LONG TERM CONSEQUENCES OF SLE: VASCULAR AND BONE COMPLICATIONS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在系统性红斑狼疮（SLE）患者中，低骨密度（BMD）与冠状动脉血管钙化和颈动脉斑块指数升高之间存在显著关联。这就提出了有关血管疾病和骨质疏松症的潜在机制的问题，骨质疏松症的临床问题先前部分归因于无SLE的绝经后妇女的衰老。此外，由于少数民族女性患狼疮的风险和疾病的严重程度增加，因此将研究非裔美国女性与白人SLE女性在骨质疏松症和动脉粥样硬化发生率方面的潜在种族/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骨密度有关，即使考虑到传统的心血管危险因素，低骨密度也能预测SLE女性的心血管结局。要检验的主要假设是：(1)骨密度与SLE患者血管钙化呈负相关，与年龄和种族匹配的对照组无关，与传统的心血管危险因素无关。(2)骨密度与SLE患者颈动脉斑块和/或内膜中膜厚度呈负相关，与年龄和种族匹配的对照组无关，与传统的心血管危险因素无关。次要假设是：(1)炎性标志物与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)oxLDL自身抗体与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；(3)OPG浓度与SLE患者血管钙化和/或颈动脉斑块呈负相关；独立于传统的动脉粥样硬化危险因素。与匹兹堡大学的一项合作研究将解决有关以下方面的探索性假设：(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)确定SLE女性和对照组随访3年后颈动脉斑块进展率；(3)确定骨质疏松或动脉粥样硬化的替代标志物是否能预测SLE女性或年龄和种族匹配的对照组未来心血管结局。

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.