LUPUS ATHEROSCLEROSIS PREVENTION STUDY (LAPS)\PAR }

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。心血管疾病，特别是动脉粥样硬化，是发达国家SLE患者死亡的主要原因。冠状动脉疾病和中风是存活患者长期发病的原因之一。SLE的动脉粥样硬化是多因素的，免疫/炎症性内皮损伤、传统的心血管危险因素、血栓形成前因子都起着重要作用。多组研究表明，高脂血症可预测SLE患者后期动脉粥样硬化。在一般人群中，他汀类药物已成为预防动脉粥样硬化事件的首选药物，通过两种机制：降低脂质有助于防止进展，稳定斑块以防止破裂。在狼疮动脉粥样硬化预防试验中，我们将确定阿托伐他汀是否能减少动脉粥样硬化的进展，通过螺旋CT和颈动脉双相评估。最近的研究证实他汀类药物具有免疫调节作用。这项研究还将确定他汀类药物是否能改善临床狼疮活动或狼疮血清学（抗dsdna和补体）。该临床试验将比较阿托伐他汀40mg与安慰剂，结果是颈动脉双相测量的新动脉粥样硬化斑块或进展性斑块。另一个结果是颈动脉内膜内侧厚度，这是动脉粥样硬化的替代变量。我们将利用螺旋CT评估他汀类药物治疗对冠状动脉钙化评分的影响。最终目的是确定哪些危险因素、传统心血管危险因素、狼疮活性、抗磷脂抗体和其他血栓前因子最能预测SLE的动脉粥样硬化。我们建议招募200名完成的受试者，随访2年。已向聘管局提交一份修正案，拟增加拟招聘科目的人数，以提供200名完成。本方案利用了心血管核心实验室

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. Cardiovascular disease, specifically from atherosclerosis, is the major cause of mortality in SLE in developed countries. Coronary artery disease and stroke contribute to long-term morbidity in surviving patients. Atherosclerosis in SLE is multifactorial, with immune/inflammatory endothelial damage, traditional cardiovascular risk factors, and prothrombotic factors all playing important roles. Multiple groups have shown that hyperlipidemia is predictive of later atherosclerosis in SLE. In the general population, statins have become the drug of choice in preventing atherosclerotic events, through two mechanisms: lipid lowering that helps to prevent progression, and stabilization of plaques to prevent rupture. In the Lupus Atherosclerosis Prevention Trial we will determine if atorvastatin reduces the progression of atherosclerosis assessed using helical CT and carotid duplex. Recent work has confirmed that statins have an immunomodulatory role. This study will also determine whether statins improve clinical lupus activity or lupus serologies (anti-dsDNA and complement). This clinical trial will compare atorvastatin 40 mg vs placebo with the outcome being new or progressive atherosclerotic plaque measured on carotid duplex. Another outcome will be carotid intimal medial thickness, a surrogate variable for atherosclerosis. We will evaluate the effect of statin therapy on coronary calcium score using helical CT. The final aim is to determine which risk factors, traditional cardiovascular risk factors, lupus activity, antiphospholipid antibodies, and other prothrombotic factors best predict atherosclerosis in SLE. We propose to enroll 200 completed subjects who will be followed for 2 years. An amendment has been submitted to the IRB to increase the number of subjects to the number that will be recruited to provide 200 completed. The Cardiovascular Core Lab was utilized for this protocol