VASCULAR & LIPID EFFECTS OF OMACOR IN SUBJECTS WITH MODERATELY ELEVATED TRIGLYCE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 欧米茄-3脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）在鱼类中含量丰富，已被发现在保护心血管健康方面发挥重要作用，尽管对完整的作用机制仍知之甚少。 Omega-3脂肪酸以剂量依赖性方式有效降低甘油三酯，并在一些研究中显示具有抗炎和促进血管健康的作用。Omacor是FDA批准的药物，是EPA和DHA的浓缩形式，用于降低甘油三酯非常高（> 500 mg/dL）患者的甘油三酯。在本研究中，我们将对25例中度高血脂症（150-500 mg/dL）受试者给予1 g和4 g剂量的Omacor，因为他们的心脏病风险升高，但目前未接受这种形式的血脂异常的药物治疗。 我们采用随机、安慰剂对照、双盲、交叉设计，3个8周治疗期（1 g、4 g和安慰剂），治疗之间有6周洗脱期。 我们的主要终点是对压力和流量介导的扩张（内皮健康的测量）的生理反应的测量。这两种方法都被认为可以预测心血管死亡率。 我们还将测量红细胞omega-3脂肪酸浓度（omega-3指数）和炎症标志物，并进行完整的血脂检查。 我们假设4 g剂量将降低甘油三酯20- 35%，改善应激反应性和血流介导的扩张，并可能导致炎症减少。 我们认为，研究1 g剂量以评估当前饮食建议的上限非常重要;但是，我们无法预测其对血管终点的影响。 很少有研究使用这种更适度的剂量，即使它是目前基于大规模干预和流行病学研究的心血管健康推荐的每日摄入量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are abundant in fish and have been found to play an important role in protecting cardiovascular health although the complete mechanisms of action are still poorly understood. Omega-3 fatty acids are effective in lowering triglycerides in a dose-dependent manner and have been shown to have anti-inflammatory and vascular-health-promoting effects in some studies. Omacor is an FDA-approved drug that is a concentrated form of EPA and DHA and is used to lower triglycerides in patients with very high triglycerides (> 500 mg/dL). In this study we will give 1 g and 4 g doses of Omacor to 25 subjects with moderate hypertriglyceridemia (150-500 mg/dL) because they are at elevated risk for heart disease but currently do not receive medical treatment for this form of dyslipidemia. We are using a randomized, placebo-controlled, double-blind, crossover design with three 8-week treatment periods (1 g, 4 g, and placebo) and 6-week washout periods between treatments. Our primary endpoints are measures of physiologic responses to stress and flow-mediated dilation (a measure of endothelial health). Both measures are thought to predict incidence of cardiovascular mortality. We will also measure erythrocyte omega-3 fatty acid concentration (the omega-3 index) and markers of inflammation, and perform a complete lipid panel. We hypothesize that the 4 g dose will lower triglycerides 20-35%, improve stress reactivity and flow-mediated dilation, and possibly result in decreased inflammation. We feel that it is important to study the 1 g dose to provide an evaluation of the upper level of current dietary recommendations; however we cannot predict its effects on our vascular endpoints. Little research has used this more moderate dose even though it is the current recommended daily intake for cardiovascular health based on large intervention and epidemiological studies.