Inflammation and Atherosclerosis in Rheumatoid Arthritis

描述（由申请人提供）：动脉粥样硬化和类风湿关节炎（RA）是两种炎症性疾病，在病理生物学上有明显的相似性。在一般人群中，炎症生物标志物（如C反应蛋白，CRP）升高的个体心血管事件增加。类风湿性关节炎患者CRP和其他炎症标志物的慢性升高，通常高于普通人群中与CV风险增加相关的水平。事实上，类风湿性关节炎患者有加速动脉粥样硬化和增加心血管死亡率，这不能用传统的心脏危险因素来解释，但与慢性炎症有关。然而，全身性炎症导致动脉粥样硬化的机制在类风湿关节炎中尚未得到很好的表征。此外，目前RA的治疗策略主要针对关节症状，而不是全身性炎症，这可能会增加患者患心血管疾病的风险。在动物模型和人类疾病中，炎症诱导促动脉粥样硬化脂蛋白异常、硝基氧化应激和内皮功能障碍，这是动脉粥样硬化发展的关键。然而，在RA的全谱炎症和临床表现中，这些促动脉粥样硬化标志物的研究是缺失的。我们假设炎症标志物与类风湿关节炎患者的动脉粥样硬化变化的相关性比任何疾病活动性的临床指标都强。这一假设将在UCSF RA队列患者的横断面研究中得到验证。目的1将描述RA疾病活动范围内的动脉粥样硬化变化，特别是通过血流介导的血管舒张、硝基氧化应激标志物和促动脉粥样硬化脂蛋白来测量内皮功能。Aim 2将在RA疾病活动范围内确定与这些动脉粥样硬化变化相关的因素，特别关注炎症标志物、FMD和促动脉粥样硬化脂蛋白异常之间的关联。类风湿性关节炎患者体内的炎症会增加，从而导致动脉粥样硬化或血管中斑块的积聚，这是美国人死亡的主要原因。通过研究类风湿关节炎的炎症和动脉粥样硬化，我们可以更好地了解导致动脉阻塞的原因，并提高类风湿关节炎的治疗标准，以延长患者的生命，而不仅仅是缓解症状。

DESCRIPTION (provided by applicant): Atherosclerosis and rheumatoid arthritis (RA) are two inflammatory diseases with marked similarities in pathobiology. In the general population, individuals with elevated inflammatory biomarkers (e.g. C- reactive protein, CRP) have increased CV events. Patients with RA have chronic elevations in CRP and other inflammatory markers that are usually higher than the levels associated with increased CV risk in the general population. Indeed, RA patients have accelerated atherosclerosis and increased CV mortality not explained by traditional cardiac risk factors but associated with chronic inflammation. However, the mechanisms by which systemic inflammation leads to atherosclerosis are not well characterized in RA. Moreover, current treatment strategies of RA largely target joint symptoms rather than systemic inflammation, potentially leaving patients at increased risk for CVD. In animal models and in human diseases, inflammation induces pro-atherogenic lipoprotein abnormalities, nitro-oxidative stress and endothelial dysfunction, which are pivotal in the development of atherosclerosis. However, studies of these pro-atherogenic markers in the full spectrum of inflammation and clinical manifestations in RA are missing. We hypothesize that inflammatory markers will be more strongly associated with atherogenic changes in RA patients than any clinical measure of disease activity. This hypothesis will be tested with a cross-sectional study of patients in the UCSF RA cohort. Aim 1 will characterize atherogenic changes across the spectrum of RA disease activity, specifically measuring endothelial function by flow-mediated vasodilation, markers of nitro-oxidative stress, and pro-atherogenic lipoproteins. Aim 2 will identify factors associated with these atherogenic changes across the spectrum of RA disease activity, specifically focusing on the association between inflammatory markers, FMD and pro-atherogenic lipoprotein abnormalities. Rheumatoid arthritis patients have increased inflammation in their bodies, which leads to atherosclerosis, or plaque build-up in blood vessels, the leading cause of death in the United States. By studying inflammation and atherosclerosis in RA, we can understand better what causes clogged arteries in general, as well as improve the standards of treatment for RA to prolong lives in addition to just alleviating symptoms.