LONG TERM CONSEQUENCES OF SLE: VASCULAR AND BONE COMPLICATIONS

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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. In systemic lupus erythematosus (SLE) patients there is a significant association between low bone mineral density (BMD) with the presence of vascular calcifications in the coronary arteries and higher plaque index in the carotid arteries. This raises questions concerning potential mechanisms linking vascular disease and osteoporosis, clinical problems that have been previously attributed, in part, to aging in postmenopausal women without SLE. In addition, because the risk of lupus and severity of disease is increased in minority women, potential racial/ethnic differences in the frequency osteoporosis and atherosclerosis in African-American women compared with Caucasian women with SLE will be studied. The overriding hypothesis is that vascular calcification and early atherosclerosis is associated with low BMD and that low BMD predicts cardiovascular outcomes in SLE women, even after accounting for traditional cardiovascular risk factors. The primary hypotheses to be tested are: (1) BMD is inversely associated with vascular calcifications in SLE, as well as in age and race matched controls, independent of traditional cardiovascular risk factors (2) BMD is inversely associated with carotid plaque and/or intima media thickness in SLE, as well as in age and race matched controls, independent of traditional cardiovascular risk factors. The secondary hypotheses are: (1) Inflammatory markers are associated with vascular calcification and/or carotid plaque in patients with SLE, independent of traditional risk factors for atherosclerosis (2) Autoantibodies to oxLDL are associated with vascular calcification and/or carotid plaque in patients with SLE, independent of traditional risk factors for atherosclerosis (3) The concentration of OPG, will be inversely associated with vascular calcification and/or carotid plaque in patients with SLE, independent of traditional risk factors for atherosclerosis. A collaborative study with the University of Pittsburgh will address exploratory hypotheses relating to: (1) Racial differences in the frequencies of carotid plaque and vascular calcifications in African-American and Caucasian women (2) Determining rates of progression of carotid plaque after three years of follow-up in SLE women and controls (3) Determining whether surrogate markers for osteoporosis or atherosclerosis predict future cardiovascular outcomes in SLE women or in age and race matched controls.