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

• 批准号: 8514779
• 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
• 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/8514779
• 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

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（由适用提供）：背景：与年龄和性别匹配的非RA对照相比，类风湿关节炎（RA）患者患心力衰竭（HF）和心血管（CV）事件的风险增加。 RA与普通人群之间的生存差距强调了理解原因的紧迫性，并制定有效的干预措施以减少RA中与CV相关的发病率和死亡率。理由：1）初步数据表明，基于自身免疫性的抗体抗体可能涉及RA中的心肌的自身免疫性攻击。我们假设抗CCP抗体的滴度可能与RA患者的亚临床心肌功能障碍有关。如果经过证实，该关联可能会允许早期鉴定出患有HF/CV疾病风险较高的亚组。 2）肿瘤坏死因子 - （抗TNF）的拮抗剂在治疗RA的体征和症状方面非常有效，但是，这些药物对晚期HF患者没有影响甚至有害。到目前为止，尚未直接研究抗TNF治疗对RA中心肌功能的影响。至关重要的是要阐明这些治疗剂在RA中的心脏影响，因为它可能会对这些患者的CV结果产生重大影响。目标：1）在横截面设计中，以确定抗CCP抗体的血清浓度是否与具有RA的且无体征或症状的CVD的亚临床左心室（LV）收缩压和舒张功能障碍相关。 2）在前瞻性设计中，我们将评估抗TNF疗法对LV收缩期和舒张功能参数的治疗作用，与通常的医疗服务相比。方法：本研究将是对逃生II心肌的辅助研究，该研究旨在确定RA患者的LV结构和灌注异常的相关性，并评估抗TNF治疗对心肌灌注/炎症的作用。我们将使用斑点跟踪应变超声心动图分析心肌功能，这是一种能够检测LV功能中亚临床异常的技术，无法使用传统方法检测到。在父母研究设计之后，将在150名RA患者中进行横截面分析，以评估抗CCP抗体滴度与LV收缩/舒张/舒张功能的相关性，通过斑点跟踪超声心动图。对于AIM 2，将评估50例与TNF治疗或标准治疗的严重RA活性患者的LV收缩/舒张功能，并在治疗6个月后评估治疗对心脏功能的影响。