Inflammation, Heart and Bone

点击翻译按钮获取中文摘要

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. PUBLIC HEALTH RELEVANCE: People living with HIV are getting older and suffering from several complications of HIV and its therapy, including increased risk of heart disease and osteoporosis. This study will examine the effect of a potent statin medication on these complications and will aim to understand the driver of these complications in people living with HIV. Our goal is that by using a safe agent, like statins, we will be able to decrease the risk of cardiovascular disease and thin bones in people living with HIV. In addition, we will be able to better understand the role played by chronic inflammation and oxidant stress on these complications.