Inflammation and Cardiovascular Disease in RA

心血管疾病是类风湿性关节炎(RA)发病和死亡的主要原因。这 心血管风险的增加被认为是通过共同的炎症途径来调节的；然而，这已经被 很难证明。本提案是对现有R01《RA和心血管》的续签申请 疾病“(AR050026-05)由NIAMS资助。我们在当前的资助期取得了很大的成效。 我们的一些发现包括亚临床冠状动脉和颈动脉粥样硬化的患病率更高， 与非类风湿性关节炎患者相比，类风湿性关节炎患者的左心室重量显著减少。此外，我们还有 注意到类风湿关节炎部分地通过“传统的”心血管危险因素间接地发挥其促动脉粥样硬化作用 小路。在这一更新中，我们建议询问炎症在调节加速的 通过直接对血管和心肌进行成像研究RA的动脉粥样硬化和心肌功能障碍 炎症或其后遗症(纤维化)的特点。此外，我们希望确认初步的 观察到RA易感基因(人类白细胞抗原B1*“共同表位”)也是更严重的风险因素。 亚临床动脉粥样硬化。我们的总体假设是类风湿性血管炎症和 心肌易于加速动脉粥样硬化和心肌功能障碍，这些影响是 部分由类风湿关节炎易感基因介导。我们提出以下目标： 具体目标1.在横断面分析中，我们将比较血管壁和斑块的特征 应用颈动脉MRI对RA与非RA患者的颈动脉进行对比分析。 具体目标2.在对RA受试者的横断面分析中，我们将调查 心脏磁共振延迟成像评价心肌纤维化及心肌灌注对左室结构和功能的影响 增强，第一次通过灌流和标记。 具体目标3.在对几个联合RA人群的横断面分析中，我们将评估 RA相关的人类白细胞抗原-DRB1“共享表位”(SE)基因与红斑狼疮的存在和严重程度的关系 动脉硬化。 这些研究将提供重要的新信息，这些信息将有助于RA患者的心血管风险分层 对于早期的积极干预，因此有可能降低类风湿性关节炎中心血管相关的发病率和死亡率。

Cardiovascular (CV) disease is a major cause of morbidity and mortality in rheumatoid arthritis (RA). This increased CV risk is thought to be mediated through shared inflammatory pathways; however, this has been difficult to prove. This proposal is an application for renewal of an existing R01, "RA and Cardiovascular Disease" (AR050026-05) funded by NIAMS. We have been very productive in the current funding period. Some of our findings include a higher prevalence of subclinical coronary and carotid artery atherosclerosis, and significant reduction in left ventricular mass, in RA compared to nonRA subjects. In addition, we have noted that RA exerts its pro-atherogenic effect, in part, indirectly through "conventional" CV risk factor pathways. In this renewal, we propose to interrogate the role of inflammation in mediating accelerated atherosclerosis and myocardial dysfunction in RA by directly imaging the blood vessels and myocardia for characteristics of inflammation or its sequelae (fibrosis). Furthermore, we wish to confirm preliminary observations that RA susceptibility genes (the HLA-B1* "shared epitopes") are also risk factors for more severe subclinical atherosclerosis. Our overall hypothesis is that rheumatoid inflammation of blood vessels and myocardium predisposes to accelerated atherosclerosis and myocardial dysfunction, and that these effects are mediated in part by RA susceptibility genes. We propose the following aims: Specific Aim 1. In cross-sectional analyses, we will compare blood vessel wall and plaque characteristics of carotid arteries of RA vs nonRA subjects using carotid MRI. Specific Aim 2. In cross-sectional analyses of RA subjects, we will investigate the association of measures of LV structure and function with myocardial fibrosis and perfusion using cardiac MRI with delayed enhancement, first pass perfusion and tagging. Specific Aim 3. In cross-sectional analyses of several combined RA populations, we will evaluate the association of the RA-associated HLA-DRB1 "shared epitope" (SE) genes with the presence and severity of atherosclerosis. These studies will contribute important new information that will be useful in CV risk stratifying RA patients for earlier aggressive intervention, thus potentially reducing CV associated morbidity and mortality in RA.