Longterm consequences of Lupus;vascular and bone complications

Northwestern University, Evanston IL

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Abstract

DESCRIPTION (provided by applicant): Survival has improved over the last two decades for patients with systemic lupus erythematosus (SLE). Attention is now focused on modifying complications leading to late mortality and progressive morbidity. Fracture M), stroke (CVA), and myocardial infarction (MI) commonly occur in young women with SLE, who should be protected from such events. Our preliminary data demonstrates in women with SLE an association between low bone mineral density (BMD) at the spine and hip with the presence of vascular calcifications in the coronary arteries. These observations are unique and suggest common mechanisms linking atherosclerosis and osteoporosis, clinical problems noted previously in non-SLE postmenopausal women. Potential common features in bone and vascular biology include 1) inflammatory markers/mediators, 2) autoantibodies, and 3) tumor necrosis factor (TNF) superfamily members. These features may be relevant in explaining why atherosclerosis and osteoporosis affects young women with SLE. The overriding hypothesis for this epidemiologic study is that vascular calcification and early atherosclerosis are associated with low bone mineral density (BMD), and that low BMD predicts cardiovascular outcomes in SLE women, even after accounting for traditional cardiovascular risk factors. The three specific aims of this study of 200 women with SLE and 200 age and race matched controls are to 1) measure BMD in the spine, hip, and wrist by DXA; calcification in arteries (coronary and aorta) by electron beam computed tomography (EBCT); and carotid plaque by B-mode ultrasound, 2) measure traditional cardiovascular risk factors (e.g. lipids); inflammatory markers/mediators (e.g. CRP, soluble CD40); autoantibodies (phospholipids, neoepitopes to oxLDL); and TNF superfamily molecules (OPG), and 3) contact study participants every 6 months to ascertain clinical vascular events and repeat carotid B-mode ultrasound and risk factors measurements in years 4 and 5 to assess vascular progression. Descriptive statistics and regression models will be used to analyze data. Understanding the underlying pathogenesis of, and identifying surrogate markers and risk factors for, atherosclerosis and osteoporosis are essential steps in developing intervention and prevention strategies for fx, CVA, and MI outcomes in SLE. Indeed, SLE may be an ideal 'experiment of nature' in which to further examine the role of inflammation and immune mechanisms in osteoporosis and atherogenesis.