Inflammation, Heart and Bone

描述（由申请人提供）：他汀类药物除了具有已知的降脂作用外，还是强效抗炎药。在一般人群中，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，这是一个既往未接受他汀类药物治疗的人群。最近，具有里程碑意义的JUPITER研究改变了CVD一级预防的面貌，最近，FDA扩大了他汀类药物治疗的批准范围，包括hsCRP >2 mg/L，LDL-胆固醇<130 mg/dL和一个额外的心血管风险因素的老年受试者的一级预防。然而，JUPITER的发现不应该自动外推到HIV的促炎状态。我们的假设是，在病毒学控制良好、CRP高且LDL-C正常的HIV感染患者中，瑞舒伐他汀将改善内皮功能并减少动脉粥样硬化形成，并且瑞舒伐他汀主要作为抗炎和抗氧化剂发挥作用。此外，由于炎症和骨质疏松症在一般人群中的密切联系，以及多项动物和人体研究显示他汀类药物对骨代谢的有益作用，我们将利用这一独特的机会来研究他汀类药物对骨骼健康的影响。具体目标将在一项随机、双盲、安慰剂对照试验中进行研究，该试验包括140名接受稳定抗逆转录病毒治疗且HIV病毒学控制良好的HIV感染受试者，LDL-C <130 mg/dL且hsCRP >2 mg/L。这项研究在这一人群中是新颖的，将对未来HIV感染者的管理产生重大影响，特别是在更好地完善他汀类药物治疗在一级心血管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.