The Impact of Omega three Fatty Acids on Vascular Function and cIMT in HIV

描述（由申请人提供）：有令人信服的证据表明感染艾滋病毒的患者患心血管疾病的风险增加。 HIV 感染者存在多种潜在的 CVD 风险；长期以来，致动脉粥样硬化的脂质谱与心血管疾病风险增加有关；总胆固醇和低密度脂蛋白胆固醇的升高已被证明与一般人群中这种风险增加有关。最近的数据表明，甘油三酯水平升高和高密度脂蛋白胆固醇水平降低可能是心血管疾病风险同样重要的标志。还有新的数据表明，CVD 是一种炎症性疾病，HDL-C 水平和亚型是由炎症介导的；在艾滋病毒感染者中，这些变化可能会因艾滋病毒感染而加剧。虽然治疗致动脉粥样硬化的脂质谱是理想的，但是在HIV感染个体中治疗HIV感染中的这些异常的尝试是复杂的。在感染和未感染艾滋病毒的人群中进行的研究表明，摄入高剂量的欧米伽三脂肪酸可以降低甘油三酯，并可能对高密度脂蛋白胆固醇水平产生有益的影响。摄入欧米伽三脂肪酸会改变脂质代谢，并可能通过减少花生四烯酸的产生来减少炎症。目前，还没有数据可以扩展这些观察结果，以确定在更长的时间内摄入欧米伽 3 脂肪是否也会对 HIV 感染患者的血管功能和 CVD 替代标志物产生有益影响。我们建议对甘油三酯水平升高的艾滋病毒感染者进行纯化欧米伽三脂肪酸的随机、双盲试验。虽然欧米伽三脂肪酸对血脂谱的影响应该在 12 周内显现出来，但我们建议进行整整 24 个月的试验，以检验我们的总体假设，即这种干预不仅会改善甘油三酯和 HDL-C 水平、改善 HDL 亚型和膜磷脂并减少炎症，而且还会改善肱动脉反应性，作为 24 周时衡量血管功能的指标，并导致作为替代标志物的 cIMT 进展率降低。与对照组相比，24 个月时的 CVD。该提案的具体目标包括： 1. 在甘油三酯水平升高（> 150 mg/dl）的 HIV 感染者中进行一项为期 24 个月的欧米伽三脂肪酸随机、安慰剂对照试验。 2. 证明欧米伽三脂肪酸摄入量对 TG 水平和 HDL-C 水平、HDL 亚型、膜磷脂组成、通过 CRP、sPLA2 和花生四烯酸水平测量的慢性炎症的影响。 3. 证明欧米茄三脂肪酸摄入量对 24 周时肱动脉反应性和 24 个月时 cIMT 的影响。

DESCRIPTION (provided by applicant): There is convincing evidence that there is an increased risk of cardiovascular disease in patients infected with HIV. There are multiple potential risks for CVD in HIV infected patients; atherogenic lipid profiles have long been associated with increased risk of cardiovascular disease; elevations in total and LDL cholesterol have been demonstrated to be associated with such increased risk in the general population. More recent data suggest that elevations in levels of triglycerides and decreased levels of HDL cholesterol may be equally important markers of CVD risk. There is also emerging data that CVD is an inflammatory disease, and that HDL-C levels and subprofiles are mediated by inflammation; in HIV-infected individuals these changes may be exacerbated by the HIV infection. While treatment of atherogenic lipid profiles is desirable, attempts to treat these abnormalities in HIV infection are complex in HIV infected individuals. In studies done in populations with and without HIV, intake of high doses of omega three fatty acids is demonstrated to decrease triglycerides and may have a beneficial effect on HDL-cholesterol levels. Intake of omega three fatty acids alters lipid metabolism and may decrease inflammation by decreasing production of arachidonic acid. At present, there are no data that extend these observations to determine whether intake of omega three fats over a more prolonged time period will also have a beneficial impact on vascular function and surrogate markers of CVD in HIV infected patients. We propose a randomized, double blind trial of purified omega three fatty acids in HIV infected individuals with elevated levels of triglycerides. While the impact of omega three fatty acids on lipid profiles should be evident within 12 weeks, we propose to conduct this trial for a full 24 months to test our overall hypothesis that this intervention will not only improve triglyceride and HDL-C levels, improve HDL- subprofiles and membrane phospholipids and decrease inflammation, but will also improve brachial artery reactivity as a measure of vascular function at 24 weeks and lead to a reduced rate of progression of cIMT as a surrogate marker of CVD at 24 months when compared to controls. The specific aims of this proposal include: 1. to conduct a randomized, placebo controlled trial of omega three fatty acids over 24 months in HIV- infected individuals with elevated levels of triglycerides (> 150 mg/dl). 2. To demonstrate the impact of omega three fatty acid intake on TG levels and on HDL-C levels, HDL subprofiles, composition of membrane phospholipids, chronic inflammation as measured by CRP, sPLA2 and by levels of arachidonic acid. 3. To demonstrate the impact of omega three fatty acid intake on brachial artery reactivity at 24 weeks and on cIMT at 24 months.