ENDOTHELIAL DYSFUNCTION IN CHILDREN & ADULTS W/ SYSTEMIC LUPUS ERYTHEMATOSUS

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。心血管疾病是狼疮（SLE）儿童和成人患病和死亡的主要原因。年轻女性狼疮患者的心血管疾病（CAD）患病率是年龄匹配对照组的50倍。为了识别有风险的患者并研究预防策略，重要的是检测预测SLE患者CAD发展的早期变化。我们将评估血管损伤的三种无创性检查，包括血流介导的肱动脉扩张（FMD）、超声测量颈动脉内膜中层厚度（CIMT）和螺旋计算机断层扫描（HCT）测量冠状动脉钙。FMD测量动脉对生理刺激的反应能力。FMD在成人狼疮患者中是异常的，但在儿童狼疮患者中尚未描述。目前尚不清楚是否疾病活动或抗磷脂抗体（阿帕）恶化FMD在SLE。我们将从密歇根狼疮队列中招募患者，他们以系统化的方式收集了广泛的临床数据。在基线访视时，我们将描述FMD及其与临床疾病特征、CIMT、HCT、阿帕和预测动脉损伤的实验室检查的关系。患有狼疮的成人和儿童将与“健康”对照组进行比较。我们将测试这些假设：（1）儿童和成人狼疮患者在亚临床心血管疾病的这些测量中比对照组有更多的异常，（2）阿帕和SLE活动增加预示着更严重的FMD。然后，我们将纵向跟踪狼疮患者的FMD，CIMT和HCT的测量。我们将检验一个假设，即功能异常，FMD减少，预测CAD的解剖结构变化的进展，通过CIMT和HCT测量冠状动脉钙化。如果FMD异常识别出将来会发展为CAD的患者，那么它可能作为候选治疗干预的筛选测试是有用的。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cardiovascular disease is a major cause of illness and death in children and adults with lupus (SLE). The prevalence of cardiovascular disease (CAD) in young women with lupus is 50 times that of age-matched controls. In order to identify patients at risk and to study preventive strategies, it is important to detect early changes that predict development of CAD in SLE. We will evaluate three noninvasive tests for vascular injury, including flow-mediated brachial artery dilatation (FMD), carotid intimal-medial thickness (CIMT) measurement by ultrasound, and helical computed tomography (HCT) measurement of coronary artery calcium. FMD measures the ability of arteries to respond to physiologic stimuli. FMD is abnormal in adult lupus patients but is not yet described in children with lupus. It is not known whether disease activity or antiphospholipid antibodies (APA) worsen FMD in SLE. We will recruit patients from the Michigan Lupus Cohort, who have extensive clinical data collected in a systematized fashion. At the baseline visit we will characterize FMD and its relation to clinical disease features, CIMT, HCT, APA, and laboratory tests that predict arterial injury. Adults and children with lupus will be compared with "healthy" controls. We will test these hypotheses: (1) Children and adults with lupus have more abnormalities in these measurements of subclinical cardiovascular disease than controls, and (2) APA and increased SLE activity predict worse FMD. We will then longitudinally follow the lupus patients with measurements of FMD, CIMT and HCT. We will test the hypothesis that a functional abnormality, decreased FMD, predicts progression of anatomical changes of CAD, as measured by CIMT and calcification of coronary arteries by HCT. If abnormal FMD identifies patients who will develop CAD in the future, then it may be useful as a screening test for candidate therapeutic interventions.