Inflammation and Cardiovascular Disease in RA

描述(申请人提供)：心血管疾病(CVD)是类风湿性关节炎(RA)发病率和死亡率的主要原因。与对照组相比，RA患者心血管相关死亡、充血性心力衰竭和急性心血管事件增加2-4倍，但心血管疾病的传统危险因素的患病率并未增加。我们假设类风湿关节炎引起的炎症促进和加重了心血管疾病，与传统的心血管危险因素无关。这项申请是动脉粥样硬化多种族研究(MESA)的辅助建议。我们将比较200名RA患者和1066名来自霍普金斯台地中心的非RA MESA参与者的亚临床心血管疾病的患病率和进展。在调整了传统的心血管危险因素后，将检查炎症对RA患者心血管疾病增加的影响程度。我们的具体目标如下： 具体目的1.在横断面分析中，我们将比较RA患者和对照组之间动脉粥样硬化(冠状动脉钙化)和左心室(LV)功能障碍的指标(通过磁共振成像)。我们将确定冠脉钙化和左心功能不全组之间的差异是否由类风湿性关节炎的血清炎症标记物(例如，CRP、IL-6、可溶性黏附分子)来解释。 具体目的2.在前瞻性分析中，我们将比较类风湿性关节炎患者和对照组冠脉钙化的变化。我们将确定血清炎症标志物升高对冠状动脉钙化进展的影响程度。 具体目标3.我们将评估各种炎症标志物和疾病活动性/严重性，以及传统的心血管危险因素，在基线和三年以上的RA患者中，与冠脉钙化和左心功能不全之间的关系。特别是，将检查各种炎症和疾病活动/严重程度的标记物对冠状动脉钙化和左心室功能障碍的潜在剂量-反应关系。

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). CV-related deaths, congestive heart failure, and acute CV events are increased 2-4 fold in RA patients compared to matched controls, but the prevalence of conventional risk factors for CVD is not increased. We hypothesize that inflammation due to RA promotes and exacerbates CVD, independent of conventional CV risk factors. This application is an ancillary proposal to the Multi-Ethnic Study of Atherosclerosis (MESA). We will compare the prevalence and progression of subclinical CVD in 200 RA patients to 1066 non-RA MESA participants from the Hopkins MESA Field Center. The degree to which inflammation contributes to increased CVD in RA patients will be examined, after adjusting for conventional CV risk factors. Our specific aims are as follows: Specific Aim 1. In a cross-sectional analysis we will compare a measure of atherosclerosis (coronary calcium) and measures of left ventricular (LV) dysfunction (by magnetic resonance imaging) between RA patients and controls. We will determine whether differences between the groups in coronary calcium and LV dysfunction are explained by serum markers of inflammation in RA (e.g., CRP, interleukin-6, soluble adhesion molecules). Specific Aim 2. In a prospective analysis, we will compare the changes in coronary calcium between RA patients and controls. We will determine the degree to which elevated serum markers of inflammation contribute to differences in progression of coronary calcium. Specific Aim 3. We will assess the associations of various markers of inflammation and disease activity/severity, as well as conventional CV risk factors, with coronary calcium and LV dysfunction at baseline and over three years, among RA patients. Particularly, the potential dose-response relationships of various markers of inflammation and disease activity/severity to coronary calcium and LV dysfunction will be examined.