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 i s 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
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