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: 8079697
• 负责人: Christine A Wanke
• 金额: $ 72.92万
• 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/8079697
• 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HIV的患者患心血管疾病的风险增加。HIV感染者心血管疾病存在多重潜在风险；长期以来，动脉粥样硬化脂质谱与心血管疾病风险增加有关；在一般人群中，总胆固醇和低密度脂蛋白胆固醇的升高已被证明与这种风险增加有关。最近的数据表明，甘油三酯水平的升高和高密度脂蛋白胆固醇水平的降低可能是心血管疾病风险的重要标志。也有新的数据表明CVD是一种炎症性疾病，并且HDL-C水平和亚谱是由炎症介导的；在艾滋病毒感染者中，这些变化可能因艾滋病毒感染而加剧。虽然治疗动脉粥样硬化性脂质谱是可取的，但在HIV感染者中，治疗这些HIV感染异常的尝试是复杂的。在艾滋病毒感染者和非艾滋病毒感染者中进行的研究表明，摄入高剂量的omega - 3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影响。摄入omega - 3脂肪酸可以改变脂质代谢，并可能通过减少花生四烯酸的产生来减少炎症。目前，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替代标志物产生有益影响。我们建议在甘油三酯水平升高的HIV感染者中进行纯化omega - 3脂肪酸的随机双盲试验。虽然ω - 3脂肪酸对脂质谱的影响在12周内应该是明显的，但我们建议进行为期整整24个月的试验，以验证我们的总体假设，即这种干预不仅可以改善甘油三酯和HDL- c水平，改善HDL-亚谱和膜磷脂，减少炎症，但与对照组相比，还可以改善24周时作为血管功能指标的肱动脉反应性，并导致24月时作为CVD替代指标的cIMT进展率降低。本建议的具体目标包括：1。对甘油三酯水平升高的HIV感染者进行为期24个月的omega - 3脂肪酸随机安慰剂对照试验（> - 150 mg/dl）。2. 为了证明摄入omega - 3脂肪酸对TG水平和HDL- c水平、HDL亚谱、膜磷脂组成、慢性炎症（通过CRP、sPLA2和花生四烯酸水平测量）的影响。3. 为了证明摄入omega - 3脂肪酸对24周肱动脉反应性和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。在HIV感染中治疗脂质异常是困难的，研究表明，摄入高剂量的omega - 3脂肪酸可以安全地改善脂质并减少炎症。我们建议在甘油三酯水平升高的HIV感染者中进行一项随机双盲试验，纯化omega - 3脂肪酸，以验证我们的总体假设，即这种干预不仅可以改善血脂和减少炎症，还可以改善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少。