Dietary and genetic effects on low-density lipoprotein heterogeneity.

We have tested whether differences in distribution and dietary responsiveness of low-density lipoprotein (LDL) subclasses contribute to the variability in the magnitude of LDL-cholesterol reduction induced by diets low in total and saturated fat and high in carbohydrate. Our studies have focused on a common, genetically influenced metabolic profile, characterized by a predominance of small, dense LDL particles (subclass pattern B), that is associated with a two- to threefold increase in risk for coronary artery disease. We have found that healthy normolipidemic individuals with this trait show a greater reduction in LDL cholesterol and particle number in response to low-fat, high-carbohydrate diets than do unaffected individuals (subclass pattern A). Moreover, such diets result in reduced LDL particle size, with induction of pattern B in a substantial proportion of pattern A men. Recent studies have indicated that this response is under genetic influence. Future identification of the specific genes involved may lead to improved targeting of dietary therapies aimed at reducing cardiovascular disease risk.