LDL Subclasses and CVD Risk
Director, Atherosclerosis Research, Children’s Hospital Oakland Research Institute; Guest Senior Scientist, Dept. of Genome Sciences, Lawrence Berkeley National Laboratory; Adjunct Professor, Dept. of Nutritional Sciences, UC-Berkeley
The atherogenic dyslipidemia seen in patients with the metabolic syndrome includes elevated plasma triglyceride levels, reduced high-density lipoprotein (HDL) cholesterol (C) and increased small, dense cholesterol depleted low-density lipoprotein (sdLDL) particles. Lowering sdLDL levels can reverse the risk of cardiovascular disease (CVD).
Approximately one-third of men and one-fifth of postmenopausal women have LDL phenotype B, a lipoprotein profile characterized by a predominance of sdLDL particles that is associated with a two-to-three-fold increase in CVD risk. Low fat/high-carbohydrate diets can induce expression of phenotype B in a large proportion of otherwise healthy individuals.
Recently, we tested the effects on this lipoprotein profile of moderate dietary carbohydrate reduction (54% vs. 39% vs. 26% of energy) both before and after weight loss (~7%) in 178 overweight or obese, but otherwise healthy men. In addition, effects of lower (9% of energy) vs. higher (15%) saturated fat intake were tested in conjunction with the 26% carbohydrate diet.
The effect of carbohydrate
The 26% carbohydrate/low-saturated fat diet reduced atherogenic lipid measurements, including triglyceride, sdLDL mass and total/HDL-C ratio and increased LDL particle size compared with the 54% carbohydrate diet. Lipoprotein changes with higher vs. lower saturated fat on the 26% carbohydrate diet were similar. Although LDL-C was reduced to a greater extent with low saturated fat, there were no differences in reductions of sdLDL. The lesser reduction in LDL-C with high saturated fat was due to greater offsetting increases in larger, more cholesterol-enriched LDL particles.
The effect of weight loss
Following diet-induced weight loss and stabilization, all these variables showed significantly greater changes. LDL-C was significantly more reduced in the group that remained on the 54% carbohydrate vs. the group on the 26% carbohydrate diet.
Similar improvements in atherogenic dyslipidemia can be achieved by both reduced carbohydrate intake in the absence of weight loss and by weight loss on a higher carbohydrate diet.
- There is no significant effect of saturated fat on levels of small, dense LDL particles.
- Reduced carbohydrate intake results in lower levels of small, dense LDL particles and improvements in other features of atherogenic dyslipidemia.
- Studies consistently show that carbohydrate intake (especially glycemic load) is more strongly related to CV risk than is saturated fat intake.
- Krauss RM. 2001. Dietary and genetic effects on low-density lipoprotein heterogeneity. Annu Rev Nutr 21:238-295.
- Krauss RM, Blanche PJ, Rawlings RS, Fernstrom HS, Williams PT. 2006. Separate effects of reduced carbohydrate intake and weight loss on atherogenic dyslipidemia. Am J Clin Nutr 83:1025-1031.