In this application, we will propose a series of studies of the effects of dietary fats on plasma lipids, lipoproteins and hemostatic factors. These studies will be conducted as collaborative, multi-center trials, using standardized protocols an laboratory methodologies. A key to these studies will be the ability of each field center to provide all foods to their participants and to maintain an optimal level of subject compliance with the diets. A central coordinating center will function to insure that meal preparation techniques are uniform, and that laboratory methods are standardized. NHLBI staff will play an important role in the development of the study designs and in the performance of these investigations. A unique aspect of this application is our proposed collaboration with investigators at Stanford University and at the National Defense Medical Center in taiwan to carry out each of the protocols in an Asian population. Although the effects that nutrient intake can have on the concentrations and metabolism of plasma lipids and lipoproteins are documented in a voluminous literature that has accumulated over many years, several key issues remain to be resolved. Among these are the efficacy of the Step 1 AHA diet in females, children, and the elderly, and in blacks, hispanics and Asians; the optimal replacement for saturated fatty acids in the diet, particularly in subjects with different forms of hyperlipidemia, with diabetes mellitus, and with hypertension; the effects of varying amounts of trans-hydrogenated monounsaturated fatty acids; the cholesterol-raising effects of specific saturated fatty acids such as stearic acid; the relative effects of polyunsaturated and saturated fatty acids; and the relative effects of omega-3 and omega-6 fatty acids. The final protocol, decided upon by a committee of investigators may choose other area to investigate. The reasons for a continuing need to address these issues include the lack of adequate study design or statistical power in many previous studies, the lack of data related to particular age, sex or racial groups, and the rapid advances in our ability to measure lipid and lipoprotein parameters that may be more closely related to risk for developing coronary heart disease (CHD). Our knowledge concerning the effects of dietary fats on hemostatic factors is relatively primitive compared to the existing literature on lipids and lipoproteins, and studies on hemostasis and diet are clearly needed. Using this collaborative approach, we will achieve the levels of statistical power and standardization that are necessary to answer many of the complex questions related to the role of dietary fats in the development of atherosclerotic cardiovascular disease.
