ENDOTHELIAL DYSFUNCTION IN CHILDREN & ADULTS W/ SYSTEMIC LUPUS ERYTHEMATOSUS

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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.