Relationships between dietary fatty acids and blood cholesterol and between blood cholesterol and coronary heart disease (CHD) have been widely documented. Evidence of differential effects of dietary fatty acids on serum cholesterol concentrations was first provided by Kinsell et al. and Groen et al. (1,2), who showed that feeding polyunsaturated fatty acids (PUFA) in the diet lowers total plasma cholesterol compared with saturated fatty acids (SFA). These observations were further supported by ecologic studies, such as the Seven Countries Study, in which strong correlations were found between intake of saturated fat and CHD prevalence (3). Comparison of selected cohorts indicated that the lower incidence of death from CHD was associated with the consumption of the so-called Mediterranean diet, which is enriched in monounsaturated fatty acids (MUFA) and poor in SFA. Subsequent epidemiologic studies supported the notion that monounsaturated fat was protective against CHD compared with saturated fat. MUFA effectively lowers LDL-cholesterol (LDL-C) while, in contrast to PUFA, provides no HDL-cholesterol (HDL-C) lowering (4-6).Recommendations for a preference of MUFA over PUFA for replacing SFA in the diet initially stemmed from the metabolic study of Mattson and Grundy (7) in which plasma lipid and lipoprotein concentrations were measured in 20 hypertriglyceridemic patients consuming liquid diets enriched in SFA, MUFA, or PUFA. Dietary monounsaturated and polyunsaturated fat were equally effective in reducing plasma total cholesterol and LDL-C, while polyunsaturated fat lowered HDL-C compared with monounsaturated fat. Further, within the controversy over the recommendation for restriction of specific types of dietary fat in the prevention of CHD, Katan, Grundy, and Willett (8) suggested that a diet in which the total fat content is held constant, but is relatively enriched in MUFA, offers better protection against CHD than does a low-fat diet. However, as suggested by Brown, Shelness, and Rudel (9), dietary-fat-intervention studies have only been able to show statistical correlations between MUFA and CHD risk factors and have lacked direct measurements of associations with the extent of CHD. In this paper, we review pertinent literature addressing the influence of the various dietary fat-induced modifications of lipoprotein concentrations and compositions and their associations with atherosclerosis as the underlying cause of CHD.
CHOLESTERYL OLEATE ENRICHMENT OF LDL PREDICTS ATHEROSCLEROSIS IN ANIMAL MODELSEarly indications that an atherogenic LDL particle is characterized by a lipid core enriched in cholesteryl oleate were provided by Rudel, Pitts, and Nelson (10,11). In three different species of monkeys, and in both sexes, changes in LDL molecular weight as a marker for particle size occurred in response to dietary cholesterol (12). InThe work presented here was made possible with the support of the National