HARVARD COLLEGE, PRESIDENT & FELLOWS OF

Title: Dietary Patterns and Risk of Cardiovascular Disease Conventional classifications of saturated, monounsaturated, polyunsaturated, and trans fat incompletely capture the wide heterogeneity across >50 unique fatty acids. In this proposal, we put forth and test a novel evidence-based dietary pattern theory ? that a set of indices of fatty acid lipophilicity that incorporates the wide differences in fatty acid fluidity and intermolecular binding affinity has the potential to provide a new paradigm for dietary etiology of coronary heart disease. We will create two indices: the Lipophilic Index of fatty acids, indexed on fatty acid melting points to reflect fat fluidity; and the Lipophilic Load to reflect both lipophilic fluidity and fatty acid quantity in the diet. We will test the hypothesis that these two indices are associated with risk of coronary heart disease by analyzing nutritional and biochemical data from two large ongoing prospective cohort studies -- the Nurses? Health Study and Health Professionals? Follow-up Study . This project includes two specific aims: 1) To conduct a nested case-control study of plasma and erythrocyte membrane Lipophilic Index and risk of coronary heart disease. This study will include 620 incident cases of coronary heart disease and 1,240 matched controls from the Nurses? Health Study and Health Professionals' Follow-up Study. We hypothesize that higher plasma phospholipid and erythrocyte membrane Lipophilic Index values are associated with increased coronary heart disease risk and these associations are in part mediated through biomarkers of inflammation, endothelial dysfunction, insulin resistance, and dyslipidemia. Plasma and erythrocyte fatty acids have already been measured in 170 coronary heart disease cases and 340 healthy controls in Nurses? Health Study. In this 2-year grant, we will measure plasma and erythrocyte fatty acid profile 450 coronary heart disease cases and 900 controls in Health Professionals' Follow-up Study. Because these cases and controls have already been selected in an ongoing study, we will be able to prepare blood and erythrocyte samples for laboratory analysis in a timely fashion. The laboratory analysis is expected to be completed by September, 2010. 2) To analyze relations between dietary, plasma, and erythrocyte indices of fat lipophilicity and major etiological biomarkers of coronary heart disease (inflammation, insulin resistance, lipids, and endothelial dysfunction) in the controls in both Nurses? Health Study and Health Professionals' Follow-up Study. We hypothesize that increased dietary and tissue fatty acid lipophilicity is associated with increased biomarkers of inflammation, endothelial dysfunction, insulin resistance, and dyslipidemia. These markers have already been measured in both Nurses? Health Study and Health Professionals' Follow-up Study through other grants.

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