对照相比，类风湿性关节炎 (RA) 患者发生心力衰竭 (HF) 和心血管 (CV) 事件的风险增加。 RA 与一般人群之间的生存率强调了了解原因并制定有效干预措施以减少 RA 中与 CV 相关的发病率和死亡率的紧迫性： 1) 初步数据表明，抗循环治疗。瓜氨酸肽（-CCP）抗体可能参与 RA 中基于自身免疫的心肌攻击。我们发现抗 CCP 抗体的滴度可能与 RA 患者的亚临床心肌功能障碍有关。早期识别发生 HF/CV 疾病风险较高的亚组 2) 肿瘤坏死因子-¿ 拮抗剂。（抗TNF）在治疗RA症状和体征方面非常有效，然而，这些药物被证明对晚期心力衰竭患者无效甚至有害，迄今为止，还没有研究直接研究抗TNF治疗对心肌功能的影响。 RA。阐明这些治疗药物对 RA 的心脏作用至关重要，因为它可能对这些患者的 CV 结局产生重大影响。目的：1) 在横断面设计中，确定抗 CCP 抗体的血清浓度是否存在变化。相关于RA 患者的亚临床左心室 (LV) 收缩和舒张功能障碍且无 CVD 体征或症状 2) 在前瞻性设计中，我们将评估抗 TNF 治疗对 LV 收缩和舒张功能参数的影响。方法：本研究将是 Escape II 心肌的一项辅助研究，这是一项由 NIH 资助的研究（P.I. Dr. Joan Bathon），旨在我们将使用斑点追踪应变超声心动图（一种能够检测 RA 患者亚临床异常的技术）分析心肌功能。使用传统方法无法检测左心室功能。按照母研究设计，将对 150 名 RA 患者进行横断面分析，以评估抗 CCP 抗体滴度的相关性。通过斑点追踪超声心动图检查左室收缩/舒张功能对于目标 2，将评估 50 名随机接受抗 TNF 治疗或标准治疗的重度 RA 活动患者的左室收缩/舒张功能，并评估治疗对心功能的影响。治疗6个月后进行评估。