ENDOTHELIAL DYSFUNCTION IN CHILDREN & ADULTS W/ SYSTEMIC LUPUS ERYTHEMATOSUS

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。心血管疾病是儿童和成人狼疮(SLE)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)患病率是年龄匹配的对照组的50倍。为了识别高危患者并研究预防策略，发现预测系统性红斑狼疮患者冠心病发展的早期变化是重要的。我们将评估三种血管损伤的无创性测试，包括血流介导的臂动脉扩张(FMD)，超声测量颈动脉内中膜厚度(CIMT)，以及螺旋CT(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被描述。疾病活动性或抗磷脂抗体(APA)是否会加重SLE患者的FMD尚不清楚。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大量的临床数据。在基线访问中，我们将描述FMD的特征及其与临床疾病特征、CIMT、Hct、APA和预测动脉损伤的实验室测试的关系。患有狼疮的成人和儿童将与“健康”的对照组进行比较。我们将检验这些假设：(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)APA和SLE活动增加预示着更糟糕的FMD。然后我们将纵向跟踪狼疮患者的FMD，CIMT和Hct的测量。我们将检验这一假设，即功能异常，FMD降低，预测CIMT测量的CAD解剖变化的进展和Hct测量的冠状动脉钙化。如果异常的FMD识别出将来会发展为冠心病的患者，那么它可能会作为候选治疗干预措施的筛查试验。

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.