The Hopkins Lupus Cohort is an ongoing, prospective study in which SLE patients are followed by protocol, with visits at a minimum of every 3 months, now in its 16th year. The Cohort is racially balanced, with one-half of the members being African-American, and reflects a broad socioeconomic range. The Cohort represents a 15 year investment in the study of SLE outcomes, sponsored by NIH. It has led to a unique, prospective database of demographic, social, clinical and laboratory (routine, serologic, and antiphospholipid antibody) measures. The four major accomplishments of the Cohort during the last funding period were: 1) the determination that serologic markers of disease activity, such as anti-dsDNA, C3, and C4, have limited utility in the prediction of SLE flare; 2) the determination that the cumulative prednisone dose is predictive of coronary artery disease and osteoporosis, whereas high-dose prednisone is predictive of avascular necrosis; 3) the determination that antiphospholipid antibodies are associated with future risk of thrombosis and with atherosclerosis; and 4) the finding that the poor health status of SLE patients is associated with fibromyalgia, whereas fibromyalgia itself correlates highly with neurally-mediated hypotension, a form of autonomic neuropathy. In this revised grant, four new specific aims will be undertaken. First, in the cohort as a whole and in an inception cohort followed since diagnosis, we will determine the relative importance of disease activity versus corticosteroid treatment as a predictor of specific types of organ damage. Second, in a study of 75 patients seen monthly, we will investigate cytokines and platelet-related factors as predictors of disease activity. Third, 250 patients from the inception cohort will have carotid duplex and helical CT (for coronary calcification scores) at baseline and 2 years later to determine associates and predictors of atherosclerosis, including traditional and novel cardiovascular risk factors. Fourth, we will assess, in 100 SLE patients with and 100 without fibromyalgia, the frequency of autonomic neuropathy and the correlation with health status.