LONG TERM CONSEQUENCES OF SLE: VASCULAR AND BONE COMPLICATIONS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在系统性红斑狼疮（SLE）患者中，低骨矿物质密度（BMD）与冠状动脉中血管钙化和颈动脉中斑块指数较高之间存在显著相关性。 这引起了关于血管疾病和骨质疏松症的潜在机制的问题，这些临床问题以前部分归因于绝经后无SLE妇女的衰老。 此外，由于少数民族女性的狼疮风险和疾病严重程度增加，因此将研究非裔美国女性与白人SLE女性相比骨质疏松症和动脉粥样硬化发生率的潜在种族/民族差异。 最重要的假设是，血管钙化和早期动脉粥样硬化与低BMD相关，即使在考虑了传统的心血管危险因素后，低BMD也能预测SLE女性的心血管结局。待检验的主要假设为： (1)BMD与SLE患者以及年龄和种族匹配的对照组中的血管钙化呈负相关，与传统的心血管危险因素无关 (2)BMD与SLE患者颈动脉斑块和/或内膜中层厚度呈负相关，与年龄和种族匹配的对照组也是如此，与传统的心血管危险因素无关。 次要假设为： (1)炎症标志物与SLE患者血管钙化和/或颈动脉斑块相关，独立于动脉粥样硬化的传统危险因素 (2)氧化低密度脂蛋白自身抗体与SLE患者血管钙化和/或颈动脉斑块相关，与动脉粥样硬化的传统危险因素无关 (3)OPG浓度与SLE患者的血管钙化和/或颈动脉斑块呈负相关，与动脉粥样硬化的传统危险因素无关。 与匹兹堡大学的一项合作研究将探讨与以下方面有关的探索性假设： (1)非裔美国人和白人女性颈动脉斑块和血管钙化频率的种族差异 (2)SLE女性患者和对照组患者3年随访后颈动脉斑块进展率的测定 (3)确定骨质疏松症或动脉粥样硬化的替代标志物是否预测SLE女性或年龄和种族匹配对照组的未来心血管结局。

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.