Inflammation and Coronary Endothelial Function

炎症与冠状动脉内皮功能

基本信息

批准号：
8979715
负责人：
ROBERT G WEISS
金额：
$ 60.96万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-08 至 2018-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8979715
关键词：
Address Anti-Inflammatory Agents Anti-inflammatory Atherosclerosis Autoimmune Diseases Biological Markers Biology Blinded Blood Vessels C-reactive protein Caliber Cardiovascular system Catheterization Cholesterol Clinical Clinical Trials Colchicine Coronary Coronary Arteriosclerosis Coronary Vessels Coronary artery Data Dependence Development Disease Dose Event Figs - dietary Folic Acid Guidelines Health Heart Diseases Hypertension Immune response Individual Inflammation Inflammation Mediators Inflammatory Interleukin-1 Interleukin-6 Interleukins Intervention Laboratories Magnetic Resonance Imaging Measures Medical Methods Methotrexate Nitric Oxide Outcome Pathway interactions Patients Peripheral Pharmaceutical Preparations Placebos Play Population Premature Mortality Prevention Guidelines Process Randomized Reproducibility Risk Risk Factors Role Serum TNF gene Techniques Testing Time Translating Vasomotor base brachial artery cardiovascular risk factor clinical practice conventional therapy design disability disorder risk endothelial dysfunction experience improved inflammatory marker insight next generation novel patient population placebo controlled study response treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Despite aggressive current guideline-driven therapies, coronary artery disease (CAD) patients remain at increased risk of cardiovascular events, possibly because conventional treatments do not adequately address some of the inflammatory pathways implicated in the disease. Anti- inflammatory strategies have been associated with lower cardiovascular event rates in individuals with inflammatory autoimmune disease and are appealing in more general CAD populations but are not currently used in practice because of the lack of an established and easily obtained measure of the effect of inflammation on the processes which result in coronary atherosclerosis and because no clinical trial has established whether an anti-inflammatory strategy, per se, alters these processes. Inflammation contributes to the process of coronary endothelial dysfunction which plays a pivotal role in the development, progression, and clinical manifestations of CAD, and is a marker for sub-clinical disease, an independent predictor of adverse cardiovascular events, and a potential target for medical interventions. We recently developed noninvasive, reproducible MRI-based methods to measure CEF. We propose a 2x2 blinded, placebo-controlled trial to test the hypothesis that anti-inflammatory approaches, namely very low dose methotrexate (VLDM), low dose colchicine (LDC) and/or their combination, improve impaired local CEF in stable CAD patients with increased markers of inflammation on conventional cardiovascular medications. The studies will provide novel much- needed mechanistic insight into the potential of anti-inflammatory strategies to reduce coronary endothelial dysfunction, which inflammatory biomarkers herald the CEF response, and whether a heterogeneous coronary response occurs with differential effects in more severely than mildly diseased coronary vessels, suggesting local anti-inflammatory effects. In addition to this novel mechanistic information, the findings with these clinically available drugs will guide the next generation of clinical outcome trials and can be rapidly translated to practice.

描述（由申请人提供）：尽管目前以指南驱动的疗法有进取心，但冠状动脉疾病（CAD）患者仍处于心血管事件的风险增加，这可能是因为常规治疗并不能充分解决疾病中涉及的某些炎症途径。抗炎策略与患有炎症性自身免疫性疾病的个体的心血管事件发生率较低有关，并且在更普遍的CAD种群中吸引人，但由于缺乏既定且易于获得的炎症对冠状动脉症和冠状动脉症的效果的衡量标准，目前尚未在实践中使用，因为没有临床试验，因为临床试验没有临床试验的策略，该过程是否存在抗议策略，是否存在策略，这些策略是否存在，这些策略是否存在，这些过程是否存在。炎症有助于冠状动脉内皮功能障碍的过程，该过程在CAD的发育，进展和临床表现中起关键作用，并且是亚临床疾病的标志物，这是不良心血管事件的独立预测指标，并且是医疗干预措施的潜在靶标。我们最近开发了基于MRI的非侵入性，基于MRI的方法来测量CEF。我们提出了一项盲目的安慰剂对照试验，以检验以下假设：抗炎方法，即非常低剂量的甲氨蝶呤（VLDM），低剂量的秋水仙碱（LDC）和/或组合，改善了稳定的CAD CAD患者的局部CAD患者的稳定标记患者的局部CAD稳定药物的稳定药物受损。这项研究将为抗炎策略的潜力提供急需的机械洞察力，以减少冠状动脉内皮功能障碍的潜力，炎症性生物局部标志物预示了CEF的反应，以及是否在轻度疾病的冠状动脉血管中产生差异性，是否具有异质性差异，这表明局部冠状动脉疾病更严重。除了这些新颖的机械信息外，这些临床上可用药物的发现还将指导下一代临床结果试验，并可以迅速转化为实践。