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.