Effect of Fish Oil (Omega-3 Fatty Acids) on Arteries

Overview

The overall objective of LUCHAR Specific Aims 4.1 and 4.2 is to assess the additional contribution of cardiovascular disease (CVD) risk markers to traditional biomedical risk factors in the prediction of pre-clinical CVD. Specific Aim 4.3 will test the impact of omega-3 fatty acid supplementation on risk markers and pre-clinical markers of CVD in Hispanic patients. Specific Aim 4.3: Conduct a randomized, placebo-controlled trial of the effect of omega-3 fatty acid supplementation on vascular function as measured by brachial artery reactivity (BAR) and on circulating inflammatory markers. Hypotheses: 1. Daily omega-3 fatty acid supplementation will improve vascular function in subjects at high risk for CVD. 2. Daily omega-3 fatty acid supplementation will reduce inflammatory protein panel scores in subjects at high risk for CVD.

Omega-3 fatty acids reduce triglycerides (TG) in a manner similar to fibric acids by lowering hepatic TG release, reducing VLDL production, stimulating lipoprotein lipase and enhancing TG clearance. Although statins are widely utilized among DH patients, our overall population, even those with CHD, have fairly low levels of LDL-cholesterol (Krantz et al, 2004). This likely reflects our population that is predominantly Latino with a high incidence of metabolic syndrome. Among our patients, we often achieve LDL-c NCEP targets, yet secondary goals for non-HDL, HDL, and TG are rarely achieved. This is an unmet opportunity given the strong independent contribution of non-HDL (McQueen et al, 2008), HDL (D'Agostino et al, 2008) and TG (Nordestgaard et al, 2007, Tirosh et al, 2007) to CHD risk, which may be particularly important in Latino populations. The study drug (LOVAZA) improves the TC/HDL ratio which is the strongest predictor of CHD events based on the \~30,000 patient Interheart study noted above. LOVAZA has no hepatic P450 effects and for that matter no meaningful clinical adverse effects, making it advantageous for use in a population with multiple co-morbidities who are at risk for drug-drug interactions and have difficulty with medication adherence. Given the high incidence of insulin resistance among DH's predominately Latino CHD population, and strong lipid (Harris et al, 1997; Davidson et al 2007) as well outcome data in CHD (GISSI investigators, 1999) this agent has potential clinical utility in our population. To date, improved outcomes in non-CHD populations have not been demonstrated prospectively with LOVAZA. Although recent data suggest promising effects on inflammatory makers such as LpPLA2, the impact of LOVAZA on pre-clinical markers of atherosclerosis such as BAR and CIMT have not been well characterized particularly among Latinos. Moreover, changes in inflammatory markers have been limited and more expansive evaluations are currently available. Against this background we assessed whether LOVAZA might improve atherosclerotic risk via improvement in flow mediated dilation of the brachial artery as well as through reduction in a comprehensive inflammatory marker panel.