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

欧米茄三脂肪酸对 HIV 患者血管功能和 cIMT 的影响

• 批准号: 8300894
• 负责人: Christine A Wanke
• 金额: $ 72.19万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-20 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8300894
• 关键词: Anatomy; Arachidonic Acids; Blood Vessels; Body Composition; Body Weight; Cardiovascular system; Cell membrane; Chronic; Complex; Cytochrome P450; Data; Development; Diet; Disease; Dose; Double-Blind Method; Drug Interactions; Fatty Acids; Fatty acid glycerol esters; Fibrates; General Population; HDL-triglyceride; HIV; HIV Infections; Health; High Density Lipoprotein Cholesterol; High Density Lipoproteins; Highly Active Antiretroviral Therapy; Individual; Inflammation; Inflammatory; Intake; Intervention; LDL Cholesterol Lipoproteins; Lead; Life Style; Lipids; Measures; Mediating; Membrane; Morbidity - disease rate; Omega-3 Fatty Acids; Patients; Pharmaceutical Preparations; Phospholipids; Physical activity; Population; Production; Protease Inhibitor; Randomized; Relaxation; Risk; Smoking; Surrogate Markers; Testing; Thick; Time; Triglycerides; antiretroviral therapy; brachial artery; cardiovascular disorder risk; functional outcomes; improved; lipid metabolism; non-nucleoside reverse transcriptase inhibitors; randomized placebo controlled trial

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. PUBLIC HEALTH RELEVANCE: There is convincing evidence that there is an increased risk of cardiovascular disease in patients infected with HIV. Treatment of lipid abnormalities in HIV infection is difficult in HIV and studies suggest that intake of high doses of omega three fatty acids may safely improve lipids and decrease inflammation. We propose a randomized, double blind trial of purified omega three fatty acids in HIV infected individuals with elevated levels of triglycerides to test our overall hypothesis that this intervention will not only improve lipids and decrease inflammation, but will also improve vascular function at 24 weeks and lead to a reduced progression of surrogate markers of CVD at 24 months.

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感染患者存在多种CVD潜在风险;致动脉粥样硬化脂质谱长期以来与心血管疾病风险增加相关;已证明总胆固醇和LDL胆固醇升高与一般人群中此类风险增加相关。最近的数据表明，甘油三酯水平升高和HDL胆固醇水平降低可能是CVD风险的同样重要的标志物。还有新的数据表明，CVD是一种炎症性疾病，HDL-C水平和亚谱是由炎症介导的;在HIV感染者中，这些变化可能会因HIV感染而加剧。虽然致动脉粥样硬化脂质谱的治疗是期望的，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。在有和没有艾滋病毒的人群中进行的研究中，摄入高剂量的欧米伽三脂肪酸被证明可以降低甘油三酯，并可能对HDL-胆固醇水平产生有益的影响。摄入欧米伽3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omega-3脂肪是否也会对HIV感染患者的血管功能和CVD的替代标志物产生有益的影响。我们提出了一个随机，双盲试验纯化的ω 3脂肪酸在艾滋病毒感染者的甘油三酯水平升高。虽然欧米伽三脂肪酸对血脂的影响应该在12周内就很明显，但我们建议进行这项试验整整24个月，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亚谱和膜磷脂，减少炎症，而且与对照组相比，还将改善作为24周时血管功能量度的肱动脉反应性，并导致作为24个月时CVD替代标志物的cIMT进展速率降低。该提案的具体目标包括：1.对甘油三酯水平升高（> 150 mg/dl）的HIV感染者进行为期24个月的欧米伽3脂肪酸随机、安慰剂对照试验。2.证明ω 3脂肪酸摄入对TG水平和HDL-C水平、HDL亚谱、膜磷脂组成、慢性炎症（通过CRP、sPLA 2和花生四烯酸水平测量）的影响。3.证明ω 3脂肪酸摄入对24周时肱动脉反应性和24个月时cIMT的影响。公共卫生相关性：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。治疗HIV感染中的脂质异常在HIV中是困难的，研究表明，摄入高剂量的欧米伽三脂肪酸可以安全地改善脂质和减少炎症。我们提出了一项在甘油三酯水平升高的HIV感染者中进行纯化ω-3脂肪酸的随机双盲试验，以检验我们的总体假设，即这种干预不仅会改善脂质和减少炎症，而且还会改善24周时的血管功能，并导致24个月时CVD替代标志物的进展减缓。