Background: The sex differential in coronary heart disease (CHD) risk, which is not explained by male/female differences in lipid and lipoprotein concentrations, narrows with age. We examined whether this differential CHD risk might, in part, be attributable to the sizes of lipoprotein particles or concentrations of lipoprotein subclasses.

Methods: We analyzed frozen plasma samples from 1574 men and 1692 women from exam cycle 4 (1988–1990) of the Framingham Offspring Study. Nuclear magnetic resonance (NMR) spectroscopy was used to determine the subclass concentrations and mean sizes of VLDL, LDL, and HDL particles. Concentrations of lipids and apolipoproteins were measured by standard chemical methods.

Results: In addition to the expected sex differences in concentrations of triglycerides, LDL-cholesterol, and HDL-cholesterol, women also had a lower-risk subclass profile consisting of larger LDL (0.4 nm) and HDL (0.5 nm) particles. The sex difference was most pronounced for HDL, with women having a twofold higher (8 vs 4 μmol/L) concentration of large HDL particles than men. Furthermore, similar to the narrowing of the sex difference in CHD risk with age, the observed male/female difference in HDL particle size also decreased with age. Although lipoprotein particle sizes were highly correlated with lipid and lipoprotein concentrations, the sex differences in the mean sizes of lipoprotein particles persisted (P <0.001) even after adjustment for lipid and lipoprotein concentrations.

Conclusions: Women have a less atherogenic subclass profile than men, even after accounting for differences in lipid concentrations.