Inflammation, Heart and Bone

描述(申请人提供)：他汀类药物除了具有已知的降脂作用外，还是一种强大的抗炎药。在普通人群中，大多数心血管事件发生在血脂水平正常或轻度升高的受试者中，这一人群以前没有针对他汀类药物治疗。最近，具有里程碑意义的JUPITER研究改变了心血管疾病一级预防的面貌，最近，FDA扩大了他汀类药物的批准范围，将hsCRP&gt；2 mg/L、低密度脂蛋白130 mg/dL的老年受试者纳入一级预防范围，并增加了一个心血管危险因素。然而，木星的发现不应自动推断为艾滋病毒的促炎状态。我们的假设是，在病毒学控制良好、C反应蛋白水平高、低密度脂蛋白正常的HIV感染患者中，瑞舒伐他汀可以改善内皮功能，减少动脉粥样硬化的形成，瑞舒伐他汀主要起到抗炎和抗氧化的作用。此外，由于在普通人群中炎症和骨质疏松症之间存在强烈的联系，以及多项动物和人类研究显示他汀类药物对骨骼代谢的有益影响，我们将利用这个独特的机会来研究他汀类药物对骨骼健康的影响。具体目标将在140名艾滋病毒感染者的随机、双盲、安慰剂对照试验中进行调查，这些人正在接受稳定的抗逆转录病毒治疗，艾滋病毒病毒学控制良好，使用低密度脂蛋白130 mg/dL和hsCRP&gt；2 mg/L。这项研究在这一人群中是新的，将对未来艾滋病毒携带者的管理具有重大意义，特别是在更好地完善他汀类药物在心血管一级预防中的适应症方面。

DESCRIPTION (provided by applicant): Statins drugs are powerful anti-inflammatory agents in addition to their known lipid- lowering effects. In the general population, most cardiovascular events occur in subjects with normal or mildly elevated lipid levels, a population previously not targeted for statin therapy. Recently, the landmark JUPITER study changed the face of primary CVD prevention and recently, the FDA expanded the approval of statin therapy to include primary prevention of older subjects with hsCRP >2 mg/L, LDL-cholesterol <130 mg/dL, and one additional cardiovascular risk factor. However, the findings of JUPITER should not be automatically extrapolated to the pro-inflammatory state of HIV. Our hypothesis is that in HIV-infected patients with good virologic control, high CRP and normal LDL-C, rosuvastatin will improve endothelial function and decrease atherogenesis, and that rosuvastatin acts primarily as an anti-inflammatory and anti-oxidant agent. Also, because of the strong link between inflammation and osteoporosis in the general population, and the multiple animal and human studies showing a beneficial effect of statins on bone metabolism, we will use this unique opportunity to examine the effects of statins on skeletal health. The specific aims will be investigated in a randomized, double-blind, placebo-controlled trial of 140 HIV-infected subjects who are on stable antiretroviral therapy and with good HIV virologic control, with LDL-C <130 mg/dL and hsCRP >2 mg/L. This study is novel in this population, and will have significant implications in future management of people living with HIV, specifically in better refining the indication of statin therapy in primary cardiovascular prevention.